Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria

Abstract Background The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study. Regular surveillan...

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Autores principales:	Moses Ikegbunam, Johnson A. Ojo, Kossiwa Kokou, Ugonna Morikwe, Chukwuemeka Nworu, Chibuzo Uba, Charles Esimone, Thirumalaisamy P. Velavan, Olusola Ojurongbe
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Malaria Plasmodium falciparum Drug resistance Artemisinin Pfkelch13 Nigeria Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/8a7192ce401c432e9b03a3673e625fba
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spelling	oai:doaj.org-article:8a7192ce401c432e9b03a3673e625fba2021-11-14T12:33:48ZAbsence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria10.1186/s12936-021-03968-91475-2875https://doaj.org/article/8a7192ce401c432e9b03a3673e625fba2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12936-021-03968-9https://doaj.org/toc/1475-2875Abstract Background The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study. Regular surveillance is necessary to make a definite conclusion on the emergence and pattern of possible resistance to ART. Methods This cross-sectional study was carried out in the Southwestern and Southeastern geopolitical zones of Nigeria. A total of 150, 217, and 475 participants were enrolled for the study in the Southwest (2004_Group A), Southwest (2015_Group B), and southeast (2015_Group C), respectively. Blood samples were collected from the study participants for DNA extraction and a nested PCR for P. falciparum identification. Samples that were positive for P. falciparum were genotyped for the pfk13 gene using the Sanger sequencing method. The single nucleotide polymorphisms were analysed using the Bioedit software. Results A total of 116, 125, and 83 samples were positive for P. falciparum, respectively for the samples collected from the Southwest (2004 and 2015) and southeast (2015). Parasite DNA samples collected from febrile children in 2004 (Group A; n = 71) and 2015 (Group B; n = 73) in Osogbo Western Nigeria and 2015_Group C (n = 36) in southeast Nigeria were sequenced successfully. This study did not observe mutations associated with the in vitro resistance in southeast Asia, such as Y493H, R539T, I543T, and C580Y. Two new polymorphisms V520A and V581I were observed in two samples collected in Osogbo, Southwest Nigeria. These two mutations occurred in the year 2004 (Group A) before the introduction of ACT. Six mutations were identified in 17% of the samples collected in southeast Nigeria. One of these mutations (D547G) was non-synonymous, while the remaining (V510V, R515R, Q613Q, E688E, and N458N) were synonymous. Also, one (2%) heterozygote allele was identified at codon 458 in the 2015 (Group C) samples. Conclusions None of the mutations observed in this study were previously validated to be associated with ART resistance. These results, therefore, suggest that artemisinin is likely to remain highly effective in treating malaria in the study areas that are malarious zone.Moses IkegbunamJohnson A. OjoKossiwa KokouUgonna MorikweChukwuemeka NworuChibuzo UbaCharles EsimoneThirumalaisamy P. VelavanOlusola OjurongbeBMCarticleMalariaPlasmodium falciparumDrug resistanceArtemisininPfkelch13NigeriaArctic medicine. Tropical medicineRC955-962Infectious and parasitic diseasesRC109-216ENMalaria Journal, Vol 20, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Malaria Plasmodium falciparum Drug resistance Artemisinin Pfkelch13 Nigeria Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
spellingShingle	Malaria Plasmodium falciparum Drug resistance Artemisinin Pfkelch13 Nigeria Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Moses Ikegbunam Johnson A. Ojo Kossiwa Kokou Ugonna Morikwe Chukwuemeka Nworu Chibuzo Uba Charles Esimone Thirumalaisamy P. Velavan Olusola Ojurongbe Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria
description	Abstract Background The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study. Regular surveillance is necessary to make a definite conclusion on the emergence and pattern of possible resistance to ART. Methods This cross-sectional study was carried out in the Southwestern and Southeastern geopolitical zones of Nigeria. A total of 150, 217, and 475 participants were enrolled for the study in the Southwest (2004_Group A), Southwest (2015_Group B), and southeast (2015_Group C), respectively. Blood samples were collected from the study participants for DNA extraction and a nested PCR for P. falciparum identification. Samples that were positive for P. falciparum were genotyped for the pfk13 gene using the Sanger sequencing method. The single nucleotide polymorphisms were analysed using the Bioedit software. Results A total of 116, 125, and 83 samples were positive for P. falciparum, respectively for the samples collected from the Southwest (2004 and 2015) and southeast (2015). Parasite DNA samples collected from febrile children in 2004 (Group A; n = 71) and 2015 (Group B; n = 73) in Osogbo Western Nigeria and 2015_Group C (n = 36) in southeast Nigeria were sequenced successfully. This study did not observe mutations associated with the in vitro resistance in southeast Asia, such as Y493H, R539T, I543T, and C580Y. Two new polymorphisms V520A and V581I were observed in two samples collected in Osogbo, Southwest Nigeria. These two mutations occurred in the year 2004 (Group A) before the introduction of ACT. Six mutations were identified in 17% of the samples collected in southeast Nigeria. One of these mutations (D547G) was non-synonymous, while the remaining (V510V, R515R, Q613Q, E688E, and N458N) were synonymous. Also, one (2%) heterozygote allele was identified at codon 458 in the 2015 (Group C) samples. Conclusions None of the mutations observed in this study were previously validated to be associated with ART resistance. These results, therefore, suggest that artemisinin is likely to remain highly effective in treating malaria in the study areas that are malarious zone.
format	article
author	Moses Ikegbunam Johnson A. Ojo Kossiwa Kokou Ugonna Morikwe Chukwuemeka Nworu Chibuzo Uba Charles Esimone Thirumalaisamy P. Velavan Olusola Ojurongbe
author_facet	Moses Ikegbunam Johnson A. Ojo Kossiwa Kokou Ugonna Morikwe Chukwuemeka Nworu Chibuzo Uba Charles Esimone Thirumalaisamy P. Velavan Olusola Ojurongbe
author_sort	Moses Ikegbunam
title	Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria
title_short	Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria
title_full	Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria
title_fullStr	Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria
title_full_unstemmed	Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria
title_sort	absence of plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in nigeria
publisher	BMC
publishDate	2021
url	https://doaj.org/article/8a7192ce401c432e9b03a3673e625fba
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Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria

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