Aetiology
Cats are the definitive hosts for Toxoplasma gondii, shedding large numbers of oocysts in their faeces. Other warm-blooded animals, including humans and animals consumed by humans, develop tissue cysts (bradyzoites) after exposure but do not spread infection via faeces.
Humans are infected after eating undercooked meat (usually pork or lamb) containing tissue cysts, or water or food contaminated with oocysts from cat faeces. Specific risk factors include: working with meat; having three or more kittens; eating raw minced beef and rare lamb; eating locally produced cured, dried, or smoked meat; drinking unpasteurised goat's milk; and eating raw oysters, clams, and mussels.[13] Often the specific route of transmission cannot be established because infection is usually inadvertent. In the US and similar countries the risk of exposure from ingestion of undercooked meat is much greater than from handling cat faeces because many domesticated cats are not feral and oocyst shedding is of limited duration in cats.
After T gondii oocysts or bradyzoites are ingested, they spread haematogenously from the gastrointestinal tract throughout the human body in tachyzoite form. Tachyzoites invade cells in a variety of tissues, causing a strong inflammatory response and tissue destruction. Tachyzoites encyst in tissues and organs days after infection under pressure from the host's immune response. Although tissue cysts may develop in visceral organs, they are more prevalent in neural and muscular tissues.[14] Symptomatic disease results from re-activation of intracellular bradyzoites into tachyzoites, which are able to leave the host cell, invade new cells, and disseminate. Local inflammatory response at the site of tissue cyst conversion to tachyzoite form can result in symptomatic disease that correlates to the site of conversion (i.e., conversion of bradyzoites to tachyzoites in the eye causes chorioretinitis and in the brain causes lesions that appear ring-enhancing on computed tomography or magnetic resonance imaging).
Congenital toxoplasmosis results when tachyzoites in an acutely infected pregnant woman traverse the placenta to the fetus.
Pathophysiology
The incubation period is 5-23 days.[15]
In immunocompetent adults and children, primary infection is asymptomatic in most cases, but up to 10% may have symptomatic infection. Acute infection in pregnant women is often asymptomatic.[16]
Most symptomatic infections present as isolated, non-tender cervical or occipital lymphadenopathy. Rarely, myocarditis, myositis, pneumonitis, hepatitis, or encephalitis can arise in otherwise healthy people.
Generally in congenital disease, only infections acquired in the first trimester result in fetal death and severe congenital abnormalities such as intellectual disability and blindness. These are thought to result from proliferation of the tachyzoite form, unchecked by the immature immune system of the fetus.
Fetal infections in the third trimester are often asymptomatic at birth, but the majority of these congenitally infected children (up to 85%) develop retinitis, central nervous system problems (e.g., learning disabilities or seizures) or delayed growth months to years later.[17]
In ocular disease, focal white retinal lesions surrounded by an intense vitreous inflammatory reaction characterise chorioretinitis. It can result from re-activation of latent disease in congenitally acquired infections and in people who are immunosuppressed, or from primary infection (often associated with waterborne outbreaks), and has a high rate of recurrence.[16]
Toxoplasmosis may be the initial opportunistic infection in a person living with HIV who is unaware of their HIV infection. Encephalitis, the most common clinical manifestation of Toxoplasma gondii infection in HIV-infected patients, results from re-activation of dormant encysted bradyzoites that goes unchecked by a weakened immune system. Disseminated or organ-specific disease may also result in recipients of organ transplants, either because of re-activation of latent infection in the recipient or because of re-activation of latent infection in the transplanted organ.[18]
Both innate and adaptive immune mechanisms control T gondii infection. Interleukin-12 and interferon-gamma produced by cells of the innate immune system elicit a strong adaptive Th1-biased immune response. Natural killer cells and dendritic cells are important both for activation of T cells and for control of the inflammatory response.[19][20][21] Interferon-gamma-producing CD4+ and CD8+ T cells are critical for resolution of acute infection and for control of latent, chronic infection.[22] Inflammatory monocytes recruited to sites of infection also play a role in disease control independent of the Th1 response by secreting nitric oxide, which inhibits parasite growth.[23]
Classification
Clinical presentation
Asymptomatic infection: in patients who are immunocompetent, 90% of infections are asymptomatic.
Disseminated disease: seen in HIV-infected patients, organ transplant recipients, or any patient who is immunocompromised.
Toxoplasma encephalitis: rarely seen in anyone other than people who are immunosuppressed. More commonly seen in HIV-infected patients than in transplant recipients or others with immunosuppression.
Toxoplasma chorioretinitis: may be seen in congenital disease, patients who are immunosuppressed, and patients who are immunocompetent. Is associated with waterborne spread of disease.
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