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MALARIA - Long Answer Question (LAQ) Format

Microbiology

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1. DEFINITION

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2. CAUSATIVE ORGANISM / CLASSIFICATION

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3. LIFE CYCLE

A. In the Mosquito (Sexual Phase - Sporogony)

1. Mosquito ingests male and female gametocytes from infected human blood
2. Fertilization occurs in the mosquito midgut → ookinete (motile zygote)
3. Ookinete penetrates gut wall → oocyst
4. Sporogony occurs within oocyst → sporozoites released
5. Sporozoites migrate to salivary glands; mosquito becomes infective in ~2 weeks

B. In the Human (Asexual Phase)

• Mosquito bite → sporozoites injected into bloodstream
• Sporozoites travel to liver → invade hepatic parenchymal cells
• Schizogony occurs → hepatic schizonts → rupture → release merozoites
• Duration: 8-25 days (species-dependent)
• P. vivax and P. ovale: some sporozoites become dormant hypnozoites (sleeping forms) in hepatocytes → responsible for RELAPSE months to years later

• Merozoites attach to specific RBC surface receptors → invade erythrocytes
• Progression: Ring stage → Trophozoite → Schizont → Merozoites
• Mature schizont ruptures RBC → merozoites released → invade new RBCs
• This synchronous rupture causes the periodic fever spikes
• After several cycles, some merozoites → gametocytes (sexual forms)

• P. vivax / P. ovale: 48 hours (tertian - fever every 3rd day)
• P. malariae: 72 hours (quartan - fever every 4th day)
• P. falciparum: 48 hours but asynchronous (irregular fevers)
• P. knowlesi: 24 hours (quotidian - daily fever)

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4. RBC INVASION - SPECIFICS

Key Point: Duffy-negative individuals (common in West African ancestry) are resistant to P. vivax malaria because the Duffy antigen serves as its receptor.

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5. PATHOGENESIS

Fever Mechanism

• Synchronous rupture of RBCs → release of merozoites + malarial pigment (hemozoin) + parasite toxins (GPI anchors) → stimulate macrophages → release of IL-1, TNF-α → fever, chills, rigors

Malarial Paroxysm (Classic Triad)

1. Cold stage - shivering, rigors (15-60 min)
2. Hot stage - high fever 40-41°C (2-6 hrs)
3. Sweating stage - profuse sweating, temperature falls

Anemia Mechanisms

1. Direct destruction of parasitized RBCs
2. Immune-mediated hemolysis of non-parasitized RBCs
3. Dyserythropoiesis (bone marrow suppression)
4. Splenic sequestration

P. falciparum Specific Pathogenesis (Most Dangerous)

• Infects RBCs of all ages → high parasitemia
• Forms electron-dense knobs on RBC surface → produce PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1)
• PfEMP1 mediates cytoadherence - binding to endothelium of capillaries and postcapillary venules of brain, placenta, and visceral organs
• Results in microinfarcts → cerebral malaria, placental malaria

Genetic Protective Factors

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6. CLINICAL FEATURES

Complications of P. falciparum (Severe / Complicated Malaria)

• Cerebral malaria - altered consciousness, seizures, coma
• Blackwater fever - severe intravascular hemolysis → hemoglobinuria → black/dark urine
• Acute respiratory distress syndrome (ARDS)
• Acute kidney injury
• Hypoglycemia
• Thrombocytopenia
• Placental malaria → low birth weight, maternal anemia

Relapse vs Recrudescence

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7. MICROSCOPIC MORPHOLOGY (Blood Smear Features)

Mnemonic for gametocyte shape: Falciparum = Falcate (crescent-shaped)

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8. LABORATORY DIAGNOSIS

Gold Standard: Peripheral Blood Smear

• Thick smear: Screening (detects low parasitemia) - stained with Giemsa/Leishman
• Thin smear: Species identification and morphology
• Repeat smears every 6-8 hours x 3 if initial negative

Other Methods

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9. TREATMENT

Goals of Chemotherapy

1. Suppressive/Prophylactic - prevent infection and symptoms
2. Therapeutic (clinical cure) - eradicate erythrocytic cycle
3. Radical cure - eradicate exoerythrocytic (liver) cycle (hypnozoites)
4. Gametocidal - destroy gametocytes, prevent transmission

Drug Targets by Stage

Treatment Regimens (Summary)

Note: Primaquine must not be given to G6PD-deficient patients (risk of severe hemolytic anemia). Always test G6PD before prescribing.

Drug Resistance

• Chloroquine resistance: widespread in P. falciparum (Africa, Southeast Asia); some P. vivax (Papua New Guinea, Sumatra, Indonesia, Brazil)
• Multi-drug resistance: P. falciparum now variably resistant to all drug groups including artemisinins (especially Southeast Asia)
• Management: Combination therapy (ACT) to slow resistance development

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10. PREVENTION AND CONTROL

Personal Protection

• Insecticide-treated bed nets (ITNs) - most effective intervention
• Repellents (DEET)
• Protective clothing (long sleeves, trousers at dusk/dawn)
• Indoor residual spraying (IRS)

Chemoprophylaxis

Vector Control

• Larval control (drainage of stagnant water, larvicides)
• Adult mosquito control (insecticides)
• Biological control

Vaccine

• RTS,S/AS01 (Mosquirix) - approved by WHO (2021) for children in sub-Saharan Africa; provides ~30-40% protection against severe malaria

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11. KEY POINTS / MNEMONICS

• "VOMF" - Vivax, Ovale = relapse via hypnozoites; Malariae, Falciparum = recrudescence
• Falciparum = most dangerous: banana gametocytes, knobs, PfEMP1, no hypnozoites but multi-drug resistant
• Quartan malaria (P. malariae) = 72-hr cycle; "band form" trophozoites; associated with nephrotic syndrome in children
• Duffy-negative = naturally resistant to P. vivax
• Blackwater fever = P. falciparum + massive hemolysis + hemoglobinuria
• Thick smear for detection; Thin smear for identification
• Primaquine is the only drug for hypnozoites (radical cure)

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