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      Malaria chemoprevention and drug resistance: a review of the literature and policy implications

      review-article
      Malaria Journal
      BioMed Central

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          Abstract

          Chemoprevention strategies reduce malaria disease and death, but the efficacy of anti-malarial drugs used for chemoprevention is perennially threatened by drug resistance. This review examines the current impact of chemoprevention on the emergence and spread of drug resistant malaria, and the impact of drug resistance on the efficacy of each of the chemoprevention strategies currently recommended by the World Health Organization, namely, intermittent preventive treatment in pregnancy (IPTp); intermittent preventive treatment in infants (IPTi); seasonal malaria chemoprevention (SMC); and mass drug administration (MDA) for the reduction of disease burden in emergency situations. While the use of drugs to prevent malaria often results in increased prevalence of genetic mutations associated with resistance, malaria chemoprevention interventions do not inevitably lead to meaningful increases in resistance, and even high rates of resistance do not necessarily impair chemoprevention efficacy. At the same time, it can reasonably be anticipated that, over time, as drugs are widely used, resistance will generally increase and efficacy will eventually be lost. Decisions about whether, where and when chemoprevention strategies should be deployed or changed will continue to need to be made on the basis of imperfect evidence, but practical considerations such as prevalence patterns of resistance markers can help guide policy recommendations.

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          Most cited references147

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          Malaria resurgence: a systematic review and assessment of its causes

          Background Considerable declines in malaria have accompanied increased funding for control since the year 2000, but historical failures to maintain gains against the disease underscore the fragility of these successes. Although malaria transmission can be suppressed by effective control measures, in the absence of active intervention malaria will return to an intrinsic equilibrium determined by factors related to ecology, efficiency of mosquito vectors, and socioeconomic characteristics. Understanding where and why resurgence has occurred historically can help current and future malaria control programmes avoid the mistakes of the past. Methods A systematic review of the literature was conducted to identify historical malaria resurgence events. All suggested causes of these events were categorized according to whether they were related to weakened malaria control programmes, increased potential for malaria transmission, or technical obstacles like resistance. Results The review identified 75 resurgence events in 61 countries, occurring from the 1930s through the 2000s. Almost all resurgence events (68/75 = 91%) were attributed at least in part to the weakening of malaria control programmes for a variety of reasons, of which resource constraints were the most common (39/68 = 57%). Over half of the events (44/75 = 59%) were attributed in part to increases in the intrinsic potential for malaria transmission, while only 24/75 (32%) were attributed to vector or drug resistance. Conclusions Given that most malaria resurgences have been linked to weakening of control programmes, there is an urgent need to develop practical solutions to the financial and operational threats to effectively sustaining today’s successful malaria control programmes.
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            Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum.

            Widespread use of antimalarial agents can profoundly influence the evolution of the human malaria parasite Plasmodium falciparum. Recent selective sweeps for drug-resistant genotypes may have restricted the genetic diversity of this parasite, resembling effects attributed in current debates to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America, but the number of CQR founder mutations and the impact of chlorquine on parasite genomes worldwide have been difficult to evaluate. Using 342 highly polymorphic microsatellite markers from a genetic map, here we show that the level of genetic diversity varies substantially among different regions of the parasite genome, revealing extensive linkage disequilibrium surrounding the key CQR gene pfcrt and at least four CQR founder events. This disequilibrium and its decay rate in the pfcrt-flanking region are consistent with strong directional selective sweeps occurring over only approximately 20-80 sexual generations, especially a single resistant pfcrt haplotype spreading to very high frequencies throughout most of Asia and Africa. The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum.
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              World Malaria Report 2020

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                Author and article information

                Contributors
                plowe.chris@gmail.com
                Journal
                Malar J
                Malar J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                24 March 2022
                24 March 2022
                2022
                : 21
                : 104
                Affiliations
                GRID grid.411024.2, ISNI 0000 0001 2175 4264, University of Maryland School of Medicine, ; Baltimore, MD USA
                Author information
                http://orcid.org/0000-0002-0045-9888
                Article
                4115
                10.1186/s12936-022-04115-8
                8943514
                35331231
                0f71fef6-5ac7-4611-9d67-c8cbb10b69d3
                © The Author(s) 2022

                Open AccessThis 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
                : 31 January 2022
                : 3 March 2022
                Funding
                Funded by: World Health Organization
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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