ENABLES: Enabling Livestock-keepers to Eliminate Sleeping Sickness

Lead Research Organisation: Liverpool School of Tropical Medicine
Department Name: Vector Biology

Abstract

Edges of wilderness areas, where pathogens occurring naturally in wild animals can spill over to infect people and livestock in surrounding areas, are a key risk for the emergence of new pathogens and spread of existing ones. In sub-Saharan Africa, this scenario often affects poor and marginalised human populations. The proximity of vulnerable populations to these areas provides a technical and ethical challenge: how can biodiversity and economically productive wilderness areas be preserved without threatening the health and livelihoods of vulnerable people?

ENABLES builds on our work at the edge of the Serengeti National Park in Tanzania where tsetse flies transmit trypanosomes. These single-celled parasites do not cause any overt disease in wild animals, but do cause a disease called Nagana in livestock. Humans bitten by tsetse infected with a particular species of trypanosome can develop sleeping sickness (Rhodesian human African trypanosomiasis, r-HAT), an acute and fatal disease for which there is no preventative vaccine or drug. About 12 million people in east and southern Africa are at risk of r-HAT and the preservation of wilderness areas presents a chronic and intractable source of infection. Only Botswana has been able to solve the problem of r-HAT permanently by eradicating tsetse from the Okavango wilderness area through large-scale (~15,000 km2) aerial spraying. This complex and expensive solution is not feasible for most poor communities living on the edge of wilderness areas.

Our work in Serengeti suggests that livestock-keepers are preventing the spread of r-HAT by simply applying pyrethroid insecticides to their cattle. They do this to control the ticks and tsetse that carry livestock diseases (East Coast Fever, Nagana) but this cheap (~$6/animal/year) and easy method also interrupts transmission of r-HAT. By treating livestock to prevent animal diseases, livestock-keepers are protecting local people from r-HAT. Other countries have tried but failed to encourage widespread use of pyrethroids by livestock-keepers as part of a One Health approach against r-HAT. Uptake in Tanzania appears to be stimulated, at least in part, by a government subsidy on the price of pyrethroids.

While our discoveries in Serengeti offer the exciting prospect of a One Health solution to r-HAT, we do not know (i) how widespread pyrethroid use is in different livestock systems, (ii) how generally applicable this approach is, and (iii) what conditions make farmer-led control likely and effective.

ENABLES will test the hypothesis that national policies to promote use of pyrethroids by livestock-keepers have led to large-scale control of human and animal trypanosomiasis. To achieve this, we will first use satellite data to predict where tsetse are abundant, and then test the predictions by comparing the observed and expected number of tsetse caught in traps placed at various sites. Using a validated model of tsetse abundance, we will identify 'hotspots' where transmission is predicted to be high.

In selected 'hotspots' from areas where different livestock systems (pastoralist, mixed crop-livestock, zero-grazing) predominate, we will test cattle for infection with trypanosomes and the presence of pyrethroids. We will conduct a questionnaire survey of herd owners about the decision-making underpinning methods used to control tsetse- and tick-borne diseases. We will also interview owners of veterinary outlets, national distributors of veterinary medicines and government officials to gain insights into the pyrethroid supply chain.

Finally, we will use models to integrate data on the density of tsetse, prevalence of trypanosomes and use of pyrethroids to quantify the epidemiological benefit of pyrethroid-treated cattle. Empirical findings and models will form the basis of a toolbox to assist Tanzania and other countries to formulate evidence-based policies and practices for the sustainable control of sleeping sickness.

Technical Summary

Rhodesian human African trypanosomiasis (r-HAT), caused by trypanosomes transmitted by tsetse flies, is associated with wilderness areas where tsetse and natural wild reservoir hosts are abundant. People and livestock living close to these areas are at risk of r-HAT. Studies conducted in the Serengeti District of Tanzania show that treatment of cattle with pyrethroids by livestock-keepers, to protect their cattle from animal African trypanosomiasis (AAT) and tick-borne diseases, is protecting people from r-HAT. We hypothesize that national policies to promote widespread and regular use of pyrethroids by livestock-keepers have led to large-scale control of r-HAT.

To test this hypothesis, we will:

1. Develop and test geostatistical models of the spatial correlations between satellite data and catches of tsetse from traps, to produce a high-resolution map of the predicted distribution of tsetse in northern Tanzania and identify 'hotspots' where tsetse are predicted to be abundant.

2. Sample cattle at hotspots identified in Simanjaro and Pangani Districts, where different livestock production systems (pastoralist, zero-grazing) predominate, to estimate the prevalence of Trypanosoma, using PCR-based methods, and use of pyrethroids through chemical analysis of cattle hair.

3. Conduct questionnaire surveys of livestock-keepers to assess the economic factors underpinning selection of tsetse control methods. We will also analyse the pyrethroid supply chain by conducting questionnaire surveys with retailers and distributors of veterinary medicines and government officials.

4. Use epidemiological models, parameterised with empirical data from ENABLES, to quantify the economic cost and epidemiological benefit of treating cattle with pyrethroids in different livestock production systems. Data and models will be used to produce a toolbox to help Tanzania and other countries develop evidence-based policies for the sustainable control of r-HAT and AAT.

Planned Impact

Our project will lead to more effective control strategies for reducing animal African trypanosomiasis (AAT) and Rhodesian human African trypanosomiasis (rHAT). The potential economic and societal impacts include:

Reduced incidence of HAT
Rhodesian HAT, the zoonotic form of sleeping sickness, threatens ~12M people in East and Southern Africa. In Uganda, and potentially elsewhere, cattle act as important reservoir hosts for the trypanosomes which cause HAT. Mass treatment of cattle with pyrethroids, a proven method of controlling Rhodesian HAT, will reduce this risk.

Reduced burden of AAT
The outputs from this project will be used to improve efforts to control AAT, which kills >1 million cattle a year across 35 countries of sub-Saharan Africa. Tanzania has the third largest livestock population in Africa, and a high proportion of poor livestock keepers. More than half the country and >8 million cattle are at risk of AAT. Increasing animal productivity is likely to impact particularly on the rural poor, both in Tanzania and other affected countries.

Cost-effective strategies to control AAT
Livestock keepers in Africa spend ~$35M annually on trypanocides. In Tanzania, the annual costs of treating individual cattle with an acaricide have been estimated at $6-$36 and treatment of an infected animal with therapeutic drugs at $38. Outputs from this project will provide livestock keepers, government departments, NGOs, international (AU-PATTEC, FAO) and donor (DFID, BMGF, GALVmed) organizations with a rational basis for selecting cost-effective interventions against trypanosomiasis and an understanding of the factors influencing uptake by livestock-keepers.

Strengthening the capacity of veterinary research institutions in Tanzania
The Vector and Vector-borne Diseases Research Institute (VVBDI) provides advice to the Government of Tanzania on control of vector-borne diseases of livestock. VVBDI is broadening its original scope from a focus on tsetse-borne pathogens to encompass all vector-borne diseases of veterinary importance. This project will provide the foundation of partnerships between VVBDI and world-leading researchers from a variety of disciplines and UK institutions, thereby assisting VVBDI in its mission to support livestock keepers in Tanzania through provision of evidence-based advice to the Government of Tanzania.

Robust tourism industry
Tourism is a significant contributor to the Tanzanian economy and maintenance of wilderness areas is crucial. Increasing cost-effective control of AAT will reduce conflict at the boundaries of wilderness areas where transmission from wildlife reservoir hosts can be a source of tension between resource-poor farmers and management of national parks/wildlife reserves. Even low numbers of HAT cases in tourists can have a significant impact on tourism. Preventing outbreaks of HAT is therefore important for both public and private sectors. This project will help to ensure that managers of protected areas have access to information on optimal tsetse control strategies.

Environmentally sensitive approaches
Uncontrolled use of insecticides and acaricides can impact on dung fauna which play an important role in maintaining soil fertility. A method of applying insecticide to cattle developed by our group (Restricted Application Protocol) reduces impact on non-target species.

ODA justification: The countries that would benefit most from improved control of AAT and r-HAT are classified as least developed (Tanzania, Uganda, Zambia) or low income countries (Kenya). The impacts listed above demonstrate the potential impacts of this project on areas closely linked to poverty and development: animal health, human health, tourism, the environment, and capacity building. Improvements in these areas will contribute to future economic development, for Tanzania in the first instance, and for other affected countries in the longer term.

Publications

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Vale GA (2023) Identification of the area sampled by traps: A modelling study with tsetse. in PLoS neglected tropical diseases

 
Description Our project had four research objectives.

First, we aimed to produce a high-resolution map of the predicted distribution and abundance of tsetse in northern Tanzania to identify trypanosomiasis 'hotspots'. Building on empirical results from entomological surveys carried out and reported previously, we developed a Bayesian geostatistical model previously fitted to data from Serengeti District and Serengeti National Park to predict the abundance of tsetse in Simanjiro District and Tarangire National Park. Comparisons were made between this model and a model including data from both study areas. We then compared fits to the data between the geostatistical model, a linear regression model and a generalised boosted model of tsetse abundance. In general, extrapolations from the geostatistical model fitted to data in Serengeti predicted relatively high and low areas of tsetse abundance in Simanjiro which corresponded to suitable and unsuitable habitat observed on the ground. Comparison of linear regression and geostatistical model fits to all data highlighted the existence of substantial residual spatial autocorrelation in tsetse abundance. Some of this was overcome by using a generalised boosted model. In all models, some areas of marsh within Tarangire National Park were predicted to be of high tsetse abundance but these are unsuitable for tsetse. Our results show that a combination of modelling approaches could be useful for guiding the choice of initial sites for tsetse surveillance. Where data are available for other ecologically similar sites, models could be used to obtain initial predictions and then refined with data from the new site to identify suitable areas that may have been missed using a random sampling strategy. Our geospatial models identify areas of Simanjiro where we predict tsetse to be abundant but our entomological surveys caught few or none. The unexpectedly low numbers of tsetse may be related to farmer-led treatment of cattle with pyrethroids (see below). A manuscript reporting this work was submitted to Parasites and Vectors in September 2021.

Second, we aimed to quantify the extent and impact of insecticide-treated cattle on tsetse and trypanosomiasis. Towards this objective, we collected 2964 tsetse to quantify prevalence of pathogenic trypanosomes, particularly T. b. rhodesiense and T. congolense, the pathogens causing human and animal African trypanosomiasis. Analyses of the samples was interrupted by closure of laboratories at LSTM during lockdowns related to the Covid-19 pandemic but we resumed this once these restrictions were relaxed and the work has been completed. Samples were analysed using a variety of PCR-based methods. The results showed that we did not capture any tsetse that were infected with T.b. rhodesiense, the pathogen causing human trypanosomiasis. Second, using the TBR-PCR we discovered an unexpectedly high percentage of flies with DNA from T. brucei brucei. Further analyses of these samples indicate that the contamination may be occurring in the traps, with DNA from infected tsetse contaminating uninfected ones. With funding from BMGF, we are carrying out laboratory-based studies to test this hypothesis. These novel findings may explain why other research groups have also reported implausibly high infection rates of T. brucei in wild-caught tsetse.

In addition to analysing tsetse, we analysed the blood of cattle (n=770) from 42 herds in Simanjiro district and 302 cattle from 43 households in Pangani district. In both surveys we collected blood and hair from cattle to allow us to quantify prevalence of trypanosomes and the concentration of pyrethroids. The Covid-19 pandemic delayed not only the sampling of cattle in Tanzania but also the shipping of samples from Tanzania to laboratories at LSTM and Roslin. All field collections have now been completed successfully. This has revealed that no samples are positive for T. brucei or T. vivax, and eight samples are positive for T. congolense (a provisional prevalence of 0, 0 and 4.6%, respectively). These prevalences are lower than those observed in Serengeti, which may correlate with the increased insecticide use in Pangani (see below) and/or to reduced exposure, for example due to zero grazing practices in small holder dairy households. However, these analyses are continuing, and firm conclusions can only be inferred upon completion of data generation.

Hair samples from a randomly-selected subsample of 102/770 cattle from 21 herds in Simanjiro district have been analysed by HPLC to detect and quantify insecticide present. Half of all cattle sampled were found to have no insecticide present (52%, 53/102), with a quarter of herds (24%, 5/21) found to have no insecticide-treated individuals. The insecticide used was either alphacypermethrin (31%, 32/102) or cypermethrin (17%, 17/102), with variable amounts detected (2-144ug/g hair for alphacypermethrin, 8-1245ug/g hair for cypermethrin). These results show that in Simanjiro district there is widespread use of pyrethroids effective against tsetse with the rate in Simanjiro (48% of cattle, 76% of herds) being higher than that from Serengeti (18% and 27% respectively; Lord et al., 2020). These analyses of tsetse, cattle blood and hair provide further objective evidence that widespread farmer-led treatment of cattle with pyrethroids is occurring across northern Tanzania. Our empirical data and models suggest that this treatment is contributing to the control of tsetse and both human and animal trypanosomiases at the interface of conservation and farming areas.

Our third objective was to identify the epidemiological, socio-economic and political factors influencing uptake of tsetse control measures by livestock keepers. We conducted semi-structured household questionnaires in Simanjiro district with the 42 livestock keepers whose cattle were sampled. The questionnaire included questions on: current disease control practices, expenditure and sources of cash for these expenditures, where and how the disease control items are obtained, costs of potential trypanocides and insecticides and; sources of information on control of tsetse and trypanosomiasis. To increase the sample size of the questionnaire survey, we completed interviews with an additional 50 livestock keepers in late 2020. We also completed a questionnaire survey of 78 livestock keepers in Pangani district. Analyses of the surveys show that there is widespread use of insecticides effective against tsetse with 100% and 45% of farmers from Simanjiro and Pangani districts, respectively, treating their cattle regularly with pyrethroids. The lower rate of use in Pangani district probably reflects the lower densities of tsetse and rates of trypanosome transmission as well as different livestock-keeping practices, such as zero grazing. The rates of treatment reported by livestock keepers are higher than the percentage of cattle and herds with detectable levels of pyrethroids (see above). Our questionnaire surveys also showed that few farmers have received training on the correct use of pyrethroids and incorrect dilutions and/or volumes of insecticide are being applied. Fortunately, these errors seem to cancel each other and the amounts applied appear to be broadly correct.

Our fourth and final objective was to produce a toolbox to assist Tanzanian and other governments formulate and promote evidence-based policies and practices for the sustainable, cost-effective and environmentally-acceptable control of human and animal trypanosomiasis. Unfortunately, the Covid-19 pandemic prevented travel between the UK and African countries and we have not been able to conduct a workshop with stakeholders as planned. We are preparing materials and plan to conduct workshops with national stakeholders in 2022.
Exploitation Route The methods and findings of this project contributed to the development of a successful proposal submitted to MRC. The project (STRESS-Malawi) is concerned with reducing risk of Rhodesian HAT at the interface of conservation areas in Malawi.
Sectors Agriculture, Food and Drink,Environment,Healthcare

URL https://www.lstmed.ac.uk/projects/life-on-the-edge
 
Description Glasgow 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in tsetse biology and control
Collaborator Contribution Expertise in biology and control of human and animal trypanosomiasis
Impact BBSRC-funded grants. No outputs produced to date but these are anticipated from 2020 onwards.
Start Year 2019
 
Description Roslin 
Organisation University of Edinburgh
Department The Roslin Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Conducting field- and lab-based investigations of tsetse
Collaborator Contribution Conducting field- and lab-based investigations of trypanosomes
Impact Co-authored papers (see publications outcome)
Start Year 2014
 
Description SRUC 
Organisation Scotland's Rural College
Country United Kingdom 
Sector Academic/University 
PI Contribution Field- and laboratory-based investigations of tsetse
Collaborator Contribution Field- and laboratory-based investigations of trypanosomes
Impact See joint papers in Publications Output
Start Year 2014
 
Description TTRI 
Organisation Tsetse and Trypanosomiasis Research Institute
Country Tanzania, United Republic of 
Sector Charity/Non Profit 
PI Contribution Field- and laboratory-based investigations of tsetse
Collaborator Contribution Field-based studies of tsetse
Impact None to date (24 February 2016)
Start Year 2014
 
Description ECTMIH 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation at the the European Congress on Tropical Medicine and International Health, 16-20 September 2019, Liverpool by Dr Jennifer Lord. The title of the presentation was "Trypanosome transmission and control at the wildlife-livestock interface"
Year(s) Of Engagement Activity 2019
 
Description ECTMIH 2 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation by Rachel Lea on "A novel method to monitor use of insecticide treated cattle to control human and animal African trypanosomiasis in Tanzania" to an audience of researchers.
Year(s) Of Engagement Activity 2019
URL https://www.ectmih2019.org/
 
Description ENVT summer school 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Lecture on tsetse biology and control to a summer school comprising post-graduate students and early-career researchers from Europe and Africa. The summer school is organised and hosted by the École Nationale Vétérinaire de Toulouse
Year(s) Of Engagement Activity 2019
URL http://www.envt.fr/content/universit%C3%A9-d%E2%80%99%C3%A9t%C3%A9-en-entomologie-m%C3%A9dicale-et-v...
 
Description Feedback meeting to national stakeholders convened in Arusha, Tanzania 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact We presented the findings of the ENABLES and COMBAT projects to government researchers and stakeholders. Subsequent discussions focussed on trypanocide resistance, diagnostics for trypanosomes, changes in animal trypanosomiasis and its control in Tanzania over the last 20 years. More detailed presentations on our findings were presented at the Symposium on Livestock Trypanosomasis.
Year(s) Of Engagement Activity 2023
URL https://twitter.com/SALTTz_2023/status/1625363697605435394
 
Description Feedback meeting with stakeholders from Pangani district, Tanzania 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact 20 livestock extension officers from Pangani were informed about the findings of our work with livestock keepers in Pangani district. We highlighted use of insecticides and trypanocides by the livestock keepers and how these interventions might be improved.
Year(s) Of Engagement Activity 2023
URL https://twitter.com/TorrSteve/status/1623567525433815040
 
Description Feedback meeting with stakeholders from Simanjiro district, Tanzania 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Meeting with livestock extension officers from Simanjiro district to present the findings of our research conducted in partnership with livestock keepers. We discussed how flow of information to farmers might be improved and the impact of insecticide-treated cattle on transmission of trypansomes causing sleeping sickness (human African trypanosomiasis) and nagana (animal African trypanosomiasis).
Year(s) Of Engagement Activity 2023
URL https://twitter.com/TorrSteve/status/1624304593747210240
 
Description GEOMED 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation by Rachel Lea on "Predicting tsetse abundance: remote sensing and the impact of insecticide treated cattle in Tanzania" to an audience of researchers.
Year(s) Of Engagement Activity 2019
URL https://www.gla.ac.uk/events/conferences/geomed/
 
Description Kick-off meetings for COMBAT and ENABLES projects with presentations on original ZELS project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Kick-off workshop for COMBAT and ENABLES project which build on the original ZELS project. As part of the meeting, we made presentations on the original ZELS project.
Year(s) Of Engagement Activity 2019
URL https://twitter.com/HarrietAuty/status/1100414020408897537
 
Description Panelist (1/4) for an on-line discussion about elimination of HAT 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An international meeting convened by the London Centre for Neglected Tropical Diseases and the HAT platform. The 3-day programme was concerned about research priorities to support the achievement of WHO's goal goal of eliminating transmission of HAT by 2030. Prior to the meeting, presentations were produced on a range of relevant topics. These included a presentation on tsetse control produced by Drs Inaki Tirados and Andrew Hope from LSTM. I was an invited panelist for a 2 hour live on-line discussion concerned with vector control and diagnostics.
Year(s) Of Engagement Activity 2022
URL https://www.londonntd.org/news/lcntdr-the-hat-platform-scientific-research-meeting-achieving-human-a...
 
Description Stakeholder meeting at WHO on Rhodesian Sleeping Sickness 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact The meeting reviewed current practice and policy related to the control of Rhidesian sleeping sickness. I made an invited presentation on tsetse control.
Year(s) Of Engagement Activity 2019
URL http://www.fao.org/paat/news-and-events/events/detail-events/en/c/1179507/
 
Description Trypanosomatid Meeting VI 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation by Torr of a lecture entitled "Tsetse control in a changing world" to an audience of ~100 researchers working on trypanosomes.
Year(s) Of Engagement Activity 2019
URL https://research.pasteur.fr/en/event/trypanosomatid-parasites-meeting-vi-from-the-lab-to-the-field/
 
Description TsetseNet Ghana 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation by Dr Jennifer Lord on "Tsetse and animal African trypanosomiasis control amid rapid anthropogenic change"
Year(s) Of Engagement Activity 2020
 
Description Workshop on the achievements of our project 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A workshop to other members of the ZELS program, representatives from BBSRC and DFID and the programme advisory panel. Rachel Lea made a presentation on the project and a case study of our project was made available on the world-wide web. https://bbsrc.ukri.org/documents/1902-casestudy-zels-hat/. Rachel Lea also made a presentation on a new project which will build on the findings of our original ZELS project.
Year(s) Of Engagement Activity 2019
URL https://bbsrc.ukri.org/news/health/2019/190225-n-the-fight-against-animal-to-human-diseases/