Increasing evidence of drug resistance to praziquantel, the only drug treatment for schistosomiasis (also known as bilharzia), has made the assessment of new drugs a priority. An Article published Online First and in the September edition of The Lancet Infectious Diseases shows that standard treatment with praziquantel is significantly more effective than the antimalarial drug combination of artesunate with sulfalene plus pyrimethamine at curing children with Schistosoma mansoni, the most common cause of schistosomiasis infection in Kenya.

Schistosomiasis is one of the most common parasitic diseases in the world (second only to malaria) affecting 200 million people and causing severe disease in 20 million people. About 85% of people infected with schistosomiasis live in sub-Saharan Africa. There is growing evidence of drug resistance and increased parasitic tolerance to the conventional treatment of praziquantel. This one-drug strategy is risky and new drug treatments are urgently needed to minimise the chance of resistance. It has been suggested that artemisinin-based combination therapies (ACTs), used in the control of malaria, could be safe and effective in the treatment of schistosomiasis, but evidence is scarce.

To provide more evidence, Charles Obonyo and colleagues from the Kenya Medical Research Institute in Kenya conducted a trial to investigate the safety and efficacy of artesunate with sulfalene plus pyrimethamine (an effective antimalarial drug combination) versus praziquantel for the treatment of S mansoni in schoolchildren in western Kenya.

212 children (aged 6-15 years) were randomly assigned to receive artesunate (100mg) with sulfalene (250mg) plus pyrimethamine (12.5mg) as one dose every 24 hours for 3 days or one dose of praziquantel (40mg/kg), and followed up for 28 days.

After 28 days, 69 children (65%) were cured in the praziquantel group compared with 15 (14%) in the artesunate combination group.

Both treatments were generally well tolerated. However, adverse events were more than twice as common with praziquantel compared with the artesunate combination (22% vs 49%). The most common side effects were abdominal pain and headache in the praziquantel group, and abdominal pain, diarrhoea, and cough in the artesunate group.

These findings question whether ACTs have any role in the control of schistosomiasis, and the authors conclude: "The benefit of ACTs combined with praziquantel (sequentially or simultaneously) for schistosomiasis is unknown, but this combination could target different developmental stages of the worm*. This approach needs efficacy, safety, and economic assessment in future studies."

In a Comment, Jürg Utzinger and Jennifer Keiser from the Swiss Tropical and Public Health Institute, Basel, Switzerland, say that despite the inferiority of ACTs to praziquantel they might still have some role against schistosomiasis: "First and foremost, the ACTs must be reserved for the prevention and control of Malaria...Second, in regions where both malaria and schistosomiasis coexist (eg, over large parts of sub-Saharan Africa) and where the efficacy and safety of new ACTs are being investigated against malaria, investigators should specifically look for ancillary benefits against schistosomiasis...Third, the INDEPTH network, consisting of large rural and urban populations under longitudinal health and demographic surveillance, offers a unique platform to monitor malaria incidence and changing patterns of schistosomiasis as a function of first-line and second-line ACTs and attained coverage in specific settings."

* Praziquantel is most effective against adult worms, whereas artemisinins are most effective on the juvenile stages of the worm. Therefore, the authors suggest that when combined the two drugs could have

"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
The Lancet Infectious Diseases August 11, 2010. DOI:10.1016/S1473-3099(10)70161-4

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