MALARIA - Short Note (Exam Oriented)

1. Definition & Epidemiology

2. Life Cycle

1. Exoerythrocytic (hepatic) stage: Sporozoites injected → travel to liver → infect hepatocytes via thrombospondin-related adhesive protein and circumsporozoite protein → develop into hepatic schizonts → release merozoites into blood (1-4 weeks incubation; asymptomatic). P. vivax and P. ovale form hypnozoites (dormant liver stage responsible for relapse).
2. Erythrocytic stage: Merozoites bind glycophorin on RBCs (via lectin-like molecule) → enter RBC → develop into ring trophozoites → schizonts → merozoites (lysis of RBC, cycle repeats every 24-72 h). Some trophozoites become gametocytes (infective to mosquito).

3. Pathogenesis

• Hemolytic anemia from RBC destruction; releases hematin (malarial pigment) - discolors spleen, liver, lymph nodes, bone marrow.
• Splenomegaly (massive) and occasional hepatomegaly from mononuclear phagocyte hyperplasia.
• Cytoadherence (P. falciparum specific): PfEMP1 on knob-like extensions of infected RBCs binds endothelial adhesion molecules (ICAM-1, VCAM-1, CD36) → RBC sequestration in capillaries → cerebral malaria.
• Blackwater fever (P. falciparum): massive intravascular hemolysis → hemoglobinemia, hemoglobinuria, jaundice, acute renal failure.

4. Clinical Features

• Classic malarial paroxysm: Cold stage (rigors/chills) → Hot stage (high fever 40-41°C) → Sweating stage (drenching sweats, defervescence)
• Periodicity: Every 48 h for P. vivax/ovale/falciparum, every 72 h for P. malariae, every 24 h for P. knowlesi
• Headache, myalgia, malaise, nausea, vomiting
• Splenomegaly, anemia, jaundice

• Cerebral malaria: altered consciousness, convulsions, coma
• Severe anemia (Hb <5 g/dL)
• Respiratory distress (pulmonary edema, ARDS)
• Hypoglycemia
• Blackwater fever (hemoglobinuria + renal failure)
• Circulatory collapse/algid malaria
• Hyperparasitemia (>5% RBCs parasitized)

5. Diagnosis

A. Microscopy (Gold Standard)

• Peripheral blood smear (thick + thin smear), Giemsa-stained
• Thick smear - for detection (more sensitive, concentrates parasites)
• Thin smear - for species identification and parasite density
• Each species has characteristic morphology (ring forms, schizonts, gametocytes)
• Should be examined every 12-24 hours if initially negative (3 negative smears before ruling out)

B. Rapid Diagnostic Tests (RDTs)

• Monovalent RDT: Detects P. falciparum HRP-2 antigen
• Bivalent RDT: Detects both P. falciparum and non-falciparum species
• Quick (~20 min), suitable where microscopy not available within 24 h
• Limitation: Cannot quantify parasitemia; false negatives with gene deletion variants

C. Other Methods

• QBC (Quantitative Buffy Coat): Fluorescent staining, detects parasites in buffy coat
• PCR: Most sensitive/specific; useful for mixed infections, low parasitemia, species confirmation; not routine
• Serology (ELISA/IFA): Indicates past exposure, not useful for acute diagnosis
• Antigen tests (pLDH, aldolase): Can detect all species; pLDH-based RDTs

6. Treatment

UNCOMPLICATED VIVAX MALARIA

• Primaquine eradicates hypnozoites (prevents relapse)
• Primaquine CONTRAINDICATED in: Infants, pregnant women, G6PD deficiency (causes hemolysis)

UNCOMPLICATED FALCIPARUM MALARIA

• Primaquine (single dose) given as gametocytocidal agent in falciparum (not for relapse prevention as no hypnozoites)
• Rationale for ACT: Artemisinins are fast-acting but rapidly cleared; partner drug (SP, lumefantrine) eliminates residual parasites; prevents resistance

SEVERE/COMPLICATED FALCIPARUM MALARIA

• IV Artesunate (preferred): 2.4 mg/kg IV at 0, 12, 24 h then daily
• IV Quinine (alternative): Loading dose 20 mg/kg over 4 hours, then 10 mg/kg every 8 h (with doxycycline or clindamycin); monitor for hypoglycemia, QTc prolongation

CHEMOPROPHYLAXIS (Travelers)

TREATMENT IN PREGNANCY

• P. vivax: Chloroquine safe; withhold primaquine (give after delivery)
• P. falciparum (uncomplicated): Quinine + clindamycin (1st trimester); ACT (2nd/3rd trimester)
• Severe malaria in pregnancy: IV artesunate or IV quinine regardless of trimester
• Avoid: Tetracyclines, doxycycline, atovaquone-proguanil, primaquine

7. Drug Resistance

• P. falciparum has developed resistance to chloroquine, mefloquine, quinine, sulfadoxine-pyrimethamine, and partially to artemisinins (Southeast Asia - kelch13 mutation)
• Mechanism: genetic mutation allowing parasite survival despite drug; propagated by sub-therapeutic dosing, incomplete courses
• Artemisinin partial resistance (K13 mutation): longer time to parasite clearance; partner drug activity preserved in most cases

8. Prevention

• Vector control: Insecticide-treated bed nets (ITNs/LLINs), indoor residual spraying
• Personal protection: Repellents (DEET), protective clothing
• Larval source management: Elimination of stagnant water bodies
• Chemoprophylaxis for travelers/non-immune individuals
• RTS,S/AS01 vaccine (Mosquirix): Partial protection (~30-50%) against P. falciparum; recommended by WHO for children in high-transmission areas in Africa

Quick Recall Summary

Common Treatment of Malaria

P. VIVAX (Benign Tertian)

• Primaquine kills hypnozoites in the liver (prevents relapse)
• Do NOT give Primaquine in: pregnancy, infants under 1 year, G6PD deficiency

P. FALCIPARUM (Malignant Tertian) - Uncomplicated

• Add single dose Primaquine on day 2 as gametocytocidal agent
• All tablets taken together with food and water

SEVERE / COMPLICATED FALCIPARUM

• Switch to oral ACT as soon as patient can swallow
• Quinine: always combine with doxycycline or clindamycin; monitor blood sugar (hypoglycemia risk)

MIXED INFECTION (Falciparum + Vivax)

• Treat as falciparum first (ACT-SP or ACT-AL)
• Add Primaquine 0.25 mg/kg/day x 14 days to cover vivax hypnozoites

SPECIAL SITUATIONS

DRUGS TO REMEMBER AT A GLANCE