Oral artemether for prevention of Schistosoma mansoni infection: randomised controlled trial.
BACKGROUND
Chemotherapy with praziquantel is the current strategy of choice to control schistosomiasis. However, in view of concern about praziquantel tolerance or resistance, new drugs are needed. Artemether, a derivative of the antimalarial drug artemisinin, kills immature schistosomes of Schistosoma japonicum, and reduces the incidence of infection in field trials. Laboratory studies have also showed activity by this drug against S. mansoni. We report a randomised double-blind placebo-controlled clinical trial of artemether to prevent S. mansoni infection.


METHODS
The trial was done in an area of western Côte d'Ivoire endemic for S. mansoni. 354 schoolchildren were enrolled. Stool specimens were screened over four consecutive days, followed by two mass treatments with praziquantel 4 weeks apart. All S. mansoni negative children were randomly assigned to placebo (n=151) or artemether 6 mg/kg (n=138) orally six times once every 3 weeks. Adverse events were assessed 24 h after treatment. Perceived illness episodes were recorded once a week by interviewing the children with a standardised questionnaire. 3 weeks after the final medication S. mansoni infections were assessed by screening stool samples. Blood samples were examined for Plasmodium falciparum before the first and after the last artemether treatment.


RESULTS
Oral artemether showed no adverse reactions. The group that received artemether had a significantly lower incidence of S. mansoni infection (31/128 versus 68/140, relative risk: 0.50 [95% CI 0.35-0.71], p=0.00006). The geometric mean egg output among positive children in the artemether group was significantly lower than in placebo recipients (19 vs 32 eggs/g stool, p=0.017). There was also a significant reduction in the prevalence of P. falciparum.


CONCLUSIONS
Oral artemether is safe and shows a prophylatic effect against S. mansoni. The use of artemether may be recommended in appropriated situations as an additional tool for more effective schistosomiasis control measures. However the application needs to be carefully assessed especially in view of the concern that it could select for resistant plasmodia.
Utzinger
J
J
Swiss Tropical Institute, Basel, Switzerland.
N'Goran
E K
EK
N'Dri
A
A
Lengeler
C
C
Xiao
S
S
Tanner
M
M
D000284:Administration, Oral; D000293:Adolescent; D000818:Animals; D000077549:Artemether; D037621:Artemisinins; D002648:Child; D007560:Cote d'Ivoire; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening; D010270:Parasite Egg Count; D012550:Schistosoma mansoni / Q000187:drug effects; D012555:Schistosomiasis mansoni / Q000517:prevention & control*; D012556:Schistosomicides / Q000008:administration & dosage* / Q000009:adverse effects; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000009:adverse effects
D037621:Artemisinins; D012556:Schistosomicides; D012717:Sesquiterpenes; D000077549:Artemether