Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria
<strong>Background<br></strong> 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 tafenoqui...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2021
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| _version_ | 1797106586993295360 |
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| author | Satyagraha, AW Sadhewa, A Panggalo, LV Subekti, D Elyazar, I Soebianto, S Mahpud, N Harahap, AR Baird, JK |
| author_facet | Satyagraha, AW Sadhewa, A Panggalo, LV Subekti, D Elyazar, I Soebianto, S Mahpud, N Harahap, AR Baird, JK |
| author_sort | Satyagraha, AW |
| collection | OXFORD |
| description | <strong>Background<br></strong>
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.
<br><strong>
Methods & findings<br></strong>
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).
<br><strong>
Conclusions<br></strong>
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. |
| first_indexed | 2024-03-07T07:04:37Z |
| format | Journal article |
| id | oxford-uuid:5332970d-7e6f-4046-93b8-b2569fd6d442 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:04:37Z |
| publishDate | 2021 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:5332970d-7e6f-4046-93b8-b2569fd6d4422022-04-21T12:53:56ZGenotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malariaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5332970d-7e6f-4046-93b8-b2569fd6d442EnglishSymplectic ElementsPublic Library of Science2021Satyagraha, AWSadhewa, APanggalo, LVSubekti, DElyazar, ISoebianto, SMahpud, NHarahap, ARBaird, JK<strong>Background<br></strong> 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. <br><strong> Methods & findings<br></strong> 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). <br><strong> Conclusions<br></strong> 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. |
| spellingShingle | Satyagraha, AW Sadhewa, A Panggalo, LV Subekti, D Elyazar, I Soebianto, S Mahpud, N Harahap, AR Baird, JK Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria |
| title | 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_short | 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 |
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