Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria
Abstract Background Plasmodium falciparum, the deadliest causative agent of malaria, has high prevalence in Nigeria. Drug resistance causing failure of previously effective drugs has compromised anti-malarial treatment. On this basis, there is need for a proactive surveillance for resistance markers...
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ftdoajarticles:oai:doaj.org/article:3aa355f8e1ea47b5a76305f3216da137 2023-05-15T15:11:30+02:00 Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria Abel O. Idowu Wellington A. Oyibo Sanjib Bhattacharyya Manjeet Khubbar Udoma E. Mendie Violet V. Bumah Carolyn Black Joseph Igietseme Anthony A. Azenabor 2019-09-01T00:00:00Z https://doi.org/10.1186/s12936-019-2947-z https://doaj.org/article/3aa355f8e1ea47b5a76305f3216da137 EN eng BMC http://link.springer.com/article/10.1186/s12936-019-2947-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-019-2947-z 1475-2875 https://doaj.org/article/3aa355f8e1ea47b5a76305f3216da137 Malaria Journal, Vol 18, Iss 1, Pp 1-9 (2019) Malaria Infectious disease epidemiology Antimalarial gene polymorphism Parasitic disease epidemiology and control Plasmodium Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2019 ftdoajarticles https://doi.org/10.1186/s12936-019-2947-z 2022-12-31T14:00:25Z Abstract Background Plasmodium falciparum, the deadliest causative agent of malaria, has high prevalence in Nigeria. Drug resistance causing failure of previously effective drugs has compromised anti-malarial treatment. On this basis, there is need for a proactive surveillance for resistance markers to the currently recommended artemisinin-based combination therapy (ACT), for early detection of resistance before it become widespread. Methods This study assessed anti-malarial resistance genes polymorphism in patients with uncomplicated P. falciparum malaria in Lagos, Nigeria. Sanger and Next Generation Sequencing (NGS) methods were used to screen for mutations in thirty-seven malaria positive blood samples targeting the P. falciparum chloroquine-resistance transporter (Pfcrt), P. falciparum multidrug-resistance 1 (Pfmdr1), and P. falciparum kelch 13 (Pfk13) genes, which have been previously associated with anti-malarial resistance. Results Expectedly, the NGS method was more proficient, detecting six Pfmdr1, seven Pfcrt and three Pfk13 mutations in the studied clinical isolates from Nigeria, a malaria endemic area. These mutations included rare Pfmdr1 mutations, N504K, N649D, F938Y and S967N, which were previously unreported. In addition, there was moderate prevalence of the K76T mutation (34.6%) associated with chloroquine and amodiaquine resistance, and high prevalence of the N86 wild type allele (92.3%) associated with lumefantrine resistance. Conclusion Widespread circulation of mutations associated with resistance to current anti-malarial drugs could potentially limit effective malaria therapy in endemic populations. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 18 1 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Malaria Infectious disease epidemiology Antimalarial gene polymorphism Parasitic disease epidemiology and control Plasmodium Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Infectious disease epidemiology Antimalarial gene polymorphism Parasitic disease epidemiology and control Plasmodium Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Abel O. Idowu Wellington A. Oyibo Sanjib Bhattacharyya Manjeet Khubbar Udoma E. Mendie Violet V. Bumah Carolyn Black Joseph Igietseme Anthony A. Azenabor Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria |
topic_facet |
Malaria Infectious disease epidemiology Antimalarial gene polymorphism Parasitic disease epidemiology and control Plasmodium Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Plasmodium falciparum, the deadliest causative agent of malaria, has high prevalence in Nigeria. Drug resistance causing failure of previously effective drugs has compromised anti-malarial treatment. On this basis, there is need for a proactive surveillance for resistance markers to the currently recommended artemisinin-based combination therapy (ACT), for early detection of resistance before it become widespread. Methods This study assessed anti-malarial resistance genes polymorphism in patients with uncomplicated P. falciparum malaria in Lagos, Nigeria. Sanger and Next Generation Sequencing (NGS) methods were used to screen for mutations in thirty-seven malaria positive blood samples targeting the P. falciparum chloroquine-resistance transporter (Pfcrt), P. falciparum multidrug-resistance 1 (Pfmdr1), and P. falciparum kelch 13 (Pfk13) genes, which have been previously associated with anti-malarial resistance. Results Expectedly, the NGS method was more proficient, detecting six Pfmdr1, seven Pfcrt and three Pfk13 mutations in the studied clinical isolates from Nigeria, a malaria endemic area. These mutations included rare Pfmdr1 mutations, N504K, N649D, F938Y and S967N, which were previously unreported. In addition, there was moderate prevalence of the K76T mutation (34.6%) associated with chloroquine and amodiaquine resistance, and high prevalence of the N86 wild type allele (92.3%) associated with lumefantrine resistance. Conclusion Widespread circulation of mutations associated with resistance to current anti-malarial drugs could potentially limit effective malaria therapy in endemic populations. |
format |
Article in Journal/Newspaper |
author |
Abel O. Idowu Wellington A. Oyibo Sanjib Bhattacharyya Manjeet Khubbar Udoma E. Mendie Violet V. Bumah Carolyn Black Joseph Igietseme Anthony A. Azenabor |
author_facet |
Abel O. Idowu Wellington A. Oyibo Sanjib Bhattacharyya Manjeet Khubbar Udoma E. Mendie Violet V. Bumah Carolyn Black Joseph Igietseme Anthony A. Azenabor |
author_sort |
Abel O. Idowu |
title |
Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria |
title_short |
Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria |
title_full |
Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria |
title_fullStr |
Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria |
title_full_unstemmed |
Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria |
title_sort |
rare mutations in pfmdr1 gene of plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in nigeria |
publisher |
BMC |
publishDate |
2019 |
url |
https://doi.org/10.1186/s12936-019-2947-z https://doaj.org/article/3aa355f8e1ea47b5a76305f3216da137 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 18, Iss 1, Pp 1-9 (2019) |
op_relation |
http://link.springer.com/article/10.1186/s12936-019-2947-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-019-2947-z 1475-2875 https://doaj.org/article/3aa355f8e1ea47b5a76305f3216da137 |
op_doi |
https://doi.org/10.1186/s12936-019-2947-z |
container_title |
Malaria Journal |
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18 |
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1 |
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1766342345431711744 |