Evidence map›Paper›PMID 32679084›Full record

Observational studyThe Lancet. Infectious diseases2020

Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study.

Mallika Imwong, Mehul Dhorda, Kyaw Myo Tun, Aung Myint Thu, Aung Pyae Phyo, Stephane Proux, Kanokon Suwannasin, Chanon Kunasol, Suttipat Srisutham, Jureeporn Duanguppama and 36 more

Open access · hybridAbstract readObservational Study
In one paragraph

Observational study in The Lancet. Infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 4 pooled it
19.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

96 citing papers in PubMed, 4 syntheses or guidelines pooled it, 179 citations in OpenAlex.

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  12. Parasitological efficacy of seasonal malaria chemoprevention in Nampula, northern Mozambique.Transactions of the Royal Society of Tropical Medicine and Hygiene · 2026
    Article
  13. Observational
  14. Single-cell transcriptional changes of artemisinin-sensitive K13Frontiers in cellular and infection microbiology · 2026
    Article
  15. Assessing the threat of artemisinin resistance: seasonal and ecological patterns ofFrontiers in cellular and infection microbiology · 2026
    Article
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36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

46 authors at 14 institutions in 5 countries.

Mallika ImwongDepartment of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: mallika.imw@mahidol.ac.th.
Mehul DhordaMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Worldwide Antimalarial Resistance Network, Bangkok, Thailand.
Kyaw Myo TunDepartment of Preventive and Social Medicine, Defence Services Medical Academy, Yangon, Myanmar.
Aung Myint ThuShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Aung Pyae PhyoShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Myanmar Oxford Clinical Research Unit, Yangon, Myanmar.
Stephane ProuxShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Kanokon SuwannasinMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Chanon KunasolMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Suttipat SrisuthamMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Jureeporn DuanguppamaMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Ranitha VongpromekWorldwide Antimalarial Resistance Network, Bangkok, Thailand.
Cholrawee PromnarateWorldwide Antimalarial Resistance Network, Bangkok, Thailand.
Aungkana SaejengBureau of Vector-borne Diseases, Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
Nardlada KhantikulOffice of Disease Prevention and Control Region 1, Chiang Mai, Thailand.
Rungniran SugaramBureau of Vector-borne Diseases, Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
Supinya ThanapongpichatFaculty of Medical Technology, Prince of Songkla University, Songkhla, Thailand.
Nongyao SawangjaroenDepartment of Microbiology, Faculty of Science, Prince of Songkla University, Songkhla, Thailand.
Kreepol SutawongBuntharik Hospital, Amphoe Buntharik, Ubon Ratchathani, Thailand.
Kay Thwe HanDepartment of Medical Research, Ministry of Health and Sports, Yangon, Myanmar.
Ye HtutDepartment of Medical Research, Ministry of Health and Sports, Yangon, Myanmar.
Khin LinnDepartment of Medical Research, Ministry of Health and Sports, Yangon, Myanmar.
Aye Aye WinDepartment of Tropical and Infectious Diseases, University of Medicine 1, Yangon, Myanmar.
Tin M HlaingDefence Services Medical Research Centre, Naypyitaw, Myanmar.
Rob W van der PluijmMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Mayfong MayxayInstitute of Research and Education Development, University of Health Sciences, Ministry of Health, Vientiane, Laos; Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos.
Tiengkham PongvongsaSavannakhet Provincial Health Department, Phonsavangnuea village, Kaysone-Phomvihan district, Savannakhet, Laos.
Koukeo PhommasoneLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos.
Rupam TripuraMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Thomas J PetoMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Lorenz von SeidleinMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Chea NguonNational Center for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
Dysoley LekNational Center for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
Xin Hui S ChanMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Huy RekolNational Center for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
Rithea LeangNational Center for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
Cheah HuchNational Center for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
Dominic P KwiatkowskiWellcome Sanger Institute, Hinxton, UK; Medical Research Council Centre for Genomics and Global Health, Big Data Institute, University of Oxford, Oxford, UK.
Olivo MiottoMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Sanger Institute, Hinxton, UK; Medical Research Council Centre for Genomics and Global Health, Big Data Institute, University of Oxford, Oxford, UK.
Elizabeth A AshleyCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos.
Myat Phone KyawDepartment of Medical Research, Myanmar Health Network Organization, Yangon, Myanmar.
Sasithon PukrittayakameeMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; The Royal Society of Thailand, Dusit, Bangkok, Thailand.
Nicholas P J DayMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Arjen M DondorpMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Frank M SmithuisMyanmar Oxford Clinical Research Unit, Yangon, Myanmar; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Medical Action Myanmar, Yangon, Myanmar.
Francois H NostenShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nicholas J WhiteMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Mahidol Oxford Tropical Medicine Research Unit · THMahidol University · THCambodia National Malaria Center · KHUniversity of Oxford · GBMyanmar Oxford Clinical Research Unit · MMLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit · LAMinistry of Health · MMMinistry of Public Health · THPrince of Songkla University · THMinistry of Health · LAMinistry of Health and Sports · MMUbonratchathani Cancer Hospital · THUniversity Of Medicine 1 Yangon · MMWellcome Sanger Institute · GB

Funding

Medical Research Council MR/M006212/1Wellcome Trust 101148/Z/13/ZWellcome Trust 106698/B/14/ZWellcome Trust 204911/Z/16/Z
6 · The paper itself

Abstract

backgroundThe Greater Mekong subregion is a recurrent source of antimalarial drug resistance in Plasmodium falciparum malaria. This study aimed to characterise the extent and spread of resistance across this entire region between 2007 and 2018.

methodsP falciparum isolates from Myanmar, Thailand, Laos, and Cambodia were obtained from clinical trials and epidemiological studies done between Jan 1, 2007, and Dec 31, 2018, and were genotyped for molecular markers (pfkelch, pfcrt, pfplasmepsin2, and pfmdr1) of antimalarial drug resistance. Genetic relatedness was assessed using microsatellite and single nucleotide polymorphism typing of flanking sequences around target genes.

findings10 632 isolates were genotyped. A single long pfkelch Cys580Tyr haplotype (from -50 kb to +31·5 kb) conferring artemisinin resistance (PfPailin) now dominates across the eastern Greater Mekong subregion. Piperaquine resistance associated with pfplasmepsin2 gene amplification and mutations in pfcrt downstream of the Lys76Thr chloroquine resistance locus has also developed. On the Thailand-Myanmar border a different pfkelch Cys580Tyr lineage rose to high frequencies before it was eliminated. Elsewhere in Myanmar the Cys580Tyr allele remains widespread at low allele frequencies. Meanwhile a single artemisinin-resistant pfkelch Phe446Ile haplotype has spread across Myanmar. Despite intense use of dihydroartemisinin-piperaquine in Kayin state, eastern Myanmar, both in treatment and mass drug administrations, no selection of piperaquine resistance markers was observed. pfmdr1 amplification, a marker of resistance to mefloquine, remains at low prevalence across the entire region.

interpretationArtemisinin resistance in P falciparum is now prevalent across the Greater Mekong subregion. In the eastern Greater Mekong subregion a multidrug resistant P falciparum lineage (PfPailin) dominates. In Myanmar a long pfkelch Phe446Ile haplotype has spread widely but, by contrast with the eastern Greater Mekong subregion, there is no indication of artemisinin combination therapy (ACT) partner drug resistance from genotyping known markers, and no evidence of spread of ACT resistant P falciparum from the east to the west. There is still a window of opportunity to prevent global spread of ACT resistance.

fundingThailand Science Research and Innovation, Initiative 5%, Expertise France, Wellcome Trust.

Indexed as

AntimalarialsArtemisininsAsia, SoutheasternGenetic MarkersHaplotypesHumansMalaria, FalciparumMolecular EpidemiologyPlasmodium falciparumAntimalarialsartemisininArtemisininsGenetic Markers

Identifiers

PMID32679084
PMCPMC7689289
OpenAlexW3043451577

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.