15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Artemisinin and multidrug-resistant Plasmodium falciparum – a threat for malaria control and elimination

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose of review

          Artemisinin-based combination therapies (ACTs) are globally the first-line treatment for uncomplicated falciparum malaria and new compounds will not be available within the next few years. Artemisinin-resistant Plasmodium falciparum emerged over a decade ago in the Greater Mekong Subregion (GMS) and, compounded by ACT partner drug resistance, has caused significant ACT treatment failure. This review provides an update on the epidemiology, and mechanisms of artemisinin resistance and approaches to counter multidrug-resistant falciparum malaria.

          Recent findings

          An aggressive malaria elimination programme in the GMS has helped prevent the spread of drug resistance to neighbouring countries. However, parasites carrying artemisinin resistance-associated mutations in the P. falciparum Kelch13 gene ( pfk13) have now emerged independently in multiple locations elsewhere in Asia, Africa and South America. Notably, artemisinin-resistant infections with parasites carrying the pfk13 R561H mutation have emerged and spread in Rwanda.

          Summary

          Enhancing the geographic coverage of surveillance for resistance will be key to ensure prompt detection of emerging resistance in order to implement effective countermeasures without delay. Treatment strategies designed to prevent the emergence and spread of multidrug resistance must be considered, including deployment of triple drug combination therapies and multiple first-line therapies.

          Related collections

          Most cited references70

          • Record: found
          • Abstract: found
          • Article: not found

          The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015

          Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015 and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542–753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.

            Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Artemisinin resistance in Plasmodium falciparum malaria.

              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
                Bookmark

                Author and article information

                Journal
                Curr Opin Infect Dis
                Curr Opin Infect Dis
                COIDI
                Current Opinion in Infectious Diseases
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0951-7375
                1473-6527
                October 2021
                15 July 2021
                : 34
                : 5
                : 432-439
                Affiliations
                [a ]Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
                [b ]Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
                Author notes
                Correspondence to Arjen M. Dondorp, Mahidol-Oxford Tropical Medicine Research Unit, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. Tel: +66 2 203 63 33; e-mail: arjen@ 123456tropmedres.ac
                Article
                QCO340519 00008
                10.1097/QCO.0000000000000766
                8452334
                34267045
                853a39e6-ac4f-4337-97c9-e6a778e222f8
                Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                Categories
                TROPICAL AND TRAVEL-ASSOCIATED DISEASES: Edited by Christina M. Coyle
                Custom metadata
                TRUE

                artemisinin,epidemiology,plasmodium. falciparum,resistance,treatment

                Comments

                Comment on this article