What is the recommended treatment for Plasmodium Knowlesi (Malaria) infections?

Treatment of Plasmodium Knowlesi Malaria

Artemisinin-based combination therapy (ACT) is the recommended first-line treatment for uncomplicated Plasmodium knowlesi malaria, while intravenous artesunate is the treatment of choice for severe P. knowlesi infections. 1, 2, 3

Classification and Assessment

When evaluating a patient with suspected P. knowlesi infection, determine severity based on:

• Uncomplicated malaria: Patient able to tolerate oral medication with parasitemia <5%
• Severe malaria: Any of the following 1, 4, 3:
  • Parasitemia >5% of erythrocytes infected
  • Respiratory distress
  • Acute renal failure
  • Shock
  • Inability to tolerate oral medication

P. knowlesi can be misdiagnosed as P. malariae by microscopy, but unlike P. malariae, P. knowlesi can rapidly progress to severe disease with high parasitemia. PCR confirmation is ideal but treatment should not be delayed while awaiting results 4, 2.

Treatment Algorithm

For Uncomplicated P. knowlesi Malaria:

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

   • Artemether-lumefantrine: 4 tablets at 0 and 8 hours on day 1, then 4 tablets twice daily on days 2-3 (for adults >35kg) 5, 2
   • Take with fatty meal for optimal absorption 5

2. Alternative: Chloroquine (if ACTs unavailable)

   • Total dose: 25 mg/kg over 3 days
   • Adults: 600 mg base initially, then 300 mg at 6,24, and 48 hours 5
   • Children: 10 mg/kg on days 1-2, then 5 mg/kg on day 3 5

For Severe P. knowlesi Malaria:

1. First-line: Intravenous artesunate 1, 4, 3, 6

   • Administer for 3 doses (0,12,24 hours)
   • Once patient improves (parasitemia <1%) and can tolerate oral medication, switch to oral ACT to complete treatment 1

2. Alternative (if artesunate unavailable): Intravenous quinine 1, 4

   • Loading dose: 10 mg quinidine gluconate/kg over 1-2 hours
   • Followed by constant infusion of 0.02 mg/kg/minute 1
   • Monitor ECG for QT prolongation and QRS widening
   • Monitor blood glucose for hypoglycemia

Monitoring and Follow-up

1. Parasitemia monitoring:

   • Every 12 hours after starting treatment until parasitemia <1%
   • Then every 24 hours until negative 1
   • Expect parasite clearance 1-2 days faster with artemisinin derivatives compared to chloroquine 4, 2

2. For severe malaria:

   • Continuous monitoring of cardiovascular, pulmonary, renal, and metabolic parameters
   • Monitor for hypoglycemia, which may be exacerbated by quinine/quinidine 1
   • Consider regular paracetamol (1g every 6 hours for 72 hours) for patients with severe disease or acute kidney injury to attenuate renal damage from hemolysis 1, 3

3. Post-treatment follow-up:

   • For patients treated with IV artesunate, monitor for post-artesunate delayed hemolysis (PADH) at days 7,14,21, and 28 1
   • Check hemoglobin, haptoglobin, and lactate dehydrogenase levels

Special Considerations

• Diagnostic challenges: P. knowlesi is often misdiagnosed as P. malariae by microscopy. In co-endemic regions, a unified treatment strategy of ACT for all Plasmodium species is recommended 2, 3

• Mefloquine caution: P. knowlesi shows variable sensitivity to mefloquine in vitro, and clinical failures have been reported. Avoid mefloquine for treatment of P. knowlesi infections 7

• No hypnozoite stage: Unlike P. vivax and P. ovale, P. knowlesi does not form hypnozoites, so primaquine for radical cure is not required 5, 3

• Rapid progression: P. knowlesi can progress rapidly to severe disease with high parasitemia. Early recognition and prompt treatment are essential to prevent adverse outcomes 4, 2, 3

• Mortality reduction: Implementation of early intravenous artesunate for severe P. knowlesi has been associated with reduced case-fatality rates in Malaysia 6

The evidence clearly demonstrates that artemisinin derivatives provide faster parasite clearance and better outcomes in P. knowlesi infections. Early recognition and appropriate treatment based on disease severity are critical for reducing morbidity and mortality.