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.
Praziquantel is the current drug of choice for the control of schistosome-attributable morbidity and is likely to remain so for several years. However, as there is concern that schistosomes might develop resistance to the drug, the monitoring of praziquantel's efficacy in different epidemiological settings is recommended. Here, the results of an innovative study of the drug's effectiveness, in an area in Côte d'Ivoire that is highly endemic for Schistosoma haematobium, are reported. Each of the subjects (354 schoolchildren aged 5-15 years) was given two oral doses of praziquantel (each of 40 mg/kg) 4 weeks apart. The numbers of schistosome eggs in urine samples collected over several consecutive days prior to the first and after the second treatment were then determined. High cure and egg reduction 'rates', of 93.0% and 96.6%, respectively, were found. Although mild and transient side-effects were frequently observed after the first treatments, no severe systemic complaints were recorded. When the 20 children who remained egg-positive after the second dose were each given a third dose of praziquantel, 16 (80%) of them responded and became egg-negative. Unfortunately, the schistosome strains infecting the remaining four children could not be investigated in detailed laboratory studies, because of the failure of eggs to hatch. There were therefore no unambiguous signs of resistance to praziquantel in this epidemiological setting. The benefits and disadvantages, compared with single-dose treatments, of administering praziquantel twice within a few weeks are discussed. It is anticipated that this approach might prove efficacious in areas of high infection intensity. The integration of such pharmaceutical measures with other readily available control tools is likely to mitigate the current, intolerable burden of schistosomiasis.
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