What is the recommended treatment protocol and dosage for uncomplicated malaria in adults and children, considering weight and potential resistance patterns?

Malaria Treatment Protocol with Dosing

First-Line Treatment for Uncomplicated P. falciparum Malaria

For uncomplicated P. falciparum malaria, artemisinin-based combination therapies (ACTs) are the definitive first-line treatment, with artemether-lumefantrine and dihydroartemisinin-piperaquine being the preferred options. 1

Artemether-Lumefantrine (AL) Dosing

• Adults and children >35 kg: 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 a fatty meal or drink (milk, yogurt, or fatty food) to ensure adequate absorption and prevent treatment failure 1, 2
• Cure rates: 96-100% 2
• Can be used in all trimesters of pregnancy 1, 2

Dihydroartemisinin-Piperaquine (DP) Dosing

• Adults 36-75 kg: 3 tablets daily for 3 days 1, 2
• Adults >75 kg: 4 tablets daily for 3 days 1, 2
• Critical administration requirement: Must be taken in a fasting condition (opposite of AL) 1, 2
• Superior to AL in preventing P. vivax recurrence (RR 0.32,95% CI 0.24-0.43) 1
• Longer half-life provides better protection against reinfection 3

Important Safety Considerations for ACTs

• Both AL and DP can cause QTc interval prolongation—avoid in patients at risk of QTc prolongation or taking QTc-prolonging medications 1, 3
• Monitor for post-artemisinin delayed hemolysis (PADH) on days 7,14,21, and 28 after treatment (occurs in 37.4% of patients using strict definitions) 1, 2

Second-Line Treatment Options

Atovaquone-Proguanil

• Adults >40 kg: 4 tablets daily for 3 days 2, 3
• Must be taken with a fatty meal or drink 3
• Indicated when ACTs are contraindicated (e.g., QTc prolongation risk, Southeast Asian ACT resistance) 1

Quinine-Based Regimens

• Quinine sulfate: 648 mg (two capsules) every 8 hours for 7 days 4
• Must be taken with food to minimize gastric upset 4
• Plus doxycycline: 100 mg twice daily for 7 days 3
• Or plus clindamycin as alternative to doxycycline 1
• Renal impairment dosing: Loading dose of 648 mg, then 324 mg every 12 hours starting 12 hours after loading dose 4
• Warning: Risk of serious hematologic reactions including thrombocytopenia, HUS/TTP; contraindicated in prolonged QT interval, myasthenia gravis, and optic neuritis 4

Treatment of Uncomplicated Non-Falciparum Malaria

P. vivax, P. ovale, P. malariae

• Chloroquine-sensitive regions: Chloroquine 600 mg base at 0 hours, 600 mg at 24 hours, 300 mg at 48 hours (total dose 25 mg base/kg over 3 days) 1, 2
• Chloroquine-resistant regions (Papua New Guinea, Indonesia, Sabah): Use ACTs as above 1

Radical Cure for P. vivax and P. ovale (Liver Hypnozoites)

• Critical safety step: Test for G6PD deficiency before administering 8-aminoquinolines 1, 3
• Primaquine (standard regimen): Reduces relapse risk by 80%; dosing per standard protocol after blood schizontocidal treatment 1
• Primaquine (G6PD deficiency 30-70% activity): 45 mg once weekly for 8 weeks 1
• Tafenoquine: Alternative requiring quantitative G6PD >70%; only available in US/Australia 1
• Absolute contraindication: Both primaquine and tafenoquine are contraindicated in pregnancy 1

Treatment of Severe Malaria

Severe malaria is a medical emergency requiring immediate intravenous artesunate. 1, 2

IV Artesunate Dosing

• 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasitemia <1% 1, 2
• Monitor parasitemia every 12 hours until <1%, then every 24 hours until negative 2
• Once patient improves clinically (parasitemia <1%) and can take oral medications, complete treatment with full course of oral ACT 1, 2
• Reduces mortality by 35% compared to quinine 5

Special Populations

Pregnant Women

• All trimesters: Artemether-lumefantrine is recommended 1, 2
• Multiple trials found no association between ACT treatment and congenital malformations or miscarriage in second/third trimester 1
• Cure rates in third trimester: 94.9-100% 2
• Superior tolerability compared to quinine (lower rates of tinnitus, dizziness, vomiting) 2
• Avoid: Primaquine and tafenoquine are absolutely contraindicated in pregnancy 1

High Body Weight or Suspected Malabsorption

• Consider extending artemether-lumefantrine treatment to 5 days 1

Critical Pitfalls to Avoid

• Failure to ensure adequate fat intake with AL: Results in subtherapeutic drug levels and treatment failure 1, 3
• Taking DP with food instead of fasting: Reduces absorption 1, 2
• Delayed diagnosis and treatment: Significantly increases mortality 1, 2
• Not testing for G6PD deficiency before primaquine/tafenoquine: Can cause severe hemolysis 1, 3
• Underestimating parasitemia: Can lead to treating severe malaria as uncomplicated disease 1
• Missing QTc prolongation risk: Both AL and DP prolong QTc interval 1, 3