Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil

Abstract

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria.

Methodology/principal findings: This study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed. Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test's sensitivity at the <30% threshold on both specimen types was 100% (95% confidence interval [CI] venous 93.6%-100.0%; capillary 93.8%-100.0%). Specificity was 98.6% on venous specimens (95% CI 97.9%-99.1%) and 97.8% on capillary (95% CI 97.0%-98.5%). At the 70% threshold, the test's sensitivity was 96.9% on venous specimens (95% CI 83.8%-99.9%) and 94.3% on capillary (95% CI 80.8%-99.3%). Specificity was 96.5% (95% CI 95.0%-97.6%) and 92.3% (95% CI 90.3%-94.0%) on venous and capillary specimens, respectively.

Conclusion/significance: The STANDARD G6PD Test is a promising tool to aid in POC detection of G6PD deficiency in Brazil.

Trial registration: This study was registered with ClinicalTrials.gov (identifier: NCT04033640).

Fig 1. Histogram showing the distribution of G6PD activities in the study population.

The frequency is plotted against the normalized reference assay G6PD activity in 10% increments for A) males, and B) females. The 30%, 70%, and 80% activity limits are indicated on each plot. G6PD, glucose-6-phosphate dehydrogenase.

Fig 2

ROC curves at 30% and 70% G6PD activity thresholds on A) venous specimens and B) capillary specimens. ROC, receiver operating curve.

Fig 3. Regression analysis of STANDARD G6PD Test’s G6PD activity on A) venous specimens and B) capillary specimens, compared to normalized spectrophotometric reference test on venous specimens.

Fig 4

Regression analysis of STANDARD G6PD Test total hemoglobin measurement on A) capillary specimens compared to complete blood count, B) venous specimens compared to complete blood count (Manaus only). CBC, complete blood count; Hb, hemoglobin.