Evidence map›Paper›PMID 27332904›Full record

ArticleThe New England journal of medicine2016

A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

Didier Ménard, Nimol Khim, Johann Beghain, Ayola A Adegnika, Mohammad Shafiul-Alam, Olukemi Amodu, Ghulam Rahim-Awab, Céline Barnadas, Antoine Berry, Yap Boum and 80 more

Open access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 371 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
371citing papers in PubMed, 9 pooled it
69.9field-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

371 citing papers in PubMed, 9 syntheses or guidelines pooled it, 567 citations in OpenAlex.

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311 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

90 authors at 1 institution in 1 country.

Didier MénardThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Nimol KhimThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Johann BeghainThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Ayola A AdegnikaThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Mohammad Shafiul-AlamThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Olukemi AmoduThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Ghulam Rahim-AwabThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Céline BarnadasThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Antoine BerryThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Yap BoumThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Maria D BustosThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Jun CaoThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Jun-Hu ChenThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Louis ColletThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Liwang CuiThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Garib-Das ThakurThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Alioune DieyeThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Djibrine DjalléThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Monique A DorkenooThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Carole E Eboumbou-MoukokoThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Fe-Esperanza-Caridad J EspinoThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Thierry FandeurThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Maria-Fatima Ferreira-da-CruzThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Abebe A FolaThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Hans-Peter FuehrerThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Abdillahi M HassanThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Socrates HerreraThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Bouasy HongvanthongThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Sandrine HouzéThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Maman L IbrahimThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Mohammad Jahirul-KarimThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Lubin JiangThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Shigeyuki KanoThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Wasif Ali-KhanThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Maniphone KhanthavongThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Peter G KremsnerThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Marcus LacerdaThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Rithea LeangThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Mindy LeelawongThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Mei LiThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Khin LinThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Jean-Baptiste MazaratiThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Sandie MénardThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Isabelle MorlaisThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Hypolite Muhindo-MavokoThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Lise MussetThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Kesara Na-BangchangThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Michael NamboziThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Karamoko NiaréThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Harald NoedlThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Jean-Bosco OuédraogoThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Dylan R PillaiThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Bruno PradinesThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Bui Quang-PhucThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Michael RamharterThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Milijaona RandrianarivelojosiaThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Jetsumon SattabongkotThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Abdiqani Sheikh-OmarThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Kigbafori D SiluéThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Sodiomon B SirimaThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Colin SutherlandThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Din SyafruddinThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Rachida TaharThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Lin-Hua TangThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Offianan A TouréThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Patrick Tshibangu-wa-TshibanguThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Inès Vigan-WomasThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Marian WarsameThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Lyndes WiniThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Sedigheh ZakeriThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Saorin KimThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Rotha EamThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Laura BerneThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Chanra KheanThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Sophy ChyThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Malen KenThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Kaknika LochThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Lydie CanierThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Valentine DuruThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Eric LegrandThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Jean-Christophe BaraleThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Barbara StokesThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Judith StraimerThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Benoit WitkowskiThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
David A FidockThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Christophe RogierThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Pascal RingwaldThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Frederic ArieyThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
Odile Mercereau-PuijalonThe authors' affiliations are listed in the Supplementary Appendix , available at NEJM.org.
KARMA Consortium
The Stables · GB

Funding

Southeast Asia Malaria Research CenterU19AI089672 · NIAID · UNIVERSITY OF SOUTH FLORIDA · PI CUI, LIWANG · 2010 to 2023
$28.9M
Vector Biology Research and Integrated Vector Management For Malaria ControlU19AI089702 · NIAID · CAUCASECO SCIENTIFIC RESEARCH CENTER · PI HERRERA VALENCIA, SOCRATES · 2010 to 2016
$11.5M
Peru Infectious Diseases Epidemiology Research Training ConsortiumD43TW007393 · FIC · UNIVERSIDAD PERUANA CAYETANO HEREDIA · PI Andres G Lescano · 2005 to 2026
$5.9M
Defining P. falciparum resistance to artemisinin-based combination therapiesR01AI109023 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FIDOCK, DAVID A · 2014 to 2025
$4.4M
Columbia University Graduate Training Program in Microbiology and ImmunologyT32AI106711 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Nicholas Arpaia, Uttiya Basu · 2014 to 2026
$2.1M
FIC NIH HHS D43 TW007393NIAID NIH HHS AI109023NIAID NIH HHS R01 AI109023NIAID NIH HHS R01 AI11646601NIAID NIH HHS T32 AI106711NIAID NIH HHS U19 AI089672NIAID NIH HHS U19AI089672NIAID NIH HHS U19 AI089702NIAID NIH HHS U19AI089702
6 · The paper itself

Abstract

backgroundRecent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.

methodsWe analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci.

resultsWe identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay.

conclusionsNo evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).

Indexed as

MutationPolymorphism, GeneticAlgorithmsArtemisininsAsia, SoutheasternChinaDrug ResistanceEndemic DiseasesGenotypeHumansLactonesMalaria, FalciparumPlasmodium falciparumProtozoan ProteinsSequence Analysis, DNAartemisinArtemisininsLactonesProtozoan Proteins

Identifiers

PMID27332904
PMCPMC4955562
OpenAlexW2467259677

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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.