What is the recommended treatment for malaria?

Malaria Treatment

Treatment Based on Species and Severity

For uncomplicated P. falciparum malaria, artemisinin-based combination therapy (ACT) is the first-line treatment, with artemether-lumefantrine or dihydroartemisinin-piperaquine as preferred options. 1, 2

Uncomplicated P. falciparum Malaria

Artemether-lumefantrine (AL):

• Dosing: 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2 and 3 1, 2
• Critical administration requirement: Must be taken with fatty food or drink to ensure adequate absorption 1, 2
• Cure rates of 96-100% 3
• Common pitfall: Failure to ensure adequate fat intake results in subtherapeutic drug levels and treatment failure 1, 2

Dihydroartemisinin-piperaquine (DP):

• Dosing: 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg) 1, 2
• Must be taken while fasting 1
• Superior to artemether-lumefantrine in preventing P. vivax recurrence (RR 0.32,95% CI 0.24-0.43) 2
• Preferred for P. vivax due to longer half-life of piperaquine 4

Important safety consideration: Both AL and DP can cause QTc interval prolongation and should be avoided in patients at risk for QTc prolongation or taking medications that prolong QTc 1, 2

Second-line options:

• Atovaquone-proguanil: 4 tablets daily for 3 days with fatty meal, for patients with contraindications to ACTs 2, 3
• Quinine plus doxycycline or clindamycin 2

Severe P. falciparum Malaria

Intravenous artesunate is the first-line treatment for all forms of severe malaria and should be treated as a medical emergency. 4, 1, 2

Artesunate dosing:

• 2.4 mg/kg IV at 0,12, and 24 hours, then daily 2
• Monitor parasitemia every 12 hours until <1%, then every 24 hours until negative 1, 3

Transition to oral therapy:

• Switch to oral ACT when parasite level is <1% AND patient can tolerate oral medication 1
• Complete a full course of oral ACT (artemether-lumefantrine, dihydroartemisinin-piperaquine, or atovaquone-proguanil) 4

Alternative if artesunate unavailable:

• Quinine dihydrochloride: 20 mg salt/kg over 4 hours (loading dose), followed by 10 mg/kg over 4 hours starting 8 hours after initiation, then every 8 hours 4
• Switch to oral therapy after completing at least 48 hours of IV treatment 4
• Note: Quinine is inferior to artesunate in preventing red blood cell sequestration 4

Critical post-treatment monitoring:

• Check for post-artesunate delayed hemolysis (PADH) on days 7,14,21, and 28 after treatment 1, 2
• PADH occurs in 37.4% of patients using strict definitions 2

Uncomplicated Non-Falciparum Malaria (P. vivax, P. ovale, P. malariae)

Chloroquine-sensitive regions:

• Chloroquine is the drug of choice: total dose of 25 mg base/kg over 3 days (600 mg, 600 mg, and 300 mg at 0,24, and 48 hours) 4, 2, 3

Chloroquine-resistant regions (Papua New Guinea, Indonesia, Sabah):

• Use ACT, preferably dihydroartemisinin-piperaquine due to longer half-life 4, 2
• Chloroquine resistance should be suspected when failure exceeds 10% 4

Radical cure for P. vivax and P. ovale (to eliminate liver hypnozoites and prevent relapse):

• Critical safety requirement: Test for G6PD deficiency before administering primaquine or tafenoquine 1, 2
• Primaquine: Standard dosing after blood schizontocidal treatment 4, 2
• For mild to moderate G6PD deficiency (30-70% activity, non-Mediterranean variant): Primaquine 45 mg once weekly for 8 weeks with close monitoring 4, 2
• Contraindication: Both primaquine and tafenoquine are contraindicated during pregnancy 4, 2
• Tafenoquine: Alternative for radical cure (requires quantitative G6PD >70%, not available outside US/Australia) 4

Clinical evidence: Primaquine reduces first-time relapse risk by 80% in P. vivax malaria 4

Special Populations

Pregnant women:

• Artemether-lumefantrine is recommended as a treatment option in all trimesters of pregnancy 1, 2
• Multiple trials found no association between ACT treatment and congenital malformations or miscarriage in second/third trimester 2
• Quinine plus clindamycin in first trimester when other options are unavailable 1
• Primaquine and tafenoquine are absolutely contraindicated 4, 2

Patients with epilepsy:

• Mefloquine increases risk of convulsions and should only be used for curative treatment with compelling medical reasons 5

Critical Pitfalls to Avoid

• Delayed diagnosis and treatment of P. falciparum malaria significantly increases mortality 1, 2
• Inadequate fat intake with artemether-lumefantrine leads to treatment failure 1, 2
• Not testing for G6PD deficiency before 8-aminoquinolines can cause severe hemolysis 1, 2
• QTc prolongation risk with ACTs requires avoiding use in at-risk patients 1, 2
• Mefloquine should not be used with halofantrine or ketoconazole, or within 15 weeks of last mefloquine dose due to fatal QTc prolongation risk 5
• Concomitant quinine/quinidine with mefloquine produces electrocardiographic abnormalities 5