Prevalence of Glucose 6-Phosphate Dehydrogenase Variants in Malaria-Endemic Areas of South Central Timor, Eastern Indonesia.

Primaquine is an effective anti-hypnozoite drug for Plasmodium vivax and Plasmodium ovale. However, it can trigger erythrocyte hemolysis in people with glucose 6-phosphate dehydrogenase (G6PD) deficiency. In a previous report from South Central Timor (SCT), Indonesia, we described the prevalence of Vanua Lava, Chatham, and Viangchan variants; in this study, other G6PD variants (Kaiping, Coimbra, Gaohe, Canton, and Mahidol) were subsequently analyzed. For clarity, all of these results are described together. The 381 DNA samples from the previous study during 2013-2014 were analyzed for G6PD variants by using PCR-RFLP. The prevalence of G6PD deficiency in SCT was 6.3% (24/381 cases), including 4.2% (16/381 cases), 0.5% (2/381 cases), and 1.6% (6/381 cases) for Coimbra, Kaiping, and Vanua Lava variants, respectively. No other variants were found in this population. A significant association was found between ethnicity and the distribution of G6PD Kaiping in female subjects. A positive association was shown between G6PD activity and heterozygous females carrying Coimbra genotype, hemizygous males carrying Vanua Lava, Plasmodium falciparum infection in female subjects, and P. vivax infection in male subjects. Further molecular analysis of heterozygous females, particularly in malaria-endemic areas, is needed for mapping distribution of G6PD deficiency status in Indonesia.

[1]  Encyclopedia of Malaria , 2020 .

[2]  R. Price,et al.  Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial , 2019, The Lancet.

[3]  M. Parker,et al.  Addressing the gender-knowledge gap in glucose-6-phosphate dehydrogenase deficiency: challenges and opportunities , 2018, International health.

[4]  K. Battle,et al.  Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group , 2018, Malaria Journal.

[5]  E. Ashley,et al.  Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: Divergent policies and practices in malaria endemic countries , 2018, PLoS neglected tropical diseases.

[6]  F. Nosten,et al.  Primaquine-induced haemolysis in females heterozygous for G6PD deficiency , 2018, Malaria Journal.

[7]  E. Tichy,et al.  Review and drug therapy implications of glucose‐6‐phosphate dehydrogenase deficiency , 2018, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[8]  R. Price,et al.  Barriers to routine G6PD testing prior to treatment with primaquine , 2017, Malaria Journal.

[9]  R. Price,et al.  Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study , 2017, PLoS medicine.

[10]  A. Sadewa,et al.  The first evaluation of glucose-6-phosphate dehydrogenase deficiency (G6PD) gene mutation in malaria-endemic region at South Central Timor (SCT) district, Eastern Indonesia 2015-2016 , 2017 .

[11]  H. Win,et al.  Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens , 2017, PLoS medicine.

[12]  J. Baird,et al.  Epidemiology of Plasmodium vivax in Indonesia , 2016, The American journal of tropical medicine and hygiene.

[13]  R. Arreguín-Espinosa,et al.  Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World , 2016, International journal of molecular sciences.

[14]  I. Elyazar,et al.  Assessment of Point-of-Care Diagnostics for G6PD Deficiency in Malaria Endemic Rural Eastern Indonesia , 2016, PLoS neglected tropical diseases.

[15]  R. Barnard,et al.  Phylogeny and Origin of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Mutations in Indonesia , 2015 .

[16]  K. Baird Origins and implications of neglect of G6PD deficiency and primaquine toxicity in Plasmodium vivax malaria , 2015, Pathogens and global health.

[17]  I. Elyazar,et al.  G6PD Deficiency at Sumba in Eastern Indonesia Is Prevalent, Diverse and Severe: Implications for Primaquine Therapy against Relapsing Vivax Malaria , 2015, PLoS neglected tropical diseases.

[18]  Taane G. Clark,et al.  African Glucose-6-Phosphate Dehydrogenase Alleles Associated with Protection from Severe Malaria in Heterozygous Females in Tanzania , 2015, PLoS genetics.

[19]  F. Nosten,et al.  Characterization of G6PD Genotypes and Phenotypes on the Northwestern Thailand-Myanmar Border , 2014, PLoS ONE.

[20]  R. Price,et al.  Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis , 2014, The Lancet. Infectious diseases.

[21]  Jung-Yeon Kim,et al.  First Evaluation of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency in Vivax Malaria Endemic Regions in the Republic of Korea , 2014, PloS one.

[22]  S. Hay,et al.  Spatial distribution of G6PD deficiency variants across malaria-endemic regions , 2013, Malaria Journal.

[23]  S. Hay,et al.  G6PD deficiency: global distribution, genetic variants and primaquine therapy. , 2013, Advances in parasitology.

[24]  I. Elyazar,et al.  Randomized, Open-Label Trial of Primaquine against Vivax Malaria Relapse in Indonesia , 2012, Antimicrobial Agents and Chemotherapy.

[25]  G. Shanks Control and elimination of Plasmodium vivax. , 2012, Advances in parasitology.

[26]  K. Na-Bangchang,et al.  Prevalence and distribution of glucose-6-phosphate dehydrogenase (G6PD) variants in Thai and Burmese populations in malaria endemic areas of Thailand , 2011, Malaria Journal.

[27]  S. Hay,et al.  Malaria distribution, prevalence, drug resistance and control in Indonesia. , 2011, Advances in parasitology.

[28]  T. Kanbe,et al.  Incidence and mutation analysis of glucose-6-phosphate dehydrogenase deficiency in eastern Indonesian populations. , 2010, Acta medica Okayama.

[29]  J. Baird,et al.  Resistance to chloroquine by Plasmodium vivax at Alor in the Lesser Sundas Archipelago in eastern Indonesia. , 2009, The American journal of tropical medicine and hygiene.

[30]  R. Price,et al.  Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria: A Prospective Study in Papua, Indonesia , 2008, PLoS medicine.

[31]  T. Kanbe,et al.  Further investigations of glucose-6-phosphate dehydrogenase variants in Flores Island, eastern Indonesia , 2006, Journal of Human Genetics.

[32]  S. Yoshida,et al.  Five different glucose-6-phophate dehydrogenase (G6PD) variants found among 11 G6PD-deficient persons in Flores Island, Indonesia , 2003, Journal of Human Genetics.

[33]  J. Baird,et al.  Chloroquine-resistant Plasmodium vivax in transmigration settlements of West Kalimantan, Indonesia. , 1998, The American journal of tropical medicine and hygiene.

[34]  T. Tang,et al.  Neonatal jaundice and molecular mutations in glucose‐6‐phosphate dehydrogenase deficient newborn infants , 1996, American journal of hematology.

[35]  E. Tjitra,et al.  Treatment of Uncomplicated In Vitro Chloroquine Resistant Falciparum Malaria with Artemether in Irian Jaya , 1996 .

[36]  N. Saha,et al.  Molecular variants of red cell glucose-6-phosphate dehydrogenase deficiency in Central Java, Indonesia. , 1995, Human heredity.

[37]  H. Notopuro,et al.  Glucose-6-phosphate dehydrogenase deficiency. , 1972, Paediatrica Indonesiana.