Evidence map›Paper›PMID 32669113›Full record

ArticleMalaria journal2020

Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana.

Peter Hodoameda, Nancy Odurowah Duah-Quashie, Charles Oheneba Hagan, Sena Matrevi, Benjamin Abuaku, Kwadwo Koram, Neils Ben Quashie

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

5 citing papers in PubMed, 9 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

7 authors at 3 institutions in 1 country.

Peter HodoamedaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, P. O. Box LG54, Legon, Ghana.
Nancy Odurowah Duah-QuashieEpidemiology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, P. O. Box LG581, Legon, Ghana.
Charles Oheneba HaganUniversity of Cape Coat Medical School, Cape Coast, Ghana.
Sena MatreviEpidemiology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, P. O. Box LG581, Legon, Ghana.
Benjamin AbuakuEpidemiology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, P. O. Box LG581, Legon, Ghana.
Kwadwo KoramEpidemiology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, P. O. Box LG581, Legon, Ghana.
Neils Ben QuashieWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, P. O. Box LG54, Legon, Ghana. nbquashie@ug.edu.gh.
University of Ghana · GHNoguchi Memorial Institute for Medical Research · GHUniversity of Cape Coast · GH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundArtemisinin-based combination therapy (ACT) partner drugs, currently used in Ghana are lumefantrine, amodiaquine and piperaquine. Plasmodium falciparum isolates with reduced susceptibility to these partner drugs may affect treatment outcome. Mutations in pfmdr1 gene is linked to reduced parasite susceptibility to amodiaquine and lumefantrine. In addition, the potency of the partner drugs in vivo depends on the metabolism by the cytochrome P450 (CYP) enzyme in the host. Mutations in the CYP2C8 and CYP3A4 genes are linked to reduced metabolism of amodiaquine and lumefantrine in vitro, respectively. This study investigated the host and parasite genetic factors affecting the susceptibility of the malaria parasite to ACT partner drugs.

methodsArchived samples from 240 patients age ≤ 9 years participating in anti-malarial drug resistance survey in Ghana, and given artemether with lumefantrine (AL) or artesunate with amodiaquine (AA), were selected and analysed. Polymerase chain reaction (PCR) followed by Sanger sequencing was used to determine the polymorphisms in CYP2C8, CYP3A4 and pfmdr1 genes.

resultsFor CYP3A4, all had wild type alleles, suggesting that the hosts are good metabolizers of lumefantrine. For CYP2C8 60% had wild type alleles, 35% heterozygous and 5% homozygous recessive alleles suggesting efficient metabolism of amodiaquine by the hosts. For pfmdr1 gene, at codon 86, 95% were wild type (N86) and 5% mutant (Y86). For codon 184, 36% were wild type (Y184) and 64% mutant (F184) while for codons 1034, 1042 and 1246, 100% (all) were wild type. The high prevalence of N86-F184-D1246 haplotype (NFD) suggest presence of parasites with reduced susceptibility to lumefantrine and not amodiaquine. Delayed clearance was observed in individuals with mutations in the pfmdr1 gene and not cytochrome 450 gene. Both synonymous and non-synonymous mutations were observed in the pfmdr1 at low prevalence.

conclusionThe outcome of this study indicates that the parasite's genetic factors rather than the host's are likely to drive resistance to ACT in Ghana.

Indexed as

AmodiaquineAntimalarialsATP-Binding Cassette, Sub-Family C ProteinsChildChild, PreschoolDrug ResistanceGhanaHumansInfantInfant, NewbornLumefantrinePiperazinesPlasmodium falciparumPolymorphism, GeneticQuinolinesAmodiaquineAntimalarialsATP-Binding Cassette, Sub-Family C ProteinsLumefantrineMdr1 protein, Plasmodium falciparumpiperaquinePiperazinesQuinolinesCytochromeMolecular markersMutationPolymorphismPrevalenceResistance

Identifiers

PMID32669113
PMCPMC7362516
OpenAlexW3042927689

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.