What is the recommended treatment for malaria?

Malaria Treatment

For uncomplicated P. falciparum malaria, artemether-lumefantrine (AL) is the first-line treatment, administered as 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2-3, and must be taken with fatty food to ensure adequate absorption. 1, 2, 3

Treatment Algorithm by Malaria Type and Severity

Uncomplicated P. falciparum Malaria

First-line options:

• Artemether-lumefantrine (AL): 4 tablets at hour 0,4 tablets at hour 8 on day 1, then 4 tablets twice daily on days 2 and 3 - must be taken with a fatty meal or drink to achieve therapeutic levels 1, 2, 3
• Dihydroartemisinin-piperaquine (DP): 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg) - must be taken on an empty stomach 1, 2, 3

Second-line option when ACTs are contraindicated:

• Atovaquone-proguanil: 4 tablets daily for 3 consecutive days, taken with fatty food 4, 3, 5
• Use this for patients with QTc prolongation risk or those from Southeast Asia (Greater Mekong sub-region) with ACT resistance 4

Severe P. falciparum Malaria

Immediate treatment protocol:

• Intravenous artesunate: 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasitemia <1% 1, 2, 3
• Monitor parasitemia every 12 hours until <1%, then every 24 hours until negative 2, 3
• Once patient improves clinically and parasitemia <1%, complete treatment with full course of oral ACT 1, 2, 3
• Monitor for post-artemisinin delayed hemolysis (PADH) on days 7,14,21, and 28 after treatment 4, 3

Uncomplicated P. vivax, P. ovale, or P. malariae

Initial blood stage treatment:

• Chloroquine (in chloroquine-sensitive regions): Total dose of 25 mg base/kg over 3 days - adults receive 600 mg base, then 600 mg base at 24 hours, then 300 mg base at 48 hours 4, 1, 6
• ACTs are effective alternatives and recommended by WHO for all non-falciparum species 4
• For travelers from Papua New Guinea, Indonesia, or Sabah (chloroquine-resistant areas), use ACTs instead 4

Radical cure to prevent relapse (P. vivax and P. ovale only):

• Must test for G6PD deficiency before administering 8-aminoquinolines 4, 1, 2
• Primaquine or tafenoquine to eliminate liver hypnozoites after blood stage treatment 4, 1, 2
• For mild-moderate G6PD deficiency (30-70% activity): primaquine 45 mg once weekly for 8 weeks 4
• Both primaquine and tafenoquine are contraindicated in pregnancy 4

Special Populations

Pregnant Women

• Second and third trimesters: Artemether-lumefantrine is recommended at standard adult doses 4, 1, 2
• First trimester: Mefloquine or quinine plus clindamycin are preferred; however, when these are unavailable, AL should be considered 4
• WHO and CDC now endorse AL for uncomplicated malaria in any trimester of pregnancy based on systematic review and meta-analysis showing no association with congenital malformations or miscarriage 4

Patients with Renal Impairment

• Atovaquone-proguanil should not be used for prophylaxis in severe renal impairment (creatinine clearance <30 mL/min) 5
• May be used with caution for treatment if benefits outweigh risks 5

Critical Pitfalls to Avoid

Absorption failures:

• Failing to take AL with fatty food results in subtherapeutic drug levels and treatment failure - this is the most common preventable cause of treatment failure 1, 2, 3
• Conversely, taking DP with food reduces absorption - it must be taken fasting 1, 2

Cardiac complications:

• Both AL and DP can cause QTc interval prolongation - avoid in patients at risk or taking QTc-prolonging medications 1, 2, 3

Delayed hemolysis:

• PADH occurs in 37.4% of patients treated with oral AL using strict definitions, though only 1.9% with clinical significance 4
• Monitor hemoglobin and haptoglobin on days 7,14,21, and 28 after treatment 4, 3

G6PD deficiency:

• Never administer primaquine or tafenoquine without testing for G6PD deficiency - can cause severe hemolysis 4, 1, 2

Treatment delays:

• Delayed diagnosis and treatment of P. falciparum malaria significantly increases mortality 1, 2

Geographic resistance patterns:

• Chloroquine resistance exists in most P. falciparum regions worldwide except Haiti and limited areas 7
• ACT resistance emerging in Southeast Asia (Greater Mekong sub-region) requires alternative second-line agents 4