Fasciolosis II

Fasciolosis is a major global infection of livestock causing both huge losses to the agricultural community and affecting human health as a food-borne disease. Fully updated throughout, this new edition continues to cover the life cycle, biology, and development of the parasite; clinical pathology, immunology, diagnosis and vaccine development; and emergence, cause and mechanisms of drug resistance. It reviews the temperate liver fluke Fasciola hepatica, together with molecular, biochemical, control, and epidemiologial aspects of the tropical liver fluke F. gigantica. Many fundamental advances have taken place in the last two decades, but of particular importance has been the mapping of the draft genome of Fasciola. In addition, comprehensive advances in transcriptomics, proteomics and glycomics have been made, and the book therefore pays particular attention to these developments with the addition of brand-new chapters. Also covering the impact these parasites have had on the global human population, their distribution and their ecology, this book provides a comprehensive and accessible resource for scientists, researchers and students of medical and veterinary parasitology. Cover Fasciolosis Copyright Contents Contributors Preface Acknowledgements 1 The Discovery of Fasciola hepatica and its Life Cycle 1.1 Introduction 1.2 The Discovery of the Life Cycle 1.3 The Life Cycle 1.3.1 Development and survival of the fluke egg 1.3.1.1 Temperature 1.3.1.2 Moisture 1.3.1.3 Oxygen tension and pH 1.3.2 Hatching of the miracidium from the egg and penetration of the intermediate snail host 1.3.2.1 Hatching of the egg 1.3.2.2 Survival of miracidia 1.3.2.3 Location and penetration of the snail host 1.3.3 Development and multiplication inside the snail 1.3.4 Emergence of cercariae from snails and their encystment 1.3.4.1 Encystment 1.3.4.2 Structure of the metacercarial cyst 1.3.4.3 Longevity of metacercariae 1.3.5 Ingestion of infective metacercariae 1.3.5.1 Excystation 1.3.5.2 Migration to the liver References 2 Fasciola hepatica Larval Development Within the Intermediate Host 2.1 Introduction 2.2 Snail Hosts of Fasciola hepatica 2.2.1 Snail species known to be intermediate hosts 2.2.2 Susceptibility of lymnaeid species to Fasciola hepatica 2.3 Dynamics of Larval Forms Within the Snail 2.3.1 Miracidial penetration and outcome of the sporocyst 2.3.2 Redial generations of Fasciola hepatica 2.3.2.1 Identification of redial generations 2.3.2.2 Developmental patterns of redial generations 2.3.2.3 Factors influencing the developmental pattern of redial generations 2.3.2.4 Redial generations in natural infections of snails 2.3.2.5 Consequences of redial development patterns on cercarial productivity 2.3.2.6 Concordance between these redial generations and literature data 2.4 Cercarial Shedding of Fasciola hepatica 2.4.1 Emergence and outcome of cercariae 2.4.2 Dynamics of cercarial shedding 2.4.3 Metacercariae of Fasciola hepatica 2.4.3.1 Metacercariae settled on a support 2.4.3.2 Floating metacercariae 2.5 Snail Infection by the Parasite 2.5.1 Characteristics of infection 2.5.1.1 Parameters studied 2.5.1.2 Methods used 2.5.2 Natural infections of snails 2.5.2.1 Technique for collecting snails in the field 2.5.2.2 Natural infections in Galba truncatula 2.5.2.3 Natural infections in other snail species 2.5.3 Experimental infections of snails over several successive generations 2.5.4 Factors affecting larval development of Fasciola hepatica in the snail 2.5.4.1 Interpopulation and intrapopulation variability in snail susceptibility 2.5.4.2 Environmental factors 2.5.4.3 Factors depending on the snail 2.5.4.4 Factors depending on the parasite 2.5.5 Snail resistance to the parasite 2.6 Snail Co-infections 2.6.1 Co-infections by Fasciola hepatica and Calicophoron daubneyi 2.6.2 Co-infections with Fasciola hepatica and other parasites 2.7 Consequences of Parasitism on the Snail 2.7.1 Visceral pathology in the snail 2.7.1.1 Description of tissue lesions 2.7.1.2 Development of tissue lesions and parasite infection over time 2.7.2 The other consequences of parasitism References 3 Development of Fasciola hepatica in the Mammalian Host 3.1 Introduction 3.2 Tegument 3.2.1 Surface features 3.2.2 Fine structure 3.2.3 Developmental changes 3.2.4 Glycocalyx 3.2.5 Synthetic activity 3.2.6 Functions of the tegument 3.2.6.1 Immune protection 3.2.6.2 Osmoregulation 3.2.6.3 Sensory perception 3.3 Parenchyma 3.4 Muscle 3.5 Nervous System 3.6 Cytoskeleton 3.6.1 Microfilaments 3.6.2 Microtubules 3.7 Gut 3.8 Excretory System 3.9 In vitro Models of Fluke Infection 3.10 Conclusions and Future Perspectives Acknowledgements References 4 The Reproductive System of Fasciola hepatica 4.1 Introduction 4.2 Arrangement of Gonads, Accessory Organs and Ducts 4.3 Development of the Reproductive System 4.4 Male Reproductive System 4.4.1 Testes and spermatogenesis 4.4.2 Accessory ducts and glands 4.5 Female Reproductive System 4.5.1 Ovary and oogenesis 4.5.2 Vitelline cells 4.5.3 Ootype/Mehlis’ gland complex 4.6 The Egg 4.6.1 Egg formation 4.6.2 Parthenogenesis in Fasciola spp.? 4.6.3 Embryogenesis 4.7 Conclusions and Future Perspectives Acknowledgements References 5 Pathology, Pathophysiology and Clinical Aspects 5.1 Pathology 5.1.1 Introduction 5.1.2 Prehepatic stages 5.1.3 Hepatic stages 5.1.4 Other host species 5.1.4.1 Cattle 5.1.4.2 Buffalo 5.1.4.3 Humans 5.1.4.4 Rabbits 5.1.4.5 Rats 5.1.4.6 Mice 5.2 Clinical Aspects 5.2.1 Introduction 5.2.2 Effects on blood components 5.2.2.1 Anaemia 5.2.2.2 Plasma proteins 5.2.2.3 Hepatic enzymes in blood 5.2.2.4 Leucocyte populations 5.2.2.5 Other blood components 5.3 Pathophysiology and Metabolic Aspects 5.3.1 Introduction 5.3.1.1 Weight gain, food intake and nitrogen balance 5.3.2 Organ function 5.3.2.1 Hepatic function 5.3.2.2 Bile flow and composition 5.3.2.3 Endocrine and reproductive effects 5.3.3 Effects on metabolism 5.3.3.1 Redox status 5.3.3.2 Mitochondrial bioenergetic metabolism 5.3.3.3 Carbohydrate metabolism 5.3.3.4 Protein metabolism 5.3.3.5 Lipid metabolism 5.3.3.6 Steroid metabolism 5.4 Pathogenesis 5.4.1 Hepatic pathogenesis 5.4.2 Mechanical damage 5.4.3 Fluke excretory/secretory (ES) products and other secretions 5.4.4 Inflammatory responses 5.5 Fasciola and its Host 5.5.1 Immune response 5.5.2 Immune evasion 5.5.3 Impact of concurrent infection 5.5.4 Effects on pharmacokinetics of drugs 5.6 Conclusions References 6 Epidemiology and Control 6.1 Introduction 6.2 Parasite, Host and Intermediate Host Species 6.2.1 Definitive hosts 6.2.2 Intermediate host species 6.3 The Effects of Climate and Environment on Fasciola spp. 6.3.1 Effect of temperature 6.3.1.1 On fluke eggs 6.3.1.2 On snail development 6.3.1.3 On parasite development within the snail 6.3.1.4 On metacercarial survival 6.3.1.5 Implications for the epidemiology of the infection 6.3.2 Effect of moisture 6.3.2.1 On the parasite 6.3.2.2 On the snail 6.3.2.3 Soil type 6.3.2.4 Implications for the epidemiology of the infection 6.4 Effects of Climate Change 6.5 Management Factors Affecting Transmission 6.6 Other Effects on Transmission 6.6.1 Source of infection 6.6.2 Competing infections 6.6.3 Co-morbidities 6.7 Resistance to Fasciolosis in Livestock 6.7.1 Resistance in sheep 6.7.2 Resistance in cattle 6.8 Economic Effects of Fasciolosis in Livestock 6.8.1 Effects on live-weight gain and wool production 6.9 Control Options for Fasciolosis 6.9.1 Control based on intermediate-host habitats Classification of pastures 6.9.2 Strategic treatment 6.9.3 Vaccination 6.10 Risk Maps, Models and Forecasting Systems 6.11 Conclusions References 7 Flukicidal Drugs: Pharmaco-therapeutics and Drug Resistance 7.1 Introduction 7.2 Pharmaco-therapeutics 7.2.1 Mode of flukicidal action 7.2.1.1 Benzimidazoles 7.2.1.2 Salicylanilides 7.2.1.3 Halogenated phenols 7.2.1.4 Sulfonamides 7.2.1.5 Phenoxyalkanes 7.2.1.6 Artemisinins 7.2.1.7 Mirazid 7.3 Flukicide Pharmacokinetics 7.3.1 Benzimidazoles 7.3.2 Salicylanilides 7.3.3 Halogenated phenols 7.3.4 Sulfonamides 7.4 Mechanisms of Drug Entry into Adult Liver Flukes 7.5 Flukicide Resistance 7.5.1 Detecting anthelmintic resistance in Fasciola spp. 7.5.1.1 Controlled efficacy test (CET) 7.5.1.2 FECRT 7.5.1.3 Egg hatch test 7.5.1.4 Coproantigen Reduction Test 7.5.2 Other methodologies 7.6 Mechanism(s) of Resistance 7.6.1 Candidate gene studies 7.6.2 Omics approaches to understanding drug resistance 7.7 Concluding Remarks Acknowledgement References 8 Metabolism 8.1 Introduction 8.2 Nutrition 8.2.1 Free-living stages 8.2.2 Parasitic stages 8.3 Energy Metabolism 8.3.1 Substrates of energy metabolism 8.3.2 Energy metabolism in free-living versus parasitic stages 8.3.3 Malate dismutation 8.3.4 Selected aspects of glycolysis 8.3.5 Selected aspects of mitochondrial processes 8.3.6 Succinate dehydrogenase versus fumarate reductase 8.3.7 Ubiquinone versus rhodoquinone 8.3.8 Acetate:succinate CoA-transferase 8.3.9 Transitions in energy metabolism 8.4 Biosynthetic Capacities 8.5 Lipid Metabolism 8.6 Protein Metabolism 8.7 Concluding Remarks Acknowledgement References 9 Immunological Interaction Between Fasciola and its Host 9.1 Introduction 9.2 Infection in the Natural Host 9.2.1 Cattle 9.2.2 Sheep 9.2.3 Goats 9.2.4 Other definitive hosts 9.3 Infection in Experimental Hosts 9.3.1 Mice 9.3.2 Rats 9.4 Bystander Effects of Fasciola hepatica Infection 9.5 Therapeutic Potential of Fasciola hepatica-derived Molecules 9.6 Conclusions and Future Directions References 10 Diagnostics for Animal and Human Fasciolosis 10.1 Introduction 10.2 Methods for Diagnosis of Fasciolosis at the Early Stage of Infection 10.2.1 Detection of circulating antigens 10.2.2 Detection of anti-Fasciola antibodies in serum or plasma 10.2.2.1 Methods using excretory/secretory (ES) antigens 10.2.2.2 Methods using purified native antigens 10.2.2.3 Methods using synthetic and recombinant antigens 10.3 Diagnosis During the Early Biliary and Chronic Phases of Infection 10.3.1 Detection of circulating antibodies 10.3.2 Detection of coproantigens 10.4 Detection of Ova in Stools by Microscopy 10.4.1 The Kato–Katz method 10.4.2 Sedimentation and flotation techniques 10.5 Diagnosis by Molecular Techniques 10.6 Adaptations and Complementary Diagnostic Methods 10.6.1 Methods for detection of anti-Fasciola antibodies in milk and other biological fluids 10.6.2 Fluke and egg counts at necropsy 10.6.3 Complementary laboratory findings and non-invasive imaging techniques 10.7 Concluding Remarks Acknowledgements References 11 Applying ‘Omics’ Technologies to Understand Fasciola spp. Biology 11.1 Introduction 11.2 The Mitochondrial and Nuclear Genomes 11.2.1 Fasciola spp. mitochondrial genomes 11.2.2 Nuclear genomes of F. hepatica and F. gigantica 11.2.2.1 F. hepatica genome assemblies 11.2.2.2 F. gigantica genome assemblies 11.2.2.3 Application of the liver fluke genomes 11.3 Transcriptomics and Stage-specific Gene Expression 11.3.1 F. hepatica developmental stage transcriptomes 11.3.1.1 Transcription of multi-copy gene families 11.3.1.2 Key metabolic pathways associated with the F. hepatica life cycle 11.3.1.3 Applications of F. hepatica transcriptome data 11.3.2 F. gigantica developmental stage transcriptomes 11.4 Non-coding RNAs 11.4.1 MicroRNAs 11.4.1.1 Identification of Fasciola miRNAs 11.4.1.2 Biological function of Fasciola miRNAs 11.5 Proteomics Identify Proteins in Parasite–Host Interactions 11.6 Extracellular Vesicles 11.6.1 EV biogenesis and release 11.6.2 EV uptake and function 11.6.3 EV isolation methods 11.7 Glycomics Identify Sugars in Parasite–Host Interactions 11.7.1 Fasciola hepatica glycans 11.7.2 Function of glycans 11.8 Proteomic and Transcriptomic Analyses of Host Responses to F. hepatica 11.9 Concluding Remarks References 12 Vaccines for Fasciola: New Thinking for an Old Problem 12.1 Introduction 12.2 Recent Vaccine Studies in Livestock (2014–2020) 12.2.1 Cathepsin L1 12.2.2 GST 12.2.3 Other antigens 12.2.4 Mucosal vaccine delivery 12.2.5 IgG1 and IgG2 responses in vaccinated cattle and sheep 12.3 A Potential Way Forward 12.3.1 Adjuvants 12.3.2 In vitro models to screen vaccine candidates 12.3.3 Combination vaccines 12.3.4 Conclusion to the above discussion 12.4 Identifying New Protein Vaccine Candidates on the Surface Tegument of Juvenile Flukes 12.4.1 Immunity to Fasciola associated with killing of juvenile flukes early after infection 12.4.2 Surface protein profile on surface of young F. hepatica changes after flukes enter the liver 12.4.3 Proteomic analysis of the adult F. hepatica tegument identified several novel tegument proteins 12.5 Potential Mechanisms of Immunity Against Fasciola hepatica 12.5.1 Approach 1: Proteomic analysis of antigens immunosloughed from the juvenile surface to identify new vaccine candidates 12.5.2 Approach 2: Determine the rate of turnover of individual antigens on the surface of juvenile flukes 12.5.3 Approach 3: Using the tegument proteins identified in Approaches 1 and 2, evaluate whether these are good ADCC targets and potential lead candidates for testing as vaccines in vivo 12.6 Glycans and Glycoconjugates as Vaccine Targets 12.7 Whole Exosomes, Exosome Extracts and Exosome Antigens as Vaccines 12.7.1 EVs as immunomodulators of host responses 12.7.2 Parasite EVs as vaccines 12.7.3 Characterization of EVs from F. hepatica 12.8 New Adjuvants to Enhance Liver Fluke Vaccine Efficacy 12.8.1 Adjuvants showing efficacy for vaccines against Fasciola spp. 12.8.1.1 Comparative screening of adjuvants 12.8.1.2 Oil emulsions 12.8.1.3 Alum 12.8.1.4 Quil A 12.8.1.5 Strong Th1-inducing vaccine formulations 12.8.1.6 Mucosal adjuvants 12.8.1.7 Oral vaccine delivery 12.9 Assessing Liver Fluke Vaccine Efficacy in Cattle Based on Reduction in Intensity of Fluke Burden 12.9.1 Intensity of fluke counts in naturally infected cattle 12.9.2 Other factors impacting cattle vaccine trial design and interpretation 12.9.3 Re-analysis of vaccine data based on fraction of vaccinates with low fluke counts 12.10 Commercial Considerations in Liver Fluke Vaccine Development 12.10.1 Market 12.10.2 Product development 12.10.3 Scalability and manufacturing 12.10.4 Safety 12.10.5 Efficacy 12.10.6 Regulatory requirements 12.10.7 Producer expectations 12.10.8 Pricing References 13 Fasciola gigantica and Fasciola Hybrids in Southeast Asia 13.1 Introduction 13.2 Fasciola gigantica Life Cycle 13.2.1 Introduction 13.2.2 Definitive hosts 13.2.3 Intermediate hosts 13.2.4 Production and survival of metacercariae 13.2.5 The role of the rice paddy in F. gigantica life cycle 13.2.6 Impacts of the built environment on fasciolosis 13.2.7 Prevalence and distribution of F. gigantica in Southeast Asia 13.3 Production and Economic Impacts of Fasciolosis in Southeast Asia 13.3.1 The smallholder farmer 13.3.2 Weight gain and body condition score 13.3.3 Reproduction and lactation 13.3.4 Other production and economic impacts 13.4 Control of Fasciola gigantica 13.4.1 Chemotherapy 13.4.2 Alternatives to anthelmintics 13.5 Diagnosis in the Developing World 13.5.1 Post-mortem diagnosis of fasciolosis in livestock 13.5.2 Ante-mortem diagnosis of fasciolosis 13.6 Genetic Characterization of F. gigantica and Fasciola Hybrids 13.7 Zoonosis 13.8 Future Directions for F. gigantica Research References 14 Global Impact of Human Fasciolosis 14.1 Introduction 14.2 Epidemiology 14.2.1 Geography 14.2.2 Scale of infection 14.2.3 Climate, weather and seasonal effects 14.2.4 Populations at risk 14.3 Pathology in the Human Host 14.3.1 Pathogens 14.3.2 Mechanisms of human infection 14.3.3 Role of domestic livestock in transmission 14.3.4 Clinical presentation 14.3.4.1 Hepatobiliary fasciolosis 14.3.4.2 Ectopic fasciolosis 14.3.5 Other impacts of infection 14.3.6 Diagnosis 14.4 Treatment of Human Fasciolosis 14.4.1 The challenge of treating human fasciolosis 14.4.2 Early treatments 14.4.3 Anthelminthics 14.4.4 Repurposed antiprotozoal treatments 14.4.5 Triclabendazole 14.4.5.1 A repurposed veterinary fasciolicide 14.4.5.2 Clinical trials with triclabendazole in human fasciolosis 14.4.5.3 Case series and case reports with triclabendazole 14.4.5.4 Safety and tolerability 14.4.6 Drug resistance in human fasciolosis 14.5 Future Prospects 14.5.1 Control of fasciolosis 14.5.2 Potential new therapies for human fasciolosis 14.5.3 Future possibilities References Index Back Cover "Fasciolosis is a major infection of livestock, causing huge losses to the agricultural community and affecting human health. This fully updated new edition covers parasite biology and development, immunology, diagnosis, vaccines, and emergence of drug resistance, as well as new advances in genomics, transcriptomics, proteomics and glycomics"-- Provided by publisher