Severe schistosomiasis is a devastating neglected infectious disease (NID). Without control and disease management strategies, sufferers with the manifestion of periportal fibrosis can develop portal hypertension, in its severest form causing death through haematemasis. Mass Drug Administration (MDA) programmes are the corner-stone of international efforts to control schistosomiasis as a public health problem. Uganda was at the forefront of the treatment vanguard, first administering MDA in 2003. Amongst the communities first treated were those residing on the shores of Lake Albert, an area historically with high rates of periportal fibrosis. Our recent screens of school-children in these fishing communities show that despite concerted efforts and reported community treatment coverage rates of near 80%, infection intensities are very high and periportal fibrosis common place. There is a major need for alternative strategies for these hotspots if we are to meet the aims of Sustainable Development Goal 3: Ensure health lives and promote well being for all at all ages”. For rapid uptake into national and international policy these interventions need to be built upon existing control structures and be relatively easy to facilitate. In lower transmission areas MDA is targeted at school-children, combining the epidemiological knowledge that this age-group suffers the greatest burden of infection with easier implementation. We therefore propose that increasing praziquantel treatment frequency within the schoolstructure, in addition to annual community MDA, will be an effective disease control strategy in hotspots of schistosomiasis morbidity. At the core of this proposal is a superiority randomised intervention trial that asks the question:
Does increased treatment frequency reduce the prevalence of childhood periportal fibrosis in hotspots of persistant schistosomiasis?
To ascertain the causes of high morbidity, the trial focuses on the following four areas:
A randomised superiority intervention trial of 2x and 4x annual PZQ treatment versus standard 1x annual treatment with the primary outcome – decreased prevalence of periportal fibrosis.
Anthropological investigations into perceptions of mass drug administration with praziquantel – the lived experience of standard annual MDA and the experience of multiple praziquantel treatments.
Determination of schistosome egg specific cytokine responses, quantification of circulating regulatory immune cells, antibodies and their association with periportal fibrosis.
In parallel with microsatellite genotyping, whole genome sequence analysis will identify loci associated with periportal fibrosis and praziquantel sub-optimal responses.
The Fibroschot Consortium:
A selection of images from the clinical trial site in Hoima region.
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This project is part of the EDCTP2 programme supported by the European Union.