Treatment of malaria

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WHO malaria treatment guidelines 2023 2024

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Treatment of Malaria

Decision algorithm for the treatment of malaria
Figure: Decision algorithm for treatment of malaria - Goodman & Gilman's Pharmacological Basis of Therapeutics, p. 1322

Overview

Treatment depends on three factors:
  1. Species - P. falciparum, P. vivax, P. ovale, P. malariae, or P. knowlesi
  2. Severity - uncomplicated vs. severe/complicated malaria
  3. Resistance pattern - chloroquine-sensitive vs. chloroquine/mefloquine-resistant area
All confirmed malaria cases (by microscopy or RDT) should receive prompt, effective treatment. - Park's Textbook of Preventive and Social Medicine, p. 307

1. Uncomplicated P. falciparum Malaria

A. Chloroquine-Sensitive Areas (rare globally)

DrugDose
Chloroquine phosphate1 g, then 500 mg at 6, 24, and 48 hr

B. Chloroquine-Resistant Areas (most of the world)

Artemisinin-based Combination Therapy (ACT) is the WHO-recommended first-line treatment. Artemisinin monotherapy alone is banned - it promotes resistance. - Park's, p. 307
Options (adult doses):
RegimenDose
Artemether-lumefantrine (Coartem)4 tablets (artemether 20 mg + lumefantrine 120 mg) twice daily for 3 days
Atovaquone-proguanil (Malarone)4 tablets daily for 3 days
Artesunate + sulfadoxine-pyrimethamine (ACT-SP)Artesunate x 3 days + SP single dose on Day 1; primaquine single dose 0.75 mg/kg on Day 2
Artesunate-amodiaquine (ASAQ)First-line in many African countries
Dihydroartemisinin-piperaquineHighly effective; resistance seen in parts of Southeast Asia
Quinine sulfate 650 mg TID x 3-7 days+ doxycycline 100 mg BD x 7 days (or clindamycin 600 mg BD x 7 days for children/pregnant)
Mefloquine750 mg then 500 mg after 6-8 hr (or 1250 mg single dose)
  • Goldman-Cecil Medicine, Table 316-1 & 316-2, p. 3397

C. Mefloquine-Resistant Areas (parts of Southeast Asia)

  • Atovaquone-proguanil, or
  • Quinine + tetracycline/doxycycline/clindamycin

2. Uncomplicated P. vivax / P. ovale Malaria

  • Chloroquine 25 mg/kg divided over 3 days (blood schizonticide) - Park's, p. 307
  • PLUS Primaquine 0.25 mg/kg/day for 14 days (to eliminate hypnozoites and prevent relapse)
    • Alternatively: Tafenoquine 300 mg single dose (anti-relapse)
  • Relapse rate for vivax in India is ~30%; primaquine is essential to prevent it
Important: Primaquine/tafenoquine must ONLY be given after confirming normal G6PD levels - they cause haemolytic anaemia in G6PD-deficient patients. Contraindicated in pregnancy and infants. - Goldman-Cecil Medicine, p. 3397; Park's, p. 307
For P. vivax from Papua New Guinea or Indonesia (chloroquine resistance common): use atovaquone-proguanil or quinine + doxycycline/mefloquine.

3. P. malariae and P. knowlesi

  • Treat with chloroquine (chloroquine-sensitive)
  • No primaquine needed for P. malariae (no hypnozoite stage)

4. Severe / Complicated Malaria

Features Defining Severe Malaria

  • Impaired consciousness/coma
  • Repeated convulsions
  • Renal failure (creatinine >3 mg/dL)
  • Severe anaemia (Hb <5 g/dL)
  • Pulmonary oedema/ARDS
  • Hypoglycaemia (glucose <40 mg/dL)
  • Circulatory collapse (systolic BP <80 mmHg)
  • Haemoglobinuria
  • Hyperparasitaemia (>5% parasitized RBCs)
  • Park's, p. 308

Treatment of Severe Malaria (Parenteral First)

DrugDose
IV Artesunate (preferred)2.4 mg/kg IV at 0, 12, 24 hr, then daily for 2 more days
IV Quinine dihydrochloride (if artesunate unavailable)Loading dose 20 mg/kg over 4 hr; then 10 mg/kg every 8 hr (with cardiac monitoring)
IM Artemether3.2 mg/kg IM initially; then 1.6 mg/kg/day
  • IV artesunate is now clearly preferred over IV quinine for severe malaria - more efficacious and better tolerated. - Katzung's Basic and Clinical Pharmacology; Goldman-Cecil
  • IV regimens should be maintained until oral therapy can be tolerated, then transitioned to a full oral ACT course (+ doxycycline or clindamycin)
  • Admit to ICU with cardiac monitoring (especially if using quinine)
  • Treat complications: hypoglycaemia, fluid balance, anaemia, seizures

5. Treatment in Pregnancy

TrimesterP. falciparumP. vivax
1st trimesterQuinine + clindamycin (ACTs avoided)Chloroquine
2nd and 3rd trimesterACT (artemether-lumefantrine preferred)Chloroquine
  • Primaquine is contraindicated throughout pregnancy (risk of haemolysis in foetus)
  • Severe malaria in pregnancy: IV artesunate following general severe malaria guidelines
  • In lactating mothers, chloroquine/hydroxychloroquine are preferred; atovaquone-proguanil only if infant >5 kg with normal G6PD
  • Goodman & Gilman's, p. 1322; Park's, p. 307

6. Treatment in Children

  • Same regimens as adults (paediatric weight-based dosing; dose should never exceed adult dose)
  • Tetracyclines contraindicated in children <8 years; use clindamycin instead
  • Atovaquone-proguanil approved only for children >5 kg
  • Goodman & Gilman's, p. 1322

7. Mixed Infections

  • Treat as P. falciparum malaria (most aggressive species takes priority). - Park's, p. 307

8. Key Drugs - Quick Reference

DrugClassMain UseKey Toxicity
Artesunate / ArtemetherSesquiterpene lactoneBlood schizonticide; first-line severe diseaseGenerally well tolerated
Lumefantrine / AmodiaquineACT partnerCombined with artemisininGI side effects
Chloroquine4-aminoquinolineVivax/malariae/sensitive falciparumRetinopathy (chronic); QTc prolongation
Primaquine8-aminoquinolineHypnozoite elimination (vivax/ovale)Haemolysis in G6PD deficiency
Tafenoquine8-aminoquinolineRelapse prevention (single dose)Same as primaquine; contraindicated in G6PD deficiency
QuinineCinchona alkaloidSevere disease; 1st trimester pregnancyCinchonism (tinnitus, nausea, dizziness); hypoglycaemia
Atovaquone-proguanilMixedResistant falciparumGI intolerance; not in pregnancy
Mefloquine4-methanolquinolineResistant falciparum; prophylaxisNeuropsychiatric effects; GI intolerance
DoxycyclineTetracyclinePartner drug to quininePhotosensitivity; contraindicated <8 yr, pregnancy

9. Treatment Failure

Suspect if no clinical/parasitological response within 72 hours of full treatment with no vomiting. Treat with oral quinine + tetracycline/doxycycline. Report to the concerned malaria officer for therapeutic efficacy studies. - Park's, p. 307

10. WHO 2024 Update

The WHO Guidelines for Malaria (November 2024) are the most current consolidated guidance, including updated recommendations on:
  • Malaria vaccines (RTS,S/AS01 and R21/Matrix-M)
  • Use of near-patient G6PD tests to guide anti-relapse treatment
  • Indoor residual spraying and spatial repellents (vector control)
The CDC Treatment Guidelines (June 2024) for uncomplicated and severe malaria are also available for US-specific practice.

Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics, p. 1322 | Goldman-Cecil Medicine, Tables 316-1 & 316-2 | Katzung's Basic and Clinical Pharmacology, 16th Ed. | Park's Textbook of Preventive and Social Medicine, pp. 307-308
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