Abstract

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide. Primaquine is the only licensed drug that effectively removes Plasmodium vivax hypnozoites from the human host and prevents relapse. While well tolerated by most recipients, primaquine can cause haemolysis in G6PD deficient individuals and is, therefore, underused. Rapid diagnostic tests (RDTs) could permit ascertainment of G6PD status outside of laboratory settings and hence safe treatment in remote areas. The performance of the fluorescent spot test (Trinity, Ireland; FST) and a G6PD RDT (Carestart, USA) against spectrophotometry were assessed.MethodsParticipants were enrolled during cross-sectional surveys in Laos and by purposive sampling in Cambodia. FST and RDT were performed during village surveys and 3 mL of venous blood was collected for subsequent G6PD measurement by spectrophotometry.ResultsA total of 757 participants were enrolled in Laos and 505 in Cambodia. FST and RDT performed best at 30% cut-off activity and performed significantly better in Laos than in Cambodia. When defining intermediate results as G6PD deficient, the FST had a sensitivity of 100% (95%CI 90–100) and specificity of 90% (95%CI 87.7–92.2) in Laos and sensitivity of 98% (94.1–99.6) and specificity of 71% (95%CI 66–76) in Cambodia (p < 0.001). The RDT had sensitivity and specificity of 100% (95%CI 90–100) and 99% (95%CI 97–99) in Laos and sensitivity and specificity of 91% (86–96) and 93% (90–95) in Cambodia (p < 0.001). The RDT performed significantly better (all p < 0.05) than the FST when intermediate FST results were defined as G6PD deficient.ConclusionThe interpretation of RDT results requires some training but is a good alternative to the FST.Trial registration clinicaltrials.gov; NCT01872702; 06/27/2013; https://clinicaltrials.gov/ct2/show/NCT01872702

Highlights

  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide

  • In Cambodia the study population was purposively selected and 100% G6PD activity was defined as 11.8 U/ gHb based on previous studies [16, 21]

  • Prevalence of G6PD deficiency The adjusted male median (AMM) by spectrophotometry (AMM) in Laos was 11.5 U/gHb, with 1.5% (n = 11) of all participants having G6PD activities below 10% of the AMM, 5.2% (n = 28) between 10 and below 30% and 12.2% (n = 53) having activities between 30 and below 70% of the AMM

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Summary

Introduction

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide. The glucose-6-phosphate dehydrogenase (G6PD) enzyme is an essential element of the pentose phosphate pathway (PPP), the only pathway for human red blood cells (RBC) to maintain the cells redox power [1, 2]. The gene coding for the enzyme is on the X—chromosome (Xq28); to date more than 185 G6PD clinically relevant variants have been described that result in varying degrees of reduced G6PD activity, collectively called G6PD deficiency (G6PDd) [3,4,5]. G6PDd is the most common enzymopathy worldwide with more than 400 million individuals affected [6]. Hemizygous males and homozygous females harbour homogenous RBC populations with varying degrees of enzyme deficiency which depend on the genotype [7]. The proportion of normal and deficient erythrocytes is balanced but in some heterozygous females the majority of erythrocytes are deficient resulting in false-normal qualitative tests [9]

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