Treatment Guidelines for Uncomplicated and Severe Plasmodium falciparum Malaria
Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated P. falciparum malaria, while intravenous artesunate is the treatment of choice for severe P. falciparum infections. 1
Diagnosis and Assessment
- Microscopy remains the gold standard for malaria diagnosis, allowing calculation of parasitemia percentage and monitoring treatment response
- Rapid Diagnostic Tests (RDTs) should be used when qualified microscopists are unavailable
- Nucleic Acid Amplification Tests (NAATs) are 10-100 times more sensitive than microscopy or RDTs
Treatment of Uncomplicated P. falciparum Malaria
First-line Treatment:
- Artemisinin-based combination therapy (ACT) 2, 1
- Artemether-lumefantrine: Total of 24 tablets for adults >35kg, taken with fatty meal
- Dihydroartemisinin-piperaquine
Second-line Options (when ACTs are contraindicated):
- Atovaquone-proguanil 2, 3
- Particularly for patients with risk of QT prolongation
- For patients from Southeast Asia (especially Greater Mekong sub-region) with high ACT resistance
- Adults >40kg: 4 tablets daily for 3 days
Third-line Options:
Special Considerations:
- Pregnancy: Artemether-lumefantrine is now endorsed for use in all trimesters 2, 1
- Clinical trials have shown ACT to be highly effective with 98.7% parasitological cure rates 3
- ACT treatment reduces hospital stay and produces more rapid parasite clearance compared to traditional treatments 5
Treatment of Severe P. falciparum Malaria
First-line Treatment:
- Intravenous artesunate 1
Alternative Treatment:
- Intravenous quinine if artesunate is unavailable 1
- Loading dose of 10 mg quinidine gluconate/kg over 1-2 hours
- Followed by constant infusion of 0.02 mg/kg/minute
Treatment of Non-falciparum Malaria
P. vivax and P. ovale:
- Chloroquine is the drug of choice for blood stage 2, 1
- Total dose of 25 mg base/kg over 3 days
- Adults: 600 mg (base) initially, then 300 mg at 6,24, and 48 hours
- Followed by primaquine or tafenoquine for radical cure (liver hypnozoites) 2, 1
- G6PD testing required before administration
- Primaquine: 15 mg (base) daily for 14 days
- Tafenoquine: single 300 mg dose
P. malariae:
- Chloroquine with same dosing as for P. vivax 1
Monitoring and Follow-up
- For uncomplicated malaria: Monitor parasitemia every 24 hours until negative
- For severe malaria: Monitor parasitemia every 12 hours until <1%, then every 24 hours until negative 1
- Monitor for post-artesunate delayed hemolysis (PADH) at days 7,14,21, and 28 2, 1
- Check hemoglobin, haptoglobin, and lactate dehydrogenase levels
- For severe malaria: Continuous monitoring of cardiovascular, pulmonary, renal, and metabolic parameters 1
Emerging Resistance Concerns
- Increasing artemisinin resistance in Greater Mekong sub-region and parts of Africa 1
- P. falciparum has developed resistance to chloroquine in most regions worldwide 4
- Multi-drug resistant strains are emerging in certain foci, requiring vigilant monitoring 6
Pitfalls and Caveats
- G6PD testing is mandatory before administering primaquine or tafenoquine to prevent potentially life-threatening hemolysis 1
- Primaquine and tafenoquine are contraindicated during pregnancy 2
- Monitor for hypoglycemia, especially with quinine/quinidine treatment 1
- ACTs should be taken with fatty meals for optimal absorption 1
- Patients with renal impairment require adjusted dosing of quinine 1
The evidence clearly demonstrates that ACTs provide superior efficacy for uncomplicated P. falciparum malaria with faster parasite clearance and shorter hospital stays compared to older treatments. For severe malaria, intravenous artesunate has become the standard of care globally, showing improved outcomes over traditional quinine-based therapies.