title: Praziquantel, mefloquine-praziquantel, and mefloquine-artesunate-praziquantel against Schistosoma haematobium: a randomized, exploratory, open-label trial.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
authors.affiliation: Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire; Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire.
authors.forename: Kigbafori D
authors.initials: KD
authors.lastname: Silué
authors.affiliation: Hôpital Général de Taabo, Taabo Cité, Côte d'Ivoire.
authors.forename: Lukas K
authors.initials: LK
authors.lastname: Adiossan
authors.affiliation: Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire.
authors.forename: Nicaise A
authors.initials: NA
authors.lastname: N'Guessan
authors.affiliation: Institut National de la Santé Publique, Abidjan, Côte d'Ivoire.
authors.forename: N'Chou
authors.initials: N
authors.lastname: Monsan
authors.affiliation: University of Basel, Basel, Switzerland; Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Utzinger
authors.affiliation: Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire; Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire.
authors.forename: Eliézer K
authors.initials: EK
authors.lastname: N'Goran
mesh_terms: D000293:Adolescent; D000818:Animals; D000871:Anthelmintics / Q000009:adverse effects / Q000627:therapeutic use; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use; D000077332:Artesunate; D002648:Child; D007560:Cote d'Ivoire / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D015767:Mefloquine / Q000009:adverse effects / Q000627:therapeutic use; D011223:Praziquantel / Q000009:adverse effects / Q000627:therapeutic use; D012548:Schistosoma haematobium; D012553:Schistosomiasis haematobia / Q000188:drug therapy / Q000453:epidemiology
chemical_list: D000871:Anthelmintics; D037621:Artemisinins; D000077332:Artesunate; D011223:Praziquantel; D015767:Mefloquine