Evidence map›Paper›PMID 36462526›Full record

ArticleThe Lancet. Infectious diseases2023

Malaria outbreak in Laos driven by a selective sweep for Plasmodium falciparum kelch13 R539T mutants: a genetic epidemiology analysis.

Varanya Wasakul, Areeya Disratthakit, Mayfong Mayxay, Keobouphaphone Chindavongsa, Viengphone Sengsavath, Nguyen Thuy-Nhien, Richard D Pearson, Sonexay Phalivong, Saiamphone Xayvanghang, Richard J Maude and 7 more

Abstract read
In one paragraph

Article in The Lancet. Infectious diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
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

28 citing papers in PubMed.

  1. Article
  2. Article
  3. Double Mutations inbioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Malaria: past, present, and future.Signal transduction and targeted therapy · 2025
    Review
  9. Observational
  10. Article
  11. NovelAntimicrobial agents and chemotherapy · 2025
    Article
  12. Review
  13. Review
  14. Geo-classification of drug-resistant travel-associatedAntimicrobial agents and chemotherapy · 2024
    Article
  15. Review
  16. Article
  17. AmBio · 2024
    Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Varanya WasakulMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Areeya DisratthakitMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Mayfong MayxayLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos; Institute of Research and Education Development, University of Health Sciences, Ministry of Health, Vientiane, Laos; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
Keobouphaphone ChindavongsaCentre for Malariology, Parasitology, and Entomology, Vientiane, Laos.
Viengphone SengsavathCentre for Malariology, Parasitology, and Entomology, Vientiane, Laos.
Nguyen Thuy-NhienOxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.
Richard D PearsonWellcome Sanger Institute, Hinxton, UK.
Sonexay PhalivongLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.
Saiamphone XayvanghangLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.
Richard J MaudeMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK; Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA.
Sónia GonçalvesWellcome Sanger Institute, Hinxton, UK.
Nicholas P 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, Oxford University, Oxford, UK.
Paul N NewtonLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
Elizabeth A AshleyLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
Dominic P KwiatkowskiWellcome Sanger Institute, Hinxton, 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, Oxford University, Oxford, UK.
Olivo MiottoMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK; Wellcome Sanger Institute, Hinxton, UK. Electronic address: olivo@tropmedres.ac.

Funding

Wellcome TrustWellcome Trust 204911
6 · The paper itself

Abstract

backgroundMalaria outbreaks are important public health concerns that can cause resurgence in endemic regions approaching elimination. We investigated a Plasmodium falciparum outbreak in Attapeu Province, Laos, during the 2020-21 malaria season, using genomic epidemiology methods to elucidate parasite population dynamics and identify its causes.

methodsIn this genetic analysis, 2164 P falciparum dried blood spot samples were collected from southern Laos between Jan 1, 2017, and April 1, 2021, which included 249 collected during the Attapeu outbreak between April 1, 2020, and April 1, 2021, by routine surveillance. Genetic barcodes obtained from these samples were used to investigate epidemiological changes underpinning the outbreak, estimate population diversity, and analyse population structure. Whole-genome sequencing data from additional historical samples were used to reconstruct the ancestry of outbreak strains using identity-by-descent analyses.

findingsThe outbreak parasite populations were characterised by unprecedented loss of genetic diversity, primarily caused by rapid clonal expansion of a multidrug-resistant strain (LAA1) carrying the kelch13 Arg539Thr (R539T) mutation. LAA1 replaced kelch13 Cys580Tyr (C580Y) mutants resistant to dihydroartemisinin-piperaquine (KEL1/PLA1) as the dominant strain. LAA1 inherited 58·8% of its genome from a strain circulating in Cambodia in 2008. A secondary outbreak strain (LAA2) carried the kelch13 C580Y allele, and a genome that is essentially identical to a Cambodian parasite from 2009. A third, low-frequency strain (LAA7) was a recombinant of KEL1/PLA1 with a kelch13 R539T mutant.

interpretationThese results strongly suggest that the outbreak was driven by a selective sweep, possibly associated with multidrug-resistant phenotypes of the outbreak strains. Established resistant populations can circulate at low frequencies for years before suddenly overwhelming dominant strains when the conditions for selection become favourable-eg, when front-line therapies change. Genetic surveillance can support elimination by characterising key properties of outbreaks such as population diversity, drug resistance marker prevalence, and the origins of outbreak strains.

fundingBill & Melinda Gates Foundation; The Global Fund to Fight AIDS, Tuberculosis and Malaria; Wellcome Trust. TRANSLATION: For the Lao translation of the abstract see Supplementary Materials section.

Indexed as

AntimalarialsMalariaMalaria, FalciparumDisease OutbreaksDrug ResistanceHumansLaosMolecular EpidemiologyPlasmodium falciparumProtozoan ProteinsAntimalarialsProtozoan Proteins

Identifiers

PMID36462526
PMCPMC10914674

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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.