What is the recommended treatment for complicated malaria?

Treatment of Complicated Malaria

Intravenous artesunate is the first-line treatment for complicated (severe) malaria and should be administered immediately as a medical emergency. 1

Diagnosis of Complicated Malaria

Complicated malaria is diagnosed based on WHO criteria, with the presence of even a single criterion sufficient for diagnosis:

• Clinical criteria:

  • Impaired consciousness (Glasgow Coma Scale <11) 1
  • Multiple convulsions (>2 seizures within 24h) 1
  • Prostration (unable to sit, stand, or walk without assistance) 1
  • Bleeding (recurrent or prolonged bleeding from nose, gums, venipuncture sites) 1
  • Acute renal failure 1
  • Pulmonary edema or ARDS 1

• Laboratory criteria:

  • Acidosis (pH <7.35 or plasma bicarbonate <15 mmol/L) 1
  • Hyperlactatemia (venous plasma lactate >5 mmol/L) 1
  • Severe anemia (hemoglobin <7 g/dL or hematocrit <20% with parasite count >10,000/mL) 1
  • Hypoglycemia (blood glucose <40 mg/dL) 1
  • High parasitemia (>5% in non-immune, >10% in semi-immune subjects) 1
  • Jaundice (bilirubin >3 mg/dL with parasite count >100,000/mL) 1
  • Renal impairment (creatinine >3 mg/dL or oliguria) 1

Treatment Algorithm for Complicated Malaria

First-Line Treatment

1. Intravenous artesunate:

   • Administer for 3 doses 1
   • WHO-recommended first-line treatment for all forms of severe malaria 1
   • FDA approved in 2020, EMA approved in 2021 1
   • Provides faster parasite clearance and shorter ICU stays compared to quinine 1

2. Once patient improves (parasitemia <1% and able to take oral medication):

   • Switch to a full course of oral artemisinin-based combination therapy (ACT) 1

Supportive Management

1. Fluid management:

   • Use restrictive fluid management to avoid pulmonary or cerebral edema 1
   • This approach does not worsen kidney function or tissue perfusion 1

2. For acute kidney injury:

   • Consider acetaminophen (1g every 6 hours for 72 hours) which may have reno-protective effects 1

3. For suspected bacterial co-infection:

   • Start antibiotics but continue only if blood cultures are positive 1

4. Avoid exchange blood transfusion:

   • Not recommended as it has not been shown to improve outcomes 1

Monitoring During Treatment

1. Parasitemia monitoring:

   • Check every 12 hours until parasitemia declines to <1% 1
   • Then check every 24 hours until negative 1

2. Physiological monitoring:

   • Continuous monitoring of cardiocirculatory, pulmonary, kidney, and metabolic parameters 1
   • Monitor glycemia, plasma bicarbonate, and lactate levels 1

3. Post-artesunate delayed hemolysis (PADH) monitoring:

   • Check hemoglobin, haptoglobin, and lactate dehydrogenase levels at days 7,14,21, and 28 1

Important Considerations

• Treat as a medical emergency: Complicated malaria can rapidly progress to death without prompt treatment 2
• Artesunate superiority: Studies show better survival rates with IV artesunate compared to quinine, particularly in patients with high parasitemia 3
• Potential hemolysis: Monitor for self-limiting episodes of unexplained hemolysis after reduction of parasitemia levels 3
• Alternative if artesunate unavailable: Intravenous quinine can be used but is less effective and has more side effects 1, 4
• Contraindications: Mefloquine should not be used for life-threatening malaria infections; intravenous antimalarials are required 5

Common Pitfalls to Avoid

• Delayed diagnosis: A major reason for progression from mild to severe disease is missed or delayed diagnosis 6
• Inadequate monitoring: Failure to monitor for complications like PADH can lead to missed hemolytic events 3
• Premature switch to oral therapy: Wait until parasitemia is <1% and the patient can tolerate oral medication 1
• Excessive fluid administration: Can lead to pulmonary or cerebral edema 1
• Using exchange transfusion: No longer indicated with the availability of artesunate 1

Remember that complicated malaria is a medical emergency requiring immediate treatment with IV artesunate and intensive care monitoring to reduce mortality and improve outcomes 1, 4.