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Malaria: Pathophysiology, Clinical Features, and Transmission

Malaria is a life-threatening mosquito-borne disease caused by Plasmodium parasites. Five species infect humans: P. falciparum (most severe), P. vivax, P. ovale, P. malariae, P. knowlesi.

Transmission Cycle

  1. Infected female Anopheles mosquito takes blood meal → injects sporozoites.
  2. Sporozoites → liver (hepatocytes) → exo-erythrocytic schizogony (5–16 days) → thousands of merozoites released.
  3. Merozoites invade RBCs → erythrocytic cycle (48h for falciparum/vivax/ovale; 72h for malariae; 24h for knowlesi):
    • Ring → trophozoite → schizont → rupture → release merozoites + waste (hemozoin, GPI anchors) → fever/chills.
    • Some differentiate into gametocytes (sexual forms) → taken up by mosquito.
  4. In mosquito gut: gametocytes → gametes → zygote → ookinete → oocyst → sporozoites → salivary glands.

Clinical Manifestations

Uncomplicated Malaria

  • Paroxysmal fever: Cold stage (chills, rigors) → Hot stage (high fever, 40°C+) → Sweating stage (defervescence, diaphoresis).
  • Cycle periodicity: Tertian (48h — falciparum, vivax, ovale), Quartan (72h — malariae).
  • Headache, myalgia, arthralgia, nausea, vomiting, diarrhea.

Severe Malaria (Primarily P. falciparum)

  • Cerebral malaria (altered consciousness, seizures, coma).
  • Severe anemia (hemolysis + suppressed erythropoiesis) — Hb <5 g/dL.
  • Acidosis (lactic), hypoglycemia, acute kidney injury, ARDS, DIC, hepatic dysfunction.
  • Blackwater fever: Massive intravascular hemolysis → hemoglobinuria (dark urine), renal failure.

P. vivax/ovale Specifics

  • Hypnozoites (dormant liver forms) → relapses weeks–years later.
  • Primaquine/tafenoquine needed for radical cure (test G6PD first).

Diagnosis

  • Gold standard: Giemsa-stained thick/thin blood smears (speciation, quantification).
  • Rapid diagnostic tests (RDTs): HRP2 (falciparum), pLDH/aldolase (pan-species). 15 min; field-deployable.
  • PCR: High sensitivity; species ID; low parasitemia; not point-of-care.

Treatment (WHO Guidelines)

  • Uncomplicated falciparum: ACT (artemisinin-based combination therapy) — artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine.
  • Severe malaria: IV artesunate (preferred) or quinidine; + broad-spectrum antibiotics; ICU care.
  • Vivax/ovale: Chloroquine (if sensitive) + primaquine/tafenoquine (radical cure).
  • Pregnancy: ACT in 2nd/3rd trimester; quinine+clindamycin in 1st; avoid primaquine.

Prevention

  • Vector control: ITNs (insecticide-treated nets), IRS (indoor residual spraying), larval control.
  • Chemoprophylaxis for travelers: atovaquone-proguanil, doxycycline, mefloquine, tafenoquine.
  • RTS,S/AS01 (Mosquirix) vaccine: WHO-recommended for children in moderate-high transmission areas (↓severe malaria ~30%).

Malaria remains a leading global killer (>600,000 deaths/year, mostly African children). Early diagnosis and prompt ACT save lives.

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