New approaches to characterise Schistosoma mansoni infections persisting despite mass drug administration

ERC Starting Grant SCHISTO_PERSIST 680088
PI: Poppy Lamberton

Schistosomiasis remains a major public health issue in Uganda despite extensive praziquantel mass drug administration (MDA). In one Ugandan district I have worked in since 2004 S. mansoni infection prevalence, intensities and associated morbidity all remain high. Efforts to monitor drug efficacy are impeded by an inability to differentiate between surviving worms and reinfections. As a consequence, the contribution of parasite (e.g. drug resistance, hybrid species) and host (e.g. immunology, pharmacokinetics) factors to transmission is unknown. There is a lack of understanding of the risk of reinfection from untreated individuals and those with heavy infections, limiting policy makers’ ability to optimise MDA programmes.

The main aim of my five year ERC starting grant SCHISTO_PERSIST (2016 to 2021) is to understand how we can reduce schistosomiasis transmission at a community level (Christina Faust) and how we can improve treatment success at an individual level (Rachel Francoeur and Lauren Carruthers). In close collaboration with the Vector Control Division, Ministry of Health, Uganda, we are evaluating new strategies and technologies to monitor the impact of MDA programmes, to identify threats to MDA effectiveness, and enhance control of schistosomiasis in sub-Saharan Africa. Specifically, our research focuses on five main questions, each with their own key objectives:

I. What is the best way to monitor schistosome infections and drug efficacy? 
a) Develop and optimise point-of-care DNA and antigen based diagnostic technology.
b) Utilise specific estimates of parasite egg, antigen and DNA clearance post treatment and evaluate each as markers of drug efficacy.
c) Differentiate surviving and newly-acquired worms using sibship analysis. 

2. Has drug resistance been selected for? 
a) Identify individuals not cured by repeated treatments using updated monitoring protocols.
b) Develop quantifiable in vitro drug-resistance test by adapting imaging technology.
c) Link in vitro and in vivo drug-resistance phenotypes to parasite genotypes.

3.  What is the potential for the spread of drug resistance? 
a) Establish data on parasite population structure and gene flow.
b) Parameterise local, national and international human migration models.
c) Characterise the potential risk of bi-annual treatment using mathematical models.

4. What other factors drive transmission?
a) Measure MDA coverage and associated infection prevalence.
b) Characterise the contributions of untreated groups to reinfection of treated children.
c) Characterise the contribution of individuals with high parasite intensities to reinfection of children.

5. What other factors affect parasite clearance?
a) Establish the influence of host factors such as immunology, pharmacokinetics, microbiome and co-infection on low cure rates and rapid reinfection.
b) Assess the level of S. mansoni hybrid parasites.

Our research enables a comparative assessment of how transmission is affected by untreated adults and pre-school children, individuals with heavy infections, coinfections, and drug coverage. Data will help elucidate optimal strategies to reduce transmission hotspots. Out results will help improve monitoring protocols and inform policy makers on how best to treat schistosomiasis. And our findings may be transferable across a range of MDA controlled diseases.

A University of Glasgow Lord Kelvin Adam Smith PhD student Suzan Trienekens, works on an interdisciplinary project that overlaps between this ERC SCHISTO_PERSIST project and our MRC GCRF anthropology and economics project. Suzan is using rapid ethnographic appraisals and other field sociology techniques to understand where children who are either not infected, or who are rapidly reinfected post treatment contact the water. Suzan will then collect snails from these areas and shed them for S. mansoni cercariae. She will compare the genotypes of these cercariae to miracidia characterised in SCHISTO_PERSIST to understand which parts of the community are driving reinfection in these water bodies.