232.1 🎓 醫學生版

232.1.0.1 📌 一頁重點

232.1.0.1.1 Microbiology + Life Cycle

• Pathogen: Toxoplasma gondii — apicomplexan protozoan
• Definitive host: CATS (felines) — only mammals in which sexual reproduction occurs
• Intermediate host: humans + other warm-blooded animals (asexual reproduction)
• Forms:
  • Oocyst: shed in cat feces (after primary feline infection); requires 1-5 days sporulation to be infectious
  • Tachyzoite: rapidly dividing in acute infection (host tissue invasion)
  • Bradyzoite: slowly dividing in tissue cysts (latent, lifelong)

232.1.0.1.2 Transmission

• Ingestion of oocysts in cat feces (contaminated soil, water, vegetable, fruit, sandbox)
• Ingestion of tissue cysts in undercooked meat (pork, lamb, beef, wild game)
• Vertical (mother-to-fetus during pregnancy if primary infection)
• Blood transfusion (rare)
• Organ transplant from seropositive donor to seronegative recipient

232.1.0.1.3 Epidemiology

• Seroprevalence: 30-50% of adults globally (varies by geography + dietary habits)
• High prevalence: France, Brazil, parts of Africa, parts of Mediterranean (raw/undercooked meat consumption)
• Lower: USA (~ 11%), UK
• Most healthy adults asymptomatic

232.1.0.1.4 Clinical (Immunocompetent Acquired)

• 80-90% asymptomatic
• 10-20% symptomatic:
  • Mononucleosis-like illness: fever, cervical LAP (especially posterior cervical, painless), fatigue, malaise
  • Lasts weeks to months
  • Lab: atypical lymphocytes (less than EBV)
• Rare immunocompetent severe: myocarditis, pneumonitis, hepatitis (especially in 2024+ outbreaks linked to specific strains)

232.1.0.1.5 Congenital Toxoplasmosis

• 1° maternal infection during pregnancy → fetal infection
• Transmission rate:
  • 1st trimester: low (15%) but severe disease
  • 2nd trimester: moderate (40%) + moderate severity
  • 3rd trimester: high (70%) but milder
• Severe sequelae if untreated:
  • Chorioretinitis (#1; often reactivates years later)
  • Hydrocephalus
  • Intracerebral calcifications
  • Microcephaly or macrocephaly (hydrocephalus)
  • Intellectual disability
  • Hearing loss
  • Seizures
• Most live-born congenital toxoplasmosis asymptomatic at birth but develop sequelae years later (especially chorioretinitis)

232.1.0.1.6 HIV + Toxoplasmosis (Reactivation)

• Risk: HIV + CD4 < 100 + Toxo IgG positive (latent infection)
• Toxoplasma encephalitis: most common manifestation
  • Headache, fever, focal neurological signs, seizures
  • MRI: multiple ring-enhancing lesions (basal ganglia + gray-white junction)
  • Differential: PCNSL (single + homogeneous enhancing), brain abscess, TB
• Other reactivation: chorioretinitis, pneumonitis (severe in HIV), disseminated

232.1.0.1.7 Diagnosis

• Serology: IgM (acute) + IgG (past or chronic) + IgG avidity (timing of infection)
• PCR: amniotic fluid (vertical), CSF (reactivation), tissue
• Imaging: MRI brain (reactivation in HIV), fetal US (congenital)
• Tissue biopsy + IHC (definitive)

232.1.0.1.8 Treatment

232.1.0.1.8.1 Acute Immunocompetent

• Mostly self-limited
• Treatment for severe / persistent / immunocompromise
• Same regimen as below if treatment indicated

232.1.0.1.8.2 Acute Maternal Infection

• Spiramycin (prevents vertical transmission) until fetal infection confirmed
• If fetal infection confirmed: sulfadiazine + pyrimethamine + leucovorin (after 1st trimester)
• Specialty obstetric + ID coordination

232.1.0.1.8.3 Toxoplasma Encephalitis (HIV)

• Sulfadiazine + Pyrimethamine + Leucovorin × 6 weeks
• Alternative: TMP-SMX, clindamycin + pyrimethamine
• Empirical if MRI ring lesions + IgG positive (don’t biopsy unless atypical or no response)
• Steroid for mass effect / edema
• ART (CD4 recovery)
• Maintenance until CD4 > 200 for 3 months on ART

232.1.0.1.8.4 Ocular Toxoplasmosis

• TMP-SMX (alternative)
• Sulfadiazine + pyrimethamine
• Steroid

232.1.0.1.8.5 Newborn Congenital

• Sulfadiazine + pyrimethamine + leucovorin × 1 year
• Monitor + treat sequelae

232.1.0.1.9 Prevention

• Cat care: indoor cats, daily litter box changing (gloves, mask, hand wash), don’t feed raw meat
• Pregnant women avoid:
  • Cleaning cat litter (delegate)
  • Undercooked meat (cook all meat to safe temperature, freeze < -12°C kills cysts)
  • Unwashed produce
  • Untreated water
• Maternal screening: not universal in USA but routine in France, Italy, Austria
• Pre-transplant screening: donor + recipient serology

232.1.0.1.10 2024 Notes

• Atypical highly virulent strains in S America causing severe disease in immunocompetent
• Outbreaks linked to water contamination (BC Canada historic, others)
• TMP-SMX prophylaxis in HIV (CD4 < 100) reduces toxoplasma encephalitis dramatically

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232.1.0.2 1️⃣ Microbiology + Life Cycle Detail

232.1.0.2.1 Apicomplexan

• Toxoplasma gondii — single species
• Same phylum as Plasmodium, Babesia, Cryptosporidium

232.1.0.2.2 Forms

232.1.0.2.2.1 Oocyst (Environmental)

• Shed by cats after primary acquisition
• ~ 100 million oocysts shed by one infected cat over weeks
• Requires 1-5 days sporulation to be infectious
• Resistant to environmental conditions
• Soil, water contamination

232.1.0.2.2.2 Tachyzoite (Acute)

• Rapidly dividing intracellular form
• Disseminates throughout host
• Targets immune cells + various tissues
• Eventually controlled by immunity → transformation to bradyzoite

232.1.0.2.2.3 Bradyzoite (Chronic)

• Slowly dividing
• Tissue cysts in brain, muscle, retina, heart
• Lifelong latency in host
• Reactivates when immunity compromised

232.1.0.2.3 Life Cycle

1. Cat ingests prey infected with tissue cysts
2. Bradyzoites released in cat intestine → sexual reproduction in epithelium
3. Oocysts shed in feces
4. After sporulation (1-5 d) → infectious
5. Intermediate hosts (humans, livestock) ingest oocysts (soil, water) or tissue cysts (undercooked meat)
6. Oocysts/cysts release sporozoites/bradyzoites in intestine → tachyzoites
7. Dissemination throughout intermediate host
8. Tissue cysts form (bradyzoites — latency)
9. Cycle continues when cat eats intermediate host

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232.1.0.3 2️⃣ Transmission Routes

232.1.0.3.1 Foodborne

• Undercooked meat with tissue cysts: pork, lamb, beef, wild game, ground meat
• Cook to safe internal temperature or freeze < -12°C (10°F) ≥ 3 days kills cysts

232.1.0.3.2 Oocyst-Contaminated

• Soil (sandbox, gardening)
• Water (waterborne outbreaks rare but documented)
• Vegetables / fruits contaminated with cat feces / soil
• Cat litter handling

232.1.0.3.3 Vertical (Pregnancy)

• 1° maternal infection during pregnancy
• Pre-pregnancy infection rarely transmits (lifelong immunity)
• HIV + immunocompromise reactivation can transmit (rare)

232.1.0.3.4 Blood / Tissue

• Rare with screening
• Transplant donor-recipient transmission documented

232.1.0.3.5 Cat Bites / Scratches

• Generally not significant transmission

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232.1.0.4 3️⃣ Clinical — Immunocompetent Acquired

232.1.0.4.1 Asymptomatic (80-90%)

• Most acute infections
• Lifelong latency
• Asymptomatic seroconversion

232.1.0.4.2 Symptomatic Acquired Toxoplasmosis

232.1.0.4.2.1 Mononucleosis-like Illness

• Fever
• Cervical lymphadenopathy (especially posterior cervical, painless, often persistent)
• Fatigue, malaise
• Myalgia
• Pharyngitis
• Atypical lymphocytes on smear (less than EBV mono)
• Lasts weeks to months
• Self-limited

232.1.0.4.2.2 Other Less Common

• Myocarditis (rare)
• Pneumonitis
• Hepatitis
• Polymyositis
• Atypical strains (S America) — severe in immunocompetent

232.1.0.4.3 Ocular Toxoplasmosis (Acquired Cases)

• Less common than congenital reactivation
• Posterior chorioretinitis (mass, focal lesions)
• Vision loss
• Recurrent

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232.1.0.5 4️⃣ Congenital Toxoplasmosis

232.1.0.5.1 Pathogenesis

• 1° maternal infection during pregnancy
• Tachyzoites cross placenta → fetal infection

232.1.0.5.2 Trimester-Specific Outcomes

Trimester	Transmission Rate	Severity
1st	~ 15%	Severe (often spontaneous abortion or major sequelae)
2nd	~ 40%	Moderate
3rd	~ 70%	Milder (more often asymptomatic at birth)

232.1.0.5.3 Classic Tetrad (Sabin)

• Chorioretinitis
• Hydrocephalus
• Intracerebral calcifications
• Intellectual disability + convulsions

232.1.0.5.4 Clinical at Birth

• 90% asymptomatic at birth (especially 3rd trimester transmission)
• Symptomatic at birth: severe with multi-organ involvement
  • Microcephaly OR macrocephaly (hydrocephalus)
  • Chorioretinitis (often bilateral)
  • Periventricular calcifications
  • Hepatosplenomegaly
  • Jaundice
  • Anemia, thrombocytopenia
  • Seizures
• “Classic triad”: chorioretinitis + hydrocephalus + calcifications

232.1.0.5.5 Later Sequelae (Even Asymptomatic at Birth)

• Chorioretinitis appears years later (most common late finding; reactivates)
• Vision loss
• Hearing loss
• Intellectual disability
• Cerebral palsy
• Seizures

232.1.0.5.6 Diagnosis

232.1.0.5.6.1 Prenatal

• Maternal IgM + IgG + IgG avidity (low avidity suggests recent infection)
• PCR of amniotic fluid (after 18 weeks gestation) — sensitive for fetal infection
• Fetal ultrasound (later changes — hydrocephalus, calcifications)
• Fetal MRI

232.1.0.5.6.2 Postnatal

• Newborn serology (compare with maternal — maternal IgG can persist)
• Newborn IgM (own production) — confirms congenital infection
• PCR of newborn blood, CSF, amniotic fluid
• Examination: ophthalmologic, neurological, audiologic, imaging
• Treatment regardless if congenital infection confirmed

232.1.0.5.7 Treatment

232.1.0.5.7.1 Maternal Treatment (Prevent Vertical Transmission)

• Spiramycin (macrolide, doesn’t cross placenta well — used to prevent transmission)
• Continued until pregnancy ends or fetal infection ruled out
• Reduces transmission ~ 50%

232.1.0.5.7.2 Fetal Infection Confirmed

• Sulfadiazine + Pyrimethamine + Leucovorin (after 1st trimester — pyrimethamine teratogenic)
• Spiramycin continued

232.1.0.5.7.3 Newborn Confirmed

• Sulfadiazine + Pyrimethamine + Leucovorin × 1 year
• Long course critical for outcome
• Sequelae monitoring + treatment

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232.1.0.6 5️⃣ HIV + Toxoplasma Reactivation

232.1.0.6.1 Risk

• HIV + CD4 < 100 AND Toxo IgG positive (latent infection from prior exposure)
• Other immunocompromise: BMT, organ transplant, chemo (less common)

232.1.0.6.2 Most Common Manifestation: Toxoplasma Encephalitis

• Subacute (days-weeks)
• Headache + fever + focal neurological signs + seizures + altered mental status
• Hemiparesis, ataxia, aphasia, cranial nerve deficits
• 90% in HIV-related Toxo

232.1.0.6.3 Imaging

• MRI brain: multiple ring-enhancing lesions (basal ganglia + gray-white junction)
• Edema
• Differential:
  • PCNSL (single, homogeneously enhancing)
  • Brain abscess
  • TB
  • Other CNS infections

232.1.0.6.4 Differential CNS Lesions in HIV (CD4 < 100)

Feature	Toxoplasmosis	PCNSL
Lesions	Multi-ring enhancing	Often single, homogeneous
EBV PCR CSF	Negative	Positive (90%)
Thallium SPECT	Negative	Positive uptake
Response to empirical Toxo Tx	Yes (1-2 wk)	No

232.1.0.6.5 Empirical Treatment (vs Biopsy)

• Standard: empirical Toxo Tx if MRI ring lesions + IgG positive + CD4 < 100
• Brain biopsy reserved for:
  • Atypical presentation
  • Failure to respond to 1-2 wk empirical Tx
  • Single lesion + concerning for PCNSL

232.1.0.6.6 Treatment

232.1.0.6.6.1 Induction (6 weeks)

• Sulfadiazine 1-1.5 g PO q6h + Pyrimethamine 200 mg PO × 1 → 75 mg PO qd + Leucovorin 10-25 mg PO qd
• • Steroid (dexamethasone) for edema / mass effect

232.1.0.6.6.2 Maintenance (Until Immune Recovery)

• Lower-dose sulfadiazine + pyrimethamine + leucovorin
• Until CD4 > 200 for 3 months on ART

232.1.0.6.6.3 Alternatives

• TMP-SMX (alternative, similar efficacy)
• Clindamycin + pyrimethamine + leucovorin
• Atovaquone + pyrimethamine + leucovorin

232.1.0.6.6.4 ART

• Critical — restore immunity
• IRIS uncommon but possible

232.1.0.6.7 Prophylaxis

• Primary: CD4 < 100 + Toxo IgG positive → TMP-SMX (also covers PJP)
• Secondary: continue maintenance until immune recovery

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232.1.0.7 6️⃣ Ocular Toxoplasmosis

232.1.0.7.1 Forms

• Congenital reactivation (most ocular Toxo)
• Acquired (less common)

232.1.0.7.2 Clinical

• Posterior chorioretinitis
• Vitritis, focal retinal lesions
• “Searchlight” pattern (active lesion + old scar)
• Vision loss
• Recurrent attacks

232.1.0.7.3 Diagnosis

• Clinical (ophthalmology)
• Anti-Toxo antibody titer (suspicion)
• Aqueous humor PCR (occasionally)

232.1.0.7.4 Treatment

• TMP-SMX or sulfadiazine + pyrimethamine + leucovorin × 4-6 wk
• • topical / oral steroid (selective)
• Surgery rare

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232.1.0.8 7️⃣ Prevention

232.1.0.8.1 Pregnancy

• Routine maternal serology in some countries (France, Italy, Austria)
• USA: not universal — high-risk pregnant women + symptomatic
• Pregnant women avoid:
  • Cleaning cat litter (delegate; if must, gloves + hand wash + daily change)
  • Undercooked meat (cook to safe temp; freeze < -12°C × 3 d kills cysts)
  • Unwashed produce
  • Untreated water
  • Gardening (gloves)

232.1.0.8.2 Cat Care (Pre-Pregnancy + Generally)

• Keep cats indoors (less hunting → less acquisition)
• Daily litter box changing (oocysts not infectious for 24 hr — daily prevents)
• Feed cooked / commercial food (not raw meat)
• Hand wash after handling

232.1.0.8.3 HIV / Immunocompromise

• TMP-SMX prophylaxis CD4 < 100 + Toxo IgG positive (also covers PJP)

232.1.0.8.4 Pre-Transplant Screening

• Donor + recipient serology
• D+/R-: high-risk for primary transmission
• Prophylaxis or monitoring

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