Can G6PD Deficiency Be Triggered by Infection?
Yes, infections can trigger hemolytic crises in individuals with G6PD deficiency, though the deficiency itself is an inherited genetic condition that cannot be "triggered" or acquired—only the hemolytic episodes are triggered by infections and other oxidative stressors. 1, 2
Understanding the Mechanism
G6PD deficiency is an X-linked inherited enzymatic disorder that impairs the red blood cell's ability to handle oxidative stress through reduced NADPH production 2. The deficiency itself is present from birth, but hemolytic anemia occurs episodically when triggered by specific stressors 2.
Infections as Hemolytic Triggers
Bacterial and viral infections are well-established triggers of acute hemolytic anemia in G6PD-deficient patients, alongside certain drugs and foods 2, 3
Rocky Mountain Spotted Fever (RMSF) demonstrates this clearly: G6PD deficiency is associated with fulminant cases of RMSF that follow a rapidly fatal clinical course within 5 days of onset, with G6PD deficiency affecting approximately 12% of U.S. Black males being a specific host factor for severe disease 1
Acute HIV infection has been documented to trigger the first episode of G6PD-associated hemolysis, despite the virus-induced hemolytic events being rarely reported in this population 4
Severe G6PD deficiency can lead to susceptibility to bacterial infections through impaired neutrophil function, reduced NADPH oxidase activity, and absent neutrophil extracellular trap (NET) formation—creating a bidirectional relationship where infection both triggers hemolysis and occurs more frequently 5
Clinical Implications for Infection-Related Hemolysis
Variant-Specific Severity
Mediterranean variant (Gdmed) typically causes more severe hemolytic reactions and may result in life-threatening hemolysis when triggered by infection 6, 7
African variant (GdA-) generally produces milder, self-limited hemolysis even when triggered by infectious stressors 6, 7
Fetal and Neonatal Considerations
Fetal infections including parvovirus, cytomegalovirus, syphilis, and toxoplasmosis can cause nonimmune hydrops fetalis in G6PD-deficient fetuses through mechanisms of anemia, anoxia, and endothelial damage 1
Neonatal jaundice occurs in G6PD deficiency, likely due to impairment of liver function rather than solely hemolysis 8
Critical Management Points
Monitoring During Infections
Watch for hemolysis warning signs including jaundice, back or abdominal pain, and declining hemoglobin when G6PD-deficient patients develop infections 6, 9
Baseline and ongoing monitoring should include complete blood count with hemoglobin determination when treating infections in known G6PD-deficient patients 6
Medication Selection During Infections
Avoid oxidant antimicrobials including dapsone, primaquine, and methylene blue when treating infections in G6PD-deficient patients 6, 7
Penicillins (such as amoxicillin) are safe alternatives for bacterial infections and are not contraindicated in G6PD deficiency 9
Artemisinin-based combination therapies can be used safely for malaria treatment in G6PD-deficient patients 7
Common Pitfall to Avoid
Do not assume G6PD deficiency is acquired or develops later in life—it is always inherited, but may remain clinically silent until the first hemolytic trigger (which can be an infection) occurs 2, 8. Testing during acute hemolysis may yield falsely elevated G6PD levels due to young reticulocytes having higher enzyme activity, requiring repeat testing 3 months later for accurate diagnosis 9.