Working within a One Health framework, the overarching aim of our ZELS projects is to elucidate the complex dynamics of zoonotic hybrid schistosomiasis transmission, with the ultimate goals of improving the health of affected people and their livestock.

Challenge

Hybridisation amongst parasitic agents, particularly concerning those with zoonotic potential, is a major emerging public and veterinary health concern at the interface of evolution, epidemiology, ecology, and control. Co-infections, where individual hosts are infected by more than one infectious agent at the same time, are the norm within humans and animals. Increasing levels of anthropogenic changes are shifting the opportunities for encountering new infections of both human and animal origin, and thereby also the occurrence of co-infections with multiple agent species and strains.

Co-infection can have a significant impact on the pathogens involved, often as a result of synergistic or antagonistic interactions, where changes in establishment, growth, maturation, reproductive success, and/or drug efficacy have all been documented. Furthermore, co-infections between parasites can allow for heterospecific (between-species or between-lineage) mate pairings, resulting in either infertility or parthenogenesis (asexual reproduction where eggs occur without fertilization), introgression (the introduction of alleles of one species into the gene pool of another through repeated backcrossing of an inter-specific hybrid with one of its parent species), or whole genome admixture.

One group of infectious agents where opportunities for, and subsequent evidence of, hybridisation between parasites of humans with those from animals is rapidly emerging are those of the neglected tropical diseases (NTDs)—highly debilitating diseases infecting more than a fifth of the world’s human population, and their livestock, with devastating consequences. One such major NTD is schistosomiasis, caused by Schistosoma spp. trematodes, is a freshwater-snail-borne Neglected Tropical Disease (NTD) of global medical and veterinary importance, with over 220 million people currently infected and untold millions of livestock. The disease causes abdominal pain, bloody urine and stools and can damage the liver, spleen, intestines, lungs and bladder, ultimately leading to death to many cases.

Whilst in endemic regions of Asia, animal hosts are acknowledged as important zoonotic reservoirs, within SSA, in contrast, the zoonotic component of schistosomiasis transmission and the implications of the multi-host aspects of schistosomiasis for disease control and reaching the elimination targets has, until recently, been largely ignored. This was particularly the case for S. haematobium, the causative agent of urogenital schistosomiasis in humans, which was assumed to be an exclusively human infection – and thus amenable to elimination by targeting treatment at humans alone.

In 2013, the World Health Organization (WHO) set ambitious goals for controlling schistosomiasis morbidity by 2020, eliminating it as a public health problem (EPHP) in all endemic countries by 2025, and complete interruption of transmission in selected regions by 2025, with the revised 2021 WHO-NTD Roadmap aiming for EPHP by 2030. However, despite decades of mass administration of the anthelmintic praziquantel to, predominantly, school-aged children, reports of schistosomiasis being more prevalent than previously thought, its persistence and/or re-emergence in previously cleared areas, together with potential reduced drug efficacy in populations under high drug pressure, all serve to highlight that additional control strategies must be introduced if this major disease is to ever reach elimination.

Solution

The objective of the RVC research is a better understanding of the evolution, ecology, transmission dynamics and morbidity impact of this potentially emerging disease threat, of paramount important to the health of humans and their livestock, particularly amongst the poorest of the poor. More generally, this research enhances our understanding of a wide spectrum of multi-host parasitic diseases of humans and animals, and in particular the role of evolution of host ranges and introgressions within major taxonomic groups, in our rapidly changing world.

The RVC project informs and contributes to sustainable control and development strategies for these people. Extensive parasite sampling in humans, livestock, wildlife and snail intermediate hosts and the application of novel molecular and diagnostic tools, as well as mathematical modelling and socio-economic surveys, are being used to elucidate the epidemiology of novel zoonotic hybrid schistosomes and its impact on host spectrum, PZQ efficacy, host morbidity and ultimately transmission potential.

Impact  

The threat to public health presented by zoonotic spillover of pathogens from animal reservoirs is predicted to increase with rapid anthropogenic changes and global trends such as migration and changing land use. This research highlights the importance of recognising the multi-host multi-parasite aspects of disease systems under evolutionary pressure. The work to date has demonstrated how zoonotic spillover and complex interactions between pathogen species, such as parasite hybridisation, may have implications such as resilience to current disease control strategies, as well as facilitating the spread of tropical diseases such schistosomiasis beyond their original geographical boundaries.

The outcomes of this study have already substantially contributed to a change in international policy on disease control and knowledge, modifying attitudes and practice of those inflicted with the threat of this disease. Pressure will now be placed for the implementation of modified praziquantel treatment regimes and diagnostic tools for both people and animals living in zoonotic high transmission zones with the application of a One Health framework for schistosomiasis control.

The research contributes to the major push to control and eliminate schistosomiasis as a public health problem, as set by the WHO NTD roadmap and the London Declaration of the NTD coalition, which pledge to contribute towards the control or elimination of schistosomiasis by the end of the decade.

Funders and Partners  

• Biotechnology and Biological Sciences Research Council
• Department for International Development/UK-Aid
• Economic and Social Research Council
• Medical Research Council
• Natural Environment Research Council
• Department for International Development
• University of Gaston Berger, Senegal
• RISEAL, Niger
• Institute of Developmental Studies
• Natural History Museum

Publications

News / In the media     

• https://www.ukri.org/news/uk-scientists-inform-roadmap-to-eliminate-disease-of-poverty
• http://www.londonntd.org/research/projects-search/epidemiology-and-evolution-of-zoonotic-schistosomiasis-in-a-changing-world
• https://bbsrc.ukri.org/documents/1902-casestudy-zels-schistosomiasis
• http://www.londonntd.org/news/zoonotic-parasites-an-underappreciated-area-%E2%80%93-an-interview-with-joanne-webster
• https://www.id-hub.com/2017/09/21/zoonotic-parasites-underappreciated-area-interview-joanne-webster
• https://www.telegraph.co.uk/news/2019/02/25/hybrid-flatworms-pass-livestock-humans-uk-backed-research-finds