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Background: Chloroquine, a previous highly efficacious, easy to use and affordable anti-malarial agent was withdrawn from malaria endemic regions due to high levels of resistance. This review collated evidence from published-reviewed articles to establish prevalence of Pfcrt 76T and Pfmdr-1 86Y alleles in malaria affected countries following official discontinuation of chloroquine use., Methods: A review protocol was developed, registered in PROSPERO (#CRD42018083957) and published in a peer-reviewed journal. Article search was done in PubMed, Scopus, Lilacs/Vhl and Embase databases by two experienced librarians (AK, RS) for the period 1990-to-Febuary 2018. Mesh terms and Boolean operators (AND, OR) were used. Data extraction form was designed in Excel spread sheet 2007. Data extraction was done by three reviewers (NL, BB and MO), discrepancies were resolved by discussion. Random effects analysis was done in Open Meta Analyst software. Heterogeneity was established using I 2 -statistic., Results: A total of 4721 citations were retrieved from article search (Pubmed = 361, Lilac/vhl = 28, Science Direct = 944, Scopus = 3388). Additional targeted search resulted in three (03) eligible articles. After removal of duplicates (n = 523) and screening, 38 articles were included in the final review. Average genotyping success rate was 63.6% (18,343/28,820) for Pfcrt K76T and 93.5% (16,232/17,365) for Pfmdr-1 86Y mutations. Prevalence of Pfcrt 76T was as follows; East Africa 48.9% (2528/5242), Southern Africa 18.6% (373/2163), West Africa 58.3% (3321/6608), Asia 80.2% (1951/2436). Prevalence of Pfmdr-1 86Y was; East Africa 32.4% (1447/5722), Southern Africa 36.1% (544/1640), West Africa 52.2% (1986/4200), Asia 46.4% (1276/2217). Over half, 52.6% (20/38) of included studies reported continued unofficial chloroquine use following policy change. Studies done in Madagascar and Kenya reported re-emergence of chloroquine sensitive parasites (IC 50  < 30.9 nM). The average time (years) since discontinuation of chloroquine use to data collection was 8.7 ± 7.4. There was high heterogeneity (I 2  > 95%)., Conclusion: The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chloroquine use. However, Pfcrt K76T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries.

Background: Malaria control and prevention efforts continue to rely heavily on the use of medicines especially artemisinin agents. However, currently, the emergence of artemisinin resistance threatens this effort globally. The K13-gene polymorphisms associated with artemisinin resistance have been detected in Southeast Asia. In countries outside Southeast Asia, artemisinin resistance has not yet been confirmed., Methods/design: The articles will be obtained from the search of MEDLINE via PubMed, Scopus, EMBASE, and LILACS/VHL databases. Mesh terms will be used in the article search. Boolean operators ("AND", "OR") will be used in the article search. Article search will be done independently by two librarians (RS and AK). The articles will be screened for inclusion using set criteria and following the PRISMA guidelines. Data extraction will be done by two independent reviewers (NL and BB), Kappa statistic will be calculated, and any discrepancies resolved by discussion. Heterogeneity in the articles will be established using I 2 statistic., Discussion: This review will focus on establishing the K13-gene polymorphisms among Plasmodium falciparum parasites reported from previous studies in malaria-affected countries. Artemisinin resistance has not been widely reported among parasites in Africa and other malaria-endemic countries outside Southeast Asia. However, several studies on artemisinin resistance have reported different K13-gene polymorphisms from the validated mutations found in Southeast Asia. This study will collate evidence from previous studies on the commonly reported K13 -gene polymorphisms among P. falciparum parasites in malaria-affected countries., Systematic Review Registration: PROSPERO CRD 42018084624.