Screening for Glucose-6-Phosphate Dehydrogenase Deficiency Using Three Detection Methods: A Cross-Sectional Survey in Southwestern Uganda

Abstract

Despite the potential benefit of primaquine in reducing Plasmodium falciparum transmission and radical cure of Plasmodium vivax and Plasmodium ovale infections, concerns over risk of hemolytic toxicity in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd) have hampered its deployment. A cross-sectional survey was conducted in 2014 to assess the G6PDd prevalence among 631 children between 6 and 59 months of age in southwestern Uganda, an area where primaquine may be a promising control measure. G6PDd prevalence was determined using three detection methods: a quantitative G6PD enzyme activity assay (Trinity Biotech G-6-PDH kit), a qualitative point-of-care test (CareStart G6PD rapid diagnostic test [RDT]), and molecular detection of the G6PD A- G202A allele. Qualitative tests were compared with the gold standard quantitative assay. G6PDd prevalence was higher by RDT (8.6%) than by quantitative assay (6.8%), using a < 60% activity threshold. The RDT performed optimally at a < 60% threshold and demonstrated high sensitivity (≥ 90%) and negative predictive values (100%) across three activity thresholds (below 60%, 30%, and 40%). G202A allele frequency was 6.4%, 7.9%, and 6.8% among females, males, and overall, respectively. Notably, over half of the G202A homo-/hemizygous children expressed ≥ 60% enzyme activity. Overall, the CareStart G6PD RDT appears to be a viable screening test to accurately identify individuals with enzyme activities below 60%. The low prevalence of G6PDd across all three diagnostic modalities and absence of severe deficiency in our study suggests that there is little barrier to the use of single-dose primaquine in this region.

The prevalence of glucose-6-phosphate dehydrogenase deficiency in the Cape Verdean population in the context of malaria elimination

“…This value is more than three times higher in males (5.7%) than in females (1.6%). These results are consistent with results from a preliminary study in the country in 2010 [36], and similary to the reports from other studies conducted in other African countries, as Mauritania [37], Uganda [38], Mozambique [39] Senegal [40,41] and Gambia [42]. The high G6PDd prevalence in the African or Afro-descendant population as shown by several studies [39][40][41][42][43] may reflect the population's exposure to malaria endemicity or ethnicity related [8][9][10][11][12][13][14][15][16].…”

Barriers to routine G6PD testing prior to treatment with primaquine

“…Some interviewees highlighted that a limitation of the FST test was its subjective interpretation and low performance. While currently available RDTs for G6PD have comparable performance to the FST [ 16 , 32 ], their operational characteristics are more favourable to the FST. Most currently available G6PD RDTs do not require a cold chain or laboratory infrastructure [ 33 , 34 ], and can be undertaken at the bed-side on an individual basis (point-of-care).…”

Wide range of G6PD activities found among ethnic groups of the Chittagong Hill Tracts, Bangladesh

“…Malaria status was not a significant predictor of G6PD activity irrespective of diagnostic assay applied, however our study was neither designed nor powered to this effect. Although G6PD genotype is a key determinant of enzyme activity [43], we observed poor correlation between G6PD genotype and phenotype, a phenomenon that reflect both assay variability as well as host and environmental factors [44][45][46][47][48][49]. Almost 25% of females heterozygous for a known local G6PD variant had activities above 70%, likely due to lyonization patterns in favor of the G6PD normal allele [50].…”