Evidence map›Paper›PMID 28068997›Full record

ArticleMalaria journal2017

Absence of in vivo selection for K13 mutations after artemether-lumefantrine treatment in Uganda.

Betty Balikagala, Toshihiro Mita, Mie Ikeda, Miki Sakurai, Shouki Yatsushiro, Nobuyuki Takahashi, Shin-Ichiro Tachibana, Mary Auma, Edward H Ntege, Daisuke Ito and 8 more

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, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 5% 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, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
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  10. Reactive Oxygen Species as the Brainbox in Malaria Treatment.Antioxidants (Basel, Switzerland) · 2021
    Review
  11. Article
  12. Article
  13. Identification of Mutations in Antimalarial Resistance GeneTropical medicine and infectious disease · 2020
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. 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

18 authors at 7 institutions in 2 countries.

Betty BalikagalaDivision of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan.
Toshihiro MitaDepartment of Molecular and Cellular Parasitology, School of Medicine, Juntendo University, Tokyo, 113-8421, Japan. tmita@juntendo.ac.jp.
Mie IkedaDepartment of Molecular and Cellular Parasitology, School of Medicine, Juntendo University, Tokyo, 113-8421, Japan.
Miki SakuraiDepartment of International Affairs and Tropical Medicine, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Shouki YatsushiroHealth Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan.
Nobuyuki TakahashiDepartment of International Affairs and Tropical Medicine, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Shin-Ichiro TachibanaDepartment of Molecular and Cellular Parasitology, School of Medicine, Juntendo University, Tokyo, 113-8421, Japan.
Mary AumaSt. Mary's Hospital LACOR, Gulu, Uganda.
Edward H NtegeDivision of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan.
Daisuke ItoDivision of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan.
Eizo TakashimaDivision of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan.
Nirianne Marie Q PalacpacDepartment of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Thomas G EgwangMed Biotech Laboratories, Kampala, Uganda.
Joseph Okello OnenDepartment of Biology, Faculty of Science, Gulu University, Gulu, Uganda.
Masatoshi KataokaHealth Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan.
Eisaku KimuraDepartment of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Toshihiro HoriiDepartment of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Takafumi TsuboiDivision of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan. tsuboi.takafumi.mb@ehime-u.ac.jp.
Ehime University · JPJuntendo University · JPOsaka University · JPNational Institute of Advanced Industrial Science and Technology · JPTokyo Women's Medical University · JPGulu University · UGSt. Mary's Hospital Lacor · UG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIndividual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether-lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein.

methodsArtemether-lumefantrine efficacy study with a follow-up period of 28 days was conducted in northern Uganda in 2014. The above-mentioned genotypes were comparatively analysed before drug administration and on days; 3, 7, and 28 days after treatment.

resultsIn 61 individuals with successful follow-up, artemether-lumefantrine treatment regimen was very effective with PCR adjusted efficacy of 95.2%. Among 146 isolates obtained before treatment, wild-type alleles were observed in 98.6% of isolates in pfkelch13 and in all isolates in the six putative background genes except I356T in pfcrt, which had 2.4% of isolates as mixed infections. In vivo selection study revealed that all isolates detected in the follow-up period harboured wild type alleles in pfkelch13 and the six background genes.

conclusionMutations in pfkelch13 and the six background genes may not play an important role in the in vivo selection after artemether-lumefantrine treatment in Uganda. Different mechanisms might rather be associated with the existence of parasites after treatment.

Indexed as

Drug ResistanceSelection, GeneticAdolescentAdultAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsChildChild, PreschoolDrug CombinationsEthanolaminesFemaleFluorenesHumansInfantMalaria, FalciparumAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsDrug CombinationsEthanolaminesFluorenesProtozoan ProteinsArtemether–lumefantrineDrug resistanceIn vivo selectionpfkelch13Plasmodium falciparumPolymorphisms

Identifiers

PMID28068997
PMCPMC5223472
OpenAlexW2569387503

What OpenQuestion holds

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LicenceCC BY
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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.