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      Emergence of Plasmodium falciparum strains with artemisinin partial resistance in East Africa and the Horn of Africa: is there a need to panic?

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      Author(s): 1 , 2 , , 3 , 1
      Publication date (Electronic):
      Journal: Malaria Journal
      Publisher: BioMed Central

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          Abstract

          The emergence and spread of artemisinin partial resistance in East and Horn of Africa is alarming. However, artemisinin-based combination therapy (ACT) generally remains efficacious for the treatment of falciparum malaria. The emergence of partial artemisinin resistance does not currently meet the criteria to initiate change on treatment guidelines nor affect ACT routine procurement and distribution. It is high time for scientists and transitional researchers to be more critical and vigilant on further changes so that national programmes will be able to make informed decisions as well as remain alert and prepared for any change that may be required in the future.

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          Artemisinin resistance in Plasmodium falciparum malaria.

          Arjen M. Dondorp, François Nosten, Poravuth Yi … (2009)
          Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance. In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmacokinetics, and molecular markers of resistance. We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate-mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P=0.31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups. P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed. (ClinicalTrials.gov number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.) 2009 Massachusetts Medical Society
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            Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda

            Aline Uwimana, Eric Legrand, Barbara H. Stokes … (2020)
            Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa 1–4 . Here we genotyped the P. falciparum K13 (Pfkelch13) propeller domain, mutations in which can mediate artemisinin resistance 5,6 , in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda 7 . While cure rates were >95% in both treatment arms, the Pfkelch13 R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka. Phylogenetic analysis revealed the expansion of an indigenous R561H lineage. Gene editing confirmed that this mutation can drive artemisinin resistance in vitro. This study provides evidence for the de novo emergence of Pfkelch13-mediated artemisinin resistance in Rwanda, potentially compromising the continued success of antimalarial chemotherapy in Africa.
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              Evidence of Artemisinin-Resistant Malaria in Africa

              Betty Balikagala, Naoyuki Fukuda, Mie Ikeda … (2021)
              In the six Southeast Asian countries that make up the Greater Mekong Subregion, Plasmodium falciparum has developed resistance to derivatives of artemisinin, the main component of first-line treatments for malaria. Clinical resistance to artemisinin monotherapy in other global regions, including Africa, would be problematic.
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                Author and article information

                Contributors
                Ashenafi Assefa: ashyaega@yahoo.com
                Journal
                Journal ID (nlm-ta): Malar J
                Journal ID (iso-abbrev): Malar J
                Title: Malaria Journal
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1475-2875
                Publication date (Electronic): 25 January 2024
                Publication date PMC-release: 25 January 2024
                Publication date Collection: 2024
                Volume: 23
                Electronic Location Identifier: 34
                Affiliations
                [1 ]Ethiopian Public Health Institute, ( https://ror.org/00xytbp33) Addis Ababa, Ethiopia
                [2 ]GRID grid.10698.36, ISNI 0000000122483208, Institute of Global Health and Infectious Diseases, , University of North Carolina School of Medicine, ; Chapel Hill, NC USA
                [3 ]Center for Computational Molecular Biology, Brown University, ( https://ror.org/05gq02987) Providence, RI USA
                Article
                Publisher ID: 4848
                DOI: 10.1186/s12936-024-04848-8
                PMC ID: 10809756
                PubMed ID: 38273360
                SO-VID: 5ad7e170-d1b7-4bf3-82a5-b840d7b92648
                Copyright © © The Author(s) 2024
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                Date received : 16 December 2023
                Date accepted : 10 January 2024
                Categories
                Subject: Perspective
                Custom metadata
                issue-copyright-statement © BioMed Central Ltd., part of Springer Nature 2024

                ScienceOpen disciplines: Infectious disease & Microbiology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology

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