Randomized, Double-Blind, Placebo-Controlled Trial of Oral Artemether for the Prevention of Patent Schistosoma Haematobium Infections

Abstract

Artemether is an efficacious antimalarial drug that also displays antischistosomal properties. Laboratory studies have found that artemether curtails the development of adult worms of Schistosoma japonicum, S. mansoni, and S. haematobium, and thus prevents morbidity. These findings have been confirmed in clinical trials for the former two parasites; administered orally once every 2-3 weeks, artemether significantly reduced the incidence and intensity of patent infections. Here, we present the first randomized, double-blind, placebo-controlled trial of artemether against S. haematobium, done in a highly endemic area of Côte d'Ivoire. Urine specimens from 440 schoolchildren were examined over 4 consecutive days, followed by two systematic praziquantel treatments 4 weeks apart. S. haematobium-negative children were randomized to receive 6 mg/kg artemether (N ‫ס‬ 161) or placebo (N ‫ס‬ 161). Medication was administered orally for a total of six doses once every 4 weeks. Adverse events were assessed 72 hours after medication, and perceived illness episodes were monitored throughout the study period. Incidence and intensity of S. haematobium infections, and microhematuria and macrohematuria were assessed 3 weeks after the final dosing. We also monitored malaria parasitemia and treated positive cases with sulfadoxine-pyrimethamine (SP). Oral artemether was well tolerated. The incidence of patent S. haematobium infections in artemether recipients was significantly lower than in placebo recipients (49% versus 65%, protective efficacy: 0.25, 95% CI: 0.08-0.38, P ‫ס‬ 0.007). The geometric mean infection intensity in the artemether group was less than half that of the placebo recipients (3.4 versus 7.4 eggs/10 mL urine, P < 0.001). Heavy S. haematobium infections, microhematuria and macrohematuria, and the incidence of malaria parasitemia were all significantly lower in artemether recipients. In conclusion, previous findings of efficacy of artemether against S. japonicum and S. mansoni were confirmed for S. haematobium, although the protective efficacy was considerably lower. These findings enlarge the scope and potential of artemether and further contribute to discussions of its role as an additional tool for integrated schistosomiasis control.

Acute schistosomiasis mansoni: revisited and reconsidered

“…After egg laying, the importance of lung involvement has been described by many authors in different countries (Sami 1951, Bogliolo 1964, Gelfand 1966, Rocha et al 1995a, Cooke et al 1999, N'Goran 2003. Bogliolo (1964), during autopsy of four patients who died during the acute phase of schistosomiasis, found a miliary distribution of eggs in the lungs of three and one had pleural effusion.…”

Combination Chemotherapy of Schistosomiasis in Laboratory Studies and Clinical Trials

“…Artemether was safe, showed no or only a few but transient side effects, and was efficacious in reducing the incidence and intensity of infection (50,67,79).…”

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

“…Administration of two courses of PZQ was advocated for such situations (Renganathan and Cioli, 1998) and this has resulted in higher cumulative cure rates (Picquet et al 1998 ;Utzinger et al 2000 a ;N'Goran et al 2003 ;Sacko et al see in this special issue).…”