Praziquantel, Mefloquine-Praziquantel, and Mefloquine-Artesunate-Praziquantel against Schistosoma haematobium: A Randomized, Exploratory, Open-Label Trial

Jennifer Keiser, Kigbafori D Silué, Lukas K Adiossan, Nicaise A N'Guessan, N'Chou Monsan, Jürg Utzinger and Eliézer K N'Goran

PLOS Neglected Tropical Diseases, 2014, vol. 8, issue 7, 1-10

Abstract: Background: Treatment 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. Methodology: We 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 Findings: Sixty-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/Significance: The 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. Author Summary: The antimalarial drug mefloquine shows activity against blood flukes that cause the disease schistosomiasis. In animal studies it has been found that a mefloquine-praziquantel combination kills blood flukes more effectively than praziquantel alone. Combining praziquantel with another drug might therefore increase efficacy, broaden the spectrum of activity, and delay the development of drug resistance. We designed a study in Ivorian school children to assess the efficacy and tolerability of mefloquine and mefloquine-artesunate combined with praziquantel against the blood fluke Schistosoma haematobium. The administration of the antimalarials and praziquantel was spaced by a day. Treatment outcomes were assessed twice, on days 21–22 and 78–79 after the first dosing to determine the effect against adult and juvenile S. haematobium, respectively. At both follow-ups, high reduction in the intensity of infection (egg reduction rates of 94–96%), but low cure rates (26–33%) were observed in the three treatment groups. Adverse events were common, particularly in children treated with mefloquine-praziquantel and mefloquine-artesunate-praziquantel. Our study suggests that the addition of mefloquine and mefloquine-artesunate to praziquantel has no benefit in the treatment of chronic S. haematobium infection. However, further investigations are warranted to evaluate the effect of combination therapy on juvenile flukes and longer-term morbidity profiles.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pntd00:0002975

DOI: 10.1371/journal.pntd.0002975

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