Evidence suggests that artemether could have a major impact on the control of schistosomiasis. Since the early 1990s, evidence has been accumulating to support the prophylactic use of the artemesinins (artesunate and artemether) against Schistosoma japonicum infections. In addition to their well-known effect against the malaria parasite, these drugs also kill juvenile (schistosomula) forms of schistosomes. The artemisinins have now been shown to be effective against S. mansoni in animals and humans (1-3) while laboratory work on S. haematobium has been completed and field studies are under way with support from The WHO/World Bank/UNDP Special Programme for Research and Training in Tropical Diseases. Since these species are responsible for the majority of schistosome infections and are predominant in Africa, the outcome could be a major impact on control of schistosomiasis.
In a study on the use of artemether in S. mansoni infections in hamsters and mice, very few animals developed schistosomiasis when treated during the first month after infection and the parasite was particularly susceptible between weeks 3 and 4 (2). Single treatment with artemether gave cure rates of up to 82%, while follow-up therapy raised this to almost 100%. In animals with repeated infection, representing more closely the situation in nature, there was almost complete protection. Previous studies using S. mansoni had shown no effect of artemether, but had concentrated on the adult parasite, not the schistosomula. A clinical trial in Côte d'Ivoire has confirmed this potential of artemether to significantly reduce S. mansoni infection (3).
Artemether is already in use as an antimalarial and has a good safety profile. Praziquantel is a drug that has been used against schistosomiasis for more than two decades. It is safe and effective but has to be given repeatedly due to rapid reinfection. Combined treatment with the two drugs has been studied in rabbits infected with S. japonicum parasites at different developmental stages, representing the natural situation in areas where infection occurs throughout the year. Using this animal model, combined treatment significantly increased the single effects of the individual drugs (4).
Praziquantel and artemether affect schistosomes at different developmental stages and work surprisingly well together in this respect. Praziquantel affects the adult parasites, but also the very young stage during the first day in the host: times at which artemether has no effect. Conversely, artemether affects the juvenile stages except immediately after infection, thereby blocking the development of the adult stages.
Whether the two drugs can actually be administered at the same time and whether there is any pharmacological interaction remains to be investigated. Since artemether blocks the development of adult worms, even a limited period of treatment with this drug could theoretically eliminate parasite transmission in certain areas. Praziquantel on the other hand, cannot stop the infection, but remains the cornerstone of control since it retards the development of morbidity. The different species of parasite are sensitive to artemether for slightly different lengths of time. S. japonicum is susceptible up to 21 days of age, while S. mansoni responds to the drug for up to 42 days, and S. haematobium, due to the longer time it takes to develop into the adult, has an even longer period of sensitivity.
In areas that are endemic for both malaria and schistosomiasis, the use of artemether is precluded because of the possibility that its regular use might contribute to the development of resistance of the malaria parasite. On the other hand, the drug could safely be recommended for use in schistosomiasis in areas where there is no regular malaria transmission (e.g. in China, southern Brazil, countries north of the Sahara, parts of the Middle East). Of particular interest are those areas where human schistosomiasis has been very much reduced, but final eradication has proved difficult such as Saudi Arabia or Morocco and where artemether could contribute to breaking its transmission. It could also play an important role in the control of schistosomiasis in Egypt.
1. de Clerq, D., Vercruyse, J., Verlé, P. et al. Efficacy of artesunate against Schistosoma mansoni infections in Richard Toll, Senegal. Transactions of the Royal Society of Tropical Medicine and Hygiene, 94: 90-91 (2000).
2. Shuhua, X., Chollet, J., Weiss, N.A. et al. Preventive effect of artemether in experimental animals infected with Shistosoma mansoni. Parasitology International, 49: 19-24 (2000).
3. Utzinger, J., N'Goran, E.K., N'Dri, A. et al. Oral artemether for prevention of Schistosoma mansoni infection: randomized controlled trial. Lancet, 355: 1320-1325 (2000).
4. Shuhua, X., Jiqing, Y., Jinying, M. et al. Effect of praziquantel together with artemether on Shistosoma japonicum parasites of different ages in rabbits. Parasitology International, 49: 25-30 (2000).