The year 2020 marks a decade since the final visit was made in the 'Infectious Diseases of East African Livestock' (IDEAL) project. However, data generation from samples obtained during this ambitious longitudinal study still continues. As the project launches its extensive open-access database and biobank to the scientific community, we reflect on the challenges overcome, the knowledge gained, and the advantages of such a project. We discuss the legacy of the IDEAL project and how it continues to generate evidence since being adopted by the Centre for Tropical Livestock Genetics and Health (CTLGH). We also examine the impact of the IDEAL project, from the authors perspective, for each of the stakeholders (the animal, the farmer, the consumer, the policy maker, the funding body, and the researcher and their institution) involved in the project and provide recommendations for future researchers who are interested in running longitudinal field studies.

Most studies of infectious diseases in East African cattle have concentrated on gastro-intestinal parasites and vector-borne diseases. As a result, relatively little is known about viral diseases, except for those that are clinically symptomatic or which affect international trade such as foot and mouth disease, bluetongue and epizootic haemorrhagic disease. Here, we investigate the seroprevalence, distribution and relationship between the viruses involved in respiratory disease, infectious bovine rhinotracheitis virus (IBR), bovine parainfluenza virus Type 3 (PIV3) and bovine viral diarrhoea virus (BVDV) in East African Shorthorn Zebu calves. These viruses contribute to the bovine respiratory disease complex (BRD) which is responsible for major economic losses in cattle from intensive farming systems as a result of pneumonia. We found that calves experience similar risks of infection for IBR, PIV3, and BVDV with a seroprevalence of 20.9%, 20.1% and 19.8% respectively. We confirm that positive associations exist between IBR, PIV3 and BVDV; being seropositive for any one of these three viruses means that an individual is more likely to be seropositive for the other two viruses than expected by chance.

In early 2014, abortions and death of ruminants were reported on farms in Maputo and Gaza Provinces, Mozambique. Serologic analysis and quantitative and conventional reverse transcription PCR confirmed the presence of Rift Valley fever virus. The viruses belonged to lineage C, which is prevalent among Rift Valley fever viruses in southern Africa.

SUMMARY Parasite burden varies widely between individuals within a population, and can covary with multiple aspects of individual phenotype. Here we investigate the sources of variation in faecal strongyle eggs counts, and its association with body weight and a suite of haematological measures, in a cohort of indigenous zebu calves in Western Kenya, using relatedness matrices reconstructed from single nucleotide polymorphism (SNP) genotypes. Strongyle egg count was heritable (h 2 = 23·9%, s.e. = 11·8%) and we also found heritability of white blood cell counts (WBC) (h 2 = 27·6%, s.e. = 10·6%). All the traits investigated showed negative phenotypic covariances with strongyle egg count throughout the first year: high worm counts were associated with low values of WBC, red blood cell count, total serum protein and absolute eosinophil count. Furthermore, calf body weight at 1 week old was a significant predictor of strongyle EPG at 16–51 weeks, with smaller calves having a higher strongyle egg count later in life. Our results indicate a genetic basis to strongyle EPG in this population, and also reveal consistently strong negative associations between strongyle infection and other important aspects of the multivariate phenotype.

Lumpy skin disease (LSD) is an economically important disease caused by LSD virus (LSDV), a Capripoxvirus, characterized by fever and circumscribed skin lesions. It is suspected to be transmitted mechanically by biting flies. To assess the vector potential of Amblyomma hebraeum in transmission of LSDV, mechanical/intrastadial and transstadial modes of transmission of the virus by this tick species were investigated. Two cattle were artificially infected as sources (donors) of infection to ticks. Ticks were infected as either nymphs or adults. Male A. hebraeum ticks were partially fed on donor animals and transferred to recipient animals to test for mechanical/intrastadial transmission. Nymphal A. hebraeum were fed to repletion on donor animals. The emergent adult ticks were placed on recipient animals to test for transstadial transmission of the virus. Successful transmission of LSDV infection was determined in recipient animals by monitoring development of clinical signs, testing of blood for the presence of LSDV by real-time PCR, virus isolation and the serum neutralization test. This report provides further evidence of mechanical/intrastadial and, for the first time, transstadial transmission of LSDV by A. hebraeum. These findings implicate A. hebraeum as a possible maintenance host in the epidemiology of the disease.

SUMMARY Tick-borne diseases are a major impediment to improved productivity of livestock in sub-Saharan Africa. Improved control of these diseases would be assisted by detailed epidemiological data. Here we used longitudinal, serological data to determine the patterns of exposure to Theileria parva, Theileria mutans, Babesia bigemina and Anaplasma marginale from 548 indigenous calves in western Kenya. The percentage of calves seropositive for the first three parasites declined from initial high levels due to maternal antibody until week 16, after which the percentage increased until the end of the study. In contrast, the percentage of calves seropositive for T. mutans increased from week 6 and reached a maximal level at week 16. Overall 423 (77%) calves seroconverted to T. parva , 451 (82%) to T. mutans , 195 (36%) to B. bigemina and 275 (50%) to A. marginale. Theileria parva antibody levels were sustained following infection, in contrast to those of the other three haemoparasites. Three times as many calves seroconverted to T. mutans before seroconverting to T. parva . No T. parva antibody response was detected in 25 calves that died of T. parva infection, suggesting that most deaths due to T. parva are the result of acute disease from primary exposure.

Lumpy skin disease (LSD) is of substantial economic importance for the cattle industry in Africa and the Near and Middle East. Several insect species are thought to transmit the disease mechanically. Recent transmission studies have demonstrated the first evidence for a role of hard (ixodid) ticks as vectors of lumpy skin disease virus (LSDV). The aim of this study was to attempt in vitro growth of the virus in Rhipicephalus spp. tick cell lines and investigate in vivo the presence of the virus in ticks collected from cattle during LSD outbreaks in Egypt and South Africa. No evidence was obtained for replication of LSDV in tick cell lines although the virus was remarkably stable, remaining viable for 35 days at 28 °C in tick cell cultures, in growth medium used for tick cells and in phosphate buffered saline. Viral DNA was detected in two-thirds of the 56 field ticks, making this the first report of the presence of potentially virulent LSDV in ticks collected from naturally infected animals.

Due to the unpredictable and explosive nature of Rift Valley fever (RVF) outbreaks, rapid and accurate diagnostic assays for low-resource settings are urgently needed. To improve existing diagnostic assays, monoclonal antibodies (MAbs) specific for the nucleocapsid protein of RVF virus (RVFV) were produced and characterized. Four IgG2a MAbs showed specific binding to denatured nucleocapsid protein, both from a recombinant source and from inactivated RVFV, in Western blot analysis and in an enzyme-linked immunosorbent assay (ELISA). Cross-reactivity with genetically related and non-related arboviruses including Bunyamwera and Calovo viruses (Bunyaviridae family), West Nile and Dengue-2 viruses (Flaviviridae family), and Sindbis and Chikungunya viruses (Togaviridae family) was not detected. These MAbs represent a useful tool for the development of rapid diagnostic assays for early recognition of RVF.

Lumpy skin disease is a debilitating cattle disease caused by the lumpy skin disease virus (LSDV), belonging to the genus Capripoxvirus. Epidemics of the disease usually occur in summer, when insect activity is high. Limited information is available on how LSDV persists during inter-epidemic periods. Transmission of LSDV by mosquitoes such as Aedes aegypti has been shown to be mechanical, there is no carrier state in cattle and the role of wildlife in the epidemiology of the disease seems to be of minor importance. Recent studies in ticks have shown transstadial persistence of LSDV in Rhipicephalus appendiculatus and Amblyomma hebraeum as well as transovarial persistence of the virus in Rhipicephalus decoloratus, R. appendiculatus and A. hebraeum. The over-wintering of ticks off the host as part of their life cycles is well known: A. hebraeum and R. appendiculatus over-winter, for example, on the ground as engorged nymphs/unfed (emergent) adults while R. decoloratus over-winters on the ground as engorged females. In this study, transstadial and transovarial persistence of LSDV from experimentally infected A. hebraeum nymphs and R. decoloratus females after exposure to cold temperatures of 5 °C at night and 20 °C during the day for 2 months was reported. This observation suggests possible over-wintering of the virus in these tick species.

Lumpy skin disease (LSD) is an economically important disease caused by LSD virus (LSDV), a Capripoxvirus, characterized by fever and circumscribed skin lesions. It is suspected to be transmitted mechanically by biting flies. To assess the vector potential of Amblyomma hebraeum in transmission of LSDV, mechanical/intrastadial and transstadial modes of transmission of the virus by this tick species were investigated. Two cattle were artificially infected as sources (donors) of infection to ticks. Ticks were infected as either nymphs or adults. Male A. hebraeum ticks were partially fed on donor animals and transferred to recipient animals to test for mechanical/intrastadial transmission. Nymphal A. hebraeum were fed to repletion on donor animals. The emergent adult ticks were placed on recipient animals to test for transstadial transmission of the virus. Successful transmission of LSDV infection was determined in recipient animals by monitoring development of clinical signs, testing of blood for the presence of LSDV by real-time PCR, virus isolation and the serum neutralization test. This report provides further evidence of mechanical/intrastadial and, for the first time, transstadial transmission of LSDV by A. hebraeum. These findings implicate A. hebraeum as a possible maintenance host in the epidemiology of the disease.

Lumpy skin disease is an economically important disease of cattle that is caused by the lumpy skin disease virus (LSDV), which belongs to the genus Capripoxvirus. It is endemic in Africa and outbreaks have also been reported in the Middle-East. Transmission has mostly been associated with blood-feeding insects but recently, the authors have demonstrated mechanical transmission by Rhipicephalus appendiculatus as well as mechanical/intrastadial and transstadial transmission by Amblyomma hebraeum. Saliva is the medium of transmission of pathogens transmitted by biting arthropods and, simultaneously, it potentiates infection in the vertebrate host. This study aimed to detect LSDV in saliva of A. hebraeum and R. appendiculatus adult ticks fed, as nymphs or as adults, on LSDV-infected animals, thereby also demonstrating transstadial or mechanical/intrastadial passage of the virus in these ticks. Saliva samples were tested for LSDV by real-time PCR and virus isolation. Supernatants obtained from virus isolation were further tested by real-time PCR to confirm that the cytopathic effects observed were due to LSDV. Lumpy skin disease virus was detected, for the first time, in saliva samples of both A. hebraeum and R. appendiculatus ticks. At the same time, mechanical/intrastadial and transstadial passage of the virus was demonstrated and confirmed in R. appendiculatus and A. hebraeum.

Lumpy skin disease (LSD) is an economically important, acute or sub-acute, viral disease of cattle that occurs across Africa and in the Middle East. The aim of this study was to investigate if lumpy skin disease virus (LSDV) can be transmitted mechanically by African brown ear ticks (Rhipicephalus appendiculatus Neum.). Laboratory-bred R. appendiculatus males were fed on experimentally infected viraemic 'donor' cattle. Partially fed male ticks were then transferred to feed on an uninfected 'recipient' cow. The recipient animal became viraemic, showed mild clinical signs of LSD and seroconverted. Additionally, R. appendiculatus males were found to transmit LSDV through feeding on skin lacking visible lesions, demonstrating that viraemic animals without lesions at the feeding site of ticks may be a source of infection. This is the first time that transmission of poxviruses by a tick species has been demonstrated and the importance of this mode of transmission in the spread of LSDV in endemic settings is discussed.

Rift Valley fever (RVF) is endemic in most parts of Africa and has also been reported to occur in the Arabian Peninsula. It is responsible for significant morbidity and mortality, particularly in livestock, but also in humans. During the last two decades several outbreaks of RVF have been reported in countries in Southern Africa. In contrast to other countries, no clinical disease has been reported in Mozambique during this period. In a serological study conducted in 2007 in five districts of Zambézia Province, Mozambique, of a total of 654 small ruminants sampled (277 sheep and 377 goats), 35.8% of sheep sera and 21.2% of goat sera were positive for RVF virus (RVFV) antibodies in a virus neutralization test (VN) and in an IgG enzyme-linked immunosorbent assay (ELISA). In 2010, a cross-sectional survey was conducted in 313 sheep and 449 goats in two districts of the same province. This study revealed an overall seropositivity rate of 9.2% in sheep and 11.6% in goat and an increased likelihood of being seropositive in older animals (OR = 7.3; p<0.001) using an IgG ELISA. 29 out of 240 animals assessed for RVF specific IgM by ELISA were positive, suggesting recent exposure to RVFV. However, a longitudinal study carried out between September 2010 and April 2011 in a cohort of 125 of these animals (74 sheep and 51 goats) failed to demonstrate seroconversion. The results of the study indicate that RVFV circulates sub-clinically in domestic small ruminants in Zambézia Province.

SUMMARY The co-occurrence of different pathogen species and their simultaneous infection of hosts are common, and may affect host health outcomes. Co-infecting pathogens may interact synergistically (harming the host more) or antagonistically (harming the host less) compared with single infections. Here we have tested associations of infections and their co-infections with variation in growth rate using a subset of 455 animals of the Infectious Diseases of East Africa Livestock (IDEAL) cohort study surviving to one year. Data on live body weight, infections with helminth parasites and haemoparasites were collected every 5 weeks during the first year of life. Growth of zebu cattle during the first year of life was best described by a linear growth function. A large variation in daily weight gain with a range of 0·03–0·34 kg, and a mean of 0·135 kg (0·124, 0·146; 95% CI) was observed. After controlling for other significant covariates in mixed effects statistical models, the results revealed synergistic interactions (lower growth rates) with Theileria parva and Anaplasma marginale co-infections, and antagonistic interactions (relatively higher growth rates) with T. parva and Theileria mutans co-infections, compared with infections with T. parva only. Additionally, helminth infections can have a strong negative effect on the growth rates but this is burden-dependent, accounting for up to 30% decrease in growth rate in heavily infected animals. These findings present evidence of pathogen–pathogen interactions affecting host growth, and we discuss possible mechanisms that may explain observed directions of interactions as well as possible modifications to disease control strategies when co-infections are present.

This paper is the first attempt to accurately describe the hematological parameters for any African breed of cattle, by capturing the changes in these parameters over the first 12 months of an animal’s life using a population-based sample of calves reared under field conditions and natural disease challenge. Using a longitudinal study design, a stratified clustered random sample of newborn calves was recruited into the IDEAL study and monitored at 5-weekly intervals until 51 weeks of age. The blood cell analysis performed at each visit included: packed cell volume; red cell count; red cell distribution width; mean corpuscular volume; mean corpuscular hemoglobin concentration; hemoglobin concentration; white cell count; absolute lymphocyte, eosinophil, monocyte, and neutrophil counts; platelet count; mean platelet volume; and total serum protein. The most significant age-related change in the red cell parameters was a rise in red cell count and hemoglobin concentration during the neonatal period. This is in contrast to what is reported for other ruminants, including European cattle breeds where the neonatal period is marked by a fall in the red cell parameters. There is a need to establish breed-specific reference ranges for blood parameters for indigenous cattle breeds. The possible role of the postnatal rise in the red cell parameters in the adaptability to environmental constraints and innate disease resistance warrants further research into the dynamics of blood cell parameters of these breeds.

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 ii 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 an integrated approach to control of worm, tick and tsetse-borne diseases.

The presence of bluetongue virus (BTV) and Epizootic Haemorrhagic Disease virus (EHDV) in indigenous calves in western Kenya was investigated. Serum was analysed for BTV and EHDV antibodies. The population seroprevalences for BTV and EHDV for calves at 51 weeks of age were estimated to be 0.942 (95% CI 0.902-0.970) and 0.637 (95% CI 0.562-0.710), respectively, indicating high levels of circulating BTV and EHDV. The odds ratio of being positive for BTV if EHDV positive was estimated to be 2.57 (95% CI 1.37-4.76). When 99 calves were tested for BTV and EHDV RNA by real-time RT-PCR, 88.9% and 63.6% were positive, respectively. Comparison of the serology and real-time RT-PCR results revealed an unexpectedly large number of calves that were negative by serology but positive by real-time RT-PCR for EHDV. Eight samples positive for BTV RNA were serotyped using 24 serotype-specific real-time RT-PCR assays. Nine BTV serotypes were detected, indicating that the cattle were infected with a heterogeneous population of BTVs. The results show that BTV and EHDV are highly prevalent, with cattle being infected from an early age.

Lumpy skin disease (LSD) is an economically important cattle disease. The disease is endemic in many African countries, but outbreaks have also been reported in Madagascar and the Middle East. The aim of this study was to investigate the potential role of ixodid (hard) ticks in the transmission of the disease. Cattle were infected with a virulent, South African field isolate of lumpy skin disease virus (LSDV). Three common African tick species (genera Rhipicephalus, Amblyomma and Rhipicephalus (Boophilus)) in different life cycle stages were fed on the infected animals during the viraemic stage and on skin lesions. Post-feeding, the partially fed male ticks were transferred to the skin of non-infected 'recipient' animals, while females were allowed to lay eggs that were then tested using the polymerase chain reaction (PCR) method and virus isolation. Nymphs were allowed to develop for 2-3 weeks after which time they were tested. The non-infected 'recipient' cattle were closely monitored, both skin and blood samples were tested using PCR and virus isolation, and serum samples were tested by the serum neutralization test. This is the first report showing molecular evidence of potential transmission of LSDV by ixodid ticks. The study showed evidence of transstadial and transovarial transmission of LSDV by R. (B.) decoloratus ticks and mechanical or intrastadial transmission by R. appendiculatus and A. hebraeum ticks.

The globalisation of trade and food, the increased volume and speed of international travel, climate change, and the related escalation of emerging and re-emerging infectious diseases mean that countries are now more interconnected and interdependent than ever before. Africa is beleaguered by a range of endemic infectious and parasitic tropical diseases which, due to its diverse wildlife populations and indigenous livestock, can serve as a reservoir of high-impact or transboundary diseases and play a role in the emergence of disease, particularly at the wildlife, domestic animal and human interfaces. It is therefore essential to integrate animal and public health issues into the veterinary curriculum.Veterinary training in most parts of sub-Saharan Africa has focused on producing veterinarians to serve the livestock sector although socio-economic changes and privatisation of Veterinary Services have caused curriculum adjustments, as have globalisation and the increased risk of the spread of transboundary diseases. In South Africa, undergraduate veterinary training is more clinically oriented than in other regions. Animal and public health issues are covered in the curriculum, although their global relevance is not emphasised.The authors describe the undergraduate veterinary curriculum and summarise post-graduate programmes in South Africa. They also discuss a more comprehensive core-elective approach to the current curriculum and the need to adapt to new challenges facing the profession. Finally, they examine the potential use of innovative technology in undergraduate and post-graduate training and professional development, the importance of regional and international collaboration and the accreditation and recognition of veterinary training.