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Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA

INTRODUCTION: specific mutations on the Plasmodium falciparum dihydropteroate synthase (Pfdhps) gene mediate sulphadoxine/pyrimethamine (SP) resistance and thus, pose a threat to the efficacy of SP-Intermittent Preventive Therapy (SP-IPT) in malaria chemoprevention in children, including those with...

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Autores principales: Enato, Izehiuwa Gertrude, Sadoh, Ayebo Evawere, Ibadin, Okoeguale Michael, Odunvbun, Magdalene Erhieyouvbe, Osaigbovo, Iriagbonse Iyabo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The African Field Epidemiology Network 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789784/
https://www.ncbi.nlm.nih.gov/pubmed/36590995
http://dx.doi.org/10.11604/pamj.2022.43.80.34334
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author Enato, Izehiuwa Gertrude
Sadoh, Ayebo Evawere
Ibadin, Okoeguale Michael
Odunvbun, Magdalene Erhieyouvbe
Osaigbovo, Iriagbonse Iyabo
author_facet Enato, Izehiuwa Gertrude
Sadoh, Ayebo Evawere
Ibadin, Okoeguale Michael
Odunvbun, Magdalene Erhieyouvbe
Osaigbovo, Iriagbonse Iyabo
author_sort Enato, Izehiuwa Gertrude
collection PubMed
description INTRODUCTION: specific mutations on the Plasmodium falciparum dihydropteroate synthase (Pfdhps) gene mediate sulphadoxine/pyrimethamine (SP) resistance and thus, pose a threat to the efficacy of SP-Intermittent Preventive Therapy (SP-IPT) in malaria chemoprevention in children, including those with sickle cell anaemia (SCA). This study determined the distinct pattern and prevalence of Pfdhps mutations in children with SCA and in those with homozygous haemoglobin A (HbAA) in Benin City, Nigeria; showing the impact of haemoglobin phenotype. METHODS: this was a cross-sectional study involving children with SCA and HbAA. Those with successfully amplified Pfdhps genes were included in the study. Point mutations and mutant haplotypes of the Pfdhps gene were identified. Parasite density (PD) was determined by estimating the parasite numbers/μl of blood from the thick film. Descriptive, univariable and multivariable analysis were used appropriately. RESULTS: a total of 146 children: 71 with SCA and 75 with HbAA were recruited, with a mean age of 46.6 ± 13.0 and 36.4 ± 17.6 respectively; proportion of males were 45(63.4%) and 43(57.3%) respectively. I431V, S436A, A437G, A581G, and A613G mutations were present; but the K540E mutation was absent. ISGKAA 41(28.1%) and VAGKGS 61(41.8%) were the most prevalent mutant haplotypes in this study. The prevalence of VAGKGS haplotype 43(57.3%) was significantly higher in HbAA group compared to that 18(25.4%) in the SCA group (p < 0.001). The prevalence of ISGKAA in SCA group 25(35.2%) was significantly higher than that 16(21.3%) in the HbAA group (p=0.032). HbAA phenotype was the only significant predictor for the presence of the VAGKGS mutant haplotype (aOR: 3.0, 95%CI: 1.375 to 6.499; p=0.006). CONCLUSION: the HbAA phenotype was a significant predictor for the occurrence of the quintuple mutant haplotype (VAGKGS). The K540E mutation was absent; thus, SP-IPT can be explored in children younger than five years with SCA.
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spelling pubmed-97897842022-12-29 Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA Enato, Izehiuwa Gertrude Sadoh, Ayebo Evawere Ibadin, Okoeguale Michael Odunvbun, Magdalene Erhieyouvbe Osaigbovo, Iriagbonse Iyabo Pan Afr Med J Research INTRODUCTION: specific mutations on the Plasmodium falciparum dihydropteroate synthase (Pfdhps) gene mediate sulphadoxine/pyrimethamine (SP) resistance and thus, pose a threat to the efficacy of SP-Intermittent Preventive Therapy (SP-IPT) in malaria chemoprevention in children, including those with sickle cell anaemia (SCA). This study determined the distinct pattern and prevalence of Pfdhps mutations in children with SCA and in those with homozygous haemoglobin A (HbAA) in Benin City, Nigeria; showing the impact of haemoglobin phenotype. METHODS: this was a cross-sectional study involving children with SCA and HbAA. Those with successfully amplified Pfdhps genes were included in the study. Point mutations and mutant haplotypes of the Pfdhps gene were identified. Parasite density (PD) was determined by estimating the parasite numbers/μl of blood from the thick film. Descriptive, univariable and multivariable analysis were used appropriately. RESULTS: a total of 146 children: 71 with SCA and 75 with HbAA were recruited, with a mean age of 46.6 ± 13.0 and 36.4 ± 17.6 respectively; proportion of males were 45(63.4%) and 43(57.3%) respectively. I431V, S436A, A437G, A581G, and A613G mutations were present; but the K540E mutation was absent. ISGKAA 41(28.1%) and VAGKGS 61(41.8%) were the most prevalent mutant haplotypes in this study. The prevalence of VAGKGS haplotype 43(57.3%) was significantly higher in HbAA group compared to that 18(25.4%) in the SCA group (p < 0.001). The prevalence of ISGKAA in SCA group 25(35.2%) was significantly higher than that 16(21.3%) in the HbAA group (p=0.032). HbAA phenotype was the only significant predictor for the presence of the VAGKGS mutant haplotype (aOR: 3.0, 95%CI: 1.375 to 6.499; p=0.006). CONCLUSION: the HbAA phenotype was a significant predictor for the occurrence of the quintuple mutant haplotype (VAGKGS). The K540E mutation was absent; thus, SP-IPT can be explored in children younger than five years with SCA. The African Field Epidemiology Network 2022-10-13 /pmc/articles/PMC9789784/ /pubmed/36590995 http://dx.doi.org/10.11604/pamj.2022.43.80.34334 Text en Copyright: Izehiuwa Gertrude Enato et al. https://creativecommons.org/licenses/by/4.0/The Pan African Medical Journal (ISSN: 1937-8688). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Enato, Izehiuwa Gertrude
Sadoh, Ayebo Evawere
Ibadin, Okoeguale Michael
Odunvbun, Magdalene Erhieyouvbe
Osaigbovo, Iriagbonse Iyabo
Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA
title Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA
title_full Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA
title_fullStr Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA
title_full_unstemmed Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA
title_short Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA
title_sort distinct pattern and prevalence of plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin aa in benin city, nigeria: the impact of hbaa
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789784/
https://www.ncbi.nlm.nih.gov/pubmed/36590995
http://dx.doi.org/10.11604/pamj.2022.43.80.34334
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