Evidence map›Paper›PMID 24610872›Full record

ArticleThe Journal of infectious diseases2014

Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children.

Melissa D Conrad, Norbert LeClair, Emmanuel Arinaitwe, Humphrey Wanzira, Abel Kakuru, Victor Bigira, Mary Muhindo, Moses R Kamya, Jordan W Tappero, Bryan Greenhouse and 2 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
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. It is linked to trial NCT00527800 (Interactions Between HIV and Malaria in African Children), which is not on this map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
15.7field-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.

NCT00527800 phase3completednot on this map

Interactions Between HIV and Malaria in African Children

TypeinterventionalSponsorUniversity of California, San FranciscoRan2007 to 2013Enrolled351ConditionsMalaria, HIV InfectionsArmsDihydroartemisinin-piperaquine, Artemether-lumefantrine, Trimethoprim-sulfamethoxazole
3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.

  1. Pooled it
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  6. Changing Antimalarial Drug Sensitivities in Uganda.Antimicrobial agents and chemotherapy · 2017
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  12. Impact of intermittent preventive treatment with dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014
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  20. Frontiers in cellular and infection microbiology · 2022
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Melissa D ConradDepartment of Medicine, University of California, San Francisco.
Norbert LeClairDepartment of Medicine, University of California, San Francisco.
Emmanuel ArinaitweInfectious Diseases Research Collaboration.
Humphrey WanziraInfectious Diseases Research Collaboration.
Abel KakuruInfectious Diseases Research Collaboration.
Victor BigiraInfectious Diseases Research Collaboration.
Mary MuhindoInfectious Diseases Research Collaboration.
Moses R KamyaDepartment of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Jordan W TapperoCenter for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Bryan GreenhouseDepartment of Medicine, University of California, San Francisco.
Grant DorseyDepartment of Medicine, University of California, San Francisco.
Philip J RosenthalDepartment of Medicine, University of California, San Francisco.
Infectious Diseases Research Collaboration · UGUniversity of California, San Francisco · USCenters for Disease Control and Prevention · USMakerere University · UG

Funding

Transmission ProjectU19AI089674 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHEW G DORSEY, MOSES Robert KAMYA · 2010 to 2026
$29.3M
Resistance of Malaria Parasites to Artemisinin-Based TherapiesR01AI075045 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENTHAL, PHILIP JON · 2009 to 2024
$8.4M
Resistance of Malaria Parasites to Artemisinin-Based Combination TherapiesR56AI075045 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENTHAL, PHILIP JON · 2008 to 2008
$618k
NIAID NIH HHS AI075045NIAID NIH HHS AI089674NIAID NIH HHS R01 AI075045NIAID NIH HHS R56 AI075045NIAID NIH HHS U19 AI089674PEPFAR
6 · The paper itself

Abstract

backgroundArtemisinin-based combination therapies, including artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), are recommended to treat uncomplicated falciparum malaria. Sensitivities to components of AL and DP are impacted by polymorphisms in pfmdr1 and pfcrt. We monitored changes in prevalences of polymorphisms in Tororo, Uganda, from 2008 to 2012.

methodsPolymorphic loci in pfmdr1 and pfcrt were characterized in samples from 312 children randomized to AL or DP for each episode of uncomplicated malaria (50 samples per arm for each 3-month interval) utilizing a fluorescent microsphere assay. Treatment outcomes and impacts of prior therapies were also characterized.

resultsPrevalence increased significantly over time for pfmdr1 N86 (AL: odds ratio [OR], 2.08 [95% confidence interval {CI}, 1.83-2.38]; DP: 1.41 [95% CI, 1.25-1.57]), pfmdr1 D1246 (AL: 1.46 [95% CI, 1.29-1.64]; DP: 1.36 [95% CI, 1.23-1.50]), and pfcrt K76 (AL: 3.37 [95% CI, 1.85-6.16]; DP: 5.84 [95% CI, 1.94-17.53], and decreased for pfmdr1 Y184 (AL: 0.78 [95% CI, .70-.86]; DP: 0.84 [95% CI, .76-1.50]); changes were consistently greater in the AL arm. Recent AL treatment selected for pfmdr1 N86, D1246, and 184F in subsequent episodes; DP selected for the opposite alleles.

conclusionsGenotypes with decreased sensitivity to AL components increased over time. This increase was greater in children receiving AL, suggesting that the choice of treatment regimen can profoundly influence parasite genetics and drug sensitivity. CLINICAL TRIALS REGISTRATION: NCT00527800.

Indexed as

Polymorphism, GeneticAllelesArtemisininsChild, PreschoolDrug ResistanceFemaleHumansInfantMalaria, FalciparumMalePlasmodium falciparumUgandaartemisininArtemisininsartemether-lumefantrinedihydroartemisinin-piperaquinepfcrtpfmdr1Plasmodium falciparum

Identifiers

PMID24610872
PMCPMC4110461
OpenAlexW2155737651

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.