Comparison of glucose-6 phosphate dehydrogenase status by fluorescent spot test and rapid diagnostic test in Lao PDR and Cambodia

Gisela Henriques, Koukeo Phommasone, Rupam Tripura, Thomas J Peto, Shristi Raut, Coco Snethlage, Im Sambo, Nou Sanann, Chea Nguon, Bipin Adhikari, Tiengkham Pongvongsa, Mallika Imwong, Lorenz von Seidlein, Nicholas P Day, Nicholas J White, Arjen M Dondorp, Paul Newton, Benedikt Ley, Mayfong Mayxay, Gisela Henriques, Koukeo Phommasone, Rupam Tripura, Thomas J Peto, Shristi Raut, Coco Snethlage, Im Sambo, Nou Sanann, Chea Nguon, Bipin Adhikari, Tiengkham Pongvongsa, Mallika Imwong, Lorenz von Seidlein, Nicholas P Day, Nicholas J White, Arjen M Dondorp, Paul Newton, Benedikt Ley, Mayfong Mayxay

Abstract

Background: Glucose-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.

Methods: Participants 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.

Results: A 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.

Conclusion: The interpretation of RDT results requires some training but is a good alternative to the FST. Trial registration clinicaltrials.gov; NCT01872702; 06/27/2013; https://ichgcp.net/clinical-trials-registry/NCT01872702.

Keywords: Glucose-6-phosphate dehydrogenase; Malaria; Rapid diagnostic test; Southeast Asia.

Figures

Fig. 1
Fig. 1
G6PD activity distribution by spectrophotometry in Laos. Red lines indicate 10, 30, 70 and 100% G6PD activity of the adjusted male median
Fig. 2
Fig. 2
Distribution of G6PD normal and G6PD deficient test result by quantitative G6PD activity per assay and stratified by country. Red triangles = G6PD deficient test result, blue circles = G6PD normal test result. Red horizontal lines correspond to 10, 30, 70 and 100% G6PD activity of the AMM (from bottom to top), invalid RDT results are excluded

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