Malaria and Related Conditions Treatment Guidelines

Diagnosis and Treatment Considerations

• The Centers for Disease Control and Prevention recommends avoiding primaquine or limiting to 5 days in populations with high G6PD deficiency prevalence, while the World Health Organization suggests testing for G6PD deficiency before administering primaquine or tafenoquine 1, 2
• The World Health Organization advises against using tafenoquine if G6PD activity is <70%, and individuals with the Mediterranean variant (B-) have a very high risk of severe hemolysis compared to the African variant (A-) 2
• Hydroxocobalamin acts as a nitric oxide scavenger and does not cause methemoglobin formation or hypotension, making it a preferred treatment for cyanide toxicity due to its better safety profile 3, 4

Vasoplegic Syndrome Treatment

• The British Journal of Anaesthesia recommends α1-adrenergic agonist vasopressors as first-line therapy for vasoplegic syndrome (Class I, Level C), with second-line therapy including vasopressin or terlipressin, and third-line therapy including methylene blue 1-2 mg/kg IV bolus followed by continuous infusion (Class IIa, Level B) 5, 6, 7

Methemoglobinemia Diagnosis and Treatment

• Methemoglobinemia can be diagnosed using co-oximetry of multiple wavelengths, which is not detectable by standard pulse oximetry or arterial blood gases, and clinical suspicion is high in the presence of cyanosis despite adequate supplemental oxygen supply 8
• Methylene blue is the first-line treatment for methemoglobinemia in the general population, with a standard dose of 1-2 mg/kg IV over 3-5 minutes, but is contraindicated in G6PD deficient patients due to the risk of severe hemolytic anemia (Class 1, Level B-NR) 8, 9, 10, 11
• Ascorbic acid (vitamin C) is recommended as the treatment of choice for methemoglobinemia in G6PD deficient patients, with dosing options including 0.5-1g every 12 hours, 1.5-2g IV, 5g every 6 hours, or 10g as a single dose for adults, and 0.5g every 12 hours or 1g every 4 hours for children 10
• The following treatment options are available for methemoglobinemia:

• Monitor methemoglobin levels after treatment and watch for rebound phenomenon, and ensure adequate intravenous hydration, oxygen supplementation, and glucose availability, as recommended by the American Journal of Hematology 10

G6PD Deficiency Screening and Considerations

• The American Society of Hematology recommends screening for G6PD deficiency, which should include a thorough history of prior drug-induced hemolytic anemia and ethnic background 12
• Dapsone can cause significant hemolysis in G6PD deficient individuals, and ideally, all patients should be tested for G6PD deficiency before methylene blue administration, as recommended by the American Journal of Hematology 10, 13
• Methylene blue is contraindicated in patients taking SSRIs due to the high risk of potentially life-threatening serotonin syndrome, as recognized by the American Heart Association and American Journal of Hematology 10, 11, 6