Evidence map›Paper›PMID 25564249›Full record

Observational studyThe Journal of infectious diseases2015

The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women.

Julie Gutman, Linda Kalilani, Steve Taylor, Zhiyong Zhou, Ryan E Wiegand, Kyaw L Thwai, Dyson Mwandama, Carole Khairallah, Mwayi Madanitsa, Ebbie Chaluluka and 7 more

Registry-linked trialOpen access · hybridAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04147546 (Operational Feasibility, Impact of Additional Screening Using Highly-sensitives RDTs Combined With High Coverage of IPTp on Placental Malaria and Low Birth Weight), which is not on this map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
7.0field-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.

NCT04147546 phase3completednot on this mapstarted 2020, after this paper: background citation

Operational Feasibility, Impact of Additional Screening Using Highly-sensitives RDTs Combined With High Coverage of IPTp on Placental Malaria and Low Birth Weight

TypeinterventionalSponsorInstitut de Recherche en Sciences de la Sante, Burkina FasoRan2020 to 2021Enrolled340ConditionsPlasmodium Falciparum Malaria, Malaria DiagnosisArmsAdditional screening using ultra sensitive RDTs, Dihydroartemisinin-piperaquin, Reminders
3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.

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  4. Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
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  17. Persistent and CirculatingPathogens (Basel, Switzerland) · 2026
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  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 3 countries.

Julie GutmanDivision of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia.
Linda KalilaniCollege of Medicine, University of Malawi Department of Community Health, College of Medicine, Blantyre.
Steve TaylorDuke University Medical Center, Durham University of North Carolina, Chapel Hill.
Zhiyong ZhouDivision of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia.
Ryan E WiegandDivision of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia.
Kyaw L ThwaiDuke University Medical Center, Durham.
Dyson MwandamaMalaria Alert Centre, University of Malawi College of Medicine.
Carole KhairallahLiverpool School of Tropical Medicine, United Kingdom.
Mwayi MadanitsaCollege of Medicine, University of Malawi Department of Community Health, College of Medicine, Blantyre.
Ebbie ChalulukaCollege of Medicine, University of Malawi Department of Community Health, College of Medicine, Blantyre.
Fraction DzinjalamalaCollege of Medicine, University of Malawi Malaria Alert Centre, University of Malawi College of Medicine.
Doreen AliNational Malaria Control Program, Lilongwe, Malawi.
Don P MathangaMalaria Alert Centre, University of Malawi College of Medicine Department of Community Health, College of Medicine, Blantyre.
Jacek SkarbinskiDivision of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia.
Ya Ping ShiDivision of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia.
Steve MeshnickDuke University Medical Center, Durham.
Feiko O ter KuileLiverpool School of Tropical Medicine, United Kingdom.
University of Malawi · MWCenters for Disease Control and Prevention · USDuke Medical Center · USLiverpool School of Tropical Medicine · GBDivision of Parasitic Diseases and Malaria · USPublic Health Institute of Malawi · MW

Funding

Strengthening National Capacity in Operations ResearchU01CI000189 · CI · UNIVERSITY OF MALAWI · PI BOWIE, CAMERON · 2004 to 2009
$2.0M
NCPDCID CDC HHS 5 U01 CI000189NCPDCID CDC HHS U01 CI000189
6 · The paper itself

Abstract

backgroundThe A581 G: mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called sextuple mutant, has been associated with increased placental inflammation and decreased infant birth weight among women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) during pregnancy.

methodsBetween 2009 and 2011, delivering women without human immunodeficiency virus infection were enrolled in an observational study of IPTp-SP effectiveness in Malawi. Parasites were detected by polymerase chain reaction (PCR); positive samples were sequenced to genotype the dhfr and dhps loci. The presence of K540 E: in dhps was used as a marker for the quintuple mutant.

resultsSamples from 1809 women were analyzed by PCR; 220 (12%) were positive for P. falciparum. A total of 202 specimens were genotyped at codon 581 of dhps; 17 (8.4%) harbored the sextuple mutant. The sextuple mutant was associated with higher risks of patent infection in peripheral blood (adjusted prevalence ratio [aPR], 2.76; 95% confidence interval [CI], 1.82-4.18) and placental blood (aPR 3.28; 95% CI, 1.88-5.78) and higher parasite densities. Recent SP use was not associated with increased parasite densities or placental pathology overall and among women with parasites carrying dhps A581 G: .

conclusionsIPTp-SP failed to inhibit parasite growth but did not exacerbate pathology among women infected with sextuple-mutant parasites. New interventions to prevent malaria during pregnancy are needed urgently.

Indexed as

Drug ResistanceMutation, MissenseDihydropteroate SynthaseDNA, ProtozoanDrug CombinationsFemaleGenotypeHumansInfant, NewbornMalaria, FalciparumMalawiPlasmodium falciparumPoint MutationPolymerase Chain ReactionPregnancyPyrimethamineDihydropteroate SynthaseDNA, ProtozoanDrug Combinationsfanasil, pyrimethamine drug combinationPyrimethamineSulfadoxineTetrahydrofolate Dehydrogenasedihydropteroate synthaseintermittent preventive therapymalariaMalawiPlasmodium falciparumpregnancysulfadoxine-pyrimethamine

Identifiers

PMID25564249
PMCPMC4539907
OpenAlexW2107150651

What OpenQuestion holds

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Registered trials

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.