Sustainable control of livestock schistosomiasis in Africa to improve human and animal health and productivity

Lead Research Organisation: Royal Veterinary College
Department Name: Pathobiology and Population Sciences

Abstract

The One Health approach recognises that the health of humans is connected to the health of animals and the environment, and aims to identify and implement holistic solutions that create co-benefits for all. A critical aspect of One Health is the co-production of knowledge and solutions and therefore encourages collaborative efforts of multiple agencies and population groups to achieve the best outcomes for each. Schistosomiasis is a neglected tropical disease of profound medical importance. Over 240 million people are infected, 90% of these amongst the poorest of sub-Saharan Africa. Although generally ignored, schistosomiasis is also a disease of substantial veterinary importance. Recent environmental and anthropogenic changes appear to exacerbating opportunities for the mixing and subsequent viable hybridization between human and animal schistosomes. We have demonstrated that novel zoonotic hybrid schistosomes within West Africa are having a substantial impact on the epidemiology, evolution and clinical outcomes of disease, with further challenges and constraints for effective control. It is thus apparent that schistosomiasis in many parts of sub-Saharan Africa cannot be eliminated if there are animal reservoirs of infection leading to continued transmission to both humans and animals. Furthermore, animals often suffer severe morbidity and mortality due to schistosomiasis, further impacting the livelihoods of their owners. Livestock are vital for and integral to the social construction of human life and productivity in these regions.
This new research will provide increased knowledge on human-livestock interactions, quantify the costs incurred to subsistence farmers with infected animals, elucidate the potential risks of drug resistance developing if both animal and humans are accessing drug treatments, help enable access to and appropriate use of suitable veterinary-approved drug formulations and ultimately, working within a One Health framework, aim to implement and improve sustainable disease control. Inherent within our design, this research aims to improve local capacity, influence national and international policy, and improve human and animal health, lifting rural human populations out of poverty in both the short and the sustained longer term.

Technical Summary

Schistosomiasis is a NTD of profound medical and veterinary importance, inflicting suffering on poor rural communities in many parts of the developing world. This research has the potential to disentangle the metaphorical Gordian knots imperative if the WHO's recent ambitious goals towards 'elimination of schistosomiasis as a public health problem in Africa' are to be achieved.
Our directly-applied research will, through evaluating and designing a sustainable treatment plan for livestock, reduce the risk of animal Schistosoma species circulating in the environment for hybridized ongoing transmission to humans and at the same time reduce the morbidity and mortality inflicted upon infected animals.
Using a range of disciplines (from social surveys, economic and predictive mathematical models, empirical parasitological and molecular data), we will quantify cost-benefits, potential acceptance and impact of a targeted test-and-treat policy to maximise the impact on livestock health whilst at the same time minimizing the risk of evolving PZQ-resistance emergence.
We will enhance the capacity of the staff of our African partner institution in aspects of disease research, surveillance and control, as well as help accommodate local farmers and key stakeholders' perspectives to help co-construct new platforms. Contributing to the effectiveness of the project will enhance local veterinarians' and community members' ability to anticipate, recognize and respond to schistosomiasis infections in livestock and humans, better understand the importance of animal-human interactions for cross-infection, and underscore identification of 'at risk' practices that may be in play. Results will be fed into, from local community workshops and broader symposia, to national and international policy and control progamme implementation. The outcomes should lead to improved animal management practices with a concurrent increase in animal and human health.

Planned Impact

With the vision of "a world free of schistosomiasis", the World Health Organization's (WHO) revised strategic plan, in conjunction with the London Declaration and NTD coalition, recently set the ambitious goals for the control, elimination as a public health problem (EPHP) and/or interruption of transmission of schistosomiasis within selected SSA countries by 2020 and 2025 respectively. Much of this success rests on the assumption that schistosomiasis in SSA, in contrast to the situation in Asia, is a human-only disease, and thus targeted Mass Drug Administration (MDA) aimed at school-aged children alone should achieve these targets. The potential role of animal schistosomiasis in SSA, either in terms of disease control, economic impact, or in terms of a potential zoonotic risk for maintaining transmission to humans, has been largely ignored for decades. This research has the potential to disentangle the metaphorical Gordian knots imperative if the WHO's ambitious goals towards are to be achieved.
Lessons learned should inform and guide future control activities and assist local livestock farmers. In terms of both international impact, as well as national impact on society, the new research proposed here should minimize both socioeconomic losses due to the direct effects of animal schistosomiasis-associated morbidity and mortality, and minimise the significant risk we have demonstrated in terms of ongoing schistosomiasis transmission through viable hybridization between human and livestock schistosomes. Together these should help achieve targets and improve the health and welfare of the poorest of the poor people and their animals.
The results of the research will be disseminated through publication in open access international scientific journals and by presentation at national and international conferences. In country co-applicants have direct connections with their Ministries within Government particularly the Ministries of Health and Education, as well as local and national veterinary services departments, and will use these links to directly communicate findings of interest and relevance to ongoing control programmes. Results will be discussed at WHO Expert Advisory Group meetings on evaluating drug efficacy and the new 'WHO Guideline Development Group (GDG) for the implementation of control and elimination of schistosomiasis'.
A further impact component will be the evaluation and optomization rapid, inexpensive, point-of-contact diagnostics assays. New molecular data relating to parasites will also be generated throughout the project, and new DNA sequences generated will be deposited in the NCBI GenBANK open access sequence repository for access by other workers. Schistosome collections will be archived at the SCAN facility. Prevalence and intensity data will be made available to interested parties (such as WHO, NGO's, national ministries of health and of environment etc) and shared with the Infectious Disease Data Observatory (iddo.org) schistosomiasis.
Detailed appreciation of interactions between schistosomes of humans and animals, coupled with enhanced understanding of how famers and communities approach schistosomiasis treatment, will provide decision-makers and national and community health services with improved tools to target interventions. Pressure can then be placed for the access and implementation of alternative PZQ treatment regimens for both people and animals living in zoonotic high transmission zones, applying a One Health framework for schistosomiasis control. Such helps ensure the sustained efficacy of the only available drug for human and animal schistosomes whilst improving the health and productivity of humans and their livestock now.
The high quality research produced from this research will help scientists and policy-makers alike realise that animal schistosomiasis, and their hybridization with human schistosome species, is an emerging public and veterinary health concern.
 
Description Our ZELS-SR CATTLES project started less than a year ago and the work is still ongoing.
To date we have conducted 96 individual interviews and 12 focus group in order to evaluate the impact of schistosomiasis on human health and wellbeing, analyse the social uptake of a test and treat control programme for livestock schistosomiasis and collect data to quantify the economic impact of livestock schistosomiasis to subsistence farmers and their families.
Important progress has been made in order to improve community access to livestock schistosomiasis control measures and the efficacy of veterinary drugs currently available as well as improving guidelines for their correct usage.
200 livestock urine samples have been analysed with various diagnostic tests with the aims of developing low cost diagnosis and point of care tools.
Our findings are already being incorporated into International Policy (WHO), as well as national practice (TenicurePlus veterinary dose-appropriate praziquantel in country).
Exploitation Route The information gathered is already being incorporated into WHO Guidelines and policy:

WHO Technical Working Group: Protocols to Verify Interruption of Transmission of Schistosomiasis.

WHO Schistosomiasis Guideline Development Group (GDG),
https://www.who.int/schistosomiasis/news/public-consultation-experts-guideline-development-group/en/index1.html


Optimisation of diagnostic tests with Leiden University, and we are currently in discussion with an additional pharma company in Leiden, Medinet, about producing a livestock-specific commercial POC-CCA diagnostic test.

Distribution of Tenicure Plus with appropriate guidelines for usage in partnership with Senevet, UGB and Laboratoires CALIER Maroc S.A.

Collaboration has been made with LSTHM in order to use new Open Data Kit (ODK) digital data collection system for the recording of data during interviews and focus group discussion.

All molecular data and additional samples collected as part of our ZELS work is stored in an international repository SCAN (give link) for access by other research groups to expand new collaborative research - already leading to a number of additional high impact papers, including, but not exclusive to those published in, for example:

1) Platt, R.N., McDew-White, M., Le Clec'h, W., Chevalier, D., Allan, F., Emery, A.M., Garba, A., Hamidou, A., Ame, S.M., Webster, J.P., Rollinson, D., Webster, B.L. & T.J.C. Anderson. (2019). Ancient hybridization and introgression of an invadolysin gene in schistosome parasites. Molecular Biology and Evolution msz154, doi.org/ 10.1093/molbev/msz154 IF 14.80

2) Wood, C.L., Sokolow, S., Jones, I., Chamberlin, A., Lafferty, K.D., Kuris, A.M., Jocque, M., Hopkins, S., Adams, G., Schneider, M., Buck, J.C., Lund, A., Vedrenne, A.E.G., Fiorenza, E., Rohr, J., Lambin, E., Allan, F., Webster, B., Rabone, M., Rollinson, D., Webster, J.P., Bandagny, L., Ndione, R., Senghor, S., Jouanard, N., Riveau, G & De Leo, G. (2019) Precision mapping of snail habitat provides a powerful indicator of human schistosomiasis transmission. Proceedings of the National Academy of Sciences (PNAS direct submission). 116 (46): 23182-23191 (10 pages) IF 9.58 * Altmetrics N=136 places this 'in the top 5% of all research outputs scored by Altmetric, 98% compared to outputs of the same age.

3) Chevalier, F.D., Le Clec'h, W., McDew-White, M., Menon, M., Guzman, M.A., Holloway, S.P., Cao, X., Taylor, A.B., Kinungi, S., Gouvras, A., Webster, B., Webster, J.P., .. LoVerde, P.T. & Anderson, T.G.C. (2019) Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment. PLoS Pathogens. 15 (10): e1007881 (25 pages). IF 6.67

4) Doyle, S.R.,Sankaranarayan, G., Berger, D., Castro, P.D., Collins, J.B., Crellen, T., Duque, M., Ellis, P., Jaleta, T.G., Laing, R., Maitland, K., McCarthy, C., Moundai, T., Softley, B., Thiele, E., Ouakou, P.T., Tushabe, J.V., Webster, J.P., Weiss, A.J., Lok, J., Devaney, E., Kaplan, R.M., Cotton, J.A., Berriman, M. & Holroyd, N. (2019) Evaluation of DNA extraction methods on individual helminth egg and larval stages for whole genome sequencing. Frontiers in Genetics, 10 (826) 10.3389/fgene.2019.00826 IF 4.15


Similarly, all drug efficacy data to be entered into a new WHO open access data platform for which Joanne is part of the Expert Advisory Board from 2018.

WHO Open Access Data Platform Group.
https://www.iddo.org/news/schistosomiasis-and-sths-platform-launched
https://www.iddo.org/schistosomiasissths/schisto-sth-scientific-advisory-committee/professor-joanne-webster



Our paper: Catalano, S., Sene, M., Diouf, N.D., Fall, C.B., Borlase, A., Leger, E, Ba, K., & Webster, J.P. (2018). Rodents as natural hosts of zoonotic Schistosoma species and hybrids: an epidemiological and evolutionary perspective from West Africa. The Journal of Infectious Diseases. 218 (3) 429-433. https https://doi.org/10.1093/infdis/jiy029 IF 6.273

Was adapted into English and French TeenScience journal versions with highest recorded 2019 downloads and media coverage.


Increased awareness for local communities of livestock schistosomiasis and the risk of zoonotic transmission through workshops and distribution of educational material including a colouring book. We presented schistosomiasis in West Africa being driven not just by the human of form of the parasite as previously assumed, but rather through hybridized animal and human schistosome species. These hybrid species are increasing the distribution of the disease and ultimately challenging current elimination efforts. We presented policy makers with the evidence that to be successful schistosomiasis disease elimination programmes can't ignore the animal reservoirs of infection within sub-Saharan Africa.


As I was unable to upload the url links above, further details can be found at:

http://www.rvc.ac.uk/about/our-people/joanne-webster ;

https://jowebstergroup.co.uk/ ;

https://twitter.com/JoWebster_Group; @jowebstergroup ;

http://www.londonntd.org/news/all-party-parliamentary-group-on-malaria-and-ntds-%C2%A0translating-ntd-research-into-policy ;

'Zoonotic parasites, an underappreciated Area' for the Infectious Disease Hub (September 2018) http://www.londonntd.org/news/zoonotic-parasites-an-underappreciated-area-%E2%80%93-an-interview-with-joanne-webster

https://www.londonntd.org/news/one-health-approach-to-schistosomiasis-control-in-africa-the-cattles-project

https://www.londonntd.org/news/schistosomiasiss-evolutionary-response-to-a-changing-world-can-we-keep-up

https://www.telegraph.co.uk/news/2019/02/25/hybrid-flatworms-pass-livestock-humans-uk-backed-research-finds/ (Feb 25th, 2019);


Five Inspirational women shaping the future of International Development.
Included in List for International Women's Day 2019
https://lidc.ac.uk/five-inspirational-women-shaping-the-future-of-international-development/
https://www.rvc.ac.uk/research/news/general/LIDC-list-of-five-inspirational-women

BBSRC Innovator of the Year Finalist: International Impact.

The data gathered from both ZELS-SHEEP and ZELS:SR-CATTLES projects have been incorporated into the revised WHO Guidelines for Schistosomiasis elimination - the final draft for which is pending:


WHO Schistosomiasis Guideline Development Group (GDG),
https://www.who.int/schistosomiasis/news/public-consultation-experts-guideline-development-group/en/index1.html


Likewise, following our work, the role of animal schistosomiasis within sub Saharan Africa has been incorporated, for the first time, into the revised WHO Health and Sanitation document.

WHO Guidelines of Sanitation and Health: https://apps.who.int/iris/bitstream/handle/10665/274939/9789241514705-eng.pdf?ua=1
Sectors Agriculture, Food and Drink,Education,Environment,Healthcare,Leisure Activities, including Sports, Recreation and Tourism,Government, Democracy and Justice,Pharmaceuticals and Medical Biotechnology,Other

URL https://www.telegraph.co.uk/news/2019/02/25/hybrid-flatworms-pass-livestock-humans-uk-backed-research-finds/
 
Description Our paper: Catalano, S., Sene, M., Diouf, N.D., Fall, C.B., Borlase, A., Leger, E, Ba, K., & Webster, J.P. (2018). Rodents as natural hosts of zoonotic Schistosoma species and hybrids: an epidemiological and evolutionary perspective from West Africa. The Journal of Infectious Diseases. 218 (3) 429-433. https https://doi.org/10.1093/infdis/jiy029 IF 6.273 Was adapted into English and French TeenScience journal versions with highest recorded 2019 downloads and media coverage. Increased awareness for local communities of livestock schistosomiasis and the risk of zoonotic transmission through workshops and distribution of educational material including a colouring book. We presented schistosomiasis in West Africa being driven not just by the human of form of the parasite as previously assumed, but rather through hybridized animal and human schistosome species. These hybrid species are increasing the distribution of the disease and ultimately challenging current elimination efforts. We presented policy makers with the evidence that to be successful schistosomiasis disease elimination programmes can't ignore the animal reservoirs of infection within sub-Saharan Africa. WHO guidelines as detailed above
First Year Of Impact 2019
Sector Agriculture, Food and Drink,Communities and Social Services/Policy,Education,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural,Societal,Economic,Policy & public services

 
Description GCRF Action against Stunting Hub - Co-Investigator (Co-I) and Theme Leader (14 partners).
Amount £19,755,947 (GBP)
Funding ID MR/S01313X/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 07/2019 
End 06/2024
 
Description Evaluation of POC-CCA diagnostic testing of zoonotic schistosomiasis 
Organisation Leiden University
Country Netherlands 
Sector Academic/University 
PI Contribution Shipment of urines from cattle, sheep and goats previously collected and stored in Senegal was organised by us and sent to Leiden University. All these urines had previously been tested with the current Point of Care - Circulating Cathodic Antignes (POC-CCA) diagnostic test for schistosomiasis. This test has been proven to be very reliable for the detection of Schistosoma mansoni however the specificity and sensitivity is not as good for other human and livestock species including hybrids between these two.
Collaborator Contribution Dr. Govert Van Dam, Mrs Claudia de Dood, Dr Paul Corstjens These urines were therefore tested with other POC-CAA (Circulating Anodic Antigens) diagnostic tests in Leiden in order to obtain more information on the reliability of the previous tests used but also for the optimisation a novel diagnostic tests for S. haematobium human schistosome and S. bovis and S. curassoni livestock schistosomes and hybrids between these species. The optimisation is currently ongoing.
Impact Pending further analyses
Start Year 2019
 
Description IDDO Open Access Data Platform Group. 
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 https://www.iddo.org/news/schistosomiasis-and-sths-platform-launched
https://www.iddo.org/schistosomiasissths/schisto-sth-scientific-advisory-committee/professor-joanne-webster

Schistosomiasis and soil-transmitted helminth (STH) platform launched
With IDDO, launched a new global scientific collaboration dedicated to schistosomiasis and STHs with TDR (the Special Programme for Research and Training in Tropical Diseases). This aims to expand data re-use and collaboration and accelerate better treatment and control of these diseases, which affect more than a billion people globa. My role as a member of the scientific advisory committee.
Year(s) Of Engagement Activity 2019,2020
URL https://www.iddo.org/news/schistosomiasis-and-sths-platform-launched
 
Description Invited Expert Advisor presentation/working group leader. 
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 Invited Expert Advisor /working group leader. World Health Organisation (WHO) headquarters, Geneva, Switzerland

Monitoring and Evaultion of drug efficacies in mass drug administration programmes.
Year(s) Of Engagement Activity 2018,2019,2020
 
Description Patient (local villagers and farmers) workshops and focal groups within Senegal 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Education workshops and training - grass roots levels within Senegal.
Educational material has been developed and distributed to interviews, focus group and workshop participants. This included information colouring books, pencil, feeback posters.
Training of key persononell (including PhD student, technicians, economist, teachers and veterinarians) also took place in Senegal during two weeks while these social survey were conducted.
Year(s) Of Engagement Activity 2019
 
Description Social surveys within Senegal 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Evaluate and adapt for social acceptance/uptake of proposed T3 programmes for livestock schistosomiasis. A large social survey was conducted in two contrasting areas of Northern Senegal to evaluate the social acceptance and likely uptake of the proposed T3 programme for livestock schistosomiasis. 12 focus group discussions and 96 individual interviews were conducted. Interviews were transcripted and translated and data analysis is curently underway.
Year(s) Of Engagement Activity 2019
 
Description WHO Schistosomiasis Guideline Development Group (GDG) - Drafting revised WHO Guidelines for Schistososomiasis 
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 Development of Revised Guidelines for implementation of control and elimination of schistosomiasis and verification of interruption of transmission - Expert Advisor

General scope and objectives

Currently, there is no guidance available to evaluate the interruption of schistosomiasis transmission. The existing implementation guidelines are based mainly on expert opinion and need to be revised according to the available scientific evidence.

The goal of this GDG meeting will be to provide evidence-based recommendations to countries in their efforts to control morbidity from schistosomiasis and eventually interrupt transmission. They will help countries to implement national schistosomiasis control programmes and to verify whether transmission of the disease has been interrupted in the country.
Year(s) Of Engagement Activity 2019,2020
URL https://www.who.int/schistosomiasis/news/public-consultation-experts-guideline-development-group/en/...
 
Description WHO Technical Working Group: Protocols to Verify Interruption of Transmission of Schistosomiasis. 
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 WHO Technical Working Group: Protocols to Verify Interruption of Transmission of Schistosomiasis.

Expert Advisor for drawing up WHO protocols and guildelines.
Year(s) Of Engagement Activity 2019,2020