Performance and Safety of Praziquantel for Treatment of Intestinal Schistosomiasis in Infants and Preschool Children

Abstract

In 2012 the WHO formally recognised that infants and preschool children are at significant risk of schistosomiasis and qualify for treatment with praziquantel (PZQ). Targeted surveys determining both the performance and safety of this drug are now needed in endemic areas. We have formally assessed parasitological cure and putative side-effects in a prospective cohort of Schistosoma mansoni-infected children (aged 5 months–7 years old) in lakeshore settings of Uganda. From a total of 369 children found to be egg-patent for intestinal schistosomiasis, 305 were followed-up three to four weeks after PZQ treatment and infection status re-assessed. Separately, a previously tested side-effect questionnaire was employed before and 24 hours after PZQ treatment to assess incidence and amelioration of symptoms in young children and their mothers. While the overall observed parasitological cure was 56.4%, a significant difference was found between a sub-set of children who had a history of multiple PZQ treatments (between one and four in an 18 month period), where cure rate was 41.7%, and those who had never received treatment (cure rate was 77·6%). PZQ proved to be safe, with only mild reported side effects which cleared within a month after treatment. Prevalence of reported symptoms was significantly lower in children than in mothers, and fewer side-effects were reported upon subsequent rounds of PZQ treatment. Our findings show that PZQ treatment of young children resulted in satisfactory cure rates, and marked reduction in egg-output, with only mild and transient reported side-effects. However, the cure rate is clearly lower in younger children and those with history of previous treatment. Cure rate, but not egg reduction rate, was also lower in children with heavier pre-intervention infection intensity. With chemotherapy now recommended as a long-term strategy for disease control in young children, research into optimising the periodicity of targeted treatment strategies is now crucial. Although there is now extensive evidence for infection in preschool-aged children, and even a change in WHO guidelines endorsing treatment of this young age class in endemic areas, very little work has been published on the performance of praziquantel in children below the age of six. Previous work on praziquantel performance in preschool aged children focused on Schistosoma haematobium infections (urogenital schistosomiasis), with few observational studies published for S. mansoni infections (intestinal schistosomiasis). With a formalised protocol, we show that delivery of praziquantel to preschool-aged children living in endemic areas is safe and efficacious. However, this work has also shed light on dynamics never previously explored. History of previous treatment and age below three years proved to be determining factors for the outcome of treatment. This work provides firm evidence that in an endemic population certain young individuals were simply not cured (no egg or antigen cessation) after standard doses of praziquantel. This potential for non-cure should not go overlooked since exposure to drug without cure (either due to parasite or human factors) can lead to emergence and spread of resistance to praziquantel. Bearing in mind that praziquantel is the only commercially available drug against schistosomiasis, we recommend further research to understand these dynamics.