Abstract
SummaryBackgroundThe increase in artemisinin resistance threatens malaria elimination in Asia by the target date of 2030 and could derail control efforts in other endemic regions. This study aimed to develop up-to-date spatial distribution visualisations of the kelch13 (K13) gene markers of artemisinin resistance in Plasmodium falciparum for policy makers.MethodsIn this systematic review and spatiotemporal analysis we used the WorldWide Antimalarial Resistance Network (WWARN) surveyor molecular markers of artemisinin resistance database. We updated the database by searching PubMed and SCOPUS for studies published between Jan 1, 1990, and March 31, 2021. Articles were included if they contained data on K13 markers of artemisinin resistance from patients' samples in Asia and articles already included in the WWARN database were excluded. Data were extracted from the published articles and authors were contacted when information was missing. We used the lowest administrative unit levels for the sampling locations of all the K13 data to describe the spatiotemporal distribution. The numbers of samples tested and those with each molecular marker in each administrative unit level were aggregated by year to calculate the marker prevalence over time.FindingsData were collated from 72 studies comprising K13 markers from 16 613 blood samples collected from 1991 to 2020 from 18 countries. Most samples were from Myanmar (3842 [23·1%]), Cambodia (3804 [22·9%]), and Vietnam (2663 [16·0%]). The median time between data collection and publication was 3·6 years (range 0·9–25·0, IQR 2·7 [2·5–5·2]). There was a steady increase in the prevalence of WHO-validated K13 markers, with the lowest of 4·3% in 2005 (n=47) and the highest of 62·9% in 2018 (n=264). Overall, the prevalence of Cys580Tyr mutation increased from 48·9% in 2002 to 84·9% in 2018.InterpretationFrom 2002 to 2018, there has been a steady increase in geographical locations and the proportion of infected people with validated artemisinin resistance markers. More consistent data collection, over more extended periods in the same areas with the rapid sharing of data are needed to map the spread and evolution of resistance to better inform policy decisions. Data in the literature are reported in a heterogeneous way leading to difficulties in pooling and interpretation. We propose here a tool with a set of minimum criteria for reporting future studies.FundingThis research was funded in part by the Wellcome Trust.
Highlights
Malaria has been declining globally with a 50% reduction of reported cases and an 84% reduction in deaths during the Millennium Development Goals era (2000–15); no significant progress in reducing the number of global malaria cases has been made since 2015
This study aimed to determine the spatial and temporal distribution of the genetic markers of artemisinin resistance in Asia using data from the published literature on K13 markers, present this evidence of artemisinin-resistant Plasmodium falciparum malaria in a policy maker-friendly format to help guide the planning of malaria control and elimination strategies
We obtained 11 132 published papers from the PubMed and Scopus search. 8640 articles were excluded because they were duplicates of articles in the WorldWide Antimalarial Resistance Network (WWARN) database, had titles that did not include either malaria-related or P falciparum-related information, or did not use blood samples taken from patients
Summary
Malaria has been declining globally with a 50% reduction of reported cases and an 84% reduction in deaths during the Millennium Development Goals era (2000–15); no significant progress in reducing the number of global malaria cases has been made since 2015. Malaria case incidence declined by 27% between 2000 and 2015 and has been increasing since 2015.1 Due to the remaining high morbidity and mortality caused by malaria worldwide, global mobilisation efforts have been made for its elimination. Managing artemisinin resistance requires tools to monitor its spread over time and space to guide interventions to control or ideally eliminate resistant parasites.[8] The identification of mutations in the propeller region of the kelch[13] (K13) gene associated with artemisinin resistance (with the phenotype of slower parasite clearance) in 2014 has enabled monitoring for artemisinin resistance in research studies and Lancet Microbe 2022
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