Toxoplasmosis

Toxoplasmosis is a disease caused by the obligate intracellular parasite Toxoplasma gondii. Transmission occurs either through ingestion of cysts found, for example, in raw meat or cat feces, or from mother to fetus through the placenta. The clinical presentation depends on the patient's immune status: In immunocompetent individuals, 90% of cases are harmless and asymptomatic, with the remaining 10% displaying mild mononucleosis-like symptoms. In immunosuppressed patients (e.g., those who are HIV-positive), infection may result in cerebral toxoplasmosis (headache, confusion, focal neurological deficits) or toxoplasmic chorioretinitis (eye pain, reduced vision). Treatment is indicated for immunosuppressed patients, infected mothers, congenital toxoplasmosis, and immunocompetent patients with more severe symptoms. The treatment of choice is usually a combination of pyrimethamine, sulfadiazine, and leucovorin (folinic acid), with the exception of new infections during pregnancy, which are treated with spiramycin.

For the congenital variant and how to manage infection in pregnant women, see “Toxoplasmosis in pregnancy.”

• Prevalence
  • In the US: ∼ 10% of adults
  • In some tropical climates: up to 95%

References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: : Toxoplasma gondii, an obligate intracellular, single-celled protozoan
• Route of transmission
  • Oral ingestion: The oocysts are excreted in the feces of cats (final host) and are orally ingested by other mammals such as humans, hoofed animals, and birds (intermediate hosts). Primary modes of transmission include the following:
    • Cat feces
    • Raw or insufficiently cooked meat (most common)
    • Unpasteurized milk (especially goat milk)
  • Transplacental transmission: see toxoplasmosis in pregnancy
  • Via organ transplantation or blood transfusion

References:^[2]

• Incubation time: 5 days to 3 weeks ^[3]
• Immunocompetent patients: typically primary infection ^[4][5]
  • Mainly asymptomatic (∼ 90% of patients)
  • Symptomatic (< 10% of patients) ^[6]
    • Mononucleosis-like symptoms with bilateral cervical adenopathy (but negative heterophile antibody test) ^[7]
    • Rarely: ocular toxoplasmosis
  • After initial infection, latent tissue cysts remain.
• Immunosuppressed patients (e.g., patients with AIDS): primary infection or reactivation in previously infected individuals ^[4]
  • Symptoms of encephalitis in cerebral toxoplasmosis
  • Visual impairments and pain in ocular toxoplasmosis
  • Other symptoms depend on affected organs (e.g., lungs, heart).

Indications for testing may include uveitis or retinochoroiditis with no known history of congenital toxoplasmosis, organ transplantation, and a new diagnosis of HIV. ^[4][8]

• Serology ^[4][9]
  • IgM antibody test: positive within first week of acute infection ^[9]
  • IgG antibody test; : positive 2 weeks following infection and remains positive for life
• PCR using, e.g.:
  • Amniotic fluid for suspected intrauterine disease
  • CSF for suspected cerebral toxoplasmosis
• Additional diagnostics, e.g.:
  • CT/MRI of the brain for suspected cerebral toxoplasmosis
  • Fundoscopy for suspected ocular toxoplasmosis

• Indications include immunosuppression; , pregnancy, and severe infection (e.g., active ocular toxoplasmosis).
• Treatment of choice
  • Pyrimethamine PLUS sulfadiazine PLUS leucovorin
  • Spiramycin for toxoplasmosis in pregnancy before the 18^th week ^[10]
• For details, including dosages, see:
  • “Treatment of cerebral toxoplasmosis”
  • “Treatment of ocular toxoplasmosis”

Immunocompetent patients do not usually require treatment.

Description ^[5][8][11]

• A necrotizing encephalitis affecting immunocompromised individuals that is caused by reactivation of T. gondii
• The most common neurological disorder associated with AIDS
  • Considered an AIDS-defining condition
  • Typically occurs at CD4 count < 100 cells/μL

Clinical features ^[8]

• Fever
• Headache
• Mental status changes
• Seizures
• Focal neurological deficits

Diagnostics ^[8][11]

A definitive diagnosis requires the presence of clinical features, biopsy findings of T. gondii, and ≥ 1 mass lesion seen on imaging. Empiric treatment is usually initiated based on typical clinical features and currently available imaging and serology results. ^[8][11]

• Imaging: CT or MRI with contrast
  • Multiple ring-enhancing lesions (brain abscesses)
  • Lesions located predominantly in the basal ganglia and/or the subcortical white matter
• CSF: pleocytosis, ↑ protein, PCR positive for T. gondii ^[12]
• Serology: IgM and IgG antibody tests ^[4]
• Biopsy: may be required if treatment fails and/or to differentiate from other diagnoses ^[4][8]
  • Toxoplasma tachyzoites: parasites in their replicative state; predominant during active infection
  • Toxoplasma bradyzoites: parasites in their dormant state with reduced metabolism
  • Chronic inflammation and necrosis of brain tissue ^[4]

Treatment of cerebral toxoplasmosis ^[13][14]

See “Approach to undifferentiated neurological symptoms in patients with HIV” for initial management of this patient group.

• Preferred regimen ^[13]
  • Pyrimethamine
  • PLUS sulfadiazine
  • PLUS leucovorin
• Treatment duration: at least 6 weeks, followed by chronic maintenance therapy
• Supportive treatment ^[8]
  • Patients with a history of seizures: anticonvulsants during the acute therapy phase
  • Patients with AIDS: Initiate ART within 2–3 weeks (if not already started).
  • Consider glucocorticoids if there is concern for mass effect.
• Disposition: Admission, potentially to a critical care unit, is usually required.

Primary CNS lymphoma is a differential diagnosis of cerebral toxoplasmosis. Until this differential is ruled out, avoid glucocorticoids, as they can alter neuroimaging and biopsy findings and may delay a diagnosis.

Prophylaxis for HIV patients ^[13]

• Adequate HIV treatment (cART)
• Trimethoprim/sulfamethoxazole
• See: “Prevention of opportunistic infections in HIV”

• ABCDE assessment and treatment as required
• Management of acute seizures and status epilepticus
• Evaluate for and manage critical causes of AMS and coma.
• Consult infectious diseases.
• Basic laboratory studies (e.g., BMP, CBC)
• Toxoplasma serology
• CT/MRI head with contrast
• Lumbar puncture for toxoplasma PCR and to rule out meningitis
• HIV testing including CD4 count
• Initiate treatment of cerebral toxoplasmosis.
• Consider admission, potentially to critical care unit.

Clinical features ^[15][16]

• Chorioretinitis
  • Visual impairment, floaters, scotomas
  • Defects in the visual field at the site of inflammation
  • Pain (but may be painless in some patients)
  • Optic atrophy or macular scar formation can progress to blindness.
  • Typically self-limited in immunocompetent patients
  • Frequently recurrent in immunocompromised patients
• Retinochoroiditis juxtapapillaris (Jensen disease): visual field defects caused by retinochoroidal lesions adjacent to the optic disc ^[17]

Diagnostics ^[16]

Ocular toxoplasmosis is typically a clinical diagnosis.

• Fundoscopy
  • Acute toxoplasmosis ^[18]
    • Yellow-white retinal lesion
    • Marked vitreous reaction: Severe vitritis may result in a "headlight in the fog” appearance.
    • Concomitant vasculitis
  • Previous toxoplasmosis
    • Formation of scars with white atrophic areas
    • Dark, sharply defined retinal pigmentation
• Adjunctive tests: PCR or antibody titers of ocular fluid if the diagnosis is uncertain

Treatment of ocular toxoplasmosis ^[16][19][20]

• Preferred regimens
  • Pyrimethamine PLUS sulfadiazine PLUS leucovorin
  • OR trimethoprim/sulfamethoxazole (off-label)
• Treatment duration: 4–6 weeks
• Supportive treatment: Consider adding glucocorticoids after initial antibiotic therapy. ^[19]