Evidence map›Paper›PMID 24994911›Full record

ArticleThe Journal of infectious diseases2014

Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT.

Gisela Henriques, Rachel L Hallett, Khalid B Beshir, Nahla B Gadalla, Rachel E Johnson, Rebekah Burrow, Donelly A van Schalkwyk, Patrick Sawa, Sabah A Omar, Taane G Clark and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% 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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

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28 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

12 authors at 4 institutions in 3 countries.

Gisela HenriquesDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Rachel L HallettDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Khalid B BeshirDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Nahla B GadallaDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Rachel E JohnsonDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Rebekah BurrowDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Donelly A van SchalkwykDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Patrick SawaHuman Health Division, International Centre for Insect Physiology and Ecology, Mbita Point.
Sabah A OmarKenya Medical Research Institute, Nairobi.
Taane G ClarkDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Teun BousemaDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Colin J SutherlandDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
London School of Hygiene & Tropical Medicine · GBInternational Centre of Insect Physiology and Ecology · KEKenya Medical Research Institute · KERadboud University Nijmegen · NL

Funding

Medical Research Council
6 · The paper itself

Abstract

backgroundThe efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria may be threatened by parasites with reduced responsiveness to artemisinins. Among 298 ACT-treated children from Mbita, Kenya, submicroscopic persistence of P. falciparum on day 3 posttreatment was associated with subsequent microscopically detected parasitemia at days 28 or 42.

methodsDNA sequences of resistance-associated parasite loci pfcrt, pfmdr1, pfubp1, and pfap2mu were determined in the Mbita cohort before treatment, on days 2 and 3 after initiation of treatment, and on the day of treatment failure.

resultsParasites surviving ACT on day 2 or day 3 posttreatment were significantly more likely than the baseline population to carry the wild-type haplotypes of pfcrt (CVMNK at codons 72-76; P < .001) and pfmdr1 (NFD at codons 86, 184, 1246; P < .001). In contrast, variant alleles of the novel candidate resistance genes pfap2mu (S160N/T; P = .006) and pfubp-1 (E1528D; P < .001) were significantly more prevalent posttreatment. No genetic similarities were found to artemisinin-tolerant parasites recently described in Cambodia.

conclusionsAmong treated children in western Kenya, certain P. falciparum genotypes defined at pfcrt, pfmdr1, pfap2mu, and pfubp1 more often survive ACT at the submicroscopic level, and contribute to onward transmission and subsequent patent recrudescence.

Indexed as

Selection, GeneticAntimalarialsArtemisininsATP-Binding Cassette, Sub-Family C ProteinsCambodiaChildChild, PreschoolDrug ResistanceDrug Therapy, CombinationFemaleGenotypeHumansInfantKenyaMalaria, FalciparumMaleAntimalarialsartemisininArtemisininsATP-Binding Cassette, Sub-Family C ProteinsMdr1 protein, Plasmodium falciparumMembrane Transport ProteinsPfCRT protein, Plasmodium falciparumProtozoan Proteinsartemisinindrug resistancegeneticsmalaria

Identifiers

PMID24994911
PMCPMC4241946
OpenAlexW2111017284

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.