Factors driving co-occurrence of Schistosoma mansoni and S. haematobium at the micro-geographical level

Brief introduction: Several studies have shown that the two major human Schistosoma species, Schistosoma mansoni and Schistosoma haematobium, co-exist in the same individuals at the micro-geographical level. However, the drivers of this co-occurrence are still largely unknown. Here, we studied whether coexposure and/or host immune responses might explain this phenomenon. Methods and materials: A multidisciplinary study was conducted in two neighboring rural communities in northern Senegal, where S. mansoni and S. haematobium are co-endemic (n=857). Kato-Katz and urine filtration were used for microscopic detection of the respective Schistosoma species. Households were located using handheld differential global positioning system in the largest community (n=599), and the Kulldorff's scan statistic was used to detect spatial clusters of infection. Schistosoma-specific cytokine responses (IL-10, IL-5, IFN-γ, TNF-a, and IL-2) were assessed in 72h whole blood culture supernatants (n=200), and analyzed by the multivariate technique nonmetric multidimensional scaling (nMDS). Results: Classical epidemiological analyses showed that the two parasites were more likely to co-occur in the same individuals (p<0.001). Moreover, co-infected subjects had significantly higher infection levels than their mono-infected counterparts (p<0.001; adjusted for age and gender). In contrast, micro-geographical analyses revealed a very focal spatial distribution with S. mansoni clustering in one (p=0.002) and S. haematobium infections in another section (p=0.023) of the community. nMDS analysis of the cytokine data indicated that the characteristic modified Th2 response was most pronounced in co-infected subjects. Conclusions: The divergent geographical distribution of S. mansoni and S. haematobium in this community could not explain why the two infections cluster in the same individuals. This implies that co-infection is not driven by coexposure, but by within-host interactions. Cytokine profiles suggested that co-occurrence of the two species may be due to host immunological factors and/or parasite-induced immunomodulation. However, other factors may also play a role.