Stage specific immune responses to schistosomes may explain conflicting results in malaria-schistosome coinfection studies

Malaria and schistosomiasis are two of the most clinically important human parasitic diseases in terms of morbidity and mortality, collectively causing approximately 800,000 deaths annually. Coinfection with their causative parasites, <i>Plasmodium</i> spp. and <i>Schistosoma</i> spp., is common, particularly in sub-Saharan Africa. These parasites may interact with each other via their effects on the host immune system, but studies to date report conflicting consequences of such interactions, some suggesting that schistosomes are associated with reduced parasitaemia in malaria infection while others report increased parasitaemia. Schistosomes stimulate different immune components in early versus late infection. Using agent-based modelling we explore whether stage of infection could be a factor explaining the conflicting coinfection outcomes. Effects of schistosomes on blood stage malaria were modelled by adjusting the immune components within the model according to the response provoked by each schistosome stage. We find the dynamics of malaria infections are greatly influenced by the stage of schistosomes, with acute and chronic schistosome infections having opposite effects on both peak infected erythrocyte counts and duration. Our findings offer a possible explanation for the apparent contradictions between studies and highlight the importance of considering the stage of schistosome infection when exploring the relationship between these two parasites.