Evidence map›Paper›PMID 34732201›Full record

Trial reportMalaria journal2021

Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018.

Catherine M Dentinger, Tovonahary Angelo Rakotomanga, Antsa Rakotondrandriana, Arinomenjanahary Rakotoarisoa, Marie Ange Rason, Leah F Moriarty, Laura C Steinhardt, Laurent Kapesa, Jocelyn Razafindrakoto, Samaly S Svigel and 4 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Malaria journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. [Pcr-rflp genotyping ofMedecine tropicale et sante internationale · 2022
    Article
  8. Article
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

14 authors at 4 institutions in 2 countries.

Catherine M DentingerMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, Georgia. Cdentinger@cdc.gov.ORCID http://orcid.org/0000-0001-9971-457X
Tovonahary Angelo RakotomangaNational Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.
Antsa RakotondrandrianaNational Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.
Arinomenjanahary RakotoarisoaNational Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.
Marie Ange RasonNational Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.
Leah F MoriartyMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, Georgia.
Laura C SteinhardtMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, Georgia.
Laurent KapesaUS President's Malaria Initiative, USAID, Antananarivo, Madagascar.
Jocelyn RazafindrakotoUS President's Malaria Initiative, USAID, Antananarivo, Madagascar.
Samaly S SvigelMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, Georgia.
Naomi W LucchiMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, Georgia.
Venkatachalam UdhayakumarMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, Georgia.
Eric S HalseyMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, Georgia.
C Arsène RatsimbasoaNational Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.
Centers for Disease Control and Prevention · USU.S. President's Malaria Initiative · USUniversité de Fianarantsoa · MGUniversity of Antananarivo · MG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSince 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance.

methodsChildren aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000-100,000 parasites/µl determined by microscopy were enrolled from May-September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted.

resultsOf 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100-100) and 95% (95% CI 91-100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97-100) in Ankazomborona and 83% (95% CI 76-92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100-100) and 98% (95% CI 95-100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99-100) in Ankazomborona and 95% (95% CI 91-100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72-76.

conclusionPCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.

Indexed as

AdolescentAmodiaquineAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsATP-Binding Cassette, Sub-Family C ProteinsChildChild, PreschoolDNA, ProtozoanDrug CombinationsFemaleHumansInfantMadagascarMalaria, FalciparumMaleAmodiaquineamodiaquine, artesunate drug combinationAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsATP-Binding Cassette, Sub-Family C ProteinsDNA, ProtozoanDrug CombinationsMdr1 protein, Plasmodium falciparumAnti-malarialArtemisinin-based combination therapyEfficacyMadagascarResistance

Identifiers

PMID34732201
PMCPMC8565026
OpenAlexW3178815982

What OpenQuestion holds

Textmetadata
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.