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BackgroundWHO recommended seasonal malaria chemoprevention (SMC) in 2012 for Sahel countries in Africa with the aim to reduce malaria among children under 5 years old by using sulphadoxine-pyrimethamine and amodiaquine (SP+AQ). This strategy was scaled up in Mali from 2012. The use of millions of doses of SP+AQ could generate potential Plasmodium falciparum resistance in mutant parasites. The aim of this study was to monitor the prevalence of Pfdhfr +Pfdhps+pfcrt +pfmdr1 mutations in parasites infecting the target population.MethodsTwo cross-sectional surveys were conducted before (August 2012, n=662) and after (June 2014, n=670) a pilot implementation of SMC in the health district of Koutiala. Children aged 3–59 months received 3 and 4 rounds of curative doses of SP+AQ over two malaria seasons in 2012 and 2013, respectively. Genotypes of P. falciparum Pfdhfr codons 51, 59, 108 and 164; Pfdhps codons 437 and 540, Pfcrt codon 76 and Pfmdr1 codon 86 were analysed by PCR on DNA of parasites from SMC population blood samples (after and before) and non-SMC patients aged 7 years or above (November 2014, n=500).ResultsIn the SMC population 191 and 85 children before and after SMC implementation, respectively, were included in’the molecular analysis. In the non-SMC patients, 220 were’successfully PCR analysed. In the SMC population, the’prevalence of the six-mutation Pfcrt [Pfdhfr-dhps quintuple +Pfcrt-76T] genotype increased significantly after SMC implementation, from 0.0% to 7.1% (p=0.0008). The post-intervention prevalence of the six-mutation Pfmdr1 [Pfdhfr-dhps quintuple +Pfmdr1–86Y] and the seven-mutation Pfcrt +Pfmdr1 [Pfdhfr-dhps quintuple +Pfmdr1–86Y+Pfcrt-76T] genotypes were both 1.2% among the SMC population. No six-mutation and seven-mutation genotypes were observed among SMC population at baseline nor in the non-SMC patient population (p=0.30).ConclusionSMC increased the prevalence of the six-mutation Pfcrt genotype of P. falciparum that can lead to resistance in a population exposed to SMC with SP+AQ.

Background The detailed assessment of the QT and corrected QT (QTc) intervals prolongation is recommended when testing new drugs. The electrocardiograph automatically displays generally reliable values of the QT interval and corrected QT but morphological variations of the T wave may cause reading errors, hence the use of the manual measurement as an alternative method. Our objective was to evaluate the correlation between the automatic and manual measurement of QT values. Methods In Kolle from March 2012 to December 2015, an open randomised, phase III-b/IV study comparing dihydroartemisinine-piperaquine, pyronaridine-artesunate and artemether-lumefantrine was conducted. An electrocardiograph cartridge 12 electrodes coupled to a computer with the Tele Touch software was used for the electrocardiogram on Day 0 before the study drugs administration and on Day 2, 2–4 hours after the administration of the last dose of the antimalarial. The manual measurement of QT and QTc was made using the Bazett method [QTcB_m=(Number leaded×0.04×QTcF) / QTcB]. For prolonged QTc cases on Day 2, another measurement was done during the next scheduled visit (Days 7, 14, 21, 28, 35 and 42) until the QTc normalisation. Results A total of 764 ECG was recorded with 398 participants. Different automatic and manual values of QT and QTc are scattered around different medium. Comparisons of different values of QT (p=0.1245) and QTc (p Conclusions Our results indicate no perfect match between automatic and manual methods for QT and QTc. Manual reading remains important to correct any machine errors during clinical studies.

Background Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP)+amodiaquine (AQ) is being scaled up in countries of the Sahel in West Africa. However, the potential development of Plasmodium falciparum resistance to the respective component drugs is a major concern. Methods Two cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3–59 months received 7 rounds of curative doses of SP+AQ over two malaria seasons. Genotypes of P. falciparum dhfr codons 51, 59 and 108; dhps codons 437 and 540, pfcrt codon 76 and pfmdr1codon 86 were analysed by PCR on DNA from samples collected before and after SMC, and in non-SMC controls. Results In the SMC population 191/662 (28.9%) and 85/670 (13.7%) of children were P. falciparum- positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the control population 220/310 (71%) were successfully PCR analysed. In the SMC children the prevalence of all molecular markers of SP resistance increased significantly after SMC including the dhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p=0.02). The prevalence of Pfmdr1–86Y significantly decreased from 26.7% to 15.3% (p=0.04) while no significant change was seen for pfcrt K76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC control population (p Conclusions SMC increased the prevalence of molecular markers of P. falciparum resistance to SP in the treated children. However, there was no significant flow of these resistance genes into the general parasite population after 2 years and 7 rounds of SMC.