Epidemiology and evolution of zoonotic schistosomiasis in a changing world

Schistosomiasis, caused by schistosome parasitic worms is a disease of profound medical and veterinary importance, inflicting unnecessary suffering on poor rural communities in many parts of the developing world, with the greatest burden within sub-Saharan Africa. Environmental change, through natural phenomena or human interventions, such as dam constructions or drug treatments, can substantially impact upon the dynamics and distribution of this disease, with potential positive and negative effects upon human and animal health. Such activities, combined with changes in agricultural practices, place selective pressures on human and animal schistosomes and increase the opportunities for mixing of different species. This mixing within the human or animal hosts can result in novel hybrids which may influence their potential for disease transmission and morbidity. Focusing within Niger and Senegal, our multidisciplinary proposal aims to understand the populations at risk of infection and disease with novel zoonotic hybrid schistosomes. The results obtained regarding the potential role of animal schistosomiasis in maintained infection hot spots, should prove valuable for control programmes, including recent plans for schistosomiasis elimination. We will also enhance the capacity of our West African partner institutions, from schistosome and host identification, population genetic analyses, together with partnership with industry to produce and evaluate new rapid mapping diagnostic tools for the field.

Schistosomiasis is a disease caused by different species of parasitic worms, called schistosomes. It is a Neglected Tropical Disease (NTD) of profound medical and veterinary importance, inflicting unnecessary suffering on poor rural communities in many parts of the developing world, with the greatest burden within sub-Saharan Africa (SSA). Recent changes in selective pressures following, for instance, new dam constructions/irrigation systems and/or altered agricultural practices, combined with increased mass drug administration programmes, may all impact the availability of suitable definitive and intermediate hosts for schistosomes, and hence potential for both intra- and inter-specific interactions within such hosts. Furthermore, when humans and their livestock come into closer water contact, novel zoonotic hybrid schistosome species may evolve and establish as a consequence, with subsequent changes in parasite life history traits, transmission potential, morbidity profiles and intervention success. Empirical studies of such potential evolutionary changes under natural conditions are lacking. The research proposed here will contribute to the major push to control and eliminate schistosomiasis as a public health problem as recently put forward in the WHO NTD roadmap. It is essential to discover fully the extent of schistosome zoonotic infections as this may well influence progress in reducing transmission in many regions of West Africa in addition to Niger and Senegal. We hope to learn lessons that will inform and guide future control activities and assist local livestock farmers. Very little attention has been paid to the impact of animal schistosomiasis on domestic ruminants in SSA and in the vast majority of rural settings little is done in the way of treatment. Our findings will play a significant role in helping to control this debilitating disease that is so commonly associated with impoverished rural populations.

Schistosomiasis is a NTD of profound medical and veterinary importance, inflicting unnecessary suffering on poor rural communities in many parts of the developing world, with the greatest burden within SSA. Our research will contribute to the major push to control and eliminate schistosomiasis as a public health problem as recently put forward in the WHO NTD roadmap. It is essential to discover fully the extent of schistosome zoonotic infections as this may well influence progress in reducing transmission in many regions of West Africa in addition to Niger and Senegal.

The proposed research will also provide development, optimization and application of SOPs for novel diagnostics, future mapping and genetic analyses of zoonotic hybrid schistosomes in SSA and in doing so will enhance the capacity of the staff of our African partner institutions in aspects of disease research, surveillance and control. There are many man-made environmental changes planned and in progress in Senegal and Niger associated with water development which will impact on schistosomiasis, these changes will alter the distribution of human and animal populations and will lead to changes in the distribution of the snail intermediate hosts essential for transmission. By capacity building and training we hope to increase expertise within local research teams so that they are better able to monitor and assess the impact of these environmental changes.

The results produced here will be fed directly back into international and national policy, including WHO guidelines and national control progamme implementation. This will be directly achievable here through our Niger coapplicant AG, and our Senegalese Research Partner IT, directing the national control programmes within county, assisted by SCI and hence the PI JPW and the Research Partner AF.

Our pilot data from one area in Niger has indicated an apparent 'hot-spot' transmission area in Niger - where very high prevalence (82% 2006-96.4% 2009) and intensities of apparent urogenital schistosomiasis were maintained despite high coverage annual/bi-annual MDA. Our molecular analyses revealed that 87% of these children were in fact infected with a novel zoonotic hybrid infection. If the current studies reveal further hotspots of maintained transmission are due to zoonotic infections this has implications for control. If our PZQ efficacy assays reveal continued high efficacy of PZQ in terms of ERR, but high reinfection rates, we can propose more regular PZQ treatments/MDA in such areas to impact the juvenile maturing worms (which are not responsive to PZQ). If our PZQ efficacy assays reveals, in contrast, a reduced efficacy in hybrid versus single infections we can propose higher PZQ doses, from 40 mg/kg to 60 mg/kg and emphasize further the need for PZQ alternatives. If the outputs from our research so indicate, pressure will be placed for the implementation of concurrent methods for schistosomiasis control in livestock, including potential bovine vaccine development and/or PZQ chemotherapy, akin to that currently employed for zoonotic S. japonicum transmission in China. This will thereby assure impact and benefit to those people, and their livestock, in Niger and Senegal in both the short and the long term.

A full appreciation of the interactions taking place between schistosomes of humans and animals and associated morbidities will ultimately lead to improved animal management practices with a concurrent improvement in animal health which will in turn assist in lifting rural human populations out of poverty.

Furthermore, in addition to the applied significance of this work, which translates directly into control, we hope the research findings will also be of fundamental value to the academic community as we believe that we are witnessing the evolution of a zoonotic infection.