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 haematemesis. Mass Drug Administration (MDA) programmes are the cornerstone 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 with historically 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 commonplace. 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 school structure, 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:
Clinical
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.
Anthropology
Anthropological investigations into perceptions of mass drug administration with praziquantel – the lived experience of standard annual MDA and the experience of multiple praziquantel treatments.
Immunology
Determination of schistosome egg specific cytokine responses, quantification of circulating regulatory immune cells, antibodies and their association with periportal fibrosis.
Genomics
In parallel with microsatellite genotyping, whole genome sequence analysis will identify loci associated with periportal fibrosis and praziquantel sub-optimal responses.
The Fibroschot Consortium:
Lead Investigator
Affiliation: University Of Cambridge
Project Coordinator
Co-Principal Investigator
Affiliation: Vector Control Division, MoH
Trial Site Co-ordinator
Programme Officer
Affiliation: Vector Control Division, MoH
Fieldwork Management
Scientist
Affiliation: Royal Veterinary College
Parasite Genetics
Trial Data Clerk
Affiliation: Makerere University
Data Uganda
Co-Principal Investigator
Affiliation: Wellcome Trust Sanger Institute (now University of Glasgow)
Parasite Genomics
MSc Student/Technician
Affiliation: Makerere University
Parasitology
Co-Principal Investigator
Affiliation: Cambridge Clinical Trials Unit
Trial Statistician
Co-Principal Investigator
Affiliation: Uganda Research Institute, LSHTM
Host Immunopathology
Student Mentor
Affiliation: Wellcome Trust Sanger Institute (now University of Glasgow)
Parasite Genomics
Statistician
Affiliation: Cambridge Clinical Trials Unit
Analysis Plan Statistician
Senior Trial Co-ordinator
Affiliation: Cambridge Clinical Trials Unit
Sponsor Oversight
Trial Nurse
Affiliation: Makerere University
Fieldwork Manager
Immunologist
Affiliation: Uganda Research Institute, LSHTM
Host Immunopathology
Scientist
Affiliation: Royal Veterinary College
Mathematical modelling
Co-Principal Investigator
Affiliation: Makerere University
Anthropology
Co-Principal Investigator
Affiliation: Makerere University
Trial Procedural Oversight
Research Nurse
Affiliation: Vector Control Division, MoH
Fieldwork
PhD Student
Affiliation: Makerere University
Anthropology
Scientist
Affiliation: University of Cambridge
Mathematical modelling, Immunology & Logistics
Database Manager
Affiliation: Vector Control Division, MoH
Data Management Uganda
Co-Principal Investigator
Affiliation: University of Copenhagen
Clinical Oversight
Co-Principal Investigator
Affiliation: Royal Veterinary College
Mathematical Modelling
Co-Principal Investigator
Affiliation: Royal Veterinary College
Parasite Genetics
Previous Consortium Members
Scientist
Affiliation: Royal Veterinary College
Parasite Genetics
Scientist
Affiliation: Royal Veterinary College
Mathematical modelling
PhD Student
Affiliation: Makerere University
Anthropology
MSc Student
Affiliation: Makerere University
Bioinformatics
Medical Officer
Affiliation: Makerere University
Fieldwork Clinician/Manager
Data Manager
Affiliation: University of Cambridge
Data & Logistics
Mawa PA, Kincaid-Smith J, Tukahebwa EM, Webster JP, Wilson S. Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity. Front Immunolo. 2021 Mar 12; 12:635869. doi: 10.3389/fimmu.2021.635869.
Fall CB, Lambert S, Léger E, Yasenev L, Garba AD, Diop SD, Borlase A, Catalano S, Faye B, Walker M, Sene M, Webster JP. Hybridized Zoonotic Schistosoma Infections Result in Hybridized Morbidity Profiles: A Clinical Morbidity Study amongst Co-Infected Human Populations of Senegal. Microorganisms. 2021 Aug 20;9(8):1776. doi: 10.3390/microorganisms9081776.
Lets get in touch. Send us a message:
Email: info@fibroschot.eu
This project is part of the EDCTP2 programme supported by the European Union.