Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa
Abstract Background Primaquine (PQ) is recommended as an addition to standard malaria treatments in pre-elimination settings due to its pronounced activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for onward transmission to mosquitoes. However, PQ may trigger...
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ftdoajarticles:oai:doaj.org/article:6c2bb4ceb44748fda199f4f6223ea274 2023-05-15T15:15:19+02:00 Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa Shehu S. Awandu Jaishree Raman Takalani I. Makhanthisa Philip Kruger John Frean Teun Bousema Jandeli Niemand Lyn-Marie Birkholtz 2018-03-01T00:00:00Z https://doi.org/10.1186/s12936-018-2271-z https://doaj.org/article/6c2bb4ceb44748fda199f4f6223ea274 EN eng BMC http://link.springer.com/article/10.1186/s12936-018-2271-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2271-z 1475-2875 https://doaj.org/article/6c2bb4ceb44748fda199f4f6223ea274 Malaria Journal, Vol 17, Iss 1, Pp 1-11 (2018) Malaria Primaquine Malaria elimination G6PD deficiency CYP2D6 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2018 ftdoajarticles https://doi.org/10.1186/s12936-018-2271-z 2022-12-31T01:06:42Z Abstract Background Primaquine (PQ) is recommended as an addition to standard malaria treatments in pre-elimination settings due to its pronounced activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for onward transmission to mosquitoes. However, PQ may trigger haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. Additional human genetic factors, including polymorphisms in the human cytochrome P450 2D6 (CYP2D6) complex, may negatively influence the efficacy of PQ. This study assessed the prevalence of G6PD deficiency and two important CYP2D6 variants in representative pre-elimination settings in South Africa, to inform malaria elimination strategies. Methods Volunteers (n = 248) attending six primary health care facilities in a malaria-endemic region of South Africa were enrolled between October and November 2015. G6PD status was determined phenotypically, using a CareStart™ G6PD rapid diagnostic test (RDT), and genotypically for two common African G6PD variants, namely A+ (A376G) and A− (G202A, A542T, G680T & T968C) by PCR, restriction fragment length polymorphisms (RFLP) and DNA sequencing. CYP2D6*4 and CYP2D6*17 variants were determined with PCR and RFLP. Results A prevalence of 13% (33/248) G6PD deficiency was observed in the cohort by G6PD RDT whilst by genotypic assessment, 32% (79/248) were A+ and 3.2% were A−, respectively. Among the male participants, 11% (6/55) were G6PD A− hemizygous; among females 1% (2/193) were G6PD A− homozygous and 16% (32/193) G6PD A− heterozygous. The strength of agreement between phenotyping and genotyping result was fair (Cohens Kappa κ = 0.310). The negative predictive value for the G6PD RDT for detecting hemizygous, homozygous and heterozygous individuals was 0.88 (95% CI 0.85–0.91), compared to the more sensitive genotyping. The CYP2D6*4 allele frequencies for CYP2D6*4 (inferred poor metabolizer phenotype) and CYP2D6*17 (inferred intermediate metabolizer phenotype) were 3.2 and 19.5%, respectively. ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 17 1 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Malaria Primaquine Malaria elimination G6PD deficiency CYP2D6 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Malaria Primaquine Malaria elimination G6PD deficiency CYP2D6 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Shehu S. Awandu Jaishree Raman Takalani I. Makhanthisa Philip Kruger John Frean Teun Bousema Jandeli Niemand Lyn-Marie Birkholtz Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa |
topic_facet |
Malaria Primaquine Malaria elimination G6PD deficiency CYP2D6 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Primaquine (PQ) is recommended as an addition to standard malaria treatments in pre-elimination settings due to its pronounced activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for onward transmission to mosquitoes. However, PQ may trigger haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. Additional human genetic factors, including polymorphisms in the human cytochrome P450 2D6 (CYP2D6) complex, may negatively influence the efficacy of PQ. This study assessed the prevalence of G6PD deficiency and two important CYP2D6 variants in representative pre-elimination settings in South Africa, to inform malaria elimination strategies. Methods Volunteers (n = 248) attending six primary health care facilities in a malaria-endemic region of South Africa were enrolled between October and November 2015. G6PD status was determined phenotypically, using a CareStart™ G6PD rapid diagnostic test (RDT), and genotypically for two common African G6PD variants, namely A+ (A376G) and A− (G202A, A542T, G680T & T968C) by PCR, restriction fragment length polymorphisms (RFLP) and DNA sequencing. CYP2D6*4 and CYP2D6*17 variants were determined with PCR and RFLP. Results A prevalence of 13% (33/248) G6PD deficiency was observed in the cohort by G6PD RDT whilst by genotypic assessment, 32% (79/248) were A+ and 3.2% were A−, respectively. Among the male participants, 11% (6/55) were G6PD A− hemizygous; among females 1% (2/193) were G6PD A− homozygous and 16% (32/193) G6PD A− heterozygous. The strength of agreement between phenotyping and genotyping result was fair (Cohens Kappa κ = 0.310). The negative predictive value for the G6PD RDT for detecting hemizygous, homozygous and heterozygous individuals was 0.88 (95% CI 0.85–0.91), compared to the more sensitive genotyping. The CYP2D6*4 allele frequencies for CYP2D6*4 (inferred poor metabolizer phenotype) and CYP2D6*17 (inferred intermediate metabolizer phenotype) were 3.2 and 19.5%, respectively. ... |
format |
Article in Journal/Newspaper |
author |
Shehu S. Awandu Jaishree Raman Takalani I. Makhanthisa Philip Kruger John Frean Teun Bousema Jandeli Niemand Lyn-Marie Birkholtz |
author_facet |
Shehu S. Awandu Jaishree Raman Takalani I. Makhanthisa Philip Kruger John Frean Teun Bousema Jandeli Niemand Lyn-Marie Birkholtz |
author_sort |
Shehu S. Awandu |
title |
Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa |
title_short |
Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa |
title_full |
Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa |
title_fullStr |
Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa |
title_full_unstemmed |
Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa |
title_sort |
understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern africa |
publisher |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12936-018-2271-z https://doaj.org/article/6c2bb4ceb44748fda199f4f6223ea274 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 17, Iss 1, Pp 1-11 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12936-018-2271-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2271-z 1475-2875 https://doaj.org/article/6c2bb4ceb44748fda199f4f6223ea274 |
op_doi |
https://doi.org/10.1186/s12936-018-2271-z |
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Malaria Journal |
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17 |
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1766345678558068736 |