Reference and point-of-care testing for G6PD deficiency: Blood disorder interference, contrived specimens, and fingerstick equivalence and precision

Abstract

Certain clinical indications and treatments such as the use of rasburicase in cancer therapy and 8-aminoquinolines for Plasmodium vivax malaria treatment would benefit from a point-of-care test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Three studies were conducted to evaluate the performance of one such test: the STANDARD™ G6PD Test (SD BIOSENSOR, South Korea). First, biological interference on the test performance was evaluated in specimens with common blood disorders, including high white blood cell (WBC) counts. Second, the test precision on fingerstick specimens was evaluated against five individuals of each, deficient, intermediate, and normal G6PD activity status. Third, clinical performance of the test was evaluated at three point-of-care settings in the United States. The test performed equivalently to the reference assay in specimens with common blood disorders. High WBC count blood samples resulted in overestimation of G6PD activity in both the reference assay and the STANDARD G6PD Test. The STANDARD G6PD Test showed good precision on multiple fingerstick specimens from the same individual. The same G6PD threshold values (U/g Hb) were applied for a semiquantitative interpretation for fingerstick- and venous-derived results. The sensitivity/specificity values (95% confidence intervals) for the test for G6PD deficiency were 100 (92.3–100.0)/97 (95.2–98.2) and 100 (95.7–100.0)/97.4 (95.7–98.5) for venous and capillary specimens, respectively. The same values for females with intermediate (> 30% to ≤ 70%) G6PD activity were 94.1 (71.3–99.9)/88.2 (83.9–91.7) and 82.4 (56.6–96.2)/87.6(83.3–91.2) for venous and capillary specimens, respectively. The STANDARD G6PD Test enables point-of-care testing for G6PD deficiency.

Quantitative G6PD point-of-care test can be used reliably on cord blood to identify male and female newborns at increased risk of neonatal hyperbilirubinaemia: a mixed method study

“…In settings where phototherapy is available, this study indicates that the Biosensor is a better option than FST to support clinical management of neonates. Technical performance of the Biosensor using ROC-derived threshold was comparable to that observed in adult blood in laboratory and field studies [26][27][28][29].…”

“…Poor performance of FST can be explained by the higher G6PD enzymatic activity at birth as compared to adulthood [31,32]; this is probably the result of several haematological factors including younger red cell age, increased number of reticulocytes with higher G6PD activity [33,34] and higher WBC count [28] as observed here. Importantly, because of higher enzymatic activity in cord blood, Biosensor haemoglobin values had a moderate correlation with those assessed by automatic haematology analyser.…”

“…Among intermediate phenotypes, 80% were identified as either deficient or intermediate, allowing a better identification of neonates at potential jaundice risk as compared to the currently used FST-based diagnosis [14, 30]. Poor performance of FST can be explained by the higher G6PD enzymatic activity at birth as compared to adulthood [31, 32]; this is probably the result of several haematological factors including younger red cell age, increased number of reticulocytes with higher G6PD activity [33, 34] and higher WBC count [28] as observed here. Importantly, because of higher enzymatic activity in cord blood, thresholds established in adult blood cannot be used to identify deficient or intermediate phenotypes by either spectrophotometry or Biosensor at birth and would have missed identification of 10% (3/29) deficient neonates (2/26 deficient males and 1/4 deficient females) and 86% (19/22) intermediate females.…”

Clinical performance validation of the STANDARD G6PD Test: A multi-country pooled analysis

“…Data were included from similar cross-sectional diagnostic accuracy studies conducted in seven countries: Bangladesh, 21 Brazil, 20 Ethiopia (unpublished), India (unpublished), Thailand, 19 the United Kingdom, 22 and the United States 19,22 (Supplementary Table 1). Collectively, these studies span a varied range of underlying G6PD epidemiology and malaria incidence.…”

“…Cross-sectional diagnostic accuracy studies have been conducted in a wide range of settings and locations, to evaluate the performance of the STANDARD G6PD Test . [19][20][21][22] Pooling data from these studies allows for a robust diagnostic performance analysis across diverse populations representative of multiple contexts and use cases for POC G6PD testing. Our aim was to 1) present these data for the STANDARD G6PD Test, 2) explore how a common set of thresholds to classify G6PD deficient or intermediate individuals with POC testing can be applied across populations, and 3) consider the implications of the test performance on 8-aminoquinoline malaria treatment regimens.…”