Toxoplasmosis & Plasmodium Falciparum

📚 TOXOPLASMOSIS

🖇 I. ETIOLOGY, NAMING & PREVALENCE

📌 Origin of Name

• Toxoplasma from Greek word Toxos = arc or bow
• Named because parasite adopts crescent or arc shape

📌 Discovery

• First discovered in species of rats/mice in North Africa

🚨 Prevalence (Exam Point)

• 1 out of every 3 people worldwide is infected
• Highly significant parasite
• Infected individuals may or may not show symptoms

📌 Common Association

• Disease commonly associated with cats
• Known concern for pregnant women who own cats
• Actual scientific data regarding transmission sources needs clarification

🖇 II. FORMS (STAGES) OF THE PARASITE

🟠 THREE MAIN FORMS:

🟣 1. TACHYZOITE

📌 Etymology & Characteristics:

• Tachy = rapid
• Rapid replication (fast division) (Exam Point)
• Shape: Arc or crescent

🚨 Clinical Significance: (Exam Point)

• Form responsible for acute infection

📌 Location:

• Strictly found in nucleated cells
• Cannot exist in non-nucleated cells (e.g., RBCs/erythrocytes)
• Requires nucleus for nutrition and protection

🟣 2. BRADYZOITE (TISSUE CYST)

📌 Etymology & Characteristics:

• Brady = slow
• Very, very slow division

🚨 Structure & Behavior: (Exam Point)

• Do NOT survive alone
• Live together in groups
• Surrounded by thick wall
• Forms structure called Tissue Cyst

🚨 Clinical Significance: (Exam Point)

• Associated with chronic infection

🟣 3. OOCYST

📌 Nature:

• Sexual form of parasite

🚨 Location: (Exam Point)

• Found ONLY in definitive host = cat (feline)

📌 Structure:

• Strong wall
• Contains 2 spheres inside
• Each sphere = sporocyst
• Each sporocyst contains 4 sporozoites

🖇 III. HABITAT & LIFE CYCLE

🟠 A. HABITAT & NATURE

🚨 Key Characteristic: (Exam Point)

• Obligate intracellular parasite
• Habitat = within cells
• Cannot live outside host cell

📌 Host Classification:

• Definitive Host: Cat (feline) - sexual cycle occurs here
• Intermediate Hosts: Humans, mice, birds

🟠 B. LIFE CYCLE IN CAT (DEFINITIVE HOST)

📌 Steps:

1. Cat ingests infected intermediate host (e.g., mouse with tissue cyst in muscle)
2. Tissue cyst releases bradyzoites
3. Bradyzoites invade cat's intestinal lining (villi/epithelium)
4. Parasites multiply and undergo differentiation
5. Male and female gametes fuse (syngamy) → form zygote
6. Zygote develops wall → forms oocyst
7. Unsporulated oocyst passed in cat's feces into environment (soil)

🟠 C. SPORULATION & ENVIRONMENTAL CONTAMINATION

📌 Process:

• Oocyst undergoes sporulation in environment
• Forms 2 sporocysts
• Each sporocyst contains 4 sporozoites

📌 Fate of Sporulated Oocysts:

• Ingested by mice or birds
• Contaminate drinking water
• Contaminate grass/feed eaten by grazing animals

🟠 D. PATHOGENESIS IN HUMANS (INTERMEDIATE HOST)

📌 Infection Route:

• Humans ingest either:
• • Sporulated oocyst, OR
  • Tissue cyst

📌 Pathogenesis Steps:

1. Both forms release Tachyzoites in intestine
2. Tachyzoites invade nucleated cells
3. Multiply rapidly within cell
4. Cell bursts (lysis) → releases Tachyzoites
5. Tachyzoites infect neighboring cells
6. Can be transported to different organs (CNS, muscle) by macrophages
7. When immune system controls acute infection:
8. • Tachyzoites transform into Bradyzoites
   • Form Tissue Cyst

🖇 IV. MODES OF TRANSMISSION

🟠 MAJOR ROUTES OF TRANSMISSION:

🟣 1. INGESTION OF OOCYSTS

• Through contaminated water
• Contaminated fruits or vegetables
• Fecal-oral route
• Environmental contamination

🟣 2. INGESTION OF TISSUE CYSTS

🚨 Source: (Exam Point)

• Found in raw or undercooked meat
• Especially grilled meat

🚨 Clinical Note: (Exam Point)

• Consumption of undercooked meat accounts for approximately 50% of transmission
• Often overlooked as major source

🟣 3. TACHYZOITES (Vertical or Iatrogenic)

📌 Routes:

• Transplacental (congenital transmission - mother to fetus)
• Transfusion (blood)
• Transplantation (organ)

🖇 V. CLINICAL MANIFESTATIONS

📌 General Note:

• Parasite can infect any nucleated cell
• Has clear pathway to CNS
• Clinical outcomes based on immune status and age

🟠 A. IMMUNOCOMPETENT NON-PREGNANT ADULTS

🚨 Statistics: (Exam Point)

• 90% asymptomatic
• 10% symptomatic

📌 Symptomatic Presentation:

• Mononucleosis-like illness
• Lymphadenopathy often present
• Infection enters latent (chronic) phase

🟠 B. CONGENITAL TOXOPLASMOSIS (INFECTED FETUS/CHILD)

🟣 Infection Rate vs Severity (Exam Point)

📌 Later Trimesters (2nd & 3rd):

• Higher rate of vertical transmission to fetus
• Lower severity of disease

📌 Early Pregnancy (1st Trimester):

• Lower transmission rate
• Severe outcome if transmitted
• Commonly leads to:
• • Fetal death, OR
  • Severe complications

🟣 Outcomes in First Year of Life (If Infected):

Three Possible Outcomes:

1. Fetal/infant death
2. Symptoms in first year:
3. • CNS manifestations (e.g., hydrocephalus)
   • Ocular manifestations (e.g., chorioretinitis)
3. Asymptomatic at birth:
4. • May later develop severe symptoms (e.g., chorioretinitis) around age 2, OR
   • Remain asymptomatic (latent)

🟠 C. IMMUNOCOMPROMISED INDIVIDUALS (REACTIVATION)

🟣 Risk Group:

• Individuals with low T-lymphocyte counts (T-cell deficiency)
• AIDS patients (CD4 count < 200)
• Organ transplant recipients
• Chemotherapy patients

🚨 Key Risk: (Exam Point)

• High risk for Reactivation of chronic Toxoplasmosis

🚨 Clinical Note - Diagnosis: (Exam Point)

• If immunocompromised patient (cancer/AIDS) suddenly develops CNS symptoms
• Toxoplasmosis reactivation MUST be included in differential diagnosis

🟣 Manifestations of Reactivation:

1. TOXOPLASMIC ENCEPHALITIS (CNS) - Most common

📌 Mechanism:

• Tachyzoite replication causes cell destruction/necrosis

🚨 Lesion Pattern: (Exam Point)

• Multiple space-occupying lesions (SOLs)
• Primarily in:
• • Cerebral cortex
  • Basal ganglia
  • Cerebellum

2. OCULAR TOXOPLASMOSIS (CHORIORETINITIS)

• Often accompanies CNS involvement
• Occurs in approximately 65% of cases

3. PNEUMONITIS

🖇 VI. DIAGNOSIS

📌 Primary Tool: Serology

• Other methods for confirmation or specific populations

🟠 A. SEROLOGY (IgG & IgM)

🟣 IgG Testing

📌 Indicates:

• Past exposure (chronic infection)

🚨 Clinical Note - Pregnancy: (Exam Point)

• If pregnant woman is IgG positive = typically reassuring
• Indicates prior immunity

📌 IgG Avidity Test:

• Measures binding strength of IgG

Interpretation:

• High Avidity = old infection (antibodies bind strongly)
• Low Avidity = recent infection (antibodies bind weakly)
• Helps distinguish acute from chronic infection

🟣 IgM Testing

📌 Indicates:

• Recent, acute infection

🚨 Clinical Notes:

• IgM levels can persist for months
• If pregnant woman is IgM positive = active infection
• • Requires immediate treatment
• IgM testing in infants suggests congenital infection
• Maternal IgG passively transferred to infant is NOT diagnostic

🟠 B. OTHER DIAGNOSTIC METHODS

🟣 1. PCR (Polymerase Chain Reaction)

• Detects parasite DNA
• Used especially in:
• • Congenital cases (amniotic fluid)
  • Immunocompromised patients

🟣 2. Direct Parasite Detection

• Tissues or fluids inoculated into mouse
• Mouse observed for subsequent infection

🟣 3. Sabin-Feldman Dye Test (SFDT)

📌 Mechanism:

• Classic diagnostic test
• Determines if patient's serum contains antibodies capable of destroying parasite

📌 Procedure:

• Live Tachyzoites incubated with:
• • Patient serum
  • Complement
  • At 37°C for 1 hour

📌 Interpretation:

POSITIVE (Antibodies Present):

• Tachyzoites destroyed (lysis/degeneration)
• When Methylene Blue dye added
• Destroyed Tachyzoites do NOT stain blue

NEGATIVE (Antibodies Absent):

• Tachyzoites remain intact
• Stain blue

🖇 VII. TREATMENT

📌 Treatment varies by patient population

🟠 A. STANDARD TREATMENT COMPONENTS

🚨 Three-Drug Regimen:

1. Pyrimethamine
2. Sulfadiazine
3. Folinic Acid

📌 Folinic Acid Role:

• Counteracts side effects of Pyrimethamine
• Pyrimethamine is toxic to bone marrow
• CRUCIAL: Use Folinic Acid (Leucovorin)
• NOT Folic Acid

🟠 B. TREATMENT PROTOCOLS BY POPULATION

🟣 1. Immunocompetent/Immunocompromised Adults:

• Pyrimethamine + Sulfadiazine + Folinic Acid

🟣 2. Pregnant Women:

Before 17 weeks gestation:

• Spiramycin ONLY
• Avoids potential teratogenic effects of Pyrimethamine/Sulfadiazine

After 17 weeks gestation:

• Pyrimethamine + Sulfadiazine + Folinic Acid

🟣 3. Congenital Toxoplasmosis (Infant):

📌 Regimen:

• Pyrimethamine
• Sulfadiazine
• Folinic Acid
• Corticosteroids (Prednisone/Dexamethasone)

📌 Duration:

• Treatment should last 1 year

🟠 C. ROLE OF CORTICOSTEROIDS

📌 General Note:

• Corticosteroids are generally immunosuppressive
• Used selectively in severe cases alongside anti-parasitic drugs

🚨 Indications: (Exam Point)

1. Severe Ocular Toxoplasmosis (Chorioretinitis):

• Reduce severe inflammatory action
• Prevents permanent vision loss

2. Toxoplasmic Encephalitis:

• Reduce severe cerebral edema
• Prevents coma and death

🖇 VIII. PREVENTION

📌 General Measures:

• General hygiene
• Washing hands
• Control food and water quality
• Ensure meat is well-cooked

🟠 TORCH SCREENING

📌 Component:

• Toxoplasmosis (T) = part of routine TORCH screening
• Requested for pregnant women

🚨 Timing of Screening: (Exam Point)

📌 IDEAL TIME:

• Before marriage/conception (premarital screening)

📌 Goal:

• Identify susceptible women, OR
• Identify those with acute infections
• Treat BEFORE pregnancy
• Prevents congenital transmission

Key Focus Areas for Exams:

• Three forms: Tachyzoite (acute), Bradyzoite (chronic), Oocyst (sexual/cat only)
• 50% transmission via undercooked meat
• Congenital: higher transmission rate in later trimesters but lower severity
• IgG positive in pregnancy = reassuring (prior immunity)
• Treatment: Pyrimethamine + Sulfadiazine + Folinic Acid (NOT Folic Acid)
• Pregnant women before 17 weeks: Spiramycin only
• Corticosteroids for severe chorioretinitis or encephalitis
• Screening ideally before marriage/conception