Identifying shared and parasite-specific determinants of Plasmodium falciparum and Schistosoma mansoni co-infection in a large-scale community-based study in rural Uganda

Malaria and schistosomiasis are co-endemic across much of sub-Saharan Africa, yet it remains unclear whether co-infections reflect shared risk factors, unexplained biological determinants, or chance co-occurrence. We analysed data collected at recruitment from 4290 individuals aged 5-90 years across 52 villages in rural Uganda within the SchistoTrack cohort. A bivariate copula model was developed to separate shared and disease-specific associations from residual dependence. Prevalence was 41.47% for Schistosoma mansoni , 41.19% for Plasmodium falciparum , and 18.51% for co-infection. Prevalence overlapped in school-aged children with co-infection prevalence peaking at 13 years. Greater distance to a government health centre was the strongest shared determinant, apart from age, male gender and living in western districts, increasing the risk of both. Local water ecology influenced each pathogen in opposing directions. Fishing was associated with higher S. mansoni and co-infection risks, but not P. falciparum risk. A modelled scenario combining household drinking-water treatment, handwashing facilities and protected water sources with cessation of freshwater contact reduced co-infection prevalence by 32%. Our findings support integrated control around shared demographics and limited healthcare access and household water infrastructure, while highlighting the need for non-integrated approaches for ecological interventions aiming to reduce parasite-specific transmission determinants.