Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymopathy globally, and deficient individuals may experience severe hemolysis following treatment with 8-aminoquinolines. With increasing evidence of Plasmodium vivax infections throughout sub-Saharan Africa, there is a pressi...

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Autores principales:	Musab M. Ali Albsheer, Andrew A. Lover, Sara B. Eltom, Leena Omereltinai, Nouh Mohamed, Mohamed S. Muneer, Abdelrahim O. Mohamad, Muzamil Mahdi Abdel Hamid
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/6bc07374e7a940a796c0236775e89b78
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id	oai:doaj.org-article:6bc07374e7a940a796c0236775e89b78
record_format	dspace
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 Musab M. Ali Albsheer Andrew A. Lover Sara B. Eltom Leena Omereltinai Nouh Mohamed Mohamed S. Muneer Abdelrahim O. Mohamad Muzamil Mahdi Abdel Hamid Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan
description	Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymopathy globally, and deficient individuals may experience severe hemolysis following treatment with 8-aminoquinolines. With increasing evidence of Plasmodium vivax infections throughout sub-Saharan Africa, there is a pressing need for population-level data at on the prevalence of G6PDd. Such evidence-based data will guide the expansion of primaquine and potentially tafenoquine for radical cure of P. vivax infections. This study aimed to quantify G6PDd prevalence in two geographically distinct areas in Sudan, and evaluating the performance of a qualitative CareStart rapid diagnostic test as a point-of-care test. Blood samples were analyzed from 491 unrelated healthy persons in two malaria-endemic sites in eastern and central Sudan. A pre-structured questionnaire was used which included demographic data, risk factors and treatment history. G6PD levels were measured using spectrophotometry (SPINREACT) and first-generation qualitative CareStart rapid tests. G6PD variants (202 G>A; 376 A>G) were determined by PCR/RFLP, with a subset confirmed by Sanger sequencing. The prevalence of G6PDd by spectrophotometry was 5.5% (27/491; at 30% of adjusted male median, AMM); 27.3% (134/491; at 70% of AMM); and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. The first-generation CareStart rapid diagnostic test had an overall sensitivity of 81.5% (95%CI: 61.9 to 93.7) and negative predictive value of 98.8% (97.3 to 99.6). All persons genotyped across both study sites were wild type for the G6PD G202 variant. For G6PD A376G all participants in New Halfa had wild type AA (100%), while in Khartoum the AA polymorphism was found in 90.7%; AG in 2.5%; and GG in 6.8%. Phenotypic G6PD B was detected in 100% of tested participants in New Halfa while in Khartoum, the phenotypes observed were B (96.2%), A (2.8%), and AB (1%). The African A- phenotype was not detected in this study population. Overall, G6PDd prevalence in Sudan is low-to-moderate but highly heterogeneous. Point-of-care testing with the qualitative CareStart rapid diagnostic test demonstrated moderate performance with moderate sensitivity and specificity but high negative predicative value. The two sites harbored primarily the African B phenotype. A country-wide survey is recommended to understand GP6PD deficiencies more comprehensively in Sudan. Author summary Malaria is caused by five species of parasites; of these Plasmodium falciparum and P. vivax cause the majority of global morbidity and mortality. Plasmodium vivax infection is an emerging public health problem in sub-Saharan Africa, including Sudan. Primaquine and other 8-aminoquinolines including tafenoquine are the primary treatments to target the silent liver stage (hypnozoites) in P. vivax infections. However, these regimens can cause severe intravascular hemolysis in patients suffering from glucose-6-phosphate dehydrogenase deficiency (G6PDd). To support safe and efficacious use of primaquine, and potentially tafenoquine in Sudan, this study aimed to estimate the prevalence of G6PDd across two sites in Sudan using spectrophotometry and a qualitative CareStart rapid diagnostic test. Subsequent genetic analysis by PCR/RFLP and sequencing of G6PD genetic variants was performed. This survey found an overall prevalence was 5.5% (27/491; 30% of adjusted male median, AMM), and 27.3% (134/491; 70% of AMM) and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. Important differences in distribution of genetic variants of G6PD were found across the two sites, and the African A- was not observed. In univariate analysis a few parameters showed significant association with G6PD deficiency. In conclusion the prevalence of G6PDd was low to moderate but heterogonous, and the first-generation qualitative CareStart rapid diagnostic test showed moderate performance in both males and females.
format	article
author	Musab M. Ali Albsheer Andrew A. Lover Sara B. Eltom Leena Omereltinai Nouh Mohamed Mohamed S. Muneer Abdelrahim O. Mohamad Muzamil Mahdi Abdel Hamid
author_facet	Musab M. Ali Albsheer Andrew A. Lover Sara B. Eltom Leena Omereltinai Nouh Mohamed Mohamed S. Muneer Abdelrahim O. Mohamad Muzamil Mahdi Abdel Hamid
author_sort	Musab M. Ali Albsheer
title	Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan
title_short	Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan
title_full	Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan
title_fullStr	Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan
title_full_unstemmed	Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan
title_sort	prevalence of glucose-6-phosphate dehydrogenase deficiency (g6pdd), carestart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in sudan
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6bc07374e7a940a796c0236775e89b78
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spelling	oai:doaj.org-article:6bc07374e7a940a796c0236775e89b782021-11-04T08:09:04ZPrevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan1935-27271935-2735https://doaj.org/article/6bc07374e7a940a796c0236775e89b782021-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547650/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymopathy globally, and deficient individuals may experience severe hemolysis following treatment with 8-aminoquinolines. With increasing evidence of Plasmodium vivax infections throughout sub-Saharan Africa, there is a pressing need for population-level data at on the prevalence of G6PDd. Such evidence-based data will guide the expansion of primaquine and potentially tafenoquine for radical cure of P. vivax infections. This study aimed to quantify G6PDd prevalence in two geographically distinct areas in Sudan, and evaluating the performance of a qualitative CareStart rapid diagnostic test as a point-of-care test. Blood samples were analyzed from 491 unrelated healthy persons in two malaria-endemic sites in eastern and central Sudan. A pre-structured questionnaire was used which included demographic data, risk factors and treatment history. G6PD levels were measured using spectrophotometry (SPINREACT) and first-generation qualitative CareStart rapid tests. G6PD variants (202 G>A; 376 A>G) were determined by PCR/RFLP, with a subset confirmed by Sanger sequencing. The prevalence of G6PDd by spectrophotometry was 5.5% (27/491; at 30% of adjusted male median, AMM); 27.3% (134/491; at 70% of AMM); and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. The first-generation CareStart rapid diagnostic test had an overall sensitivity of 81.5% (95%CI: 61.9 to 93.7) and negative predictive value of 98.8% (97.3 to 99.6). All persons genotyped across both study sites were wild type for the G6PD G202 variant. For G6PD A376G all participants in New Halfa had wild type AA (100%), while in Khartoum the AA polymorphism was found in 90.7%; AG in 2.5%; and GG in 6.8%. Phenotypic G6PD B was detected in 100% of tested participants in New Halfa while in Khartoum, the phenotypes observed were B (96.2%), A (2.8%), and AB (1%). The African A- phenotype was not detected in this study population. Overall, G6PDd prevalence in Sudan is low-to-moderate but highly heterogeneous. Point-of-care testing with the qualitative CareStart rapid diagnostic test demonstrated moderate performance with moderate sensitivity and specificity but high negative predicative value. The two sites harbored primarily the African B phenotype. A country-wide survey is recommended to understand GP6PD deficiencies more comprehensively in Sudan. Author summary Malaria is caused by five species of parasites; of these Plasmodium falciparum and P. vivax cause the majority of global morbidity and mortality. Plasmodium vivax infection is an emerging public health problem in sub-Saharan Africa, including Sudan. Primaquine and other 8-aminoquinolines including tafenoquine are the primary treatments to target the silent liver stage (hypnozoites) in P. vivax infections. However, these regimens can cause severe intravascular hemolysis in patients suffering from glucose-6-phosphate dehydrogenase deficiency (G6PDd). To support safe and efficacious use of primaquine, and potentially tafenoquine in Sudan, this study aimed to estimate the prevalence of G6PDd across two sites in Sudan using spectrophotometry and a qualitative CareStart rapid diagnostic test. Subsequent genetic analysis by PCR/RFLP and sequencing of G6PD genetic variants was performed. This survey found an overall prevalence was 5.5% (27/491; 30% of adjusted male median, AMM), and 27.3% (134/491; 70% of AMM) and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. Important differences in distribution of genetic variants of G6PD were found across the two sites, and the African A- was not observed. In univariate analysis a few parameters showed significant association with G6PD deficiency. In conclusion the prevalence of G6PDd was low to moderate but heterogonous, and the first-generation qualitative CareStart rapid diagnostic test showed moderate performance in both males and females.Musab M. Ali AlbsheerAndrew A. LoverSara B. EltomLeena OmereltinaiNouh MohamedMohamed S. MuneerAbdelrahim O. MohamadMuzamil Mahdi Abdel HamidPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 10 (2021)

Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan

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