The associations betweenSchistosoma mansoniinfection, pre-treatment symptoms, praziquantel side effects, and treatment efficacy in Ugandan school-aged children

Background Over 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.

Using 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 Findings At 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.

We 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 summary Schistosomiasis 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 Organization’s 2030 elimination goals. Competing Interest Statement The authors have declared no competing interest. Funding Statement Field work was funded by the Schistosomiasis Control Initiative. During the field study, PHLL was funded by a Medical Research Council PhD studentship (under the supervision of JPW). JPW was funded by a Royal Society University Research Fellowship. PHLL is now funded by ERC Consolidator Grant EPX0270821. JC is funded by NERC NE/W003333/1. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted as part of research conducted by the Schistosomiasis Control Initiative (now Unlimit Health), Imperial College London and the Vector Control Division of the Ministry of Health, Uganda. Protocols were approved by the Uganda National Council for Science and Technology (Memorandum of Understanding: sections 1.4, 1.5, 1.6) and the Imperial College Research Ethics Committee (EC NO: 03.36. R&D No: 03/SB/033E). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data and anonymised code are available at https://github.com/iamjessclark/symptomsSideEffects.git