Harrison's Practice: Toxoplasmosis

Harrison's Practice

Toxoplasmosis

Definition

Toxoplasmosis is caused by infection with the obligate intracellular parasite Toxoplasma gondii.
Clinical syndromes associated with acute and chronic toxoplasmosis
- Lymphadenopathy
- Encephalitis
- Myocarditis
- Pneumonitis
Congenital toxoplasmosis results from transplacental passage of the parasite from an infected mother to a fetus.

Epidemiology

Seroprevalence depends on the locale and age of the population.
- Generally, a hot, arid climate is associated with a low prevalence of infection.
- In the U.S. and most European countries, the prevalence of seroconversion increases with age and exposure.
  - In the U.S.
    - Among persons 6–49 years old, 10.8% seroprevalence
    - Among women 15–44 years old, 11.0% seroprevalence
    - Seroprevalence increases by ~1% per year of age.
    - Prevalence has declined from 14% to 9% over the past 10 years in persons 12–49 years old.[1]
- Seroprevalence is higher in:
  - Central America
  - France
  - Turkey
  - Brazil

Toxoplasma encephalitis in the U.S.
- ~2100 cases each year
- Around one-third of the 15–40% of adult patients with AIDS who are latently infected with T. gondii develop Toxoplasma encephalitis.

Ocular toxoplasmosis
- Estimated to cause 35% of cases of chorioretinitis in the U.S. and Europe
- Most ocular involvement is believed to be due to congenital infection; incidence is low following acquired infection.
- 1–3% of patients with AIDS develop debilitating chorioretinitis due to T. gondii.

Congenital toxoplasmosis
- Occurs in 400–4000 infants each year in the U.S.

Risk Factors

Initial infection
- Ingestion of substances contaminated with T. gondii (higher risk in areas with highest prevalence of disease; see Epidemiology)
  - Soil
  - Undercooked or insufficiently frozen meat
    - Ingestion of a single cyst can lead to infection.
- Receipt of blood or organ products contaminated with T. gondii

Infants born to infected mothers are at risk for congenital infection.
- About one-third of women who acquire infection during pregnancy transmit the parasite to the fetus.
- Women who are seropositive before pregnancy usually are protected against acute infection and do not give birth to infected neonates.
- There is no risk if the mother becomes infected ≥ 6 months before conception.
- If infection is acquired < 6 months before conception, the likelihood of transplacental infection increases as the interval between infection and conception decreases.
- In pregnancy
  - Maternal infection during the first trimester: Risk for transplacental infection is lowest (~15%), but the disease in the neonate is most severe.
  - Maternal infection during the third trimester: Risk for transplacental infection is highest (65%), but the infant is usually asymptomatic at birth.
  - Only 20% of women infected with T. gondii develop clinical signs of infection. Often the diagnosis is first appreciated when routine postconception serologic tests show evidence of specific antibody.
Immunocompromised individuals
- Cell-mediated immunity impairment (e.g., due to AIDS or chemotherapeutic treatment of lymphoproliferative disorders) predisposes to acute toxoplasmosis, either from reactivation of latent infection or from acquisition of new infection.
Reactivation disease
- Immunocompromised status
  - More than 95% of cases of AIDS-associated Toxoplasma encephalitis are believed to be due to recrudescent infection.
    - In patients with AIDS, most cases of Toxoplasma encephalitis develop when the CD4+ cell count falls below 100/µL.

Etiology

T. gondii is an intracellular parasite.
There are 2 stages in the life cycle of T. gondii.
- The nonfeline stage: Tissue cysts are ingested by an intermediate host (e.g. humans, many other mammals, and birds).
  - Ingested tissue cysts are digested, releasing bradyzoites that enter the small-intestinal epithelium.
  - Bradyzoites transform into rapidly dividing tachyzoites, which can infect and replicate in all mammalian cells except erythrocytes.
  - Most tachyzoites are eliminated by the host’s immune system, and tissue cysts containing bradyzoites develop.
- The feline stage: The principal stage (sexual phase) in the life cycle takes place in cats (the definitive host) and their prey.
  - Bradyzoitic tissue cysts are ingested, which, after many stages of development, culminate in the production of gametes that fuse and are secreted in the feces as unsporulated oocysts.
  - These oocysts sporulate and can be ingested by an intermediate host.
Transmission
- Oral transmission by human ingestion of:
  - Oocysts from contaminated soil
  - Tissue cysts from undercooked or insufficiently frozen meat (ingestion of a single cyst is sufficient for human infection)
    - 10–20% of lamb products (U.S.)
    - 25–35% of pork products (U.S.)
    - 1% of beef products (U.S.)
- Transmission via blood or organs
  - Direct transmission of the parasite by blood or organ products during transplantation takes place at a low rate.
- Transplacental transmission
  - About one-third of women who acquire infection with T. gondii during pregnancy transmit the parasite to the fetus.
Pathogenesis
- After host ingestion of tissue cysts containing bradyzoites or of oocysts containing sporozoites, parasites are released from the cysts during digestion.
- Bradyzoites are resistant to the effect of pepsin and invade the host’s GI tract.
- From the GI tract, parasites disseminate to a variety of sites, particularly:
  - Lymphatic tissue
  - Skeletal muscle
  - Myocardium
  - Retina
  - Placenta
  - Central nervous system (CNS)
- At these sites, the parasite infects host cells, replicates, and invades adjacent cells.
- Both humoral and cellular immunity are important, but infection commonly persists even in immunocompetent hosts.
  - Such lifelong infection usually remains subclinical.
  - Compromised hosts cannot control infection; progressive focal destruction and organ failure occur.

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