Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial

Abstract

Abstract Background Reliance on praziquantel for treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis. Methods This was an open-label, randomized clinical trial with 426 school-age children (7–15 years old) diagnosed with S. mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg) or a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at six weeks post-treatment in the available case population. Adverse events were assessed within 3 hours after treatment. Results Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data was available for 398 children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%; egg reduction rates were 95.6%, 97.1%, and 97.7%. 71 (16.7%) children reported mild-intensity adverse events. No serious adverse events were reported. Combination therapy was associated with a significantly higher proportion of adverse events. Conclusion A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and the artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes. Clinical Trial Registration: Pan-African Clinical Trials Registry, PACTR202211501227743