Efficacy and safety of ascending doses of praziquantel against Schistosoma haematobium infection in preschool-aged and school-aged children: a single-blind randomised controlled trial

Abstract

BackgroundDespite decades of experience with praziquantel treatment in school-aged children (SAC) and adults, we still face considerable knowledge gaps relevant to the successful treatment of preschool-aged children (PSAC). This study aimed to assess the efficacy and safety of escalating praziquantel dosages in PSAC infected with Schistosoma haematobium.MethodsWe conducted a randomised, dose-finding trial in PSAC (2–5 years) and as comparator a cohort of SAC (6–15 years) infected with S. haematobium in Côte d’Ivoire. A total of 186 PSAC and 195 SAC were randomly assigned to 20, 40 or 60 mg/kg praziquantel or placebo. The nature of the dose-response relationship in terms of cure rate (CR) was the primary objective. Egg reduction rate (ERR) and tolerability were secondary outcomes. CRs and ERRs were assessed using triplicate urine filtration over 3 consecutive days. Available-case analysis was performed including all participants with primary endpoint data.ResultsA total of 170 PSAC and 174 SAC received treatment. Almost 90% of PSAC and three quarters of SAC were lightly infected with S. haematobium. Follow-up data were available for 157 PSAC and 166 SAC. In PSAC, CRs of praziquantel were 85.7% (30/35), 78.0% (32/41) and 68.3% (28/41) at 20, 40 and 60 mg/kg and 47.5% (19/40) for placebo. In SAC, CRs were 10.8% for placebo (4/37), 55.6% for 20 mg/kg (25/45), 68.3% for 40 mg/kg (28/41) and 60.5% for 60 mg/kg (26/43). ERRs based on geometric means ranged between 96.5% (60 mg/kg) and 98.3% (20 mg/kg) in PSAC and between 97.6% (20 mg/kg and 60 mg/kg) and 98.6% (40 mg/kg) in SAC. Adverse events were mild and transient.ConclusionsPraziquantel revealed dose-independent efficacy against light infections of S. haematobium. Over the dose range tested, praziquantel displayed a ceiling effect with the highest response for 20 mg/kg in PSAC. In SAC maximum efficacy was obtained with 40 mg/kg praziquantel. Further investigations are required in children with moderate to heavy infections.Trial registrationThis trial is registered with International Standard Randomised Controlled Trial Number ISRCTN15280205.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1066-y) contains supplementary material, which is available to authorized users.

Mapping the Process and the Resources that are Needed to Implement A Praziquantel Mass Drug Administration Program for Children Aged Five Years Old and Below in Resource Limited Settings.

“…All the studies that we reviewed reported that praziquantel is e cacious against schistosomiasis in children under ve years. The lowest PZQ dose that was e cacious against schistosomiasis in this age group was 20 mg/kg [25,26]. All the studies reported on the PZQ dose of 40 mg/kg to treat schistosomiasis in this age group.…”

“…All the studies we reviewed reported PZQ to be safe for use to treat schistosomiasis in children aged ve years old and below. The highest safe dose of PZQ reported was 60 mg/kg [25,26]. All the studies reported that there were no serious adverse events reported after treating schistosomiasis in children aged ve years and below with PZQ doses of between 20 mg/kg to 60 mg/kg.…”

“…Bread and juice [13,25,[27][28][29]34], millet wafer [14] and porridge [14] were the food items that were used in the studies we reviewed. PZQ tablets were crushed with spoons [27] or pestle and mortar [25,26] to make them small enough for the children to take in. The studies used honey and sugar [31], juice and syrup avored water as sweeteners [13,25,[27][28][29]34] to mask the bitter taste of PZQ.…”

A prospective risk assessment of the implementation of a Schistosomiasis Preventive Mass Drug Administration for children aged five years and below in the uMkhanyakude District of KwaZulu-Natal.

“…This dosage is supported by studies that have shown than increasing the dosage to 60mg/kg does not significantly increase the efficacy of the drug [19,46]. Under dosing below 40mg/kg will reduce the efficacy of the drug and below 20mg/kg the efficacy of the drug can be entirely lost [19]. A PZQ overdose beyond 60mg/kg is unsafe for children aged below five [14].…”

“…WHO and studies on the safety and efficacy of PZQ in children aged below five recommend a PZQ dose of 40mg/kg [2]. This dosage is supported by studies that have shown than increasing the dosage to 60mg/kg does not significantly increase the efficacy of the drug [19,46]. Under dosing below 40mg/kg will reduce the efficacy of the drug and below 20mg/kg the efficacy of the drug can be entirely lost [19].…”