Treatment of Malaria

Decision Algorithm (from Goodman & Gilman's Pharmacological Basis of Therapeutics):

Malaria treatment decision algorithm showing diagnostic and treatment pathways based on species and resistance patterns

Principles of Management

All confirmed malaria cases (by microscopy or RDT) should receive prompt, effective treatment. The choice of agent depends on:

Plasmodium species (falciparum vs. non-falciparum)
Severity (uncomplicated vs. severe)
Geographic resistance patterns (chloroquine-sensitive vs. resistant area)
Special populations (pregnancy, children, G6PD deficiency)

1. Uncomplicated P. falciparum Malaria

Chloroquine-Resistant Areas (most of the world)

These are the preferred regimens (Goldman-Cecil Medicine):

Regimen	Dose
Artemether-lumefantrine (Coartem)	4 tablets twice daily x 3 days
Atovaquone-proguanil (Malarone)	4 tablets daily x 3 days
Quinine + Doxycycline	Quinine 650 mg TID x 3-7 days + Doxycycline 100 mg BD x 7 days
Quinine + Clindamycin	Quinine 650 mg TID + Clindamycin 600 mg BD x 7 days
Mefloquine	750 mg then 500 mg 6-8 hrs later (or 1250 mg single dose)

In India, the National Programme recommends Artesunate + Sulphadoxine-Pyrimethamine (ACT) for 3 days plus a single dose of Primaquine (0.75 mg/kg) on Day 2 as a gametocidal agent. In North-Eastern states (SP resistance), Artemether + Lumefantrine is used instead. - Park's Textbook of Preventive and Social Medicine

Artemisinin monotherapy is banned - it drives resistance. Always use combination therapy.

Chloroquine-Sensitive Areas

Chloroquine phosphate: 1 g, then 500 mg at 6, 24, and 48 hours
Add Primaquine (30 mg base daily x 14 days) only for P. vivax and P. ovale to eliminate hypnozoites

2. Uncomplicated P. vivax / P. ovale / P. malariae

Chloroquine remains the drug of choice: 25 mg/kg total dose over 3 days
Add Primaquine 0.25 mg/kg/day x 14 days (P. vivax/P. ovale only) to prevent relapse from liver hypnozoites
Tafenoquine (300 mg single dose) is an alternative to primaquine for radical cure

Check G6PD status before giving primaquine or tafenoquine - both can cause severe haemolysis in G6PD-deficient patients. These drugs are also contraindicated in pregnancy and infants. - Park's Textbook; Goldman-Cecil Medicine

3. Severe / Complicated Malaria

Features of Severe Malaria (P. falciparum)

Impaired consciousness/coma (cerebral malaria)
Repeated convulsions
Renal failure (creatinine >3 mg/dL)
Severe anaemia (Hb <5 g/dL)
Pulmonary oedema / ARDS
Hypoglycaemia (<40 mg/dL)
Circulatory collapse / shock
Haemoglobinuria, jaundice, DIC
Hyperparasitaemia (>5% in low-endemic, >10% in high-endemic areas)

Treatment (Parenteral - Medical Emergency)

Drug	Dose
IV Artesunate (first-line)	2.4 mg/kg IV at 0, 12, 24 hrs, then daily
IV Quinine dihydrochloride	20 mg/kg over 4 hrs loading; then 10 mg/kg q8h
IM Artemether	3.2 mg/kg IM loading; then 1.6 mg/kg/day

After clinical improvement and ability to tolerate oral medications, switch to a full oral regimen (ACT, Malarone, mefloquine, or quinine + doxycycline/clindamycin). - Goldman-Cecil Medicine

Supportive Care for Severe Malaria

Maintain fluids, electrolytes, and glucose (hypoglycaemia is common and life-threatening)
Anticonvulsants for seizures
Mechanical ventilation for respiratory failure
Haemofiltration/haemodialysis for acute renal failure
Blood transfusion for severe anaemia (Hb <5 g/dL)
Presumptive antibiotics if sepsis is suspected
Cardiac monitoring during IV quinine (QT prolongation risk)

4. Malaria in Pregnancy

Trimester	P. falciparum	P. vivax
1st trimester	Quinine (ACT avoided)	Chloroquine
2nd & 3rd trimester	ACT	Chloroquine

Primaquine is contraindicated in pregnancy
Atovaquone-proguanil, mefloquine, tetracycline, and doxycycline should be avoided in pregnancy
Severe malaria in pregnancy is treated with IV artesunate per general guidelines, with attention to drug contraindications

5. Malaria in Children

Dosing is generally the same as adults (paediatric dose should never exceed adult dose)
Tetracyclines (tetracycline, doxycycline): avoid in children <8 years
Atovaquone-proguanil: approved only for children >5 kg
Artemether-lumefantrine: not for children <5 kg

6. Drug Resistance

Suspect resistance if no clinical or parasitological response within 72 hours of full treatment (with no vomiting or diarrhoea)
ACT-resistant cases: treat with oral quinine + tetracycline/doxycycline
P. vivax chloroquine resistance (Papua New Guinea, Indonesia): use atovaquone-proguanil, quinine + tetracycline/doxycycline, or mefloquine

7. Key Drug Notes

Drug	Key Toxicities / Notes
Quinine	Cinchonism (tinnitus, headache, nausea), hypoglycaemia, QT prolongation, haemolysis in G6PD deficiency; "Blackwater fever" (rare)
Chloroquine	Well tolerated; retinal toxicity with long-term use
Primaquine/Tafenoquine	Haemolytic anaemia in G6PD deficiency; check G6PD before use
Artemether-lumefantrine	Avoid in 1st trimester and <5 kg; not monotherapy
Mefloquine	Neuropsychiatric effects (anxiety, nightmares, psychosis); avoid with concurrent quinine
Atovaquone-proguanil	GI side effects; requires fatty meal for absorption
Doxycycline	Phototoxicity; not in pregnancy or children <8 yrs

8. Chemoprophylaxis (for Travellers)

For travel to endemic regions, options include:

Atovaquone-proguanil: start 1-2 days before, continue 7 days after travel
Doxycycline: daily, start 1-2 days before, continue 4 weeks after
Mefloquine: weekly, start 2-3 weeks before, continue 4 weeks after
Chloroquine: for chloroquine-sensitive areas only

Sources: Goldman-Cecil Medicine (26th Ed.) | Goodman & Gilman's Pharmacological Basis of Therapeutics (14th Ed.) | Park's Textbook of Preventive and Social Medicine | Katzung's Basic and Clinical Pharmacology (16th Ed.)

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