Ticks: Biology, Ecology, and Diseases 032391148X, 9780323911481

Table of contents :
Front Cover
Ticks
Ticks Biology, Ecology, and Diseases
Copyright
Dedication
Contents
Preface
1 - A brief introduction to ticks
Why study ticks? (And write a book about them)
A note on naming of ticks
The structure of the book
Conclusions
References
2 - Tick classification and diversity
Introduction
Tick taxonomy
The families
The Ixodidae: the hard ticks
The Argasidae: the soft ticks
The Nuttalliellidae: Nuttalliella namaqua the odd one out!
Tick morphology
Identification of ticks using morphology
Identification of ticks using genetic sequence
Identification of ticks using proteomics
Conclusions
References
3 - The tick life cycle
Introduction
Hard ticks
Ixodes ricinus (Linnaeus, 1758)—a questing tick
Ixodes uriae (White, 1852)—a nest dweller
Amblyomma americanum (Linnaeus, 1758)—a vector on the rise
Dermacentor reticulatus (Fabricius, 1794)—an ornamented tick
Hyalomma marginatum (Koch, 1844)—a hunting tick
Rhipicephalus microplus (Canestrina, 1888)—a one host tick
Rhipicephalus sanguineus (Latreille, 1806)—a tick adapted to man's best friend
Haemaphysalis longicornis (Neumann, 1901)—the invader
Soft ticks
Ornithodoros moubata (Murray, 1877)—into the burrows
Argas vespertilionis (Latreille, 1802)—life on the wing
Conclusions
References
4 - Blood feeding as a life choice and the multiple functions of tick saliva
Introduction
Finding a host
Attachment
Engorgement
Detachment
Problems associated with blood feeding
Thermoregulation
Water balance
Interrupted feeding
Hyperparasitism
The exception to the blood-feeding rule
Tick saliva
Structure of the tick salivary gland
The functions of tick salivary glands and saliva
The effect on skin at the bite site
The role of tick saliva in pathogen transmission
Antitick vaccination using components of tick saliva
Conclusions
References
5 - An introduction to tick-borne disease
Africa
Asia
Australia and New Zealand
Europe
North America
South and Central America
Summary
References
6 - Tick-borne diseases of humans
Introduction
Tick-borne disease caused by viruses
Alkhurma hemorrhagic fever
Colorado tick fever
Crimean–congo hemorrhagic fever
Eyach virus
Kyasanur Forest disease
Omsk hemorrhagic fever
Powassan encephalitis and deer tick virus
Tick-borne encephalitis
Tick-borne diseases caused by bacteria
Human granulocytic anaplasmosis
Lyme borreliosis
Ehrlichiosis
Rickettsiosis
Tularemia
Coxiella burnetii—Q fever
Tick-borne diseases caused by protozoa
Babesiosis
Nonpathogen-associated disease
Conclusions
References
7 - Tick-borne diseases of animals
Introduction
Tick-borne diseases—viruses
African swine fever
Ovine encephalitis (louping ill)
Nairobi sheep disease
Thogoto virus
Tick-borne diseases—protozoa
Babesiosis
Theileriosis
Bovine theileriosis
Tick-borne diseases—bacteria
Tick-borne fever (anaplasmosis in animals)
Heartwater/cowdriosis
Canine ehrlichiosis
Hepatozoonosis
Conclusions
References
8 - Emerging diseases and the impact of the microbiome
References
9 - Emerging tick-borne diseases
Introduction
The discovery of Severe fever with thrombocytopenia syndrome in China and the emergence of Heartland virus in North America
The discovery of Beiji virus in China
Bourbon virus in the United States
The emergence of Babesia microti in North America
The emergence of Theileria orientalis type Ikeda in New Zealand
Conclusions
References
10 - The tick microbiome
Introduction
Technologies used to detect pathogens
The tick virome
Discovery of segmented flaviviruses
Pathogen discovery in Ixodes scapularis, North America
The tick bacteriome
Other microbiota associated with ticks
Conclusions
References
11 - Climate change and control of ticks and tick-borne diseases
References
12 - The impact of climate change on ticks and tick-borne disease transmission
Introduction
Impact of climate change in temperate regions
Europe
The example of the British Isles
North America
Impact of climate change in tropical and subtropical regions
Impact of climate change at the poles
Conclusions
References
13 - Controlling ticks and tick-borne disease transmission
Introduction
Surveillance: its importance in controlling ticks and tick-borne disease
Surveying for ticks
Environmental collection of ticks
On-host collections of ticks
Citizen science and surveys
Detection of tick-associated pathogens
The challenge of invasive species
Methods for studying tick-borne disease biology and transmission
Tick colonies for investigating tick–pathogen interactions
Tick cell lines as an alternative model system
Acaricides
Land management
Vaccines
Vaccines directed at individual tick-borne pathogens
Vaccines directed at ticks
Public information
Conclusions
References
14 - Synthesis: future developments in tick research
New discoveries and species redistribution
Ticks as vectors
Climate change and ticks
Tick genomics
Harnessing the sialome
Closing remarks
References
Index
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D
E
F
G
H
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Back Cover

Citation preview

Ticks

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Ticks Biology, Ecology, and Diseases

Nicholas Johnson Animal and Plant Health Agency, Surrey, United Kingdom

Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1650, San Diego, CA 92101, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom Copyright © 2023 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. ISBN: 978-0-323-91148-1 For information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals Publisher: Nikki P. Levy Acquisitions Editor: Kelsey Connors Editorial Project Manager: Kyle Gravel Production Project Manager: Kiruthika Govindaraju Cover Designer: Typeset by TNQ Technologies

This book is dedicated to my sons, Jack and Harry.

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Contents Preface ................................................................................................ xiii

CHAPTER 1 A brief introduction to ticks..................................... 1 Why study ticks? (And write a book about them).................... 1 A note on naming of ticks................................................... 3 The structure of the book .................................................... 4 Conclusions ...................................................................... 5 References........................................................................ 6

CHAPTER 2 Tick classification and diversity .............................. 9 Introduction...................................................................... 9 Tick taxonomy .................................................................10 The families ....................................................................11 The Ixodidae: the hard ticks ...............................................12 The Argasidae: the soft ticks ..............................................13 The Nuttalliellidae: Nuttalliella namaqua the odd one out! ......13 Tick morphology ..............................................................14 Identification of ticks using morphology ...............................17 Identification of ticks using genetic sequence ........................18 Identification of ticks using proteomics ................................20 Conclusions .....................................................................20 References.......................................................................21

CHAPTER 3 The tick life cycle..................................................25 Introduction.....................................................................25 Hard ticks........................................................................27 Ixodes ricinus (Linnaeus, 1758)da questing tick ...............27 Ixodes uriae (White, 1852)da nest dweller.......................29 Amblyomma americanum (Linnaeus, 1758)da vector on the rise ...................................................................31 Dermacentor reticulatus (Fabricius, 1794)dan ornamented tick............................................................31 Hyalomma marginatum (Koch, 1844)da hunting tick.........33 Rhipicephalus microplus (Canestrina, 1888)da one host tick......................................................................34 Rhipicephalus sanguineus (Latreille, 1806)da tick adapted to man’s best friend ...........................................35

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Haemaphysalis longicornis (Neumann, 1901)dthe invader..36 Soft ticks.........................................................................37 Ornithodoros moubata (Murray, 1877)dinto the burrows....37 Argas vespertilionis (Latreille, 1802)dlife on the wing.......38 Conclusions .....................................................................39 References.......................................................................40

CHAPTER 4 Blood feeding as a life choice and the multiple functions of tick saliva...........................................45 Introduction.....................................................................45 Finding a host ..................................................................46 Attachment......................................................................48 Engorgement....................................................................49 Detachment .....................................................................49 Problems associated with blood feeding................................50 Thermoregulation .............................................................50 Water balance ..................................................................51 Interrupted feeding............................................................51 Hyperparasitism ...............................................................51 The exception to the blood-feeding rule................................52 Tick saliva.......................................................................52 Structure of the tick salivary gland ......................................53 The functions of tick salivary glands and saliva .....................54 The effect on skin at the bite site.........................................56 The role of tick saliva in pathogen transmission.....................57 Antitick vaccination using components of tick saliva ..............58 Conclusions .....................................................................59 References.......................................................................59

CHAPTER 5 An introduction to tick-borne disease .....................65 Africa.............................................................................67 Asia ...............................................................................68 Australia and New Zealand ................................................68 Europe............................................................................69 North America .................................................................70 South and Central America.................................................71 Summary.........................................................................71 References.......................................................................72

CHAPTER 6 Tick-borne diseases of humans ..............................75 Introduction.....................................................................75 Tick-borne disease caused by viruses ...................................77 Alkhurma hemorrhagic fever ..........................................77

Contents

Colorado tick fever .......................................................78 Crimeanecongo hemorrhagic fever..................................78 Eyach virus .................................................................80 Kyasanur Forest disease.................................................80 Omsk hemorrhagic fever................................................81 Powassan encephalitis and deer tick virus .........................84 Tick-borne encephalitis..................................................85 Tick-borne diseases caused by bacteria.................................87 Human granulocytic anaplasmosis ...................................87 Lyme borreliosis...........................................................87 Ehrlichiosis..................................................................89 Rickettsiosis ................................................................90 Tularemia....................................................................90 Coxiella burnetiidQ fever .............................................92 Tick-borne diseases caused by protozoa................................93 Babesiosis ...................................................................93 Nonpathogen-associated disease ..........................................95 Conclusions .....................................................................96 References.......................................................................97

CHAPTER 7 Tick-borne diseases of animals ............................ 107 Introduction................................................................... 107 Tick-borne diseasesdviruses ............................................ 109 African swine fever..................................................... 109 Ovine encephalitis (louping ill) ..................................... 110 Nairobi sheep disease .................................................. 112 Thogoto virus............................................................. 112 Tick-borne diseasesdprotozoa.......................................... 113 Babesiosis ................................................................. 113 Theileriosis................................................................ 115 Bovine theileriosis ...................................................... 117 Tick-borne diseasesdbacteria........................................... 118 Tick-borne fever (anaplasmosis in animals)..................... 118 Heartwater/cowdriosis ................................................. 119 Canine ehrlichiosis...................................................... 121 Hepatozoonosis .......................................................... 121 Conclusions ................................................................... 122 References..................................................................... 123

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CHAPTER 8 Emerging diseases and the impact of the microbiome ......................................................... 131 References..................................................................... 134

CHAPTER 9 Emerging tick-borne diseases............................... 137 Introduction................................................................... 137 The discovery of severe fever with thrombocytopenia syndrome in China and the emergence of Heartland virus in North America............................................................ 138 The discovery of Beiji virus in China................................. 140 Bourbon virus in the United States .................................... 142 The emergence of Babesia microti in North America............ 142 The emergence of Theileria orientalis type Ikeda in New Zealand.............................................................. 144 Conclusions ................................................................... 146 References..................................................................... 147

CHAPTER 10

The tick microbiome............................................. 153 Introduction................................................................... 153 Technologies used to detect pathogens ............................... 154 The tick virome.............................................................. 155 Discovery of segmented flaviviruses................................... 160 Pathogen discovery in Ixodes scapularis, North America....... 161 The tick bacteriome ........................................................ 161 Other microbiota associated with ticks ............................... 163 Conclusions ................................................................... 163 References..................................................................... 165

CHAPTER 11

Climate change and control of ticks and tick-borne diseases .............................................. 171 References..................................................................... 174

CHAPTER 12

The impact of climate change on ticks and tick-borne disease transmission ........................... 177 Introduction................................................................... 177 Impact of climate change in temperate regions .................... 179 Europe...................................................................... 179 The example of the British Isles........................................ 180 North America ............................................................... 181 Impact of climate change in tropical and subtropical regions.. 182

Contents

Impact of climate change at the poles ................................ 185 Conclusions ................................................................... 186 References..................................................................... 188

CHAPTER 13

Controlling ticks and tick-borne disease transmission ........................................................ 193 Introduction................................................................... 193 Surveillance: its importance in controlling ticks and tick-borne disease ........................................................... 195 Surveying for ticks.......................................................... 196 Environmental collection of ticks ...................................... 196 On-host collections of ticks .............................................. 197 Citizen science and surveys .............................................. 198 Detection of tick-associated pathogens ............................... 199 The challenge of invasive species ...................................... 200 Methods for studying tick-borne disease biology and transmission................................................................... 202 Tick colonies for investigating tickepathogen interactions..... 202 Tick cell lines as an alternative model system...................... 203 Acaricides ..................................................................... 204 Land management........................................................... 206 Vaccines........................................................................ 206 Vaccines directed at individual tick-borne pathogens............. 206 Vaccines directed at ticks ................................................. 207 Public information .......................................................... 207 Conclusions ................................................................... 208 References..................................................................... 209

CHAPTER 14

Synthesis: future developments in tick research .............................................................. 217 New discoveries and species redistribution.......................... 217 Ticks as vectors.............................................................. 218 Climate change and ticks ................................................. 220 Tick genomics................................................................ 221 Harnessing the sialome.................................................... 222 Closing remarks ............................................................. 222 References..................................................................... 223

Index...................................................................................................227

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Preface For most humans, ticks are not a major concern. However, a chance encounter, something as trivial as brushing past tall grass while walking in woodland or along the side of a field, can lead to a tick bite. If not removed promptly, it can result in transmission of a virus, bacteria, or protozoan pathogen that in the worst cases cause a life-threatening illness. Even the tick bite itself can lead to an autoimmune disease and allergy. Each year, thousands of people are affected by diseases such as tickborne encephalitis, Lyme’s disease, and babesiosis, a cause of anemia. This is mainly based on the reporting of disease in North America, Europe, and parts of Asia. The full impact of tick-borne disease in large parts of Africa and South America is not recorded. Despite the threat to human health, the greatest impact is to domestic animals, including companion animals, but especially livestock. The concentration of increasingly large numbers of cattle and sheep has provided a ready target for a range of tick species that have exploited this ever since animals were first domesticated. Beyond the welfare impact to the animals of heavy tick infestations, the worldwide cost of tick predation through the transmission of disease runs to billions of dollars annually. And the use of chemicals to suppress tick infestations are not inexpensive and may rapidly lose their efficacy due to the development of acaracide resistance. The combination of agricultural losses and the impact on human health provide the main drivers for research on the biology of ticks, their ecology, and the diseases they transmit. In this book I have tried to cover all three aspects, but a book could be written on each of the main chapters that consider the historical investigations that have led to our current understanding, recent developments and disagreements, particularly around tick taxonomy, and future innovations. I have tried to condense this breadth of information into a series of chapters that review the key elements of tick biology, tick-borne pathogens of humans and animals, and the control of ticks. No book should be without a chapter on the impact of climate change, and this one is no exception. I must acknowledge a legion of scientists who have contributed to our knowledge and understanding of the subject of ticks and their pathogens. While not naming them, I hope that the citation of their work throughout this book acknowledges their impact. I also need to thank the many scientists, mainly in Europe, who I have worked with since developing an interest in tick-borne viruses. Of these, the one I will name is my former colleague, Paul Phipps. After fifty years as a scientist within the British Civil Service, Paul retired in March 2022. Much of his career was in the field of livestock parasitology, and he maintained an interest and expertise in ticks and tick-borne diseases long after it was deemed uninteresting or fundable. Despite my interest in viruses, he encouraged me to consider the vector alongside the pathogen and to step outside of the laboratory to literally look in the field where

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transmission occurs. This emphasized the importance of investigating the biology of the vector to understand the transmission process, appreciate the ecology of the vector to understand when and where transmission occurs, and then to marry this with what we know of the pathogen to begin to prevent or control disease. Nicholas Johnson 2022

CHAPTER

A brief introduction to ticks

1

Why study ticks? (And write a book about them) Ticks are fairly unpleasant creatures, and for most people, the first encounter with one will be the discovery of a tick in the process of biting them or their pets. Unlike most other biting arthropods, ticks hang around at the bite site, so are often caught in the act. Unless removed promptly, there is also the possibility that the resulting encounter may lead to the transmission of one of a vast range of pathogens that in some cases can cause debilitating disease and in extreme cases death. This raises the question of what role, either positive or negative, they play within the ecosystems they exist in. For the owners of livestock around the world, ticks represent a threat to the health and well-being of virtually all domesticated animals and one to which huge resources are directed at suppressing tick infestation. The combination of a source of disease and the economic threat they pose means that ticks cannot be ignored and that understanding their biology, ecology, and disease transmission is an important first step in combatting tick-borne infections. Aristotle (384e322 BCE) described them as present on a range of domestic animals including sheep, cattle, and dogs. He may also have set the tone by describing them as “disgusting parasites,” a view shared by many who encounter them after venturing outdoors. The disgust comes from their only interaction with us (humans) and most other vertebrates of biting us and then remaining, often for over a week as it takes a blood meal. They do this as it is their only source of nutrition, and, like any animal that bites, this makes them excellent vectors for transmitting diseases. As a result, ticks are one of the main sources of disease for humans, livestock, and companion animals throughout the world. Ancient Egyptian art may well have captured the first images of a tick on a jackal-headed beast in 1500 BC (Arthur, 1965), but it is only in the past 150 years that research has focused on the diversity of ticks and the diseases they transmit. Ticks are related to spiders, mites, and fleas placing them in the class Arachnida and sharing the common feature of eight legs in the adult form. Ticks can be divided into two basic categories of hard and soft ticks based on their anatomy, and this will be discussed further in the next chapter. All tick species have four life stages, egg, larva, nymph, and adult (Fig. 1.1). The adult stage is sexually dimorphic with male and female forms. All mobile life stages must locate a host, attach to it, and take a Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00001-0 Copyright © 2023 Elsevier Inc. All rights reserved.

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FIGURE 1.1 A simplified schematic of the tick life cycle from egg, through two immature forms, larva and nymph, to adult.

blood meal. This can take minutes to days depending on the life stage and species and can lead to a huge distension of the tick abdomen. Once the blood meal has been imbibed, the tick will detach. For larvae and nymphs, this supplies the nutrition required to enable them to metamorphose, more commonly referred to as moulting, to the next stage. In the case of adults, the female takes a blood meal to support egg development, while the male usually does not take a blood meal, focusing instead on finding a female and mating with it. An engorged female, one that has swollen to its maximum size will detach from the host, seek a safe location to digest the blood meal, and allow eggs to mature. It will then lay the eggs in a process termed oviposition. This can lead to thousands of eggs that will produce the next generation of ticks. Ticks are found wherever their vertebrate hosts are present. The greatest diversity is found in tropical regions where ticks have adapted to predation on virtually all vertebrate groups of species. Some, such as the Asian blue tick, Rhipicephalus microplus, and the brown dog tick, Rhipicephalus sanguineus, have adapted to feeding, specifically on cattle and dogs, respectively. This represents an adaption to human modification of the environment such as the domestication of animals

A note on naming of ticks

and wholesale translocation of species around the world. This leads directly to conflict with human activities, particularly livestock management, and has prompted attempts to suppress tick feeding as a means of controlling disease transmission. However, ticks can be found on all continents. This includes extreme environments such as the Antarctic, where the seabird tick Ixodes uriae can be found infesting sea birds and their nests (Mun˜oz-Leal and Gonza´lez-Acun˜a, 2015). This tick is tough enough to withstand temperatures as low as 30 C experienced in polar regions (Lee and Baust, 1987; Benoit et al., 2007) and the extreme windswept conditions found in remote bird nesting colonies. Its association with birds has almost certainly led to its global distribution. In contrast, isolated regions such as New Zealand have evolved their own tick fauna in response to their separation from the major continents. Even the giant tortoises of the Galapagos Islands are plagued by ticks that have evolved with them (Hoogstraal and Kohls, 1966).

A note on naming of ticks Throughout this book ticks will be named by their latin name for clarity. See the International Code of Zoological Nomenclature website for further information (https://code.iczn.org/). Another common feature of naming species is to include the name of the scientist that first described the species and the year in which the description was published. Indeed, it was Carl Linneaus who produced some of the first detailed descriptions of some of the species of tick discussed in the following chapters. The complete naming of a tick species is illustrated in Fig. 1.2 for the naming of the common sheep tick that Linneaus first described in 1758. This also illustrates the ephemeral nature of species naming as this can change as our understanding of the relationship between species changes and with developments in technology. Throughout this book, the first mention of a tick species within in each chapter will include all aspects of the naming but will then restrict to the latin name for clarity. Some authors, although not all, also include details within the title of a publication of aspects of the classification of a species such as its subclass and family. In the case of Ixodes ricinus, this would be (Acari: Ixodidae). A number of other terms are often encountered when dealing with species. These are the terms “sensu stricto” from the latin meaning “in a narrow sense” and “sensu lato” meaning “in the broad sense.” The former term is used when a species has been clearly delineated morphologically, phenotypically, or genetically as a well-defined species and is usually denoted as s.s. The later term is commonly used when a group of tentative species, often morphologically similar are grouped together and denoted with s.l. The brown dog tick is sometimes referred to as R. sanguineus s.l. to indicate that the variants under discussion are considered a complex of species and not necessarily a single unified entity (Dantas-Torres et al., 2013). Another term used when describing a specimen is “cf” or compare with. This indicates that the writer believes that the specimen being described is similar, but not the same, as a known species.

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FIGURE 1.2 A schematic with definitions on the naming of the sheep tick Ixodes ricinus.

Another form of classification that is commonly encountered when researching ticks is that applied to geography in the definition of biogeographic regions. The distribution of tick species is intimately linked with the ecological and climatic conditions that enable the tick to persist, and they do not follow country boundaries but limited by larger climatic regions. A classification of the world regions was developed by Miklos Udvardy of the California State University, USA (http://portals. iucn.org/library/efiles/documents/op-018.pdf Accessed 17/02/2021), who divided the land surfaces of the earth into eight areas that shared similar habitat types (Fig. 1.3). Studies on tick biology and taxonomy often focus on these regions rather than the geopolitical boundaries of countries and continents as this better reflects the influences of climate, vertebrate assemblages, and geographical boundaries such as mountains and oceans (Pereira de Oliveira et al., 2019; Hornok et al., 2021; EstradaPen˜a et al., 2021).

The structure of the book This book has been divided into three sections. The first deals with the biology and ecology of ticks in three chapters. Biology deals with activities of an organism, while ecology studies its relationship with other species and the environment. The three chapters consider the classification and diversity of ticks, the tick life cycle, and finally the challenges of finding a host and then feeding on it. The second section

Conclusions

FIGURE 1.3 A map of the world showing six of the eight biogeographical regions. The two remaining regions are the Oceanic region covering islands in the Pacific Ocean and Antarctica.

reflects my own interest in tick-borne diseases with chapters on diseases of humans, animals, and of particular relevance for the future with a chapter on emerging diseases of ticks. The third and final section covers topical subjects including control of ticks, the complete microbiome of ticks, and the impact of climate change on ticks and tick-borne diseases. Each chapter is written as a stand-alone essay although information in the first section informs aspects of tick-borne disease and control.

Conclusions In order to understand the source of disease and attempt to control and prevent transmission, we need to study tick biology, how particular species feed, reproduce, and the adaptations that enable them to survive in often hostile environments. We also need to investigate their ecology, the relationships within and between species, and their environment. This is clearly relevant to understanding the profound effects of climate change. Finally, we need to understand the diseases they cause, what pathogens are related to which ticks species, when and where transmission occurs, and then use this information to develop means to prevent this from occurring or ameliorating the effects if disease does develop. Developments in molecular biology, and particularly genetic sequencing, have had a dramatic impact on the ability to identify tick species and the diseases they transmit. Tick classification, originally based on morphological discrimination, is constantly evolving in response to new ways of distinguishing specimens. The

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introduction of genomic sequence data is allowing a reassessment of the classification of hard and soft ticks, often resulting in the taxonomic revision of existing species. When venturing into almost any group of species, including pathogens, one of the first challenges is to understand the nomenclature and in part the history that has led to that nomenclature. In my own experience, this has been experienced with the genus Babesia, a protozoan tick-transmitted parasite that infects red blood cells. For much of the 20th century, Babesias were described as small or large based on the morphology of the parasite in red blood cells. However, as more species were identified, this means of describing the pathogen was inevitably going to prove limiting. Genomic sequenced-based methods are now helping address this challenge, but even with this support, there is still uncertainty that some are a true babesia species or represent a separate, distinct genera with a different evolutionary history. Also, some diseases are caused by a species complex containing a bewildering array of genotypes, often identified on the basis of a single DNA sequence. Take, for example, Theileria orientalis, found in many locations in Eurasia but only causing disease in cattle in East Asia. As scientists and authors, we need to try and work within what is considered a reasonable interpretation of the current classification. But with the acknowledgment that whatever is written today may be obsolete tomorrow as a result of new discoveries, progress in technology, and novel reinterpretations of existing data. Part of the reason to write this book is to increase my own knowledge on the subject and investigate themes that I would not normally consider. As a source of references, I have tried to use open access publications from the past 10 years to give an as up-to-date perspective as possible and reference material the readers can easily access.

References Arthur, D.R., 1965. Ticks in Egypt in 1500 B.C. Nature 206 (4988), 1060e1061. https:// doi.org/10.1038/2061060a0. Benoit, J.B., Yoder, J.A., Lopez-Martinez, G., Elnitsky, M.A., Lee, R.E., Denlinger, D.L., 2007. Habitat requirements of the seabird tick, Ixodes uriae (Acari: Ixodidae), from the Antarctic Peninsula in relation to water balance characteristics of eggs, nonfed and engorged stages. Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology 177 (2), 205e215. https://doi.org/10.1007/s00360-006-0122-7. Dantas-Torres, F., Latrofa, M.S., Annoscia, G., Giannelli, A., Parisi, A., Otranto, D., 2013. Morphological and genetic diversity of Rhipicephalus sanguineus sensu lato from the New and Old Worlds. Parasites & Vectors 6 (1), 213. https://doi.org/10.1186/17563305-6-213. Estrada-Pen˜a, A., Binder, L.C., Nava, S., Szabo´, M.P.J., Labruna, M.B., 2021. Exploring the ecological and evolutionary relationships between Rickettsia and hard ticks in the Neotropical region. Ticks and Tick-Borne Diseases 12 (5), 101754. https://doi.org/ 10.1016/j.ttbdis.2021.101754.

References

Hoogstraal, H., Kohls, G.M., 1966. Argas (Microargas) transversus banks (New Subgenus) (Ixodoidea, Argasidae), a diminutive parasite of the galapagos giant tortoise: redescription of the holotype male and description of the larva. Annals of the Entomological Society of America 59 (2), 247e252. https://doi.org/10.1093/aesa/59.2.247. Hornok, S., Meyer-Kayser, E., Kontscha´n, J., Taka´cs, N., Plantard, O., Cullen, S., Gaughran, A., Szekeres, S., Majoros, G., Beck, R., Boldogh, S.A., Horva´th, G., Kutasi, C., Sa´ndor, A.D., 2021. Morphology of Pholeoixodes species associated with carnivores in the western Palearctic: pictorial key based on molecularly identified Ixodes (Ph.) canisuga, I. (Ph.) hexagonus and I. (Ph.) kaiseri males, nymphs and larvae. Ticks and Tick-Borne Diseases 12 (4), 101715. https://doi.org/10.1016/j.ttbdis.2021.101715. Lee, R.E., Baust, J.G., 1987. Cold-hardiness in the antarctic tick, Ixodes uriae. Physiological Zoology 60 (4), 499e506. https://doi.org/10.1086/physzool.60.4.30157912. Mun˜oz-Leal, S., Gonza´lez-Acun˜a, D., 2015. The tick Ixodes uriae (Acari: Ixodidae): hosts, geographical distribution, and vector roles. Ticks and Tick-Borne Diseases 6 (6), 843e868. https://doi.org/10.1016/j.ttbdis.2015.07.014. Pereira de Oliveira, R., Hutet, E., Paboeuf, F., Duhayon, M., Boinas, F., Perez de Leon, A., Filatov, S., Vial, L., Le Potier, M.-F., Gladue, D., 2019. Comparative vector competence of the Afrotropical soft tick Ornithodoros moubata and Palearctic species, O. erraticus and O. verrucosus, for African swine fever virus strains circulating in Eurasia. PLoS One 14 (11), e0225657. https://doi.org/10.1371/journal.pone.0225657.

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CHAPTER

Tick classification and diversity

2

Ticks are classified into three families, the hard ticks or Ixodidae, the soft ticks or Argasidae, and a third family, the Nuttaliellidae, of which there is a single species of tick found only in Southern Africa, Nuttalliella namaqua. This species shares morphological features of the other two families but is clearly distinct. This chapter gives a brief description of the diversity and nomenclature of ticks focusing on the main approaches to identification and classification of ticks. Historically this has been dominated by morphological structure and has also been the source of much debate on how this leads to the classification of ticks, much of which remains to be resolved. The chapter will also consider alternative means of identifying ticks, particularly the growing field and role of molecular methods for identifying specimens and in turn what this tells us about tick evolution and the relationships between tick species around the world. While offering some benefits, these technologies still have their limitations, mainly in their cost, accessibility, and their dependence on existing classifications.

Introduction Ticks are ancient! We know this primarily because of examples of fossilized ticks that have been found trapped in amber and visualized using high-resolution microscopy (Chitmia-Dobler et al., 2017; Estrada-Pen˜a and de la Fuente, 2018; Pen˜alver et al., 2017). The morphology of the mouth parts, legs, and body are clearly comparable to tick species present today. Some specimens have been dated within the Miocene period, approximately 25 million years ago (mya), although others are much older and associated with the late Cretaceous at around 100 mya. It is striking to think that tick species similar to those found today were feeding on dinosaurs, and many extant tick species still feed preferentially on reptiles. However, as ancient as these dates are, evolutionary clock analysis based on the segments of the tick genome suggests that they can be traced further back to 200 mya (Beati and Klompen, 2019), with some authors suggesting an even earlier evolution going back to the Devonian period at over 360 mya (Mans et al., 2016). What precursor species lead to the evolution of ticks remains uncertain, but they evolved the distinct morphological structures what we would currently recognize as a parasitic tick. This implies a very early evolution and persistence through long periods of time in which the earth, its fauna and flora, and even its geography have changed dramatically. This Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00013-7 Copyright © 2023 Elsevier Inc. All rights reserved.

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suggests that the evolution of parasitism through blood feeding on vertebrates was an early and highly successful strategy for the early ticks.

Tick taxonomy Taxonomy is the science of naming, describing, and classifying organisms. Biologists have been naming, comparing, and classifying ticks for over 300 years beginning with the developer of the binomial naming system, Carl Linneaus, who described a number of species including what we now know as Ixodes ricinus, the common sheep tick. Morphological taxonomy is based on the identification of type specimens on which a new species is based with features that are unique to those specimens and allow discrimination from other species. Some of the individuals who have identified prominent tick species are listed in Box 2.1. Ticks are classified within the class Arachnida and are distantly related to spiders, mites, and scorpions; animals that in their adult form have eight legs arranged into four pairs. They are then placed within the subclass Acari (Box 2.2), with other parasitic forms such as mites. Like all other organisms, tick species are given a binomial latin name, and when first cited within a text, the species is usually accompanied by further information concerning who and when the species was first formerly described. Most species have one or more common names that reflect their distribution or host preference. For example, as mentioned above, I. ricinus is commonly called the common sheep tick, but it is also described as the deer tick or castor bean tick. Some tick species have different names in different locations. This highlights the benefit of the Linnean system, giving each species a unique binomial name

Box 2.1 Prominent tick taxonomists from the past three centuries. Gerald Augustus Harold Bedford (1891e1938): A British entomologist who specialized in ticks of South Africa and based at the University of Pretoria. He described seven species of tick including N. namaqua, Bedford (1931). Giovanni Canestrini (1835e1900): Italian zoologist and a strong supporter of Darwinism made a number of contributions to the study of ticks and described Rhipicephalus microplus, Canestrini 1888. Johan Christian Fabricius (1745e1808): Danish zoologist who studied under Carl Linnaeus. He specialized in the study of arthropods and named over 10,000 species including the tropical bont tick Amblyomma variegatum, Fabricius 1794. Harry Hoogstraal (1917e1986): An American entomologist and parasitologist who worked in North Africa. He made major contributions to tick discovery and taxonomy. Carl Ludwig Koch (1779e1857): German entomologist and arachnologist who classified many spiders and tick species such as Hyalomma marginatum Koch 1844. Pierre Andre´ Latreille (1762e1833): French zoologist specialized in arthropod biology. He first described the brown dog tick Rhipicephalus sanguineus, Latreille 1806. Carl Linnaeus (1707e1778): Swedish taxonomist who formalized the binomial naming system and was the first to describe I. ricinus, Linnaeus 1758. Thomas Say (1787e1834): American naturalist who described a number of North American ticks including Ixodes scapularis, Say 1821.

The families

Box 2.2 Tick classification Kingdom Phylum Subphylum Class Subclass Superorder Order Families

Animalia Arthropoda Chelicerata Arachnida Acari Parasitiformes Ixodida Ixodidae Argasidae Nuttaliellidae

for use within the scientific community. In theory, this ensures consistency when investigating the biology of a particular species. Taxonomy is also a subject that attracts remarkable disagreement between scientists. Any discussion of tick classification needs to acknowledge that a taxonomy is a snapshot of what is considered the scientific consensus on the identification, ordering, and naming of genera at a particular point in time. It is subject to constant change, often quite dramatic, as opinions vary, new species are detected and characterized, and new technologies offer different ways at defining taxa. This change is often the trigger for disagreement. An example of a dramatic change in tick classification was the reassignment of five species formerly classified within the genus Boophilus into the genus Rhipicephalus (Murrell and Barker, 2003). Thus, the tick commonly called the Asian blue tick and a tropical parasite of cattle that has been much investigated due to its prominent role as a vector of livestock disease, was renamed from Boophilus microplus, a name found throughout the scientific literature, to R. microplus. Also, any list of genera and the number of species within it is also subject to constant revision, so the table provided (Table 2.1) of tick genera and species numbers is given as a guide rather than a definitive classification. Numerous articles are regularly updating this at a country, regional, and global level for each genus. From the table, it is clear that certain genera are well represented and will be discussed in more detail in the following chapters.

The families Where there is consensus is that there are three well-defined families within the order Ixodida (Mans et al., 2016). This includes the Ixodidae or hard ticks, the Argasidae or soft ticks, and the Nuttaliellidae consisting of a single species. However,

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Table 2.1 Summary of tick families and key genera. Family

Genus (approximate number of species)

Nuttaliellidae Argasidae

Nuttalliella (1) Antricola (17) Argas (61) Ornithodoros (112) Otobius (2) Nothoaspis (1) Africaniella (2) Amblyomma (130) Anomalohimalya (3) Archeocroton (1) Bothriocroton (7) Cosmiomma (1) Cornuupalpatum (1) Dermacentor (34) Haemaphysalis (166) Hyalomma (27) Ixodes (246) Margaropus (3) Nosomma (2) Rhipicentor (2) Rhipicephalus (82) Robertsicus (1)

Ixodidae

Adapted from Gulielmone et al. (2010).

even here the exact relationship of these families to each other is debated. Different interpretations of the shared morphological characteristics and various phylogenetic analyses based on partial genomic sequences suggest multiple routes through which the families could have evolved to their current status. The following sections provide a brief overview of key features of each family.

The Ixodidae: the hard ticks The Ixodidae contains the largest number of species with representatives found in all biogeographical regions. Many transmit an array of pathogens to humans, livestock, and domestic pets. They are distinct by the morphological structure of the scutum or hard shield that covers the whole dorsal (upper) surface in males but only partially covers the surface in females. The capitulum, or mouth parts, is prominent and projects forward from the body and can be viewed dorsally. The hypostome is typically longer than those found on soft ticks and has more numerous denticles or backward facing “teeth.” Eyes, if present, are found close to the side of the scutum. Hard ticks have three life stages, larva, nymph, and adult, with each stage taking a single blood

The Nuttalliellidae: Nuttalliella namaqua the odd one out!

meal. Adult males may or may not take a blood meal depending on whether the species requires this for sperm development. The adult female generally feeds once on the host over the course of a number of days and can become engorged to many times its original size. This single feed enables the female of many Ixodid species to oviposit (egg laying) thousands of eggs. Hard ticks are found throughout the world, even in some of the most extreme environments such as Antarctica.

The Argasidae: the soft ticks Argasid ticks are both morphologically and behaviorally distinct from hard ticks. Immature and adult life stages do not have a dorsal scutum but a thickened cuticle that prevents loss of water. This is an adaptation to survival in tropical and subtropical regions, and furthermore they have the ability to tolerate high environmental temperatures. However, soft ticks are nidicolous, spending the majority of their existence within the burrows, nests, and caves that their vertebrate hosts occupy (Vial, 2009). This also includes human structures where they can be occasionally encountered, such as the infestation of houses by the bat tick, Argas vespertilionis (Socolovschi et al., 2012). By living predominantly in these locations, it buffers the tick from the extremes of drought and temperature experienced in more exposed locations. A further difference is observed in the feeding cycle with the nymphal stage being composed of multiple instars (immature forms within each life stage where the instar sheds it outer layer followed by rapid growth). Each instar feeds from the vertebrate host. This often lasts less than one hour, and molting to the next stage, of which there can be as many as 10. In addition, adult females will take multiple feeds, ovipositing a relatively small clutch of eggs (up to 500) after each blood meal. All of these may represent adaptions to host scarcity and extreme climatic conditions. However, the tick attempts to remain, if at all possible, within the hosts’ burrow.

The Nuttalliellidae: Nuttalliella namaqua the odd one out! The neat division of ticks into hard and soft ticks was confounded by the report of an unusual tick from Southern Africa in 1931. The species was found under rocks in Namaqualand, a region of Southern Africa that spans parts of Namibia and the Northern Cape Province of South Africa. The find was reported by the English entomologist Gerald Bedford (Bedford et al., 1931) who specialized in the ticks of South Africa. The specimens found were striking in that they appeared to share features of the well-characterized hard and soft ticks. These included a partly sclerotized pseudoscutum (hard tick), an apical capitulum (hard tick), a leathery integument (soft tick), few denticles on the hypostome (soft tick), and a preanal groove (hard tick). Very few specimens of this species were found over the coming years, which meant

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that an understanding of its biology and host-feeding preference were limited to speculation based on the vertebrates found in the region. By the late 20th century, less than 20 adult specimens had been described, all from sites in Namibia and South Africa and associated with a range of hosts including birds, lizards, and mammals. The age of the specimens, all prior to 1984, precluded the extraction of DNA for evolutionary analysis based on genetic sequence. A discovery of a new group of specimens published in 2011 (Mans et al., 2011) confirmed the morphological features of the species and allowed the application of molecular phylogeny to the classification of this species. A phylogeny based on the 18S rRNA gene placed N. namaqua as a basal group to the Argasidae and Ixodidae and enabled speculation about the original evolution of ticks.

Tick morphology Morphology underpins the classification of ticks, and a basic knowledge of tick anatomy is critical in identifying specimens to genus and species. Ticks can be viewed from above (dorsally) or from below (ventrally). Magnification is usually required to visualize most of the key morphological features of ticks as even the adult tick body is rarely more than a few millimeters in diameter. This becomes essential for immature forms that are much smaller. In the unfed state, ticks are remarkably thin but during feeding can expand to many times their prefeed weight and size. The tick body is composed of a form of chitin, termed sclerotin, which forms the toughened structure that encloses the tick body. Sclerotin is formed from a number of poorly characterized proteins that are heavily cross-linked with disulfide bonds. When first formed, it is flexible but hardens rapidly to form a horn-like structure and is prominent in structures such as the mouth parts and the scutum where mechanical strength is required. Ticks are not segmented, as found in many arthropod taxa, but can be divided into two partsdthe gnathosoma, also termed the capitulum, which forms the mouth parts of the tick, and the idiosoma, which includes the main body and legs (Fig. 2.1). The gnathosoma contains the basis capitulum, a structure that links the mouth parts to the body of the tick. Two palps, or sense organs, project from the basis capitulum and surround the hypostome, an inflexible harpoon-like structure that the tick inserts into the vertebrate host. Paired chelicerae are located ventrally to the hypostome and act as a series of blades that create the initial incision of the hosts’ skin. They are composed of a series of digits that allow flexibility and have lateral teeth that cut the skin and initiate the attachment process. The hypostome and chelicerae combine to form the preoral channel through which saliva is secreted and blood inbibed. This basic structure is found in all life stages of the tick. Larval ticks have three pairs of legs, while nymphs and adult ticks have four pairs. These are highly articulated giving the tick great maneuverability. The legs are attached to the body at a structure termed the coxa (I near the mouthparts and followed by II, III, and IV) and are composed of five sections, the trochanter

Tick morphology

FIGURE 2.1 Morphological features on the dorsal surface of a female Ixodes ricinus tick. The numbers refer to the (1) trochanter, (2) femur, (3) patella, (4) tibia, (5) tarsus, and (6) clasps. Image courtesy of Arran Folly.

attached to the coxa, femur, patella, tibia, and tarsus (Fig. 2.1). Attached to the tarsus are a pair of clasps that allow the tick to attach to vegetation or the host. On the dorsal surface of hard ticks is the scutum, a hardened shield-like structure that covers the entire surface of the male and partially covers the dorsal surface of the female tick. This can be a single color for genera such as Ixodes and Haemaphysalis or for some genera such as Dermacentor and Amblyomma can be ornate with multiple colors and patterns (Fig. 2.2). On the ventral surface are the genital and anal apertures, and in hard ticks, the anal grove. This can be used as a means of differentiating prostriata, such as Ixodes species, where the anal grove is anterior to the anus. Conversely, the metastriata are those where the anal grove is posterior and includes such genera as Haemaphysalis, Dermacentor, Rhipicephalus, Amblyomma, and Hyalomma. On both sides of the tick body after coxa IV are spiracular plates (Fig. 2.3) that forms the interface between the internal structures of the tick and the environment. This allows gaseous exchange. The plates join a network of spiracles (tubes) within the tick, which extend throughout the body. Around the fringes of the dorsal surface of some species are grooves, termed festoons, that can be used for morphological identification.

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FIGURE 2.2 Dorsal image of the palps surrounding the hypostome and the ornate scutum of a male Dermacentor reticulatus. Photo N. Johnson.

FIGURE 2.3 Scanning electron microscopic image of the spiracular plate of an adult Haemaphysalis punctata (red sheep tick) shown below the fourth leg. Image courtesy of Bill Cooley.

Identification of ticks using morphology

Identification of ticks using morphology Identifying ticks remains an important task for acarologists, ecologists, public health officials, and veterinarians due to the association between certain tick species and pathogens of medical or animal health importance. Morphological identification is usually achieved through established keys that allow the identification of ticks from a defined area such as a country or a region. The application of morphological keys usually requires some experience and ideally tuition to master. Clear inspection of a tick specimen necessitates that it is clean, achieved through washing in ethanol, and dry. If still alive, then it should be immobilized by placing on a sticky surface (blue tack or tape can achieve this) but able to be manipulated with fine tweezers. Magnification is almost always necessary to visualize a tick, especially for immature forms that can be less than a millimeter in diameter. Electron microscopy such as that used to create Fig. 2.3 is sometimes used to obtain high-resolution images to visualize tick anatomical structures. For engorged specimens, key features may not be visible due to the swollen appearance of the tick. In the case of larvae or nymphs, one solution is to allow the tick to molt to the adult form before attempting a definitive identification. This can be achieved through storage at ambient temperatures within a tube where humidity is kept high. Box 2.3 provides a summary of the morphological features that can assist in identifying a tick at least to genera (Mathison and Pritt, 2014). Long-term storage of specimens to ensure that morphological features are retained is possible through immersion in alcohol and/or at low temperatures. A 10% glycerol solution is also commonly used for storage at room temperature. The key benefits to morphological identification are its speed, minimal cost, and low technological requirements. However, it is also subject to a number of problems. Tick specimens can become damaged or distorted between collection and inspection. Furthermore, certain morphological features can be highly variable and closely related species can hybridize leading to a mix of structures. Immature forms of ticks and engorged females can also present a challenge to identification. Often voucher specimen or high-quality photographs are not available to support identification. More fundamentally, some type specimens have been poorly described or have

Box 2.3 Key morphological features for identifying ticks (Mathison and Pritt, 2014). Magnification of the specimen is recommended to visualize features that will enable identification. Specialist keys are available for many species. 1. Presence (Ixodid tick) or absence (Argasidae) of a dorsal shield. Complete dorsal coverage in males, anterior third in females. Color markings (ornamentation) on the scutum in some genera. 2. Shape of the basis capitulum. 3. Structure and visibility of the mouthparts. Length and width of the palps. 4. Presence or absence of eye structures on the body. 5. Presence or absence of festoons on the dorsal surface. 6. Orientation of the anal groove. A groove anterior to the anus indicates an Ixodes species.

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Table 2.2 Examples of morphological keys used to identify ticks. Tick group

References

Ticks within the Amblyomma genus from Africa.

Voltzit, O.V., Kierans, J.E. 2003. A review of African Amblyomma species (Acari, Ixodid, Ixodidae). Acarina 11, 135e214. Kierans, J.E., Litwak, T.R. 1989. Pictorial key to the adults of hard ticks, family Ixodidae (Ixodida: Ixodoidea), east of the Mississippi River. Journal of Medical Entomology 26, 435e438. Hillyard, P.D. 1996. Ticks of North-West Europe, published by Field Studies Series, Shrewsbury, United Kingdom. Estrada-Pen˜a, A., Mihalca, A.D., Petney, T.N. 2017. Ticks of Europe and North Africa, published by Springer International Publishing AG. Kwak, M.L. 2017. Keys for the morphological identification of the Australian paralysis ticks (Acari: Ixodidae), with scanning electron micrographs. Experimental and Applied Acarology 72, 93e101.

Hard ticks of the Northeast United States of America

Ticks of North-West Europe

Ticks of Europe and North Africa Morphological identification of Australian ticks responsible for cases of paralysis including Ixodes holocyclus, Ixodes cornuatus, and Ixodes hirsti. Morphological keys for identification of Hyalomma marginatum.

Apanaskevich, D.A. and Horak, I.G. (2008). The genus Hyalomma Koch (1844); V. Re-evaluation of the taxonomic rank of taxa comprising the H. (Euhyalomma) marginatum Koch complex of species (Acari: Ixodidae) with redescription of all parasitic stages and notes on biology. International Journal of Acarology 34, 13e42.

been lost, and for others, taxonomic status has not been agreed or is subject to dispute. Many identification keys have been developed but are often aimed at the species present in a particular country or region, and inevitably, rare species are not included (Table 2.2).

Identification of ticks using genetic sequence The challenges of relying on morphological identification alone have led researchers to develop alternative methods for identifying ticks. The application of sequence data to identify specimens has been widely adopted by scientists. This can be derived from the tick genome or the mitochondrial genome present in all cell types. This approach is useful when expertise in tick morphology is not available. It can also be the method of choice for specimens where key morphological features are damaged or absent, or for immature forms that lack these features. However, it is dependent on prior studies that have established sequence data for voucher specimens of morphologically confirmed species.

Identification of ticks using genetic sequence

The most common approach for species identification is the barcoding method that utilizes the cytochrome oxidase 1 mitochondrial gene (Cox1) to differentiate to species level (Hajibabaei et al., 2007). Examples of its application include the identification of ticks present in a defined area, for example, medically important ticks within a country (Ondrejicka et al., 2016; Filipe et al., 2017), the identification of immature forms of rare species (Lv et al., 2018), or the source of a tick blood meal (Lumsden et al., 2021). The approach can also be used to identify exotic ticks that have been brought into a country accidentally or illegally such as the detection of Hyalomma ticks in northern Europe (Bilbija et al., 2019; Uiterwijk et al., 2021; McGinley et al., 2021). Finally, the sequence data derived from this approach can also provide information on the relationship between a tick and other tick populations from across the species distribution range. For example, revealing the origin of the Asian long-horned tick (Haemaphysalis longicornis), whose natural range is across Asia but has recently been introduced into North America (Egizi et al., 2020). The approach can also be used to track the spread of a particular species. An extension to this approach is to use other components of the mitochondria genome including ribosomal RNA coding sequences as has been applied to the analysis of Rhipicephalus species (Coimbra-Dores et al., 2018). Taken to its ultimate end, the complete mitochondrial genome, consisting of between 14.5 and 15.3 kilobase pairs depending on the species, has been used to support the classification of tick groups. Kelava et al. (2021) have used this to provide insight into the evolution of Amblyomma ticks at a global scale. Alternative genomic sequence used for tick species identification include the internal transcribed spacer 2 (ITS-2) and the 18S rRNA gene. These sequences have been used to develop soft tick phylogeny (Burger et al., 2014). However, these sequences are usually used for detecting tick-borne pathogens rather than the tick itself. A general consensus is that two specimens that share over 96% sequence identity are likely to be from the same species (Lv et al., 2014). However, this is dependent on other scientists having made particular species sequence available for comparison, and there remain many gaps that limit definitive identification using this approach. Further disadvantages of this approach include the technology required to generate the sequence and the cost needed to obtain the result. These are clearly beyond the means of the amateur. Whereas morphological identification may be as straightforward as magnification and reference to an identification key, molecular identification can require homogenization of the sample, either the whole tick or a component such as a leg, extraction of DNA, polymerase chain amplification, and then sequencing. Then the application of bioinformatic analysis is required to make sense of the sequence information. Another major problem for a sequencebased approach is its reliance on the need for well-characterized specimens, identified by morphology, to which a sequence can be paired with. If such a sequence does not exist or limited sequence identity is achieved, then the specimen cannot be identified with any certainty. I have recently experienced this with an attempt to identify an African Amblyomma species that was brought into the United Kingdom in a consignment of leopard tortoise (Stigmochelys pardalis) from Zambia.

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Morphological identification based on relatively recent keys (Voltzit and Kierans, 2003) of the adult male specimen identified this to one of two closely related species, Amblyomma marmoreum or Amblyomma sparsum. DNA barcoding, using a partial sequence of the Cox I gene produced 658 base pairs of sequence, but when this was used to search sequence databases, the nearest hit was for A. marmoreum but at less than 95% identity suggesting that the specimen might be another species. No equivalent sequence was available for A. sparsum. A final problem is the misidentification of voucher specimens leading to misidentification of the sequence derived from it. In short, this approach, as applied to ticks remains in its infancy with a considerable amount of research required before it can reliably be applied to species identification in all circumstances and in all regions of the world. Despite these challenges, once sequences are consistently associated with particular species, this proves to be a very robust means of identifying all life stages of a tick species.

Identification of ticks using proteomics The alternative to using the genetic sequence of an organism to identify it is to use its protein content. This can be achieved using a process called matrix-assisted laser desorption ionization time-of-flight mass spectrometry or MALDI-TOF MS for short. This technique reduces the protein content of a sample, through proteolytic digestion, to a series of peptides and analyses the profile produced for a voucher specimen. The process is in the early stages of development but is being used to characterize a range of arthropod species (Murugaiyon and Roesler, 2017), many of medical importance. Recent applications of this method have been to identify African ticks (Diarra et al., 2017) and a panel of neotropical ticks (Gittens et al., 2020). The advocates of this approach suggest that it can rapidly identify a large number of ticks. However, the technology required to achieve this is very expensive and requires a high level of expertise to interpret data.

Conclusions Tick classification is a complex and often controversial subject, only touched on briefly in this chapter. Morphological assessment remains an essential method for the identification of ticks to genera and for significant tick vectors of disease, ideally to species. The main benefit of using this approach is its speed and low cost although requiring a high degree of expertise in those attempting to identify specimens, particularly for rarely encountered ticks or for discrimination between similar species. Immature forms or engorged specimens can also be difficult to identify. Even experts can be challenged by relatively good specimens as revealed by a recent comparative study of European experts where the initial misidentification rate

References

from a group of 14 institutions was 29.6% (Estrada-Pen˜a et al., 2017). Technological alternatives for tick identification, such as genetic or proteomic approaches, have been developed but require well-characterized specimens to begin with and require considerable investment to implement, well beyond the reach of the amateur acarologist. However, these technologies are providing support to existing classification systems and will be a cornerstone of tick taxonomy in the future, especially as the complete genomes of ticks are obtained and annotated (Barrero et al., 2017).

References Barrero, R.A., Guerrero, F.D., Black, M., McCooke, J., Chapman, B., Schilkey, F., Pe´rez de Leo´n, A.A., Miller, R.J., Bruns, S., Dobry, J., Mikhaylenko, G., Stormo, K., Bell, C., Tao, Q., Bogden, R., Moolhuijzen, P.M., Hunter, A., Bellgard, M.I., 2017. Geneenriched draft genome of the cattle tick Rhipicephalus microplus: assembly by the hybrid Pacific Biosciences/Illumina approach enabled analysis of the highly repetitive genome. International Journal for Parasitology 47 (9), 569e583. https://doi.org/10.1016/ j.ijpara.2017.03.007. Beati, L., Klompen, H., 2019. Phylogeography of ticks (Acari: Ixodida). Annual Review of Entomology 64, 379e397. https://doi.org/10.1146/annurev-ento-020117-043027. Bedford, G.A.H., 1931. Nuttalliella namaqua, a new genus and species of tick. Parasitology 23 (2), 230e232. https://doi.org/10.1017/S0031182000013573.  ´, P., 2019. Long term persistence of introduced Amblyomma geoBilbija, B., Auer, M., Siroky emydae tick population under indoor conditions in Austria. Medical and Veterinary Entomology 33 (2), 317e321. https://doi.org/10.1111/mve.12361. Burger, T.D., Shao, R., Labruna, M.B., Barker, S.C., 2014. Molecular phylogeny of soft ticks (Ixodida: Argasidae) inferred from mitochondrial genome and nuclear rRNA sequences. Ticks and Tick-Borne Diseases 5 (2), 195e207. https://doi.org/10.1016/j.ttbdis.2013. 10.009. Chitimia-Dobler, L., De Araujo, B.C., Ruthensteiner, B., Pfeffer, T., Dunlop, J.A., 2017. Amblyomma birmitum a new species of hard tick in Burmese amber. Parasitology 144 (11), 1441e1448. https://doi.org/10.1017/S0031182017000853. Coimbra-Dores, M.J., Maia-Silva, M., Marques, W., Oliveira, A.C., Rosa, F., Dias, D., 2018. Phylogenetic insights on Mediterranean and Afrotropical Rhipicephalus species (Acari: Ixodida) based on mitochondrial DNA. Experimental & Applied Acarology 75 (1), 107e128. https://doi.org/10.1007/s10493-018-0254-y. Diarra, A.Z., Almeras, L., Laroche, M., Berenger, J.M., Kone´, A.K., Bocoum, Z., Dabo, A., Doumbo, O., Raoult, D., Parola, P., 2017. Molecular and MALDI-TOF identification of ticks and tick-associated bacteria in Mali. PLoS Neglected Tropical Diseases 11 (7), e0005762. https://doi.org/10.1371/journal.pntd.0005762. Egizi, A., Bulaga-Seraphin, L., Alt, E., Bajwa, W.I., Bernick, J., Bickerton, M., Campbell, S.R., Connally, N., Doi, K., Falco, R.C., Gaines, D.N., Greay, T.L., Harper, V.L., Heath, A.C.G., Jiang, J., Klein, T.A., Maestas, L., Mather, T.N., Occi, J.L., Fonseca, D.M., 2020. First glimpse into the origin and spread of the Asian longhorned tick, Haemaphysalis longicornis, in the United States. Zoonoses and Public Health 67 (6), 637e650. https://doi.org/10.1111/zph.12743.

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Estrada-Pen˜a, A., D’Amico, G., Palomar, A.M., Dupraz, M., Fonville, M., Heylen, D., Habela, M.A., Hornok, S., Lempereur, L., Madder, M., Nu´ncio, M.S., Otranto, D., Pfaffle, M., Plantard, O., Santos-Silva, M.M., Sprong, H., Vatansever, Z., Vial, L., Mihalca, A.D., 2017. A comparative test of ixodid tick identification by a network of European researchers. Ticks and Tick-Borne Diseases 8 (4), 540e546. https://doi.org/ 10.1016/j.ttbdis.2017.03.001. Estrada-Pen˜a, A., de la Fuente, J., 2018. The fossil record and the origin of ticks revisited. Experimental & Applied Acarology 75 (2), 255e261. https://doi.org/10.1007/s10493018-0261-z. Filipe, D., Parreira, R., Pereira, A., Galva˜o, N., Cristo´va˜o, J.M., Nunes, M., Viera, M.L., Campino, L., Maia, C., 2017. Preliminary comparative analysis of the resolving power of COX1 and 16S-rDNA as molecular markers for the identification of ticks from Portugal. Veterinary Parasitology: Regional Studies and Reports 24, 100551. https:// doi.org/10.1016/jvprsr.2021.100551. Gittens, R.A., Almanza, A., Bennett, K.L., Mejı´a, L.C., Sanchez-Galan, J.E., Merchan, F., ´ lvarez, E., Kern, J., Miller, M.J., Esser, H.J., Hwang, R., Dong, M., De Leo´n, L.F., A Loaiza, J.R., 2020. Proteomic fingerprinting of neotropical hard tick species (Acari: Ixodidae) using a selfcurated mass spectra reference library. PLoS Neglected Tropical Diseases 14 (10), 1e18. https://doi.org/10.1371/journal.pntd.0008849. Guglielmone, A.A., Robbins, R.G., Apanaskevich, D.A., Petney, T.N., Estrada-Pe na, A., Horak, I.G., Shao, R., Barker, S.C., 2010. The Argasidae, Ixodidae and Nuttalliellidae (Acari: Ixodida) of the world: a list of valid species names. Zootaxa 2528, 1e28. https://doi.org/10.11646/zootaxa.2528.1.1. Hajibabaei, M., Singer, G.A.C., Hebert, P.D.N., Hickey, D.A., 2007. DNA barcoding: how it complements taxonomy, molecular phylogenetics and population genetics. Trends in Genetics 23 (4), 167e172. https://doi.org/10.1016/j.tig.2007.02.001. Kelava, S., Mans, B.J., Shao, R., Moustafa, M.A.M., Matsuno, K., Takano, A., Kawabata, H., Sato, K., Fujita, H., Ze, C., Plantard, O., Hornok, S., Gao, S., Barker, S., Barker, S.C., Nakao, R., 2021. Phylogenies from mitochondrial genomes of 120 species of ticks: insights into the evolution of the families of ticks and of the genus Amblyomma. Ticks and Tick Borne Diseases 12 (1), 101577. https://doi.org/10.1016/j.ttbdis.2020.101577. Lumsden, G.A., Zakharov, E.V., Dolynskyj, S., Weese, J.S., Lindsay, L.R., Jardine, C.M., 2021. The application of next-generation sequence-based DNA barcoding for bloodmeal detection in host-seeking wild-caught Ixodes scapularis nymphs. BMC Research Notes 14 (1), 67. https://doi.org/10.1186/s13104-021-05481-3. Lv, J., Wu, S., Zhang, Y., Chen, Y., Feng, C., Yuan, X., Jia, G., Deng, J., Wang, C., Wang, Q., Mei, L., Lin, X., 2014. Assessment of four DNA fragments (COI, 16S rDNA, ITS2, 12S rDNA) for species identification of the Ixodida (Acari: Ixodida). Parasites & Vectors 7, 93. https://doi.org/10.1186/1756-3305-7-93. Lv, J., De Marco, M.D.M.F., Goharriz, H., Phipps, L.P., McElhinney, L.M., Herna´ndezTriana, L.M., Wu, S., Lin, X., Fooks, A.R., Johnson, N., 2018. Detection of tick-borne bacteria and babesia with zoonotic potential in Argas (Carios) vespertilionis (Latreille, 1802) ticks from British bats. Scientific Reports 8 (1), 1865. https://doi.org/10.1038/ s41598-018-20138-1. Mans, B.J., Klerk, Pienaar, R., Latif, A.A., 2011. Nuttaliella namaqua: a living and closest relative to the ancestral tick lineage: implications for the evolution of blood-feeding in ticks. PLoS One 6, e49461. https://doi.org/10.1371/journal.pone.0049461.

References

Mans, B.J., de Castro, M.H., Pienaar, R., de Klerk, D., Gaven, P., Genu, S., Latif, A.A., 2016. Ancestral reconstruction of tick lineages. Ticks and Tick-Borne Diseases 7 (4), 509e535. https://doi.org/10.1016/j.ttbdis.2016.02.002. Mathison, B.A., Pritt, B.S., 2014. Laboratory identification of arthropod ectoparasites. Clinical Microbiology Reviews 27 (1), 48e67. https://doi.org/10.1128/CMR.00008-13. McGinley, L., Hansford, K.M., Cull, B., Gillingham, E.L., Carter, D.P., Chamberlain, J.F., Hernandez-Triana, L.M., Phipps, L.P., Medlock, J.M., 2021. First report of human exposure to Hyalomma marginatum in England: further evidence of a Hyalomma moulting event in north-western Europe? Ticks and Tick-Borne Diseases 12 (1), 101541. https:// doi.org/10.1016/j.ttbdis.2020.101541. Murrell, A., Barker, S.C., 2003. Synonymy of Boophilus Curtice, 1891 with Rhipicephalus Koch, 1844 (Acari: Ixodidae). Systematic Parasitology 56 (3), 169e172. https://doi.org/ 10.1023/B:SYPA.0000003802.36517.a0. Murugaiyan, J., Roesler, U., 2017. MALDI-TOF profiling e advances in species identification of pests, parasites and vectors. Frontiers in Cellular and Infection Microbiology 7, 184. https://doi.org/10.3389/fcimb.2017.00184. Ondrejicka, D.A., Morey, K.C., Hanner, R.H., 2016. DNA barcodes identify medically important tick species in Canada. Genome 60 (1), 74e84. https://doi.org/10.1139/gen-20150179. Pen˜alver, E., Arillo, A., Delclo`s, X., Peris, D., Grimaldi, D.A., Anderson, S.R., Nascimbene, P.C., Fuente, D.P.L., 2017. Ticks parasitized feathered dinosaurs as revealed by cretaceous amber assemblages. Nature Communications 8, 1924. https://doi.org/ 10.1038/s41467-017-01550-z. Socolovschi, C., Kernif, T., Raoult, D., Parola, P., 2012. Borrelia, Rickettsia, and Ehrlichia species in bat ticks, France, 2010. Emerging Infectious Diseases 18 (12), 1966e1975. https://doi.org/10.3201/eid1812.111237. Uiterwijk, M., Iba´n˜ez-Justicia, A., Vossenberg, Jacobs, F., Overgaauw, P., Nijsse, R., Daberkaussen, C., Stroo, A., Sprong, H., 2021. Imported Hyalomma ticks in the Netherlands 2018-2020. Parasit. Vectors 14 (1), 244. https://doi.org/10.1086/s13071021-04738-x. Vial, L., 2009. Biological and ecological characteristics of soft ticks (Ixodida: Argasidae) and their impact for predicting tick and associated disease distribution. Parasite 16 (3), 191e202. https://doi.org/10.1051/parasite/2009163191. Voltzit, O.V., Kierans, J.E., 2003. A review of African Amblyomma species (Acari, Ixodida, Ixodidae). Acarina 11 (2), 13e214.

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CHAPTER

The tick life cycle

3

Ticks, irrespective of classification, share a number of common features. The vast majority obtain nutrition through blood feeding on a vertebrate host, and all have multiple life stages from egg through to adult. However, within this life cycle, there is wide variation. To illustrate this, the following chapter describes the life cycles of a number of hard and soft ticks. Examples that include common ticks such as Ixodes ricinus and the African tick, Ornithodoros moubata, will illustrate the main features of the tick life cycle. A number of other species, such as one that feeds exclusively on bats, are included to illustrate particular behaviors that demonstrate this variation.

Introduction All ticks have multiple life stages, shown schematically in Fig. 3.1. The first is the larval stage that emerges from an egg. This seeks a host, takes a blood meal, and uses this to enable a molt to the nymphal stage. Again, the nymph takes a blood meal and molts to the adult stage, becoming either a male or female. Mating can occur on or off the host, and the female will use its blood meal to produce eggs. Although the term molting is commonly used to describe the transition of ticks from one stage to the next, it is actually a metamorphosis. The transition between each stage requires anatomical changes such as the development of a fourth pair of legs during the transition from larva to nymph and the development of sexual organs in the transition from nymph to an adult female or male. However, the term molting is commonly used to describe these processes. The tick life cycle is dominated by the need to obtain nutrition. While this is true for all organisms, in the case of ticks, especially for hard ticks, this is a single event that must be completed before moving to the next life stage. Soft ticks feed more often within each life stage, and this is especially critical at the nymphal stage where there are multiple instar stages, phases where the developing tick molts, after each blood meal, with as many as seven for some species. Only then will the nymph develop into an adult. For female soft ticks, oviposition, the act of laying eggs, may follow after a brief blood meal, but this might happen multiple times, whereas hard ticks tend to oviposit one large batch of eggs after a single blood meal. Once a blood meal has been acquired, the rate of development of a tick is highly dependent on the environmental conditions experienced (Estrada-Pen˜a, 2015). Higher temperatures will promote molting and oviposition, although Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00005-8 Copyright © 2023 Elsevier Inc. All rights reserved.

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FIGURE 3.1 Schematic showing the simplified life cycle of hard and soft ticks. There are two immature stages, larva and nymph, that precede the adult stage. Hard tick nymphs take a single blood meal, whereas soft tick nymphs will take multiple blood meals, molting after each.

reduced humidity will increase water loss, a feature that can threaten tick viability. Low temperatures restrict development and can also lead to the death of a tick. Adaptation to life within the host’s burrow, endophilous behavior, can mitigate to some extent the impact of variations in weather. However, climate can have a dramatic effect on ticks, and why predictions of climate change are critical to understanding future distribution and abundance of many important tick species. Tick mating varies depending on the genera. Ixodes species mate on and off the host, whereas species belonging to the genera Dermacentor, Amblyomma, and Rhipicephalus only mate while on the host while the female feeds (Kiszewski et al., 2001). Males produce a spermatophore, a protein capsule containing spermatozoa that they manipulate with their palps and insert into the female’s genital aperture. Fertilization occurs once the female has taken a blood meal. Eggs mature and the female oviposits, often laying thousands of eggs. During oviposition, females are

Hard ticks

at risk of predation by a range of predators including spiders, wasps, and birds (Guglielmone and Mosa, 1991; Dantas-Torres, 2010). Within these generalizations, there is great variety in the life cycles of particular ticks. To explore this further, ten tick species have been selected to illustrate this (Table 3.1). Variation in the type of host selected by each life stage and the environments preferred are all discussed, ranging from extreme environments such as those found in Antarctica through to the comfort found in human habitations. The choice of host also dictates whether a tick will interact with humans or their domestic animals and whether it can act as an effective vector of disease.

Hard ticks

Ixodes ricinus (Linnaeus, 1758)da questing tick I. ricinus was first described by Carl Linnaeus (1707e78), the Swedish taxonomist who formalized the binomial naming system. I. ricinus, commonly referred to as the castor bean, sheep, or deer tick, is the most abundant and widespread tick species found across Europe, including Iceland (Alfredsson et al., 2017). In North America, the black-legged tick, Ixodes scapularis, and from Eastern Europe to East Asia, the taiga tick, Ixodes persulcatus, occupy a similar ecological niche to I. ricinus. I. ricinus has also been detected in small foci in North Africa. Despite this widespread abundance, the species is highly susceptible to desiccation when off the host and spends the vast majority of its life within the vegetative layer where humidity levels are above 80%. It only ventures out to seek a vertebrate host. This limits its presence to areas with moderate to high rainfall, and within areas of deciduous Table 3.1 Summary of ticks reviewed in this chapter. Family

Specie

Common name

Ixodidae

Ixodes ricinus (Linnaeus, 1758) Ixodes uriae (White, 1852) Dermacentor reticulatus (Fabricius, 1794) Hyalomma marginatum (Koch, 1844)

Castor, sheep, deer tick Seabird tick Ornate cattle, winter tick Mediterranean Hyalomma tick Lone-star tick Asian blue tick Brown dog tick Asian long-horned tick

Argasidae

Amblyomma americanum (Lineaus, 1758) Rhipicephalus microplus (Canestrini, 1888) Rhipicephalus sanguineus (Latreille, 1806) Haemaphysalis longicornis (Neumann, 1901) Argas vespertilionis (Latreille, 1802) Ornithodoros moubata (Murray, 1877)

Short-legged bat tick African hut tampan

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CHAPTER 3 The tick life cycle

woodland or mixed forest. The species can also be found in upland grazing areas and is increasingly being found in urban areas where the opportunity to bite and transmit pathogens to humans is increased (Rizzoli et al., 2014). I. ricinus activity follows two peaks, one during the spring and early summer when all life stages can be found, and then a later summer peak when adults again begin to host seek. There is virtually no activity during the winter months. Larvae emerge and are barely visible to the naked eye but are distinguished by having only 3 pairs of legs. After feeding, they develop into nymphs whose body is between 1.3 and 1.5 mm in diameter and have the full complement of 4 pairs of legs. The adults are larger again with males being between 2.4 and 2.8 mm and females being 3 to and 3.6 mm. Ixodes spp. ticks are characterized by an anterior anal groove, the scutum lacks ornamentation, and they lack eye structures. The male scutum covers the entire dorsal surface, whereas the females’ scutum only covers approximately half the surface and is a simple means of distinguishing male and female unfed ticks. The reduced scutum coverage allows the female to engorge to as long as 1 cm in length and increasing to almost 100 times its original weight (see Fig. 3.2). Mating can occur on or off the host. The mated female will detach from the host and digest the blood meal, using this to develop more than 1000 eggs that it will oviposit in a single egg-laying session that can take days to complete. After this the female dies. I. ricinus locates its host through an ambush strategy, termed questing, with the tick climbing to a prominent location on vegetation and waiting for the host to pass. To aid the tick, it has sense or Haller’s organ, on the tarsus of the first pair of legs that detects changes in temperature and CO2. As the host approaches, the tick typically raises its front two legs with any contact with host fur or feathers allowing the tick to

FIGURE 3.2 Engorged female Ixodes ricinus ticks removed from cattle in southwest England. Note male attempting to mate with one of the engorged females. Three of these ticks oviposited approximately eight weeks after removal from the host. Photo N. Johnson.

Hard ticks

grasp the host using its paired claws. The tick then selects a site on the host, usually where the host is unable to access the tick and begins the feeding process (see next chapter). The species is a three-host tick with each life stage feeding once before progressing to the next life stage in the case of immature forms, or to egg development and oviposition for mated females. This can take up to three years to complete depending on the success of the questing tick in finding and then feeding on a host. The hosts selected by different life stages of I. ricinus are determined by size and the height to which each life stage quests. Immature forms generally feed on smaller mammals, reptiles, and birds, whereas adults will take on the largest of mammals, including livestock. Having said this, the choice of hosts selected by this species is vast with some authors suggesting over 160 vertebrate hosts reported to be fed on by this species (Estrada-Pen˜a and de la Fuente, 2016). This in parts means that I. ricinus can vector a large number of pathogens to a wide variety of hosts, often in ways that are poorly understood. Despite being one of the most highly studied vectors of disease, many questions remain about its ecology and effective means to predict and control disease transmission by this species (Gray et al., 2021).

Ixodes uriae (White, 1852)da nest dweller Ixodes uriae, also known as the seabird tick, has a global distribution and is probably the most widely found tick species in the world (Dietrich et al., 2014). This is almost certainly due to its preferential feeding on seabirds, with over 84 species being reported to be predated by the species (Mun˜oz-Leal and Gonza´lez-Acun˜a, 2015). Long distance movement of birds with attached ticks have likely seeded the species around the globe. Most reports of its identification come from coastal locations and islands, but this includes findings in both the Arctic and Antarctic and most points in between. Some authors have suggested that the species originated in Australia and has achieved a bi- and circumpolar distribution through the migration of seabirds (Gylfe et al., 2001). In addition to feeding on seabirds, the species is occasionally found on other vertebrates including humans where it can give a particularly painful bite. As described for I. ricinus, the species has four life stages with each postembryonic stage feeding on a host. I. uriae appears to show a combination of behaviors to locate a host. Adults quest to encounter adult bird species, whereas immature forms are restricted to the nests and burrows of birds to feed on chicks (Muzaffar and Jones, 2007). Adult females (Fig. 3.3) are relatively large, with a body up to 4 mm, with narrow, pointed palps clearly separated either side of the hypostome. Depending on the life stage, feeding can take between 3 and 12 days to complete engorgement. The engorged tick then drops off, finds a sheltered location close to where the host nests, and develops into the next stage within the substrate. Males are usually detected in the substrate suggesting that mating occurs off the host. The time taken to complete the life cycle varies from two years where conditions permit to up to seven years. This is heavily influenced by the hosts’ breeding season, which dictates the availability of new hosts on which to feed, and can be of short

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FIGURE 3.3 Image of Ixodes uriae showing two engorged females and two nymphs removed from a gannet (Morus bassanus). Photo N. Johnson.

duration when the host is using the breeding colony. The other factor influencing development is that of environmental temperatures that can be very low in regions of the world where the tick species and its seabird host are found. Periods of tick activity are intimately linked with breeding behavior within colonies of birds (Barton et al., 1996; Frenot et al., 2001; Major et al., 2009). This can lead to reproductive isolation of tick populations as they become isolated in bird colonies. If the bird colony fails or moves to another location, the resident tick population will eventually perish. A number of bacterial species have been detected in I. uriae, including Borrelia garinii, Borrelia burgdorferi sensu stricto, Rickettsia spp., and Coxiella spp. A striking feature of I. uriae is the preponderance of viruses detected in the species (Labuda and Nuttall, 2004). Some reports put this at over 100 viruses (see Table 3.2), which is even more remarkable when most were detected before the development of mass sequencing techniques. The discovery of diverse viruses associated with I. uriae has continued using more recent detection methods (Major et al., 2009; Pettersson et al., 2020). Despite this abundance of viruses, they do not appear to cause disease

Table 3.2 Summary of viruses associated with Ixodes uriae. Virus family

Virus genus

Group

Number of viruses

Reoviridae Bunyaviridae

Orbivirus Nairovirus Phlebovirus

Flaviviridae

Flavivirus

Great Island virus Hughes virus Sakhalin virus Uukuniemi virus Seabird tick-borne virus Unassigned tick-borne virus

33 6 9 17 3 4

Adapted from Mun˜oz-Leal, S., Gonza´lez-Acun˜a, D. 2015. Ticks and Tick-Borne Diseases 6 (6), 843e868. https://doi.org/10.1016/j.ttbdis.2015.07.014.

Hard ticks

within the bird populations on which the ticks feed and which many of the viruses must infect in order to persist.

Amblyomma americanum (Linnaeus, 1758)da vector on the rise Amblyomma americanum was first described by Carl Linnaeus, presumably derived from specimens brought to Europe as the species is only found in North America. The species is commonly known as the lone star tick due to the distinctive pale gray spot on the posterior of the scutum of females. In the United States, it is found between Texas and the east coast, and to the north with populations present as far as the state of Maine in the far north-east around latitude of 45 . To the south, it is found across central and southern Mexico. The species appears to be spreading north in response to climate change and is a concern for disease threats to humans (Sonenshine, 2018). Similar to Ixodes spp., A. americanum is a three-host tick with each of the life stages feeding on a different host. The adults preferentially feed on large mammals with very high infestations, occasionally reaching over 2000 ticks, being recorded on the ears of cattle and deer. In cattle, this can lead to the deformation of the ear caused by secondary infections. Hyperinfestation in juvenile deer can lead to premature death. Human biting by A. americanum is commonly reported across its range. The species is sexually dimorphic, but both males and females are brown with the only difference being the pale spot on the dorsal surface of the females. Males have mixed colored scutum covering the whole dorsal surface with distinctive festoons, the grooved areas that form the margin of the tick body. Females have less distinct festoons, and the scutum covers only half the dorsal surface. The mouthparts are long and thin with a substantial hypostome. Female engorgement can take a number of days and a fully fed tick can weigh 5 g. Mating occurs on the host, and the species is remarkably productive with fertilized females able to lay in excess of 20,000 eggs. There is strong evidence that A. Americanum can transmit a range of diseases such as transmission of Ehrlichia chaffeensis, the etiological agent of human monocytotropic ehrlichiosis, and Francisella tularensis (Goddard and Varela-Stokes, 2009). In addition, feeding on deer enables the tick species to transmit the protozoan parasite Theileria cervi between deer (Yabsley et al., 2005). The transmission of other pathogens has been suggested but there is less conclusive evidence to support this, for example, the recently described Heartlands virus in the United States (Brault et al., 2018). Due to its role as a disease vector, changes in its distribution in response to climate change are being investigated with predictions that it will spread further north and into the American Midwest (Raghavan et al., 2019).

Dermacentor reticulatus (Fabricius, 1794)dan ornamented tick Dermacentor reticulatus was first described by Johan Christian Fabricius (1745e1808), a Danish zoologist who specialized in the study of arthropods and

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a student of Carl Linnaeus. A prolific taxonomist who named over 10,000 animal species. D. reticulatus goes by a number of common names including the ornate cattle tick, the winter tick, and marsh tick reflecting it feeding on livestock, activity during the winter months, and prevalence in waterlogged habitats. The genus Dermacentor contains over 35 species with both D. reticulatus and its closely related and morphologically similar sibling, Dermacentor marginatus, present in Europe. They are distinct from other tick species in Europe by the presence of white ornamentation on the scutum (Fig. 3.4) Adult D. marginatus are slightly larger than D. reticulatus with the latter having a palpal spur that is absent in D. marginatus. The species is present across much of Europe and Central Asia (extensively reviewed by Fo¨ldava´ri et al., 2016). D. reticulatus is another three-host tick, but the larval and nymphal stages are nidicolous, remaining in the burrows and feeding on small mammals and birds (Pfa¨ffle et al., 2015). The adult life stages are exophilic and prefer to feed on medium to large mammals. As a result, immature forms are rarely collected by flagging surveys. Adults feed for between 7 and 15 days to achieve full engorgement. Mating occurs on the host with fertilized females dropping off and laying between 3000 and 7000 eggs. Larvae emerge to feed during May and June, molting into nymphs during the same summer with resulting nymphs active between July and August. Adults will then feed during the late summer or diapause over the winter as unfed adults resulting in two periods of activity in early spring and autumn (Fig. 3.5). As a result, the tick species has one of the shortest life cycles of any hard tick, sometimes being complete within a single year. Although not as abundant and widespread as I. ricinus, D. reticulatus is a vector of a range of pathogens of livestock, companion animals, and humans (Table 3.3). Discovery of new populations of this tick species represents increased risk of disease transmission to humans and certain domestic species such as dogs, horses, and cattle (Hofmeester et al., 2016).

FIGURE 3.4 Dorsal view of a male Dermacentor reticulatus showing scutum ornamentation. Photo C. Phipps.

Hard ticks

FIGURE 3.5 Seasonal activity of the different life stages of Dermacentor reticulatus in Europe.

Table 3.3 A summary of pathogens transmitted by Dermacentor reticulatus. Animal pathogens

Human pathogens

Babesia canis Babesia caballi Theileria equi Anaplasma marginale

Omsk hemorrhagic fever Tick-borne encephalitis virus Rickettsia slovaca Rickettsia raoultii Francisella tularensis Coxiella burnetii

Hyalomma marginatum (Koch, 1844)da hunting tick Hyalomma marginatum was first described by Carl Ludwig Koch (1778e1857), a German entomologist and arachnologist who classified many spider and tick species. The genus Hyalomma consists of a large number of aggressive ticks that transmit a range of pathogens. The name Hyalomma is derived from the Greek for glass (hyalos) and eye (omma) due to the presence of eye structures on the dorsal surface of species within the genus. H. marginatum is distributed across Africa, southern Europe, the Middle East, and Asia. The species is a hard tick with a dark brown scutum that lacks ornamentation. The legs have small white spots that can appear band-like when magnified. The larvae and nymphs are challenging to identify to species using morphological keys, and it is recommended to allow engorged nymphs to molt to adulthood prior to attempting identification. Recent studies have used sequencing of the cytochrome oxidase subunit I (COI) gene to discriminate the members of the H. marginatum complex (Schultz et al., 2020). The species is a two-host tick with the larvae selecting small mammals such as rabbits and hares or ground-dwelling birds to feed on (Valca´rcel et al., 2020). Once engorged, the larvae will molt while on the host and the resulting nymph will feed on the same host before detachment to molt on the ground. This means that it is rare to find the nymphal stage of H. marginatum in the environment. Whereas all postembryonic life stages of sympatric species such as H. lusitanicum, a three-host tick, can be detected (Valca´rcel et al., 2020). The adult that emerges will usually diapause in an unfed state over winter before actively “hunting” for a vertebrate host, usually a large ungulate, on which to feed. A range of methods are used to detect the prey

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including carbon dioxide, chemicals released from urine, vibration, body heat, and movement. Once detected, the tick runs rapidly toward the host over a number of meters and for up to 10 min. The tick attaches rapidly. When observed, H. marginatum ticks have been observed to attach, retract palps, and insert the hypostome within seconds of contact with the host. Domestic cattle are a common prey species, and the tick also readily feeds on humans. Mating occurs on the host and fertilized females detach, laying over 15,000 eggs. The extended time spent by the immature stages on birds means that dispersal by bird migration is possible and Hyalomma ticks are regularly detected on birds migrating to northern Europe (Capek et al., 2014; England et al., 2016). However, the species favors warmer climates and are generally active at temperatures above 22 C. There is currently evidence that Hyalomma spp. can molt successfully in Central Europe (ChitimiaDobler et al., 2019) when introduced leading to concerns that species such as H. marginatum will start to colonize more northerly latitudes. At extreme temperatures above 30 C, H. marginatum will seek shelter (Choubdar et al., 2019). H. marginatum has been associated with a number of pathogenic agents including Anaplasma marginale and Rickettsia conorii, but the one that is of most concern is CrimeaneCongo hemorrhagic fever virus. As the name suggests, infection in humans lead to systemic infection that can in severe cases lead to bleeding from mucosal surfaces. Infections have been reported in the Balkans and Iberian Peninsula of Europe, areas where the tick is endemic. Recent tick surveys have shown that the virus is firmly established in Hyalomma spp. across Spain (Sa´nchez-Seco et al., 2022).

Rhipicephalus microplus (Canestrina, 1888)da one host tick Rhipicephalus microplus was first described by the Italian naturalist and botanist Giovanni Canestrini (1835e1900) who was active in a number of biological fields including acarology. Until quite recently, the species was classified within the genus Boophilus, and this name is often included as a subgenus, Rhipicephalus (Boophilus). However, the species is considered a complex that includes R. (Boophilus) microplus, Rhipicephalus (Boophilus) annulatus, and Rhipicephalus (Boophilus) australis, and another three species (Burger et al., 2014). R. microplus has the dubious distinction of being considered the most important tick species of livestock in the world. It has achieved this through widespread invasion of tropical and subtropical regions on three continents, the debilitating effects of hyperinfestation, and the impact of the diseases it transmits to cattle. It also readily feeds on other domestic animals including horses, goats, sheep, and pigs. To add to the challenge, this tick species has a long history of showing a high tolerance for, and rapidly developing resistance to, acaricides (Kumar et al., 2020). The species has a range of common names depending on its location, the Asian blue tick in India and Africa, Australian cattle tick in Australia, and the Southern Cattle tick in North America. R. microplus was originally indigenous to South and Southeast Asia but hitchhiked on cattle being transported to Madagascar and East Africa during the 19th

Hard ticks

century and then on to South America (Barre´ and Uilenberg, 2010). It has also been introduced into Australia and was present in the southern United States, before being eliminated during the early 20th century through a concerted campaign implemented over decades. In recent years, R. microplus has been introduced into West Africa (Madder et al., 2007) where it has outcompeted indigenous tick species (Muhanguzi et al., 2020) and threatens livestock, and ultimately the food supply to millions of Africans. Apart from its notoriety as a vector of disease to livestock, R. microplus is distinct from the other tick species discussed in this chapter as it is a one-host tick meaning that all stages of the species feed on the same animal. The larva seeks a host, attaches, and feeds. It will then molt to the nymphal stage, feed, and then molt again to reach the adult stage. Males take a blood meal before becoming sexually active on the host. Mated females take a blood meal before detaching and ovipositing in a protected place such as below stones. Remarkably, the life cycle can be completed within three to four weeks leading to heavy infestations of cattle. Such infestations can lead to hide damage and failure to thrive in young animals. The species is also a vector of babesiosis and anaplasmosis.

Rhipicephalus sanguineus (Latreille, 1806)da tick adapted to man’s best friend Rhipicephalus sanguineus was first described by Pierre Andre´ Latreille (1762e1833), a French zoologist who specialized in entomology and described a large number of arthropods. He introduced the concept of “type species” to represent the typical morphology of a genus. R. sanguineus, commonly called the brown dog or kennel tick, is found throughout the world and may be the most widespread tick species. This has resulted from the feeding preference of the species for the domestic dog and the ability of the tick to infest human habitation. This has enabled the tick to spread to almost anywhere humans and their dogs are present (Dantas-Torres, 2010). The coloring of its body ranges from yellow to brown, and despite having a relatively short hypostome compared to other Ixodid species, attaches firmly to the host during feeding. The length of blood feeding can vary from two to five days for larvae, three to six days for nymphs, and up to two weeks for females. Males also take short blood meals while on the host as they require nutrition for sperm development and have been observed detaching from one host, then locating and feeding on a second (Little et al., 2007). Mating occurs on the host. Although a three-host tick species, all life stages will preferentially feed on the domestic dog. R. sanguineus will feed on other mammals that are encountered within enclosed habitats including cats, rodents, and occasionally humans. Once a host has been located, the tick has preferred sites for attachment, including the ears, interdigital spaces, and the inguinal region. Once fully engorged, the tick detaches and mated females will locate a concealed space to allow egg development and oviposition. Females of the species can produce as many as 4000 eggs.

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Although much is known about R. sanguineus, the widespread distribution of the species and the variable descriptions of their morphology means that the taxonomic status of the species is disputed. Some authors have suggested that the species should be considered a complex that includes at least 12 species (see Gray et al., 2013; Nava et al., 2015). Preferential feeding on the domestic dog means that R. sanguineus is an effective vector of canine disease such as babesiosis and ehrlichiosis. It occasionally transmits rickettsial diseases to humans, particularly Mediterranean spotted or boutonneuse fever caused by infection with R. conorii. Although predominantly found in tropical and subtropical regions, R. sanguineous is regularly introduced into more northerly temperate regions through movement of pet dogs. The tick species has not established at these latitudes although examples of infestation in which the ticks overwinter in centrally heated houses have been documented (Hansford et al., 2015).

Haemaphysalis longicornis (Neumann, 1901)dthe invader The Asian long-horned tick, Haemaphysalis longicornis, is native to East Asia where it feeds on a range of wildlife and livestock. Morphologically, the species is typical of the genus with a brown patterned scutum and a light-brown body. In females, the body measures approximately 2 mm in length but can increase to almost a centimeter in the engorged state. The species is distinct as a vector of a wide range of pathogens to humans and livestock. In addition, it has proven highly invasive with populations established in both Australia and New Zealand where it readily feeds on cattle and has become a significant vector of the protozoan cattle pathogen Theileria orientalis (Heath, 2016). Recently, the species has been introduced into the United States of America and spread into States on the East Coast. Modeling predicts that the species is capable of further spread to South America, Europe, and Africa if given the opportunity by human-mediated translocation (Zhao et al., 2020). Its invasive properties are assisted by the ability of some populations of the tick to reproduce through parthenogenesis or asexual reproduction without the requirement of egg fertilization. All other aspects of the tick life cycle are retained including multiple life phases and the requirement to blood feed. The property was observed in the 1970s and although rare has been observed in a small number of tick species. In China, populations of parthenogenic H. longicornis are found sympatrically with bisexual groups. There are chromosomal differences between the two types (Oliver et al., 1973) and minor morphological differences (Oliver and Herrin, 1976; Chen et al., 2012), with parthenogenic females being larger than corresponding bisexual equivalents, but producing similar volumes of eggs but with a slightly lower hatching success rate. All parthenogenic offspring are females and capable of further reproduction. There was no evidence of hybridization between the two types. However, the ability to reproduce in this way has increased the species ability to establish in new location.

Soft ticks

Soft ticks

Ornithodoros moubata (Murray, 1877)dinto the burrows O. moubata was described by Andrew Murray (1812e78), a Scottish naturalist who worked in Edinburgh and London. O. moubata is commonly called the African hut tampan in Southern Africa. This is due to it being commonly found in human houses across African (Haresnape and Mamu, 1986) and tampan being a name for a tick in Southern Africa. The species is distributed across a large region of East and Southern Africa. It belongs to a growing genus of Afrotropical soft ticks that share similar morphology and biology (Bakkes et al., 2018). As a soft tick, the mouth parts of all life stages of the tick are found on the underside of the tick and are not visible from above (Fig. 3.6, right hand panel). Adults lack a scutum but have a leathery cuticle covering the dorsal surface that is black or dark brown. O. moubata lack eyes, hence the alternative common name of the eyeless tampan. Females are typically 10 mm in length with males being slightly smaller at 8 mm. When engorged, females increase in size approximately fivefold, considerably less than the 100-fold increase observed for most hard ticks (Flynn et al., 2020). Egg laying occurs off the host in sheltered sites. Larvae emerge and require one blood meal before developing into the nymphal stage. Nymphs will take multiple feeds, molting to the next instar between two and seven times before development into the adult stage. Adults, particularly females, will take multiple feeds

FIGURE 3.6 Images of the Africa hut tick Ornithodoros moubata showing the ventral (left-hand panel) and dorsal (right-hand panel) views of the tick. Photo N. Johnson.

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ovipositing after each feed. The natural hosts for O. moubata are wild swine such as the African warthog (Phacochoerus africanus), with all life stages of the tick occupying animal burrows. Domestic pigs and poultry are also bitten by the tick, and livestock accommodation can become infested. Humans are occasionally bitten by O. moubata. The species is associated with tick-borne relapsing fever due to transmission of a number of Borrelia species including Borrelia duttoni (Cutler et al., 2009; Elbir et al., 2013) and African swine fever in domestic pigs (Sa´nchez-Vicaı´no et al., 2015). Trials have shown that Ornithodoros species are susceptible to commercial acaricides (Sharma et al., 2017) offering a means of suppressing tick populations. Attempts to identify potential protein targets for antitick vaccines are being made directed at the saliva contents of O. moubata (Oleaga et al., 2021).

Argas vespertilionis (Latreille, 1802)dlife on the wing Some ticks focus on a particular host that in turn has led to adaptation to feeding on that host. This is the case of those tick species that feed on bats (Sa´ndor et al., 2019). Prominent within this group is the soft tick Argas vespertilionis. The species is commonly called the short-legged bat tick and feed predominantly on insectivorous bats such as the common pipistrelle (Pipistrellus pipistrellus) and the Daubenton’s bat (Myotis daubentonii). Like its host, A. vespertilionis has a wide geographical distribution from Western Europe to East Asia. There have also been reports of this tick species in North Africa. The species’ adaptation to bats means that it is restricted to a single host for all its life stages. Larvae (Fig. 3.7) attach to the bat host and will feed for a number of days. The nymph and adult stages will only feed on the host briefly, while the bat roosts, typically for less than an hour. As a result, surveys of bats usually only detect larvae (Lv et al., 2018). The body of adults has a diameter of approximately 4 mm. In order to feed on bats, A. vespertilionis is only found in locations where bats roost including caves and tree holes. The periods of the year when the species is active also reflects those times when the bats are most active with peaks in spring, during the months of April and May, and during the summer and autumn months (Sa´ndor et al., 2019). During the winter months when temperatures are low, often below freezing, insectivorous bats in the Northern Hemisphere hibernate and A. vespertilionis is inactive. A. vespertilionis has a reputation for being an aggressive biter of humans when it is encountered. On one occasion, biting by the tick resulted in severe erythema and ulceration on the arms and legs of two people who were bitten while asleep (Jaenson et al., 1994). Of further concern is the long list of zoonotic pathogens detected in the species including Babesia, Borrelia, and Rickettsia species (Socolovschi et al., 2012; Lv et al., 2018). However, examples of transmission of disease from bat ticks to humans are very rare.

Conclusions

FIGURE 3.7 Dorsal view of Argas vespertilionis larvae removed from a bat in the United Kingdom. Photo N. Johnson.

Conclusions The choice of host appears to be a defining feature of all tick species. This dictates the likelihood of the tick encountering humans or livestock, transmitting disease and being considered sufficiently detrimental to require active suppression. Species such as I. ricinus and R. microplus definitely fall into this group. Other species such as I. uriae and A. vespertilionis, which having adapted to feeding on a particular host are rarely encountered. Where the choice of host changes with different life stages, this creates a highly complex web of interactions, along which tick-borne pathogens are transmitted. This can also influence methods of tick surveillance, for example, failure to detect Hyalomma nymphs as larvae remain on the host during the molt into the nymphal life stage. This raises a fundamental question for tick biology. Why have multiple life stages when the acquisition of a blood meal is probably the most hazardous event a tick will undertake in its life? If the tick is unable to locate a host, fails to complete the blood meal, or the host is able to remove the feeding tick, then it will not complete its life cycle. While off the host and undergoing molting, the tick is also at risk of dehydration, so again, undergoing multiple stages appears to be a risky strategy. The reason for the multiple life stages is probably due to the limitations placed on the tick by the method of blood feeding and the restriction on growth from having a rigid exoskeleton. On taking a blood meal, a tick will swell to many times its original size making it more visible to the host and increasing the likelihood that it will be removed or damaged. A single blood meal taken by a larva is unable to provide sufficient nutrition to produce an adult tick, so a further life stage is required with another round of feeding. Again, a single blood meal taken by a nymph is not

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sufficient to produce eggs by an adult female, so a further blood meal is required to provide the nutrients and energy to enable egg development. At each stage, the tick molts and a larger more mature form develops. Despite these challenges, ticks have been remarkably successful and highly adaptable to the opportunities provided by human modification, particularly domestication of livestock and the spread of domestic animals around the globe. Although humans are relatively large mammals, found on all continents and highly abundant, we have not found ourselves to be an exclusive host for any tick species, yet.

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Gylfe, A., Yabuki, M., Drotz, M., Bergstro¨m, S., Fukunaga, M., Olsen, B., 2001. Phylogenetic relationships of Ixodes uriae (Acari: Ixodidae) and their significance to transequatorial dispersal of Borrelia garinii. Hereditas 134 (3), 195e199. https://doi.org/10.1111/ j.1601-5223.2001.00195.x. Hansford, K.M., Pietzsch, M.E., Cull, B., Medlock, J.M., Wall, R., 2015. Overwintering of the brown dog tick in residential properties in England - raising awareness. The Veterinary Record 177 (6), 156. https://doi.org/10.1136/vr.h4227. Haresnape, J.M., Mamu, F.D., 1986. The distribution of ticks of the Ornithodoros moubata complex (Ixodoidea: Argasidae) in Malawi, and relation to African swine fever epizootiology. Journal of Hygiene 96 (3), 535e544. https://doi.org/10.1017/ s0022172400066341. Heath, A.C.G., 2016. Biology, ecology and distribution of the tick, Haemaphysalis longicornis Neumann (Acari: Ixodidae) in New Zealand. New Zealand Veterinary Journal 64 (1), 10e20. https://doi.org/10.1080/00480169.2015.1035769. Hofmeester, T.R., van der Lei, P.B., Docters Van Leeuwen, A., Sprong, H., van Wieren, S.E., 2016. New foci of Haemaphysalis punctata and Dermacentor reticulatus in the Netherlands. Ticks and Tick-Borne Diseases 7 (2), 367e370. https://doi.org/10.1016/ j.ttbdis.2015.12.009. Jaenson, T.G.T., Ta¨Lleklint, L., Lundqvist, L., Olsen, B., Chirico, J., Mejlon, H., 1994. Geographical distribution, host associations, and vector roles of ticks (Acari: Ixodiae, Argasidae) in Sweden. Journal of Medical Entomology 31 (2), 240e256. https:// doi.org/10.1093/jmedent/31.2.240. Kiszewski, A.E., Matuschka, F.R., Spielman, A., 2001. Mating strategies and spermiogenesis in Ixodid ticks. Annual Review of Entomology 46, 167e182. https://doi.org/10.1146/ annurev.ento.46.1.167. Kumar, R., Sharma, A.K., Ghosh, S., 2020. Menace of acaricide resistance in cattle tick, Rhipicephalus microplus in India: Status and possible mitigation strategies. Veterinary Parasitology 278, 108993. https://doi.org/10.1016/j.vetpar.2019.108993. Labuda, M., Nuttall, P.A., 2004. Tick-borne viruses. Parasitology 129, S221eS245. https:// doi.org/10.1017/S0031182004005220. Little, S.E., Hostetler, J., Kocan, K.M., 2007. Movements of Rhipicephalus sanguineus adults between co-housed dogs during active feeding. Veterinary Parasitology 150, 139e145. https://doi.org/10.1016/j.vetpar.2007.08.029. Lv, J., De Marco, M.D.M.F., Goharriz, H., Phipps, L.P., McElhinney, L.M., Herna´ndezTriana, L.M., Wu, S., Lin, X., Fooks, A.R., Johnson, N., 2018. Detection of tick-borne bacteria and Babesia with zoonotic potential in Argas (Carios) vespertilionis (Latreille, 1802) ticks from British bats. Scientific Reports 8 (1). https://doi.org/10.1038/s41598018-20138-1. Madder, M., Thys, E., Geysen, D., Baudoux, C., Horak, I., 2007. Boophilus microplus ticks found in West Africa. Experimental & Applied Acarology 43 (3), 233e234. https:// doi.org/10.1007/s10493-007-9110-1. Major, L., Linn, M.L., Slade, R.W., Schroder, W.A., hyatt, A.D., Gardner, J., Cowley, J., Suhrbier, A., 2009. Ticks associated with Macquiarie Island penguins carry arboviruses from four genera. PLoS One 4, e4375. https://doi.org/10.1371/journal.pone.0004375. Muhanguzi, D., Byaruhanga, J., Amanyire, W., Ndekezi, C., Ochwo, S., Nkamwesiga, J., Mwiine, F.N., Tweyongyere, R., Fourie, J., Madder, M., Schetters, T., Horak, I., Juleff, N., Jongejan, F., 2020. Invasive cattle tick in East Africa: mophological and

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molecular confirmation of the presence of Rhipicephalus microplus in south-eastern Uganda. Parasites & Vectors 13 (1), 165. https://doi.org/10.1186/s13071-020-04043-z. Muzaffar, S.B., Jones, I.L., 2007. Activity periods and questing behaviour of the seabird tick Ixodes uriae (Acari: Ixodidae) on Gull Island, Newfoundland: the role of puffin chicks. The Journal of Parasitology 93 (2), 258e264. https://doi.org/10.1645/GE-877R1.1. Mun˜oz-Leal, S., Gonza´lez-Acun˜a, D., 2015. The tick Ixodes uriae (Acari: Ixodidae): Hosts, geographical distribution, and vector roles. Ticks and Tick-Borne Diseases 6 (6), 843e868. https://doi.org/10.1016/j.ttbdis.2015.07.014. Nava, S., Estrada-Pen˜a, A., Petney, T., Beati, L., Labruna, M.B., Szabo´, M.P.J., Venzal, J.M., Mastropaolo, M., Mangold, A.J., Guglielmone, A.A., 2015. The taxonomic status of Rhipicephalus sanguineus (Latreille, 1806). Veterinary Parasitology 208 (1e2), 2e8. https:// doi.org/10.1016/j.vetpar.2014.12.021. Oleaga, A., Carnero-Mora´n, A., Valero, M.L., Pe´rez-Sa´nchez, R., 2021. Proteomics informed by transcriptomics for a qualitative and quantitative analysis of the sialoproteome of adult Ornithodoros moubata. Parasites & Vectors 14 (1), 396. https://doi.org/10.1186/s13071021-04892-2. Oliver, J.H., Herrin, C.S., 1976. Differential variation of parthenogenic and bisexual Haemaphysalis longicornis (Acari: Ixodiadae). The Journal of Parasitology 62 (3), 475e484. https://doi.org/10.2307/3279161. Oliver, J.H., Tanaka, K., Sawada, M., 1973. Cytogenetics of ticks (Acari: Ixodoidea). Chromosoma 42 (3), 269e288. https://doi.org/10.1007/bf00284775. Pettersson, J.H.O., Ellstro¨m, P., Ling, J., Nilsson, I., Bergstro¨m, S., Gonza´lez-Acun˜a, D., Olsen, B., Holmes, E.C., 2020. Circumpolar diversification of the Ixodes uriae tick virome. PLoS Pathogens 16 (8), e1008759. https://doi.org/10.1371/JOURNAL.PPAT. 1008759. Pfa¨ffle, M., Littwin, N., Petney, T., 2015. Host preference of immature Dermacentor reticulatus (Acari: Ixodidae) in a forest habitat in Germany. Ticks and Tick-Borne Diseases 6 (4), 508e515. https://doi.org/10.1016/j.ttbdis.2015.04.003. Raghavan, R.K., Peterson, A.T., Cobos, M.E., Ganta, R., Foley, D., Munderloh, U.G., 2019. Current and future distribution of the lone star tick, Amblyomma americanum (L.) (Acari: Ixodidae) in North America. PLoS One 14 (1), e0209082. https://doi.org/10.1371/ journal.pone.0209082. Rizzoli, A., Silaghi, C., Obiegala, A., Rudolf, I., Huba´lek, Z., Fo¨ldva´ri, G., Plantard, O.,  ´ , E., Kazimı´rova´, M., 2014. Ixodes ricinus Vayssier-Taussat, M., Bonnet, S., Spitalska and its transmitted pathogens in urban and peri-urban areas in Europe: New hazards and relevance for public health. Frontiers in Public Health 2, 251. https://doi.org/ 10.3389/fpubh.2014.00251. Sa`nchez-Vizcaı´no, J.M., Mur, L., Bastos, A.D.S., Penrith, M.L., 2015. New insights into the role of ticks in African swine fever epidemiology. OIE Revue Scientifique et Technique 34 (2), 503e511. https://doi.org/10.20506/rst.34.2.2375. Sa´nchez-Seco, M.P., Sierra, M.J., Estrada-Pen˜a, A., Valca´rcel, F., Molina, R., De Arellano, E.R., Olmeda, A.S., Miguel, L.G.S., Jime´nez, M., Romero, L.J., Negredo, A., 2022. Widespread detection of multiple strains of Crimean-Congo hemorrhagic fever virus in ticks. Emerging Infectious Diseases 28 (2), 394e402. https://doi.org/10.3201/ eid2802.211308. ´ ., Mihalca, A.D., Barti, L., CsTsz, I., SzTke, K., Sa´ndor, A.D., Corduneanu, A., Pe´ter, A Hornok, S., 2019. Bats and ticks: host selection and seasonality of bat specialist ticks

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in Eastern Europe. Parasites & Vectors 12 (1), 605. https://doi.org/10.1186/s13071-0193861-5. Schulz, A., Karger, A., Bettin, B., Eisenbarth, A., Sas, M.A., Silaghi, C., Groschup, M.H., 2020. Molecular discrimination of Hyalomma tick species serving as reservoirs and vectors for Crimean-Congo hemorrhagic fever virus in sub-saharan Africa. Ticks and TickBorne Diseases 11 (3), 101382. https://doi.org/10.1016/j.ttbdis.2020.101382. Sharma, N., Singh, V., Shyma, K.P., Parsani, H.R., 2017. Comparative efficacy of commercial preparation of deltamethrin and cypermethrin against Ornithodoros spp. of North Gujarat. Journal of Parasitic Diseases 41 (4), 1139e1142. https://doi.org/10.1007/s12639-0170947-x. Socolovschi, C., Kernif, T., Raoult, S., Parola, P., 2012. Borrelia, Rickettsia, and Erhlichia species in bat ticks, France, 2010. Emerging Infectious Diseases 18, 1966e1975. https://doi.org/10.3201/eid1812.111237. Sonenshine, D.E., 2018. Range expansion of tick disease vectors in North America: implications for spread of tick-borne disease. International Journal of Environmental Research and Public Health 15 (3), 478. https://doi.org/10.3390/ijerph15030478. Valcarel, F., Gonzalez, J., Gonzalez, M.G., Sanchez, M., Tercero, J.M., Elhachimi, L., Carbonell, J.D., Olmeda, A.S., 2020. Comparative ecology of Hyalomma lusitanicum and Hyalomma marginatum Koch 1844 (Acarina: Ixodiadae). Insects 11, 303. https:// doi.org/10.3390/insects11050303. Yabsley, M.J., Quick, T.C., Little, S.E., 2005. Theileriosis in a white-tailed deer (Odocoileus verginianus) fawn. Journal of Wildlife Diseases 41 (4), 806e809. https://doi.org/10.7589/ 0090-3558-41.4.806. Zhao, L., Li, J., Cui, X., Jia, N., Wei, J., Xia, L., Wang, H., Zhou, Y., Wang, Q., Liu, X., Yin, C., Pan, Y., Wen, H., Wang, Q., Xue, F., Sun, Y., Jiang, J., Li, S., Cao, W., 2020. Distribution of Haemaphysalis longicornis and associated pathogens: analysis of pooled data from a China field survey and global published data. The Lancet Planetary Health 4 (8), e320ee329. https://doi.org/10.1016/S2542-5196(20)30145-5.

CHAPTER

Blood feeding as a life choice and the multiple functions of tick saliva

4

As obligate hematophagous arthropods, acquiring a blood meal is fundamental to transition from one life stage to the next. However, unlike many other bloodfeeding organisms, ticks have evolved a pool-feeding strategy where the tick embeds itself into the skin of the host and consumes a volume of digested blood and tissue. Each immature life stage of the tick must find and feed from a vertebrate host before progressing to the next stage. Adult females require a blood meal to provide nutrition for egg development, and in some species, males will also take a blood meal. For hard ticks, this requires attachment to a host for long periods, often for days. Conversely, soft ticks have developed a little-and-often strategy, taking a brief blood meal, multiple times during each life stage. To achieve this, the tick must locate a host, select a site in which to pierce its dermal layers, and remain attached. It then alternates injection of saliva into the wound and ingestion of blood and digested tissue. Tick saliva plays a key role in this process and contains a vast array of molecules that enable attachment to the host, digestion of the blood meal, and suppression of many host responses that might be detrimental to the tick. Understanding the contents of tick saliva has received considerable attention due to its role in pathogen transmission. The potential to utilize salivary products as a component of a vaccine that could suppress tick feeding and prevent pathogen transmission has been a goal of many investigators. The range of functions that tick saliva deliver is remarkable and reflects the long and successful evolution of ticks. However, studying this complex cocktail of proteins, peptides, and lipids has proven challenging, and despite over 60 years of scientific endeavor, many aspects of both the contents and function of tick saliva remain unresolved. In addition, not all ticks are the same and there are clear differences between the two main tick families based on their different feeding strategies. There are also a number of anomalies represented by those ticks that have moved away from a strict hematophagous diet. This chapter provides a brief introduction to the subject and highlights what is known about tick feeding, and critically what remains to be discovered about this multifunctional secretion, tick saliva.

Introduction Almost all ticks are obligate hematophagous arthropods, which means that they derive all nutrition from feeding on other animals. Immature stages must take a Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00011-3 Copyright © 2023 Elsevier Inc. All rights reserved.

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blood meal to acquire the nutrition required to molt/metamorphose into the next life stage. Adult females require a blood meal to support the development of eggs, and some adult males require a blood meal to promote spermatogenesis. This strategy has also been adopted by the equally successful sister clade, the mites. The origin of this strategy is not known but may have evolved from an ancestral arthropod scavenging food from dead animals, but finding that predation on live animals was more successful. In order to achieve this, ticks have evolved anatomical structures to enable attachment to the host and the ability to imbibe and digest a blood meal. This includes specialized mouthparts adapted for this process and the ability to control the flow of saliva into the wound and then reversing the flow to take up the blood meal. The discovery of ticks trapped in amber indicate that the tick mouthparts evolved early in the evolution of ticks enabling them to feed on vertebrates for millions of years without significant modification (Dunlop et al., 2016). This would appear to be a highly successful strategy for survival although the mouthparts are incapable of acquiring nutrition in any other way and make the tick entirely dependent on finding a vertebrate host or face starvation. And this is a challenge that each life stage of a three-host tick species must overcome, whereas for one-host ticks, only the larval stage must locate the host. Why then target more than one host? One theory suggests that this may be an adaption to life in temperate regions where winter temperatures drop below that at which the tick can function and vertebrate hosts are limited. Detachment from the host allows a period of delay to the next life stage, or diapause, until temperatures rise and hosts become available. The alternative is to take the route taken by nidicolous hard and soft ticks that spend the majority of their life within the relative constant conditions within the burrows and nests of their hosts. The main significance of tick blood feeding, from an anthropocentric point of view, is its relevance to pathogen transmission, both to the vertebrate host that can be infected following a tick bite and to the transfer of a pathogen to a feeding tick from an infected host. The length of time that a tick feeds is critical to this process. The Ixodidae tend to feed for longer periods (days), and during this time, both viruses (within hours), bacteria and protozoa (>24 h) can be transmitted to the host. The Argasidae tend to feed for short periods (hours) often while the host is inactive but do this repeatedly and is associated with transmission of viruses.

Finding a host Blood feeding requires intimate contact with the host, so ticks have evolved a range of strategies for locating a host and getting sufficiently close to “bite” it. Many ticks cohabit in the burrows of the host on which they feed and so have ready access to a blood meal. Alternatively, ticks use either an ambush strategy, waiting in a prominent location on vegetation for a host to pass close by, or a hunting strategy where the tick uses its limited ambulatory capacity to approach the host. The ambush strategy is characterized by a behavior termed questing. Ixodes ricinus uses this to locate

Finding a host

prey, climbing to the tips of vegetation and waiting for a host to brush past. An example of a hunting strategy is that shown by Hyalomma marginatum, where the tick will follow a potential host for tens of meters in order to make contact with it. Ticks are able to detect a range of host-derived cues using Haller’s organs located in a small cavity on the terminal segment (tarsus) of the first pair of legs (Fig. 4.1). Within the cavity are sensory setae or hairs that are able to detect changes in CO2, humidity, and temperature that could indicate the presence of a host. Some tick species have primitive eye structures such as those within the genus Hyalomma. These are present on both sexes and are found as paired structures between the first and second pair of legs on the scutum (Bergerman et al., 1997). Although basic, they are used to detect visual signals that assist the tick in locating a moving prey. When contact is made with the host, the tick uses the paired clasps at the end of each leg (Fig. 4.1) to remain attached to the host and locate a suitable site to feed. For larvae of Rhipicephalus microplus attached to a fully grown cow, this is quite a journey as the tick favors concealed sites on the body, such as the axilla (between the limb and body) where the cow is less likely to able to remove the feeding tick. For I. ricinus ticks feeding on humans, adult females were more often removed from the head and torso, whereas larvae and nymphs were found on limbs (Cull et al., 2020). Ticks that feed on birds such as Ixodes frontalis tend to feed on locations on the head, particularly around the eyes, to reduce the opportunity for the bird to remove it during grooming (Fig. 4.2).

FIGURE 4.1 A scanning electron microscopy image of the terminal clasps of an Ixodes ricinus larva. Also present on the tarsus is the Haller’s organ on showing the hair-like setae that detect host-derived cues such as carbon dioxide. Image courtesy of W. Cooley.

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FIGURE 4.2 Photograph of an engorged Ixodes frontalis tick attached below the eye of a chaffinch (Fringilla coelebs). Image courtesy of Paul Holmes.

Attachment Ticks use their highly adapted mouthparts (capitulum) in a series of actions that will lodge the tick firmly in the host and allow acquisition of the blood meal. The palps that surround the main mouth parts have a sensory function that enables the tick to select a site on the host in which to engage. Once a site is selected, the palps retract revealing the mouth parts. The first structures to act are the paired chelicera. These consist of a muscular base, an elongated shaft attached to a terminal digit that consists of a series of blades that make the initial incisions on the outer skin and penetrate through the dermis of vertebrate hosts. Even the toughened skin of reptiles can be pierced by ticks belonging to the genera Amblyomma and Hyalomma. This provides an incision to insert the principal mouthpart, the hypostome (Fig. 4.3), a solid immovable extension from the basis capitulum, which anchors the tick to the host. This has a series of backward-facing barbs or denticles on its ventral surface that anchor the tick head-first into the host, while its dorsal surface forms a channel (preoral canal) with the chelicera through which saliva can be injected and tissue fluid/blood can be ingested. The Ixodidae can be attached to the host for an extended period, in some instances, for over a week. In addition to the insertion of the hypostome and chelicerae, hard ticks produce a salivary excretion, appropriately termed cement that binds the tick to the surface of the host (Suppan et al., 2018). In addition, this seals the wound and prevents excessive bleeding. The Argasidae do not produce this substance. Although often described as feeding on blood, tick feeding is more appropriately described as pool feeding. Ticks ingest a mixture of digested blood and tissue from what is termed a “feeding pool” (see Fig. 4.4), so are both hematophagic, feeding on blood, and histiophagic, feeding on tissue.

Detachment

FIGURE 4.3 The left-hand panel shows a scanning electron microscopy image of the ventral surface of the hypostome of an Ixodes ricinus larva. A chelicera is visible below the hypostome. Note the rear-facing denticles that tether the tick to the upper layers of the host’s skin. Image courtesy of W. Cooley. The right-hand panel shows a dorsal view of the hypostome of an adult female Ixodes ricinus, after the loss of one of the palps after removal from a sheep. Photo N. Johnson©.

Engorgement In addition to the cement described above, the tick salivary glands undergo development during attachment to the host and secrete an array of substances to enable the tick to feed. A recent study has used X-ray computing tomography to visualize the tick mouthparts embedded in a host and the structures that enable alternation between injection of saliva and ingestion of the blood meal (Vancova´ et al., 2020). This alternation is achieved through the musculature that surrounds the salivarium, the tube that connects the salivary glands to the preoral canal, and the pharynx that leads to the midgut via the esophagus. During salivation, the pharynx is closed and saliva is ejected from the salivary glands into the feeding pool. This is then reversed with the closure of the salivarium and the opening of the pharyngeal valve that creates suction drawing fluid into the esophagus and begins filling the midgut. A detailed description of tick saliva is given below, but the injection of saliva achieves a number of roles including suppression of wound healing and vasorelaxants, and the introduction of digestive enzymes that solubilize the host’s tissue. The uptake of a relatively large volume of liquid presents a challenge as the majority taken up by the tick is water that needs to be separated and excreted to allow further uptake of blood and digested tissue. Argasid ticks achieve this through excretion of water and unwanted ions through coxal glands during blood feeding (Hoogstraal, 1985).

Detachment The change to the tick following completion of engorgement is striking. Female I. ricinus can increase in size almost 200-fold (Bartosik and Buczek, 2012) and leads to the swollen appearance that reflects a castor bean. Completion of feeding triggers the detachment of the tick from the host. For immature life stages, this will be

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FIGURE 4.4 Schematic of the tick feeding showing the bidirectional transfer of saliva into the feeding pool and the ingestion of digested blood and tissue.

followed by a period of metamorphosis into the next life stage. Mated females will locate a sheltered position in which to allow release of nutrients from the blood meal to support egg maturation and subsequent oviposition.

Problems associated with blood feeding So far so good for the tick, but this life choice brings with it a number of particular challenges that the feeding tick must overcome if it is to successfully complete engorgement. For soft ticks, this is less of a challenge as they generally go for a little and often strategy, whereas hard ticks are in for the long haul. The sudden increase in volume puts physical stress on the gut and alloscutum. Furthermore, ingestion from a warm-blooded host can lead to a dramatic rise in body temperature requiring strategies to maintain thermoregulation. The rapid intake of the blood meal contains a large volume of water, influx of ions, and potentially toxic nitrogenous products. Finally, having taken a blood meal, the tick may become a target itself for feeding by other ticks, a process called hyperparasitism. The feeding tick must respond to all of these challenges. The following sections consider each of these in turn.

Thermoregulation Ticks are poikilothermic, meaning they are unable to regulate their body temperature, which varies with the environment they are in. When taking a blood meal

Hyperparasitism

from a warm-blooded vertebrate, the body temperature can rise by over 20
C, placing the tick under considerable heat stress. To avoid this, ticks have evolved measures to control this physiological challenge (Benoit et al., 2019). These fall into two categories, thermoregulatory activities that modulate the temperature to reduce stress, and thermotolerance, usually physiological responses, which enables the tick to function under certain temperature conditions. An example of thermoregulation has been observed in the response of the soft tick Ornithodoros rostrus, which excretes fluid from coxal glands during feeding (Lazzari et al., 2021). These secretions spread over the cuticle surface and cool the tick through evaporation. However, the mechanisms that enable ticks to resist the effects of rapid temperature increases during blood feeding require further research.

Water balance A further challenge to the tick is maximizing the nutrient content of the blood meal and discarding the large volume of water that is ingested but has no nutrient value. Soft ticks achieve this through eliminating excess fluid through coxal glands as described above (Larzzari et al., 2021). Hard ticks have a greater challenge and have developed a mechanism for returning excess water from the blood meal back into the host.

Interrupted feeding Detachment can be triggered prematurely for a number of reasons. Firstly, defensive actions by the host, such as grooming or scratching stimulated by the irritation caused by the tick bite, can lead to the physical detachment of the tick. For humans, this can be achieved using a tick removal tool. Detachment in this way can lead to damage of the tick mouthparts preventing further feeding. However, if feeding is interrupted and the mouth parts remain intact, the tick will actively seek a further host to complete the blood meal (Tahir et al., 2020). Alternatively, the host may produce an active immune response (antibodies, chemokines, T-cell responses) to salivary gland secretions (SGSs) that in turn attack tick structures including the midgut lining. The host may die while the tick is attached, and it is believed that in the case of feeding on mammals and birds, the tick can sense the drop in body temperature leading to the rapid detachment from the host.

Hyperparasitism Hyperparasitism is the phenomenon where an engorged tick becomes the target for feeding by other ticks, either conspecifically or interspecifically by ticks of another

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species. Males and partially engorged females have been observed showing this behavior that involves full insertion of the hypostome into the idiosoma, the part of the tick surface not covered by the scutum. It has been observed in both hard and soft tick species (Buczek et al., 2019). The effect of this causes some damage to the engorged tick and can occur repeatedly. It has been suggested that reducing body temperature during feeding (see above) may reduce susceptibility to hyperparasitism.

The exception to the blood-feeding rule Despite the success of blood feeding as a means of acquiring nutrition, it appears that not all ticks use this approach. The specialist bat tick Agricola delacruzi is found in South American caves where large bat colonies roost. Although its larvae are readily found feeding on cave-dwelling bats of the genus Pteronotus, the nymphs and adults of this species are only found on cave walls and in the layers of bat guano on the floor of the cave (Labruna et al., 2008). This and the small hypostome that lacks denticles (teeth) have led some researchers to suggest that the later life stages of this species feed on guano and have evolved away from blood feeding. Bat guano is a surprisingly nutritious excrement that accumulates in large quantities in bat caves. Transcriptomic analysis of the salivary glands of A. delacruzi females have provided support for this hypothesis with transcripts for proteins that have chitin-binding domains being overexpressed but with lower levels of transcripts found in bloodfeeding soft and hard ticks (Ribeiro et al., 2012). This may represent an evolutionary step to avoid predation by the bat species of the larger life stage and to take advantage of an alternative food source.

Tick saliva The Ixodidae and Argasidae have evolved different approaches to blood meal acquisition. The Ixodidae are slow feeders, often taking up to seven days for an adult female to become fully engorged. However, each life stage will only take one blood meal, and in the case of females, this blood meal will be sufficient to produce eggs. The Argasidae are fast feeders, often completing a blood feed within 30 min. However, they will take multiple blood meals during each life stage. This presents different challenges to the form and function of the saliva that is produced, and this manifests as differences in both the structure of their salivary glands and the contents of saliva. The extended period over which hard ticks feed indicates that their blood meal acquisition differs and is likely to be more complex than other hematophagous arthropods. The development of inflammation at the site of the tick bite and the occurrence of tick paralysis (see chapter 6) in response to the bite

Structure of the tick salivary gland

were early indications that the tick was secreting something into the wound to which the vertebrate host was reacting too. In addition, the methodologies used to investigate the “sialome,” the complete inventory of all elements secreted by the tick salivary gland, have evolved considerably over the past 50 years (Mans, 2020). The totality of proteins within the salivary gland is termed salivary gland extract (SGE). This is prepared by dissecting out the salivary gland and homogenizing it, so that it includes both the saliva and the components of the glandular tissue that produce it. The alternative is the SGS, which is prepared only from secreted saliva. Both preparations have been used to investigate the contents of tick saliva. Early investigators used chromatography to fractionate SGS but were unable to identify individual proteins or their function. This approach developed further through the application of two-dimensional SDS-PAGE linked to proteomic analysis using mass spectrometry. This enabled large numbers of proteins to be identified and characterized. This benefitted immensely from the parallel developments in tick genomics and transcriptomics that could definitively identify a protein and confirm that particular proteins were tick-derived (Hovius et al., 2008). During feeding, the structure of the tick salivary gland changes (Binnington, 1978) and the contents of tick saliva changes to include a large component of the blood meal itself, particularly excretion of excess water and ions, as host proteins that have been digested in the midgut are transferred back to the salivary glands via the hemolymph. The process of blood feeding is therefore a sequential, bidirectional process beginning with the secretion of saliva, uptake of liquefied contents into the midgut and then return of waste products back into the wound site, and uptake of more liquefied contents into the midgut. Over a decade ago, a review of putative salivary proteins cataloged over 3500 components from a range of tick species (Francischetti et al., 2009). This list continues to grow as the complexity and function of tick saliva increases.

Structure of the tick salivary gland Ticks have paired salivary glands positioned anterolaterally below the pharynx and midgut. When dissected from the tick, they have a “bunch of grapes” structure with round acinus budding off a series of ducts (Nuttall, 2019). These ducts coalesce into the main salivary duct, the salivarium, which empties into the buccal cavity. Each grape-like structure is formed from groups of acini that have different functions  depending on the species of tick, with up to four types being identified (Simo et al., 2017). Argasidae have only two types, I and II, reflecting the reduced time, and presumably need, for salivary gland function. Ixodidae have four types, IeIV. Acini type I are found most proximal to the main salivary duct and play a role in water uptake in the unfed tick. Acini types II and III are located in female ticks at the proximal and distal sections of the salivary gland, respectively. The cells forming these acini have a granular appearance and are the source of de novo protein

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production and preformed granules that are secreted once the tick has achieved attachment to the host. They also grow in size and undergo modification during feeding in order to increase saliva production and mediate return of water, ions, and excess host proteins, thus enabling homeostatic control during feeding. Type IVasini are found in male ticks and secrete saliva to assist in the insertion of the spermatophore into the female genital pore (Feldman-Muhsam et al., 1970). Salivary secretion is controlled. Each acinus is surrounded by a branched axonal projection linked to the synganglion or tick central nervous system. These axonal projections contact with the acinar basal epithelium and the myoepithelium that form around the lumen forming a valve structure (Vancova´ et al., 2019). Release of dopamine and neuropeptides from the axons triggers contraction of the myoepithelium and expulsion of saliva from the acinus. This accumulates in the luminal duct of the salivary gland until it is ejected into the feeding pool (Fig. 4.4).

The functions of tick salivary glands and saliva Tick saliva is a multifunctional secretion that supports a number of fundamental processes that contribute to tick survival (Table 4.1). A key function is the proteolytic digestion of blood and tissue within the feeding pool that starts the process of digesting the blood meal that continues in the midgut. However, parasitic feeding presents the tick with a number of challenges including avoiding host responses, both physical and physiological. The tick also has to deal with the blood meal contents, not all of which has value to the tick. Tick saliva plays a number of roles, most associated with the feeding process, but a vital off-host function is the acquisition of water (Rudolph and Knulle, 1974). Ticks are unable to consume water directly but do require ingestion of water during Table 4.1 List of the functions associated with tick salivary glands and saliva. Function Water homeostasis Cementation Pain suppression Proteolytic enzymes Prevent vasoconstriction Block wound healing Suppress blood coagulation and platelet aggregation Inhibit complement Block the innate and acquired immune response

The functions of tick salivary glands and saliva

long periods prior to or after digestion of a blood meal. This is achieved through production of a hygroscopic solution containing high levels of sodium and potassium from the type 1 acini. This is secreted onto the mouth parts of the tick while in an environment with a high relative humidity (>85%). While off host, ticks favor environments with high humidity such as the vegetative layer and are at risk of desiccation if they remain where there is low humidity. The high concentration of ions in the solution allows absorption of water from the surrounding atmosphere that is ingested back into the type 1 acini where water is absorbed. This absorption can be inhibited by the steroid hormone ouabain that targets the Naþ/Kþ ATPase suggesting its role in the process (Kim et al., 2017). The next product of saliva assists in the host attachment process. The initial secretion from the salivary gland following insertion of the hypostome is the production of a substance termed cement (Suppan et al., 2018). In addition to “glueing” the tick to the host, it creates a seal around the wound site that prevents blood loss at the site of tick attachment, enhances tick binding to the host, particularly for ixodid ticks, and prevents infection of the wound. Another function of cement is to block the host immune response from access to the ticks’ mouthparts. The main constituents of tick cement are poorly characterized although are believed to be dominated by glycine-rich proteins (GRPs) and a number of metalloproteases (Suppan et al., 2018). Through the generation of cDNA libraries generated from the salivary glands of a number of tick species, the level of GRP expression was measured. This demonstrated that tick species with short mouth parts produces more GRPs than ticks with longer mouth parts. This suggested a greater reliance on cement in those species with a relatively short hypostome to remain attached to the host (Maruyama et al., 2010). Once attached to the host, the tick must suppress the pain and itching response at the wound site generated by the insertion of the hypostome. In the absence of this, the host would react to remove the tick if possible. Pain suppression is achieved through secretion in saliva of proteins such as an angiotensin-converting enzyme metalloprotease that blocks the action of host bradykinin (Ribeiro and Mather, 1998). A major challenge to a tick that remains attached and feeding on a host is that of preventing host hemostasis, the mechanisms that are triggered shortly after injury that prevent blood loss and initiate tissue repair. This is a common problem to most blood-feeding arthropods but is particularly challenging for ticks that require a constant flow of blood into the wound site and ingestion of blood over an extended period. Preventing the normal host responses of vasoconstriction, platelet deposition that reduces blood flow, and coagulation through the formation of fibrin clots are key functions of tick saliva. Early secretion of apyrases breaks down the clotting stimulant adenosine diphosphate within the wound (Francischetti, 2010). A serine protease inhibitor secreted in saliva targets thrombin to block clotting. For Amblyomma variegatum, a 32 amino acid peptide termed variegin has been identified that binds the thrombin active sites (Cho et al., 2007). Ultimately, these activities prevent wound healing until after the tick detaches.

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The main function of blood feeding is to obtain the meal. In addition to the basic acquisition of protein, carbohydrates, and lipids, ticks require iron for the production of heme which they are unable to synthesize, so must acquire them from the blood meal. A major component of the salivary contents are proteases that begin the process of digesting both blood and tissue within the wound into a sufficiently liquid form to ingest. Antioxidants are also secreted to reduce exposure to toxic hydroxyl radicals. A combination of physical damage caused by the tick bite and the introduction of foreign proteins in saliva would normally trigger inflammatory and immune responses (extensively reviewed by Kota´l et al., 2015). Secretion of a family of proteins termed evasins block cytokine responses (Hayward et al., 2017), while other salivary proteins prevent complement deposition within the feeding pool (Lawrie et al., 1999). Both innate and acquired immune responses are thought to be inhibited although hosts that are repeatedly fed on by ticks do develop immunity to the con tents of tick saliva (Simo et al., 2017). Tick salivary glands and saliva play a role in maintaining osmotic balance during the feeding process. The rapid uptake of a relatively large volume of the blood meal, dominated by water and ions that the tick does not need, means that unwanted components need to be removed, but this occurs before the blood meal itself is fully digested. Hard ticks achieve this through transfer of water from the midgut, back to the salivary glands and returned to the host. A series of studies have investigated a time series of tick salivary secretions during the duration of blood feeding (Kim et al., 2016, 2020). This combined mass spectrometry detection of proteins with current databases of matched genomes to identify the protein profile secreted during each 24-hour period. This showed that the majority of proteins were involved with regulating feeding functions. There were, however, a proportion of proteins to which no known function could be attributed. This approach also demonstrated that over 280 proteins detected were conserved between Amblyomma americanum and Ixodes scapularis, Haemaphysalis longicornis, Dermacentor andersoni, Rhipicephalus microplus, R. sanguineus, and the soft tick Ornithodoros moubata.

The effect on skin at the bite site Tick saliva and the physical damage resulting from the tick bite can lead to immediate inflammatory responses that cause pruritus (itchy skin). When the tick detaches, this can leave a papular lesion that usually heals within a week (Haddad et al., 2018). If fragments of the tick mouthparts are left within the wound, these can lead to secondary reactions that can persist for months. Further skin manifestation such as a gradually expanding rash or erythema migrans, or widespread hemorrhagic rashes are due to bacterial infections (see chapter 6). The components of tick saliva have been identified as the likely cause of the recently described alpha-gal syndrome. The syndrome is caused by the development

The role of tick saliva in pathogen transmission

of IgE antibodies against the carbohydrate galactose-a-1,3-galactose (a-gal) that causes anaphylactic shock on consumption of meat containing a-gal. The relationship between a tick bite and the subsequent development of allergy was first observed in 2007 (van Nunen et al., 2009). Since then, cases have been increasing and have been reported in Australia, Europe, Asia, and the Americas. Symptoms can present as an urticarial rash, vomiting, and in some cases, difficulty breathing (Khoury et al., 2018; Bansal et al., 2021). Treatment with antihistamines is effective, and those affected are advised to avoid consumption of red meat. The allergy results from bites from a growing list of tick species including members of the genera Ixodes, Amblyomma, and Rhipicephalus (Sharma and Karim, 2021). Despite the identification of salivary proteins containing a-gal from I. scapularis and Amblyomma americanum (Crispell et al., 2019), an individual protein that triggers the allergy has not been identified. A common theme of those that do develop a-gal syndrome is the repeated exposure to tick bites, some numbering over 100. However, other, asyet undetermined factors are likely to contribute to susceptibility to the allergy (de la Fuente et al., 2019).

The role of tick saliva in pathogen transmission Tick saliva plays a key role in the transmission of tick-borne pathogens to the host (de la Fuente et al., 2017). Pathogens are ingested in the blood meal of a feeding tick at the larval and nymph stages, cross the gut epithelium, invade the hemocoel, and then must infect the salivary gland epithelium before the tick feeds again. For adult females, the pathogen must infect the ovaries in order to pass to the next generation of ticks. The presence of pathogens in tick organs has rarely been documented, but recent investigations have detected Borrelia species and Anaplasma phagocytophilum in the salivary glands of I. ricinus (Lejal et al., 2019). Numerous studies have demonstrated that tick SGE and SGS are able to promote virus transmission in a process termed saliva-assisted transmission. This has been shown for the transmission of Thogoto virus (Jones et al., 1992), tick-borne encephalitis virus (Labuda et al., 1993), and Powassan virus (Hermance and Thangamani, 2015). Tick saliva provides the vehicle for transmission with viruses being transmitted within an hour of tick attachment, whereas bacteria and protozoa can take days to be transmitted to the host, hence the advice to remove attached ticks as soon as they are observed. Tick saliva also appears to enhance pathogen transmission during nonviremic transmission of tick-borne viruses, a method of transmission between cofeeding ticks that appears to bypass the vertebrate host (Jones et al., 1987, 1989). Until recently, the components in tick saliva that promoted pathogen transmission were not known, but recent research has begun to identify individual proteins associated with transmission. For example, the salivary cystatin, sialostatin L2, secreted by I. scapularis saliva suppresses interferon production by blocking expression pathways in dendritic cells that in turn promotes virus replication (Lieskovska´

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et al., 2015). An increasing list of salivary-associated proteins that enhance transmis sion of both bacteria and viruses has been reported (Simo et al., 2017).

Antitick vaccination using components of tick saliva The development of immunity to ticks was observed as early as the late 1930s (Trager, 1939). The later observation that repeated exposure to tick bites from pathogen-free ticks lead to a reduction in pathogen transmission (Nazario et al., 1998) suggested that an immune response generated against components of tick salivary excretions protect the host against infection with pathogens and offered a route to the development of an antitick vaccine or one that could at least suppress pathogen transmission (Karasuyama et al., 2020). With the development of new “omics” technologies, the ability to identify potential vaccine candidates has dramatically increased (Rego et al., 2019). Antitick vaccines target components of the tick midgut and reduce tick survival and the ability to reproduce. This is the approach used by the one licensed vaccine for the control of R. microplus on cattle. This targets the tick rather than pathogens that it might transmit, but by suppressing the tick population, this has the effect of reducing pathogen transmission overall. Research over the past 20 years has shown how particular proteins secreted in saliva suppress the host immune response and in turn promote transmission of certain pathogens. For example, tick mannose-binding protein lectin inhibitor (TSPLI, see Table 4.2) produced by I. scapularis inhibits the complement cascade that in turn promotes infection by Borrelia burgdorferi. A range of other proteins perform similar functions, suppressing components of the mammalian immune system that in turn enhance transmission of pathogens to the vertebrate host. As a result, these proteins are being considered as potential candidates for antipathogen transmission vaccines (Labuda et al., 2006; van Oosterwijk, 2021).

Table 4.2 Tick salivary gland proteins identified as potential antigens that block pathogen transmission. Salivary gland protein Tick mannose-binding protein lectin inhibitor (TSPLI) Salivary gland protein 15 (Salp 15) Cement protein 64P Salivary gland protein 16 (Salp 16)

Tick species

Pathogen

Key reference

Ixodes scapularis Ixodes scapularis Ixodes ricinus Ixodes scapularis

Borrelia burgdorferi (s.l.) Borrelia burgdorferi (s.l.) Tick-borne encephalitis virus Anaplasma phagocytophilum

Schuijt et al. (2011) Dai et al. (2009) Labuda et al. (2006) Sukumaran et al. (2006)

References

Conclusions From the design of the tick mouth parts, the ability to alternate salivation and ingestion, the complex nature of salivary secretions, to the ability to effectively deal with waste components of a blood meal, ticks have evolved a highly successful means of acquiring nutrients. While some tick species show great specificity in selecting a host, for example, Argasid ticks that only feed on bats (Sa´ndor et al., 2021) or in the case of R. microplus, cattle, others show a much greater flexibility in host selection. I. ricinus has been reported to feed on over 300 different vertebrate species (Gray et al., 2021). This combination of specificity and flexibility has enabled ticks to inhabit all continents of the world and to feed on a vast range of vertebrate hosts. Both the extended feeding of the Ixodidae and the short-but-often approach adopted by the Argasidae appear effective. The contents of tick saliva are highly complex. Despite the large number of proteins identified in tick saliva and the recognition of a vast array of functions, many subverted by pathogens to promote transmission, a single candidate protein that could form the basis of a vaccine has not emerged that effectively blocks pathogen transmission. This has led to more focus on glycosylated proteins as vaccine targets as these appear to be the critical component that elicits antitick responses (Narasimhan et al., 2020). The ultimate goal of a vaccine that specifically prevents transmission of a pathogen is an ambition of many research groups around the world (van Oosterwijk, 2021) but is one that has remained particularly elusive. Irrespective of the feeding preference, ticks have been phenomenally successful and have survived over millions of years. This longevity has enabled pathogens of vertebrates to adapt to ticks as an effective means of transmission. It is this transmission of microorganisms that lead to disease in the host, and this will be the theme of the next chapters.

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CHAPTER

An introduction to tickborne disease

5

Diseases transmitted by arthropod vectors account for more than 17% of all human infectious diseases, and after mosquitoes, ticks are the main source of infection (https://www.int/news-room/fact-sheets/detail/vector-borne-diseases). The impact is even higher for tick-borne diseases of livestock, where the economic burden is most severe on those populations that rely on domestic animals for both food and a source of income. The following chapters will give an overview of tick-borne disease in humans and livestock. The impact of disease translocation by invasive ticks and the major drivers for disease transmission will also be considered. While there are almost 1000 tick species, the vast majority of tick-borne diseases are transmitted by a small number that show little specificity in the choice of large vertebrate hosts. As far as we know, there are no tick species that have yet evolved to feed exclusively on humans in a way that other hematophagous arthropods have such as the yellow fever mosquito (Aedes aegypti). But with a growing human population numbering billions, often gathered together in high-density cities, it is not beyond the realm of imagination to expect that an enterprising tick will achieve this in the future. Humans are therefore considered incidental hosts for ticks and do not act as a reservoir for onward transmission of pathogens. The provision of a blood meal and the subsequent development of disease is an unfortunate consequence of that interaction. Tick-borne pathogens fall into three main categories: viruses, bacteria, and protozoa. Viruses tend to be transmitted early during the blood meal, often within hours of blood feeding, while bacteria and protozoa require feeding for a number of days before the pathogen is introduced to the host (Eisen, 2018). However, the removal of a feeding tick immediately after it is detected is always recommended. When considering tick-borne disease transmission, the main direction of transmission is from the tick to the vertebrate host, termed horizontal transmission (Fig. 5.1). If the vertebrate host is a reservoir species, this usually indicates that the host supports high levels of pathogen without succumbing to disease and is readily bitten by the tick vector. This is critical to the persistence of the pathogen and it’s spread through the tick population. Humans are usually dead-end hosts, so although disease may ensue, it does not lead to further transmission either to other humans or back into the tick population. A further consideration is transmission within the tick. With multiple postembryonic life stages, a pathogen must transfer from one life stage to the next, larva to nymph and nymph to adult. This is termed transstadial transmission, and most tick pathogens Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00004-6 Copyright © 2023 Elsevier Inc. All rights reserved.

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FIGURE 5.1 Schematic for vertical and horizontal transmission of tick-borne diseases within a population of ticks.

successfully achieve this. In addition, there is transmission from the adult female to progeny eggs, termed transovarial transmission or vertical transmission (Fig. 5.1). Not all pathogens can do this, although those that do have the ability to persist in tick populations irrespective of the relationship with vertebrate hosts. However, transovarial transmission occurs at low frequency, and without further transmission to vertebrate hosts, the pathogen will fade out of the tick population. Transtadial transmission is particularly important in temperate regions where it enables pathogens to persist in the tick population during the winter months when ticks undergo diapause and do not actively seek hosts. This combination of vertical and horizontal transmission can add considerable

Africa

complexity to the transmission of tick-borne diseases making certain life stages critical for acquiring and transmitting pathogens. An example of this complexity is the transmission cycle of Babesia microti, the cause of human babesiosis in North America. Transovarial transmission does not occur with this protozoan parasite in the North American tick Ixodes scapularis. As a result, larva do not transmit the parasite to humans. They do, however, become infected if they take a blood meal from an infected rodent. The critical life stages for transmission to the human population are the nymph and adult stages. Conversely, surveillance for B. microti in the tick host need to only focus on nymphs and adults (Gray et al., 2010). In contrast to this human pathogen, the cause of bovine babesiosis and occasional cases of human babesiosis, Babesia divergens can be transmitted in Ixodes ricinus ticks both transovarially and transstadially. This means that all active life stages of the tick can be infected and transmit the parasite, although transmission to cattle is then dictated by the feeding preference of the larvae, nymph, or adult. The following sections give a brief overview of the key tick species and tickborne diseases that are found around the world.

Africa In the African continent, tick-borne diseases place a heavy burden of disease on livestock (Table 5.1). Cattle are affected by diseases such as East Coast fever caused by Theileria annulata (Gachohi et al., 2012) and heartwater caused by infection with Ehrlichia ruminantium (Kasaija et al., 2021). Ticks also transmit a number of viruses to sheep and swine including Nairobi sheep disease virus (Marczinke and Nichols, 2002) and African swine fever virus (Jori et al., 2013). Tick-borne disease in humans remains underreported in Africa due to a lack of surveillance and limited diagnostic capability throughout much of the continent. Occasional cases of diseases such as babesiosis (Kumar et al., 2022) and CrimeaneCongo Table 5.1 Tick-borne diseases of Africa. Tick species

Pathogen

Disease

Amblyomma variegatum Hyalomma spp

Ehrlichia ruminantium

Heartwater

CrimeaneCongo hemorrhagic disease virus Theileria annulata Theileria parva Nairobi sheep disease virus

Hemorrhagic fever

Rhipicephalus appendiculatus Ornithodoros moubata

African swine fever virus

Bovine theileriosis East Coast fever Ovine hemorrhagic gastroenteritis African swine fever

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hemorrhagic fever virus (Shahhosseini et al., 2021) have been documented but are rare considering the diversity of tick species present and the size of the human population.

Asia The land mass of Asia is vast, encompassing a wide range of ecological zones. Throughout much of this, tick-borne diseases are again a major constraint to the livestock industry and cause high morbidity and mortality in humans (Table 5.2). This is particularly true for rural regions of the Middle East (Perveen et al., 2021), India (Ghosh and Nagar, 2014; Mondal et al., 2013; Negi et al., 2021), China (He et al., 2021), Central Asia (Hay et al., 2016), and Japan (Yamaji et al., 2018). In temperate regions of Eastern Russia and Japan, transmission of diseases such as highly virulent tick-borne encephalitis virus, the related Powassan virus (Leonova et al., 2009), and Lyme disease occur.

Australia and New Zealand Of the 72 species of tick reported in Australia, 17 are reported to bite humans, including five Argasidae spp. and 12 Ixodidae spp. (Dehhaghi et al., 2019). From these encounters, a number of diseases are transmitted including bacterial infections Table 5.2 Tick-borne diseases of Asia. Tick species

Pathogen

Disease

Dermacentor reticulatus Haemaphysalis flava Haemaphysalis longicornis Haemaphysalis qinghaiensis

Omsk hemorrhagic fever virus

Hemorrhagic fever

Rickettsia japonica

Japanese spotted fever

Severe fever with thrombocytopenia syndrome virus Theileria luwenshuni Theileria uilenbergi Kyasanur forest disease virus

Severe fever with thrombocytopenia syndrome Ovine theileriosis Ovine theileriosis Hemorrhagic fever

CrimeaneCongo hemorrhagic fever virus Tick-borne encephalitis virus Borrelia burgdoferi Babesia bigemina

Hemorrhagic fever Encephalitis Lyme disease Bovine babesiosis

Rickettsia conorii Babesia canis

Spotted fever Canine babesiosis

Haemaphysalis spinigera Hyalomma spp. Ixodes persulcatus Rhipicephalus microplus Rhipicephalus sanguineus

Europe

Table 5.3 Tick-borne diseases of Australia and New Zealand. Tick species

Pathogen

Disease

Haemaphysalis longicornis Ixodes holocyclus Rhipicephalus microplus

Theileria orientalis Autoimmune reaction Babesia bovis Babesia bigemina Anaplasma marginale

Bovine theileriosis Tick paralysis Bovine babesiosis Bovine babesiosis Bovine anaplasmosis

such as Q fever (Coxiella burnetii), rickettsial infections (various Rickettsia spp.), anaplasmosis (Anaplasma phagocytophilum) and Bartonellosis (Bartonella henselae). The presence of Lyme disease in Australia has been proposed but has been controversial without evidence of Borrelia burgdorferi sensu lato within its tick population. Tick paralysis caused by the bite of certain species including Ixodes holocyclus occurs on the East Coast of Australia (Table 5.3). A number of viruses have been detected in Australian ticks, but there has been no evidence for transmission and disease in humans (O’Brien et al., 2018). The main tick species feeding on cattle in Australia is the Asian blue tick, Rhipicephalus microplus, an invasive species that has also brought with it a number of pathogens of livestock. These include Babesia bovis and Babesia bigemina, both causes of bovine babesiosis and Anaplasma marginale, the cause of bovine anaplasmosis (Ramsay, 2017). The susceptibility to disease varies with the breeds of cattle with Bos taurus breeds being more susceptible than the South Asian zebu (Bos indicus). Cross-bred cattle show an intermediate susceptibility, and the use of certain breeds offers an option for reducing the burden of disease. Other strategies include acaricide treatment to suppress tick populations and vaccination against particular diseases. Combined vaccines are available for use in the cattle industry. A second introduced species, the Asian long-horned tick, Haemaphysalis longicornis is responsible for transmission of bovine theileriosis caused by Theileria orientalis strain Ikeda (Kamau et al., 2011; Hammer et al., 2015). In New Zealand, there are 11 tick species, most feeding on seabirds and one feeding on an indigenous reptile species, reflecting the geographical isolation of the fauna of the islands making up the country. The only tick species to bite livestock is the introduced species H. longicornis. This has been held responsible for outbreaks of bovine anemia caused by T. orientalis in cattle herds in recent decades (McFadden et al., 2011; Lawrence et al., 2016). Apart from this, there are no other human or animal tick-borne diseases in the country.

Europe The main tick-borne vector of human and animal disease in Northern Europe is the common sheep tick, I. ricinus (Springer et al., 2020). It is also the most widely

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Table 5.4 Major tick-borne diseases of Europe. Tick species

Pathogen

Disease

Dermacentor marginatus Dermacentor reticulatus Hyalomma marginatum Ixodes ricinus

Rickettsia raoulti

Tick-borne lymphadenopathy Canine babesiosis

Rhipicephalus sanguineus

Babesia canis Crimean Congo hemorrhagic fever virus Borrelia burgdorferi Babesia divergens Tick-borne encephalitis virus Ehrlichia canis Rickettsia conorii

Hemorrhagic fever Lyme disease Bovine babesiosis Tick-borne encephalitis Canine ehrlichiosis Mediterranean spotted fever

distributed and abundant species. In addition to the transmission of commonly encountered pathogens such as B. burgdorferi and tick-borne encephalitis virus, I. ricinus transmits a number of rare pathogens that cause a small number of human infections each year (Table 5.4). These include diseases such as human babesiosis and relapsing fever caused by Borrelia miyamotoi (Azagi et al., 2020), and the sheep pathogen, louping ill virus, in the British Isles (Jeffries et al., 2014). In Southern Europe, lower rainfall and higher temperatures favors a different range of tick species. As a result, different tick species dominate and the diseases they transmit vary. In both Spain and the Balkan countries, the presence of Hyalomma species including Hyalomma marginatum and Hyalomma lusitanicum results in the transmission of CrimeaneCongo hemorrhagic fever virus (Portillo et al., 2021). Rhipicephalus sanguineus is also widely distributed in countries around the Mediterranean Sea and transmits a range of canine diseases. Two species of Dermacentor are found in Europe, Dermacentor reticulatus and Dermacentor marginatus (Rubel et al., 2016), both vectors of spotted fever group rickettsiae (Buczek et al., 2020).

North America Four key tick vectors of disease threaten humans, livestock, and companion animals (Table 5.5), and each are showing signs of increasing geographical range and increasing in abundance (Sonenshine, 2018). These are the American dog tick (Dermacentor variabilis), the lone star tick (Amblyomma americanum), the Gulf Coast tick (Amblyomma maculatum), and the black-legged tick (I. scapularis). The reasons for these changes have been attributed to less extreme winter temperatures over recent decades that have reduced tick mortality, land use change such as reforestation associated with an increase in deer populations, and also increased awareness

Summary

Table 5.5 Significant tick vectors and tick-borne diseases of North America. Tick species

Pathogen

Disease

Ixodes scapularis

Anaplasma phagocytophilum Borrelia burgdorferi Borrelia miyamotoi Babesia microti Powassan virus Ehrlichia chaffeensis Heartland virus Bourbon virus Rickettsia rickettsia Borrelia burgdorferi

Human granulocytic anaplasmosis Lyme disease Relapsing fever Human babesiosis Powassan encephalitis Human monocytic ehrlichiosis Heartland virus disease Bourbon virus disease Rocky mountain spotted fever Lyme disease

Amblyomma americanum Dermacentor variabilis Ixodes pacificus

and surveillance for ticks and tick-borne diseases. At the most northerly range of tick distribution, there is expected to be poleward expansion putting increasing human populations at risk of exposure to tick-borne disease (Ogden et al., 2021). A further challenge has been caused by the introduction of H. longicornis that are infected with T. orientalis into the United States (Thompson et al., 2020). This in turn has led to outbreaks of bovine theileriosis caused by T. orientalis strain Ikeda, as observed in Australia (Oakes et al., 2020).

South and Central America In Central America and the Caribbean, the major tick-borne diseases are transmitted by introduced species including R. microplus, R. sanguineus, and A. variegatum (Nari et al., 1995; Charles et al., 2021). Canine babesiosis is found throughout South America wherever R. sanguineus is found (Dantas-Torres and Figueredo, 2006). In humans, rickettsial infections are the most common tick-borne disease and are transmitted by Amblyomma spp. (Szabo´ et al., 2013). A brief summary of tick vectors, pathogens, and the diseases they cause in Central and South America is provided in Table 5.6.

Summary The previous sections have provided brief overviews of the main tick vectors and the diseases they transmit from around the world. All the major continents are affected by a range of tick-borne diseases although in Europe and North America, human tick-borne disease is more commonly reported whereas in the remaining continents, it is the impact of tick-borne diseases on livestock, mainly large ruminants that are

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Table 5.6 Tick vectors and tick-borne diseases of South America. Tick species

Pathogen

Disease

Amblyomma cajennense Amblyomma variegatum Rhipicephalus microplus Rhipicephalus sanguineus

Rickettsia rickettsia

Brazilian spotted fever Heartwater

Ehrlichia ruminantium Anaplasma marginale Babesia spp. (Babesia gibsoni, Babesia canis, Babesia vogeli) Ehrlichia canis

Bovine anaplasmosis Canine babesiosis Tropical canine pancytopenia

the focus of research directed at prevention and control. The following chapters give a more detailed outline of tick-borne disease in humans and animals, including the vector, the disease distribution, and the characteristics of disease.

References Azagi, T., Hoornstra, D., Kremer, K., Hovius, J.W.R., Sprong, H., 2020. Evaluation of disease causality of rare Ixodes ricinus-borne infections in europe. Pathogens 9 (2), 150. https:// doi.org/10.3390/pathogens9020150. Buczek, W., Koman-I_zko, A., Buczek, A.M., Buczek, A., Bartosik, K., Kulina, D., Ciura, D., 2020. Spotted fever group rickettsiae transmitted by Dermacentor ticks and determinants of their spread in europe. Annals of Agricultural and Environmental Medicine 27 (4), 505e511. https://doi.org/10.26444/aaem/120602. Charles, R.A., Bermu´dez, S., Banovic, P., Alvarez, D.O., Dı´az-Sa´nchez, A.A., CoronaGonza´lez, B., Etter, E.M.C., Gonza´lez, I.R., Ghafar, A., Jabbar, A., Moutailler, S., Cabezas-Cruz, A., 2021. Ticks and tick-borne diseases in central America and the caribbean: a one health perspective. Pathogens 10 (10). https://doi.org/10.3390/ pathogens10101273. Dantas-Torres, F., Figueredo, L.A., 2006. Canine babesiosis: a Brazilian perspective. Veterinary Parasitology 141 (3e4), 197e203. https://doi.org/10.1016/j.vetpar.2006.07.030. Dehhaghi, M., Panahi, H.K.S., Holmes, E.C., Hudson, B.J., Schloeffel, R., Guillemin, G.J., 2019. Human tick-borne diseases in Australia. Frontiers in Cellular and Infection Microbiology 9, 3. https://doi.org/10.3389/fcimb.2019.00003. Eisen, L., 2018. Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks. Ticks and Tick-Borne Diseases 9 (3), 535e542. https://doi.org/10.1016/ j.ttbdis.2018.01.002. Gachohi, J., Skilton, R., Hansen, F., Ngumi, P., Kitala, P., 2012. Epidemiology of East Coast fever (Theileria parva infection) in Kenya: past, present and the future. Parasites & Vectors 5, 194. http://doi.org/10.1186/1756-3305-5-194. Ghosh, S., Nagar, G., 2014. Problem of ticks and tick-borne diseases in India with special emphasis on progress in tick control research: a review. Journal of Vector Borne Diseases 51 (4), 259e270. http://www.mrcindia.org/journal/issues/514259.pdf.

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Gray, J., Zintl, A., Hildebrandt, A., Hunfeld, K.P., Weiss, L., 2010. Zoonotic babesiosis: overview of the disease and novel aspects of pathogen identity. Ticks and Tick-Borne Diseases 1 (1), 3e10. https://doi.org/10.1016/j.ttbdis.2009.11.003. Hammer, J.F., Emery, D., Bogema, D.R., Jenkins, C., 2015. Detection of Theileria orientalis genotypes in Haemaphysalis longicornis ticks from southern Australia. Parasites & Vectors 8 (1), 229. https://doi.org/10.1186/s13071-015-0839-9. Hay, J., Yeh, K.B., Dasgupta, D., Shapieva, Z., Omasheva, G., Deryabin, P., Nurmakhanov, T., Ayazbayev, T., Andryushchenko, A., Zhunushov, A., Hewson, R., Farris, C.M., Richards, A.L., 2016. Biosurveillance in central Asia: successes and challenges of tickborne disease research in Kazakhstan and Kyrgyzstan. Frontiers in Public Health 4, 4. https://doi.org/10.3389/fpubh.2016.00004. He, L., Bastos, R.G., Sun, Y., Hua, G., Guan, G., Zhao, J., Suarez, C.E., 2021. Babesiosis as a potential threat for bovine production in China. Parasites & Vectors 14 (1), 460. https:// doi.org/10.1186/s13071-021-04948-3. Jeffries, C.L., Mansfield, K.L., Phipps, L.P., Wakeley, P.R., Mearns, R., Schock, A., Bell, S., Breed, A.C., Fooks, A.R., Johnson, N., 2014. Louping ill virus: an endemic tick-borne disease of Great Britain. Journal of General Virology 95 (5), 1005e1014. https://doi.org/ 10.1099/vir.0.062356-0. Jori, F., Vial, L., Penrith, M.L., Pe´rez-Sa´nchez, R., Etter, E., Albina, E., Michaud, V., Roger, F., 2013. Review of the sylvatic cycle of African swine fever in sub-Saharan Africa and the Indian ocean. Virus Research 173 (1), 212e227. https://doi.org/10.1016/ j.virusres.2012.10.005. Kamau, J., De Vos, A.J., Playford, M., Salim, B., Kinyanjui, P., Sugimoto, C., 2011. Emergence of new types of Theileria orientalis in Australian cattle and possible cause of theileriosis outbreaks. Parasites & Vectors 4 (1), 22. https://doi.org/10.1186/1756-3305-4-22. Kasaija, P.D., Estrada-Pen˜a, A., Contreras, M., Kirunda, H., de la Fuente, J., 2021. Cattle ticks and tick-borne diseases: a review of Uganda’s situation. Ticks and Tick-Borne Diseases 12 (5), 101756. https://doi.org/10.1016/j.ttbdis.2021.101756. Kumar, A., O’Bryan, J., Krause, P., 2022. The global emergence of human babesiosis. Pathogens 10, 1447. https://doi.org/10.3390/pathogens1011447. Lawrence, K., McFadden, A.M.J., Gias, E., Pulford, D.J., Pomroy, W.E., 2016. Epidemiology of the epidemic of bovine anaemia associated with Theileria orientalis (Ikeda) between August 2012 and March 2014. New Zealand Veterinary Journal 64 (1), 38e47. https:// doi.org/10.1080/00480169.2015.1090894. Leonova, G.N., Kondratov, I.G., Ternovoi, V.A., Romanova, E.V., Protopopova, E.V., Chausov, E.V., Pavlenko, E.V., Ryabchikova, E.I., Belikov, S.I., Loktev, V.B., 2009. Characterization of Powassan viruses from far eastern Russia. Archives of Virology 154 (5), 811e820. https://doi.org/10.1007/s00705-009-0376-y. Marczinke, B.I., Nichol, S.T., 2002. Nairobi sheep disease virus, an important tick-borne pathogen of sheep and goats in Africa, is also present in Asia. Virology 303 (1), 146e151. https://doi.org/10.1006/viro.2002.1514. McFadden, A.M.J., Rawdon, T.G., Meyer, J., Makin, J., Morley, C.M., Clough, R.R., Tham, K., Mu¨llner, P., Geysen, D., 2011. An outbreak of haemolytic anaemia associated with infection of Theileria orientalis in naı¨ve cattle. New Zealand Veterinary Journal 59 (2), 79e85. https://doi.org/10.1080/00480169.2011.552857. Mondal, D.B., Sarma, K., Saravanan, M., 2013. Upcoming of the integrated tick control program of ruminants with special emphasis on livestock farming system in India. Ticks and Tick-Borne Diseases 4 (1e2), 1e10. https://doi.org/10.1016/j.ttbdis.2012.05.006.

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Nari, A., 1995. Strategies for the control of one-host ticks and relationship with tick-borne diseases in South America. Veterinary Parasitology 57 (1e3), 153e165. https://doi.org/ 10.1016/0304-4017(94)03117-F. Negi, T., Kandari, L.S., Arunachalam, K., 2021. Update on prevalence and distribution pattern of tick-borne diseases among humans in India: a review. Parasitology Research 120 (5), 1523e1539. https://doi.org/10.1007/s00436-021-07114-x. Oakes, V.J., Yabsley, M.J., Schwartz, D., LeRoith, T., Bissett, C., Broaddus, C., Schlater, J.L., Todd, S.M., Boes, K.M., Brookhart, M., Lahmers, K.K., 2020. Theileria orientalis Ikeda genotype in cattle. Emerging Infectious Diseases 25, 1653e1959. https://doi.org/10.3201/ eid2509.190088. Ogden, N.H., Ben Beard, C., Ginsberg, H.S., Tsao, J.I., 2021. Possible effects of climate change on Ixodid ticks and the pathogens they transmit: predictions and observations. Journal of Medical Entomology 58 (4), 1536e1545. https://doi.org/10.1093/jme/tjaa220. O’Brien, C.A., Hall-Mendelin, S., Hobson-Peters, J., Deliyannis, G., Allen, A., LewTabor, A., Rodriguez-Valle, M., Barker, D., Barker, S.C., Hall, R.A., 2018. Discovery of a novel iflavirus sequence in the eastern paralysis tick Ixodes holocyclus. Archives of Virology 163 (9), 2451e2457. https://doi.org/10.1007/s00705-018-3868-9. Perveen, N., Muzaffar, S.B., Al-Deeb, M.A., 2021. Ticks and tick-borne diseases of livestock in the middle east and north africa: a review. Insects 12 (1), 1e35. https://doi.org/10.3390/ insects12010083. Portillo, A., Palomar, A.M., Santiba´n˜ez, P., Oteo, J.A., 2021. Epidemiological aspects of Crimean-Congo hemorrhagic fever in western Europe: what about the future? Microorganisms 9 (3), 1e19. https://doi.org/10.3390/microorganisms9030649. Ramsay, G.C., 2017. Decisions to manage endemic ectoparasites: the case of ticks and tickborne diseases in northern Australia. OIE Revue Scientifique et Technique 36 (1), 237e244. https://doi.org/10.20506/rst.36.1.2625. Rubel, F., Brugger, K., Pfeffer, M., Chitimia-Dobler, L., Didyk, Y.M., Leverenz, S., Dautel, H., Kahl, O., 2016. Geographical distribution of Dermacentor marginatus and Dermacentor reticulatus in europe. Ticks and Tick-Borne Diseases 7 (1), 224e233. https://doi.org/10.1016/j.ttbdis.2015.10.015. Shahhosseini, N., Wong, G., Babuadze, G., Camp, J.V., Ergonul, O., Kobinger, G.P., Chinikar, S., Nowotny, N., 2021. Crimean-Congo hemorrhagic fever virus in Africa. Asia and Europe. Microorganisms 9, 1907. https://doi.org/10.3390/microorganisms9091907. Sonenshine, D.E., 2018. Range expansion of tick disease vectors in north America: implications for spread of tick-borne disease. International Journal of Environmental Research and Public Health 15 (3), 478. https://doi.org/10.3390/ijerph15030478. Springer, A., Glass, A., Topp, A.K., Strube, C., 2020. Zoonotic tick-borne pathogens in temperate and cold regions of Europeda review on the prevalence in domestic animals. Frontiers in Veterinary Science 7, 604910. https://doi.org/10.3389/fvets.2020.604910. Szabo´, M.P.J., Pinter, A., Labruna, M.B., 2013. Ecology, biology and distribution of spottedfever tick vectors in Brazil. Frontiers in Cellular and Infection Microbiology 3, 27. https:// doi.org/10.3389/fcimb.2013.00027. Thompson, A.T., White, S., Shaw, D., Egizi, A., Lahmers, K., Ruder, M.G., Yabsley, M.J., 2020. Theileria orientalis Ikeda in host-seeking Haemaphysalis longicornis in Virginia, U.S.A. Ticks and Tick-Borne Diseases 11 (5), 101450. https://doi.org/10.1016/j.ttbdis.2020.101450. Yamaji, K., Aonuma, H., Kanuka, H., 2018. Distribution of tick-borne diseases in Japan: past patterns and implications for the future. Journal of Infection and Chemotherapy 24, 499. https://doi.org/10.1016/j.jiac.2018.03.012.

CHAPTER

Tick-borne diseases of humans

6

This chapter focuses on the numerous tick-borne diseases that affect humans. Critical among these are Lyme borreliosis, tick-borne encephalitis (TBE), babesiosis, severe fever and thrombocytopenia, and CrimeaneCongo hemorrhagic fever. This group is dominated by pathogenic bacteria and viruses that cause severe disease and occasionally deaths in humans that are infected. In most cases, transmission occurs during tick feeding, but for others, infection can occur through inhalation of the pathogen or consumption of contaminated food products, and the tick does not play a direct role. The measures required to prevent transmission of tick-borne diseases range from prevention of tick bites through application of tick repellants and wearing clothing to prevent tick access to the skin, through to vaccination. In some regions of the world, the risk of exposure to a disease such as TBE is sufficiently high that vaccination is provided by the government in a bid to reduce the burden of disease. Most bacterial and protozoal pathogens transmitted by ticks are treated with antibiotics. However, for some tick-borne diseases, effective vaccines have not been developed and particularly for viruses, drug-based treatments are not available.

Introduction The list of tick-borne diseases is large and affects human populations on all continents of the world. Table 6.1 provides a list of the major human diseases caused by ticks, the pathogen that causes it, and the tick species most associated with transmission of the pathogen. However, as descriptions of disease improve and molecular techniques allow discrimination of closely related species, what were once considered a single pathogen have become a cluster of closely related species that cause similar but recognizable conditions. This can present a challenge for accurate diagnosis of the causative agent of some infections. Examples of this include disease caused by the Borrelias and Rickettsias. In some cases, new diseases have been recognized based on revision of the clinical presentation. For some diseases, a single tick species may be associated with transmission; however, this does not exclude others from transmitting the pathogen, which can often infect a variety of tick species. In many cases, the transmission to humans is dictated by the feeding preference of a particular tick and whether it has the opportunity to feed on people. Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00006-X Copyright © 2023 Elsevier Inc. All rights reserved.

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Table 6.1 List of human diseases transmitted by ticks. Disease

Pathogen

Vector

Alkhurma hemorrhagic fever

Ornithodoros savigny

Bourbon virus fever

Alkhurma hemorrhagic fever virus Babesia microti/Babesia divergens Bourbon virus

Colorado tick fever

Colorado tick fever virus

CrimeaneCongo hemorrhagic fever Ehrlichiosis

CrimeaneCongo hemorrhagic fever virus Ehrlichia chaffeensis

Eyach virus Human granulocytic anaplasmosis Kyasanur Forrest disease

Neuropathy Anaplasma phagocytophilum Kyasanur Forest disease virus Borrelia burgdorferi Omsk hemorrhagic fever virus Powassan virus SFTSV/Heartland virus

Babesiosis

Lyme borreliosis Omsk hemorrhagic fever Powassan encephalitis Severe fever with thrombocytopenia syndrome Rickettsiosis (e.g., Rocky Mountain spotted fever) Tick-borne encephalitis Tularemia

Rickettsia spp. (Rickettsia rickettsia) Tick-borne encephalitis virus Francisella tularensis

Ixodes scapularis Amblyomma americanum Dermacentor andersoni Hyalomma spp. Amblyomma americanum Ixodes ricinus Ixodes scapularis Haemaphysalis spp. Ixodes ricinus Dermacentor reticulatus Ixodes scapularis Haemaphysalis spp. Numerous hard tick species Ixodes ricinus/Ixodes persulcatus Dermacentor spp, Ixodes ricinus

When considering the impact of disease on any population, there is usually a need to quantify a range of parameters of those affected to establish the absolute number of people experiencing disease (morbidity), number of deaths (mortality), incidence trends, and comparing the impact with other diseases. The most common measure is to cite the absolute number of cases in a particular year. If two areas or countries are being compared, then this is often expressed as cases per 100,000 of the population. Table 6.2 gives a summary of measures used to establish the impact of tick-borne disease. In the United States, tick-borne disease cases have nearly doubled between 2004 and 2016 to over 48,000 reports (Rosenberg et al., 2018). By far the most common is Lyme borreliosis, followed by human granulocytic anaplasmosis (HGA), spotted fever rickettsiosis, babesiosis, and tularemia.

Tick-borne disease caused by viruses

Table 6.2 Measures of disease burden. Measure

Definition

Examples

Mortality

Measures the incidence of human death or the case fatality rate. Measures the incidence of human disease.

Beaute´ et al. (2012) Cocchio et al. (2020)  Smit (2012)

Morbidity Quality-adjusted life years (QALY) Daily-adjusted life years (DALY)

QALY is a generic measure of disease burden, including both the quality and the quantity of life lived. DALY is a measure of overall disease burden, expressed as the number of years lost due to ill health, disability, or early death.

Van den Wijngaard et al. (2015)

The vast majority of pathogen transmissions to vertebrate hosts occurs through the tick bite (see chapter 4). The pathogen, be it bacterial, viral, or protozoal, infects the salivary glands of the tick vector and is secreted into the saliva that the tick introduces into the feeding site. This enables the pathogen to infect cells of the host. An alternative means of infection is through the consumption of contaminated milk products. Here, infection of a ruminant host can occur through a tick bite, often without the pathogen causing disease, and therefore an asymptomatic infection, but contaminates that milk and provides the opportunity to infect those who consume the milk without prior treatment such as pasteurization. This route of infection has caused repeated cases of TBE in northern Europe (Brockmann et al., 2016). Another means of acquiring a tick-borne infection is through contact with an animal carcass contaminated with a pathogen. This method of transmission has been reported in South Africa (Swanepoel et al., 1985) and is responsible for an increase in cases of CrimeaneCongo hemorrhagic fever (CCHF) in south-east Europe and Turkey (Ergo¨nu¨l, 2006). The following sections provide a comprehensive overview of some of the most important tick-borne diseases that infect and cause disease in humans. It considers when they were recognized and the manifestations of the diseases they cause. A number of recently emerging human diseases that have been reported as of tick origin are discussed in a later chapter (Chapter 9).

Tick-borne disease caused by viruses Alkhurma hemorrhagic fever

Alkhurma hemorrhagic fever virus (AHFV) was first isolated in 1995 from a patient with hemorrhagic manifestations and fever in the city of Alkhurma in Saudi Arabia (Zaki, 1997). The whole genome of AHFV was completely sequenced and shown to be a tick-borne virus from the genus Flavivirus, family Flaviviridae (Horton et al.,

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2016). The flaviviruses consist of a positive-sense single-stranded RNA genome that codes for three structural and seven nonstructural proteins. Virion particles are enveloped with a single virus surface protein projecting from the virus membrane. The virus initially isolated shared almost 90% genetic sequence identity with Kyasanur Forest disease virus (KFDV) (Charrel et al., 2001) suggesting that AHFV may be a variant of KFDV but with a different geographical distribution. AHFV has been identified in both Argasid ticks such as Ornithodoros savignyi and Ixodid ticks including Hyalomma dromedarii (Charrel et al., 2007). Although the distribution of the virus appears to be limited to the Arabian Peninsula, the wider distribution of Ornithodoros and Hyalomma spp. ticks suggests that the geographic limits of AHFV may be much larger. This is supported by the report of a clinical case from Najran on the SaudieYemeni border and detection of AHFV in ticks from the Horn of Africa (Memish et al., 2005; Horton et al., 2016).

Colorado tick fever Colorado tick fever (CTF) was first recognized as a distinct disease in the 1930s although it was recognized by explorers and pioneers in the Rocky Mountains of the United States long before infection was associated with tick bites. Cases of CTF are characterized by an abrupt onset of fever and headache that subsides for two to three days but then returns, often in a more severe form for a further two to three days. In severe cases, encephalitis can develop and only supportive treatment can be offered to aid recovery (Cimolai et al., 1988). The etiological agent is a virus now termed Colorado tick fever virus (CTFV) and was first isolated in the late 1940s (Florio et al., 1946). The virus is now classified within the genus Coltivirus, family Reoviridae. Virions are composed of two outer capsids that enclose 12 double-stranded RNA segments that make up the virus genome (Attoui et al., 2000). New coltiviruses are being discovered around the world although their role as human pathogens has not been established. The United States reports around five cases of CTF a year (Yendell et al., 2015). Cases occur during the spring and summer across the range of its principal vector, the Rocky Mountain wood tick, Dermacentor andersoni. This includes large areas of the United States of America and the south-west of Canada. Surveys for tick in areas where human incidence rates of CTF are high found large numbers of CTFV-infected D. andersoni (>20%) (Geissler et al., 2014).

Crimeanecongo hemorrhagic fever CCHF is one of the most severe tick-borne virus infections known with case fatality rates reaching >30% in some outbreaks (Shahhosseini et al., 2021). The disease is caused by the virus now known as CCHF virus (CCHFV). It was first described during an outbreak of hemorrhagic fever in Red Army soldiers in the Crimea during the final years of the Second World War (Ergo¨nu¨l, 2006). This virus was shown to be antigenically similar to a second virus isolated from a human in what is now the

Tick-borne disease caused by viruses

Democratic Republic of the Congo (Simpson et al., 1967). Worldwide, many tick species have been found infected with CCHFV and could be implicated in transmission of this virus (Mertens et al., 2016). However, the main tick group associated with transmission are species belonging to the genus Hyalomma (Gargili et al., 2017). By the late 20th century, CCHFV had one of the most extensive distributions of any tick-borne virus with infections being reported from the Middle East, Asia, and sub-Saharan Africa. During the late 20th and early 21st century, further spread occurred with cases of CCHF reported at locations around the Mediterranean Basin. CCHF virus belongs to the family Nairoviridae, genus Orthonairovirus. Other members of this genus include Hazara virus and Nairobi sheep disease virus (see Chapter 7). The virus genome is a trisegmented negative-sense RNA genome that encodes four structural proteins, the nucleoprotein (N), two glycoproteins (GN and GC), and the RNA-dependent RNA polymerase (L). The virus is particularly virulent for humans but appears to have little or no pathogenic effect on livestock. Infection following a tick bite is followed by a short incubation period of between three and seven days leading to a brief febrile illness characterized by fever, headache, and myalgia. Hemorrhagic manifestations of disease develop four to five days after the development of fever and include bleeding from the nose, gastrointestinal system, and urinary tract. The fatality rate ranges from three to over 30% during outbreaks of disease. Treatment is supportive, including replacement of fluids and blood constituents. There is no licensed antiviral treatment or licensed vaccine for CCHF. Surveys of tick-infested livestock have shown the presence of CCHFV in Hyalomma ticks (Sang et al., 2011) indicating that livestock are exposed to infection but remain asymptomatic. Human exposure through butchery of infected animals is one of the main routes of infection. Reports of infection around the Mediterranean Basin began around 2002 with cases reported in Turkey (Karti et al., 2004) and the Balkans (Papa et al., 2005). In Europe, the main tick vector is H. marginatum, a species found throughout the Iberian Peninsula, southern France, Italy, the Balkans, and Turkey. In 2010, the virus was detected in H. lusitanicum ticks in Spain (Estrada-Pen˜a et al., 2012), followed six years later with two human cases of autochthonous transmission (Garcia Rada, 2016). Phylogenetic analysis of virus detected in ticks indicated that the virus present in Spain shared greater identity with CCHFV in West Africa than that spreading in the Balkans. This suggested that it was a separate introduction into Europe with tick-infested migrating birds considered the most likely mechanism of entry (Estrada-Pen˜a et al., 2012; Palomar et al. 2016). H. marginatum have been detected on birds migrating into Europe on numerous occasions (Capek et al., 2014) including as far north as the United Kingdom (Jameson et al., 2012). It is likely that the severity of the winters prevents establishment of this tick species in countries of northern Europe. However, the existence of populations of Hyalomma spp. in Spain, Portugal, France, and Italy puts these countries at greater risk of CCHFV persisting if introduced. A recent report has suggested that there is serological evidence for CCHF infection in blood donors from Hungary, possibly linked to the presence of H. marginatum (Magyar et al., 2021).

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Eyach virus Eyach virus is a rarely encountered virus in Europe. It is a Coltivirus, related to CTFV, and has been implicated in cases of neurological disease in the former Czechoslovakia (Ma´lkova et al., 1980). Although there has been no further evidence of it causing disease in human populations, it has been detected in Ixodes ricinus ticks from across western Europe (Moutailler et al., 2016).

Kyasanur Forest disease KFDV was isolated following an outbreak of hemorrhagic fever among villagers living in the Kyasanur Forest in Karnataka State, India, in 1957 (Work and Trapido, 1957). Between 400 and 500 cases are reported from this region of south-western India each year (Holbrook, 2012) and with a case fatality rate of 3% (Patel et al., 2021). There is increasing evidence for its emergence in or spread to other states along the Western Ghats, a mountain range that runs parallel to the west coast of India (Chakraborty et al., 2019; Yadav et al., 2020). The main clinical manifestation of disease in humans is hemorrhagic fever. In addition, nonhuman primates are also susceptible to infection, and the recovery of KFDV from Haemaphysalis spinigera ticks removed from the carcasses of primates (Trapido et al., 1959) indicated that ticks were the likely vector for Kyasanur Forest disease. A second virus, Kaisodi virus, has been isolated from H. spinigera sampled in India (Pavri and Casals, 1966). Although transovarial transmission of KFDV has been demonstrated in H. spinigera (Singh et al., 1963), it is the nymph and adult stages that are critical to transmission of virus to small mammals and humans. KFDV is a member of the genus Flavivirus, family Flaviviridae. KFDV is closely related to Alkhurma virus and a virus isolated in Yunnan Province, China (Wang et al., 2009). Phylogenetic studies on KFDV and AHFV suggest that they diverged over 700 years ago (Dodd et al. 2011) and that the virus has spread slowly within Karnataka, reflecting dissemination by the tick vector, which primarily feeds on small- to medium-sized mammals. Long-distance movement that has separated the progenitors of both viruses could have been mediated by infected ticks attaching to migrating birds (Mehla et al., 2009). In recent years, there have been reports of KFDV infections in both Karnataka province (Mourya et al., 2013; Yadav et al., 2014) and in the neighboring provinces of Kerala (Tandale et al., 2015; Sadanandane et al., 2018), Tamil Nadu and Maharashtra (Mourya and Yadav, 2016). As in previous reports, outbreaks are often preceded by disease in monkeys, and contact with carcasses can lead to infection (Mourya et al., 2013).The appearance of dead monkeys, particularly target species such as the red-face bonnet monkey (Macaca radiata) and the black-faced langur (Semnopithecus entellus) are considered sentinels for the presence of KFDV at a site (Murhekar et al., 2015). Flagging studies have shown that H. spinigera is the most abundant tick species and confirmed the presence of virus in pools of trapped ticks (Sadanandane et al., 2018). The spread of KFDV in recent years could reflect further gradual spread of the virus by the tick vector, improvements in diagnosis

Tick-borne disease caused by viruses

(Mourya et al., 2012), and surveillance leading to increased frequency of reporting (Mourya et al., 2012). Increased human exploitation of the environment leading to greater contact between humans and ticks could also contribute to this apparent spread. All of the affected regions are parts of the Western Ghats. This in turn suggests that the areas affected share climatic features that are favorable to the tick vector, which is currently poorly studied. The presence of the tick species could indicate a risk of KFDV. Further surveillance assessing the distribution and abundance of H. spinigera could reveal the true extent of KFDV in India.

Omsk hemorrhagic fever The group of viruses grouped together as tick-borne flaviviruses is dominated by tick-borne encephalitis virus (TBEV), a virus species found across Eurasia from Western Europe to Japan. As its name suggests, infection can lead in a proportion of cases to encephalitis that can be fatal. Related tick-borne flaviviruses such as Powassan virus (POWV) in North America and louping ill virus in the United Kingdom also cause encephalitis as the main manifestation of disease. However, this constellation of features, tick transmission and encephalitis, is not shared by all tick-borne flaviviruses, a small number cause hemorrhagic fever. The first cases of a new febrile disease were recorded in the early 1940s from the Omsk region of southern Siberia. The striking feature of this disease was the development of hemorrhaging by those affected. Sporadic cases continued to be reported throughout the decade. In 1947, a virus was isolated from the blood of a sevenyear-old boy suffering from fever, leukopenia, and hemorrhage (Shope, 2003). Antigenically, this virus appeared to be related to the Far Eastern subtype of tick-borne flaviviruses. This new virus, Omsk hemorrhagic fever virus (OHFV) as it subsequently became known, is now classified within the tick-borne flavivirus group, genus Flavivirus (https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-senserna-viruses/w/flaviviridae/360/genus-flavivirus). This group of viruses are found across a vast geographical area from British Isles in the west, in the form of the sheep pathogen, louping ill virus, through continental Europe and Eurasia in the form of TBEV to POWV, found in Eastern Russia and North America. This has led to the theory that the tick-borne flaviviruses are associated with a climatic cline (Zanotto et al., 1995; Heinze et al., 2012) and intimately associated with the tick vector, species of the genus Ixodes (I. ricinus, Ixodes persulcatus, and Ixodes scapularis). The main manifestation of infection of these viruses in mammals is primarily a febrile infection that in some cases leads to encephalitis, and it is encephalitis and not hemorrhagic fever that is the most prominent clinical feature of infection with tick-borne flaviviruses marking OHFV out as unusual. In order to strengthen the taxonomic position of OHFV, its genome has been fully sequenced (Lin et al., 2003). This clearly shows its close relationship with the other members of the TBEV group. The ability to cause hemorrhagic fever is a property shared with the KFDV (Holbrook, 2012). The reason for this difference in disease manifestations remains unresolved. Infection in humans occurred in both epidemic

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and sporadic cases from the Omsk and Novosibirsk regions of southern Russia during the second half of the 20th century (R uzek et al., 2010). The incubation period ranged from three to seven days with preliminary manifestations of elevated temperature, headache, and muscle pain. Gastrointestinal symptoms can develop along with bleeding from the nose and mouth. This phase of infection can last for up to 15 days. Most patients make a full recovery although others, approximately 30%, experience reoccurrence of symptoms. The death rate of OHFV is low with mortality around 1%. There is no specific treatment for infection, and no vaccine has been developed specifically for this virus, although there is evidence that vaccine for TBEV can provide some protection (Chidumayo et al., 2014). The symptoms observed for OHFV are quite distinct, and no cases that fit the description of disease had been reported prior to 1941 suggesting that some change had occurred leading to its emergence. An early observation during the first outbreak was an association between patients involved with hunting and skinning animals, particularly muskrats. A further investigation isolated the virus from the brain of a muskrat carcass (Gould et al., 2003). The muskrat (Ondatra zibethicus) is not native to Eurasia and originates from North America where it is found across the continent in Canada, the United States, and northern Mexico. Adult muskrats are between 40 and 70 cm in length and can weigh up to 2 kg making it the heaviest member of the family Cricetidae. It is primarily herbivorous, although they will eat small animals, and favors wetlands as they are adapted to a partially aquatic lifestyle with semiwebbed hind feet and thick fur. It is the muskrat pelt that has attracted the species to man. Both Native Americans and subsequent European settlers to North America have exploited the muskrat as a source of fur for clothing. In the vein of ill-conceived animal transfers, during the early 19th century, a series of North American mammals were transferred to Russia to enhance the fur industry across Siberia. This included muskrats from Canada, the American mink (Neovison vison), the North American beaver (Castor canadensis), and the raccoon (Procyon lotor) (Neronov et al., 2008). From a series of introductions between 1928 and 1939, the species spread across most of Russia. Muskrats were also introduced across Europe during this period where again they became endemic. In the United Kingdom, muskrat and coypus (Myocastor coypus) were introduced in the 1920s. As a result of the ensuing environmental damage, a concerted effort was made to eliminate the species and this was eventually achieved in 1939 (Gosling and Baker, 1989). From an ecological perspective, the successful colonization of Russia by the muskrat was considered to have had a detrimental effect through habitat destruction. The timing of the introduction also preceded the emergence of OHFV and thus could have triggered the outbreak, but no other country had observed cases of the disease, so it seems unlikely that the virus was transferred with the muskrats. Therefore, what role did the muskrat play in the emergence of the virus? OHFV has never been isolated or disease reported from North America. This contrasts with another tick-borne flavivirus, Powassan virus, which is found in both Eastern Russia and North America. All human cases of Omsk hemorrhagic fever, with the exception of a number of laboratory acquired cases, have occurred in the

Tick-borne disease caused by viruses

Omsk and Novosibirsk regions of southern Russia (R uzek et al., 2010). The alternative hypothesis is that OHFV was present in this region, unobserved or encountered by humans, until the introduction of the muskrat. Detailed phylogenetic analysis on a panel of viruses appears to support the hypothesis that the virus evolved in Central Asia and spread slowly within the regions of southern Russia (Karan et al., 2014). It appears that the muskrat is a highly susceptible species and having never encountered the virus before, it is not surprising that muskrats were susceptible to infection with OHFV and show overt clinical disease. Contact with muskrat carcasses through skinning or butchery practices appeared to be responsible for many cases of human infection. What then was the origin of the virus? A further development was the isolation of virus from Dermacentor species ticks during the original surveillance efforts to identify the source of the outbreak. Epidemiological investigations of the early epidemic showed a late summer peak in infections that could be correlated with peak tick activity (R uzek et al., 2010). This corresponds with the period of activity of Dermacentor reticulatus, a species found across Eurasia and a vector of pathogens of public and animal health concern (Fo¨ldava´ri et al., 2016). OHFV has also been isolated from I. persulcatus, a species normally associated with TBEV (Mansfield et al., 2009). The introduction of an exotic, susceptible species that are infected by indigenous ticks could have amplified the virus and provided a pathway to exposure of humans (Fig. 6.1). Ticks harbor a large array of microorganisms, many of which appear to be commensal organisms with no disease causing potential, but a small number that can cause severe disease (Ahantarig et al., 2013; de la Fuente et al., 2017). These are some of the most serious pathogens of livestock and humans and includes a number of viruses (Labuda and Nuttall, 2004; Bonnet et al., 2014). OHFV has likely been present in hard ticks in Siberia for centuries prior to the introduction of muskrats, a theory supported by phylogenetic analysis. Occasional infections in humans may have occurred, but these are likely to have been sporadic cases resulting from tick bites that were not associated with a new disease. A combination of factors, the human introduction of an exotic species, its susceptibility to infection with a virus, and

FIGURE 6.1 Schematic of transmission of Omsk hemorrhagic fever virus from ticks to muskrats and then on to humans.

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human exploitation of the species, in this case removal of fur that exposed people to the virus all contributed to the emergence of a new disease. With this knowledge, it is relatively easy to protect human populations at risk of exposure through avoiding tick bites and using personal-protective equipment while handling the carcasses of muskrats. This may explain the absence of reports of OHFV apart from obligatory mention in all reviews about flaviviruses. Alternatively, the area affected is limited to the Russian Federation, and contemporary reports of the disease may be restricted to the Russian language literature (R uzek et al., 2010).

Powassan encephalitis and deer tick virus Powasan virus (POWV) causes fatal encephalitis in a proportion of humans that become infected. Between 2013 and 2015, eight cases of POWV encephalitis were reported from hospitals in Massachusetts and New Hampshire (Piantadosi et al., 2016). This represented the most recent evidence of an increasing trend for human cases of POWV in the United States where nine cases were reported between 1999 and 2005 (Hinten et al., 2008). POWV is a flavivirus, causing a febrile disease that can develop into severe meningoencephalitis. The virus was first reported from a fatal case in a five-year-old child in Powassan, Ontario in 1958 (McLean and Donohue, 1959). Preliminary virological analysis suggested an association with tick-borne viruses such as Russian Spring Summer encephalitis virus and pointed researchers in the direction of ticks as the vector. Subsequent field surveillance detected POWV in pools of Ixodes cookei ticks and provided evidence that small mammals such as groundhogs (Marmota monax) contribute to the maintenance of virus (McLean et al., 1967). Surveillance by groups in the United States detected POWV in Colorado (Thomas et al., 1960) and New York State (Whitney and Jamnback, 1965). Numerous examples of POWV have now been isolated from the black-legged tick I. scapularis (Anderson and Armstrong, 2012) indicating that this tick species may be the most abundant vector of the virus across the eastern states of the United States and southern states of Canada. In a further twist, POWV has been reported from the eastern province of Russia, Primorsky Krai, and is suspected of being established across a larger geographical area (Leonova et al., 2009; Deardorff et al., 2013). Here, the tick vector is considered to be I. persulcatus. Phylogenetic analysis of North American POWV strains indicates that POWV diverged from a common ancestor present approximately 500 years ago (Pesko et al., 2010). The viruses in Russia could be an introduction due to their similarity with American isolates. One possible means of introduction of the virus could be the importation of North American species such as mink (N. vison) with infected ticks during the expansion of the Russian fur trade. The number of human cases of POWV infection across its range in North America has increased in recent years. The underlying cause is unclear but could be due to an increased awareness among clinicians and diagnosticians. Alternatively, the increase could be related to ecological factors that lead to the increase in abundance of the tick population driven in turn by increases in the number and range of

Tick-borne disease caused by viruses

mammalian hosts such as deer. This is believed to have been behind the increase in Lyme disease, caused by Borrelia burgdorferi, across many regions in the United States of America (Barbour and Fish, 1993). However, the nymphal form of the tick is suspected of being responsible for most cases of transmission, and abundance of this life stage is more dependent on the availability of small mammals such as rodents, for example, the white-footed mouse (Peromyscus leucopus). Therefore, factors that influence rodent abundance such as predator decline, the red fox (Vulpes vulpes), for example, may have greater impact on disease transmission by ticks (Levi et al., 2012). Deer tick virus (DTV), a flavivirus in the TBE group, is a genetically distinct lineage (subtype) of POWV that can cause neuroinvasive infection in humans in parts of North America. DTV was originally isolated from the Rocky Mountain wood tick, D. andersoni, but it is mainly found in I. scapularis collected from states in the north-east of the United States (Telford et al., 1997; Aliota et al., 2014) and has since been responsible for a human case of encephalitis (Tavakoli et al., 2009). Although the first recognized human case of DTV encephalitis occurred in 1997, evidence of the causative virus, based on sequence data, was not available until 2001 (Gholam et al., 1999; Kuno, 2001). The DTV genome shares 84% sequence identity with POWV and 94% amino acid identity between the virus polyproteins. However, DTV and POWV are regarded as antigenically indistinguishable and the infecting virus cannot be determined by serologic testing, genetic analysis is needed to make a definitive diagnosis. DTV is maintained in an enzootic cycle between I. scapularis and the white-footed mouse (P. leucopus). Until now, there are a small number of published cases of proven DTV infection encephalitis (Kuno, 2001), one from Canada and three from the United States of America. Based on the detection of virus genome, prevalence with DTV ranged up to 5% in I. scapularis from several geographic areas including Hudson Valley, Nantucket Island, and Prudence Island (Aliota et al., 2014). The increase in the number of human cases of POWV encephalitis that have been reported since 2010 is remarkable. Most of these cases were diagnosed by serological assays (El Khoury et al., 2013), and it is possible that DTV could be responsible for some of these cases.

Tick-borne encephalitis The etiological agent of TBE is a virus transmitted by the bite of Ixodes spp. ticks. Its incidence and geographical range across Eurasia have been increasing in recent decades. Most infections are asymptomatic, although a small proportion progresses to severe neurological disease. There are no specific antiviral treatments for TBE, but immunization with a vaccine based on inactivated virus is highly effective at preventing disease. The first descriptions of TBE in humans were reported from Scandinavia in the 18th century, although the causative neurotropic agent, TBEV, was first described by Zilber in 1939 (Zlobin et al., 2017). TBEV is transmitted in the saliva of feeding ticks of the genus Ixodes, mainly I. ricinus in Europe and I. persulcatus in Asia (see Fig. 6.2). Other tick vectors of

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FIGURE 6.2 Approximate geographical distribution of Ixodes vectors of tick-borne encephalitis virus in Eurasia. The shaded regions approximate to the range of Ixodes ricinus (blue), Ixodes persulcatus (yellow), and Ixodes ovatus (gray).

TBEV include Ixodes ovatus in Japan and Dermacentor reticulatus, found across many regions of Eurasia. I. ricinus and I. persulcatus ticks feed on a wide range of small mammals, birds, and large mammals during their life cycles. However, the primary animal reservoirs of the virus are small rodents, which are hosts for larval and nymphal ticks. Humans are accidental hosts and do not play a role in the persistence of TBEV. TBE is caused by a range of subtypes that include the Western (TBEV-Eu), Siberian (TBEV-Sib), and Far Eastern (TBEV-FE). Far Eastern subtypes are considered more virulent with more cases progressing to encephalitis and death. A further two subtypes have been reported, named Baikal (TBEV-Bkl) and Himalayan (TBEV-Him) (Michelitsch et al., 2019). Human cases occur during April to November, the spring and summer months in the Northern Hemisphere, when ticks are actively seeking hosts to take a blood meal and is endemic in Europe, Far Eastern Russia, Siberia, Northern China, and Japan (Linquist and Vapalahti, 2008). Transmission of the virus may be direct from an infected tick to the uninfected host but may also be passed from infected ticks to

Tick-borne diseases caused by bacteria

uninfected ticks when cofeeding in close proximity to one another on the vertebrate host. Endemic TBE occurs in regions where coincident larval and nymphal tick feeding occurs on small mammal reservoir hosts (Mansfield et al., 2009). In more recent years, there is evidence that TBEV has emerged in the Netherlands (Dekkar et al., 2019) and has been detected in Southern England (Holding et al., 2020). In addition to transmission by tick bite, infection can result from consumption of unpasteurized milk, or milk products from livestock infested with TBEV-infected ticks is an alternative route of infection (Fig. 6.3). In such cases, the incubation period may be reduced to 2e3 days (Krı´z et al., 2009). Prevention from tick-borne transmission is limited to covering bare skin during outdoor activity and the application of tick repellent compounds that reduce the risk of tick bite. Vaccination is highly effective at preventing infection.

Tick-borne diseases caused by bacteria Human granulocytic anaplasmosis

HGA is caused by the Gram-negative bacterium now known as Anaplasma phagocytophilum, a name that has replaced three synonyms, Cytoecetes phagocytophila, Erhlichia phagocytophila, and Erhlicha equi (Dumler et al., 2001). The bacterium has long been associated with the livestock disease tick-borne fever but has relatively recently been recognized as a human disease in North America (Chen et al., 1994). Total numbers of cases in north-eastern states, such as Maine, have increased dramatically from virtually no cases to as many as 1800 in a single year (Elias et al., 2020). Patients present with nonspecific symptoms such as headache, fever, and myalgia. Further investigation may show evidence of leukopenia and thrombocytopenia with thin blood smears showing the presence of granulocytic vacuoles within neutrophils. Transmission occurs following the bite of Ixodes species ticks (Table 6.3). Cases of HGA are rare in Europe (Azagi et al., 2020) despite the ubiquity of the main vector, I. ricinus, across the continent and a high rate of infection with A. phagocytophilum observed in field surveys for the pathogen (Stuen et al., 2013).

Lyme borreliosis In 1975, a cluster of pediatric arthritis cases in Lyme, Connecticut was investigated by the State Department of Health. Within a few years, the disease, now termed Lyme disease, had been described and bites from the black-legged tick, I. scapularis, were considered the source of the infection. By 1982, the cause of infection was proposed to be a spirochaete and subsequently named B. burgdorferi after the lead author of the paper (Burgdorfer et al., 1982). A firsthand account of the events leading to the identification of a spirochaete as the etiological agent has recently been published (Barber and Benach, 2019). B. burgdorferi

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FIGURE 6.3 Transmission of TBEV by Ixodes tick species with larva emerging from eggs and feeding on a small vertebrate host, developing into an intermediate nymph stage that will usually feed on a larger vertebrate host. This develops into the adult stage (male or female) that are usually associated with feeding on humans. The transmission phases are (1) transovarial from infected adult to the egg and then to the larval stage, (2) transstadial between the different feeding forms of the tick, (3) Cofeeding where virus can be transmitted to other life stages when feeding on the same host, (4) transmission to humans by direct feeding, and (5) infection acquired by consumption of contaminated milk from an infected ruminant.

Tick-borne diseases caused by bacteria

Table 6.3 Vectors of Anaplasma phagocytophilum. Continent

Vector

Europe North America

Ixodes Ixodes Ixodes Ixodes

Asia

ricinus (sheep tick) scapularis (deer tick or black-legged tick) pacificus (Western black-legged tick) persulcatus (taiga tick)

is now recognized as a species complex with an increasing number of genospecies (Stanekc and Reiter, 2011). In Europe, I. ricinus is the main vector of disease. Infection occurs from a tick bite although is dependent on the tick remaining attached for over 24 h with the risk of infection increasing with longer attachment. This emphasizes the need for prompt and complete removal of ticks once they are noticed. Human cases occur during the spring, summer, and autumn months of the year reflecting the periods of the year when the tick vectors are active in the Northern Hemisphere. Rodents and deer can act as reservoirs for Borrelia species with humans, and occasionally dogs (Little et al., 2010), being hosts susceptible to disease. The initial manifestation of disease is the development of a distinctive circular rash at the bite site termed erythema migrans, which develops between 3 and 30 days after infection. Within six months if left untreated, this can develop into systemic disease within the nervous and musculoskeletal system, characterized by meningitis, radicular pain (pain radiating from the back or hips), and arthritis (Biesiada et al., 2012). Diagnosis is initially based on presenting symptoms, history of a tick bite, and detection of antiborrelia antibodies in the patient’s serum. Treatment with antibiotics (doxycycline, amoxicillin, or cefuroxime) are highly effective, particularly when given early following infection. Systemic infection requires treatment with a higher dosage. A number of questions remain to be resolved for Lyme borreliosis: ➢ Is the range of Lyme increasing? ➢ What are the differences between infection with different genospecies? ➢ Are all the tick vectors known?

Ehrlichiosis Ehrlichiosis is a disease caused by bacteria of the genus Ehrlichia and like the related Rickettsia are obligate intracellular Gram-negative bacteria. Also like the Rickettsia, they share many of the symptoms and geographical range. Human ehrlichiosis is a relatively recently described disease. Prior to this, the disease was more commonly associated with livestock and domestic animals (see Chapter 7). The first case study was reported in 1987 (Maeda et al., 1987) and later attributed to a particular species, Ehrlichia chaffeensis (Anderson et al., 1991). The first human case of Ehrlichiosis in Europe was reported from Portugal in 1991 (David Morais et al., 1991).

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Following infection through a tick bite, Ehrlichia preferentially infect human monocytic cells including monocytes and macrophages. It initially presents as a nonspecific febrile illness with fever, headache, and myalgia. This can progress to a multisystemic disease that in some cases leads to a life-threatening meningoencephalitis (Saito and Walker, 2016). Treatment with doxycycline is effective. The vector in the North America, where most cases are reported, is the lone star tick, Amblyomma americanum.

Rickettsiosis The term rickettsiosis covers a range of diseases caused by an even greater number of pathogens grouped within the spotted fever Rickettsias. These are obligate intracellular bacteria belonging to the family Rickettsiaceae, order Rickettsiales, genus Rickettsia, all named after Howard T Ricketts, who demonstrated that Rocky Mountain spotted fever, a disease well known in the United States was transmitted by a tick vector and made the first tentative step toward describing the pathogen (Ricketts, 1906). The confirmation of a bacterial cause was made some years later by Simeon Burt Wolbach (Wolbach, 1919) following the early death of Ricketts in 1910 (Grob and Scha¨fer, 2011). The other disease associated with the Rickettsias is typhus, transmitted by fleas. As obligate intracellular bacteria, the Rickettsias have experienced gene loss relying on their host, the tick, to supply many of the requirements for growth and survival (Merhej et al., 2009). This has resulted in a considerable reduction in the genome size compared to other bacteria. Vertical transmission enables the Rickettsia to pass from adult to offspring and maintains the pathogen within the tick population. Humans are “dead end” or accidental hosts. Tick-borne rickettsiosis has been reported from around the world (Table 6.4) and transmitted by a vast range of hard ticks. Infection occurs following a tick bite and can lead to a localized inflammatory reaction and tissue necrosis with a black crust termed an inoculation eschar. In the case of Rocky Mountain spotted fever caused by Rickettsia rickettsia, this is followed a few days later by a papular skin rash, often starting at the wrists and ankles but spreading to other areas of the body. A spotted fever is often described for disease experienced by other species within the Rocky Mountain spotted fever (RMSF) group including Mediterranean spotted fever, also called boutonneuse fever (Rickettsia conorii), African tick-bite fever (Rickettsia Africae), and Japanese spotted fever (Rickettsia japonica). Infection with Rickettsia can cause a range of medical conditions termed TIBOLAR (tick-borne lymphadenopathy), SENLAT (scalp eschar and neck lymphadenopathy), and LAR (lymphangitis-associated rickettsiosis) making diagnosis based on clinical presentation challenging. Treatment with doxycycline is effective.

Tularemia Tularemia, commonly called rabbit fever, results from infection with the Gramnegative coccobacillus Francisella tularensis. The bacterium is highly infectious

Tick-borne diseases caused by bacteria

Table 6.4 Rickettsial species. Rickettsia species Rickettsia aeschlimannii Rickettsia africae Rickettsia australis Rickettsia sp. Strain Atlantic rainforest or Bahia Rickettsia conorii Rickettsia heilongjiangensis Rickettsia helvetica Rickettsia honei Rickettsia japonica Rickettsia massiliae

Tick vectors

Disease

Distribution

Amblyomma spp., Rhipicephalus spp., Hyalomma spp. Amblyomma spp., Hyalomma spp. Ixodes holocyclus, Ixodes tasmani, Ixodes cornuatus Amblyomma ovale, Amblyomma aureolatum, Rhipicephalus sanguineus

Spotted fever

Africa, Asia, Europe

African tick bite fever Queensland tick typhus Rash, eschar, and lymphadenopathy

Africa, America, Asia Australia

Rhipicephalus spp.

Mediterranean spotted fever Far Eastern spotted fever Human infections detected in Asia Flinders Island spotted fever Japanese spotted fever Spotted fever

Europe, Africa, Asia Asia

Haemaphysalis spp. Ixodes persulcatus, Ixodes Ricinus Bothriocroton hydrosauri, Ixodes spp. Haemaphysalis spp. Rhipicephalus spp.

Rickettsia monacensis Rickettsia parkeri

Ixodes ricinus, Ixodes persulcatus Amblyomma, Spp. Dermacentor variabilis

Rickettsia philipii

Dermacentor occidentalis

Mild escharassociated illness

Rickettsia raoultii Rickettsia rickettsia

Dermacentor spp. Dermacentor spp., Amblyomma spp.

SENLAT Rocky Mountain spotted fever

Rickettsia sibirica

Hyalomma spp., Dermacentor spp., Dermacentor marginatus, Dermacentor reticulatus Amblyomma testudinarium

LAR

Rickettsia slovaca Rickettsia tamurae

Spotted fever Mild rickettsiosis

SENLAT Infection reported in Japan and Laos

South America

Asia, Europe Asia, Australia Asia Asia, Europe, North and South America Europe, North Africa North and Central America North and Central America Asia, Europe North and Central America Europe, Asia, Africa Asia, Europe, North Africa Asia

Adapted from Parola, P., Paddock, C.D., Socolovschi, C., Labruna, M.B., Mediannikov, O., Kernif, T., Abdad, M.Y., Stenos, J., Bitam, I., Fournier, P.E., Raoult, D., 2013. Update on tick-borne rickettsioses around the world: a geographic approach. Clinical Microbiology Reviews 26(4), 657e702. https://doi. org/10.1128/CMR.00032-13

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with an infectious dose of below 10 bacteria sufficient to cause infection. Disease develops between 3 and 21 days of exposure from a bite from infected arthropods. Symptoms range from the development of a skin ulcer at the bite site, swollen lymph nodes, and febrile illness. Mortality in untreated cases can be as high as 15%. A range of antibiotics including streptomycin, gentamicin, doxycycline, and ciprofloxacin are effective treatments for the disease. F. tularensis is found throughout the Northern Hemisphere, although there are strain variations related to different geographical regions. The main tick species associated with transmission in North America are D. andersoni, Dermacentor variabilis, and A. americanum (Petersen et al., 2009). In Europe, I. ricinus and D. reticulatus have been associated with F. tularensis (Gehringer et al., 2013; Huba´lek et al., 1996). Although in Europe, mosquitoes are more commonly linked to transmission, particularly in Scandinavia. However, many questions remain on the role of ticks in maintaining F. tularensis within the environment (Zellner and Huntley, 2019). Here the role of lagomorphs, particularly rabbits and rodents, as the vertebrate host may be critical and thus arthropods that feed on these species should be considered vectors. One of these is the rabbit tick, Haemaphysalis leporispalustris Packard, 1869. This species has a long association with F. tularensis with it being reported in the tick since 1938 (Philip and Parker, 1938).

Coxiella burnetiidQ fever The final bacterium in this section is Coxiella burnetii, the cause of Q fever. It was first reported in Australia in the early 1930s among abattoir workers, and its name was derived from the term Query fever, in early reports. Animals are asymptomatically infected although it can cause abortion in ruminants, and it is through association with domestic ruminants that humans become infected (Van den Brom et al., 2015). Infection occurs following the inhalation of aerosolized bacteria that are found in animal excreta, birth fluids, and contaminated dust. Ingestion of unpasteurized milk has also been shown to result in infection. Initial infection is an acute flu-like illness but can progress to a long-term form with endocarditis, vascular infection, and chronic fatigue. Diagnosis relies on detection of the organism in blood during the acute phase or serology. Treatment is achieved through administration of antibiotics such as doxycycline. Q fever is reported from around the world and is a risk to all those who have close contact with animals including farm workers, veterinarians, and abattoir workers. Cases are usually sporadic, although the Netherlands experienced the largest outbreak of disease between 2007 and 2010 with over 4000 cases reported (Delsing et al., 2010). What then is the role of ticks in Q fever transmission? Surveys over many years have detected C. burnetii in over 40 hard and soft tick species. Indeed, one of the early pathogenic strains of C. burnetii, named “nine mile” was isolated from guinea pigs that were fed on by D. andersonii. Experimental evidence for transovarial, transstadial, and blood feeding transmission has been demonstrated. Despite this, direct transmission of the bacterium to humans, and possibly other vertebrate hosts,

Tick-borne diseases caused by protozoa

FIGURE 6.4 Transmission route of Coxiella burnetii to humans. The size of the arrow indicates the importance for pathogen transmission. Adapted from Duron, O., Sidi-Boumedine, K., Rousset, E., Moutailler, S., Jourdain, E., 2015. The importance of ticks in Q fever transmission: what has (and has not) been demonstrated? Trends in Parasitology 31 (11), 536e552. https://doi.org/10.1016/j.pt..2015.06.014

is considered rare with aerosol transmission by tick excreta being considered a means of infection due to high levels of bacterium in tick feces (Duron et al., 2015). The detection of C. burnetii in ticks has also been complicated by the presence of what are presumed to be nonvirulent Coxiella-like symbionts within many tick species. Genomic sequencing is required to differentiate the two bacterial forms. It seems likely that ticks play a role in maintaining C. burnetii in the environment with occasional transmission to vertebrates (Duron et al., 2015). This is shown schematically in Fig. 6.4.

Tick-borne diseases caused by protozoa Babesiosis

Cases of human hemolytic anemia or babesiosis, caused by tick-borne protozoa belonging to the genus Babesia, are generally rare but have been reported throughout the world. The exception to this has been in North America where there are almost 2000 cases of babesiosis per year (Rosenberg et al., 2018) caused by infection with Babesia microti, a species normally associated with infection in rodents (Vannier et al., 2015). In Europe, the main cause of babesiosis is due to infection with Babesia divergens or Babesia venatorum. Transmission occurs from the bite of an infected tick (Fig. 6.5) or from transfusion of contaminated blood. Babesia are related to malarial parasites, and infection of erythrocytes leads to their destruction and resulting anemia. Mild infections can lead to a flu-like illness, whereas severe cases can progress to anemia and organ failure.

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FIGURE 6.5 Schematic showing babesia sporozoite invasion of erythrocytes and development into merozoites within the vertebrate bloodstream. (A) Tick feeding leads to the introduction of babesia sporozoites into the blood stream, (B) invasion of erythrocytes, (C) formation of the ring form or trophozoite, (D) formation of two merozoites by binary fission, (E) release of merozoites to infect further red blood cells or infect a feeding tick. Inset shows the presence of Babesia merozoites within an erythrocyte on a Giemsa-stained thin blood smear.

Victor Babes discovered protozoal parasites as a cause of hemolytic anemia in cattle in the 1880s, hence the name Babesia. There are now over 100 species identified within the genus associated with infection in vertebrates. Their transmission by ticks has been recognized for almost as long as their discovery. Healthy individuals are usually either resistant or experience asymptomatic infection. Occasional cases develop with nonspecific symptoms such as fever, fatigue, headache, and nausea. As the parasitemia develops with higher levels of blood-borne forms, erythrocyte destruction leads to severe anemia. Acute infections, usually associated with asplenic or immune-compromised individual and the very young or very old, can experience respiratory, cardiac, renal, or hepatic failure. In such cases, treatment may alleviate disease but can lead to a persistent infection (Bloch et al., 2019). A history of a tick bite can be indicative of babesiosis although many other pathogens

Nonpathogen-associated disease

are transmitted by this means. In North America, B. microti is transmitted by the deer or black-legged tick, I. scapularis (Westblade et al., 2017). In Europe, B. microti is associated with I. trianguliceps, a species that rarely feeds on large mammals. B. divergens is transmitted by the common sheep tick, I. ricinus in Europe. I. persulcatus is considered a key vector in Asia (Zhou et al., 2014). Babesiosis might be suspected if anemia occurs subsequent to a tick bite. Preliminary diagnosis can be made by detecting the paired merozoite stage within erythrocytes in Giemsa-stained thin blood smears. Parasites appear as dark piriform (pear-like) structures, often paired, within the red blood cell. Occasionally, four merozoites form to give the appearance of a Maltese cross-like structure. Laboratory diagnosis can be based on serological means (Immunofluorescent Antibody Test) or by polymerase chain reaction on DNA extracted from a blood sample. While there are some differences in morphological appearance of different Babesia species when infected erythrocytes are viewed under a microscope, accurate delineation of species is dependent on genomic sequencing. Occasionally, the veterinary drug imizol (imidocarb diproprionate) has been used in humans to treat babesiosis under special license. The treatment of choice is atovaquone (hydroxyl-naphthoquinone), which is licensed for human use and has effective antiparasite activity (Gray et al., 2010). Human babesiosis is considered rare in Europe and usually associated with infection with B. divergens or to a lesser extent B. venatorum (Gray et al., 2010). A review of cases identified 11 due to infection with B. divergens and three due to B. venatorum (Azagi et al., 2020). Disease is often reported in patients that are immunocompromised and most have had their spleen removed prior to infection. Patients become infected after being bitten by the I. ricinus tick. Infection can be fatal but is treatable. The disease is characterized by fever and hemolytic anemia associated with destruction of red blood cells by the parasite. The last case of human babesiosis in the United Kingdom was in a 34-year-old male from Scotland in 1978 (Entrican et al., 1979). In this case, the patient had previously undergone a splenectomy as a result of Hodgkin’s disease. Based on the morphology of parasites in the patients’ erythrocytes and serological responses, the causative agent was identified as B. divergens. A further case of human babesiosis in the British Isles was in a 79year-old Republic of Ireland resident in 2015 (O’Connell et al., 2017).

Nonpathogen-associated disease By their nature, tick bites are damaging to the skin of the host as the tick’s aim is to penetrate the upper layers of the dermis to access tissue and blood below the surface. In humans, once the tick has been removed or detaches, it can leave small demarcated lesions that can become inflamed but usually resolves within a few days. A more dramatic reaction to a tick bite is the development of alpha-gal syndrome, often referred to a meat allergy. This occurs due to an immunological reaction to galactose-a-1,3-galactose (a-gal), a carbohydrate present in mammalian

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meat or meat products, although not found in humans. The main symptom associated with the allergy is urticaria (skin rash), although severe anaphylaxis can result after consumption of meat. Sensitivity appears to be caused by exposure to certain components of tick saliva that causes the development of anti-a-gal IgE. Not all ticks can trigger this response with the main species being A. americanum, I. ricinus, Ixodes holocyclus, and Haemaphysalis longicornis (Young et al., 2021). A condition known as STARI (Southern Tick-Associated Rash Illness) has been described in the United States that presents with a rash similar to that caused by B. burgdorferi. This develops following a bite from the lone star tick A. americanum and can progress with symptoms including fatigue, fever, and headache with joint and muscle pains (Masters et al., 2008). Currently, the causative agent for this condition has not been identified. A final condition associated with tick bites is that of tick paralysis. This rare condition primarily affects young children bitten by ticks. A toxin within tick saliva from a range of tick species causes progressive neuromuscular paralysis (HallMendelin et al., 2011). Removal of the tick can lead to gradual recovery although the patient may require ventilator support, and if untreated, the condition can be fatal. The species I. holocyclus, found along the east coast of Australia has been most commonly associated with cases of tick paralysis.

Conclusions There is a great diversity of pathogens that ticks transmit to humans across the globe. In many regions, ticks are the main arthropod vectors of disease. The previous sections of this chapter have dealt individually with particular pathogens, but many ticks are infected with multiple pathogenic organisms (Swanson et al., 2006) and can in turn infect humans with multiple pathogens. For example, coinfection with Babesia microti and B. burgdorferi, both transmitted by I. scapularis has been documented in North America (Diuk-Wasser et al., 2016; Parveen and Bhanot, 2019). The overlapping disease signs and symptoms of many of the tick-borne disease mean that detecting such cases relies on serological demonstration of a response against different pathogens or molecular detection of the individual agents. In extreme cases, coinfection with three pathogens (B. burgdorferi, Babesia microti, and POWV) has been reported (Khan et al., 2019). Where possible prevention of tick bites is the most effective means of avoiding infection, the main means of prevention is for humans to avoid areas where ticks are present, and if that is not feasible, wear clothing that covers skin that may be at risk of tick exposure. If a tick is found, it should be removed immediately using tweezers to grasp the mouth parts to avoid leaving fragments of the tick in the wound as squeezing the tick could lead to injection of the tick contents. Vaccination against some tick-borne diseases is well established. However, further research is needed to develop vaccines against a large number of the pathogens discussed in this chapter and the design of effective treatments to reduce the severity of the disease once diagnosed.

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Masters, E.J., Grigery, C.N., Masters, R.W., 2008. STARI, or Masters disease: lone star tickvectored lyme-like illness. Infectious Disease Clinics of North America 22 (2), 361e376. https://doi.org/10.1016/j.idc.2007.12.010. McLean, D.M., Cobb, C., Gooderham, S.E., Smart, C.A., Wilson, A.G., Wilson, W.E., 1967. Powassan virus: persistence of virus activity during 1966. Canadian Medical Association Journal 96 (11), 660e664. McLean, D.M., Donohue, W.L., 1959. Powassan virus: isolation of virus from a fatal case of encephalitis. Canadian Medical Association Journal 80 (9), 708e711. Mehla, R., Kumar, S.R.P., Yadav, P., Barde, P.V., Yergolkar, P.N., Erickson, B.R., Carroll, S.A., Mishra, A.C., Nichol, S.T., Mourya, D.T., 2009. Recent ancestry of Kyasanur Forest disease virus. Emerging Infectious Diseases 15 (9), 1431e1437. https://doi.org/ 10.3201/eid1509.080759. Memish, Z.A., Balkhy, H.H., Francis, C., Cunningham, G., Hajeer, A.H., Almuneef, M.A., 2005. Alkhumra haemorrhagic fever: case report and infection control details. British Journal of Biomedical Science 62 (1), 37e39. https://doi.org/10.1080/ 09674845.2005.11978070. Merhej, V., Royer-Carenzi, M., Pontarotti, P., Raoult, D., 2009. Massive comparative genomic analysis reveals convergent evolution of specialized bacteria. Biology Direct 4, 13. https:// doi.org/10.1186/1745-6150-4-13. Mertens, M., Schuster, I., Sas, M.A., Vatansever, Z., Hubalek, Z., Gu¨ven, E., Deniz, A., Georgiev, G., Peshev, R., Groschup, M.H., 2016. Crimean-Congo hemorrhagic fever virus in Bulgaria and Turkey. Vector Borne and Zoonotic Diseases 16 (9), 619e623. https:// doi.org/10.1089/vbz.2016.1944. Michelitsch, A., Wernike, K., Klaus, C., Dobler, G., Beer, M., 2019. Exploring the reservoir hosts of tick-borne encephalitis virus. Viruses 11 (7), 669. https://doi.org/10.3390/ v11070669. Mourya, D.T., Yadav, P.D., 2016. Recent scenario of emergence of Kyasanur Forest disease in India and public health importance. Current Tropical Medicine Reports 3 (1), 7e13. https://doi.org/10.1007/s40475-016-0067-1. Mourya, D.T., Yadav, P.D., Mehla, R., Barde, P.V., Yergolkar, P.N., Kumar, S.R.P., Thakare, J.P., Mishra, A.C., 2012. Diagnosis of Kyasanur Forest disease by nested RTPCR, real-time RT-PCR and IgM capture ELISA. Journal of Virological Methods 186 (1e2), 49e54. https://doi.org/10.1016/j.jviromet.2012.07.019. Mourya, D.T., Yadav, P.D., Sandhya, V.K., Reddy, S., 2013. Spread of Kyasanur Forest disease, Bandipur Tiger Reserve, India, 2012-2013. Emerging Infectious Diseases 19 (9), 1540e1541. https://doi.org/10.3201/eid1909.121884. Moutailler, S., Popovici, I., Devillers, E., Vayssier-Taussat, M., Eloit, M., 2016. Diversity of viruses in Ixodes ricinus, and characterization of a neurotropic strain of Eyach virus. New Microbes and New Infections 11, 71e81. https://doi.org/10.1016/j.nmni.2016.02.012. Murhekar, M.V., Kasabi, G.S., Mehendale, S.M., Mourya, D.T., Yadav, P.D., Tandale, B.V., 2015. On the transmission pattern of Kyasanur Forest disease (KFD) in India. Infectious Diseases of Poverty 4 (1). https://doi.org/10.1186/s40249-015-0066-9. Neronov, V.M., Khlyap, L.A., Bobrov, V.V., Warshavsky, A.A., 2008. Alien species of mammals and their impact on natural ecosystems in the biosphere reserves of Russia. Integrative Zoology 3 (2), 83e94. https://doi.org/10.1111/j.1749-4877.2008.00084.x. O’Connell, S., Lyons, C., Abdou, M., Patowary, R., Aslam, S., Kinsella, N., Zintl, A., Hunfeld, K.-P., Wormser, G.P., Gray, J., Merry, C., Alizadeh, H., 2017. Splenic dysfunction from celiac disease resulting in severe babesiosis. Ticks and Tick-Borne Diseases 8 (4), 537e539. https://doi.org/10.1016/j.ttbdis.2017.02.016.

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Zlobin, V.I., Pogodina, V.V., Kahl, O., 2017. A brief history of the discovery of tick-borne encephalitis virus in the late 1930s (based on reminiscences of members of the expeditions, their colleagues, and relatives). Ticks and Tick-Borne Diseases 8 (6), 813e820. https:// doi.org/10.1016/j.ttbdis.2017.05.001.

CHAPTER

Tick-borne diseases of animals

7

In many regions of the world, farmers in developing countries rely heavily on livestock for subsistence and as the foundation of the rural economy. For much of the rest, intensive livestock rearing is required to supply growing urban populations with food. Both economic scenarios are threatened by tick-borne diseases. This chapter will focus on the major tick-borne diseases affecting livestock, domestic animals, and, where relevant, the role of wildlife in maintaining these diseases. Each section will describe the disease, the etiological agent of that disease, and the ticke host relationship. For some diseases, treatment or vaccination is available, although not for all. Many of the diseases described in this chapter could justifiably be described as neglected.

Introduction The association between ticks and disease transmission to livestock began in the late 19th century, almost simultaneously, on separate continents. In Europe, Victor Babes, a Romanian bacteriologist, identified the piriform structures of what are now called Babesia in the blood of cattle. Coincidentally, in the United States, Theobald Smith and Frederick Kilbourne demonstrated the link between ticks and Texas fever in cattle (Assadian and Stanek, 2002). Over the course of the following century, scientific innovations including the ability to culture pathogenic agents and the advent of molecular biology have enabled the discovery and description of numerous tick-borne pathogens of animals. This process continues to this day. However, ticks alone are rarely the single link in transmission. Other vertebrates usually play a role in maintaining pathogens within an ecosystem and are deemed a reservoir species (Fig. 7.1). Despite the simplicity of Fig. 7.1, there are often overlapping infection cycles with wildlife acting as a reservoir that maintains the pathogen without any overt manifestations of disease. Livestock and domestic animals, which are often highly susceptible to developing disease, are infected when they are exposed to tick bites when introduced into an area in which the reservoir cycle is occurring. The tick vector plays a pivotal role in maintaining a pathogen within an ecosystem and transmitting the pathogen to animals. A typical example is the movement of susceptible cattle onto tick-infested pasture triggering a subsequent outbreak of disease. Within the domestic sphere, pet reptiles are included for their ability to facilitate tick movement resulting in the translocation of exotic ticks Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00012-5 Copyright © 2023 Elsevier Inc. All rights reserved.

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FIGURE 7.1 Schematic for tick-borne infection in animals. The arrows are bidirectional to indicate that pathogens can be transmitted either way.

(Mihalca, 2015). This can result in the infestation of reptile housing such as the importation of Amblyomma marmoreum into the United States (Allan et al., 1998). Livestock are relatively large mammals and often held at high density providing a ready target for obligate blood-feeding ticks. Tick-borne infectious diseases present one of the greatest challenges to the livestock industry, particularly in regions of Africa and Asia, regions where access to veterinary support is at its weakest, and the impact on food supply and economy is at its greatest (Sungirai et al., 2016). In areas of the world such as South America and Australia, where cattle ranching has developed into intensive mass production, ticks can cause significant morbidity and mortality. In addition to the impact of tick-borne diseases, tick infestation can have direct affects. These include blood loss during heavy infestations and failure to put on weight. The act of infestation by ticks can cause further economic cost through hide damage and predispose the animal to further infection with

Tick-borne diseasesdviruses

Table 7.1 A summary of the major diseases of livestock, the causative pathogen, and the tick vector. Disease

Pathogen

Vector

African swine fever Babesiosis Ovine meninogoencephalitis Theileriosis Nairobi sheep disease

African swine fever virus Babesia spp. Louping ill virus

Ornithodoros spp. Ixodes ricinus Ixodes ricinus

Theileria spp. Nairobi sheep disease virus

Various tick species Rhipicephalus appendiculatus Ixodes ricinus Various tick species

Anaplasmosis

Heartwater Canine ehrlichiosis

Anaplasma phagocytophilum Anaplasma marginale Ehrlichia ruminantium Ehrlichia canis

Amblyomma variegatum Rhipicephalus sanguineus

bacteria such as Dermatophilus congolensis (Ambrose, 1996), fungal infections, and infestation with fly larvae such as the screw-worm (Cochliomyia hominivorax). Pathogen infection can reduce milk yields and muscle mass. Loss of fertility can reduce the ability of farmers to replace livestock requiring importation of immunologically naı¨ve animals that in turn can result in further disease. Then there are the costs of introducing tick control in the form of acaricides and vaccination (see Chapter 13). However, breaking the transmission link through targeting the vector offers the main opportunity for control of tick-borne disease in animals. While the majority of scientific research is focused on the tick-borne diseases of livestock, domestic animals such as dogs and cats that readily enter environments where they will encounter ticks are also subject to infection with a range of tickborne pathogens. And there are tick species such as Rhipicephalus sanguineous, which are capable of infesting human habitation allowing all life stages to feed on resident pets. The following sections consider the major tick-borne diseases, summarised in Table 7.1, affecting animals throughout the world.

Tick-borne diseasesdviruses African swine fever

African swine fever (ASF) is caused by African swine fever virus (ASFV), a doublestranded DNA virus and the only member of the family Asfarviridae. The virus evolved in Africa where it is transmitted by soft ticks within the genus Ornithodoros. Its recent introduction and rapid spread in Europe are one of the most significant threats to the pig production industry in decades. However, transmission in temperate regions occurs directly between susceptible animals in the absence of the tick vector.

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In Africa, ASFV is transmitted by the burrow-dwelling soft ticks of the genus Ornithodoros such as Ornithodoros moubata. Infection in native porcine species, such as warthogs (Phacochoerus africanus), causes subclinical disease, and distribution of the virus is limited by that of the vector and native vertebrate hosts to parts of East and Southern Africa. This forms the natural reservoir cycle. The introduction of domestic pigs (Sus domesticus) that are considerably more susceptible to infection compared to their nondomesticated cousins leads to spillover into livestock and has caused devastating outbreaks of disease with mortality reaching 100% in some cases (Dixon et al., 2019). Infection causes hemorrhagic disease in susceptible pigs associated with the depletion of a range of blood cell types (Blome et al., 2013). Transmission to domestic pigs can take a number of routes. These include transmission following tick infestation, contact with infected wild pigs, or contact with other infected domestic pigs. This makes the epidemiological cycles of ASF very complex in Africa and challenges approaches to control. ASFV was introduced in the Caucasus region in 2007. Even in the absence of a tick vector, it spread rapidly north into the Russian Federation, presumably through the movement of domestic pigs. It then entered the wild boar population in the Baltic States, a wild species that does not develop significant disease. From this source, ASF emerged in Western Europe in the summer of 2018 (Garligliany et al., 2019; Linden et al., 2019). In Northern Europe, there are no known tick vectors, so transmission is exclusively through direct contact between animals. In the absence of an effective vaccine and the means to deliver it to a wildlife reservoir, the only response has been to control disease spread through the culling of wild boar populations.

Ovine encephalitis (louping ill) Ovine encephalitis is caused by a group of tick-borne flaviviruses, family Flaviviridae, found exclusively in Europe. The disease, also referred to as louping ill, has been observed in sheep for centuries, but it was not until the late 1920s that the infectious agent was isolated from the central nervous system of sheep showing neurological disease signs and demonstrated, through filtration, to be a virus. The main example of this group of viruses is louping ill virus (LIV), the only indigenous tick-transmitted virus of livestock currently present in the United Kingdom. The disease results from viral encephalomyelitis, mainly affecting sheep, which manifests as incoordination, altered gait, and ataxia. Other mammals can be infected although cases are rare but have included a domestic dog (Dagleish et al., 2018). Red grouse (Lagopus lagopus scoticus) are also susceptible to infection, and sustained transmission can lead to significant economic losses. As a result of the distribution of sheep and grouse, and the relative abundance of the tick vector, infections are mainly reported in upland areas of the British Isles (Fig. 7.2), with sporadic reports of disease in sheep from the west of Scotland, Cumbria, Wales, and Devon (Jeffries et al., 2014). Wildlife may play a role in maintaining LIV within the tick population, and certain deer species are susceptible to infection.

Tick-borne diseasesdviruses

FIGURE 7.2 Map of the British Isles showing areas where louping ill infections are reported.

The role of Ixodes ricinus ticks in disease transmission was established in the 1930s (Macleod and Gordon, 1932). Ticks can also be infected with LIV through cofeeding (defined as feeding in close proximity to another infected tick), without infection or viraemia in the host (Jones et al., 1997). This contributes to the persistence of LIV even when control measures in sheep, such as vaccination, are applied. Coinfection with other tick-borne infections such as Anaplasma phagocytophilum can increase the susceptibility to infection and lead to greater sheep mortality (Reid et al., 1986). Acaricide treatment of sheep and habitat management that suppresses ticks are the main measures to reduce infection. A number of closely related flaviviruses have been reported in Europe that also appear to be transmitted by I. ricinus ticks and cause encephalitis in ovine species. These viruses appear to be restricted geographically to locations around the Mediterranean Basin. Recent examples have been reported in Greece (Papa et al., 2008) and northern Spain (Balseiro et al., 2012), both causing encephalitis in goats.

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Although closely related to tick-borne encephalitis virus, which is rarely reported to cause disease in anything other than humans, cases of louping ill infection in humans are rare (Davidson et al., 1991). The reason for this difference in virulence for humans and other animals remains unresolved.

Nairobi sheep disease Nairobi sheep disease (NSD) is an acute disease of small ruminants, principally sheep and goats, which occurs following infection with Nairobi sheep disease orthonairovirus (NSDV). The virus is classified within the genus Orthonairovirus and family, Nairoviridae. It is closely related to the human pathogen CrimeaneCongo hemorrhagic fever (Kuhn et al., 2016). These viruses have a negative-stranded RNA genome composed of three segments that code for the structural and nonstructural proteins that make up the virus. Human infections with NSDV have been reported, but it is primarily considered a disease of livestock that threatens the economy of low-income countries (Krasteva et al., 2020). Signs of infection, following tick infestation, begin with a fever with temperatures above 40 C and progresses to severe diarrhea caused by hemorrhagic gastroenteritis. Abortion can occur, and nasal discharge is often observed. Mortality within flocks can reach over 90%. Goats, while less susceptible than sheep, also experience disease. The vector for NSDV varies with continent. In Africa, where the disease was first described in 1910, Rhipicephalus appendiculatus is the main species responsible for transmission (Lewis, 1946). In India, where the virus is named Ganjam virus, the vector is Haemaphysalis intermedia (Joshi et al., 2005). Genetic analysis has shown that the two viruses are virtually identical. A recent development has been the detection of NSDV genetic material in Haemaphysalis longicornis ticks in China (Gong et al., 2015; Yang et al., 2019). The viruses detected in China appear to be quite divergent from those in Africa and India, and there have been no reports of NSD in livestock. Livestock present on tick-infested land appear to develop an immunity to NSDV, and disease occurs when naı¨ve animals are moved onto land where ticks are present. Attempts to identify wildlife reservoirs in Africa have been unsuccessful (Davies, 1978), although this may only mean that they are yet to be found. Despite the potential impact on the economies in low-income countries, there is no specific treatment for NSD in livestock and no commercially available vaccine (Baron and Holzer, 2015). This only leaves acaricides in the form of pour-on formulations or dips for the suppression of the tick population. However, these are not considered effective in the long term.

Thogoto virus Another virus that has occasionally been reported to cause disease in African livestock is Thogoto virus, an orthomyxovirus related to Bourbon virus, a cause of human tick-borne disease in North America. Reports suggest that this causes a febrile

Tick-borne diseasesdprotozoa

episode and abortion in sheep (Davies et al., 1984). The virus has been detected in both R. appendiculatus and Amblyomma variegatum ticks (Sureau et al., 1976; Davies et al., 1990). There are also early reports of this virus being present in Europe, although it has not been associated with the disease (Lledo´ et al., 2020).

Tick-borne diseasesdprotozoa Babesiosis

Babesiosis is a tick-borne intraerythrocytic protozoan disease that affects mammals. It is caused by a large number of species within the genus Babesia (Table 7.2), a group of protozoans related to the malaria parasite, within the phylum Apicomplexa and the order Piroplasmida. The name piroplasm was derived from the Latin word for pear (pirum) based on the appearance of the “pear-shaped” intracellular structures, or merozoites, observed within red blood cells of infected animals. The group is related to the Theilerias discussed in the next section. Table 7.2 provides a list of Babesia species and the main tick vectors. Disease in animals may be subclinical or present as a low-grade fever with anorexia that might be missed. Severe clinical disease results from a combination of hemolytic anemia caused by the destruction of erythrocytes and the hosts’ response to infection. This can lead to hemoglobinuria, and in cattle, the common name for the disease in the United Kingdom is redwater fever. Death can result Table 7.2 Babesia species affecting animals and their tick vector. Species

Babesia species

Principal tick vector

Key reference

Cattle

B. bovis B. bigemina B. major B. divergens B. ovis B. ovata B. motasi B. canis B. rossi B. vogeli B. gibsoni B. felis B. caballi/Theileria equi

Rhipicephalus annulata Rhipicephalus microplus Haemaphysalis punctata Ixodes ricinus ?a ? Haemaphysalis punctata Dermacentor reticulatus Haemaphysalis elliptica Rhipicephalus sanguineus Haemaphysalis longicornis ? Dermacentor reticulatus/ marginatus Hyalomma spp. ? Rhipicephalus spp.

Bock et al. (2004)

Ruminants

Dogs

Cats Horses

Pigs a

B. perroncitoi B. trautmanni

The tick vector is uncertain.

Schnittger et al. (2003) Irwin (2009)

Oosthuizen (2020) Onyiche et al. (2020) Avenant et al. (2021)

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from hepatic and respiratory complications, and renal congestion caused by the deposition of hemoglobin in the renal tubules. Following recovery, low levels of infection may be maintained within erythrocytes of affected animals for a number of years without signs of clinical disease and which may form a reservoir of infection for feeding ticks. Calves below nine months of age demonstrate an inverse, agerelated resistance, unrelated to maternal immunity and do not suffer clinical disease. As this declines, animals become more susceptible to infection. Babesia spp. infect ticks after they have fed on infected animals, and the parasite can be transmitted via transovarial transmission from a female tick to the next larval generation, then transstadially to nymphs and adults. As a result, one complete generation of ticks is capable of transmitting the disease to naı¨ve animals following a single blood meal in the previous generation, enabling the parasite to persist over multiple years. The most significant species causing babesiosis in cattle are Babesia bigemina and Babesia bovis (Bock et al., 2004) with both species being found on most continents. The most common species causing disease in Europe is Babesia divergens, a species that was first described in England by McFadyean and Stockman in 1911 (McFadyean and Stockman, 1911). Its distribution is limited in Europe by that of its tick vector, I. ricinus. In Europe, many deer species play a role as reservoir host to a range of Babesia species, including B. divergens (Hrazdkilova´ et al., 2020). Other Babesia species have been detected in British cattle transmitted by Haemaphysalis punctata in the southeast and based on its morphology was considered to be the relatively nonpathogenic species Babesia major (Brocklesby and Sellwood, 1973). Additional species that can infect cattle include Babesia ovata in Eastern Asia, Babesia occultans in Africa and more recently the Mediterranean area, and Babesia venatorum (formerly Babesia sp.EU1) (Bock et al., 2004). Treatment includes supportive therapy including intravenous administration of fluids, blood transfusion, and administration of vitamins as well as antiprotozoal chemotherapy using imidocarb diproprionate. Babesiosis in horses is termed equine piroplasmosis and caused by infection with one of two piroplasms, Babesia caballi or Theileria equi. Transmission is by many species of ticks, mainly belonging to the genera Dermacentor, Hyalomma, or Rhipicephalus (Scholes and Ueti, 2015). A major method of spread of this disease is through the international movement of horses for racing, polo, or breeding (Onyiche et al., 2020). A number of Babesia species cause mild disease in sheep and goats. These include B. ovis, Babesia motasi, and Babesia crassa (Schnittger et al., 2003). In Europe, disease presents as hemolytic anemia and chronic wasting, although it is rarely reported. Infection of small ruminants is particularly prevalent in countries of the Middle East (Haghi et al., 2017) and in China. Babesiosis in pigs is rare and, when detected, due to infection with species including Babesia perroncitoi, Babesia trautmanni, and Babesia suis (Uilenberg, 2006; Avenant et al., 2021). Canine babesiosis is encountered around the world (Irwin, 2009) and caused by a small number of Babesias transmitted by different tick species (see Table 7.2).

Tick-borne diseasesdprotozoa

Disease can be unapparent, but in severe cases, dogs can develop a fatal anemia (Matiatko et al., 2012). The movement of dogs between disease-endemic regions to disease-free areas is a regular occurrence, although in the absence of the vector, cases are sporadic and the disease fails to become endemic (de Marco et al., 2017). A number of Babesia spp. have been detected in wild felids that might be distinct from well-described species. The tick vector for these species remains unknown. Babesiosis in domestic cats is rare, and investigations have often found infection by canid variants (Oosthuizen, 2020).

Theileriosis Theileriosis is a significant cause of disease in livestock around the world and a challenge to livestock management, particularly in sub-Saharan Africa. The Theilerias are classified within the phylum Apicomplexa and order Piroplasmida, and together with the Babesias are a significant cause of livestock disease throughout the world. Theilerias have a complex life cycle with multiple forms involved in replication within the vertebrate host and sexual reproduction occurring in the tick vector. The tick inoculates sporozoites into the vertebrate host during feeding, and these initially infect nucleated cells within the blood (leukocytes) to form a schizont. These mature and are released as merozoites that infect red blood cells where further replication occurs. Erythrocyte destruction, shared with Babesia, leads to one of the defining features of theileriosis, hemolytic anemia. Onward transmission to the tick occurs on subsequent feeding (reviewed by Mans et al., 2015). A critical step is the effect on leukocytes with some Theileria spp. causing transformation following development of the schizont stage (Sivakumar et al., 2014). This can lead to cellular replication and uncontrolled proliferation of schizonts resulting in diseases of cattle such as Corridor disease caused by Theileria annulata and East Coast fever caused by Theileria parva. Ovine theileriosis is a disease of small ruminants, mainly sheep (Ovis aries) and goats (Capra aegagrus hircus), following tick-borne transmission of a Theileria species (Uilenberg, 1997). A malignant theileriosis of sheep and goats is caused by Theileria lestoquardi. In countries where there is a high dependence on ovine livestock husbandry, theileriosis can have a significant impact. Countries such as China, Pakistan, and Turkey have reported high incidence of the disease. In China, cases of ovine theileriosis were considered to be infection with T. lestoquardi. However, certain biological characteristics of the blood-borne stage and the absence of Hyalomma spp. ticks in affected areas lead to the suspicion that other Theileria species were present. This suspicion was supported by sequence analysis on Theilerias detected in livestock (Yin et al., 2007) leading to the identification of two further Theileria species, Theileria luwenshuni and Theileria uilenbergi. Both appear to be vectored by Haemaphysalis qinghaiensis. Two further species, Theileria ovis and Theileria separata have been detected in livestock in Africa (Gebrekidan et al., 2014), and the former has been detected in livestock surveys from across

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Asia (Al-Fahdi et al., 2017; Hakimi et al., 2019). Table 7.3 provides a summary of the tick species associated with the transmission of Theilerias to ovine species. Theileria species OT3 was first reported in a prevalence survey of healthy sheep in Spain (Nagore et al., 2004). Polymerase chain amplification of the 18S rRNA gene was used to detect Theileria DNA within the blood of sampled sheep revealing the presence of three species, T. ovis, Theileria OT1 (subsequently renamed as T. luwenshuni), and Theileria OT3. Theileria OT3 has now been detected across Europe (Hornok et al., 2015), the Middle East (Tabaei et al., 2018), and Asia (Tian et al., 2014). Detection of Theileria OT3 in Europe has been from sheep and H. punctata ticks (Hornok et al., 2015). Subsequent studies in Spain (Garcı´aSanmartı´n et al., 2007; Remesar et al., 2019) detected a high prevalence of Theileria OT3 in healthy red deer (Cervus elephas) and roe deer (Capreolus capreolus) suggesting that deer may be the natural host for this Theileria and infection in sheep represents a spillover infection. A final Theileria species, reported as Theileria MK, has been detected in Turkey (Altay et al., 2007). Repeated surveys have detected this species in both sheep and goats (Aydin et al., 2013), and an unpublished 18S rRNA sequence reported as Theileria MK isolated from sheep has been documented from Pakistan. The tick vector has not been identified. The principal means of detecting Theilerias, and piroplasms in general, is by the microscopic examination of thin blood smears (Lempereur et al., 2017). This relies on the detection of the red blood celleassociated merozoites and while technically

Table 7.3 Theileria species with a strong association with infection in small ruminants (sheep/goats). Species

Vector

Distribution

Lymphocyte transforming

Theileria ovis

Rhipicephalus spp Hyalomma spp.

Africa, Asia

No

Africa, Asia

Yes

Haemaphysalis spp. Haemaphysalis spp Rhipicephalus spp Haemaphysalis sp. Unknown

Asia, Europe

No

Asia

No

Africa

No

Europe, Asia

Unknown

Middle East (Turkey, Pakistan)

Unknown

Theileria lestoquardi ( also referred to as T. hirci in some studies) Theileria luwenshuni (formerly Theileria sp. 1 China) Theileria uilenbergi (formerly Theileria sp. 2 China) Theilera separata Theileria OT3 Theileria MK

Tick-borne diseasesdprotozoa

simple, can be time-consuming and subjective. An alternative to this approach is the use of molecular detection methods. Techniques such as polymerase chain reaction (PCR) (Kirvar et al., 1998) and reverse line blot (Gubbels et al., 1999; Iqbal et al., 2013) have been applied to the detection of Theileria spp. These can be used to detect piroplasm DNA within blood samples and can be highly sensitive. In addition, PCR generates an amplicon that can be sequenced, which in turn can be used to identify the species of infecting piroplasm based on existing sequence data (Schnittger et al., 2003). If the sequence is of sufficient length, it can be used to assess the phylogenic relationship between samples. A common target for detection is either the full length or partial sequence of the 18S rRNA gene. The Theileria species found across Europe are considered to be low- or nonpathogenic, although examples of disease outbreaks have been observed. During the 1970s and 1980s, Theileria species were detected in the United Kingdom livestock based on the observation of merozoites in blood smears and serological responses of animals following infection (Morzaria et al., 1974 and references therein). This was prior to the ability to sequence the genetic elements of the parasite. Recent detections of Theileria species in livestock suggest that there is another species present in the United Kingdom that can cause disease in sheep under certain circumstances (Phipps et al., 2016). Using molecular techniques, a range of studies in Europe have detected Theileria spp. in sheep in different countries. A survey of randomly selected animals from Spanish sheep flocks detected three Theileria species including T. ovis, Theileria sp. OT1 (subsequently T. luwenshuni), and species OT3 (Nagore et al., 2004). In South Croatia, T. ovis was detected in blood collected from healthy sheep and Rhipicephalus spp. ticks (Rhipicephalus turanicus and Rhipicephalus bursa), while Theileria sp. OT3 was detected in sheep with signs of piroplasmosis (Duh et al., 2008). A range of Theileria spp. were detected in both Haemaphysalis spp. ticks, sheep, and goats from a survey in Greece (Chaligiannis et al., 2018). Haemaphysalis parva but not H. punctata was associated with infection with T. annulata, T. ovis, and T. lestoquardi. A similar study investigating the presence of pathogens in ticks removed from animals including cattle, sheep, and foxes from sites across Romania only detected Theileria buffeli in two R. bursa removed from cattle (Andersson et al., 2017). In Portugal, Theileria spp. were detected in R. bursa removed from livestock (Ferrolho et al., 2016). These were tentatively identified as T. annulata and T. equi.

Bovine theileriosis A number of Theileria species can cause disease in cattle. The major species are T. parva and T. annulata in Africa where their ability to transform lymphoid cells leads to widespread morbidity and mortality. Due to the extreme impact of these diseases on cattle rearing across Africa, considerable effort has been applied to the development of effective vaccines. Control of T. parva has been dependent on vaccination with live sporozoites derived from three strains, known as the Muguga cocktail (Nene and Morrison, 2016). As the vaccine is live and capable of causing disease, animals also need

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to be treated with antibiotics to enable a transient infection that induces sufficient immunity to protect against subsequent exposure to the parasite. Infection with nontransforming Theileria species results from erythrocyte destruction. Principal among these is Theileria orientalis. This species was historically known by a number of names, T. buffeli and Theileria sergenti, derived from investigations from different parts of the world. However, it is now recognized as a single species (Uilenberg, 1985) with a very wide distribution with infections occurring in Europe (Hornok et al., 2014; Ferna´ndez de Marco et al., 2016), Asia (Fukushima et al., 2021), Australia (Eamens et al., 2013), and New Zealand (James et al., 1984). It has also reached North America following the introduction of the tick vector (Thompson et al., 2020). Within the species, 11 types have been identified based on the sequence of the major piriform surface protein and with types Chitose and Ikeda being associated with severe clinical disease (Sivakumar et al., 2014; Gebrekidan et al., 2020). Clinical disease from T. orientalis infection is considered mild and often goes unnoticed. Early signs include weakness, abortion, and reluctance to walk. Severe disease is associated with excessive destruction of erythrocytes and anemia. Diagnosis can be made by the detection of piroforms within erythrocytes from Giemsa-stained blood smears, but confirmation of the species requires detection by PCR and sequencing the product. The main vector of T. orientalis is H. longicornis. Originally found in East Asia, its spread to Australia and New Zealand has been accompanied by infections in domestic cattle in both these countries (Watts et al., 2016). It is clear from researching this subject that there is a heavy reliance on molecular detection and species delineation of Theileria in livestock, and many studies use partial sequences of the 18S rRNA gene to identify to the species level. This reliance has been criticized by some authors who observe that Theileria-vertebrate host associations are often suggested with minimal support other than the detection of Theilerial DNA, a problem for many piroplasmids (Uilenberg et al., 2018). For ovine theileriosis, the list of potential species that could cause disease is growing (see Table 7.3). However, for some species, detection has relied on molecular methods alone to detect the causative Theileria, and there is limited biological evidence for species such as Theileria OT3 and Theileria MK as pathogens. On occasion, their detection has been in healthy animals, and in the case of Theileria sp. MK, there are no data on the tick host. It may well be that over time that with more research in the area, consensus will be reached on the range of Theilerias that consistently cause disease in livestock and the vectors that transmit them.

Tick-borne diseasesdbacteria

Tick-borne fever (anaplasmosis in animals) Anaplasmosis is a collective term for infection with variants of the Gram-negative intracellular bacterium A. phagocytophilum. The species name has replaced three

Tick-borne diseasesdbacteria

synonyms, Cytoecetes phagocytophila, Erhlichia phagocytophila, and Erhlicha equi (Dumler et al., 2001) and is also the causative agent of human granulocytic anaplasmosis. Many animals can be infected with the bacterium, and disease presents as a febrile episode and anorexia, with evidence of cytopenia affecting granulocytes and neutrophils. Tick-borne fever (TBF) was originally reported as a discrete disease of cattle in the late 1940s (Hudson, 1950), and livestock are the main species affected. Dairy herds experience a drop in milk yields, and more serious infections can result in abortion and stillbirth. Some animals experience respiratory distress. In Europe, A. phagocytophilum is transmitted by I. ricinus, so in a manner similar to B. divergens, its occurrence is dictated by the presence and abundance of this tick species. The disease has been reported in the British Isles, Spain, France, Germany, and Scandinavia. A. phagocytophilum is also present in North America and transmitted by ticks such as Ixodes scapularis but does not appear to cause significant disease in livestock. Outbreaks of TBF generally occur following the introduction of naı¨ve cattle onto tick-infested fields (Woldehiwet, 2010). Transmission of the bacterium leads to the infection of leukocytes, detected by the presence of bacterial merulae within infected granulocytes on peripheral blood smears. This coincides with the onset of fever with a temperature in cattle of over 40 C (the normal body temperature of cattle is 38.5 C). Due to the destruction of leukocytes resulting in granulocytopenia and neutropenia, infected animals become immunosuppressed. This results in increased susceptibility to other infections such as tick pyemia in lambs caused by Staphylococcus aureus causing significant loses to sheep flocks (Brodie et al., 1986). Successful treatment is possible with the administration of antibiotics such as oxytetracycline or sulfamethazine. However, most infections are unapparent, and it is possible that persistent infection occurs in many animals and only detected when a second tick-borne pathogen causes disease. In Africa and Australia, bovine anaplasmosis is caused by Anaplasma marginale. This can also be successfully treated with antibiotics such as tetracycline. Despite the diversity of A. marginale isolates, development of a vaccine should offer greater protection of livestock (Quiroz-Castan˜eda et al., 2016). Table 7.4 provides an overview of the other animals affected by infection with A. phagocytophilum and the related species A. marginale and Anaplasma platys. Canine anaplasmosis was first identified in California in the early 1980s, and cases have been reported from across America and Europe (Carrade et al., 2009). Infection causes an acute febrile illness with lethargy and occasionally lameness, vomiting, and hemorrhages. Similarly, equine granulocytic anaplasmosis was also detected in California but in the late 1960s (Madigan and Gribble, 1987). Infection causes a febrile episode with lethargy and inappetence. Although cases have been reported widely across North America and Europe, they are rare (Dziegiel et al., 2013).

Heartwater/cowdriosis Heartwater is a severe disease in ruminants caused by the obligate intracellular Gram-negative bacterium Ehrlichia ruminantium. The bacterium, formerly

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Table 7.4 Animal diseases caused by Anaplasma species in Europe. Anaplasma species

Disease

Host

Tick vector

Anaplasma phagocytophilum Anaplasma marginale

Tick-borne fever

Ruminants

Ixodes ricinus

Bovine anaplasmosis

Cattle

Anaplasma centrale Anaplasma bovis

Bovine anaplasmosis

Cattle

Ixodes ricinus, Rhipicephalus sanguineus, R. bursa, R. annulatus As above

Bovine mononuclear or agranulocytic anaplasmosis Ovine anaplasmosis

Cattle

Anaplasma ovis Anaplasma platys

Canine infectious cyclic thrombocytopenia

Sheep, goats Dogs

Hyalomma excavatum, Rhipicephalus sanguineus, R. turanicus Rhipicephalus bursa Rhipicephalus bursa, R. turanicus

named Rickettsia ruminantium and then Cowdria ruminantium, is transmitted by ticks belonging to the genus Amblyomma (Allsopp et al., 2015). Disease develops in susceptible breeds within 18 days of a tick bite and can present with a variety of signs. These include mild signs including elevated temperature, loss of appetite, and depression, through to more severe manifestations such as convulsions and recumbency. Death can follow rapidly. Postmortem examination can reveal hydropericardium or fluid accumulation within the pericardial cavity, with edema in the lungs and brain. The majority of cases occur in wild and domestic ruminants in Africa reflecting the distribution of the most important vectors, A. variegatum and Amblyomma hebraeum. Ticks become infected following feeding for two to three days on an infected host. Transstadial transmission occurs between life stages, but transovarial transmission in ticks has not been reported for E. ruminantium. The disease is found mainly in Africa, but the exception to this has resulted from the translocation of A. variegatum and E. ruminantium to islands in the Caribbean during the 18th century associated with the importation of cattle from Africa. Initially, only the islands of Guadeloupe, Marie Galante, and Antigua were affected, but during the latter half of the 19th century, A. variegatum has spread to a further 14 islands (Barre´ et al., 1995). Although the method of translocation is not certain, it is suspected to be due to the movement of another African import, the cattle egret (Bubulcus ibis) on which the tick feeds. This spread has not been linked to cases of disease in cattle but has prompted calls for an invasive tick eradication program throughout the whole Caribbean to eliminate the risk of heartwater disease spreading.

Tick-borne diseasesdbacteria

Canine ehrlichiosis Three species of Ehrlichia infect dogs. The most common is Ehrlichia canis causing canine monocytic ehrlichiosis, transmitted by Rhipicephalus sanguineus and found around the world. In North America, Ehrlichia ewingii transmitted by Amblyomma americanum, causes canine granulocytic ehrlichiosis. The third rarely reported species is Ehrlichia chaffeensis, although this is more commonly reported to cause infection in humans (Saito and Walker, 2016). Transmission of the E. canis by R. sanguineus can occur within three hours of tick attachment (Fourie et al., 2013). The bacteria infect leukocytes, and this can be detected in a blood smear as an aggregate of bacteria in a small number of cases (2 months)

Extreme weather event: flooding

Excessive rainfall leading to an overflow of water beyond normal limits.

Extreme weather event: excessive high temperatures

Temperatures well above historical levels for extended periods.

a

Effects on ticks and tickborne pathogen transmission • Increased survival of ticks at all stages of development leading to a larger population during the next active season. • Tick questing activity earlier in the year leading to earlier pathogen transmission. • Increased risk of pathogens overwintering in tick populations. • Potential for introduced exotic ticks surviving and establishing a breeding population. • The length of the breeding cycle of ticks could reduce leading to more abundant tick populations. • Virus infection and disseminationa rates could rise with higher temperatures leading to a higher prevalence of pathogens within tick populations. • Reduced rainfall could reduce areas with suitable habitat for off-host periods, i.e., a humid layer below the vegetation. This could reduce the tick population and limit it to those areas of that retain higher rainfall. • Dryer conditions may make some regions more permissive for soft tick species that are resistant to desiccation. • This may be detrimental to tick populations as life stages are washed away and if flooding persists, ticks will eventually die. • Excessively high temperatures would increase the likelihood of tick and habitat desiccation leading to a reduction of the tick population. • Higher temperatures might promote pathogen prevalence in those ticks that survive.

Infection rate measures the ability of a virus to productively infect a tick, dissemination rate measures the ability of a virus to cross the midgut and infect other tissues such as salivary glands.

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CHAPTER 12 The impact of climate change

FIGURE 12.1 Map of the world showing distribution expansion of certain tick species in response to climate change. The red line represents the Arctic Circle.

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Frenot, Y., De Oliveira, E., Gauthier-Clerc, M., Deunff, J., Bellido, A., Vernon, P., 2001. Life cycle of the tick Ixodes uriae in penguin colonies: relationships with host breeding activity. International Journal for Parasitology 31 (10), 1040e1047. https://doi.org/ 10.1016/S0020-7519(01)00232-6. Gillingham, E.L., Cull, B., Pietzsch, M.E., Phipps, L.P., Medlock, J.M., Hansford, K., 2020. The unexpected holiday souvenir: the public health risk to UK travellers from ticks acquired overseas. International Journal of Environmental Research and Public Health 17 (21), 1e37. https://doi.org/10.3390/ijerph17217957. Grandi, G., Chitimia-Dobler, L., Choklikitumnuey, P., Strube, C., Springer, A., Albihn, A., Jaenson, T.G.T., Omazic, A., 2020. First records of adult Hyalomma marginatum and H. rufipes ticks (Acari: Ixodidae) in Sweden. Ticks and Tick-Borne Diseases 11 (3), 101403. https://doi.org/10.1016/j.ttbdis.2020.101403. Gray, J.S., Dautel, H., Estrada-Pen˜a, A., Kahl, O., Lindgren, E., 2009. Effects of climate change on ticks and tick-borne diseases in Europe. Interdisciplinary Perspectives on Infectious Diseases 2009, 1e12. https://doi.org/10.1155/2009/593232. Gray, J.S., Ogden, N.H., 2021. Ticks, human babesiosis and climate change. Pathogens 10, 1430. https://doi.org/10.3390/pathogens10111430. Hvidsten, D., Frafjord, K., Gray, J.S., Henningsson, A.J., Jenkins, A., Kristiansen, B.E., Lager, M., Rognerud, B., Sla˚tsve, A.M., Stordal, F., Stuen, S., Wilhelmsson, P., 2020. The distribution limit of the common tick, Ixodes ricinus, and some associated pathogens in north-western Europe. Ticks and Tick-Borne Diseases 11 (4), 101388. https://doi.org/ 10.1016/j.ttbdis.2020.101388. Jaenson, T.G.T., Jaenson, D.G.E., Eisen, L., Petersson, E., Lindgren, E., 2012. Changes in the geographical distribution and abundance of the tick Ixodes ricinus during the past 30 years in Sweden. Parasites & Vectors 5 (1), 8. https://doi.org/10.1186/1756-3305-5-8. Korotkov, Y., Kozlova, T., Kozlovskaya, L., 2015. Observations on changes in abundance of questing Ixodes ricinus, castor bean tick, over a 35-year period in the eastern part of its range (Russia, Tula region). Medical and Veterinary Entomology 29 (2), 129e136. https://doi.org/10.1111/mve.12101. Lawrence, K.E., Summers, S.R., Heath, A.C.G., McFadden, A.M.J., Pulford, D.J., Tait, A.B., Pomroy, W.E., 2017. Using a rule-based envelope model to predict the expansion of habitat suitability within New Zealand for the tick Haemaphysalis longicornis, with future projections based on two climate change scenarios. Veterinary Parasitology 243, 226e234. https://doi.org/10.1016/j.vetpar.2017.07.001. Leighton, P.A., Koffi, J.K., Pelcat, Y., Lindsay, L.R., Ogden, N.H., 2012. Predicting the speed of tick invasion: an empirical model of range expansion for the Lyme disease vector Ixodes scapularis in Canada. Journal of Applied Ecology 49 (2), 457e464. https://doi.org/ 10.1111/j.1365-2664.2012.02112.x. Lindgren, E., Ta¨lleklint, L., Polfeldt, T., 2000. Impact of climatic change on the northern latitude limit and population density of the disease-transmitting European tick Ixodes ricinus. Environmental Health Perspectives 108 (2), 119e123. https://doi.org/10.2307/3454509. Marques, R., Kru¨ger, R.F., Peterson, A.T., De Melo, L.F., Vicenzi, N., Jime´nez-Garcı´a, D., 2020. Climate change implications for the distribution of the babesiosis and anaplasmosis tick vector, Rhipicephalus (Boophilus) microplus. Veterinary Research 51 (1), 81. https:// doi.org/10.1186/s13567-020-00802-z. Medlock, J.M., Hansford, K.M., Bormane, A., Derdakova, M., Estrada-Pen˜a, A., George, J.C., Golovljova, I., Jaenson, T.G.T., Jensen, J.K., Jensen, P.M., Kazimirova, M., Oteo, J.A., Papa, A., Pfister, K., Plantard, O., Randolph, S.E., Rizzoli, A., Santos-Silva, M.M., Sprong, H.,

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Van Bortel, W., 2013. Driving forces for changes in geographical distribution of Ixodes ricinus ticks in Europe. Parasites & Vectors 6 (1), 1. https://doi.org/10.1186/1756-3305-6-1. Metzger, M.J., Bunce, R.G.H., Jongman, R.H.G., Mu¨cher, C.A., Watkins, J.W., 2005. A climatic stratification of the environment of Europe. Global Ecology and Biogeography 14 (6), 549e563. https://doi.org/10.1111/j.1466-822X.2005.00190.x. Mihalca, A.D., 2015. Ticks imported to Europe with exotic reptiles. Veterinary Parasitology 213 (1e2), 67e71. https://doi.org/10.1016/j.vetpar.2015.03.024. Molaei, G., Andreadis, T.G., Anderson, J.F., Iii, K.C.S., 2018. An exotic hitchhiker: a case report of importation into Connecticut from Africa of the human parasitizing tick, Hyalomma truncatum (Acari: Ixodidae). The Journal of Parasitology 104 (3), 302e305. https://doi.org/10.1645/18-13. Ogden, N.H., Lindsay, L.R., 2016. Effects of climate and climate change on vectors and vector-borne diseases: ticks are different. Trends in Parasitology 32 (8), 646e656. https://doi.org/10.1016/j.pt.2016.04.015. Ogden, N., Gachon, P., 2019. Climate change and infectious diseases: what can we expect? Canada Communicable Disease Report 45 (4), 76e80. https://doi.org/10.14745/ccdr.v45i04a01. Oliveira, S.V.d., Romero-Alvarez, D., Martins, T.F., Santos, J.P.d., Labruna, M.B., Gazeta, G.S., Escobar, L.E., Gurgel-Gonc¸alves, R., 2017. Amblyomma ticks and future climate: range contraction due to climate warming. Acta Tropica 176, 340e348. https://doi.org/10.1016/ j.actatropica.2017.07.033. Olwoch, J.M., Reyers, B., Engelbrecht, F.A., Erasmus, B.F.N., 2008. Climate change and the tick-borne disease, Theileriosis (East Coast fever) in sub-Saharan Africa. Journal of Arid Environments 72 (2), 108e120. https://doi.org/10.1016/j.jaridenv.2007.04.003. Parkinson, A.J., Evengard, B., Semenza, J.C., Ogden, N., Børresen, M.L., Berner, J., Brubaker, M., Sjo¨stedt, A., Evander, M., Hondula, D.M., Menne, B., Pshenichnaya, N., Gounder, P., Larose, T., Revich, B., Hueffer, K., Albihn, A., 2014. Climate change and infectious diseases in the Arctic: establishment of a circumpolar working group. International Journal of Circumpolar Health 73, 1e7. https://doi.org/10.3402/ijch.v73. 25163. Randolph, S.E., 2010. To what extent has climate change contributed to the recent epidemiology of tick-borne diseases? Veterinary Parasitology 167 (2e4), 92e94. https://doi.org/ 10.1016/j.vetpar.2009.09.011. Randolph, S.E., 2013. Is expert opinion enough? A critical assessment of the evidence for potential impacts of climate change on tick-borne diseases. Animal Health Research Reviews 14 (2), 133e137. https://doi.org/10.1017/s1466252313000091. Revich, B., Tokarevich, N., Parkinson, A.J., 2012. Climate change and zoonotic infections in the Russian arctic. International Journal of Circumpolar Health 71 (1), 28792. https:// doi.org/10.3402/ijch.v71i0.18792. Rocklo¨v, J., Dubrow, R., 2020. Climate change: an enduring challenge for vector-borne disease prevention and control. Nature Immunology 21 (5), 479e483. https://doi.org/ 10.1038/s41590-020-0648-y. Romanenko, V., Leonovich, S., 2015. Long-term monitoring and population dynamics of Ixodid ticks in Tomsk city (Western Siberia). Experimental & Applied Acarology 66 (1), 103e118. https://doi.org/10.1007/s10493-015-9879-2. Sagurova, I., Ludwig, A., Ogden, N.H., Pelcat, Y., Dueymes, G., Gachon, P., 2019. Predicted northward expansion of the geographic range of the tick vector Amblyomma americanum in North America under future climate conditions. Environmental Health Perspectives 127 (10), 107014. https://doi.org/10.1289/EHP5668.

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Salkeld, D.J., Porter, W.T., Loh, S.M., Nieto, N.C., 2019. Time of year and outdoor recreation affect human exposure to ticks in California, United States. Ticks and Tick-Borne Diseases 10 (5), 1113e1117. https://doi.org/10.1016/j.ttbdis.2019.06.004. Semenza, J.C., Suk, J.E., 2018. Vector-borne diseases and climate change: a European perspective. FEMS Microbiology Letters 365 (2), fnx244. https://doi.org/10.1093/femsle/fnx244. Sonenshine, D.E., 2018. Range expansion of tick disease vectors in North America: implications for spread of tick-borne disease. International Journal of Environmental Research and Public Health 15 (3), 478. https://doi.org/10.3390/ijerph15030478.  ´ , E., 2015. Arthropods and associated Sparagano, O., George, D., Giangaspero, A., Spitalska arthropod-borne diseases transmitted by migrating birds. The case of ticks and tick-borne pathogens. Veterinary Parasitology 213 (1e2), 61e66. https://doi.org/10.1016/ j.vetpar.2015.08.028. Sutherst, R.W., 2001. The vulnerability of animal and human health to parasites under global change. International Journal for Parasitology 31 (9), 933e948. https://doi.org/10.1016/ S0020-7519(01)00203-X. Teo, E.J.M., Vial, M.N., Hailu, S., Kelava, S., Zalucki, M.P., Furlong, M.J., Barker, D., Barker, S.C., 2021. Climatic requirements of the eastern paralysis tick, Ixodes holocyclus, with a consideration of its possible geographic range up to 2090. International Journal for Parasitology 51 (4), 241e249. https://doi.org/10.1016/j.ijpara.2020.08.011. Titcomb, G., Allan, B.F., Ainsworth, T., Henson, L., Hedlund, T., Pringle, R.M., Palmer, T.M., Njoroge, L., Campana, M.G., Fleischer, R.C., Mantas, J.N., Young, H.S., 2017. Interacting effects of wildlife loss and climate on ticks and tick-borne disease. Proceedings of the Royal Society B: Biological Sciences 284 (1862), 20170475. https://doi.org/10.1098/ rspb.2017.0475. Tokarevich, N., Tronin, A., Gnativ, B., Revich, B., Blinova, O., Evengard, B., 2017. Impact of air temperature variation on the ixodid ticks habitat and tick-borne encephalitis incidence in the Russian Arctic: the case of the Komi Republic. International Journal of Circumpolar Health 76 (1), 1298882. https://doi.org/10.1080/22423982.2017.1298882. Vial, L., 2009. Biological and ecological characteristics of soft ticks (Ixodida: Argasidae) and their impact for predicting tick and associated disease distribution. Parasite 16 (3), 191e202. https://doi.org/10.1051/parasite/2009163191. Yao, X.Y., Tian, N., Ma, B., Zhang, Y., Cun, D.J., Li, L.H., 2021. Effects of climate changes on the distribution of Rhipicephalus microplus in China. Chinese Journal of Schistosomiasis Control 33 (3), 267e273. https://doi.org/10.16250/j.32.1374.2020298.

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Controlling ticks and tickborne disease transmission

13

For over 100 years, roughly the time period since the role of ticks as a source of infectious disease was recognized, attempts have been made to control the tick vector and tick-borne disease in cattle. The earliest method applied and still a popular option to this day has been to suppress ticks on the host through the widespread use of acaricides, chemical agents that target arthropods within the subclass Acari. Initial successes resulted in the elimination of certain species of Rhipicephalus from the United States. However, with the intensification of livestock farming around the world, overuse of acaricides has led to the emergence of resistance and greater awareness of the ecological impact this has on the wider invertebrate community. This approach has considerable disadvantages and has prompted the need for other means of controlling both tick infestation, which can have detrimental effects on livestock, and tick-borne pathogens of public and animal health. Underpinning any control effort is the need for extensive surveillance to understand the tick species responsible for pathogen transmission, their distribution, and the circumstances where transmission occurs. In addition, tick populations that are exposed to acaricides should ideally be surveyed for the emergence of acaricide resistance. Another key component for preventing tick-borne disease is the development of vaccines. For some pathogens such as tick-borne encephalitis virus, there is a highly effective vaccine that is widely available in regions where the disease occurs. However, for most tick-borne pathogens, there is still a need to develop cost-effective vaccines that will protect at-risk populations. This chapter will cover the range of approaches to the control of tick and tick-borne diseases.

Introduction Tick infestation alone rarely causes life-threatening illness although it is unpleasant for humans and potentially debilitating for livestock. In some regions of the world, animal infestation can be severe with larger livestock species hosting hundreds of feeding ticks (Nonga et al., 2012). Direct effects on livestock from tick infestation include damage to the animals hide, which in cattle can reduce its value or suitability for use in the production of leather goods (Kemal et al., 2016). Other direct effects include blood loss in the case of heavy infestations and reduction in body weight that can be significant for meat production. A further problem is the effect of secondary Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00009-5 Copyright © 2023 Elsevier Inc. All rights reserved.

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parasitism through arthropods such as the screw worm fly (Cochliomyia hominivorax) that can lay its eggs in the wound created by tick bites. Indirect effects are those that result from the transmission of pathogens by tick feeding, and these can have profound effects on human and animal health. The financial costs associated with prevention, treatment, and the withdrawal of diary and meat products containing acaricides from entering the food supply can be large. In those communities that rely on livestock for food and income, tick-borne diseases can be a major threat to provision of food and a constraint on economic development. Infection with some pathogens can lead to the disruption of trade within countries and between them. One estimate has put the economic impact of tick-borne diseases to the cattle industry as high as US$30 billion annually (Lew-Tabor and Rodriguez Valle, 2016). Linking ticks as vectors of disease began in the late 19th century and was the first step in attempting to break the chain of transmission. This initiated the first tentative steps in suppressing tick infestation as a means of preventing the diseases they transmit. One of the earliest successes in control of a tick-borne disease was the elimination of cattle fever from the southern states of the USA. This was initiated by the identification of the vector, formerly Boophilus annulatus, now Rhipicephalus annulatus, known locally as the cattle tick, and the cause of Babesiosis resulting from infection with Babesia bigemina (Smith and Kilbourne, 1892). This link enabled the formulation of a control strategy centered around the dipping of cattle in 1906. Initially, this was achieved by submersing the cattle in oil but was later replaced with a dip containing arsenical compounds. The southern states were declared free of disease in 1960 making an estimated saving of one billion dollars per year to the livestock industry (Graham and Hourrigan, 1977). However, ongoing surveillance along the MexicoeUS border remains to this day to prevent the reintroduction of the disease. The persistence of both the tick vector and the pathogen in wildlife reservoirs threatens to undo this achievement and cause future disease outbreaks in cattle (Guerrero et al., 2007; Giles et al., 2014). For humans, the main method of control is prevention of tick bites. This is principally by public education that identifies the hazards and describes practical means of preventing a tick bite through measures such as covering exposed skin and the application of insect repellents. It does require individuals to act on the information given. Vaccination for some tick-borne diseases is available if the threat of transmission is high, but many tick-borne diseases do not have effective vaccines. On discovery of ticks on humans, the tick should be removed in such a way as to completely remove the tick mouthparts from the wound to reduce the risk of pathogen transmission or development of a skin infection. For companion animals, ticks should be removed where possible and a spot-on acaricide treatment applied to prevent further infestations (Pfister and Armstrong, 2016). Livestock and companion animals can be treated with acaricides although this has been an ongoing battle between the emergence of resistance within tick populations and the development of new chemical treatments.

Surveillance: its importance in controlling ticks and tick-borne disease

Surveillance: its importance in controlling ticks and tickborne disease Tick-borne disease is an ever-present challenge to public and animal health wherever ticks are present. The etiology of many of these diseases has been well known for decades, and their associations with certain tick species has been recognized. However, novel emerging tick-borne diseases are continually being identified and characterized (Mansfield et al., 2017). Further threats such as the importation of exotic ticks through a combination of human activity or bird migration, combined with the effects of climate change could radically alter the disease landscape. Prevention and control of tick-borne diseases is critically dependent on an understanding of the species of tick or ticks that vector disease and measurement of the incidence of particular diseases in a target population. This is achieved through surveillance (Eisen and Paddock, 2021), defined as the continuous, systematic collection and analysis of data on disease-causing agents, for the purpose of informing public and animal health practices. This requires a range of activities in order to yield data on the what, where, and when tick-borne pathogens are transmitted in order to inform control of ticks and tick-borne diseases. Data should be quantifiable in time and space to enable trends to be measured. Presence/absence determinations of ticks and tick-borne diseases are a useful start but offer limited information on vector abundance. Quantifiable data assist in predicting changes due to climate change, landscape management, human behavior, and livestock/wildlife management. It also enables superior risk forecasting. Tick surveillance complements disease surveillance by demonstrating the distribution and abundance of the vector and can be linked to the distribution and prevalence of the pathogen. It also highlights where exposure to tick-borne pathogens occurs and offers the best opportunity to prevent transmission by informing the public and certain occupations on measures to avoid exposure to tick bites. A significant component of surveillance is the ability to identify the species of tick infesting humans, livestock, and companion animals. This helps to assess the disease risk associated with a particular tick species (Mathison and Pritt, 2014). For animal diseases, the detection of tick species known to infest livestock within the habitat occupied by animals can point to the source of disease. In the case of exotic tick species, identification can require expertise to identify key morphological traits that differentiate to genus level, but ideally to the species as this is critical to indicate pathogen associations. If morphological identification is not possible either due to lack of expertise, detailed keys are not available, or the state of the specimen precludes identification, alternative methods may be needed. These can include polymerase chain reaction linked to sequencing or mass spectrometry (Mediannikov and Fenollar, 2014). However, these options are technically demanding alternatives that can prove expensive if required for a large number of specimens. Another useful piece of information is the length of time a tick has been attached. If the tick is removed immediately after attachment, the risk of pathogen

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transmission is considerably reduced. Conversely, if the tick has become engorged, this indicates that it has been attached for longer (days) and the risk of transmission of both viruses and bacterial pathogens is increased.

Surveying for ticks Collecting, identifying, and detecting pathogens within ticks is an essential step in understanding the relationship between a particular tick species and transmission of disease. It can also add environmental context to the presence of ticks and identify where vertebrateetick contact occurs. The majority of tick species spend a short proportion of their life feeding on the host, and the remainder is spent within the environment. Both phases offer an opportunity to collect ticks.

Environmental collection of ticks There are a range of methods for surveying/collecting ticks from the environment, the most appropriate being dependent on the behavior of the tick and the resources available for the collection process. Identifying areas to survey is usually indicated by reports of tick biting from humans, observations on livestock, reports of disease, or particular vegetation types that are associated with certain tick species. If the tick species quests, actively searching vegetation during a walk-through of an area can give an initial indication of tick presence. The surveyor can visually inspect or walk-through vegetation and then inspect clothing for attached ticks. Information on the type of vegetation associated with ticks and questing height should be recorded. This approach is likely to favor collection of adult forms and can be adapted to investigate contact rates between ticks and at-risk populations. Geissler and coworkers monitored employees of National Parks in Wyoming, USA, who worked outdoors for contact with Dermacentor andersoni (Geissler et al., 2014). They showed that 37% of employees had found ticks of this species on clothing and that 10% had experienced an attached tick. This highlights the obvious risk associated with this approach and testing of ticks from the areas where staff worked demonstrated that a number were seropositive for Colorado tick fever virus (Geissler et al., 2014). A common method for collecting ticks on vegetation is that of dragging or flagging. This involves drawing a cloth or wool blanket attached to a wooden pole over vegetation. Questing ticks will attach to the cloth and can be collected when the cloth is turned over. White material is ideal, so that attached ticks contrast against a light background. As with visual inspection, this can be used in an unstructured way to detect the presence or absence of ticks and collect large numbers of all life stages for some tick species. Alternatively, structured surveys using standard sizes of cloth can be drawn consistently over an area to compare different locations

On-host collections of ticks

and at different times (Newman et al., 2019). In addition to the collection of ticks, data associated with environmental conditions such as temperature, windspeed, and humidity can be recorded to provide further ecological context on the triggers for tick behavior. Tick samples can then be tested for the presence of pathogenic organisms, and when applied consistently, and over a number of years, this approach can measure the prevalence of pathogens within the tick population of a defined area over time and potentially detect the emergence of a new pathogen. Tick-borne encephalitis virus was detected following repeated surveillance for Ixodes species on islands off the coast of Finland in the absence of disease in the human population (Sormunen et al., 2018). Although inexpensive in terms of equipment, this can be a labor-intensive approach requiring regular site visits and intensive collection of data during each sampling. In addition, surveying can be impeded if the collection area is wet or experiencing rainfall during tick collection as wet cloth is ineffective. A method that can augment dragging is the use of lure traps, usually with CO2 but occasionally with other chemical attractants. The majority of ticks do not move far in search of a host, but such traps can provide additional data on tick presence in an area. A typical trap consists of a white surface, often cloth, 1
1 m with the attractant in the center; in the case of CO2, this can be dry ice in a perforated container allowing gas to escape. Ticks that cross the surface can be collected. This approach has been used, alongside dragging to measure Amblyomma species in Brazil (Oliveira et al., 2000; Ramos et al., 2014). Many tick species feed on mammalian and avian hosts that live in nests and burrows. While off host, these ticks can be detected at such sites. Enclosed burrows present a particular challenge to tick collection. However, methods such as vacuum aspiration, the use of a motor-driven suction device to draw up ticks from a substrate or from between rocks can be used to collect ticks. This approach has been used to study Ornithodoros ticks infesting the burrows of warthogs (Phacochoerus africanus) in Mozambique (Quembo et al., 2018).

On-host collections of ticks Collecting ticks directly from animals, including humans, offers some benefits in the understanding of tickehostepathogen interactions but also a number of problems. Clearly removing a tick from an animal demonstrates that the tick feeds on that particular host and demonstrates the parts of the host to which the tick preferentially feeds such as the ears or inguinal areas. Engorged ticks (Fig. 13.1) at all life stages are easy to spot, particularly with heavy infestations although engorgement can make morphological identification challenging and relies on features that are not affected by the engorgement process. Testing the tick in its entirety for pathogens makes it impossible to differentiate between the tick and the host, via the blood meal, as the source of the pathogen in the tick. Careful removal of components of the tick such as the legs can enable this discrimination although this can be time consuming when dealing with large numbers of ticks.

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FIGURE 13.1 Engorged Ixodes ricinus ticks removed from cattle, United Kingdom, 2019 (Photo N. Johnson 2019 ©).

Some host species can be challenging to work with and may need veterinary support. Larger animals, for example, cattle, and potentially dangerous animals such as large carnivores may require restraint or even anesthesia in order to inspect. Some studies are conducted on animals after death, for example, the detection of Amblyomma testudinarium on a brown bear (Ursus arctos yesoensis) captured in Hokkaido, Japan (Nakao et al., 2021). Coverings of fur or feathers can delay a thorough inspection of an animal. However, the benefits of establishing direct contact between the tick and the host have been used in many studies. In Great Britain, collection of ticks from grouse chicks over two decades has provided evidence that Ixodes ricinus ticks are increasing in abundance and distribution (Scharlemann et al., 2008). Removal of ticks from livestock at markets in Kenya has identified CrimeaneCongo hemorrhagic fever virus in Rhipicephalus decolaratus ticks and Rickettsia africae from Amblyomma variegatum (Chiuya et al., 2021). It has also revealed the diversity of pathogens in ticks infesting cattle in Pakistan and evidence for multiple infections (Ghafar et al., 2020).

Citizen science and surveys In addition to research and surveillance by specialist scientists, there is now a greater realization that the general public can play a role in collecting data, so-called citizen science (Roche et al., 2020). The traditional form of using nonspecialists to generate data on disease is the use of surveys. Responses to a series of questions are analyzed to identify parameters that influence a particular problem. This remains a useful means of assessing the extent and impact of tick-borne disease in both humans (Mowbray et al., 2014) and animals (Zintl et al., 2014; Lihou et al., 2020). In the United Kingdom, this has been augmented with a national tick surveillance scheme delivered by the UK Health Security Agency (formerly Public Health England). This

Detection of tick-associated pathogens

scheme encourages members of the public to send ticks and related information for identification and if novel can lead to further investigation (Cull et al., 2018, 2020). Across Europe, this approach has been used to map tick populations, identify hotspots for tickehuman interactions, and generate samples for pathogen testing (Garcia-Marti et al., 2018; Laaksonen et al., 2018; Lernout et al., 2019 Drehmann et al., 2020). In North America, a national tick surveillance scheme has been coordinated from the Northern Arizona University and used to collect geo-referenced specimens of samples of Ixodes scapularis and Ixodes pacificus (Porter et al., 2021). These samples were then used to determine the prevalence and distribution of Borrelia species, Anaplasma phagocytophilum and Babesia microti across the United States. Targeted surveys that focused on private veterinary surgeons submitting ticks have resulted in studies on infestations in domestic dogs (Abdullah et al., 2016) and cats (Davies et al., 2017). A recent approach has used electronic records submitted directly from veterinary surgeries to rapidly collate information on tick attachments and monitor trends in companion animals (Tulloch et al., 2017). A similar approach could be developed for other fields of veterinary medicine such as the collection of data on tick infestation and tick-borne disease in large animal practice. Citizen science offers a number of benefits, especially the cost-effective generation of large datasets. However, it does have a number of limitations (Eisen and Eisen, 2021). Firstly, it relies on citizens to be honest and accurate, with little opportunity to corroborate the precision of data submissions. Critical information, such as tick speciation is usually beyond most people’s ability and requires experience, some form of magnification and access to morphological keys. It is no surprise that all the tick-associated projects cited above that deal with submissions of ticks require identification by experienced scientists. Another area of difficulty is establishing the location where a tick first encounters a host. For humans, this can, in extreme cases, be a different continent due to international air travel (Stafford et al., 2022), although usually it relies on the submitter providing sufficient information to decide the most likely site of the original encounter, usually a recent outdoor excursion.

Detection of tick-associated pathogens The appearance of clinical signs in a susceptible host, including humans, is usually the first step in detecting tick-borne disease. Some disease signs may provide a strong suspicion of a particular disease and can be directly linked to the site of a tick bite. For example, the initial bullseye rash or erythema migrans, that is an early clinical sign for Lyme borreliosis in humans. Alternatively, some signs may be regarded as specific to a particular disease or pathognomonic, such as the appearance of blood in urine for bovine babesiosis. However, many disease signs are nonspecific and often discordant with the original tick bite, typically causing febrile episodes, and require confirmation by a diagnostic test. This may involve isolation or microscopical identification of the causative agent, detection by serological means, or

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molecular detection using nucleic acid amplification tests such as the polymerase chain reaction. For many pathogens of livestock, a large array of tests are now available to detect the etiological cause of disease (Johnson et al., 2012). Serology can also be used to provide evidence of past exposure to tick-borne diseases. Ticks themselves can also be tested for the presence of pathogens (Gondard et al., 2018), although this does not demonstrate causality without supporting evidence such as the presence of an infected tick attached to an infected animal. Indeed, novel viruses are regularly being detected in tick populations. Some are confirmed as pathogens affecting humans such as the recently described severe fever with thrombocytopenia syndrome virus (Liu et al., 2014). However, a growing number of viruses and bacteria detected using the novel technologies described in Chapter 10 have no association with disease and may not be capable of replicating outside of the tick host (Pettersson et al., 2017). What is clear is that ticks are capable of hosting multiple viruses, bacteria, and protozoa that can either individually or in combination cause disease (Sanchez-Vicente et al., 2019). Detection of pathogens within ticks can be difficult in part as ticks are structurally tough and usually thin along the horizontal plan. They usually require some form of disruption to release sufficient nucleic acids for molecular detection methods. Whole fixed ticks can be embedded in paraffin wax and treated like other tissue types for histochemical observation. Complete disruption of a tick can take the form of something as simple as cutting with scissors or scalpel blade although this is time-consuming and impractical for large numbers of ticks. Sample homogenization using stainless steel beads in a liquid medium such as phosphate-buffered saline and with a dedicated item of equipment such a commercial homogenizer, e.g., TissueLyzer II (QIAgen), are often used to disrupt ticks. This enables the rapid homogenization of large number of samples, either as individual ticks for adults and engorged life stages or pools for immature forms. A sample of homogenate can then be used to isolate live pathogen in the case of viruses in tissue culture or an aliquot removed for the extraction of nucleic acid prior to the application of a detection technique such as polymerase chain reaction (Johnson et al., 2012). Bacterial and protozoal pathogens use DNA extractions, whereas the majority of viruses infecting ticks have an RNA genome, with the exception of the Asfarviridae (Table 13.1).

The challenge of invasive species An invasive species is one that causes ecological or economic harm in a new environment. For some invasive species, this can also increase the risk of pathogen transmission to animals and humans. Over the past 500 years, invasive species have emerged through human actions reflecting the increased mobility due to trade and population migrations. Species can also be translocated through natural processes, which for ticks can involve movements of vertebrate hosts such as bird migration.

The challenge of invasive species

Table 13.1 Genomic details of the major tick-borne virus families. Virus family Asfarviridae Flaviviridae Orthomyxoviridae Nairoviridae Reoviridae a b

Example African swine fever virus Tick-borne encephalitis virus Thogoto virus CrimeaneCongo hemorrhagic fever virus Colorado tick fever virus

Genome type (strand polarity) a

Segmentation

DNA DS RNA SSb (þ)

Nonsegmented Nonsegmented

RNA SS () RNA SS ()

Eight segments Three

RNA DS

10e12

Double stranded. Single stranded.

Surveillance is critical to enable the detection of introduced tick species early and offer the best chance of preventing particular species becoming established within a new area. A dramatic example of this has been the introduction and spread of the Asian longhorned tick, Haemaphysalis longicornis, in North America. This tick species was indigenous to East Asia and had spread extensively through Australia and New Zealand, where in both countries, it has been responsible for driving the spread of Theileria orientalis strain Ikeda in cattle (Forshaw et al., 2020). Screening of livestock entering the United States had picked up examples of this tick species on imports, so the potential for its emergence in the country was high. This was realized in 2017 with the discovery of infestations with this species feeding on sheep in New Jersey (Rainey et al., 2018). Following from this initial discovery, the species was detected in 15 other states within a year. The ability of H. longicornis to reproduce by parthenogenesis has in part assisted the establishment of this species. Habitat suitability modeling suggests that it will continue to spread to further regions of North America creating another tick-borne threat to public and animal health (Namoval et al., 2020). In the United Kingdom, a focal outbreak of canine Babesiosis in southern England was suspected to be linked to the importation of Dermacentor reticulatus ticks on dogs entering the country (de Marco et al., 2017). An example of an introduced species that has failed to establish in northern Europe is that of the brown dog tick Rhipicephalus sanguineus. This species is widely distributed around the world but is believed to have originated in Europe and transported to other countries by human activity (Hekimo
glu et al., 2016). However, its distribution is limited to southern Europe. The frequent travel of dogs from northern European countries to the Mediterranean region and then returning provides an effective method of transporting R. sanguineus back to the dogs’ country of origin. This can lead to infestations of kennels and houses that can be difficult to control, often requiring intensive fumigation to reach every individual tick (Hansford et al., 2017). However, further spread of the species away from human

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habitation has been limited by the reliance on the tick for warmer temperatures than those experienced in northern latitudes to complete its life cycle. This is only possible in the confines of centrally heated properties in northern European countries. A concern is that one of the effects of climate change will make northerly latitudes more hospitable for the species and enabling it to bring with it a range of canine pathogens (Dantas-Torres, 2008). A similar situation exists for the introduction of Hyalomma species to northern Europe, although here the introductions are made by migrating birds. Juvenile life stages of species such as Hyalomma rufipes has been reported on birds flying north (Toma et al., 2021). But again, the climatic conditions found in northern Europe, at the present time, are not considered suitable for their establishment. However, this may be changing rapidly with over 40 reports of adult Hyalomma ticks in Sweden in 2018 and 2019 (Grandi et al., 2020). Without continuous surveillance, these events will not be detected and trends identified until sufficient numbers of an invasive species have established to a point where they become an established breeding population. Once present, the ticks will become an obvious nuisance to the human population or responsible for the transmission of disease. This emphasizes the need for ongoing surveillance to detect any change in the tick species present in a particular region.

Methods for studying tick-borne disease biology and transmission To study the infection process within the tick and the factors that enhance or restrict transmission, appropriate tick-based models are required. This could involve live ticks, either trapped from the field or bred in dedicated colonies. An alternative is to use cell lines derived from ticks that enable the study of tickepathogen interactions at the molecular level. The ultimate aim of these studies is to identify means of intervening to prevent transmission of tick-borne diseases.

Tick colonies for investigating tickepathogen interactions Colonized ticks offer the ability to generate large numbers of a particular species when required for pathogen infection experiments. Soft ticks, especially those of the genus Ornithodoros have been available in colonized form for decades (Schwan et al., 1991). For hard ticks, there are a number of challenges to colonization. Firstly, the extended period that many Ixodid species take to achieve maturity, which can be measured in years in natural tick populations. In order to maintain a colony, every life stage needs to be completed repeatedly to achieve true colonization (Levin and Schumacher, 2016). By manipulating the conditions, principally temperature, ticks maintained in the laboratory can be accelerated through their life cycle (see

Tick cell lines as an alternative model system

Table 13.2 Minimum time required by North American tick species to complete one life cycle at 22e24 C (Troughton and Levin, 2007). Species

Range (days)

Ixodes scapularis Ixodes pacificus Rhipicephalus sanguineus Haemaphysalis leporispalustris Dermacentor variabilis Dermacentor occidentalis Amblyomma americanum

204e219 214e229 162e177 209e224 176e191 180e195 192e211

Table 13.2). However, all the figures cited show that it takes a minimum of approximately 160 days to complete a single cycle. This represents quite an investment to get to the point where an experiment can be attempted. A further challenge is to ensure that colonized ticks can obtain sufficient nutrition through a blood meal to transition to the next life stage. This has often involved the use of live animals. Artificial means of feeding ticks have now been pioneered for all life stages of I. ricinus (Militzer et al., 2021) that reduce the requirement for animal hosts, reduce costs, and provide a convenient alternative. A final problem is the need to keep ticks within a moist environment. The maintenance of high humidity is critical to avoid tick desiccation, but this can accelerate fungal growth that can, particularly for larvae, be lethal (Bonnet et al., 2021). Treatment of ticks with an antifungal agent such as nystatin can reduce this problem. Despite the challenges in establishing a colonized line, the ability to access all life stages of a particular species and control the transition from one stage to the next provides an opportunity to investigate tickepathogen relationships, the ability of pathogens to undergo transmission between life stages and a model for suppressing tick infection. Examples of the application of colonized ticks include the demonstration of transstadial and transovarial persistence of Babesia divergens within I. ricinus (Bonnet et al., 2007) and the effect of an endosymbiont on the vector competence of Amblyomma americanum for Rickettsia rickettsia (Levin et al., 2018).

Tick cell lines as an alternative model system An alternative to using intact ticks is the use of cell lines derived from ticks. The first such lines were derived in the 1970s from Rhipicephalus appendiculatus (Varma et al., 1975). Since then, a large number of cell lines from Ixodid ticks have been prepared, most from embryonic tissues (Bell-Sakyi et al., 2007). A small number of cell lines from Argasid ticks are now available. Typically, tick cells grow between

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28 and 34 C, lower than the temperature required for mammalian cell lines; they do not require additional CO2 and do not adhere to plastic substrates. As a result, they are usually slow growing and have a pleomorphic appearance. They can tolerate lower temperatures between 4 and 12 C. However, they can be difficult to resuscitate after storage below 0 C. The main applications for tick-derived cells include isolation of tick-borne pathogens (Bell-Sakyi and Attoui, 2016), propagation of viruses and bacteria as an alternative to mammalian cells, and as a model for transcriptomic or proteomic methods to investigate tickepathogen interactions (Weisheit et al., 2015). Tick cell lines can also be used to assess acaricide resistance and the mechanisms of acaricide action (Al-Rofaai and Bell-Sakyi, 2020).

Acaricides The use of chemicals to control ticks affecting livestock began towards the end of the 19th century in North America and Australia. It was prompted by the need to control excessive tick infestation and disease in cattle. Chemical suppression of ticks was considered a rapid and cost-effective means of targeting all tick life stages present on cattle (Agwunobi et al., 2021). The original acaricides included arsenic as the active component. Animals were dipped in vats containing large volumes containing 0.2% arsenic tetraoxide to reduce infestation with Rhipicephalus microplus and R. annulatus. Extensive application of acaricides was instrumental in leading to the elimination of Rhipicephalus species that fed on cattle from the United States of America (see Introduction). However, its repeated use, arguably overuse, over 40 years has led to a number of adverse effects including acaricide resistance, environmental damage, and ill health in those Table 13.3 A list of acaricide groups developed during the 19th and 20th centuries, the year they were first used and the year when resistance was first documented. Acaricide

First used

Resistance documented

Arsenicals Organochlorines Organophosphates Carbamates Formamidines Pyrethroids Macrocylic lactones Growth regulators (Fluazurin) Phenylpyrazoles

1895 (USA) 1940s 1950s 1956 Mid 1970s 1970s 1981 1994 Mid 1990s

1936 1952 Mid 1960s ? Early 1980s 1980s 2001 2014 2007

Acaricides

exposed to such chemicals. This scenario has repeated with almost every synthetic chemical developed to treat tick infestation of cattle. Table 13.3 provides a list of acaricide groups and when resistance in tick populations was first observed. Resistance can be defined as the ability of a tick strain to survive and achieve reproductive success despite exposure to an acaricide used at the recommended dose. Resistance can result from an inherited trait that reduces the tick sensitivity to a chemical, socalled acquired resistance. Alternatively, there is cross-resistance where resistance to one acaricide results in resistance to another. Resistance was first noted for arsenicals in the late 1940s. Environmental contamination leads to the indiscriminant destruction of other arthropods, many of which provide what are termed as ecosystem services, e.g., pollinators. The loss of these can have severe ecological consequences and contributes to the overall reduction in biodiversity. Finally, many of the chemicals developed as pesticides and acaricides are toxic to humans. Most acaricides are neurotoxins targeting components of the tick nervous system, for example, the inhibition of acetylcholinesterases by carbamate. The exception to this are those such as Fluazuron that target growth regulators, which inhibits egg production of engorged females and prevents the molting process in immature life stages. However, these effects can also affect vertebrate hosts and their continued use can lead to exposure and poisoning of those that use them (Boedeker et al., 2020). This has caused debilitating neurological illness, and thus extreme caution should be taken when handling acaricides to avoid direct contact with skin or inhalation. A variety of means are available for applying acaricides. Traditional methods involve full emersion of livestock, but alternatives are the directed spraying of chemicals or a pour-on approach. For some acaricides, it is possible to deliver the chemical through an injection or as an intraruminal bolus, leading to a gradual release of the chemical over a number of weeks (Rodriguez-Vivas et al., 2018). The main target for acaricides globally is still R. microplus infestation of cattle. But as stated above, it has shown itself to be very capable of developing resistance to virtually every synthetic chemical developed. It is now clear that acaricides should be used in combination with other methods that aim to suppress tick numbers, and the emergence of resistance has prompted the development of vaccine candidates that target the tick vector rather than a particular disease (see below). Approaches such as reducing the frequency of acaricide application, rotating acaricide treatments, and combining this with nonacaricide methods such as environmental management and breeding disease resistance in cattle are likely to reduce the development of resistance and extend the effective life of current acaricides. Avoidance of acaricide resistance is clearly desirable, and it is critical that regular monitoring for resistance in tick populations occurs. Methods for reducing the development of resistance should be applied, although this adds a level of complexity and will incur higher costs to the livestock owner. Improving the nutritional status of cattle and increasing genetic resistance to tick infestation are also considered important to reducing the impact of tick infestation.

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Land management Land management to suppress ticks can take a number of forms. In the United Kingdom, improvement of pastures to increase the grass quality generally reduces the ability of field systems to support ticks. Burning pastures has been used as a means of reducing tick burden in North America, Africa, and Australia (Abbas et al., 2014). This directly destroys tick eggs and all life stages of the tick and removes the vegetation layer in which ticks reside when not on the host. However, in addition to the short-term destruction of pasture, a systematic study on the effect of burning as a component of a management strategy in South Africa showed that repeated use had no consistent effect on the tick assemblage with some study areas showing an increase in tick numbers, whereas others showed a decrease (Horak et al., 2006). Presumably, the process of recovery reintroduces the tick population that increases over time. Another means of suppressing tick populations is that of alternating periods when cattle are present on pastures. If applied for sufficiently long periods, it removes the principal food source for Rhipicephalus species larvae, leading to their starvation.

Vaccines Vaccination is the main approach to preventing many diseases of both public and animal health concern. This is also true for tick-borne pathogens where a number of vaccines are now available to prevent disease if exposure occurs through a tick bite. This reveals the triangular nature of pathogen transmission involving the tick, the pathogen, and the mammalian host (Rego et al., 2019). This in turn opens a further option for vaccination against the tick itself.

Vaccines directed at individual tick-borne pathogens For humans, the main successes have been the development of effective vaccines against tick-borne encephalitis virus. Two vaccines are licensed in Europe FSMEImmun and Encepur, both widely available and highly effective at preventing diseases. A further two are produced in the Russian Federation (Table 13.4). Other vaccines for rarer diseases such as Kyasanur Forest disease virus are available in India, where the disease is endemic in parts of the southwest of the country (Rajaiah, 2019). For other diseases, such as Lyme borreliosis, vaccines have been developed and made available but then withdrawn due to lack of uptake (Plotkin, 2011). A range of livestock vaccines are available but are often not ideal, for example, live vaccines for treatment of theileriosis in Africa can induce disease (Nene and Morrison, 2016) and thus many vaccines are still required to protect against animal

Public information

Table 13.4 Vaccines licensed in Europe and the Russian Federation for prevention of tick-borne encephalitis. Trade name

Manufacturer

Licenced for use

FSME-ImmunÒ EncepurÒ TBE-Moscow EnceVirÒ

Pfizer Bavarian Nordic Chumakov Federal Scientific Center NP0 Microgen

Europe Europe Russian Federation Russian Federation

diseases transmitted by ticks. This gap makes the development of vaccines that target the tick vector itself attractive.

Vaccines directed at ticks The purpose of antitick vaccines is to induce an immune response that will interfere with the attachment and/or feeding process, block pathogen transmission from the tick to the host or suppress the tick population. A key challenge has been the identification of an antigen or antigens that when vaccinated into a mammalian host induce immune responses that achieves one or more of these functions. One antigen, termed BM86, a protein expressed on the surface of midgut cells, has been successfully commercialized to control R. microplus in cattle (Odongo et al., 2007; Carreo´n et al., 2012). However, this appears to have a limited effect on other tick species, even those related to R. microplus, and has prompted a search for alternative antigens both from within the tick midgut and from salivary gland components that are introduced into the feeding wound. This has been assisted by advancements in the “omics” technologies including transcriptomics, proteomics, and metabolomics that allow large numbers of protein targets to be investigated simultaneously in order to rationally design potential vaccine candidates (Artigas-Jero´nimo et al., 2018; de la Fuente, 2021).

Public information Finally, one of the most cost-effective means of preventing tick-borne diseases is the education of the public, livestock keepers, and those involved in delivering public and animal health in the prevention of tick bites. For humans, this can be achieved by avoiding areas where ticks are abundant or the times of day when they are likely to be active. In temperate regions of the world, tick behavior is seasonal with activity limited to those times when temperatures permit tick activity. If humans do enter areas where ticks are active, they can ensure that exposed areas of the body, i.e., limbs, are covered and the use of repellents can prevent biting from a range of

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arthropods. If a tick is detected, the instruction on the appropriate removal should be given ensuring that all the mouthparts are removed from the wound. For animals, preventing contact with ticks is problematic as livestock are normally held in areas that are contiguous with the environment. Again, limiting periods when animals are in contact with ticks is an option in some parts of the world but needs accurate information on the behavior of key tick species. For domestic animals such as dogs and cats, eliminating contact may not be possible, but the use of antitick treatments should be recommended and has the added benefit of suppressing other arthropod parasites.

Conclusions Control of ticks and tick-borne diseases can take many forms. Key among these is the establishment of an effective surveillance program in areas where the risk of tick-borne disease transmission is high. In addition, surveillance offers the best means of assessing the impact of anthropogenic change; key among these is the effects of climate change over time. The key objectives for such a surveillance program should include: • • • • •

Long-term surveillance to characterize the distribution and abundance of ticks on a sufficiently large scale to encompass areas of tickevertebrate interaction. Determination of the presence and prevalence of tick-borne pathogens in at-risk host populations and within indigenous tick instars that transmit the pathogen. Provide evidence-based information for public and animal health policy to identify, mitigate, and control tick-borne disease transmission. Detect the emergence of acaricide resistance in tick populations. Rapid detection of introduced exotic tick species and provide timely interventions to prevent establishment or spread to the wider environment.

Surveillance provides the bedrock on which other facets of tick and tick-borne disease control can be built. A clear understanding of who or what is at risk of tick-borne disease transmission allows the identification of at-risk populations who can be targeted for vaccination programs. Early detection of acaricide resistance allows alternative strategies to be introduced such as the rotation of different chemical agents. If areas where ticks are abundant are known, livestock can be directed away from such areas and attempts made to improve the pasture that in turn suppresses tick populations. Greater knowledge of ticks and the pathogens that they transmit requires basic research using experimental models. As outlined above, this can take the form of tick cells, colonized ticks, or sampling of wild tick populations. All can contribute to a greater understanding of the tickepathogen interaction and lead to novel strategies that suppress tick populations, inhibit pathogen transmission, or protect humans and livestock from developing disease.

References

The initial success of eradicating tick-borne diseases of cattle in North America during the early 20th century provided an example for the application of acaricides around the world. Unfortunately, this success has not been duplicated, and the overuse of chemical agents brings with it many detrimental effects to both the humans that apply it and the wider environment. No one measure has been universally successful at controlling ticks and tick-borne diseases. Therefore, a range of options need to be considered when attempting to control ticks, prevention of tick contact, and the suppression of disease. Acaricide treatment has been used extensively to control tick infestations, but this has led inexorably to the development of resistance in tick populations around the world. Even in developed countries, there are still challenges to overcome in preventing disease transmission to humans, not least the cost of introducing control measures (Eisen and Stafford, 2021). For many countries, a so-called integrated pest management strategy is needed where every step of the tickehost interaction is considered and multiple control measures applied to suppress tick populations and prevent transmission to mammalian hosts from occurring (Stafford et al., 2017). A range of measures, including breeding increased resistance into livestock, developing vaccines that both prevent the development of disease and suppress tick populations that feed on livestock all play a role in achieving control of ticks and tick-borne diseases.

References Abbas, R.Z., Zaman, M.A., Colwell, D.D., Gilleard, J., Iqbal, Z., 2014. Acaricide resistance in cattle ticks and approaches to its management: the state of play. Veterinary Parasitology 203 (1e2), 6e20. https://doi.org/10.1016/j.vetpar.2014.03.006. Abdullah, S., Helps, C., Tasker, S., Newbury, H., Wall, R., 2016. Ticks infesting domestic dogs in the UK: a large-scale surveillance programme. Parasites & Vectors 9 (1), 391. https://doi.org/10.1186/s13071-016-1673-4. Agwunobi, D.O., Yu, Z., Liu, J., 2021. A retrospective review on ixodid tick resistance against synthetic acaricides: implications and perspectives for future resistance prevention and mitigation. Pesticide Biochemistry and Physiology 173. https://doi.org/10.1016/j.pestbp.2021.104776. Al-Rofaai, A., Bell-Sakyi, L., 2020. Tick cell lines in research on tick control. Frontiers in Physiology 11, 152. https://doi.org/10.3389/fphys.2020.00152. Artigas-Jero´nimo, S., De La Fuente, J., Villar, M., 2018. Interactomics and tick vaccine development: new directions for the control of tick-borne diseases. Expert Review of Proteomics 15 (8), 627e635. https://doi.org/10.1080/14789450.2018.1506701. Bell-Sakyi, L., Zweygarth, E., Blouin, E.F., Gould, E.A., Jongejan, F., 2007. Tick cell lines: tools for tick and tick-borne disease research. Trends in Parasitology 23 (9), 450e457. https://doi.org/10.1016/j.pt..2007.07.009. Bell-Sakyi, L., Attoui, H., 2016. Virus discovery using tick cell lines. Evolutionary Bioinformatics 12, 31e34. https://doi.org/10.4137/EBO.S39675. Boedeker, W., Watts, M., Clausing, P., Marquez, E., 2020. The global distribution of acute unintentional pesticide poisoning: estimations based on a systemic review. BMC Public Health 20, 1875. https://doi.org/10.1186/s12889-020-09939-0.

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Bonnet, S.I., Blisnick, T., Al Khoury, C., Guillot, J., 2021. Of fungi and ticks: morphological and molecular characterization of fungal contaminants of a laboratory-reared Ixodes ricinus colony. Ticks and Tick-Borne Diseases 12 (5), 101732. https://doi.org/10.1016/ j.ttbdis.2021.101732. Bonnet, S, Joughlin, M, Malandrin, L, Becker, C, Agoulon, A, L’hostis, M, Chauvin, A, 2007. Transtadial and transovarial persistence of Babesia divergens DNA in Ixodes ricinus colony. Parasitology 12 (2), 197e207. https://doi.org/10.1017/S0031182006001545. Carreo´n, D., Pe´rez de la Lastra, J.M., Almaza´n, C., Canales, M., Ruiz-Fons, F., Boadella, M., Moreno-Cid, J.A., Villar, M., Gorta´zar, C., Reglero, M., Villarreal, R., De la Fuente, J., 2012. Vaccination with BM86, subolesin and akirin protective antigens for the control of tick infestations in white tailed deer and red deer. Vaccine 30 (2), 273e279. https:// doi.org/10.1016/j.vaccine.2011.10.099. Chiuya, T., Masiga, D.K., Falzon, L.C., Bastos, A.D.S., Fe`vre, E.M., Villinger, J., 2021. Tickborne pathogens, including Crimean-Congo haemorrhagic fever virus, at livestock markets and slaughterhouses in Western Kenya. Transboundary and Emerging Diseases 68 (4), 2429e2445. https://doi.org/10.1111/tbed.13911. Cull, B., Pietzsch, M.E., Hansford, K.M., Gillingham, E.L., Medlock, J.M., 2018. Surveillance of British ticks: an overview of species records, host associations, and new records of Ixodes ricinus distribution. Ticks and Tick-Borne Diseases 9 (3), 605e614. https:// doi.org/10.1016/j.ttbdis.2018.01.011. Cull, B., Pietzsch, M.E., Gillingham, E.L., McGinley, L., Medlock, J.M., Hansford, K.M., 2020. Seasonality and anatomical location of human tick bites in the United Kingdom. Zoonoses and Public Health 67 (2), 112e121. https://doi.org/10.1111/zph.12659. Dantas-Torres, F., 2008. The brown dog tick, Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae): from taxonomy to control. Veterinary Parasitology 152 (3e4), 173e185. https://doi.org/10.1016/j.vetpar.2007.12.030. Davies, S., Abdullah, S., Helps, C., Tasker, S., Newbury, H., Wall, R., 2017. Prevalence of ticks and tick-borne pathogens: Babesia and Borrelia species in ticks infesting cats of Great Britain. Veterinary Parasitology 244, 129e135. https://doi.org/10.1016/ j.vetpar.2017.07.033. de la Fuente, J, 2021. Translational biotechnology for the control of ticks and tick-borne diseases. Ticks and Tick-borne Diseases 12 (5), 101738. https://doi.org/10.1016/ j.ttbdis.2021.101738. De Marco, M.d.M.F., Herna´ndez-Triana, L.M., Phipps, L.P., Hansford, K., Mitchell, E.S., Cull, B., Swainsbury, C.S., Fooks, A.R., Medlock, J.M., Johnson, N., 2017. Emergence of Babesia canis in southern England. Parasites & Vectors 10 (1), 241. https://doi.org/ 10.1186/s13071-017-2178-5. Drehmann, M., Springer, A., Lindau, A., Fachet, K., Mai, S., Thoma, D., Schneider, C.R., Chitimia-Dobler, L., Bro¨ker, M., Dobler, G., Mackenstedt, U., Strube, C., 2020. The spatial distribution of Dermacentor ticks (Ixodidae) in Germanydevidence of a continuing spread of Dermacentor reticulatus. Frontiers in Veterinary Science 7, 578220. https://doi.org/10.3389/fvets.2020.578220. Eisen, L., Stafford, K.C., 2021. Barriers to effective tick management and tick-bite prevention in the United States (Acari: Ixodidae). Journal of Medical Entomology 58 (4), 1588e1600. https://doi.org/10.1093/jme/tjaa079. Eisen, L., Eisen, R.J., 2021. Benefits and drawback of citizen science to complement tranditional data gathering approaches for medically important hard ticks (Acari: Ixodidae) in

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Synthesis: future developments in tick research

14

The preceding chapters have provided overviews of many aspects of tick biology, ecology, and disease. This final chapter will look ahead and consider what might be the future developments for research on ticks. This encompasses basic observations that lead to a greater understanding of biology and ecology. Further discoveries of how tick physiology influences pathogen transmission and the continued search to find effective means of suppressing tick numbers and preventing the diseases they transmit, all are intimately linked to new developments in technology. Human modification of the environment and the expansion of intensive agricultural practice, together with climate change will all contribute to the future challenges of tickborne disease.

New discoveries and species redistribution While many facets of tick biology are known, there is much more to be discovered. Research has been directed at those tick species that transmit disease to humans and livestock, and the interactions between tick biology, ecology, and pathogen transmission. The assemblage of ticks in many parts of the world has been established. However, in other regions, such as the tropics and more remote locations, new tick species will continue to be discovered or new host associations will be found. In Australia, a new species of hard tick, Ixodes woyliei, has been described, which feeds specifically on the woylie or brush-tailed bettong (Bettongia penicillata), a rare marsupial found in the southern States (Ash et al., 2017). Attempts to characterize the great biodiversity in tropical and subtropical regions will discover new tick species and new tickehost interactions. Unfortunately, there will also be further examples of invasive tick species spreading to new regions. The direction of travel has been predominantly Old World to New World, mainly associated with livestock movements with examples such as Rhipicephalus microplus, Amblyomma variegatum (Le´ger et al., 2013), and most recently Haemaphysalis longicornis (Tufts and Diuk-Wasser, 2021) being prime examples. However, it is possible that the trend could reverse with New World species transported to Europe, Africa, and Asia. The vector of these translocations is likely to be humans themselves. A survey of ticks imported to the United Kingdom associated with travelers identified a range of North American species including Ticks. https://doi.org/10.1016/B978-0-323-91148-1.00014-9 Copyright © 2023 Elsevier Inc. All rights reserved.

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Amblyomma americanum, Dermacentor andersonii, Dermacentor variabilis, and Ixodes pacificus (Gillingham et al., 2020). Travelers had also imported tick species indigenous to South America, southern Africa, Asia, and Australia. Another report documented the human importation of Amblyomma mixtum into Germany from Cuba (Chitimia-Dobler et al., 2020). These studies report relatively small numbers of ticks, suggesting that the barriers to establishment are high. What is not considered are the unknown numbers of unreported cases and the ability of a single engorged tick to produce thousands of eggs. This suggests that such an introduction is possible, and with them, the introduction of a range of new diseases. Pathogenic strains of protozoa and bacteria, such as Babesia microti and Anaplasma phagocytophilum, respectively, cause human disease in North America, but the strains of these organisms found in Europe do not. The introduction of pathogenic strains in association with North American ticks could change the risk of disease in Europe profoundly. In parallel to human transportation is the movement of ticks from tropical regions to locations further north or south by birds (Sparagano et al., 2015). This occurs on an annual basis with large mass migrations of many bird species but until recently has been limited by the failure of tropical and subtropical species to establish breeding populations in cooler northerly latitudes. As the effects of climate change begin to influence the seasons in temperate regions, the frequency of tick translocations could lead to the establishment of exotic tick populations and again the emergence of diseases that they transmit (Buczek et al., 2020). This is driving the geographic expansion of indigenous Ixodes species in Eurasia to higher latitudes than previously observed and at higher altitudes (De Pelsmaeker et al., 2021), and the range expansion of hard ticks in North America (Sonenshine, 2018).

Ticks as vectors Ticks have been recognized as one of the most important arthropod vectors of disease-causing pathogens to humans, livestock, and domestic pets for over 100 years. Wildlife has also been recognized to play a role in supporting tick populations, acting as a reservoir for tick-borne pathogens and more recently as being influenced by the impact of both tick infestation and disease. In the most extreme cases, this can play a role in reducing wildlife populations and exacerbate the long-term survival of endangered species. A recent study (Orozco et al., 2020) documented factors influencing the morbidity and mortality of South American marsh deer (Blastocerus dichotomus). In Argentina, the species is considered vulnerable and under threat of local extinction. Investigations of animals with poor body condition identified heavy infestations of Amblyomma triste and R. microplus. In parallel, the investigators detected a range of tick-borne pathogens including Theileria cervi, Ehrlichia chaffiensis, and Anaplasma species. Normally, tick infestations or disease do not drive vertebrate species to extinction, but the combination of these infections,

Ticks as vectors

along with the usual human-mediated factors such as hunting and habitat destruction, can threaten the long-term viability of bush deer populations. A major driver for studying ticks, and the main motivation for this book, is the study of tick-borne diseases, both those caused by existing pathogens and identification of emerging tick-borne diseases (Rochlin and Toledo, 2020). Chapters 6, 7 and 9 have provided and overview of this with Chapter 9 focussing on recently emerged pathogens. In the future, there is likely to be further discoveries of rare human diseases, some of which may be fatal. The identification of Beiji virus in China is part of a long-term trend of discovery that will certainly continue as diagnostic techniques become more sensitive, public health professions become more aware of new threats, and the ability to genetically characterize pathogens is readily available. In North America, the trends for virus emergence, in the case of Bourbon virus (Kosoy et al., 2015), and invasive ticks, have collided with the detection of this virus in the recently introduced species H. longicornis (Cumbie et al., 2022). And the discovery of new pathogens could occur anywhere in the world where ticks actively feed on humans and livestock. A clear trend that has developed over recent decades has been the development of citizen science in supporting research and public health efforts in determining the distribution of ticks and tick-borne disease (Eisen and Eisen, 2021). The major advantages of these programs are the ready access to samples and data on tick encounters with humans and domestic animals. The approach is also highly cost-effective and has the added benefit of raising public awareness and engagement with the risks of tick-acquired disease. The key disadvantages are the quality of data supplied and limitations on accurate morphological identification by nonspecialists. Technology can play a role with many people being able to capture an image of a tick and uploading this to a website in minutes. Developing automated methods of identifying these images, at least to genus level through machine learning would support efforts to map tick distribution (Luo et al., 2022). For diseases of livestock, the future will be dominated by continued efforts to suppress or eradicate the transmission of tick-borne diseases. While many options are available for tick control, no one approach appears to be entirely effective. Despite the early success of acaricide treatment in eliminating R. microplus from the United States using highly toxic chemicals, the human health and ecological costs of this have not been fully determined, and it has not been repeated anywhere else in the world. In fact, the opposite appears to be the case with the emergence of resistance to many commercial acaricides that have been developed over the past 50 years. History suggests that ticks will continue to be a formidable threat that can develop resistance to acaricides and persist, despite the best efforts of modern science. Monitoring the development of resistance will be the only way of prolonging the effectiveness of the acaricides currently in use and modifying their use, either limiting applications or rotating multiple acaricides. The discovery of new pathogens supported by the increasing studies of the assemblage of microorganisms associated with ticks will continue. Interest in the tick microbiome in recent years has resulted in evermore studies that have revealed

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the huge number and diversity of microorganisms associated with ticks. This ranges from well-characterized pathogens through to obligate endosymbiotic bacteria. Such studies have been aided by the rapid development of both mass sequencing technologies and the bioinformatic methodologies needed to analysis the data generated. Reductions in cost are also a significant factor enabling the application of these technologies by evermore researchers. The current challenge for research is to go beyond mere description and identify interactions between components of the microbiome and the tick or with particular pathogens. An example of this has been the discovery that A. phagocytophilum can manipulate protein expression in the tick gut to promote bacterial colonization (Abraham et al., 2017). Such discoveries can assist in finding ways of manipulating the microbiome with the purpose of reducing pathogen transmission (Wu-Chung et al., 2021).

Climate change and ticks The climate is changing around the world, and this will have profound effects on tick populations everywhere. Changes to the climate will benefit some species, especially those that can take advantage of warmer temperatures or increased rainfall. This will allow an increase in tick abundance or enable the species to spread into different regions. This is a three-step process of introduction (by human translocation or host migration); establishment where environmental conditions permit survival, especially when off the host and through winter periods; and persistence, where vertebrate hosts can be found. Conversely, changes to climate may be detrimental to some tick species, either through reduced access to vertebrate hosts or environmental changes, and may limit tick survival. The majority of studies have focused on the positive effects climate change will have on tick populations. Changes to temperatures, rainfall, and snow cover could influence survival and accelerate development through the tick life cycle (Medlock et al., 2013). However, some effects of climate change will have a negative impact on ticks. Climatic change that leads to a loss of vegetation and the vertebrate assemblage in certain regions could in extreme cases lead to the extinction of potential hosts. As an obligate parasite, the loss of a host will inevitably lead to extinction for the tick. The loss of a moist vegetative layer due to increased temperatures and lower rainfall would remove a critical habitat for the survival of Ixodes species in temperate regions during the extended interval between host feeding. A further challenge to understanding the impact of climate change is disentangling the actual impacts of a changing climate and anthropogenic changes. Modification of the environment is primarily driven by human activity, converting natural habitat to agricultural land or into urban areas. Land given over to livestock may be beneficial to ticks in providing a ready source of vertebrate hosts. However, land used for crop rearing is unlikely to benefit ticks. A long-term trend away from meat consumption to a plant-based diet by the human population would result in reduced numbers of livestock, especially large

Tick genomics

ruminants. This could restrict those tick species that feed on livestock during one or more life stages. Despite some studies highlighting the presence of ticks in urban environments (Hansford et al., 2022), towns and cities are generally hostile for ticks. Only those tick species that can parasitize abundant urban animals, such as Argas reflexus feeding on feral pigeons (Columba livia) and Rhipicephalus sanguineus feeding on the domestic dog (Dantas-Torres, 2009; Uspensky, 2014), can survive in a human modified environment are likely to persist.

Tick genomics A final area for development is the genetic manipulation of ticks. Whereas this is well developed for the other major vector of disease, mosquitoes, partly due to the relatively close relationship with fruit flies, there is little comparable research on ticks. However, this will change in the near future with the increase in the number of complete tick genomes now available for Ixodes scapularis (Gulia-Nuss et al., 2016) and Rhipicephalus species (Guerrero et al., 2016), improved knowledge on embryogenesis within tick eggs, and the development of CRISPR/Cas9 to enable mutagenesis of target sequences (Nuss et al., 2021). Such innovations will enable genetic manipulation. The extended tick life cycle and the challenge of providing multiple blood meals present further barriers to the development of genetically modified ticks. However, this approach could aid in the understanding of tick development, the role of particular tick salivary proteins and further antitick vaccine candidates identified. All ultimately leading to tick control and prevention of pathogen transmission. Other tick species being targeted for complete genome assembly include Ixodes ricinus and Ornithodoros moubata. A further benefit of increased tick genome data is its contribution to clarifying the taxonomic status of members of a particular species complex and correcting misidentified specimens. Throughout the writing of this book, the repeated challenge was to wade through the disagreements concerning tick taxonomy. This doesn’t seem unique to tick biology, and there are similar conflicts over the naming and classification of a variety of pathogenic organisms. This may well be the outcome whenever two taxonomists enter a discussion. However, the increase in sequence data moves the argument away from reliance on morphology where the absence or inaccessibility of type specimens is a major problem in deriving definitive identifications. Comparison of the complete mitochondrial genome has enabled a greater understanding of the relationship and evolution of ticks at the family level and within particular genera (Kelava et al., 2021). The mitochondrial genome is proving a useful and manageable target, at just under 15,000 base pairs in length, for these applications (Mohamed et al., 2022). Where the members of a species complex based on morphological similarities exist, such as for R. sanguineus (Gray et al., 2013), genomic sequence analysis can reveal differences within that species complex (Liu et al., 2013).

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In parallel to the generation of large volumes of sequence data has been the necessary development of bioinformatics analysis to make sense of biological processes, so called “omics” technologies. These include transcriptomics (RNA transcription), proteomics (protein expression) and metabolomics (metabolic pathway analysis). It is from these analyses that new vaccine candidates and targets for tick control will emerge (de la Fuente, 2021).

Harnessing the sialome The vast majority of ticks are obligate blood-feeding parasites that can take minutes to weeks to obtain a blood meal. To achieve this, the tick has evolved both the physical structures (mouth parts, expandable gut and body, and salivary glands) and the physiological capability (immunomodulatory proteins, proteases, and cement) to successfully feed and obtain a blood meal. Great strides have been made in characterizing the contents of tick saliva and matching them to the multifunctional requirements of acquiring a blood meal in a process that can take days to complete. While there is great optimism that an understanding of the contents of salivary secretions will lead to new vaccine approaches and therapeutics that could protect against immune-mediated disease resulting from tick bites (Chmelar et al., 2016). It is also clear that more research will be required to realize these goals. Vast amounts of transcriptomic and proteomic data can be generated from a single sample derived from a single species, but this has only revealed the extent of the complexity of the tick sialome, the set of RNA transcripts, and proteins present. Further studies are required to define the structure of tick proteins (Denisov and Dijkgraaf, 2021) and their function (Ferna´ndez-Ruiz and Estrada-Pen˜a, 2022) that in turn will inform how they can be used as targets for vaccines and therapies. Furthermore, an understanding of the host response to these proteins is also critical in order to predict an effective antitick response for future biological products (Ali et al., 2022). However, what works for one tick species may not function for an unrelated species suggesting that comparative studies between datasets will be needed to identify proteins with similar structural motifs and functions. The long evolutionary history of ticks suggests that different genera may have evolved different approaches to solving the same physiological problem.

Closing remarks Despite the wealth of knowledge on tick biology, there is still much more to learn. Areas where a clearer understanding include the precise structure of sclerotin and how it is synthesized by the tick. There is also little information on the mating strategies of most tick species, usually limited to statements such as on- or off-host. The ecology of ticks and how this influences interactions with humans is receiving much

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Index ‘Note: Page numbers followed by “f ” indicate figures, “t” indicate tables and “b” indicate boxes.’

A Acaricides, 173, 204e205, 204t Alkhurma hemorrhagic fever virus (AHFV), 77e78 Alternative model system, tick cell lines as, 203e204 Amblyomma americanum, 31 Anaplasma phagocytophilum, 89t, 133 Antitick vaccination, 58 A. phagocytophilum, 133 Argasidae, 13 Argas vespertilionis, 38, 39f Aristotle, 1

B Babesia microti, North America, 142e144, 143f Babesiosis, 93e95, 94f, 113e115, 113t Bacteria, 118e122 Bites site, skin at, 56e57 Blood feeding attachment, 48, 49fe50f bites site, skin at, 56e57 detachment, 49e50 engorgement, 49 exception to, 52 host, 46e47, 47f hyperparasitism, 51e52 interrupted feeding, 51 problems associated with, 50 thermoregulation, 50e51 tick saliva, 52e53 tick salivary gland antitick vaccination, 58 functions of, 54e56, 54t pathogen transmission, 57e58 structure of, 53e54 water balance, 51 Borrelia burgdorferi, 133 Bourbon virus (BRBV), 142 Bovine theileriosis, 117e118

C Canine ehrlichiosis, 121 China, Beiji virus in, 140e141 Climate change CO2 emissions, 178

Fifth Assessment Report (FAR), 178 human-mediated climate change, 171 Hyalomma species, 172 Intergovernmental Panel on Climate Change (IPCC), 178 Ornithodoros, 172 temperate regions British Isles, 180, 181t Europe, 179e180 North America, 181e182 at the poles, 185 tropical and subtropical regions, 182e184 tick infestation, 173 vaccines, 173 CO2 emissions, 178 Colorado tick fever (CTF), 78 Controlling ticks acaricides, 204e205, 204t alternative model system, tick cell lines as, 203e204 citizen science, 198e199 environmental collection of, 196e197 indirect effects, 194 invasive species, challenge of, 200e202 land management, 206 linking ticks, 194 on-host collections of ticks, 197e198, 198f public information, 207e208 surveillance, 195e196 tick-associated pathogens, detection of, 199e200, 201t tick-borne disease biology, 202 tickepathogen interactions, tick colonies for, 202e203, 203t ticks, surveying for, 196 transmission, 202 vaccines, 206 directed at ticks, 207 individual tick-borne pathogens, 206e207 Coxiella burnetiidQ fever, 92e93, 93f CrimeaneCongo hemorrhagic fever, 78e79, 172

D Deer tick virus, 84e85 Dermacentor reticulatus, 31e32, 32f, 33t Detachment, 49e50

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Index

Detect pathogens, technologies used to, 154e155 Disgusting parasites, 1

E Ehrlichiosis, 89e90 Engorgement, 49 Eyach virus, 80

F Fifth Assessment Report (FAR), 178

G Genetic sequence, 18e20

H Haemaphysalis longicornis, 36 Hard ticks Amblyomma americanum, 31 Dermacentor reticulatus, 31e32, 32f, 33t Haemaphysalis longicornis, 36 Hyalomma marginatum, 33e34 Ixodes ricinus, 27e29, 28f Ixodes uriae, 29e31, 30f, 30t Rhipicephalus microplus, 34e35 Rhipicephalus sanguineus, 35e36 Heartland virus (HRTV), 140 Heartwater/cowdriosis, 119e120 Hepatozoonosis, 121e122 Human granulocytic anaplasmosis, 87 Human-mediated climate change, 171 Hyalomma marginatum, 33e34 Hyalomma species, 172 Hyperparasitism, 51e52

I Individual tick-borne pathogens, 206e207 Intergovernmental Panel on Climate Change (IPCC), 178 Interrupted feeding, 51 Invasive species, challenge of, 200e202 Ixodes persulcatus, 131e133 Ixodes ricinus, 3, 27e29, 28f Ixodes scapularis, North America, 161, 162t Ixodes uriae, 29e31, 30f, 30t Ixodidae, 12e13

K Kyasanur forest disease, 80e81

L Land management, 206 Lyme borreliosis, 87e89

M Microbiome A. phagocytophilum, 133 detect pathogens, technologies used to, 154e155 Ixodes persulcatus, 131e133 Ixodes scapularis, North America, 161, 162t other microbiota, 163 ribonucleic acid (RNA), 133e134 segmented flaviviruses, discovery of, 160e161 tick bacteriome, 161e163 tick-borne diseases, 131e133 tick microbiome (See Tick microbiome) tick-related drivers, 133 tick virome, 155e160, 156te157t, 158f, 159b

N Nairo-like viruses, 141t Nuttalliella namaqua, 13e14

O Omsk hemorrhagic fever, 81e84 Ornithodoros, 172 Ornithodoros moubata, 37e38, 37f

P Pathogen transmission, 57e58 Powassan encephalitis, 84e85 Proteomics, 20

R Rhipicephalus microplus, 2e3, 34e35, 173 Rhipicephalus sanguineus, 2e3, 35e36 Ribonucleic acid (RNA), 133e134 Rickettsiosis, 90, 91t

S Segmented flaviviruses, discovery of, 160e161 Sensu stricto, 3 Severe fever with thrombocytopenia syndrome (SFTS), 138, 140 Severe fever with thrombocytopenia syndrome virus (SFTSV), 138e140 Soft ticks Argas vespertilionis, 38, 39f Ornithodoros moubata, 37e38, 37f Surveillance, 195e196

Index

Synthesis climate change, 220e221 genomics, 221e222 new discoveries, 217e218 sialome, harnessing, 222 species redistribution, 217e218 vectors, 218e220

T Temperate regions British Isles, 180, 181t Europe, 179e180 North America, 181e182 at the poles, 185 tropical and subtropical regions, 182e184 Theileria orientalis, 6, 144e146 Theileriosis, 115e117, 116t Thermoregulation, 50e51 Tick-associated pathogens, detection of, 199e200, 201t Tick-borne disease Africa, 67e68, 67t African swine fever (ASF), 109e110 alkhurma hemorrhagic fever virus (AHFV), 77e78 animals, 109t Asia, 68, 68t Australia, 68e69, 69t Babesia microti, North America, 142e144, 143f bacteria Anaplasma phagocytophilum, 89t Coxiella burnetiidQ fever, 92e93, 93f Ehrlichiosis, 89e90 human granulocytic anaplasmosis, 87 Lyme borreliosis, 87e89 rickettsiosis, 90, 91t tularemia, 90e92 biology, 202 Bourbon virus (BRBV), 142 China, Beiji virus in, 140e141 Colorado tick fever (CTF), 78 Crimeanecongo hemorrhagic fever, 78e79 deer tick virus, 84e85 Europe, 69e70, 70t Eyach virus, 80 Heartland virus (HRTV), 140 human diseases, 76t Kyasanur forest disease, 80e81 measures of, 77t Nairobi sheep disease (NSD), 112 Nairo-like viruses, 141t New Zealand, 68e69, 69t Nonpathogen-associated disease, 95e96 North America, 70e71, 71t

Omsk hemorrhagic fever, 81e84 Ovine encephalitis, 110e112 Powassan encephalitis, 84e85 protozoa, 113e118 babesiosis, 93e95, 94f, 113e115, 113t bacteria, 118e122 bovine theileriosis, 117e118 canine ehrlichiosis, 121 heartwater/cowdriosis, 119e120 hepatozoonosis, 121e122 theileriosis, 115e117, 116t tick-borne fever, 118e119, 120t severe fever with thrombocytopenia syndrome (SFTS), 138, 140 severe fever with thrombocytopenia syndrome virus (SFTSV), 138e140 South and Central America, 71, 72t Theileria orientalis, 144e146 Thogoto virus, 112e113 tick-borne encephalitis, 85e87, 86f, 88f Tick-borne fever, 118e119, 120t Tickepathogen interactions, tick colonies for, 202e203, 203t Ticks argasidae, 13 classification, 11b families, 12t genetic sequence, 18e20 infestation, 173 ixodidae, 12e13 life cycle hard ticks. See Hard ticks soft ticks. See Soft ticks morphology, 14e15, 15fe16f identification, 17e18, 17b naming of, 3e4, 4fe5f Nuttalliella namaqua, 13e14 proteomics, 20 Rhipicephalus microplus, 2e3 Rhipicephalus sanguineus, 2e3 surveying for, 196 taxonomy, 10e11, 10b Tick virome, 155e160, 156te157t, 158f, 159b Transmission, 202 Tularemia, 90e92

V Vaccines, 173, 206 directed at ticks, 207 individual tick-borne pathogens, 206e207

W Water balance, 51

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