Evidence map›Paper›PMID 27301419›Full record

ArticleNature communications2016

A broad analysis of resistance development in the malaria parasite.

Victoria C Corey, Amanda K Lukens, Eva S Istvan, Marcus C S Lee, Virginia Franco, Pamela Magistrado, Olivia Coburn-Flynn, Tomoyo Sakata-Kato, Olivia Fuchs, Nina F Gnädig and 16 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
16.9field-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

82 citing papers in PubMed, 130 citations in OpenAlex.

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 8 institutions in 4 countries.

Victoria C CoreyDepartment of Pediatrics, School of Medicine, University of California San Diego, 9500 Gilman Drive 0741, La Jolla, California 92093, USA.
Amanda K LukensDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.
Eva S IstvanDepartment of Medicine and Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Marcus C S LeeDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Virginia FrancoTres Cantos Medicines Development Campus, Malaria DPU, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Pamela MagistradoDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.
Olivia Coburn-FlynnDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Tomoyo Sakata-KatoDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.
Olivia FuchsDepartment of Pediatrics, School of Medicine, University of California San Diego, 9500 Gilman Drive 0741, La Jolla, California 92093, USA.
Nina F GnädigDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Greg GoldgofDepartment of Pediatrics, School of Medicine, University of California San Diego, 9500 Gilman Drive 0741, La Jolla, California 92093, USA.
Maria LinaresTres Cantos Medicines Development Campus, Malaria DPU, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Maria G Gomez-LorenzoTres Cantos Medicines Development Campus, Malaria DPU, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Cristina De CózarTres Cantos Medicines Development Campus, Malaria DPU, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Maria Jose Lafuente-MonasterioTres Cantos Medicines Development Campus, Malaria DPU, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Sara PratsTres Cantos Medicines Development Campus, Malaria DPU, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Stephan MeisterDepartment of Pediatrics, School of Medicine, University of California San Diego, 9500 Gilman Drive 0741, La Jolla, California 92093, USA.ORCID http://orcid.org/0000-0003-2436-7037
Olga TanaseichukThe Genomics Institute of the Novartis Research Foundation, 10675 John J Hopkins Drive, San Diego, California 92121, USA.
Melanie WreeDepartment of Pediatrics, School of Medicine, University of California San Diego, 9500 Gilman Drive 0741, La Jolla, California 92093, USA.
Yingyao ZhouThe Genomics Institute of the Novartis Research Foundation, 10675 John J Hopkins Drive, San Diego, California 92121, USA.
Paul A WillisMedicines for Malaria Venture, PO Box 1826, 20 route de Pre-Bois, 1215 Geneva 15, Switzerland.
Francisco-Javier GamoTres Cantos Medicines Development Campus, Malaria DPU, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Daniel E GoldbergDepartment of Medicine and Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
David A FidockDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Dyann F WirthDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.
Elizabeth A WinzelerDepartment of Pediatrics, School of Medicine, University of California San Diego, 9500 Gilman Drive 0741, La Jolla, California 92093, USA.
GlaxoSmithKline (France) · FRUniversity of California San Diego · USColumbia University · USBroad Institute · USGenomics Institute of the Novartis Research Foundation · USHarvard University · USWashington University in St. Louis · USMedicines for Malaria Venture · CH

Funding

Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
Novel Genetic Mechanism of Artemisinin Resistance for MalariaR01AI099105 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HARTL, DANIEL L, WIRTH, DYANN F · 2013 to 2021
$5.4M
Defining the targets of broad intervention antimalarial agentsR01AI103058 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WINZELER, ELIZABETH A · 2013 to 2016
$2.6M
NIAID NIH HHS R01 AI099105NIAID NIH HHS R01 AI103058NIGMS NIH HHS T32 GM008666
6 · The paper itself

Abstract

Microbial resistance to chemotherapy has caused countless deaths where malaria is endemic. Chemotherapy may fail either due to pre-existing resistance or evolution of drug-resistant parasites. Here we use a diverse set of antimalarial compounds to investigate the acquisition of drug resistance and the degree of cross-resistance against common resistance alleles. We assess cross-resistance using a set of 15 parasite lines carrying resistance-conferring alleles in pfatp4, cytochrome bc1, pfcarl, pfdhod, pfcrt, pfmdr, pfdhfr, cytoplasmic prolyl t-RNA synthetase or hsp90. Subsequently, we assess whether resistant parasites can be obtained after several rounds of drug selection. Twenty-three of the 48 in vitro selections result in resistant parasites, with time to resistance onset ranging from 15 to 300 days. Our data indicate that pre-existing resistance may not be a major hurdle for novel-target antimalarial candidates, and focusing our attention on fast-killing compounds may result in a slower onset of clinical resistance.

Indexed as

Drug ResistanceAnimalsAntimalarialsClone CellsINDEL MutationMutationParasitesPlasmodium falciparumPolymorphism, Single NucleotideAntimalarials

Identifiers

PMID27301419
PMCPMC4912613
OpenAlexW2440524256

What OpenQuestion holds

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Registered trials

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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.