Evidence map›Paper›PMID 25753626›Full record

ArticleAntimicrobial agents and chemotherapy2015

Impact of antimalarial treatment and chemoprevention on the drug sensitivity of malaria parasites isolated from ugandan children.

Patrick Tumwebaze, Melissa D Conrad, Andrew Walakira, Norbert LeClair, Oswald Byaruhanga, Christine Nakazibwe, Benjamin Kozak, Jessica Bloome, Jaffer Okiring, Abel Kakuru and 11 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00948896 (A Randomized Controlled Trial of Monthly Dihydroartemisinin-piperaquine Versus Monthly Sulfadoxine-pyrimethamine Versus Daily Trimethoprim-sulfamethoxazole Versus No Therapy for the Prevention of Malaria), which is not on this map. Cited by 54 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 2 pooled it
8.3field-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.

NCT00948896 phase3completednot on this map

A Randomized Controlled Trial of Monthly Dihydroartemisinin-piperaquine Versus Monthly Sulfadoxine-pyrimethamine Versus Daily Trimethoprim-sulfamethoxazole Versus No Therapy for the Prevention of Malaria

TypeinterventionalSponsorUniversity of California, San FranciscoRan2010 to 2014Enrolled600ConditionsMalariaArmstrimethoprim-sulfamethoxazole (TS, TMP/SMX), sulfadoxine-pyrimethamine (SP), dihydroartemisinin-piperaquine (DP)
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Changing Antimalarial Drug Sensitivities in Uganda.Antimicrobial agents and chemotherapy · 2017
    Trial
  7. Trial
  8. Trial
  9. Trial
  10. Imported malaria predominates in near-elimination settings in Southwestern Uganda.medRxiv : the preprint server for health sciences · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Day 3 parasitemia andmedRxiv : the preprint server for health sciences · 2024
    Article
  18. Article
  19. Article
  20. Review
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

21 authors at 4 institutions in 2 countries.

Patrick TumwebazeInfectious Diseases Research Collaboration, Kampala, Uganda.
Melissa D ConradDepartment of Medicine, University of California, San Francisco, California, USA.
Andrew WalakiraInfectious Diseases Research Collaboration, Kampala, Uganda.
Norbert LeClairDepartment of Medicine, University of California, San Francisco, California, USA.
Oswald ByaruhangaInfectious Diseases Research Collaboration, Kampala, Uganda.
Christine NakazibweInfectious Diseases Research Collaboration, Kampala, Uganda.
Benjamin KozakDepartment of Medicine, University of California, San Francisco, California, USA.
Jessica BloomeDepartment of Medicine, University of California, San Francisco, California, USA.
Jaffer OkiringInfectious Diseases Research Collaboration, Kampala, Uganda.
Abel KakuruInfectious Diseases Research Collaboration, Kampala, Uganda.
Victor BigiraInfectious Diseases Research Collaboration, Kampala, Uganda.
James KapisiInfectious Diseases Research Collaboration, Kampala, Uganda.
Jennifer LegacDepartment of Medicine, University of California, San Francisco, California, USA.
Jiri GutDepartment of Medicine, University of California, San Francisco, California, USA.
Roland A CooperDepartment of Natural Sciences and Mathematics, Dominican University of California, San Rafael, California, USA.
Moses R KamyaSchool of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Diane V HavlirDepartment of Medicine, University of California, San Francisco, California, USA.
Grant DorseyDepartment of Medicine, University of California, San Francisco, California, USA.
Bryan GreenhouseDepartment of Medicine, University of California, San Francisco, California, USA.
Samuel L NsobyaInfectious Diseases Research Collaboration, Kampala, Uganda.
Philip J RosenthalDepartment of Medicine, University of California, San Francisco, California, USA prosenthal@medsfgh.ucsf.edu.
University of California, San Francisco · USInfectious Diseases Research Collaboration · UGDominican University of California · USMakerere University · UG

Funding

San Francisco Vaccine and Prevention UnitUM1AI069496 · NIAID · PUBLIC HEALTH FOUNDATION ENTERPRISES · PI Susan Buchbinder, Diane V Havlir · 2012 to 2026
$30.5M
Transmission ProjectU19AI089674 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHEW G DORSEY, MOSES Robert KAMYA · 2010 to 2026
$29.3M
The immunologic consequences of prenatal exposure to malariaP01HD059454 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHARLEBOIS, EDWIN DUNCAN · 2008 to 2017
$22.6M
Resistance of Malaria Parasites to Artemisinin-Based TherapiesR01AI075045 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENTHAL, PHILIP JON · 2009 to 2024
$8.4M
Pharmacological insights into antimalarial exposure, clinical outcomes, and drug resistance in AfricaR01AI117001 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AWEEKA, FRANCESCA T., ROSENTHAL, PHILIP JON · 2015 to 2024
$7.1M
Training In Malaria Research in UgandaD43TW007375 · FIC · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENTHAL, PHILIP JON · 2005 to 2019
$2.9M
Resistance of Malaria Parasites to Artemisinin-Based Combination TherapiesR56AI075045 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENTHAL, PHILIP JON · 2008 to 2008
$618k
FIC NIH HHS D43 TW007375FIC NIH HHS TW007375NIAID NIH HHS AI075045NIAID NIH HHS AI089674NIAID NIH HHS R01 AI075045NIAID NIH HHS R01 AI117001NIAID NIH HHS R56 AI075045NIAID NIH HHS U19 AI089674NIAID NIH HHS UM1 AI069496NICHD NIH HHS HD059454NICHD NIH HHS P01 HD059454
6 · The paper itself

Abstract

Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. Over time, ex vivo sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of pfcrt K76 and pfmdr1 N86 and D1246 increased, and the prevalences of pfdhfr and pfdhps polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased ex vivo lumefantrine sensitivity and increased prevalence of pfcrt K76 and pfmdr1 N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of pfmdr1 86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively.

Indexed as

AmodiaquineAntimalarialsArtemisininsATP-Binding Cassette, Sub-Family C ProteinsChild, PreschoolChloroquineClinical Trials as TopicEthanolaminesFluorenesHumansInfantLumefantrineMembrane Transport ProteinsParasitic Sensitivity TestsPiperazinesPlasmodium falciparumAmodiaquineAntimalarialsArtemisininsartenimolATP-Binding Cassette, Sub-Family C ProteinsChloroquinedesethylamodiaquineEthanolaminesFluorenesLumefantrineMdr1 protein, Plasmodium falciparumMembrane Transport ProteinsPfCRT protein, Plasmodium falciparumpiperaquinePiperazinesProtozoan ProteinsQuinineQuinolines

Identifiers

PMID25753626
PMCPMC4432194
OpenAlexW2111367011

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.