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      High therapeutic efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated falciparum malaria in Somalia

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          Abstract

          Background

          Artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA/PPQ) are the recommended first- and second-line treatments, respectively, for uncomplicated falciparum malaria in Somalia. The studies reported here were conducted to assess the efficacy of these artemisinin-based combinations and the mutations in Plasmodium falciparum K13-propeller ( Pfk13) domain and amplification in Pfplasmepsin 2 ( Pfpm2) gene in Somalia.

          Methods

          One-arm prospective studies were conducted to assess the clinical and parasitological responses to DHA/PPQ and AL at two sites in 2016 and 2017, respectively, using the standard WHO protocol. The patterns of molecular markers associated with artemisinin and PPQ resistance were investigated for the first time in Somalia.

          Results

          A total of 339 patients were enrolled with 139 for AL and 200 for DHA/PPQ. With AL, no parasite recurrence was observed among patients treated at either site, corresponding to 100% clinical and parasitological responses. For DHA–PPQ, an adequate clinical and parasitological response rate > 97% was observed. All study patients on both treatments at both sites were parasite-free on day 3. Of the 138 samples with interpretable results for the polymorphism in Pfk13, only one (0.7%), from Bosaso, contained a non-synonymous mutation (R622I), which is not one of the known markers of artemisinin resistance. No Pfpm2 amplification was observed among the 135 samples with interpretable results.

          Conclusions

          AL and DHA/PPQ were highly effective in the treatment of uncomplicated falciparum malaria, and there was no evidence of resistance to artemisinin or PPQ. These two combinations are thus relevant in the chemotherapeutic strategy for malaria control in Somalia.

          Trial registration ACTRN12616001005448 (Jowhar DP study), ACTRN12616000553471 (Bosaso DP study), ACTRN12617001055392 (AL study in Bosaso and Jowhar)

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          Most cited references 38

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          Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study.

          Artemisinin resistance in Plasmodium falciparum threatens to reduce the efficacy of artemisinin combination therapies (ACTs), thus compromising global efforts to eliminate malaria. Recent treatment failures with dihydroartemisinin-piperaquine, the current first-line ACT in Cambodia, suggest that piperaquine resistance may be emerging in this country. We explored the relation between artemisinin resistance and dihydroartemisinin-piperaquine failures, and sought to confirm the presence of piperaquine-resistant P falciparum infections in Cambodia.
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            Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia.

            The emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia threatens malaria treatment efficacy. Mutations in a kelch protein encoded on P. falciparum chromosome 13 (K13) have been associated with resistance in vitro and in field samples from Cambodia. P. falciparum infections from artesunate efficacy trials in Bangladesh, Cambodia, Laos, Myanmar, and Vietnam were genotyped at 33 716 genome-wide single-nucleotide polymorphisms (SNPs). Linear mixed models were used to test associations between parasite genotypes and parasite clearance half-lives following artesunate treatment. K13 mutations were tested for association with artemisinin resistance, and extended haplotypes on chromosome 13 were examined to determine whether mutations arose focally and spread or whether they emerged independently. The presence of nonreference K13 alleles was associated with prolonged parasite clearance half-life (P = 1.97 × 10(-12)). Parasites with a mutation in any of the K13 kelch domains displayed longer parasite clearance half-lives than parasites with wild-type alleles. Haplotype analysis revealed both population-specific emergence of mutations and independent emergence of the same mutation in different geographic areas. K13 appears to be a major determinant of artemisinin resistance throughout Southeast Asia. While we found some evidence of spreading resistance, there was no evidence of resistance moving westward from Cambodia into Myanmar. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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              Emergence of Indigenous Artemisinin-Resistant Plasmodium falciparum in Africa.

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                Author and article information

                Contributors
                dahan2004@hotmail.com
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                11 July 2019
                11 July 2019
                2019
                : 18
                Affiliations
                [1 ]ISNI 0000000121633745, GRID grid.3575.4, Global Malaria Programme, World Health Organization, ; 20 Avenue Appia, 1211 Geneva 27, Switzerland
                [2 ]World Health Organization, Mogadishu, Somalia
                [3 ]Ministry of Health, Puntland, Somalia
                [4 ]INTERSOS, Jowhar Hospital, Jowhar town, Jowhar, Somalia
                [5 ]GRID grid.418537.c, Malaria Molecular Epidemiology Unit, , Pasteur Institute in Cambodia, ; Phnom Penh, Cambodia
                [6 ]Ministry of Health and Human Service, Mogadishu, Somalia
                [7 ]World Health Organization, Hargeisa, Somalia
                [8 ]ISNI 0000 0001 2353 6535, GRID grid.428999.7, Malaria Translational Research Unit, , Pasteur Institute, ; Paris, France
                [9 ]ISNI 0000 0000 9919 9582, GRID grid.8761.8, Present Address: University of Gothenburg, ; Gothenburg, Sweden
                Article
                2864
                10.1186/s12936-019-2864-1
                6624891
                31296223
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1140599
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

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