Evidence map›Paper›PMID 32513171›Full record

ArticleMalaria journal2020

Surveillance of genetic markers associated with Plasmodium falciparum resistance to artemisinin-based combination therapy in Pakistan, 2018-2019.

Abdul Qader Khan, Leyre Pernaute-Lau, Aamer Ali Khattak, Sanna Luijcx, Berit Aydin-Schmidt, Mubashir Hussain, Taj Ali Khan, Farees Uddin Mufti, Ulrika Morris

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2020. 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
2.7field-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, 20 citations in OpenAlex.

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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.

Abdul Qader KhanDepartment of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
Leyre Pernaute-LauDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Aamer Ali KhattakDepartment of Medical Lab Technology, The University of Haripur, Haripur, Pakistan.
Sanna LuijcxDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Berit Aydin-SchmidtDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Mubashir HussainDepartment of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
Taj Ali KhanDepartment of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
Farees Uddin MuftiDepartment of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan.
Ulrika MorrisDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. ulrika.morris@ki.se.ORCID http://orcid.org/0000-0003-4734-5754
Karolinska Institutet · SEKohat University of Science and Technology · PKQuaid-i-Azam University · PKUniversity of Haripur · PKUniversity of Lisbon · PT

Funding

Higher Education Commission, Pakistan IRSIP-42 BMS-24Karolinska Institutet 2018-01515Vetenskapsrådet 2017-05644
6 · The paper itself

Abstract

backgroundThe spread of artemisinin resistance in the Greater Mekong Subregion of Southeast Asia poses a significant threat for current anti-malarial treatment guidelines globally. The aim of this study was to assess the current prevalence of molecular markers of drug resistance in Plasmodium falciparum in the four provinces with the highest malaria burden in Pakistan, after introducing artemether-lumefantrine as first-line treatment in 2017.

methodsSamples were collected during routine malaria surveillance in Punjab, Sindh, Baluchistan, and Khyber Pakhtunkhwa provinces of Pakistan between January 2018 and February 2019. Plasmodium falciparum infections were confirmed by rapid diagnostic test or microscopy. Plasmodium falciparum positive isolates (n = 179) were screened by Sanger sequencing for single nucleotide polymorphisms (SNPs) in the P. falciparum kelch 13 (pfk13) propeller domain and in P. falciparum coronin (pfcoronin). SNPs in P. falciparum multidrug resistance 1 (pfmdr1) N86Y, Y184F, D1246Y and P. falciparum chloroquine resistance transporter (pfcrt) K76T were genotyped by PCR-restriction fragment length polymorphism.

resultsNo artemisinin resistance associated SNPs were identified in the pfk13 propeller domain or in pfcoronin. The pfmdr1 N86, 184F, D1246 and pfcrt K76 alleles associated with reduced lumefantrine sensitivity were present in 83.8% (150/179), 16.9% (29/172), 100.0% (173/173), and 8.4% (15/179) of all infections, respectively. The chloroquine resistance associated pfcrt 76T allele was present in 98.3% (176/179) of infections.

conclusionThis study provides an update on the current prevalence of molecular markers associated with reduced P. falciparum sensitivity to artemether and/or lumefantrine in Pakistan, including a first baseline assessment of polymorphisms in pfcoronin. No mutations associated with artemisinin resistance were observed in pfk13 or pfcoronin. However, the prevalence of the pfmdr1 N86 and D1246 alleles, that have been associated with decreased susceptibility to lumefantrine, remain high. Although clinical and molecular data suggest that the current malaria treatment guidelines for P. falciparum are presently effective in Pakistan, close monitoring for artemisinin and lumefantrine resistance will be critical to ensure early detection and enhanced containment of emerging ACT resistance spreading across from Southeast Asia.

Indexed as

Genetic MarkersAntimalarialsArtemether, Lumefantrine Drug CombinationDrug ResistancePakistanPlasmodium falciparumAntimalarialsArtemether, Lumefantrine Drug CombinationGenetic MarkersArtemether–lumefantrineArtemisinin-based combination therapyChloroquineDrug resistancePakistanP. falciparum coroninP. falciparum kelch 13 propeller domainpfcrtpfmdr1Plasmodium falciparum

Identifiers

PMID32513171
PMCPMC7282094
OpenAlexW3033781463

What OpenQuestion holds

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LicenceCC BY
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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.