Evidence map›Paper›PMID 28535801›Full record

ArticleMalaria journal2017

Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria.

Christian N Nguetse, Ayola Akim Adegnika, Tsiri Agbenyega, Bernhards R Ogutu, Sanjeev Krishna, Peter G Kremsner, Thirumalaisamy P Velavan

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.2field-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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Drug Resistance Molecular Markers ofTropical medicine and infectious disease · 2023
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  10. Characterization ofAntimicrobial agents and chemotherapy · 2021
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  12. Article
  13. Article
  14. Article
  15. An alternative dogma on reduced artemisinin susceptibility: A new shadow from east to west.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  16. Article
  17. Article
  18. Article
  19. Profiling antimalarial drug-resistant haplotypes inTherapeutic advances in infectious disease
    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

7 authors at 6 institutions in 6 countries.

Christian N NguetseInstitute of Tropical Medicine, University Tübingen, Wilhelmstrasse 27, 72074, Tübingen, Germany.
Ayola Akim AdegnikaInstitute of Tropical Medicine, University Tübingen, Wilhelmstrasse 27, 72074, Tübingen, Germany.
Tsiri AgbenyegaDepartment of Physiology, University of Science and Technology, School of Medical Sciences, Kumasi, Ghana.
Bernhards R OgutuCentre for Clinical Research, Kenya Medical Research Institute, Kisumu, Kenya.
Sanjeev KrishnaInstitute of Tropical Medicine, University Tübingen, Wilhelmstrasse 27, 72074, Tübingen, Germany.
Peter G KremsnerInstitute of Tropical Medicine, University Tübingen, Wilhelmstrasse 27, 72074, Tübingen, Germany.
Thirumalaisamy P VelavanInstitute of Tropical Medicine, University Tübingen, Wilhelmstrasse 27, 72074, Tübingen, Germany. velavan@medizin.uni-tuebingen.de.
Centre de Recherche Médicales de Lambaréné · GAFondation Congolaise Pour La Recherche Médicale · CGKenya Medical Research Institute · KEKomfo Anokye Teaching Hospital · GHSt George's, University of London · GBUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe Plasmodium falciparum multidrug resistance 1 (PfMDR1), P. falciparum Ca

methodsSamples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for pfmdr1, pfatp6 and pfk13 loci by DNA sequencing and assessing pfmdr1 copy number variation (CNV) by real-time PCR.

resultsPfmdr1-N86Y mutation was detected in 48, 10 and 10% in Lambaréné, Kumasi and Kisumu, respectively. At codon 184, the prevalence of the mutation was 73% in Lambaréné, 63% in Kumasi and 49% Kisumu. The S1034C and N1042D variants were absent at all three sites, while the frequency of the D1246Y mutation was 1, 3 and 13% in Lambaréné, Kumasi and Kisumu, respectively. Isolates with two pfmdr1 gene copy number predominantly harboured the N86Y wild-type allele and were mostly found in Kumasi (10%) (P < 0.0001). Among the main pfmdr1 haplotypes (NFD, NYD and YFD), NYD was associated with highest parasitaemia (P = 0.04). At the pfatp6 locus, H243Y and A623E mutations were observed at very low frequency at all three sites. The prevalence of the pfatp6 E431K variant was 6, 18 and 17% in Lambaréné, Kumasi and Kisumu, respectively. The L263E and S769N mutations were absent in all isolates. The pfk13 variants associated with artemisinin resistance in Southeast Asia were not observed. Eleven novel substitutions in the pfk13 locus occurring at low frequency were observed.

conclusionsArtemisinins are still highly efficacious in large malaria-endemic regions though declining efficacy has occurred in Southeast Asia. The return of chloroquine-sensitive strains following the removal of drug pressure is observed. However, selection of wild-type alleles in the multidrug-resistance gene and the increased gene copy number is associated with reduced lumefantrine sensitivity. This study indicates a need to constantly monitor drug resistance to artemisinin in field isolates from malaria-endemic countries.

Indexed as

Polymorphism, GeneticAntimalarialsATP-Binding Cassette TransportersCalcium-Transporting ATPasesChildChild, PreschoolDNA Copy Number VariationsDrug ResistanceGabonGenetic MarkersGhanaHumansInfantInfant, NewbornKenyaPlasmodium falciparumAntimalarialsATP6 protein, Plasmodium falciparumATP-Binding Cassette TransportersCalcium-Transporting ATPasesGenetic Markersmdr gene protein, PlasmodiumProtozoan ProteinsAfricaAnti-malarial drugsMalariaP. falciparumPfatp6Pfk13Pfmdr1Resistance

Identifiers

PMID28535801
PMCPMC5442681
OpenAlexW2616960498

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.