1. Compare early-life immune responses to Sm exposure and infection between LA and LV and identify co-exposures that modulate Sm-specific immune responses and morbidity risk
2. Establish a platform for local genetic surveillance of schistosome parasites in Uganda and determine whether there is a parasite genetic basis to differences in clinical outcomes in LA and LV
3. Determine which population biological determinants of Biomphalaria spp. snails act as local epidemiological drivers of Sm, filtering its diversity within and between LA and LV ecosystems; and whether detection of environmental (e)DNA signatures from Biomphalaria and Sm can be used to better predict snail/parasite diversity at transmission sites and (re)infection risk within key demographic groups

We hypothesize that factors at each step of the parasite life cycle interact to determine morbidity in schistosomiasis; in particular, that contributors to greater disease severity in LA compared to LV include:

1. Differences in the human immune response to schistosomes established early in life: factors that govern these differences are likely to include intensity of parasite exposure and immune modulation by co-infections, microbiome, nutrition and lifestyle.
2. Differences in the population genetics of schistosome parasites (acting, for example, through differential expression of immunogenic or immunoregulatory antigens; or on susceptibility to praziquantel treatment).
3. Differences in snail species, frequency and location relative to human activity; and differences in snail susceptibility to schistosome infection and replication; differentially impacting intensity of human exposure.

We will use two study designs: (i) cohorts of pre-school-age children (PSAC) in LA and LV, to explore the early evolution of immune responses that may lead to severe morbidity and (ii) an adult case control study to identify chronic exposures associated with severe disease. We will also collect parasite and snail samples from both settings, and develop a specimen archive for future studies.

Since its establishment, the U-SMRC has made significant strides in strengthening scientific capacity and advancing schistosomiasis research in Uganda. Key activities include the development of skilled local researchers through PhD and early-career training programmes, the establishment and strengthening of laboratory infrastructure to support immunological and parasitological analysis, and notable progress in understanding host immune responses and patterns of parasite exposure. These efforts have positioned the Centre as a growing hub for multidisciplinary research and innovation in schistosomiasis control.

Our work is delivered through four interconnected research working groups, each contributing to advancing schistosomiasis research and control in Uganda:

• Snail Working Group – Focuses on the ecology and distribution of freshwater snails that transmit schistosomiasis, generating data to identify transmission hotspots and guide targeted control strategies.
• Immunology Working Group – Explores how the human immune system responds to schistosomiasis infection, generating insights to support vaccine development and improve understanding of disease progression.
• Epidemiology Working Group – Examines patterns and drivers of schistosomiasis in communities, identifying risk factors and evaluating interventions to inform public health strategies.
• Capacity Strengthening Working Group – Builds sustainable research capacity through training, mentorship, and support for early- and mid-career scientists, strengthening local leadership in schistosomiasis research.