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      Glucose-6-Phosphate Dehydrogenase Deficiency in an Endemic Area for Malaria in Manaus: A Cross-Sectional Survey in the Brazilian Amazon

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          Abstract

          Background

          There is a paucity of information regarding glucose-6-phosphate dehydrogenase (G6PD) deficiency in endemic areas for malaria in Latin America.

          Methodology/Principal Findings

          This study determined the prevalence of the G6PD deficiency in 200 male non-consanguineous individuals residing in the Ismail Aziz Community, on the outskirts of Manaus (Brazilian Amazon). Six individuals (3%) were deficient using the qualitative Brewer's test. Gel electrophoresis showed that five of these patients were G6PD A . The deficiency was not associated with the ethnic origin (P = 0.571). In a multivariate logistic regression analysis, G6PD deficiency protected against three or more episodes of malaria (P = 0.049), independently of the age, and was associated with a history of jaundice (P = 0.020) and need of blood transfusion (P = 0.045) during previous treatment for malarial infection, independently of the age and the previous malarial exposure.

          Conclusions/Significance

          The frequency of G6PD deficiency was similar to other studies performed in Brazil and the finding of a predominant G6PD A variant will help the clinical management of patients with drug-induced haemolysis. The history of jaundice and blood transfusion during previous malarial infection may trigger the screening of patients for G6PD deficiency. The apparent protection against multiple malarial infections in an area primarily endemic for Plasmodium vivax needs further investigation.

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          Most cited references30

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          Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development.

          Glucose-6-phosphate dehydrogenase (G6PD) deficiency is relatively common in populations exposed to malaria. This deficiency appears to provide some protection from this infection, but it can also cause hemolysis after administration of some antimalarial drugs, especially primaquine. The risk of drug-induced G6PD deficiency-related hemolysis depends on a number of factors including the G6PD variant, the drug and drug dosage schedule, patient status, and disease factors. Although a great deal is known about the molecular biology of G6PD, determining the potential for drug-induced hemolysis in the clinical setting is still challenging. This report discusses the potential strategies for assessing drug-induced G6PD deficiency-related hemolytic risk preclinically and in early clinical trials. Additionally, the issues important for conducting larger clinical trials in populations in which G6PD deficiency is prevalent are examined, with a particular focus on antimalarial drug development.
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            Hematologically important mutations: glucose-6-phosphate dehydrogenase.

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              Distribution of glucose-6-phosphate dehydrogenase mutations in Southeast Asia.

              Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a heterogeneous enzyme abnormality with high frequency in tropical areas. We performed population screening and molecular studies of G6PD variants to clarify their distribution and features in Southeast Asia. A total of 4317 participants (2019 males, 2298 females) from 16 ethnic groups in Myanmar, Lao in Laos, and Amboinese in Indonesia were screened with a single-step screening method. The prevalence of G6PD-deficient males ranged from 0% (the Akha) to 10.8% (the Shan). These G6PD-deficient individuals and 12 G6PD-deficient patients who had been diagnosed at hospitals in Indonesia and Malaysia were subjected to molecular analysis by a combination of polymerase-chain-reaction-based single-strand conformation polymorphism analysis and direct sequencing. Ten different missense mutations were identified in 63 G6PD-deficient individuals (50 hemizygotes, 11 heterozygotes, and 2 homozygotes) from 14 ethnic groups. One missense mutation (1291 G-->A) found in an Indonesian Chinese, viz., G6PD Surabaya, was previously unknown. The 487 G-->A (G6PD Mahidol) mutation was widely seen in Myanmar, 383 T-->C (G6PD Vanua Lava) was specifically found among Amboinese, 871 G-->A (G6PD Viangchan) was observed mainly in Lao, and 592 C-->T (G6PD Coimbra) was found in Malaysian aborigines (Orang Asli). The other five mutations, 95 A-->G (G6PD Gaohe), 1003 G-->A (G6PD Chatham), 1360 C-->T (G6PD Union), 1376 G-->T (G6PD Canton), and 1388 G-->A (G6PD Kaiping) were identified mostly in accordance with distributions reported previously.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                16 April 2009
                : 4
                : 4
                : e5259
                Affiliations
                [1 ]University of the State of Amazonas, Manaus, Amazonas, Brazil
                [2 ]Tropical Medicine Foundation of Amazonas, Manaus, Amazonas, Brazil
                [3 ]Nilton Lins Universitary Center, Manaus, Amazonas, Brazil
                Instituto de Pesquisa Clinica Evandro Chagas, FIOCRUZ, Brazil
                Author notes

                Conceived and designed the experiments: MSS MVL MGB WDA MGA. Performed the experiments: MSS. Analyzed the data: MSS MVL MGB WDA MGA. Contributed reagents/materials/analysis tools: MSS. Wrote the paper: MSS MVL MGB WDA MGA.

                Article
                08-PONE-RA-05726R1
                10.1371/journal.pone.0005259
                2667256
                19370159
                2a2280ea-5493-40c4-9976-7c1f016acb6f
                Santana et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 30 July 2008
                : 12 March 2009
                Page count
                Pages: 4
                Categories
                Research Article
                Infectious Diseases
                Hematology/Disorders of Red Cell Metabolism
                Pharmacology/Adverse Reactions

                Uncategorized
                Uncategorized

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