title: Glucose-6-phosphate dehydrogenase deficiency among Yemeni children residing in malaria-endemic areas of Hodeidah governorate and evaluation of a rapid diagnostic test for its detection.
abstract: BACKGROUND
  Glucose-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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  G6PD 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.
authors.affiliation: Tropical Disease Research Center, Faculty of Medicine and Health Sciences, University of Science and Technology, Sana'a, Yemen.|Department of Parasitology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen.
authors.forename: Rashad
authors.initials: R
authors.lastname: Abdul-Ghani
authors.affiliation: Tropical Disease Research Center, Faculty of Medicine and Health Sciences, University of Science and Technology, Sana'a, Yemen. alsharaby9@yahoo.com.|Department of Parasitology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen. alsharaby9@yahoo.com.
authors.forename: Mohammed A K
authors.identifier: http://orcid.org/0000-0002-8340-5219
authors.initials: MA
authors.lastname: Mahdy
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen.
authors.forename: Reyadh
authors.initials: R
authors.lastname: Saif-Ali
authors.affiliation: Department of Critical Care Nursing, Faculty of Medicine and Health Sciences, Hodeidah University, Hodeidah, Yemen.
authors.forename: Sameer A
authors.initials: SA
authors.lastname: Alkubati
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, University of Science and Technology, Sana'a, Yemen.
authors.forename: Abdulhabib R
authors.initials: AR
authors.lastname: Alqubaty
authors.affiliation: Department of Community Medicine, Faculty of Medicine and Health Sciences, University of Science and Technology, Sana'a, Yemen.
authors.forename: Abdullah A
authors.initials: AA
authors.lastname: Al-Mikhlafy
authors.affiliation: Department of Parasitology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen.
authors.forename: Samira M
authors.initials: SM
authors.lastname: Al-Eryani
authors.affiliation: Department of Parasitology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen.
authors.forename: Abdusalam M
authors.initials: AM
authors.lastname: Al-Mekhlafi
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, University of Science and Technology, Sana'a, Yemen.
authors.forename: Ali
authors.initials: A
authors.lastname: Alhaj
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D003430:Cross-Sectional Studies; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000175:diagnosis* / Q000453:epidemiology*; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012424:Rural Population; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013997:Time Factors; D019371:Topography, Medical; D015006:Yemen / Q000453:epidemiology
keywords: Glucose-6-phosphate dehydrogenase; Malaria; Primaquine; Rapid diagnostic test; Yemen