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BackgroundAnti-malarial drug resistance remains a major threat to global malaria control efforts. In Africa,Plasmodium falciparumremains susceptible to artemisinin-based combination therapy (ACT), but the emergence of resistant parasites in multiple countries in Southeast Asia and concerns over emergence and/or spread of resistant parasites in Africa warrants continuous monitoring. The World Health Organization recommends that surveillance for molecular markers of resistance be included within therapeutic efficacy studies (TES). The current study assessed molecular markers associated with resistance to Artemether−lumefantrine (AL) and Dihydroartemisinin−piperaquine (DP) from samples collected from children aged 6–59 months enrolled in a TES conducted in Siaya County, western Kenya from 2016 to 2017.MethodsThree hundred and twenty-three samples collected pre-treatment (day-0) and 110 samples collected at the day of recurrent parasitaemia (up to day 42) were tested for the presence of drug resistance markers in thePfk13propeller domain, and thePfmdr1andPfcrtgenes by Sanger sequencing. Additionally, thePfpm2gene copy number was assessed by real-time polymerase chain reaction.ResultsNo mutations previously associated with artemisinin resistance were detected in thePfk13propeller region. However, other non-synonymous mutations in thePfk13propeller region were detected. The most common mutation found on day-0 and at day of recurrence in thePfmdr1multidrug resistance marker was at codon 184F. Very few mutations were found in thePfcrtmarker (Pfpm2gene copy number had a single gene copy. None of the associations between observed mutations and treatment outcomes were statistically significant.ConclusionThe results indicate absence ofPfk13mutations associated with parasite resistance to artemisinin in this area and a very high proportion of wild-type parasites forPfcrt. Although the frequency ofPfmdr1184Fmutations was high in these samples, the association with treatment failure did not reach statistical significance. As the spread of artemisinin-resistant parasites remains a possibility, continued monitoring for molecular markers of ACT resistance is needed to complement clinical data to inform treatment policy in Kenya and other malaria-endemic regions.

Background The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether–lumefantrine (AL), artesunate–amodiaquine (ASAQ), and dihydroartemisinin–piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications’ therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces. Methods Enrollment occurred between March and July 2017. Study participants were children with P. falciparum monoinfection from each provincial capital. Participants received a 3-day course of a quality-assured artemisinin-based combination and were monitored for 28 (AL and ASAQ arms) or 42 days (DP arm). Each ACT was assessed in two provinces. The primary study endpoints were: (1) follow-up without complications and (2) failure to respond to treatment or development of recurrent P. falciparum infection. Parasites from each patient experiencing recurrent infection were genotyped to differentiate new infection from recrudescence of persistent parasitaemia. These parasites were also analysed for molecular markers associated with ACT resistance. Results Of 608 children enrolled in the study, 540 (89%) reached a primary study endpoint. Parasitaemia was cleared within 3 days of medication administration in all participants, and no early treatment failures were observed. After exclusion of reinfections, the corrected efficacy of AL was 96% (91–100%, 95% confidence interval) in Zaire and 97% (93–100%) in Lunda Sul. The corrected efficacy of ASAQ was 100% (97–100%) in Benguela and 93% (88–99%) in Zaire. The corrected efficacy of DP was 100% (96–100%) in Benguela and 100% in Lunda Sul. No mutations associated with artemisinin resistance were identified in the pfk13 gene in the 38 cases of recurrent P. falciparum infection. All 33 treatment failures in the AL and ASAQ arms carried pfmdr1 or pfcrt mutations associated with lumefantrine and amodiaquine resistance, respectively, on day of failure. Conclusions AL, ASAQ, and DP continue to be efficacious against P. falciparum malaria in these provinces of Angola. Rapid parasite clearance and the absence of genetic evidence of artemisinin resistance are consistent with full susceptibility to artemisinin derivatives. Periodic monitoring of in vivo drug efficacy remains a priority routine activity for Angola.

Dihydroartemisinin/piperaquine (DHA/PPQ) is increasingly deployed as antimalaria drug in Africa. We report the detection in Mali of Plasmodium falciparum infections carrying plasmepsin 2 duplications (associated with piperaquine resistance) in 7/65 recurrent infections within 2 months after DHA/PPQ treatment. These findings raise concerns about the long-term efficacy of DHA/PPQ treatment in Africa., This work was supported by a Swedish Research Council Grant (no. VR-2014-3134). The WANECAM study is funded by the European and Developing Countries Clinical Trial Partnership and by the Medicines for Malaria Venture (Geneva, Switzerland) and is co-funded by the United Kingdom Medical Research Councils, the Swedish International Development Cooperation Agency, the German Ministry for Education and Research, the University Claude Bernard (Lyon, France), the University of Science, Techniques, and Technologies of Bamako (Bamako, Mali), the Centre National de Recherche et de Formation sur le Paludisme (Burkina Faso), the Institut de Recherche en Sciences de la Sante (Bobo-Dioulasso, Burkina Faso), and the Centre National de Formation et de Recherche en Sante Rurale (Guinea).J.I. was supported by EuroInkaNet/Erasmus Mundus Program. Fundacao para a Ciencia e Tecnologia supports M.S. (grant no. SFRH/BD/129769/2017), M.I.V. (grant no. SFRH/BPD/76614/2011), and P.E.F. (grant no. IF/00143/2015).