What is the recommended treatment for Plasmodium knowlesi malaria from Malaysia?

Treatment for Plasmodium Knowlesi Malaria from Malaysia

For uncomplicated Plasmodium knowlesi malaria from Malaysia, artemisinin-based combination therapy (ACT) is the recommended first-line treatment due to faster parasite clearance and lower rates of anemia compared to chloroquine. 1, 2, 3

Treatment Algorithm

Uncomplicated P. knowlesi Malaria

1. First-line treatment: Artemisinin-based combination therapy (ACT)

   • Artemether-lumefantrine (AL): Total target dose of 12 mg/kg artemether and 60 mg/kg lumefantrine 2
   • Dihydroartemisinin-piperaquine (DHA-PPQ): Preferred ACT due to longer half-life 1
   • Artesunate-mefloquine: Shows faster parasite clearance (18.0 hours vs 24.0 hours with chloroquine) 3

2. Alternative treatment: Chloroquine

   • Total dose: 25 mg/kg divided over 3 days
   • Adult dosing: 600 mg base initially, followed by 300 mg at 24 and 48 hours (total 1500 mg) 1
   • Note: While effective, chloroquine results in longer parasite clearance time and higher risk of anemia 3

Severe P. knowlesi Malaria

1. First-line treatment: Intravenous artesunate

   • Dosing: 2.4 mg/kg IV at 0,12, and 24 hours, then daily 1
   • Continue until parasitemia <1% and patient can take oral medication 4
   • Then complete treatment with a full course of oral ACT 4

2. Alternative treatment: IV quinine dihydrochloride (if artesunate unavailable) 1

3. Adjunctive therapy:

   • Consider acetaminophen (1 g every 6 hours for 72 hours) for renoprotection, especially in patients with acute kidney injury 4, 5
   • Restrictive fluid management to avoid pulmonary or cerebral edema 4
   • Antibiotics only if bacterial co-infection is suspected 4

Clinical Considerations

Monitoring

• Monitor parasitemia every 24 hours until negative for uncomplicated malaria
• For severe malaria, monitor every 12 hours until <1%, then every 24 hours until negative 1
• ACTs result in faster parasite clearance (76% aparasitemic at 24h with AL vs 60% with chloroquine) 2

Benefits of ACT over Chloroquine

• Faster parasite clearance (18h vs 24h) 3
• Lower risk of anemia (62% vs 75%) 3
• Faster fever clearance (11.5h vs 14.8h) 3
• Reduced hospital stay (2426 vs 2828 days per 1000 patients) 3

Special Populations

• ACTs are effective in both adults and children with P. knowlesi infection 2
• P. knowlesi can cause severe disease in adults with risk at least as high as falciparum malaria 6

Potential Pitfalls and Caveats

• P. knowlesi is often misdiagnosed as P. malariae by microscopy, but can cause severe disease unlike P. malariae 5
• Rapid diagnostic tests may miss P. knowlesi infections as they are designed for P. falciparum and P. vivax 1
• Chloroquine treatment risks inadequate therapy if the infection is actually drug-resistant P. falciparum or P. vivax misdiagnosed as P. knowlesi 5
• Severe P. knowlesi malaria can develop rapidly with high parasitemia, requiring prompt treatment 6
• Unlike P. falciparum, severe P. knowlesi rarely causes coma, but commonly causes respiratory distress, acute renal failure, and shock 7

A unified treatment policy using ACTs for all Plasmodium species in co-endemic areas like Malaysia is recommended to ensure effective treatment regardless of species identification challenges 3, 5.