Design and descriptive epidemiology of the Infectious Diseases of East African Livestock (IDEAL) project, a longitudinal calf cohort study in western Kenya

BACKGROUND: There is a widely recognised lack of baseline epidemiological data on the dynamics and impacts of infectious cattle diseases in east Africa. The Infectious Diseases of East African Livestock (IDEAL) project is an epidemiological study of cattle health in western Kenya with the aim of providing baseline epidemiological data, investigating the impact of different infections on key responses such as growth, mortality and morbidity, the additive and/or multiplicative effects of co-infections, and the influence of management and genetic factors. A longitudinal cohort study of newborn calves was conducted in western Kenya between 2007-2009. Calves were randomly selected from all those reported in a 2 stage clustered sampling strategy. Calves were recruited between 3 and 7 days old. A team of veterinarians and animal health assistants carried out 5-weekly, clinical and postmortem visits. Blood and tissue samples were collected in association with all visits and screened using a range of laboratory based diagnostic methods for over 100 different pathogens or infectious exposures. RESULTS: The study followed the 548 calves over the first 51 weeks of life or until death and when they were reported clinically ill. The cohort experienced a high all cause mortality rate of 16% with at least 13% of these due to infectious diseases. Only 307 (6%) of routine visits were classified as clinical episodes, with a further 216 reported by farmers. 54% of calves reached one year without a reported clinical episode. Mortality was mainly to east coast fever, haemonchosis, and heartwater. Over 50 pathogens were detected in this population with exposure to a further 6 viruses and bacteria. CONCLUSION: The IDEAL study has demonstrated that it is possible to mount population based longitudinal animal studies. The results quantify for the first time in an animal population the high diversity of pathogens a population may have to deal with and the levels of co-infections with key pathogens such as Theileria parva. This study highlights the need to develop new systems based approaches to study pathogens in their natural settings to understand the impacts of co-infections on clinical outcomes and to develop new evidence based interventions that are relevant

Epidemiology of infections and co-infections: Impact on survival and growth of zebu cattle under one year

In any host population, individuals may be infected with multiple pathogens concurrently or in sequence. The direction and strength of pathogen-pathogen interactions are often unknown and dependent on the mechanism of interaction. This thesis is concerned with the epidemiology of infections and coinfections in zebu cattle during their first year of life, and the consequences they have for hosts’ survival probabilities and growth rates. Specifically, the study aims to: a) identify the many different pathogen infections occurring in zebu cattle under one year old, b) identify the main causes of mortality and reduced growth rates, c) test for evidence of effects of pathogen-pathogen interactions on mortality and growth, and d) determine the risk factors for infections with pathogens associated with increased mortality and reduced growth rates in zebu calves. To achieve these aims data collected from an epidemiological follow-up study of a cohort of 548 indigenous zebu cattle, recruited at birth and followed for the entire first year of life was used. Growth rates were enormously variable (52 to 704% of birth-weight) and 88 (16%) of the calves died during the first year, most from infectious disease. In total, 25,104 calf weeks of observation and data from 5,337 individual calf visits were analysed. Over 50 different pathogens were identified in the cohort. The thesis begins by providing an overview of zebu cattle and the importance of cattle diseases relevant to Sub-Saharan Africa, emphasising the importance of epidemiological studies taking into account co-infections, which are common in the natural populations, as opposed to a single-pathogen focus. A detailed description of the study design, data collection and descriptive analysis of non-infectious factors, including management and environmental factors, and a descriptive analysis of all pathogens screened for in the study are provided. Using Cox proportional models with frailty terms, the study then identifies infectious and non-infectious risk factors associated with mortality. Further, the role co-infections play in decreasing survival probabilities are investigated, revealing that the hazard for death from East Coast Fever (ECF) - the single most important disease associated with 40% of all deaths - increases 10 times in animals co-infected with Trypanosoma species, and 1.3 times for every 1000 eggs per gram faeces increase in strongyle egg count. Mixed-effect models are used to study growth rates and the impact of coinfections, revealing both synergistic interactions (lower host growth rates) of T. parva and A. marginale co-infections, and antagonistic interactions (relatively higher host growth rates) of T. parva and T. mutans co-infections compared to single infections with T. parva. Further, this work shows that helminth infections can have a strong negative effect on the growth rates but this is burden-dependent. These findings provide baseline epidemiological data on the diseases with greatest impact on health and performance of young zebu cattle, information that is valuable in the prioritisation and control of diseases. Additionally, they provide evidence of co-infections affecting host growth and survival, and have important implications on disease control strategies, suggesting benefits of aan integrated approach to control of worm, tick and tsetse-borne diseases

Epidemiology and clinical outcomes associated with Theileria parva in a cohort of East African short horn zebu calves.

This thesis takes data from the Infectious Diseases of East African Livestock (IDEAL) project. The project was a longitudinal calf cohort study based in Western Kenya. Indigenous short horn zebu calves were recruited at birth and then visited every 5 weeks through their first year of life. The aim of this thesis was to improve understanding of the epidemiology of Theileria parva, with a particular focus on variation in host response. 362 of the 548 calves in the study cohort were classified as having seroconverted to T. parva, and 381 to T. mutans before 1 year old. The diagnostic tools used to identify exposure in the calf were compared, and environmental and calf level risk factors associated with the age at seroconversion were sought. Decreased elevation of the homestead and increased size of the herd were found to be significantly associated with an increased hazard of seroconversion to T. parva. There was little variation in hazard of T. mutans captured across the study site. The outcome ‘clinical episode’ was used to classify whether the calf was ill at each routine visit. A large number of calves passed through their first year of life without clinical disease being observed, and a minority of calves experienced the majority of clinical episodes. Multiple clinical episodes were apparently related in time, suggesting that they were due either to the same or connected pathogenic processes. A low birth weight, larger herds, and older farmers were all risk factors for being a sick calf. Both high helminth burden and T. parva were found to be significantly associated with clinical disease at a population level. A lot of variation was seen in the clinical presentation of disease. The clinical signs associated with fatal East Coast Fever (ECF), the clinical disease associated with T. parva infection, were found to be very variable. Although this may have been partly due to the varying times in the disease process that calves were observed prior to death, the complication of the clinical picture was also suggested to be due to co-infections. 71% of the cohort was infected with T. parva in their first year of life, but only a fraction (8.7%) went on to die from that infection. Unmatched and matched nested case control study formats were used to investigate the risk factors associated with death following T. parva infection (ECF death) in these calves. It was found that being infected young was a risk factor for death. Calves owned by older farmers were also at higher risk of death following infection. Going out grazing was found to be protective, and equivocal evidence was found for an association between prior T. mutans exposure and reduced odds of ECF death. If these initial findings from this work are correct, it is likely that T. mutans is influencing the clinical presentation of T. parva in endemic regions

Brucellosis in man and animals

Revised EditionContents : Chapter 1 : The genus Brucella - Chapter 2 : Methods of isolating Brucella - Chapter 3 : Differentiation of the species of the genus Brucella - Chapter 4 : Brucellosis in human beings : Part one : Historical Survey - Chapter 4 : Brucellosis in human beings : Part two : Brucellosis in the United States / A.V. Hardy - Chapter 4 : Brucellosis in human beings : Part 3 : Brucellosis in Malta / J.E. Debono - Chapter 4 : Brucellosis in human beings : Part 4 : Treatment - Chapter 5 : Brucellosis in animals - Chapter 6 : Laboratory diagnosis of Brucellosis - Chapter 7 : Eradication or control of sources of Brucellosis infection / Ward Giltner - Appendix, Case Reports - Bibliography - IndexN/

Epidemiology and pathogenesis of fasciolosis in eastern Nepal

Following a general introduction, the thesis is divided into three parts, covering epidemiology, pathogenesis and molecular biology. Each part contains relevant literature review, materials and methods, results and a discussion for that particular part. The thesis ends with a general discussion which, includes an estimate of the financial loss resulting from fasciolosis in Nepal but concentrates on the major conclusions reached from this study and the major recommendations.In part one, following a review of literature on the factors affecting epidemiology of fasciolosis, a 19 months field survey on the epidemiology of fasciolosis in eastern Nepal is described. Four Lymnaea spp., namely L. auricularia race rufescens, L. auricularia sensu stricto, L. viridis and L. luteola were identified. L. auricularia race rufescens was the predominant species. The main snail habitats consisted of springs or stream fed rice-fields, irrigation channels, ponds and road-side pools. The monsoon rains and rice cultivation practices contributed to the creation and expansion of the snail habitats. The snail population density was high during the dry period and declined with the onset of the monsoon. Snail egg masses and young snails were observed throughout the year. In the hills, mature Fasciola spp. infections were found in snails from May to February, while in the Terai, infected snails were found throughout the year.In the hills, the highest prevalence of fasciolosis was recorded in buffaloes (57.9%) followed by cattle (44.8%), goats (22.4%) and sheep (18.2%). The relatively high prevalence of fasciolosis observed in stall-fed buffaloes was due to feeding metacercariae contaminated, rice-straw and grass, cut and carried from rice-fields. In the Terai, the highest prevalence was found in cattle (51.4%) followed by buffaloes (41.3%) and goats (13.3%). Slaughter place surveys revealed that F. gigantica is the predominant species, although infection with F. hepatica and an intermediate form were also found. The mean fluke burden in infected buffaloes was 203.2 ± 17.9, in infected goats this was 23.7 ± 3.3. Fluke burdens increases with the age of the animals. The seasonal pattern of the infections in the intermediate and definitive hosts indicated that the bulk of the infection was derived from fluke eggs deposited on the pasture during March-May and again in October and November.A control programme for fasciolosis based on these findings requires that all animals, including goats and sheep, be treated with appropriate anthelmintics, such as oxyclosanide or triclabendazole, in February and again in late August.In part two, the literature on the pathogenesis of fasciolosis with special reference to its effects on productivity of ruminants is reviewed. Descriptions of the 5 experimental studies on the pathogenesis of fasciolosis carried out in Edinburgh and in Nepal follow. A pilot comparative study in sheep, conducted in Edinburgh indicated that F. gigantica was more pathogenic than F. hepatica. A second pilot experiment was conducted in Nepal using 11 to 14 months old 9 Baruwal sheep. With a mean burden of only 5 F. gigantica, the mean weekly liveweight gain of the infected sheep over 35 weeks was 22.0% less than that of the uninfected controls. The pathogenesis in goats was investigated using 15 to 18 months old 18 Nepalese hill goats. Burdens of more than 1.3 flukes/kg of initial liveweight produced clinical chronic fasciolosis. A burden of 3.6 flukes/kg caused death of a goat at about 33 weeks after infection. There was a significant reduction in weight gain in the infected goats.Two experiments were carried out to study the pathogenesis of fasciolosis in 12 to 18 months old 32 Nepalese hill buffaloes. During the 35 weeks of post infection monitoring, no clinical signs were observed in the buffalo calves which harboured 1.3 flukes/kg resulted in clinical fasciolosis. A chronic disease occurred in those 6 buffalo calves which had burdens between 1.3 and 4.9 flukes/kg. Two of these became moribund around 26 weeks after infection while the remaining 4 survived until the end of the experiment. The presence of 7.4 to 9.1 flukes/kg caused subacute fasciolosis resulting in the death of buffalo calves between 14 and 18 weeks after infection. In both experiments, the liveweight gain of the infected buffaloes was affected; a longer infection period with smaller fluke burden has a proportionally greater effect on the depression of liveweight gain than a shorter infection period with larger fluke burden. The mean dressing percentage was reduced by about 12.4% in the infected buffaloes.Although, eosinophils and the increased serum GLDH and GGT levels appeared to be the sensitive indicators of Fasciola spp. infections, these were not related to the intensity of infections. Infiltration of eosinophils in periportal areas and bile ducts lamina propria was markedly evident in sheep and goats, but not in buffaloes. The inferior eosinophils together with the absence of liver tissue infiltration by eosinophils in infected buffaloes may well be related to the fact that buffaloes have poorer ability to develop resistance to infection of F. gigantica even than sheep and goats. A prominent feature in subacute infections in sheep and buffaloes was aberrant flukes in various organs and accompanying haemorrhagic areas.In part three, the available literature on the advantages and disadvantages of the various methods available for speciation and differentiation of Fasciola spp. is reviewed. This is followed by a description of the molecular biology work which was undertaken and which resulted in the development of species-specific (MHFh and MHFg) and cross-reactive (MHFxl and MHFx2) DNA piobes for the identification of Fasciola spp. None of the probes reacted with any of the control or host DNA's tested. If used in conjunction these DNA probes can clearly differentiate between F. hepatica and F. gigantica. As such they present useful tools for species identification

Part 13, Authors: R To Rzoska

United States Department of Agriculture, Bureau of Animal Industr

Vaccines for Neglected Pathogens: Strategies, Achievements and Challenges

This book reviews successes and (remaining) challenges in vaccine development for the selected Neglected Tropical Diseases (NTD) of Leprosy, Leishmaniasis, Meliodoisis and Tuberculosis, which are a continuous burden for millions of people in affected areas worldwide. Written by frontline researchers, the volume deep-dives into different vaccine strategies, provides biotechnological background information and also tackles animal models in NTD therapeutics research. By bringing together state-of-the-art expert knowledge, the book contributes to the aim of ultimately ending the epidemics of neglected tropical diseases, complying with UN Sustainable Development Goal 3, Health and Well-Being. The volume highlights the activities of the research network VALIDATE (VAccine deveLopment for complex Intracellular neglecteD pAThogEns), funded by the Medical Research Council in the UK. The four NTDs discussed in the book were selected as these are in the focus of VALIDATE’s research. The book targets scientists and clinicians working on NTDs, as well as all readers with a background in biomedicine and interest in vaccine development. This is an open access book

Celebrating 120 Years of Butantan Institute Contributions for Toxinology

This is collection of original and review articles selected in recognition of the contribution of Instituto Butantan to the field of toxinology and its continued and relevant role in this field in the 120 years since its foundation. Congratulations to the Butantan Institute, its house scientists, and collaborators on its 120th anniversary