RESIST

The RESIST project is a multi-institute, multifaceted study investigating the potential for drug resistance to be a causative factor in the persistence of urogenital schistosomiasis on the island of Pemba in Tanzania’s Zanzibar archipelago.

The project integrates field-collected parasitological data quantifying Schistosoma haematobium infections with spatio-temporal genomic analysis of isolated and preserved Schistosoma haematobium larvae collected from infected study participants. The study also involves using mathematical modelling to predict the impact of past and present mass administration of praziquantel on drug resistance.

Aims

The goal of the study is to determine whether resistance to praziquantel has contributed to the persistence of Schistosoma haematobium hotspots in Pemba and, if so, how to address this. These hotspots refer to regions where prevalence remains above 5% despite repeated treatments.

The project has four major aims:

1. To determine egg reduction rates post-treatment with praziquantel in two hotspot schools, and quantify geographic variation in infection levels across an additional 15 schools.
2. To perform whole genome analysis on single isolated and preserved Schistosoma haematobium miracidia from 2012 and 2017 using part of the Schistosomiasis Collection at the Natural History Museum, and on specimens collected in 2024 and 2025. We will then identify SNPs in putative resistance markers in the TRPM_PZQ channel within the Schistosoma genome.
3. To develop an S. haematobium transmission model using data collected in the above aims. We will use this model to predict the impact of mass drug administration with praziquantel and mitigation strategies on population dynamics of drug resistance in S. haematobium in Pemba.
4. To assess the cost-efficiency of different drug efficacy survey strategies.

Who is involved?

The RESIST project brings together an international collaboration between the Public Health Laboratory Ivo de Carneri in Pemba, the Erasmus MC in Rotterdam, the Swiss Tropical Public Health Institute and the Natural History Museum.

The project team includes researchers with expertise in infectious diseases, epidemiology, parasitology, genomics, and mathematical and statistical modelling. Together with the fieldwork team in Pemba, our lab leads the larval schistosome miracidia collections from infected school-aged children and their preservation. Further whole-genome bioinformatic analysis is conducted at the Museum after schistosome DNA is isolated and quantified from each sample.

The fieldwork team in Pemba, along with colleagues at Swiss TPH, coordinate the school-based parasitological surveys, and Erasmus MC colleagues provide the expertise in modelling schistosomiasis transmission.

Methods

The project begins with three major parasitological surveys and collections.

Two of these surveys will capture urogenital schistosomiasis prevalence and egg reduction rates before treatment with praziquantel, and then two weeks after treatment in two schools with persistently high prevalence of schistosomiasis. The third survey takes place across 15 schools before the delivery of mass drug administration in 2025 and involves only a pre-treatment prevalence assessment.

The S. haematobium miracidia samples collected across these three surveys will be sequenced across the whole genome, and putative resistance SNP markers will be interrogated. Association of SNPs present in S. haematobium samples post-treatment with praziquantel will be of particular interest. Epidemiological and genomic data collected will then be used to inform the schistosomiasis transmission model that will be used to predict future trends in using mass drug administration with praziquantel to eliminate schistosomiasis on Pemba and beyond.

What is the Museum’s role in the project?

The Museum team leads the S. haematobium miracidia collections in Pemba, together with population genomic analyses.