Evidence map›Paper›PMID 19841150›Full record

Trial reportAntimicrobial agents and chemotherapy2010

Molecular correlates of high-level antifolate resistance in Rwandan children with Plasmodium falciparum malaria.

Corine Karema, Mallika Imwong, Caterina I Fanello, Kasia Stepniewska, Aline Uwimana, Supatchara Nakeesathit, Arjen Dondorp, Nicholas P Day, Nicholas J White

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
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  6. Trial
  7. Article
  8. Article
  9. Review
  10. A Narrative Review on the Prevalence ofTropical medicine and infectious disease · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Genomic characterization ofFrontiers in cellular and infection microbiology · 2022
    Article
  15. Article
  16. Article
  17. An epigrammatic status of the 'RSC medicinal chemistry · 2020
    Review
  18. Article
  19. Review
  20. 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

9 authors at 5 institutions in 3 countries.

Corine KaremaNational Malaria Control Program, Kigali, Rwanda.
Mallika Imwong
Caterina I Fanello
Kasia Stepniewska
Aline Uwimana
Supatchara Nakeesathit
Arjen Dondorp
Nicholas P Day
Nicholas J White
Mahidol Oxford Tropical Medicine Research Unit · THRwanda Biomedical Center · RWUniversity of Oxford · GBMahidol University · THNuffield Orthopaedic Centre · GB

Funding

Wellcome Trust 066439/Z/01/2Wellcome Trust 093956
6 · The paper itself

Abstract

Antifolate drugs have an important role in the treatment of malaria. Polymorphisms in the genes encoding the dihydrofolate reductase and dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa drugs, respectively. Rwanda has the highest levels of antimalarial drug resistance in Africa. We correlated the efficacy of chlorproguanil-dapsone plus artesunate (CPG-DDS+A) and amodiaquine plus sulfadoxine-pyrimethamine (AQ+SP) in children with uncomplicated malaria caused by Plasmodium falciparum parasites with pfdhfr and pfdhps mutations, which are known to confer reduced drug susceptibility, in two areas of Rwanda. In the eastern province, where the cure rates were low, over 75% of isolates had three or more pfdhfr mutations and two or three pfdhps mutations and 11% had the pfdhfr 164-Leu polymorphism. In the western province, where the cure rates were significantly higher (P < 0.001), the prevalence of multiple resistance mutations was lower and the pfdhfr I164L polymorphism was not found. The risk of treatment failure following the administration of AQ+SP more than doubled for each additional pfdhfr resistance mutation (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.01 to 5.55; P = 0.048) and each pfdhps mutation (OR = 2.1; 95% CI = 1.21 to 3.54; P = 0.008). The risk of failure following CPG-DDS+A treatment was 2.2 times higher (95% CI = 1.34 to 3.7) for each additional pfdhfr mutation, whereas there was no association with mutations in the pfdhps gene (P = 0.13). The pfdhfr 164-Leu polymorphism is prevalent in eastern Rwanda. Antimalarial treatments with currently available antifol-sulfa combinations are no longer effective in Rwanda because of high-level resistance.

Indexed as

Analysis of VarianceAntimalarialsChildChild, PreschoolDrug CombinationsDrug ResistanceFolic Acid AntagonistsGene FrequencyGenes, ProtozoanHaplotypesHumansInfantMalaria, FalciparumMutationPlasmodium falciparumPolymorphism, GeneticAntimalarialsDrug Combinationsfanasil, pyrimethamine drug combinationFolic Acid AntagonistsPyrimethamineSulfadoxineTetrahydrofolate Dehydrogenase

Identifiers

PMID19841150
PMCPMC2798539
OpenAlexW2111022117

What OpenQuestion holds

Textmetadata
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.