Evidence map›Paper›PMID 27899115›Full record

ArticleMalaria journal2016

Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi.

Matt Ravenhall, Ernest Diez Benavente, Mwapatsa Mipando, Anja T R Jensen, Colin J Sutherland, Cally Roper, Nuno Sepúlveda, Dominic P Kwiatkowski, Jacqui Montgomery, Kamija S Phiri and 5 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

33 citing papers in PubMed, 52 citations in OpenAlex.

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  18. An open dataset ofWellcome open research · 2021
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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

15 authors at 7 institutions in 4 countries.

Matt RavenhallFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.ORCID http://orcid.org/0000-0002-7818-2348
Ernest Diez BenaventeFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Mwapatsa MipandoDepartment of Physiology, College of Medicine, University of Malawi, Blantyre, Malawi.
Anja T R JensenCentre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
Colin J SutherlandFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Cally RoperFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Nuno SepúlvedaFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Dominic P KwiatkowskiWellcome Trust Sanger Institute, Hinxton, UK.
Jacqui MontgomeryLiverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Kamija S PhiriSchool of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.
Anja TerlouwLiverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Alister CraigLiverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Susana CampinoFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. susana.campino@lshtm.ac.uk.
Harold OchollaMalawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi. harold.ocholla@gmail.com.
Taane G ClarkFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. taane.clark@lshtm.ac.uk.
London School of Hygiene & Tropical Medicine · GBUniversity of Liverpool · GBUniversity of Malawi · MWLiverpool School of Tropical Medicine · GBUniversity of Copenhagen · DKUniversity of Lisbon · PTWellcome Sanger Institute · GB

Funding

Medical Research Council MC_PC_15103Medical Research Council MR/K000551/1Medical Research Council MR/M01360X/1Medical Research Council MR/N010469/1Wellcome Trust 080964
6 · The paper itself

Abstract

backgroundMalawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population.

methodsWhole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used. More than 745,000 SNPs were identified, and differences in allele frequencies between countries assessed, as well as genetic regions under positive selection determined.

resultsPositive selection signals were identified within dhps, dhfr and gch1, all components of the parasite folate pathway associated with SP resistance. Sitting predominantly on a dhfr triple mutation background, a novel copy number increase of ~twofold was identified in the gch1 promoter. This copy number was almost fixed (96.8% frequency) in Malawi samples, but found at less than 45% frequency in other African populations, and distinct from a whole gene duplication previously reported in Southeast Asian parasites.

conclusionsSP resistance selection pressures have been retained in the Malawian population, with known resistance dhfr mutations at fixation, complemented by a novel gch1 promoter duplication. The effects of the duplication on the fitness costs of SP variants and resistance need to be elucidated.

Indexed as

Genetic VariationAntimalarialsChild, PreschoolDrug CombinationsDrug ResistanceFemaleGene FrequencyGenome, ProtozoanGenotypeHumansInfantMalaria, FalciparumMalawiMaleMutationPlasmodium falciparumAntimalarialsDrug Combinationsfanasil, pyrimethamine drug combinationPyrimethamineSulfadoxine

Identifiers

PMID27899115
PMCPMC5129638
OpenAlexW2558458096

What OpenQuestion holds

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LicenceCC BY
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.