What are the alternative treatment options to IV (intravenous) artesunate for severe Plasmodium falciparum malaria?

Alternative Treatment Options for Severe Plasmodium falciparum Malaria

Intravenous quinine is the primary alternative to IV artesunate for treating severe Plasmodium falciparum malaria when artesunate is unavailable. 1

First-Line Treatment and Alternatives

IV artesunate remains the gold standard treatment for severe falciparum malaria, with demonstrated superiority over quinine in terms of:

• Faster parasite clearance
• Shorter ICU stays
• Lower mortality (15% vs 22%, absolute reduction of 34.7%) 2, 3

Alternative Options When IV Artesunate is Unavailable:

1. IV Quinine

   • Dosing: 20 mg/kg loading dose infused over 4 hours, followed by 10 mg/kg infused over 2-8 hours three times daily 1, 3
   • Continue until patient can take oral medication and parasitemia is <1%
   • Monitor closely for adverse effects, particularly:
     • Hypoglycemia (3.2 times more common than with artesunate) 3
     • QT interval prolongation
     • Cinchonism (tinnitus, hearing impairment, dizziness)

2. Combined IV Artesunate and IV Quinine

   • Can be considered in cases where limited artesunate is available
   • This combination has been found efficacious and well-tolerated in case series 4
   • May be particularly useful in settings with limited artesunate supply

Transition to Oral Therapy

Once clinical improvement occurs and parasitemia is <1%, transition to a complete oral course of:

1. Artemisinin-based Combination Therapy (ACT)

   • Dihydroartemisinin-piperaquine
   • Artemether-lumefantrine
   • Artesunate-mefloquine (4 mg/kg/day artesunate for 3 days with mefloquine 8 mg/kg/day for 3 days) 1, 5

2. Non-ACT alternatives

   • Atovaquone-proguanil
   • Mefloquine monotherapy (caution with neuropsychiatric side effects)

Monitoring During Alternative Treatments

• Check parasitemia every 12 hours until <1%, then every 24 hours until negative 2, 1
• With quinine, an increase in parasite density may be observed in the first 24 hours (not indicative of treatment failure) 2
• Monitor blood glucose closely due to higher risk of hypoglycemia with quinine 1, 3
• Perform ECG monitoring when using quinine due to risk of QT prolongation 6
• Monitor for signs of cardiotoxicity, especially with chloroquine (which is generally not recommended for falciparum malaria due to widespread resistance) 6

Important Considerations and Pitfalls

• Avoid chloroquine for treating falciparum malaria due to widespread resistance 6
• Do not delay treatment while waiting for preferred medication; mortality increases with treatment delays 1
• Exchange transfusion is no longer recommended with the availability of effective antimalarials 2, 1
• Restrictive fluid management is recommended to avoid pulmonary or cerebral edema 2, 1
• Consider acetaminophen (1g every 6 hours for 72 hours) for potential renoprotective effects 2, 1
• Start antibiotics only if bacterial co-infection is suspected 2, 1

Special Patient Populations

• Asplenic patients are at higher risk for severe malaria and complications 1
• Pregnant women can receive IV quinine or IV artesunate (when available)
• Children can be treated with the same alternative medications with weight-adjusted dosing 7

Remember that while alternatives exist, IV artesunate remains the treatment of choice for severe falciparum malaria whenever available, with quinine serving as the most established alternative.