The associations between Schistosoma mansoni infection, pre-treatment symptoms, praziquantel side effects, and treatment efficacy in Ugandan school-aged children

BackgroundOver 240 million people have schistosomiasis. Mass drug administration (MDA) with the anthelmintic praziquantel is the cornerstone of control. Treatment side effects are commonly observed and potentially associated with worms dying in heavily/infected people. However, side effects reportedly reduce MDA uptake, maybe resulting in those most in need refusing repeated treatment. An improved understanding of the association between side effects and infection intensity, pre-treatment health, and drug efficacy, may facilitate improved MDA uptake. MethodsUsing latent class analyses and GLMMs we analysed egg and antigen parasitological data and health and side-effects survey data pre- and post-treatment from two primary schools (Bugoto Lake View (LV) and Musubi Church of God (CoG)) in S. mansoni high endemicity Ugandan villages to understand whether infection status or intensity were related to 1) pre-treatment symptoms, 2) post-treatment side effects, and 3) whether parasite clearance after treatment was associated with side effects. Principal FindingsAt Bugoto LV, abdominal pain, blood-in-stool, and itching/rash were symptoms non-linearly related to pre-treatment infection intensity. Diarrhoea, headache and vomiting were side effects non-linearly associated with infection intensity. At Musubi CoG, blood-in-stool, headache, and pain-when-urinating were non-linearly related to pre-treatment infection intensity. Abdominal pain, diarrhoea, and vomiting were side-effects non-linearly associated with infection intensity. Infection status was not related to pre-treatment symptoms or post-treatment side effects at either school. At both schools, there was no association between infection clearance and side effects. ConclusionsWe show no evidence that being infected predisposes someone to side effects, nor that side effects are related to treatment efficacy. The variation between schools in relationships between infection intensity and symptoms or side effects suggest that co-infections and co-occurring sources of morbidity may impact which symptoms and side effects are reported, warranting further investigation, supporting informed discussions with communities. Author summarySchistosomiasis is a neglected tropical diseases, widely treated by mass drug administration with praziquantel, but side-effects often occur, and are also reported as a reason for low drug treatment uptake. This study examines the impact of praziquantel treatment for schistosomiasis at two schools in Uganda, focusing on the relationships between pre-treatment infection intensity, symptoms, side effects, and treatment effectiveness. Our analysis shows that relationships between symptoms or side effects and infection intensity are not linear, and often were most reported in those who did not have the highest infection intensities. However, the side effects and symptoms reported were not consistent across schools. Furthermore, the occurrence of side effects did not correlate with the probability of successful infection clearance, or with the probability of being infected pre-treatment. Despite some discomforts, praziquantel remains effective in treating schistosomiasis. Our findings highlight the complex nature of praziquantel induced side-effects. Further studies are needed to understand how and why pre-treatment symptoms and/or side effects vary even between demographicaly and geographically similar communities and individuals. This may improve community engagement, in turn improving participation in mass drug administration programs, which is vital to achieving the World Health Organizations 2030 elimination goals.