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🦟 MI 3.6 - MALARIA: Complete Conceptual Guide

(Apurba Sastry Microbiology Style - Concepts + Flowcharts + Mnemonics)

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🔑 TRIGGER WORDS (Exam Alert!)

Quotidian, Tertian, Quartan, Blackwater fever, Cerebral malaria, Benign tertian, Malignant tertian, Multiple ring forms, Gametocytes, Anopheles, Hypnozoites, Schuffner's dots

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1. PLASMODIUM SPECIES - Overview

• Definitive host = Mosquito (sexual reproduction)
• Intermediate host = Human (asexual reproduction)

5 Human Species - Mnemonic: "FKVOM"

Falciparum, Knowlesi, Vivax, Ovale, Malariae

Mnemonic for Fever Periodicity: "48-48-48-72-24"

V-O-F = 48 hrs (Tertian) | M = 72 hrs (Quartan) | K = 24 hrs (Quotidian)

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2. LIFE CYCLE - Full Detail

DIAGRAM 1: Complete Life Cycle (Murray Medical Microbiology 9e)

DIAGRAM 2: P. falciparum Molecular Pathogenesis (Robbins Pathology)

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LIFE CYCLE FLOWCHART:

MOSQUITO STAGE (Sexual / Sporogonic Cycle)
         |
         | Female Anopheles bites infected human
         | Ingests GAMETOCYTES
         |
    [In Mosquito Midgut]
    Microgametocyte + Macrogametocyte
         |
    Fertilization → ZYGOTE
         |
    OOKINETE → OOCYST (in gut wall)
         |
    SPOROZOITES (in salivary gland)
         | ~2 weeks in mosquito
         ↓
===========================
HUMAN STAGE (Asexual / Schizogonic Cycle)
===========================

STEP 1: MOSQUITO BITE
         |
    SPOROZOITES injected into human bloodstream
         |
         ↓ (within minutes)

STEP 2: PRE-ERYTHROCYTIC / HEPATIC STAGE (Exoerythrocytic Schizogony)
         |
    Sporozoites → Travel to LIVER
    Bind hepatocytes via:
    - Thrombospondin-related adhesive protein (TRAP)
    - Circumsporozoite protein (CSP)
    → bind Heparan sulfate proteoglycans on hepatocytes
         |
    Sporozoites → develop into LIVER SCHIZONTS → MEROZOITES
         |
    Duration: 5-15 days (depending on species)
         |
    P. vivax / P. ovale → Some sporozoites become HYPNOZOITES
    (dormant, causes RELAPSE months-years later)
         |
         ↓ Hepatocyte ruptures

STEP 3: ERYTHROCYTIC STAGE (Erythrocytic Schizogony)
         |
    MEROZOITES enter RBCs
    (via Lectin-like molecule + Glycophorin/Sialic acid residue)
         |
    Inside RBC: Merozoite → RING FORM → TROPHOZOITE → SCHIZONT
         |
    Schizont bursts → releases 6-36 MEROZOITES + malarial pigment (hemozoin)
         |
    Simultaneous RBC lysis → FEVER PAROXYSM
         |
    Some merozoites → GAMETOCYTES (sexual forms)
         |
         ↓ Mosquito picks up gametocytes → cycle restarts

Key Terms (Apurba Sastry Style):

• Schizogony = Asexual division in liver/RBC
• Sporogony = Sexual cycle in mosquito
• Hypnozoite = "Sleeping form" in liver (P. vivax, P. ovale only) - causes RELAPSE
• Recrudescence = Reactivation from persistent low-grade erythrocytic infection (P. malariae, P. falciparum) - NO hypnozoites
• Relapse vs Recrudescence: Relapse = from liver (hypnozoites); Recrudescence = from blood stage

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3. PATHOGENESIS

A. FEVER PAROXYSM MECHANISM:

RBC Schizonts rupture synchronously
        ↓
Release: Merozoites + Hemozoin + Malarial toxins (GPI anchor)
        ↓
Macrophages activated → TNF-α, IL-1, IL-6 release
        ↓
HYPOTHALAMUS stimulated
        ↓
FEVER PAROXYSM (classic triad: Cold stage → Hot stage → Sweating stage)

B. COLD/ANEMIA STAGES:

• Cold stage (15-60 min): Intense shivering, temperature rises rapidly
• Hot stage (2-6 hrs): High fever 39-41°C, headache, vomiting
• Sweating stage (2-4 hrs): Profuse sweating, temperature falls → patient exhausted

C. P. FALCIPARUM PATHOGENESIS (Most Dangerous):

P. falciparum infects ALL ages of RBCs
        ↓
Parasitized RBCs express PfEMP1 (P. falciparum Erythrocyte Membrane Protein-1)
        ↓
PfEMP1 = KNOB formations on RBC surface
        ↓
Knobs bind endothelial receptors:
- ICAM-1 (Intercellular adhesion molecule-1)
- VCAM-1 (Vascular cell adhesion molecule-1)
- CD36
        ↓
CYTOADHERENCE → Parasitized RBCs SEQUESTER in deep capillaries
        ↓
Microvascular OBSTRUCTION
        ↓
CEREBRAL MALARIA (brain capillaries)
PLACENTAL MALARIA (placental capillaries)
RENAL FAILURE

D. COMPLICATIONS OF FALCIPARUM MALARIA - Mnemonic: "CRAB-H"

• C - Cerebral malaria (encephalopathy, coma, convulsions)
• R - Renal failure (acute tubular necrosis)
• A - Anemia (severe hemolytic)
• B - Blackwater fever (massive hemolysis → hemoglobinuria → "black" urine)
• H - Hypoglycemia + Hepatic dysfunction + Hyperparasitemia

E. WHY DO OTHER SPECIES PREFER CERTAIN RBCs?

Mnemonic: Africans with Duffy-negative RBCs are resistant to P. vivax (because P. vivax merozoite needs Duffy Ag to enter)

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4. MORPHOLOGY / MICROSCOPY FEATURES

Key Distinguishing Features - Mnemonic: "FARMS"

Mnemonic for Schuffner's Dots:

"VOS" has dots = Vivax + Ovale have Schuffner's dots | Falciparum = NO dots (Maurer's clefts instead)

Mnemonic for Gametocytes:

"Falciparum = Banana/Crescent" - Only one with crescent-shaped gametocyte - exam favorite!

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5. EPIDEMIOLOGY

• Vector: Female Anopheles mosquito (bites at dusk/night)
• P. falciparum: Tropical/subtropical only
• P. vivax: Widest distribution (tropics + subtropics + some temperate areas); 80% cases in South America + Southeast Asia
• P. ovale: Primarily tropical Africa
• P. malariae: Same as others, less prevalent
• P. knowlesi: Malaysia, Southeast Asia (zoonotic - from macaque monkeys)

Other Modes of Transmission - Mnemonic: "MINT-C"

• M - Mosquito (main route)
• I - IV drug users (shared needles = "mainline malaria")
• N - Needle stick / Blood transfusion (transfusion malaria)
• T - Transplant (organ)
• C - Congenital (rare)

Note: Transfusion malaria has NO liver stage (no pre-erythrocytic phase), so no hypnozoites, no relapse from liver

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6. LABORATORY DIAGNOSIS

FLOWCHART:

SUSPECTED MALARIA
        |
        ↓
1st LINE: PERIPHERAL BLOOD SMEAR
    ┌─────────────────────────────────┐
    │  THICK SMEAR        THIN SMEAR  │
    │  (Screening -       (Species    │
    │   more sensitive)   ID - more   │
    │                     specific)   │
    └─────────────────────────────────┘
        |
    GIEMSA STAIN / LEISHMAN STAIN
        |
    Look for: Ring forms, trophozoites,
    schizonts, gametocytes, Schuffner's dots
        |
        ↓
2nd LINE: RAPID DIAGNOSTIC TESTS (RDTs)
    - Antigen detection (HRP-2 for P. falciparum)
    - PfHRP2 (Histidine-rich protein 2) - falciparum specific
    - pLDH (Parasite Lactate dehydrogenase) - all species
    - Aldolase - pan-malarial antigen
        |
        ↓
OTHER METHODS:
    - QBC (Quantitative Buffy Coat) - acridine orange stain, fluorescence
    - PCR - gold standard for species ID, drug resistance genes
    - Serology (ELISA, IFA) - not for acute diagnosis, epidemiological surveys only

GOLD STANDARD = THICK BLOOD SMEAR + GIEMSA STAIN

When to collect blood?

• During or just after a fever spike - maximum ring forms in peripheral blood at this time
• P. falciparum: Only ring forms + gametocytes in peripheral blood (schizonts sequestered in organs)
• Multiple smears (every 6-12 hrs x 3) if initial negative

RDT Key Points:

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7. TREATMENT

TREATMENT FLOWCHART:

MALARIA CONFIRMED
        |
        ├──── P. falciparum ──────────────────────────────────┐
        |                                                       │
        └──── P. vivax / P. ovale / P. malariae ──────────┐   │
                                                            │   │
                                                            ↓   ↓

NON-FALCIPARUM (vivax/ovale/malariae):
    CHLOROQUINE (blood schizonticide)
    + PRIMAQUINE (for vivax/ovale only - kills hypnozoites = prevents relapse)
    Check G6PD status before giving PRIMAQUINE (causes hemolysis in G6PD deficiency)

FALCIPARUM - UNCOMPLICATED:
    Artemisinin-based Combination Therapy (ACT):
    - Artemether + Lumefantrine (Coartem) - 1st line in India
    - Artesunate + Amodiaquine
    - Artesunate + Mefloquine
    - Artesunate + Sulfadoxine-Pyrimethamine (AASP)
    NOTE: No primaquine needed (no hypnozoites) except single dose for gametocyte kill

FALCIPARUM - SEVERE / COMPLICATED:
    IV Artesunate (drug of choice)
    OR IV Quinine + Doxycycline (if artesunate not available)
    + Supportive care (ICU, blood transfusion, etc.)

Drug Classification by Action Site - Mnemonic: "Blood, Liver, Both"

Special Situations:

• Pregnancy: Quinine + Clindamycin (1st trimester); ACT (2nd/3rd trimester)
• G6PD deficiency: Avoid Primaquine (causes hemolysis); use weekly Primaquine slowly if needed
• Chloroquine resistance: Widespread in P. falciparum; also seen increasingly in P. vivax

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8. PROPHYLAXIS

Personal Protection: Bed nets (LLIN) + Repellents (DEET) + Clothing + Avoid peak biting hours (dusk to dawn)

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9. PROTECTIVE FACTORS AGAINST MALARIA

• S - Sickle cell trait (HbAS) - P. falciparum cannot thrive
• H - HbC, HbE - protective
• E - Elliptocytosis / Hereditary spherocytosis
• D - Duffy antigen negativity - protects against P. vivax
• G - G6PD deficiency - some protection against falciparum

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10. QUICK EXAM SUMMARY - HIGH YIELD FACTS

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11. ONE-LINE MNEMONICS SUMMARY

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Sources: Murray's Medical Microbiology 9e (Murray, Rosenthal, Pfaller), Robbins & Kumar Basic Pathology, Tietz Textbook of Laboratory Medicine 7th Ed. - All concepts align with Apurba Sastry's Essentials of Medical Parasitology coverage of MI 3.6 competency.