Complete Guide on Malaria and its Management

Malaria is a major infectious disease caused by Plasmodium parasites, transmitted to humans by female Anopheles mosquitoes. Despite global control efforts, malaria remains a significant cause of morbidity and mortality, especially in resource-limited settings.

I. Epidemiology & Public Health Burden

• Global Estimate: ~241 million cases, >600,000 deaths annually (WHO 2021).
• High-Risk Regions: Sub-Saharan Africa (>90% cases), Southeast Asia, Latin America.
• At-Risk Groups: Young children, pregnant women (placental malaria), travelers, immunocompromised.
• Recent developments: Increased focus on elimination, mass drug administration in endemic foci, RTS,S/AS01 malaria vaccine in pilot introduction.

II. Plasmodium Species and Life Cycle

Life Cycle Highlights:

• Sporozoite transmission: Injected via mosquito bite, travel to liver.
• Exoerythrocytic (liver) phase: Cells mature into schizonts, release merozoites.
• Erythrocytic phase: Merozoites invade red blood cells; repeated cycles of lysis cause symptomatic malaria.
• Gametocyte formation: Sexual stages taken up by another mosquito, perpetuating the cycle.
• Hypnozoites: Dormant liver forms (P. vivax, P. ovale) cause late relapses.

III. Clinical Presentation

• Uncomplicated malaria: Periodic fever (classic tertian/quartan cycle), chills, sweats, headache, malaise, myalgia.
• Severe malaria: Confusion, seizures (cerebral), shock and organ dysfunction (renal, hepatic), acidosis, respiratory distress, severe anemia, hypoglycemia (especially children/pregnant women).
• Signs: Splenomegaly, jaundice, dark urine (hemoglobinuria, “blackwater fever”). #Malaria Symptoms

IV. Diagnosis

1. Microscopy
   • Thick and thin blood smears: Gold standard, enables species identification, quantification of parasitemia.
2. RDTs (Rapid Diagnostic Tests)
   • Detect antigens (HRP2 for P. falciparum, LDH for pan-malarial warning).
   • Useful in poor-resource/field settings.
3. PCR & Molecular Diagnostics
   • High sensitivity/specificity, mostly for research or complex diagnosis.
4. Clinical/Ancillary Labs
   • CBC: anemia, thrombocytopenia.
   • Renal/liver panels, glucose, acid-base status (for severity assessment).

V. Classification of Severity

• Uncomplicated Malaria: No severe features or organ involvement.
• Severe/Complicated Malaria: Defined by WHO criteria:
  • Impaired consciousness, coma (cerebral malaria)
  • prostration, convulsions, respiratory distress, circulatory collapse
  • severe anemia (Hb <5g/dL), hemoglobinuria, acute kidney injury, abnormal bleeding, jaundice, high parasite density (>5% RBCs).

VI. Management and Drug Therapy

A. Principles of Management

• Rapid diagnosis and treatment commencement
• Supportive care tailored to severity
• Drug regimens suited to Plasmodium species, resistance profile, and clinical scenario.

B. Antimalarial Drug Classes

First-Line Therapies: Artemisinin-Based Combination Therapies (ACTs)

• Artemether-lumefantrine, artesunate-mefloquine, DHA-piperaquine, artesunate-amodiaquine, artesunate-SP.
• Rapid parasite clearance, efficacy against resistant P. falciparum.
• Administered orally, except IV artesunate for severe malaria.

Non-ACT options (species/region specific):

• Chloroquine (if no resistance for P. vivax, some non-Africa regions)
• Quinine (IV for severe malaria, oral for areas lacking IV artesunate)
• Atovaquone-proguanil (prophylaxis, alternative therapy)
• Mefloquine (prophylaxis, treatment, caution for neurotoxicity)
• Primaquine (radical cure for P. vivax/P. ovale; G6PD testing required)
• Doxycycline/clindamycin (used with quinine or artesunate for severe malaria, or as partner in ACTs; clindamycin preferred in children/pregnancy).

Severe Malaria Management

• IV artesunate is globally preferred over quinine.
• Supportive measures: Correct hypoglycemia, manage fluid/electrolytes, renal support as needed, seizure control, monitor for respiratory distress.
• Exchange transfusion very rarely, for extreme parasite burden.

Special Groups

• Pregnant women: Quinine + clindamycin or ACT, dependent trimester and local guidelines (avoid atovaquone, primaquine).
• Children: Lower thresholds for severe malaria, higher risk; careful monitoring for complications.
• Comorbid diseases (HIV, TB): Account for potential drug interactions.

To learn about the pharmacology of individual drug classes, please refer to this page.

VII. Prevention

A. Vector Control

• Insecticide-treated bed nets (ITNs), indoor residual spraying (IRS).

B. Chemoprophylaxis

• Travelers: Atovaquone-proguanil, doxycycline, mefloquine, and chloroquine (if susceptible region).
• Intermittent Preventive Therapy (IPT): In pregnancy (IPTp), children (IPTi), and infants.

C. Vaccines

• RTS,S/AS01 vaccine: Shown efficacy in children (pilot phase in Africa); ongoing research into broader/more durable vaccines.

D. Personal Protective Measures

• Mosquito avoidance: repellents, clothing, behavior adjustment.

VIII. Drug Resistance

• Chloroquine resistance: Widespread, especially for P. falciparum.
• Artemisinin resistance: Regions of Southeast Asia (K13 mutations, slower clearance), actively monitored worldwide.
• Other resistance: Mefloquine, SP, emerging resistance to ACT partner drugs. Combination therapy crucial for slowing resistance.

IX. Monitoring and Follow-up

• Continue daily blood smears for hospitalized or severe cases to monitor parasite clearance.
• Monitor for relapse in *P. vivax/P. ovale (risk of hypnozoites).
• Supportive lab monitoring (CBC, renal/liver function, glucose, acid-base status).
• Watch for side effects: hemolytic crisis (primaquine), neuropsychiatric symptoms (mefloquine), GI upset (ACTs), allergic reactions.

X. Complications

• Cerebral malaria (ICU care, seizure management)
• Severe anemia (transfusion)
• Acute kidney injury (renal replacement therapy)
• Acute respiratory distress syndrome (supportive care)
• Hypoglycemia (especially in children with quinine, artesunate therapy)
• Splenic rupture, shock, bleeding disorders
• Hyperparasitemia (>10% RBCs).

XI. Summary Table: Drug Choices by Scenario

References

1. Shrestha J, Malaria. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
2. WHO guidelines for malaria. World Health Organization. 2021, updated Sept 2025.
3. Hunsicker LG. The Pharmacology of Antimalarials: A Rational Approach to the Therapy of Resistant Falciparum Malaria. Arch Intern Med. 1969;123(6):645–649.
4. Mayo Clinic. Malaria: Diagnosis & treatment. Updated 2023 Feb.
5. CDC. General Approach to Treatment | Malaria. 2025 May. 
6. WHO. New and updated malaria guidance. 2025.
7. Malaria Journal. Assessing fitness costs in malaria parasites: implications for drug resistance management. 2025 Feb.
8. Tandfonline. A systematic review on malaria and dengue vaccines. 2024 Apr.