Evidence map›Paper›PMID 37127669›Full record

ArticleMalaria journal2023

Plasmodium falciparum kelch13 polymorphisms identified after treatment failure with artemisinin-based combination therapy in Niger.

Ibrahima Issa Arzika, Neil F Lobo, Mahaman Moustapha Lamine, Ilagouma Amadou Tidjani, Houzé Sandrine, Véronique Sarrasin-Hubert, Aboubacar Mahamadou, Eric Adehossi, Demba Sarr, Ousman Mahmud and 1 more

Abstract read
In one paragraph

Article in Malaria journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Mapping Plasmodium falciparum mutations in Africa: A critical review of emerging drug resistance and implications for malaria control.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2025
    Review
  5. Article
  6. A NovelmedRxiv : the preprint server for health sciences · 2025
    Article
  7. Article
  8. 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

11 authors.

Ibrahima Issa ArzikaCentre de Recherche Médicale et Sanitaire de Niamey, Niamey, Niger.
Neil F LoboUniversity of Notre Dame, Notre Dame, USA.
Mahaman Moustapha LamineCentre de Recherche Médicale et Sanitaire de Niamey, Niamey, Niger. laminemahamanmoustapha@gmail.com.
Ilagouma Amadou TidjaniUniversity Abdou Moumouni of Niamey, Niamey, Niger.
Houzé SandrineCentre National de Référence du Paludisme, Paris, France.
Véronique Sarrasin-HubertCentre National de Référence du Paludisme, Paris, France.
Aboubacar MahamadouCentre de Recherche Médicale et Sanitaire de Niamey, Niamey, Niger.
Eric AdehossiUniversity Abdou Moumouni of Niamey, Niamey, Niger.
Demba SarrUniversity of Georgia, Athens, USA.
Ousman MahmudUniversity of Georgia, Athens, USA.
Ibrahim Maman LaminouCentre de Recherche Médicale et Sanitaire de Niamey, Niamey, Niger.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundArtemisinin-based combination therapy (ACT) is the most effective treatment for malaria, and has significantly reduced morbimortality. Polymorphisms associated with the Plasmodium falciparum Kelch gene (Pfkelch13) have been associated with delayed parasite clearance even with ACT treatment.

methodsThe Pfkelch13 gene was sequenced from P. falciparum infected patients (n = 159) with uncomplicated malaria in Niger. An adequate clinical and parasitological response (ACPR) was reported in 155 patients. Four (n = 4) patients had treatment failure (TF) that were not reinfections-two of which had late parasitological failures (LPF) and two had late clinical failures (LCF).

resultsThirteen single nucleotide polymorphisms (SNPs) were identified of which seven were non-synonymous (C469R, T508S, R515T, A578S, I465V, I437V, F506L,), and three were synonymous (P443P, P715P, L514L). Three SNP (C469R, F506L, P715P) were present before ACT treatment, while seven mutations (C469R, T508S, R515T, L514L, P443P, I437V, I465V) were selected by artemether/lumefantrine (AL)-five of which were non-synonymous (C469R, T508S, R515T, I437V, I465V). Artesunate/amodiaquine (ASAQ) has selected any mutation. One sample presented three cumulatively non-synonymous SNPs-C469R, T508S, R515T.

conclusionsThis study demonstrates intra-host selection of Pfkelch13 gene by AL. The study highlights the importance of LCF and LPF parasites in the selection of resistance to ACT. Further studies using gene editing are required to confirm the potential implication of resistance to ACT with the most common R515T and T508S mutations. It would also be important to elucidate the role of cumulative mutations.

Indexed as

AntimalarialsArtemisininsMalaria, FalciparumAmodiaquineArtemetherArtemether, Lumefantrine Drug CombinationDrug CombinationsHumansNigerPlasmodium falciparumPolymorphism, Single NucleotideTreatment FailureAmodiaquineAntimalarialsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsDrug CombinationsArtemisininNigerP. falciparumPfkelch13Resistance

Identifiers

PMID37127669
PMCPMC10150466

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Registered trials

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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.