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

## TL;DR

This study explores how schistosomiasis infection and praziquantel treatment affect symptoms and side effects in Ugandan children, finding no direct link between infection intensity and treatment outcomes.

## Contribution

The study reveals non-linear associations between infection intensity and symptoms or side effects, and shows no link between side effects and treatment efficacy.

## Key findings

- Pre-treatment symptoms and post-treatment side effects are non-linearly associated with infection intensity.
- No relationship was found between infection status and symptoms or side effects.
- Side effects do not correlate with treatment efficacy or infection clearance.

## Abstract

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 may be associated with dying worms. Side effects have also been reported as a reason for reduced MDA uptake, potentially 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 help inform education campaigns to facilitate increased MDA uptake.

Using latent class analyses, Beta regression, and dose response curves, we analysed egg and antigen parasitological data alongside health and side-effects survey data pre- and post-praziquantel-treatment from two primary schools (Bugoto Lake View (LV) and Musubi Church of God (CoG)) in Schistosoma mansoni high endemicity Ugandan villages to understand whether pre-treatment 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.

At Bugoto LV: Abdominal pain, blood-in-stool, and itching/rash symptoms were non-linearly associated with infection intensity; Diarrhoea, headache and vomiting side effects were non-linearly associated with infection intensity. At Musubi CoG: Blood-in-stool, headache, and pain-when-urinating symptoms were non-linearly associated with infection intensity; Abdominal pain, diarrhoea, and vomiting side effects were non-linearly associated with infection intensity. There was no relationship between infection status (infected/ uninfected) and symptoms or side effects at either school. No association was found between infection clearance and the presence of side effects at either school.

We show no evidence that being infected predisposes someone to side effects, nor that side effects are related to treatment efficacy. Relationships between pre-treatment infection intensity and pre-treatment symptoms or post-treatment side effects varied by school suggesting unmeasured factors such as co-infections or other health conditions could impact symptom and side effect reporting.

Schistosomiasis is a neglected tropical disease, widely treated by mass drug administration with praziquantel, but side effects often occur, and are also reported as a reason for refusing treatment. This study examined the impact of praziquantel treatment for intestinal schistosomiasis at two schools in Uganda, focusing on the relationships between pre-treatment infection intensity, pre-treatment symptoms, post-treatment side effects, and treatment efficacy. Our analyses showed that relationships between symptoms or side effects and infection intensity are not linear, and were most reported in those who did not have the highest infection intensities. The symptoms and side effects 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. Our findings highlight the complex nature of praziquantel induced side effects. Further studies are needed to understand how and why symptoms and/or side effects vary, even between demographically and geographically similar communities as well as across individuals. These insights could guide the development of health messaging, which may improve treatment uptake, therefore improving overall coverage of mass drug administration programs, which is vital to achieving the World Health Organization’s 2030 goal for schistosomiasis, of elimination as a public health problem.