Abstract

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic enzymopathy worldwide, is associated with an acute haemolytic anaemia in individuals exposed to primaquine. The present study aimed to determine G6PD deficiency among Yemeni children in malaria-endemic areas as well as to assess the performance of the CareStart™ G6PD rapid diagnostic test (RDT) for its detection.MethodsA cross-sectional study recruiting 400 children from two rural districts in Hodeidah governorate was conducted. Socio-demographic data and blood samples were collected and G6PD deficiency was qualitatively detected in fresh blood in the field using the CareStart™ G6PD RDT, while the enzymatic assay was used to quantitatively measure enzyme activity. Performance of the CareStart™ G6PD RDT was assessed by calculating its sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) against the reference enzymatic assay.ResultsThe ranges of enzyme activity were 0.14–18.45 and 0.21–15.94 units/g haemoglobin (U/gHb) for males and females, respectively. However, adjusted male median G6PD activity was 5.0 U/gHb. Considering the adjusted male median as representing 100 % normal enzyme activity, the prevalence rates of G6PD deficiency were 12.0 and 2.3 % at the cut-off activities of ≤60 and ≤10 %, respectively. Multivariable analysis showed that gender, district of residence and consanguinity between parents were independent risk factors for G6PD deficiency at the cut-off activity of ≤30 % of normal. The CareStart™ G6PD RDT showed 100 % sensitivity and NPV for detecting G6PD deficiency at the cut-off activities of ≤10 and ≤20 % of normal activity compared to the reference enzymatic method. However, it showed specificity levels of 90.0 and 95.4 % as well as positive/deficient predictive values (PPVs) of 18.0 and 66.0 % at the cut-off activities of ≤10 and ≤20 %, respectively, compared to the reference method.ConclusionsG6PD deficiency with enzyme activity of ≤60 % of normal is prevalent among 12.0 % of children residing in malaria-endemic areas of Hodeidah governorate, with 2.3 % having severe G6PD deficiency. Gender, district of residence and consanguinity between parents are significant independent predictors of G6PD deficiency at the cut-off activity of ≤30 % of normal among children in malaria-endemic areas of Hodeidah. The CareStart™ G6PD RDT proved reliable as a point-of-care test to screen for severely G6PD-deficient patients, with 100 % sensitivity and NPV, and it can be used for making clinical decisions prior to the administration of primaquine in malaria elimination strategies.

Highlights

  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic enzymopathy worldwide, is associated with an acute haemolytic anaemia in individuals exposed to primaquine

  • negative predictive value (NPV), and it can be used for making clinical decisions prior to the administration of primaquine in malaria elimination strategies

  • The prevalence of G6PD with ≤60 % of normal activity among children residing in malaria-endemic areas of Hodeidah governorate is 12.0 %, with about 2.3 % having severe G6PD deficiency of ≤10 % of normal activity

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Summary

Introduction

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic enzymopathy worldwide, is associated with an acute haemolytic anaemia in individuals exposed to primaquine. Artemisinin derivatives are effective in treating uncomplicated symptomatic falciparum malaria and reducing disease transmission by targeting young gametocytes of Plasmodium falciparum [5,6,7,8], they show little or no activity against P. falciparum mature gametocytes [9]. The effect of artemisinin-based combination therapy (ACT) on the transmission of P. falciparum is only moderate based on field data [10]. Despite being recommended by the World Health Organization (WHO) for blocking P. falciparum transmission and for preventing Plasmodium vivax relapses, primaquine has not been used widely in malaria-endemic areas due to concerns about causing acute haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency [13]

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