Comparison of Three Screening Test Kits for G6PD Enzyme Deficiency: Implications for Its Use in the Radical Cure of Vivax Malaria in Remote and Resource-Poor Areas in the Philippines

Abstract

ObjectiveWe evaluated a battery of Glucose-6-Phosphate Dehydrogenase diagnostic point-of-care tests (PoC) to assess the most suitable product in terms of performance and operational characteristics for remote areas.MethodsSamples were collected in Puerto Princesa City, Palawan, Philippines and tested for G6PD deficiency with a fluorescent spot test (FST; Procedure 203, Trinity Biotech, Ireland), the semiquantitative WST8/1-methoxy PMS (WST; Dojindo, Japan) and the Carestart G6PD Rapid Diagnostic Test (CSG; AccessBio, USA). Results were compared to spectrophotometry (Procedure 345, Trinity Biotech, Ireland). Sensitivity and specificity were calculated for each test with cut-off activities of 10%, 20%, 30% and 60% of the adjusted male median.ResultsThe adjusted male median was 270.5 IU/1012 RBC. FST and WST were tested on 621 capillary blood samples, the CSG was tested on venous and capillary blood on 302 samples. At 30% G6PD activity, sensitivity for the FST was between 87.7% (95%CI: 76.8% to 93.9%) and 96.5% (95%CI: 87.9% to 99.5%) depending on definition of intermediate results; the WST was 84.2% (95%CI: 72.1% to 92.5%); and the CSG was between 68.8% (95%CI: 41.3% to 89.0%) and 93.8% (95%CI: 69.8% to 99.8%) when the test was performed on capillary or venous blood respectively. Sensitivity of FST and CSG (tested with venous blood) were comparable (p>0.05). The analysis of venous blood samples by the CSG yielded significantly higher results than FST and CSG performed on capillary blood (p<0.05). Sensitivity of the CSG varied depending on source of blood used (p<0.05).ConclusionThe operational characteristics of the CSG were superior to all other test formats. Performance and operational characteristics of the CSG performed on venous blood suggest the test to be a good alternative to the FST.

Glucose-6-Phosphate Dehydrogenase Deficiency among Children Attending the Emergency Department of Yankin Children’s Hospital, Yangon

“…Philippines by using Trinity Biotech G6PD kit. 18 Apart from age group involved in the studies, the differences in quantitative values of G6PD activity may also be due to the different comercial kits used. LaRule, et al reported that reference values vary widely depending on the reference tests used.…”

Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria

“…A combination of phenotyping and genotyping was used for several reasons. Firstly, the FST accurately diagnoses severe G6PD deficiency [23] at activity levels below 30% of population median, but its positive predictive value is still likely to be low when the population prevalence of deficiency is low. Hence a second test to confirm the presence of a genotype compatible with deficiency was required.…”

“…Hence a second test to confirm the presence of a genotype compatible with deficiency was required. Secondly, consideration of only cases with clear deficiency on the FST was likely to be insensitive for detection of cases with intermediate levels of G6PD activity seen in a proportion of female heterozygotes [23, 29, 30]. For this reason, all cases with an intermediate result on the FST were genotyped.…”

“…The rationale for requiring genotypic as well as phenotypic evidence was that for rare conditions the positive predictive value of a test, even if it is highly specific [23], is low, leading to a high proportion of false positives (false deficients).…”

A patient with both methemoglobinemia and G6PD deficiency: A therapeutic conundrum

“…To address this challenge, there have been attempts to develop commercially available rapid screening tests for G6PD deficiency. Recent studies have identified there are a number of short‐comings associated with these tests: low sensitivity (<85%) for detecting individuals with moderate and severe deficiency, a high degree of false G6PD normal results in males and heterozygous females, and difficulty interpreting the readout signal …”