Evidence map›Paper›PMID 34795281›Full record

Trial reportNature communications2021

Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children.

Erika Wallender, Ali Mohamed Ali, Emma Hughes, Abel Kakuru, Prasanna Jagannathan, Mary Kakuru Muhindo, Bishop Opira, Meghan Whalen, Liusheng Huang, Marvin Duvalsaint and 6 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02163447 (Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants), which is not on this map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
2.6field-weighted citation impact, top 10% 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.

NCT02163447 phase3completednot on this map

Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants (PROMOTE Birth Cohort 1)

TypeinterventionalSponsorGrant Dorsey, M.D, Ph.D.Ran2014 to 2018Enrolled300ConditionsMalariaArmsMonthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy, Monthly dihydroartemisinin-piperaquine (DP) for infants, 3-monthly dihydroartemisinin-piperaquine (DP) for infants
3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Pooled it
  3. Trial
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
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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

16 authors at 3 institutions in 2 countries.

Erika WallenderDepartment of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1166-1587
Ali Mohamed AliDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Emma HughesDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Abel KakuruInfectious Diseases Research Collaboration, Kampala, Uganda.
Prasanna JagannathanDepartment of Medicine, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0001-6305-758X
Mary Kakuru MuhindoInfectious Diseases Research Collaboration, Kampala, Uganda.
Bishop OpiraInfectious Diseases Research Collaboration, Kampala, Uganda.
Meghan WhalenDepartment of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
Liusheng HuangDepartment of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2702-4486
Marvin DuvalsaintDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jenny LegacDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Moses R KamyaInfectious Diseases Research Collaboration, Kampala, Uganda.
Grant DorseyDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Francesca AweekaDepartment of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
Philip J RosenthalDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Rada M SavicDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA. rada.savic@ucsf.edu.ORCID http://orcid.org/0000-0003-3143-5579
University of California, San Francisco · USInfectious Diseases Research Collaboration · UGStanford University · US

Funding

Institutional Career Development Core SupplementKL2TR001870 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KANAYA, ALKA M., SARKAR, URMIMALA · 2016 to 2025
$19.7M
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
Enhancing immunity to malaria in young children with effective chemopreventionU01AI155325 · NIAID · STANFORD UNIVERSITY · PI JAGANNATHAN, PRASANNA · 2021 to 2025
$6.3M
NCATS NIH HHS KL2 TR001870NIAID NIH HHS R01 AI117001
6 · The paper itself

Abstract

Intermittent preventive treatment (IPT) with dihydroartemisinin-piperaquine (DP) is highly protective against malaria in children, but is not standard in malaria-endemic countries. Optimal DP dosing regimens will maximize efficacy and reduce toxicity and resistance selection. We analyze piperaquine (PPQ) concentrations (n = 4573), malaria incidence data (n = 326), and P. falciparum drug resistance markers from a trial of children randomized to IPT with DP every 12 weeks (n = 184) or every 4 weeks (n = 96) from 2 to 24 months of age (NCT02163447). We use nonlinear mixed effects modeling to establish malaria protective PPQ levels and risk factors for suboptimal protection. Compared to DP every 12 weeks, DP every 4 weeks is associated with 95% protective efficacy (95% CI: 84-99%). A PPQ level of 15.4 ng/mL reduces the malaria hazard by 95%. Malnutrition reduces PPQ exposure. In simulations, we show that DP every 4 weeks is optimal across a range of transmission intensities, and age-based dosing improves malaria protection in young or malnourished children.

Indexed as

AlgorithmsAntimalarialsArtemisininsChildChild, PreschoolDose-Response Relationship, DrugFemaleHumansIncidenceInfantMalaria, FalciparumMaleModels, BiologicalOutcome Assessment, Health CarePiperazinesPlasmodium falciparumAntimalarialsArtemisininsartenimolpiperaquinePiperazinesQuinolines

Identifiers

PMID34795281
PMCPMC8602248
OpenAlexW3212792377

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.