Toxoplasmosis
Obligate intracellular protozoan infection (Toxoplasma gondii) — usually asymptomatic, but causes severe congenital disease and CNS lesions in immunocompromised hosts.
Also known as: toxoplasmosis, Toxoplasma gondii, congenital toxoplasmosis, CNS toxoplasmosis
Overview
Infection by Toxoplasma gondii, an obligate intracellular protozoan with cats as the definitive host. Humans are intermediate hosts, acquiring infection via ingestion of oocysts (cat feces, contaminated water/soil) or tissue cysts (undercooked meat). Lifelong latent infection persists in tissue cysts.
Epidemiology
Seroprevalence ~10-20% in US adults, higher in older adults and immigrants; up to 60-80% in parts of Europe and South America. Estimated 750,000-1.1 million new US infections yearly. Second leading cause of foodborne deaths in the US.
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Risk factors
- Ingestion of undercooked or raw meat (especially pork, lamb, venison)
- Cat litter exposure (especially outdoor cats); soil/garden contact without gloves
- Unfiltered/untreated water in endemic areas
- Pregnancy (highest risk if primary infection in second/third trimester)
- Immunocompromise: HIV with CD4 <100, hematopoietic transplant, lymphoma
Pathophysiology
Ingested oocysts/cysts release sporozoites/bradyzoites that invade gut epithelium, transform into tachyzoites, and disseminate hematogenously. Cell-mediated immunity controls infection but does not eliminate tissue cysts (containing bradyzoites) in brain, muscle, eye, and heart. Reactivation occurs when CD4 cells decline (HIV) or with immunosuppression. Congenital transmission risk rises from ~10% in first trimester to ~80% in third trimester, but severity is inverse (severe disease more common with early transmission).
Clinical presentation
Symptoms
- Immunocompetent: usually asymptomatic; minority develop bilateral non-tender cervical lymphadenopathy, fatigue, low-grade fever, myalgia (mononucleosis-like)
- Ocular toxoplasmosis: blurred vision, floaters, eye pain, scotomata — usually reactivation
- Congenital toxoplasmosis: classic triad of chorioretinitis, hydrocephalus, and diffuse intracranial calcifications; may also have seizures, hepatosplenomegaly, jaundice, microcephaly, IUGR; many asymptomatic at birth but develop chorioretinitis or learning disabilities later
- AIDS-associated CNS toxoplasmosis (CD4 <100): subacute headache, focal neuro deficits, seizures, altered mental status, fever
Signs / physical exam
- Non-tender posterior cervical lymphadenopathy (acute acquired)
- Chorioretinitis on funduscopy: yellow-white focal retinal lesion with overlying vitreous inflammation
- Focal CNS deficits, hemiparesis, papilledema
- Congenital: hepatosplenomegaly, jaundice, blueberry-muffin rash, microcephaly or macrocephaly
Classic findings
AIDS patient with CD4 <100, headache, focal neuro deficit, and multiple ring-enhancing brain lesions on MRI in the basal ganglia or gray-white junction — toxoplasmosis until proven otherwise. Congenital infection: diffuse intracranial calcifications (vs. periventricular in CMV).
Differential diagnosis
- CNS lymphoma (HIV) — Single lesion (toxoplasmosis usually multiple), no response to empiric anti-toxo therapy, positive EBV PCR in CSF; thallium SPECT positive (negative in toxo)
- Tuberculous meningitis/tuberculoma — Indolent course, basal meningeal enhancement, IGRA/CSF PCR
- Progressive multifocal leukoencephalopathy (PML) — JC virus, non-enhancing white matter lesions, no mass effect; CSF PCR positive
- Cryptococcoma — Cryptococcal antigen positive; smaller lesions
- EBV mononucleosis — Pharyngitis prominent, heterophile positive
- CMV/other TORCH (congenital) — Overlapping features; targeted serology and PCR
- Glioma or metastasis — Less typical for HIV-stage 3; biopsy if no response to empiric therapy
Diagnostic workup
Diagnostic criteria
Clinical syndrome + serology/PCR + imaging. CNS toxoplasmosis in HIV often diagnosed empirically with response to therapy (2-week trial); biopsy if no improvement.
Labs
- Toxoplasma IgG (lifelong) and IgM (acute; IgM can persist >1 year)
- IgG avidity (high avidity excludes recent infection — useful in pregnancy)
- PCR — amniotic fluid (congenital diagnosis), CSF (CNS toxo), aqueous humor (ocular), blood (transplant recipients)
- Lymph node biopsy — characteristic Piringer-Kuchinka pattern in acquired adenopathy
- Negative IgG essentially excludes CNS toxoplasmosis in HIV
Imaging
- MRI brain with contrast: multiple ring-enhancing lesions with surrounding edema, predilection for basal ganglia and gray-white junction
- CT (if MRI unavailable): hypodense lesions with ring enhancement
- Fetal ultrasound: hydrocephalus, intracranial calcifications, IUGR, hepatosplenomegaly
- Funduscopic exam for chorioretinitis
Diagnostic algorithm
| Host Group | Typical Manifestation | Diagnosis | First-line Therapy |
|---|---|---|---|
| Immunocompetent | Asymptomatic or mono-like adenopathy | IgG/IgM serology | Usually none |
| Pregnant (primary) | Maternal mild, fetal risk | IgG avidity + amniotic PCR | Spiramycin; pyrimethamine-sulfa if fetal infection |
| Congenital | Chorioretinitis, hydrocephalus, calcifications | Neonatal IgM/IgA, PCR | Pyrimethamine + sulfadiazine + leucovorin x 1 yr |
| AIDS (CD4 <100) | Ring-enhancing CNS lesions | MRI + empiric trial | Pyrimethamine + sulfadiazine + leucovorin |
| Ocular | Chorioretinitis, floaters | Funduscopy ± aqueous PCR | Pyrimethamine + sulfadiazine ± steroids |
Treatment
First-line
- Acute acquired in immunocompetent host: typically no treatment unless severe or visceral disease
- Ocular toxoplasmosis: pyrimethamine + sulfadiazine + leucovorin × 4-6 weeks; corticosteroids if vision-threatening
- CNS toxoplasmosis (HIV/immunocompromised):
- • Pyrimethamine 200 mg load then 50-75 mg PO daily + sulfadiazine 1-1.5 g PO QID + leucovorin 10-25 mg daily × 6 weeks induction
- • Then chronic suppression at half doses until CD4 >200 × ≥6 months on ART
- Alternative: TMP-SMX (effective and more accessible)
- Pregnancy with primary infection: spiramycin to prevent fetal transmission; if fetal infection confirmed (amniotic fluid PCR), switch to pyrimethamine + sulfadiazine + leucovorin after 14 weeks gestation (avoid pyrimethamine in first trimester due to teratogenicity)
- Congenital toxoplasmosis: pyrimethamine + sulfadiazine + leucovorin × 1 year
Second-line / adjunct
- Clindamycin + pyrimethamine + leucovorin — sulfa allergy
- Atovaquone + pyrimethamine + leucovorin — alternative
- TMP-SMX as primary prophylaxis (CD4 <100 + positive toxo IgG) — covers both PCP and toxoplasmosis
Complications
- Vision loss from chorioretinitis (recurrence common)
- Cerebral abscess with mass effect, herniation
- Cognitive impairment, seizures from CNS disease
- Congenital: developmental delay, hearing loss, blindness, recurrent chorioretinitis
- Toxoplasma encephalitis IRIS after starting ART
PANCE pearls
- Pregnancy prevention: avoid undercooked meat, change litter daily and wear gloves, wash produce, drink filtered water.
- Toxoplasma IgM can persist >1 year — do not interpret a positive IgM as recent infection without IgG avidity testing.
- In HIV with CD4 <100 + positive toxoplasma IgG, TMP-SMX prophylaxis prevents both PCP and toxoplasmosis.
- Empiric anti-toxo therapy in HIV with ring-enhancing lesions — clinical/radiographic response within 2 weeks supports the diagnosis; failure → biopsy to evaluate for lymphoma.
- Congenital intracranial calcifications: toxoplasmosis is diffuse; CMV is periventricular.
References
- DHHS OI — Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV — Toxoplasmosis section
- CDC — Toxoplasmosis: Information for Healthcare Providers
- Maldonado 2017 — AAP Diagnosis, Treatment, and Prevention of Congenital Toxoplasmosis in the United States (Pediatrics)
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