Volume 91, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



A barrier to eliminating malaria is inadequate treatment of infected patients. 8-Aminoquinoline–based drugs clear the parasite; however, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk for hemolysis from these drugs. Understanding the performance of G6PD deficiency tests is critical for patient safety. Two quantitative assays and two qualitative tests were evaluated. The comparison of quantitative assays gave a Pearson correlation coefficient of 0.7585 with significant difference in mean G6PD activity, highlighting the need to adhere to a single reference assay. Both qualitative tests had high sensitivity and negative predictive value at a cutoff G6PD value of 40% of normal activity if interpreted conservatively and performed under laboratory conditions. The performance of both tests dropped at a cutoff level of 45%. Cytochemical staining of specimens confirmed that heterozygous females with > 50% G6PD-deficient cells can seem normal by phenotypic tests.

[open-access] 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.


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  1. Beutler E, , 1994. G6PD deficiency. Blood 84: 36133636. [Google Scholar]
  2. Domingo GJ, Winasti Satyagraha A, Anvikar A, Baird JK, Bancone G, Bansil P, Carter N, Cheng Q, Culpepper J, Eziefula C, Fukuda M, Green J, Hwang J, Lacerda M, McGray S, Menard D, Nosten F, Nuchprayoon I, Nwe Oo N, Bualombai P, Pumpradit W, Qian K, Recht J, Roca A, Satimai W, Sovannaroth S, Vestergaard LS, von Seidlein L, , 2013. G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests. Malar J 12: 391.[Crossref] [Google Scholar]
  3. von Seidlein L, Auburn S, Espino F, Shanks D, Cheng J, McCarthy J, Baird JK, Moyes C, Howes R, Menard D, Bancone G, Winasti-Satyahraha A, Vestergaard LS, Green J, Domingo GJ, Yeung S, Price R, , 2013. Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report. Malar J 12: 112.[Crossref] [Google Scholar]
  4. Howes RE, Piel FB, Patil AP, Nyangiri OA, Gething PW, Dewi M, Hogg MM, Battle KE, Padilla CD, Kaird JK, Hay SI, , 2012. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med 9: e1001339.[Crossref] [Google Scholar]
  5. Howes RE, Battle KE, Satyagraha AW, Baird JK, Hay SI, , 2013. G6PD deficiency: global distribution, genetic variants and primaquine therapy. Adv Parasitol 81: 133201.[Crossref] [Google Scholar]
  6. Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E, , 2009. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis 42: 267278.[Crossref] [Google Scholar]
  7. Cappellini MD, Fiorelli G, , 2008. Glucose-6-phosphate dehydrogenase deficiency. Lancet 371: 6474.[Crossref] [Google Scholar]
  8. Luzzatto L, Mehta A, Vulliamy TJ, Scriver CR, Beaudet AL, Sly WS, Valle D, , 2001. Glucose-6-phosphate dehydrogenase deficiency. , eds. The Metabolic and Molecular Basis of Inherited Disease. New York, NY: McGraw-Hill, 45174553. [Google Scholar]
  9. Minucci A, Moradkhani K, Hwang MJ, Zuppi C, Giardina B, Capoluongo E, , 2012. Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the “old” and update of the new mutations. Blood Cells Mol Dis 48: 154165.[Crossref] [Google Scholar]
  10. World Health Organization, 1989. Glucose-6-phosphate dehydrogenase deficiency: WHO Working Group. Bull World Health Organ 67: 601611. [Google Scholar]
  11. World Health Organization, 1967. Standardization of Procedures for the Study of Glucose-6-Phosphate Dehydrogenase: Report of a WHO Scientific Group. WHO Technical Report Series No. 366. Available at: https://extranet.who.int/iris/restricted/bitstream/10665/40660/1/WHO_TRS_366.pdf. Accessed March 17, 2014. [Google Scholar]
  12. Ainoon O, Alawiyah A, Yu YH, Cheong SK, Hamidah NH, Boo NY, Zaleha M, , 2003. Semiquantitative screening test for G6PD deficiency detects severe deficiency but misses a substantial proportion of partially-deficient females. Southeast Asian J Trop Med Public Health 34: 405414. [Google Scholar]
  13. Johnson MK, Clark TD, Njama-Meya D, Rosenthal PJ, Parikh S, , 2009. Impact of the method of G6PD deficiency assessment on genetic association studies of malaria susceptibility. PLoS ONE 4: e7246.[Crossref] [Google Scholar]
  14. Nantakomol D, Paul R, Palasuwan A, Day NP, White NJ, Imwong M, , 2013. Evaluation of the phenotypic test and genetic analysis in the detection of glucose-6-phosphate dehydrogenase deficiency. Malar J 12: 289.[Crossref] [Google Scholar]
  15. Reclos GJ, Hatzidakis CJ, Schulpis KH, , 2000. Glucose-6-phosphate dehydrogenase deficiency neonatal screening: preliminary evidence that a high percentage of partially deficient female neonates are missed during routine screening. J Med Screen 7: 4651.[Crossref] [Google Scholar]
  16. Shah SS, Diakite SA, Traore K, Diakite M, Kwiatkowski DP, Rockett KA, Wellems TE, Fairhurst RM, , 2012. A novel cytofluorometric assay for the detection and quantification of glucose-6-phosphate dehydrogenase deficiency. Sci Rep 2: 299.[Crossref] [Google Scholar]
  17. van Noorden CJ, Vogels IM, James J, Tas J, , 1982. A sensitive cytochemical staining method for glucose-6-phosphate dehydrogenase activity in individual erythrocytes. I. Optimalization of the staining procedure. Histochemistry 75: 493506.[Crossref] [Google Scholar]
  18. van Noorden CJ, Dolbeare F, Aten J, , 1989. Flow cytofluorometric analysis of enzyme reactions based on quenching of fluorescence by the final reaction product: detection of glucose-6-phosphate dehydrogenase deficiency in human erythrocytes. J Histochem Cytochem 37: 13131318.[Crossref] [Google Scholar]
  19. Wei X, Ju X, Yi X, Zhu Q, Qu N, Liu T, Chen Y, Jiang H, Yang G, Zhen R, Lan Z, Qi M, Wang J, Yang Y, Chu Y, Li X, Guang Y, Huang J, , 2011. Identification of sequence variants in genetic disease-causing genes using targeted next-generation sequencing. PLoS ONE 6: e29500.[Crossref] [Google Scholar]
  20. Kim S, Nguon C, Guillard B, Duong S, Chy S, Sum S, Nhem S, Bouchier C, Tichit M, Christophel E, Taylor WRJ, Baird JK, Menard D, , 2011. Performance of the CareStart G6PD deficiency screening test, a point-of-care diagnostic for primaquine therapy screening. PLoS ONE 6: e28357.[Crossref] [Google Scholar]
  21. Kuwahata M, Wijesinghe R, Ho MF, Pelecanos A, Bobogare A, Landry L, Bugora H, Vallely A, McCarthy J, , 2010. Population screening for glucose-6-phosphate dehydrogenase deficiencies in Isabel Province, Solomon Islands, using a modified enzyme assay on filter paper dried bloodspots. Malar J 9: 223.[Crossref] [Google Scholar]
  22. Tantular IS, Iwai K, Lin K, Basuki S, Horie T, Htay HH, Matsuoka H, Marwoto H, Wongsrichanalai C, Dachlan YP, Kojima S, Ishii A, Kawamoto F, , 1999. Field trials of a rapid test for G6PD deficiency in combination with a rapid diagnosis of malaria. Trop Med Int Health 4: 245250.[Crossref] [Google Scholar]
  23. Tinley KE, Loughlin AM, Jepson A, Barnett ED, , 2010. Evaluation of a rapid qualitative enzyme chromatographic test for glucose-6-phosphate dehydrogenase deficiency. Am J Trop Med Hyg 82: 210214.[Crossref] [Google Scholar]
  24. Kornberg A, Horecker BL, Colowick SP, Kaplan NO, , 1959. Glucose-6-phosphate dehydrogenase. , eds. Methods in Enzymology. New York, NY: Academic Press. [Google Scholar]
  25. Lohr GW, Waller HD, Bergmayer HU, , 1974. Glucose-6-phosphate dehydrogenase. , ed. Methods of Enzymatic Analysis, Vol. 1. New York, NY: Academic Press. [Google Scholar]
  26. De Niz M, Othieno L, Mbabazi E, Nabukeera D, Ssemmondo E, Gonahasa S, Tumwebaze P, Diliberto D, Maiteki-Sebuguzi C, Staedke SG, Drakeley C, , 2013. Tools for mass screening of G6PD deficiency: validation of the WST8/1-methoxy-PMS enzymatic assay in Uganda. Malar J 12: 210.[Crossref] [Google Scholar]

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  • Received : 01 Apr 2014
  • Accepted : 25 Jun 2014
  • Published online : 01 Oct 2014

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