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Study finds steady increase in WHO-validated artemisinin resistance markers in Asia

MORU

From 2002-2018, there has been a steady increase in the places and proportion of infected people reporting validated kelch13 (K13) artemisinin resistance markers, according to a study in The Lancet Microbe. This increase in artemisinin resistance threatens efforts to eliminate malaria in Asia by 2030 — and control efforts in other endemic regions. The authors say that more consistent data collection, over longer time periods in the same areas, and rapid sharing of data are needed to map the spread of resistance and better inform policy decisions.

South and Southeast Asia map, showing locations of artemisinin-resistant Plasmodium falciparum malaria in Asia © 2022. Courtesy of The Lancet Microbe.

26 January 2022 - Published in the Lancet Microbe, the study, Mapping genetic markers of artemisinin resistance in Plasmodium falciparum malaria in Asia, aimed to develop up-to-date spatial distribution visualisations of the 'WHO-validated' Kelch-13 (K13) markers of artemisinin resistance to guide policy decisions. Researchers collated data from 72 studies published between 1 January 2010 and 31 March 2021, comprising K13 markers from 16,613 blood samples collected from 1991 to 2020 from 18 countries.

They found a steady increase in the prevalence of 'WHO-validated' K13 markers, reaching 62∙9 per cent in 2018. Overall, the prevalence of C580Y mutation increased to 84∙9 per cent in 2018 from 48∙9 per cent in 2002. Data showed that from 2002 to 2018, there has been a steady increase in geographic locations and the proportion of infected people with 'validated' artemisinin resistance markers.

First identified in Cambodia’s Battambang and Pailin provinces on the border with Thailand, then identified in Cambodia, Myanmar and Thailand in 2009, these validated and associated mutations are now found in six additional countries (China, India, Laos, Papua New Guinea, Saudi Arabia, and Vietnam). Thus, increases in the prevalence and extent of WHO-validated or WHO-associated markers over time were seen in Myanmar, Thailand, Cambodia, Vietnam, Laos and, to a lesser extent, in China.

The emergence and spread of artemisinin and artemisinin-based combination therapy (ACT) partner drug resistance in the Greater Mekong Subregion (GMS) poses a significant threat to global efforts to eliminate malaria and with the potential to spread or emerge further afield, including to India, Africa and Latin America, and highlights its immediate relevance to Africa, say the researchers. 

Worryingly, a recent report in the NE Journal of Medicine showed independent emergence and local spread of clinically artemisinin-resistant P. falciparum in Africa — and an editorial in the American Journal of Tropical Medicine and Hygiene asked if artemisin-based combination therapies were beginning to fail in Africa.

This is the first study to use the 2020 revised WHO classification for K13 markers and the first to aggregate all published K13 marker data in Asia and map them by province and district. It highlights that non-uniform, patchy and delayed reporting are crucial challenges in K13 surveillance.

Currently, data in the literature are reported in an unstructured way leading to difficulties in pooling and interpretation. Researchers conclude that more consistent data collection over 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. A tool, developed by scientists from WWARN, Mahidol-Oxford Tropical Medicine Research Unit (MORU) and the University of Cape Town (UCT), with a set of minimum criteria for reporting future studies can overcome this issue, researchers say.

Read the full paper:

Mapping genetic markers of artemisinin resistance in Plasmodium falciparum malaria in Asia: a systematic review and spatiotemporal analysis. Frank M Kagoro, Karen I Barnes, Kevin Marsh, Nattwut Ekapirat, Chris Erwin G Mercado, Ipsita Sinha, Georgina Humphreys, Mehul Dhorda, Philippe J Guerin, Richard J Maude. www.thelancet.com/microbe Published online January 25, 2022 https://doi.org/10.1016/S2666-5247(21)00249-4

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