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Efficacy of praziquantel in the treatment of Schistosoma haematobium infection among school-age children in rural communities of Abeokuta, Nigeria.

ABSTRACT:

Background

Chemotherapy with praziquantel (PZQ) has been the cornerstone of schistosomiasis control over the last two decades. Being the only available drug for the treatment of over 200 million people worldwide, continuous monitoring of PZQ efficacy under the pressure of widespread use is therefore advocated.

Methods

The efficacy of taking two doses of oral PZQ for the treatment of Schistosoma haematobium was examined among school children in Nigeria. Urine specimens were collected from 350 school children and examined using the filtration technique. Blood was collected for packed cell volume (PCV) estimation, and the weight and height of each child were estimated. S. haematobium egg positive pupils were treated with two oral doses of PZQ at 40 mg/kg with a four-week interval in between. Drug efficacy was determined based on the egg reduction rate (ERR).

Results

Among 350 school children, 245 (70.0%) - of which 132 were males and 113 were females, with an age range of 4 to 15 years - were diagnosed with S. haematobium. All the 245 infected children received a single oral dose of 40 mg/kg PZQ twice with a four-week interval in between and were followed up for 12 weeks. At four, eight and twelve weeks post treatment, the ERR was 57.1%, 77.6% and 100%, respectively. The ERR was significantly higher among the children with a light infection compared to those with a heavy infection. One hundred and twenty-one children were egg negative at four weeks post treatment, among which 1 (6.3) and 120 (52.4%) had heavy and light infections, respectively. Following the second round of treatment, the cure rate at eight weeks and twelve weeks was 85.3% and 100%, respectively.

Conclusion

This study demonstrated the efficacy of taking two doses of oral PZQ for the treatment of urinary schistosomiasis among school children in Nigeria.

SUBMITTER: Ojurongbe O

PROVIDER: S-EPMC4161270 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Project description:BackgroundTreatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations.MethodologyWe comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21-22 and 78-79 after the first dosing.Principal findingsSixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21-22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11-55%), 29% (95% CI 8-50%), and 26% (95% CI 5-48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild.Conclusions/significanceThe addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis.

Project description: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 .

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