Articles www.thelancet.com/infection Vol 10 September 2010 603 Efficacy of artesunate with sulfalene plus pyrimethamine versus praziquantel for treatment of Schistosoma mansoni in Kenyan children: an open-label randomised controlled trial Charles O Obonyo, Erick M O Muok, Pauline N M Mwinzi Summary Background Schistosomiasis is an important parasitic disease in Kenya. Decreasing susceptibility of schistosomes to praziquantel, the major drug used to reduce disease morbidity, has made assessment of new antischistosomal drugs a priority. We aimed to assess the safety and efficacy of an artesunate-based combination drug in the treatment of schistosomiasis. Methods In this open-label randomised trial in Rarieda district of western Kenya, we enrolled school children (aged 6–15 years) who had Schistosoma mansoni infection according to duplicate Kato-Katz thick smears from a stool sample. Computer-generated block randomisation was used to assign children (1:1) to receive artesunate (100 mg) with sulfalene (also known as sulfamethoxypyrazine; 250 mg) plus pyrimethamine (12·5 mg) as one dose every 24 h for 3 days or one dose of praziquantel (40 mg/kg per day). The primary efficacy endpoint was the number of participants cured 28 days after treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01054651. Results Between October and December, 2009, 212 children were enrolled and assigned to receive artesunate with sulfalene plus pyrimethamine (n=106) or praziquantel (n=106). 69 patients (65%) were cured in the praziquantel treatment group compared with 15 (14%) in the artesunate with sulfalene plus pyrimethamine treatment group (p<0·0001). Adverse events were less common in patients taking artesunate with sulfalene plus pyrimethamine than in those taking praziquantel (22% [n=23] vs 49% [n=52], p<0·0001), and no drug-related serious adverse events occurred. Interpretation The standard treatment with praziquantel is more effective than artesunate with sulfalene plus pyrimethamine in the treatment of children with S mansoni infection in western Kenya. Whether artemisinin-based combination therapy has a role in the treatment of schistosomiasis is unclear. Funding Dafra Pharma, Belgium. Introduction Human schistosomiasis is a chronic debilitating disease caused by trematode worms of the genus Schistosoma. There are five species of schistosomes that can infect man, but Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum are the most important. Schistosomiasis is also one of the most prevalent parasitic infections in sub-Saharan Africa, where it is exceeded in prevalence only by malaria. An estimated 779 million people are at risk worldwide, and 200 million people are infected, of whom 120 million are symptomatic and 20 million have severe disease. 1–4 About 85% of people infected with schistosomiasis live in sub-Saharan Africa, where S mansoni and S haematobium are endemic. 4,5 In western Kenya more than 90% of infections are due to S mansoni, which is the focus of this report. 6 In the absence of a vaccine, the global control strategy for schistosomiasis is to reduce morbidity by use of chemotherapy. Praziquantel is the drug of choice for treatment of all five species of human schistosomiasis, it can be given as a single dose and is affordable, safe, and effective. Praziquantel is effective against invasive stages and adult worms, but is ineffective against the young developing stages of the parasite (schistosomules). 7,8 Evidence from laboratory studies and field trials shows reduced susceptibility of schistosomes to praziquantel, usually manifesting as low rates of cure and egg reduction. 9–11 Such findings have raised concerns over the possible emergence of drug resistance or increased parasite tolerance to praziquantel. 12–14 Together with the danger of reliance on one drug for treatment and control, these results have prompted the scientific community to focus on the development of new drugs to replace praziquantel. Potential alternatives to praziquantel are scarce. The artemisinin derivatives artesunate and artemether are promising candidates for treatment and chemo- prophylaxis of schistosomiasis. 15,16 This class of drugs is the most potent for treatment of malaria, for which they are used in combination with another drug with a different mechanism of action to delay or prevent the development of drug resistance. Artemisinins have antischistosomal activity in vitro and in vivo. 17 Unlike praziquantel, they are specifically effective against young developing forms of the parasite. 7,8 Few trials have Lancet Infect Dis 2010; 10: 603–11 Published Online August 11, 2010 DOI:10.1016/S1473- 3099(10)70161-4 See Reflection and Reaction page 579 Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya (C O Obonyo PhD, E M O Muok MSc, P N M Mwinzi PhD) Correspondence to: Dr Charles O Obonyo, Centre for Global Health Research, Kenya Medical Research Institute, PO Box 1578-40100, Kisumu, Kenya cobonyo65@yahoo.com