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Background: Reliance on praziquantel for the 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 potential 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, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma 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), 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 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment., Results: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the 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%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported., Conclusions: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes., (© 2024. The Author(s).)

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.

Background: Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya., Methods: The SCHISTOACT study is an open-label, head-to-head, five-arm, proof-of-concept, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-aged children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine, or artesunate-amodiaquine, or artesunate plus mefloquine, or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at - 10 for the risk difference in cure rates between praziquantel and the combined treatment., Discussion: This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis and to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases., Trial Registration: Pan-African Clinical Trials Registry PACTR202001919442161 . Retrospectively registered on 6 January 2020., (© 2023. The Author(s).)

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., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Background: Artemether/lumefantrine (AL) has been adopted as the treatment of choice for uncomplicated malaria in Kenya and other countries in the region. Six-dose artemether/lumefantrine tablets are highly effective and safe for the treatment of infants and children weighing between five and 25 kg with uncomplicated Plasmodium falciparum malaria. However, oral paediatric formulations are urgently needed, as the tablets are difficult to administer to young children, who cannot swallow whole tablets or tolerate the bitter taste of the crushed tablets., Methods: A randomized, controlled, open-label trial was conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6-59 months, treated over three days with either six-dose of artemether/lumefantrine tablets (Coartem) or three-dose of artemether/lumefantrine suspension (Co-artesiane) for uncomplicated falciparum malaria in western Kenya. The children were followed-up with clinical, parasitological and haematological evaluations over 28 days., Results: Ninety three percent (124/133) and 90% (121/134) children in the AL tablets and AL suspension arms respectively completed followed up. A per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0% at Day 28 in the AL tablets group and 93.4% in the AL suspension group, p = 0.40. Both drugs effectively cleared gametocytes and were well tolerated, with no difference in the overall incidence of adverse events., Conclusion: The once daily three-dose of artemether-lumefantrine suspension (Co-artesiane(R)) was not superior to six-dose artemether-lumefantrine tablets (Coartem) for the treatment of uncomplicated malaria in children below five years of age in western Kenya.

Drug resistance in Plasmodium falciparum is a major obstacle to malaria control. Artemisinin-based combination therapy (ACT) is being advocated to improve treatment efficacy and to delay development of resistance. Here we summarise the available data on the efficacy of amodiaquine plus sulfadoxine/pyrimethamine (AQ+SP) versus ACTs in the treatment of uncomplicated malaria in sub-Saharan Africa. We searched for randomised trials in which patients with uncomplicated malaria treated with AQ+SP were compared with those treated with either amodiaquine plus artesunate (AQ+AS), artesunate plus sulfadoxine/pyrimethamine (AS+SP) or artemether/lumefantrine (AL). Medline, EMBASE, Cochrane Central Register of Controlled Trials and reference lists up to July 2005 were searched. Two reviewers independently extracted the data. The primary outcome measure was treatment failure by Day 28. Outcome measures were combined using a random effects model. Seven randomised trials of 4472 children were included. Trial quality was generally high. Treatment failure of AQ+SP was significantly reduced compared with AS+SP (relative risk (RR)=0.56, 95% CI 0.42-0.75), but increased compared with AL (RR=2.80, 95% CI 2.32-3.39). The overall failure rate of AQ+SP was similar compared with AQ+AS (RR=1.12, 95% CI 0.81-1.54), but there was significant heterogeneity of results across the studies. All the treatment regimens were safe and well tolerated. AQ+SP should be considered in some settings before the full implementation of an ACT.

Plasmodium falciparum has developed resistance to almost all routinely used antimalarial drugs. Sulfadoxine-pyrimethamine (SP) has replaced chloroquine as first-line treatment of uncomplicated malaria infection in Kenya but resistance to SP is already reported. The addition of artemisinin derivatives to SP may delay the development of drug resistance, improve cure rates, and reduce transmission. The efficacy and safety of artesunate plus SP in the treatment of uncomplicated P. falciparum malaria was evaluated in a randomized trial of 600 children at Siaya District Hospital, western Kenya between October 1999 and March 2000. Children aged < 5 years were randomly assigned to receive SP alone (1.25 mg/kg based on pyrimethamine), or in combination with artesunate (4 mg/kg/d) for either 1 or 3 d. Parasitological failure by days 14 and 28 (polymerase chain reaction [PCR]-corrected for new infections) were the primary endpoints. Treatment failure rates by day 14 were 25.5% in the SP alone group, 16.2% (risk difference [delta]-9.3%, 95% CI -17.3 to -1.2%, P= 0.027) in the 1-dose artesunate group, and 9.4% (delta-16.2%, 95% CI -23.6 to -8.7%, P< 0.001) in the 3-dose artesunate group. Corresponding rates by day 28 were 46.0% in the SP alone group, 38.2% (delta-7.8%, 95% CI -17.7 to 2.1%, P= 0.16) in the 1-dose artesunate group, and 26.0% (delta-20.0%, 95% CI -29.4 to -10.6%, P < 0.001) in the 3-dose artesunate group. The artesunate and SP combination was well tolerated. There were no serious drug-related adverse events. Parasite clearance and gametocyte carriage were reduced significantly in both combination groups compared with SP alone. Three days of artesunate were required to reduce significantly the risk of treatment failure by day 28. However, the high background rate of parasitological failure with SP may make this combination unsuitable for widespread use in Kenya.