What is the recommended screening test for Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

G6PD Deficiency Screening Test

Recommended Screening Approach

Qualitative screening for G6PD deficiency is recommended upon entry into care or before starting therapy with oxidant drugs in patients with predisposing racial or ethnic backgrounds (Mediterranean, African, Indian, or Southeast Asian descent). 1

Test Selection Based on Clinical Context

For Initial Screening in Resource-Limited Settings

• Qualitative fluorescent spot test is appropriate for detecting severe G6PD deficiency (enzyme activity <10% of normal) in males and homozygous females 1
• This semiquantitative method successfully identifies hemizygous males and severely deficient individuals but misses 46-54% of heterozygous females with partial deficiency 2
• The test is economical and suitable for developing countries where severe deficiency detection is the primary goal 3

For Comprehensive Screening (Preferred Method)

• Quantitative G6PD enzyme assay should be used when accurate detection of all deficiency levels is required, particularly in females 3, 2
• Quantitative testing is essential before prescribing primaquine or tafenoquine for radical cure of P. vivax/P. ovale malaria 1
• Using a cut-off of <60% of normal mean activity (5.7 IU/gHb in adults) detects both severe and partial deficiency 3

Emerging Point-of-Care Options

• Quantitative point-of-care tests (CareStart™ Biosensor and STANDARD G6PD kits) demonstrate high sensitivity (72-100%) and specificity (92-100%) compared to spectrophotometric standards 4
• These POC tests are particularly valuable in malaria-endemic regions where rapid, accurate screening is needed before antimalarial treatment 4

For Heterozygous Female Detection

• Cytochemical assay using a cut-off of >20% negative cells provides prevalence estimates closest to molecular analysis (12.9% vs 14.2% by genetic testing) 3
• Flow cytometry-based fluorocytometric assay quantifies the percentage of G6PD-deficient RBCs and detects heterozygous females missed by spectrophotometry 5
• Flow cytometry shows high sensitivity and specificity but may yield false negatives in patients with sickle cell disease 5

Critical Clinical Considerations

High-Risk Medications Requiring Pre-Treatment Screening

• Dapsone, primaquine, and sulfonamides are the most common oxidant drugs used in HIV-infected patients that cause hemolysis in G6PD deficiency 1
• Primaquine, rasburicase, and methylthioninium chloride (methylene blue) are contraindicated in G6PD deficiency due to severe hemolytic anemia risk 6
• For P. vivax radical cure, test for quantitative G6PD before prescribing; do not use tafenoquine if activity is <70% 1

Variant-Specific Risk Stratification

• Mediterranean variant (Gdmed) causes life-threatening hemolysis and requires strict avoidance of oxidant drugs 1
• African variant (GdA-) produces milder, self-limited hemolysis that may not preclude oxidant drug use with close monitoring 1
• Patients with intermediate G6PD deficiency (30-70% activity) and non-Mediterranean variant can receive weekly primaquine (0.75 mg base/kg for 8 weeks) with close hemolysis monitoring 1

Common Pitfalls to Avoid

• Do not rely solely on fluorescent spot testing in females, as it misses approximately 46% of heterozygous females with partial deficiency who remain at risk for hemolysis 2
• Avoid testing during or immediately after hemolytic episodes, as reticulocytosis can falsely normalize G6PD activity levels 3
• Exercise caution interpreting flow cytometry results in patients with sickle cell disease, as false negatives may occur 5
• Remember that neutropenia may be present in G6PD deficiency but is not a reliable screening marker 1