Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana
Abstract Background Artemisinin-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...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2020
|
Subjects: | |
Online Access: | https://doi.org/10.1186/s12936-020-03320-7 https://doaj.org/article/88b907b5991146929c935d01dec44b76 |
id |
ftdoajarticles:oai:doaj.org/article:88b907b5991146929c935d01dec44b76 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:88b907b5991146929c935d01dec44b76 2023-05-15T15:14:05+02:00 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 2020-07-01T00:00:00Z https://doi.org/10.1186/s12936-020-03320-7 https://doaj.org/article/88b907b5991146929c935d01dec44b76 EN eng BMC http://link.springer.com/article/10.1186/s12936-020-03320-7 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-020-03320-7 1475-2875 https://doaj.org/article/88b907b5991146929c935d01dec44b76 Malaria Journal, Vol 19, Iss 1, Pp 1-8 (2020) Polymorphism Mutation Resistance Cytochrome Molecular markers Prevalence Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2020 ftdoajarticles https://doi.org/10.1186/s12936-020-03320-7 2022-12-31T04:40:37Z Abstract Background Artemisinin-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. Methods Archived 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. Results For 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. Conclusion The outcome of this study indicates that the parasite's genetic factors rather than the ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 19 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Polymorphism Mutation Resistance Cytochrome Molecular markers Prevalence Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Polymorphism Mutation Resistance Cytochrome Molecular markers Prevalence Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Peter Hodoameda Nancy Odurowah Duah-Quashie Charles Oheneba Hagan Sena Matrevi Benjamin Abuaku Kwadwo Koram Neils Ben Quashie Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana |
topic_facet |
Polymorphism Mutation Resistance Cytochrome Molecular markers Prevalence Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Artemisinin-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. Methods Archived 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. Results For 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. Conclusion The outcome of this study indicates that the parasite's genetic factors rather than the ... |
format |
Article in Journal/Newspaper |
author |
Peter Hodoameda Nancy Odurowah Duah-Quashie Charles Oheneba Hagan Sena Matrevi Benjamin Abuaku Kwadwo Koram Neils Ben Quashie |
author_facet |
Peter Hodoameda Nancy Odurowah Duah-Quashie Charles Oheneba Hagan Sena Matrevi Benjamin Abuaku Kwadwo Koram Neils Ben Quashie |
author_sort |
Peter Hodoameda |
title |
Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana |
title_short |
Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana |
title_full |
Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana |
title_fullStr |
Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana |
title_full_unstemmed |
Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana |
title_sort |
plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to act in ghana |
publisher |
BMC |
publishDate |
2020 |
url |
https://doi.org/10.1186/s12936-020-03320-7 https://doaj.org/article/88b907b5991146929c935d01dec44b76 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 19, Iss 1, Pp 1-8 (2020) |
op_relation |
http://link.springer.com/article/10.1186/s12936-020-03320-7 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-020-03320-7 1475-2875 https://doaj.org/article/88b907b5991146929c935d01dec44b76 |
op_doi |
https://doi.org/10.1186/s12936-020-03320-7 |
container_title |
Malaria Journal |
container_volume |
19 |
container_issue |
1 |
_version_ |
1766344581711921152 |