Volume 97, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Throughout many developing and tropical countries around the world, malaria remains a significant threat to human health. One barrier to malaria elimination is the ability to safely administer primaquine chemotherapy for the radical cure of malaria infections in populations with a high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency. In the current study, a field trial of the world’s first quantitative, point-of-care assay for measuring G6PD activity was conducted in Haiti. The performance of the CareStart Biosensor Analyzer was compared with the gold standard spectrophotometric assay and genotyping of the allele in schoolchildren ( = 343) from the Ouest Department of Haiti. In this population, 19.5% of participants (67/343) had some form of G6PD deficiency (< 60% residual activity) and 9.9% (34/343) had moderate-to-severe G6PD deficiency (< 30% residual activity). Overall, 18.95% of participants had the presence of the A-allele (65/343) with 7.87% (27/343) considered at high risk for drug-induced hemolysis (hemizygous males and homozygous females). Compared with the spectrophotometric assay, the sensitivity and specificity to determine participants with < 60% residual activity were 53.7% and 94.6%, respectively; for participants with 30% residual activity, the sensitivity and specificity were 5.9% and 99.7%, respectively. The biosensor overestimated the activity in deficient individuals and underestimated it in participants with normal G6PD activity, indicating the potential for a systematic measurement error. Thus, we suggest that the current version of the biosensor lacks adequate sensitivity and should be improved prior to its use as a point-of-care diagnostic for G6PD deficiency.


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  1. World Health Organization, 2015. World Malaria Report. Geneva, Switzerland: WHO. Available at: http://www.who.int/malaria/publications/world-malaria-report-2015/report/en/. Accessed December 8, 2016.
  2. Mikolajczak SA, ., 2015. Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice. Cell Host Microbe 17: 526553.[Crossref] [Google Scholar]
  3. Galappaththy GNL, Tharyan P, Kirubakaran R, , 2013. Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine. Cochrane Database Syst Rev 10: CD004389. [Google Scholar]
  4. Beutler E, , 1996. G6PD: population genetics and clinical manifestations. Blood Rev 10: 4552.[Crossref] [Google Scholar]
  5. Mason PJ, Bautista JM, Gilsanz F, 2007. G6PD deficiency: the genotype-phenotype association. Blood Rev 21: 267283.[Crossref] [Google Scholar]
  6. Luzzatto L, Metha A, Vulliamy T, , 2001. Glucose-6-phosphate dehydrogenase deficiency. Scriver CR, Beaudet AL, Sly WS, eds. The Metabolic and Molecular Bases of Inherited Disease, 9th edition. Columbus, OH: McGraw-Hill, 4517–4553.
  7. Beutler E, Duparc S, , 2007. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg 77: 779789. [Google Scholar]
  8. World Health Organization, 2015. Point-of-care G6PD testing to support safe use of primaquine for the treatment of vivax malaria. Geneva, Switzerland: WHO. Available at: http://www.who.int/malaria/mpac/mpac-march2015-erg-g6pd.pdf. Accessed November 10, 2016.
  9. Osorio L, ., 2015. Performance of binaxNOW G6PD deficiency point-of-care diagnostic in P. vivax-infected subjects. Am J Trop Med Hyg 92: 2227.[Crossref] [Google Scholar]
  10. Kim S, ., 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]
  11. Access Bio, Inc. Manufacturer Information and Instruction for the Operation of the CareStart TM G6PD Biosensor Analyzer. Available at: http://www.accessbio.net/eng/products/products03.asp. Accessed January 1, 2017.
  12. World Health Organization, 1989. Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ 67: 601611. [Google Scholar]
  13. Howes RE, ., 2013. Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malar J 12: 418426.[Crossref] [Google Scholar]
  14. Carter TE, Maloy H, von Fricken ME, St Victor Y, Romain JR, Okech BA, , 2014. Glucose-6-phosphate dehydrogenase deficiency A-variant in febrile patients in Haiti. Am J Trop Med Hyg 91: 412414.[Crossref] [Google Scholar]
  15. Tishkoff SA, ., 2001. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293: 455462.[Crossref] [Google Scholar]
  16. Landis JR, Koch GG, , 1977. The measurement of observer agreement for categorical data. Biometrics 33: 159174.[Crossref] [Google Scholar]
  17. Weppelmann TA, Carter TE, Chen Z, von Fricken ME, Victor YS, Existe A, Okech BA, , 2013. High frequency of the erythroid silent Duffy antigen genotype and lack of Plasmodium vivax infections in Haiti. Malar J 12: 30.[Crossref] [Google Scholar]
  18. Weppelmann TA, von Fricken ME, Lam B, Telisma T, Existe A, Lemoine JF, Larkin J, III Okech BA, , 2016. Sparse serological evidence of Plasmodium vivax transmission in the Ouest and Sud-Est departments of Haiti. Acta Trop 162: 2734.[Crossref] [Google Scholar]
  19. von Fricken ME, Weppelmann TA, Lam B, Eaton WT, Schick L, Masse R, Beau De Rochars MV, Existe A, Larkin J, III Okech BA, , 2014. Age-specific malaria seroprevalence rates: a cross-sectional analysis of malaria transmission in the Ouest and Sud-Est departments of Haiti. Malar J 13: 361.[Crossref] [Google Scholar]
  20. von Fricken ME, Weppelmann TA, Eaton WT, Alam MT, Carter TE, Schick L, Masse R, Romain JR, Okech BA, , 2014. Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Ouest and Sud-Est departments of Haiti. Acta Trop 135: 6266.[Crossref] [Google Scholar]
  21. von Fricken ME, Weppelmann TA, Eaton WT, Masse R, Beau de Rochars MV, Okech BA, , 2014. Performance of the CareStart glucose-6-phosphate dehydrogenase (G6PD) rapid diagnostic test in Gressier, Haiti. Am J Trop Med Hyg 91: 7780.[Crossref] [Google Scholar]
  22. Domingo GJ, ., 2013. G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests. Malar J 12: 391.[Crossref] [Google Scholar]
  23. Luzzatto L, Seneca E, , 2013. G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications. Brit J Haem 164: 469480.[Crossref] [Google Scholar]

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  • Received : 31 Aug 2016
  • Accepted : 13 Apr 2017
  • Published online : 14 Aug 2016

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