Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria.

<h4>Background</h4>Plasmodium vivax occurs as a latent infection of liver and a patent infection of red blood cells. Radical cure requires both blood schizontocidal and hypnozoitocidal chemotherapies. The hypnozoitocidal therapies available are primaquine and tafenoquine, 8-aminoquinolin...

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Autores principales: Ari Winasti Satyagraha, Arkasha Sadhewa, Lydia Visita Panggalo, Decy Subekti, Iqbal Elyazar, Saraswati Soebianto, Nunung Mahpud, Alida Rosita Harahap, J Kevin Baird
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spelling oai:doaj.org-article:62fae71b29a244dea480166be7d643bb2021-11-25T06:33:30ZGenotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria.1935-27271935-273510.1371/journal.pntd.0009610https://doaj.org/article/62fae71b29a244dea480166be7d643bb2021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009610https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Plasmodium vivax occurs as a latent infection of liver and a patent infection of red blood cells. Radical cure requires both blood schizontocidal and hypnozoitocidal chemotherapies. The hypnozoitocidal therapies available are primaquine and tafenoquine, 8-aminoquinoline drugs that can provoke threatening acute hemolytic anemia in patients having an X-linked G6PD-deficiency. Heterozygous females may screen as G6PD-normal prior to radical cure and go on to experience hemolytic crisis.<h4>Methods & findings</h4>This study examined G6PD phenotypes in 1928 female subjects living in malarious Sumba Island in eastern Indonesia to ascertain the prevalence of females vulnerable to diagnostic misclassification as G6PD-normal. All 367 (19%) females having <80% G6PD normal activity were genotyped. Among those, 103 (28%) were G6PD wild type, 251 (68·4%) were heterozygous, three (0·8%) were compound heterozygotes, and ten (2·7%) were homozygous deficient. The variants Vanua Lava, Viangchan, Coimbra, Chatham, and Kaiping occurred among them. Below the 70% of normal G6PD activity threshold, just 18 (8%) were G6PD-normal and 214 (92%) were G6PD-deficient. Among the 31 females with <30% G6PD normal activity were all ten homozygotes, all three compound heterozygotes, and just 18 were heterozygotes (7% of those).<h4>Conclusions</h4>In this population, most G6PD heterozygosity in females occurred between 30% and 70% of normal (69·3%; 183/264). The prevalence of females at risk of G6PD misclassification as normal by qualitative screening was 9·5% (183/1928). Qualitative G6PD screening prior to 8-aminoquinoline therapies against P. vivax may leave one in ten females at risk of hemolytic crisis, which may be remedied by point-of-care quantitative tests.Ari Winasti SatyagrahaArkasha SadhewaLydia Visita PanggaloDecy SubektiIqbal ElyazarSaraswati SoebiantoNunung MahpudAlida Rosita HarahapJ Kevin BairdPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 7, p e0009610 (2021)
institution DOAJ
collection DOAJ
language EN
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Ari Winasti Satyagraha
Arkasha Sadhewa
Lydia Visita Panggalo
Decy Subekti
Iqbal Elyazar
Saraswati Soebianto
Nunung Mahpud
Alida Rosita Harahap
J Kevin Baird
Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria.
description <h4>Background</h4>Plasmodium vivax occurs as a latent infection of liver and a patent infection of red blood cells. Radical cure requires both blood schizontocidal and hypnozoitocidal chemotherapies. The hypnozoitocidal therapies available are primaquine and tafenoquine, 8-aminoquinoline drugs that can provoke threatening acute hemolytic anemia in patients having an X-linked G6PD-deficiency. Heterozygous females may screen as G6PD-normal prior to radical cure and go on to experience hemolytic crisis.<h4>Methods & findings</h4>This study examined G6PD phenotypes in 1928 female subjects living in malarious Sumba Island in eastern Indonesia to ascertain the prevalence of females vulnerable to diagnostic misclassification as G6PD-normal. All 367 (19%) females having <80% G6PD normal activity were genotyped. Among those, 103 (28%) were G6PD wild type, 251 (68·4%) were heterozygous, three (0·8%) were compound heterozygotes, and ten (2·7%) were homozygous deficient. The variants Vanua Lava, Viangchan, Coimbra, Chatham, and Kaiping occurred among them. Below the 70% of normal G6PD activity threshold, just 18 (8%) were G6PD-normal and 214 (92%) were G6PD-deficient. Among the 31 females with <30% G6PD normal activity were all ten homozygotes, all three compound heterozygotes, and just 18 were heterozygotes (7% of those).<h4>Conclusions</h4>In this population, most G6PD heterozygosity in females occurred between 30% and 70% of normal (69·3%; 183/264). The prevalence of females at risk of G6PD misclassification as normal by qualitative screening was 9·5% (183/1928). Qualitative G6PD screening prior to 8-aminoquinoline therapies against P. vivax may leave one in ten females at risk of hemolytic crisis, which may be remedied by point-of-care quantitative tests.
format article
author Ari Winasti Satyagraha
Arkasha Sadhewa
Lydia Visita Panggalo
Decy Subekti
Iqbal Elyazar
Saraswati Soebianto
Nunung Mahpud
Alida Rosita Harahap
J Kevin Baird
author_facet Ari Winasti Satyagraha
Arkasha Sadhewa
Lydia Visita Panggalo
Decy Subekti
Iqbal Elyazar
Saraswati Soebianto
Nunung Mahpud
Alida Rosita Harahap
J Kevin Baird
author_sort Ari Winasti Satyagraha
title Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria.
title_short Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria.
title_full Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria.
title_fullStr Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria.
title_full_unstemmed Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria.
title_sort genotypes and phenotypes of g6pd deficiency among indonesian females across diagnostic thresholds of g6pd activity guiding safe primaquine therapy of latent malaria.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/62fae71b29a244dea480166be7d643bb
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