Pharma to Farmer: Field Challenges of Optimizing Trypanocide use in African Animal Trypanosomiasis

Trypanocides are a key control component of African animal trypanosomiasis (AAT) in tsetse-infested areas of sub-Saharan Africa. While farmers are dependent upon trypanocides, recent research highlights their inappropriate and ineffective use, problems with drug quality, and treatment failure. There are currently gaps in knowledge and investment in inexpensive AAT diagnostics, understanding of drug resistance, and the effective use of trypanocides in the field. Without this important knowledge it is difficult to develop best practice and policy for existing drugs or to inform development and use of new drugs. There needs to be better understanding of the drivers and behavioural practices around trypanocide use so that they can be incorporated into sustainable solutions needed for the development of effective control of AAT

Aedes albopictus invasion across Africa: the time is now for cross-country collaboration and control

The distribution of Aedes albopictus across west Africa is well documented. However, little has been done to synthesise data and establish the current distribution of this invasive vector in central and east Africa. In this Viewpoint, we show that A albopictus is establishing across Africa, how this is potentially related to urbanisation, and how establishment poses risks of near-term increases in arbovirus transmission. We then use existing species distribution maps for A albopictus and Aedes aegypti to produce consensus estimates of suitability and make these estimates accessible. Although urban development and increased trade have economic and other societal gains, the resulting potential changes in Aedes-borne virus epidemiology require a discussion of how cross-country collaboration and mitigation could be facilitated. Failure to respond to species invasion could result in increased transmission of Aedes-associated pathogens, including dengue, chikungunya, and Rift Valley fever viruses

Antigenic diversity in Theileria parva populations from sympatric cattle and African buffalo analysed using long read sequencing

East Coast fever (ECF) in cattle is caused by the Apicomplexan protozoan parasite , transmitted by the three-host tick . The African buffalo () is the natural host for but does not suffer disease, whereas ECF is often fatal in cattle. The genetic relationship between populations circulating in cattle and buffalo is poorly understood, and has not been studied in sympatric buffalo and cattle. This study aimed to determine the genetic diversity of populations in cattle and buffalo, in an area where livestock co-exist with buffalo adjacent to the Serengeti National Park, Tanzania. Three antigens (Tp1, Tp4, and Tp16), known to be recognized by CD8 and CD4 T cells in immunized cattle, were used to characterize genetic diversity of in cattle ( = 126) and buffalo samples ( = 22). Long read (PacBio) sequencing was used to generate full or near-full length allelic sequences. Patterns of diversity were similar across all three antigens, with allelic diversity being significantly greater in buffalo-derived parasites compared to cattle-derived (e.g., for Tp1 median cattle allele count was 9, and 81.5 for buffalo), with very few alleles shared between species (8 of 651 alleles were shared for Tp1). Most alleles were unique to buffalo with a smaller proportion unique to cattle (412 buffalo unique vs. 231 cattle-unique for Tp1). There were indications of population substructuring, with one allelic cluster of Tp1 representing alleles found in both cattle and buffalo (including the TpM reference genome allele), and another containing predominantly only alleles deriving from buffalo. These data illustrate the complex interplay between populations in buffalo and cattle, revealing the significant genetic diversity in the buffalo population, the limited sharing of parasite genotypes between the host species, and highlight that a subpopulation of is maintained by transmission within cattle. The data indicate that fuller understanding of buffalo population dynamics is needed, as only a comprehensive appreciation of the population genetics of populations will enable assessment of buffalo-derived infection risk in cattle, and how this may impact upon control measures such as vaccination

A cross-sectional survey to establish Theileria parva prevalence and vector control at the wildlife-livestock interface, Northern Tanzania

East Coast fever (ECF) in cattle is caused by the protozoan parasite Theileria parva, transmitted by Rhipicephalus appendiculatus ticks. In cattle ECF is often fatal, causing annual losses >$500 million across its range. The African buffalo (Syncerus caffer) is the natural host for T. parva but the transmission dynamics between wild hosts and livestock are poorly understood. This study aimed to determine the prevalence of T. parva in cattle, in a 30 km zone adjacent to the Serengeti National Park, Tanzania where livestock and buffalo co-exist, and to ascertain how livestock keepers controlled ECF and other vector-borne diseases of cattle. A randomised cross-sectional cattle survey and questionnaire of vector control practices were conducted. Blood samples were collected from 770 cattle from 48 herds and analysed by PCR to establish T. parva prevalence. Half body tick counts were recorded on every animal. Farmers were interviewed (n = 120; including the blood sampled herds) using a standardised questionnaire to obtain data on vector control practices. Local workshops were held to discuss findings and validate results. Overall prevalence of T. parva in cattle was 5.07% (CI: 3.70−7.00%), with significantly higher prevalence in older animals. Although all farmers reported seeing ticks on their cattle, tick counts were very low with 78% cattle having none. Questionnaire analysis indicated significant acaricide use with 79% and 41% of farmers reporting spraying or dipping with cypermethrin-based insecticides, respectively. Some farmers reported very frequent spraying, as often as every four days. However, doses per animal were often insufficient. These data indicate high levels of acaricide use, which may be responsible for the low observed tick burdens and low ECF prevalence. This vector control is farmer-led and aimed at both tick- and tsetse-borne diseases of livestock. The levels of acaricide use raise concerns regarding sustainability; resistance development is a risk, particularly in ticks. Integrating vaccination as part of this community-based disease control may alleviate acaricide dependence, but increased understanding of the Theileria strains circulating in wildlife-livestock interface areas is required to establish the potential benefits of vaccination

Ecological and epidemiological findings associated with zoonotic rabies outbreaks and control in Moshi, Tanzania, 2017–2018

Approximately 1500 people die annually due to rabies in the United Republic of Tanzania. Moshi, in the Kilimanjaro Region, reported sporadic cases of human rabies between 2017 and 2018. In response and following a One Health approach, we implemented surveillance, monitoring, as well as a mass vaccinations of domestic pets concurrently in >150 villages, achieving a 74.5% vaccination coverage (n = 29, 885 dogs and cats) by September 2018. As of April 2019, no single human or animal case has been recorded. We have observed a disparity between awareness and knowledge levels of community members on rabies epidemiology. Self-adherence to protective rabies vaccination in animals was poor due to the challenges of costs and distances to vaccination centers, among others. Incidence of dog bites was high and only a fraction (65%) of dog bite victims (humans) received post-exposure prophylaxis. A high proportion of unvaccinated dogs and cats and the relative intense interactions with wild dog species at interfaces were the risk factors for seropositivity to rabies virus infection in dogs. A percentage of the previously vaccinated dogs remained unimmunized and some unvaccinated dogs were seropositive. Evidence of community engagement and multi-coordinated implementation of One Health in Moshi serves as an example of best practice in tackling zoonotic diseases using multi-level government e orts. The district-level establishment of the One Health rapid response team (OHRRT), implementation of a carefully structured routine vaccination campaign, improved health education, and the implementation of barriers between domestic animals and wildlife at the interfaces are necessary to reduce the burden of rabies in Moshi and communities with similar profiles.The USAID funded project—OSRO/GLO/507/USA on Global Health Security Agenda for the control of zoonosis in Africa.http://www.mdpi.com/journal/ijerpham2020Veterinary Tropical Disease

Continent-wide genomic analysis of the African buffalo (<i>Syncerus caffer</i>)

AbstractThe African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest qualityde novogenome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided surprisingly little support for the currently described four subspecies, but indicated three main lineages, in Western/Central, Eastern and Southern Africa, respectively. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management

Assessing the effect of insecticide-treated cattle on tsetse abundance and trypanosome transmission at the wildlife-livestock interface in Serengeti, Tanzania

In the absence of national control programmes against Rhodesian human African trypanosomiasis, farmer-led treatment of cattle with pyrethroid-based insecticides may be an effective strategy for foci at the edges of wildlife areas, but there is limited evidence to support this. We combined data on insecticide use by farmers, tsetse abundance and trypanosome prevalence, with mathematical models, to quantify the likely impact of insecticide-treated cattle. Sixteen percent of farmers reported treating cattle with a pyrethroid, and chemical analysis indicated 18% of individual cattle had been treated, in the previous week. Treatment of cattle was estimated to increase daily mortality of tsetse by 5–14%. Trypanosome prevalence in tsetse, predominantly from wildlife areas, was 1.25% for T. brucei s.l. and 0.03% for T. b. rhodesiense. For 750 cattle sampled from 48 herds, 2.3% were PCR positive for T. brucei s.l. and none for T. b. rhodesiense. Using mathematical models, we estimated there was 8–29% increase in mortality of tsetse in farming areas and this increase can explain the relatively low prevalence of T. brucei s.l. in cattle. Farmer-led treatment of cattle with pyrethroids is likely, in part, to be limiting the spill-over of human-infective trypanosomes from wildlife areas

Genome sequence of the tsetse fly (Glossina morsitans):Vector of African trypanosomiasis

Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein-encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.IS

Ecological and public health aspects of stable flies (Diptera :muscidae): microbial interactions

Doctor of PhilosophyDepartment of EntomologyAlberto B. BroceLudek ZurekStable fly, Stomoxys calcitrans (L.), and house fly, Musca domestica L., are two major pests affecting both confined and pastured livestock in the United States. It costs livestock producers millions of dollars annually to reduce populations of these two pests. Control of stable flies and house flies based on chemical insecticides is only marginally effective and unsustainable in the long term due to the development of insecticide resistance. This has created a demand for alternative methods which are environmentally friendly and cost effective for the management of these pests. Information on stable fly and house fly oviposition behavior and the aggregation and segregation of their immatures may help in an integrated pest management control program for these pests. This research identified specific bacterial species from the surface of stable fly eggs which are suspected of releasing chemical cues used to induce gravid females to oviposit at sites where eggs have been deposited and inhibit additional deposition of eggs in the same habitat when it is already colonized. My research also showed that stable fly and house fly larvae tend to be aggregated in distribution, even in apparently homogenous habitats, and to be spatially segregated from each other. Finally, I evaluated the vector competence of stable flies for an emerging food-borne pathogen, Enterobacter sakazakii, showing that this fly species is potentially a good vector for this pathogen