BackgroundSeasonal malaria chemoprevention (SMC) is recommended in the Sahel region of Africa for children under 5 years of age, for up to 4 months of the year. It may be appropriate to include older children, and to provide protection for more than 4 months. We evaluated the effectiveness of SMC using sulfadoxine-pyrimethamine plus amodiaquine given over 5 months to children under 10 years of age in Saraya district in south-east Senegal in 2011.Methods and findingsTwenty-four villages, including 2,301 children aged 3–59 months and 2,245 aged 5–9 years, were randomised to receive SMC with community case management (CCM) (SMC villages) or CCM alone (control villages). In all villages, community health workers (CHWs) were trained to treat malaria cases with artemisinin combination therapy after testing with a rapid diagnostic test (RDT). In SMC villages, CHWs administered SMC to children aged 3 months to 9 years once a month for 5 months. The study was conducted from 27 July to 31 December 2011. The primary outcome was malaria (fever or history of fever with a positive RDT). The prevalence of anaemia and parasitaemia was measured in a survey at the end of the transmission season. Molecular markers associated with resistance to SMC drugs were analysed in samples from incident malaria cases and from children with parasitaemia in the survey. SMC was well tolerated with no serious adverse reactions. There were 1,472 RDT-confirmed malaria cases in the control villages and 270 in the SMC villages. Among children under 5 years of age, the rate difference was 110.8/1,000/month (95% CI 64.7, 156.8; p < 0.001) and among children 5–9 years of age, 101.3/1,000/month (95% CI 66.7, 136.0; p < 0.001). The mean haemoglobin concentration at the end of the transmission season was higher in SMC than control villages, by 6.5 g/l (95% CI 2.0, 11; p = 0.007) among children under 5 years of age, and by 5.2 g/l (95% CI 0.4, 9.9; p = 0.035) among children 5–9 years of age. The prevalence of parasitaemia was 18% in children under 5 years of age and 25% in children 5–9 years of age in the control villages, and 5.7% and 5.8%, respectively, in these 2 age groups in the SMC villages, with prevalence differences of 12.5% (95% CI 6.8%, 18.2%; p < 0.001) in children under 5 years of age and 19.3% (95% CI 8.3%, 30.2%; p < 0.001) in children 5–9 years of age. The pfdhps-540E mutation associated with clinical resistance to sulfadoxine-pyrimethamine was found in 0.8% of samples from malaria cases but not in the final survey. Twelve children died in the control group and 14 in the SMC group, a rate difference of 0.096/1,000 child-months (95% CI 0.99, 1.18; p = 0.895). Limitations of this study include that we were not able to obtain blood smears for microscopy for all suspected malaria cases, such that we had to rely on RDTs for confirmation, which may have included false positives.ConclusionsIn this study SMC for children under 10 years of age given over 5 months was feasible, well tolerated, and effective in preventing malaria episodes, and reduced th...

BackgroundArtesunate/sulphadoxine-pyrimethamine (AS/SP) has been the first-line treatment for falciparum malaria in Sudan since 2004. The impact of this combination on anti-malarial resistance-associated molecular markers has not been investigated. In this study, an evaluation of the efficacy and prevalence of drug resistance alleles (pfcrt, pfmdr1, pfdhfr and pfdhps) eight years after the adoption of AS/SP in eastern Sudan is reported.MethodsA 28-day follow-up efficacy trial of AS/SP was conducted in eastern Sudan during the 2012 transmission season. Blood smears were collected from patients on days 0, 1, 2, 3, 7, 14, 21 and 28. Blood spots on filter paper were obtained pre-treatment and on the day the patient was parasite positive by microscopy. Genotyping of alleles was performed by qPCR (pfcrt 72–76 and pfmdr1 copy number) and direct sequencing of pfmdr1, pfdhfr and pfdhps.ResultsSixty-three patients out of 68 (93%) completed the 28-day follow-up, adequate clinical, and parasitological response occurred in 90.5% and 85.3% of the patients in the per-protocol and intent-to-treat analyses, respectively. PCR corrected per-protocol efficacy was 93.7%. The enrolment prevalence of pfcrt-CVMNK was 30.2% and pfmdr1-N86 was 40.3%. The pfmdr1 haplotype NFD occurred in 32.8% of pre-treatment samples and was significantly higher than previous reports (Fisher’s exact p = 0.0001). The pfdhfr-51I/108N combination occurred in all sequenced isolates and 59R was observed in a single individual. pfdhps substitutions 436A, 437G, 540E, 581G and 613S were observed at 7.8, 77.3, 76.9%, 33.8% and 0.0%, respectively. Treatment failures were associated with the pfdhps haplotype SGEGA at these five codons (OR 7.3; 95% CI 0.65 - 368; p = 0.048).ConclusionThe decrease of CQR associated genotypes reflects the formal policy of complete removal of CQ in Sudan. However, the frequency of markers associated with SP failure is increasing in this study area and may be contributing to the treatment efficacy falling below 90%. Further monitoring of AS/SP efficacy and of post-treatment selection of pfdhfr and pfdhps alleles in vivo is required to inform future treatment guidelines.