New research reveals the complex multi-host-species and multi-parasite-species transmission dynamics of a major disease

A pioneering new study, produced in partnership between the Royal Veterinary College (RVC); the London School of Hygiene and Tropical Medicine (LSHTM); and the University of Gaston Berger, Senegal (UGB), has been published in the prestigious Proceedings of the National Academy of Sciences (PNAS). The research paves the way for a more comprehensive understanding of how certain zoonotic diseases, such as schistosomiasis, can be controlled and ultimately eliminated.

The current global pandemic has brought unprecedented attention to the profound threat to human health presented by spillover and host adaptation of pathogens from animal reservoirs. Rapid anthropogenic changes and trends, such as global migration, are predicted to further increase the potential for both human and animal populations to encounter new infectious agents. This in turn can lead to complex interactions between pathogen strains or species within the same host, with such mixed infections potentially leading to the exchange of genetic material between the co-infecting agents and the generation of new pathogen genotypes.

Focusing on schistosomiasis, a major disease that currently infects more than 220 million people, this study demonstrates how the complex interactions between pathogen species, including parasite hybridization, may both challenge, and be influenced by, disease control efforts. The study integrates novel mathematical modelling approaches with molecular and epidemiological data of parasites collected from humans and their livestock within Senegal, where hybridized schistosome infections are highly prevalent.

Cattle are identified as key reservoir hosts within this system, and with an estimated basic reproduction number (R₀) for hybrid schistosomes of zoonotic origin within humans to be greater than the critical threshold of 1. The implications of these results include the potential for schistosomiasis to spread and establish beyond its original geographical boundaries even without ongoing zoonotic transmission, as has been highlighted by the recent identification of hybrid schistosomes in patients within Corsica.

This vital work was funded through the ZELS and ZELS:SR programme (Zoonoses in Emerging Livestock Systems - UKRI combined BBSRC, MRC, ESRC, NERC, DSTL and DFID) and the Bloomsbury SET, for which the RVC’s Professor Joanne P. Webster was the Principal Investigator. Dr Anna Borlase, the first author, was a RVC Bloomsbury-PhD student under the supervision of Professor Joanne Webster and Dr James Rudge. 

The paper clearly demonstrates the importance of considering disease control from a multi-pathogen as well as multi-host perspective, with the trans-disciplinary approaches described here becoming more broadly relevant than ever in a rapidly changing world. Additionally, the research feeds directly into the revised World Health Organization’s Neglected Tropical Diseases Roadmap for 2021-2030 targets for schistosomiasis control and elimination. More generally, this work emphasises how, as humanity increasingly faces novel challenges in the form of emerging and re-emerging infections, understanding all aspects of the ecological processes that enable and drive the persistence and spread of threats to public health, both old and new, will be pivotal to alleviating their impact and is more critical now than ever.

Professor Andrew Fenton, Professor of Theoretical Ecology at the University of Liverpool, said:

“We are only too aware of the threats posed by zoonotic pathogens spilling over from wildlife hosts into humans but understanding and managing those risks is notoriously hard. This is especially true for parasites and pathogens that naturally circulate between multiple animal host species – identifying which of those species are responsible for maintaining those parasites is highly challenging.

"This research shows how state-of-the-art mathematical tools can be used to interpret genetic and parasitological data to understand the risk of zoonotic pathogen spillover, and identify the key animal species that are responsible for maintaining those parasites in the wild. What is unique about this research is that it specifically explores the case of novel parasites emerging through the hybridisation of parasites from domestic animals and humans, allowing a more complete understanding of the overall risk posed by these zoonotic parasites.

“Overall, this work shows how modelling tools like this can allow the targeting of control approaches to facilitate the management of zoonotic parasites circulating within complex ‘multi-host’ communities.”

Professor David Rollinson, Director of the Global Schistosomiasis Alliance (GSI), said:

“Water development projects and agriculture coupled with climatic change have had an enormous impact on the health and well-being of people living in the Senegal River Basin. This important research explores the situation concerning the disease schistosomiasis and combines detailed molecular and epidemiological data with novel mathematical modelling and statistical approaches to examine what is a complex multi-host and multi-parasite system. There are important insights here for all of us involved in schistosomiasis control and elimination.”

“The work alerts us to the potential dangers of zoonotic spillover and highlights that complex disease dynamics cannot be ignored if the 2030 goals for elimination of schistosomiasis as a public health problem, put forward in the WHO NTD 2030 Roadmap, are to be achieved. The study provides a strong endorsement of the need to adopt a One Health approach when studying complex disease systems in changing environments.”

Professor Joanne Webster, Professor of Infectious Diseases at the RVC and Principal Investigator on the programme, said:

“We are all very proud of this work and the implications and applications it has for translation into international health policy and practice, emphasising the imperative need to consider disease elimination programmes within a One Health perspective and for collaboration between public health and veterinary sectors.”

“Likewise, this work represents fundamental progress for multi-disciplinary approaches to mathematical modelling of disease transmission dynamics, here successfully incorporating molecular and epidemiological data from humans and animals to allow inclusion of multiple host species with multiple, hybridizing, species of parasite into a novel model framework. None of this would have been possible without close partnership with our key Senegalese team members throughout the years.”

“We dedicate this paper and all the work behind it to our wonderful and respected chief technician, and moreover adored friend, Mr Cheikh Thiam, who tragically died last month. Our thoughts and prayers are with his family. He is so deeply missed.

ENDS

Notes to Editors

Reference:

Borlase, A., Rudge, J.W., Leger, E., Diouf, N.D., Fall, C-B., Diop, S.D., Catalano, S., Sene, M. & Webster, J.P. (2021).  Spillover, hybridization and persistence in schistosome transmission dynamics at the human-animal interface. In press  Proceedings of the National Academy of Sciences of the United States of America.  (PNAS - Direct submission). 

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• Jasmin De Vivo (jasmin [dot] devivo [at] plmr [dot] co [dot] uk) or rvc [at] plmr [dot] co [dot] ukrvc
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