Toxoplasmosis in Emergency Medicine 

Toxoplasmosis is a zoonotic infection in humans caused by the protozoal intracellular parasite Toxoplasma gondii. Cats are the primary hosts, while humans and other mammals serve as intermediate hosts. Infection with T gondii is common among humans, and it is estimated that one third of the world's population has been exposed.^[1] However, most infections are subclinical, and disease typically only becomes apparent in congenitally acquired infection and in patients with significant immunodeficiency such as in acquired immunodeficiency syndrome (AIDS).

Toxoplasma infection is generally acquired via eating undercooked or raw meat infected with tissue cysts, via ingestion of food or water contaminated with infected cat feces, or congenitally from mother to fetus. Rare case reports of individuals becoming infected through blood transfusions or organ transplantation have also been reported.

The seroprevalence of T gondii antibodies in the human population varies geographically with prevalence rates approaching 90% in some European countries, while seropositivity rates in the United States are between 10% and 15%.^{[2, 3]} HIV infection does not seem to effect T gondii seropositivity, and there does not appear to be any difference in the rate of toxoplasmosis infection among AIDS patients with and without cats.^[3]

Life cycle of Toxoplasma gondii

The life cycle of T gondii involves several forms. The oocyte is produced in the feline intestine and produces sporozoites. Sporozoites mature outside of the cat to become tachyzoites, which infect a wide variety of tissues, producing an inflammatory response and a wide array of symptoms. Tachyzoites eventually form tissue cysts in which bradyzoites develop and replicate. In most immunocompetent hosts, bradyzoites are confined to the tissue cysts in which they are slowly replicating; however, in the setting of immune compromise bradyzoites can become tachyzoites, and thus spread infection again to different tissues.

Humans enter the life cycle of T gondii by ingesting meat infected with tissue cysts, or ingesting materials contaminated with infectious oocysts. T gondii may also be acquired transplacentally or via transplantation of infected organs or blood transfusions.^[4]

Infection in the immunocompetent host

Eighty to ninety percent of T gondii infections in immunocompetent hosts are asymptomatic.^[3] Generally, when acute infection is symptomatic, symptoms include symmetric lymphadenopathy, fever, and a nonspecific rash.^{[4, 5]} The vast majority of cases are benign and resolve within weeks. However, severe manifestations of infection, including chorioretinitis, can occur in immunocompetent hosts.

Chorioretinitis or ocular toxoplasmosis is a relatively common manifestation of T gondii infection. Ocular toxoplasmosis occurs when cysts deposited in or near the retina become active, producing tachyzoites. Focal necrotizing retinitis is the characteristic lesion, but retinal scars from prior reactivation are typically present. Presentation usually involves eye pain and decreased visual acuity. Adults who acquired disease in infancy usually present with bilateral eye involvement. Adults with acute infection generally present with unilateral ocular involvement.^{[5, 6, 7]}

Congenital infection

Approximately 10-20% of pregnant women infected with T gondii become symptomatic.^[8] The most common signs of infection are lymphadenopathy and fever. If the mother was infected prior to pregnancy, there is virtually no risk of fetal infection, as long as she remains immunocompetent; however, if the infection is acquired during the pregnancy, there is risk of infection to the fetus. The rate of transplacental infection has been estimated to be 50% for untreated mothers and 25% for treated mothers.^[8]

The rate of fetal infection varies with trimester with 10-25% of infections occurring in the first trimester, 30% in the second trimester, and 50% in the third trimester. Infection during the first or second trimesters appears to be most severe. The clinical features of congenitally acquired T gondii infection include chorioretinitis, blindness, seizures, microcephaly, anemia, and encephalitis.^[7] Infections acquired during the third trimester are usually subclinical; however, clinical disease may still occur later in life. Seventy-five percent of infants congenitally infected with T gondii manifest no symptoms, 14% had evidence of chorioretinitis and 9% demonstrate signs of CNS involvement.^[9]

Infection in immunocompromised patients

Most cases of toxoplasmosis in immunocompromised patients are a consequence of latent infection and reactivation. In patients with AIDS, T gondii tissue cysts can reactivate with CD4 counts less than 200 cells/μ L, and, with counts less than 100 cells/μ L, clinical disease becomes more likely.^[10] Patients with CD4 counts less than 100 cell/μ L and who are T gondii IgG antibody positive have a 30% risk of eventually developing reactivation disease without adequate prophylaxis or restoration of immune function.^[11]

Although toxoplasmosis in immunocompromised patients may manifest as chorioretinitis, reactivation disease in these individuals is typically in the central nervous system with brain involvement being common.

Toxoplasmic encephalitis and brain abscess presents most commonly as headache, but focal neurologic deficits and seizures are as common. With significant disease, patients may also demonstrate the signs and symptoms of elevated intracranial pressure. Cerebral toxoplasmosis is generally identified on CT scan as multiple ring-enhancing lesions; however, solitary lesions may be seen, and negative CT or MRI scans should not rule out the diagnosis of CNS toxoplasmosis.^[4]

Aside from CNS toxoplasmosis, toxoplasmic pneumonitis, myocarditis, as well as disseminated toxoplasmosis are also commonly identified in immunocompromised patients. Toxoplasmic pneumonitis typically presents with symptoms typical for an infectious pulmonary process, including fever, dyspnea, and cough. Chest radiography is often nonspecific, but findings may have an appearance similar to that of Pneumocystis jiroveci pneumonia. Diagnosis is established via bronchoalveolar lavage (BAL). Most patients with extra-CNS manifestations of toxoplasmosis will also be noted to have CNS lesions when appropriate radiographic studies have been performed.^[12]

Frequency

United States

The overall seroprevalence of T gondii in the United States is approximately 15%, and rates of T gondii exposure in HIV patients are similar to those of the general public.^[2] In patients with AIDS who have positive Tgondii antibodies, the risk of developing toxoplasmosis is roughly 30% unless prophylactic or antiretroviral medications are commenced. Among immunocompetent patients, clinically evident toxoplasmosis is more likely to occur after the fifth decade of life. Congenital toxoplasmosis is thought to depend on the trimester during which the maternal infection is acquired, with 10-25% of infections occurring in the first trimester, 30% in the second trimester, and 50% in the third trimester.^[13]

International

The seroprevalence of T gondii antibodies varies geographically with some countries such as France and some developing nations reporting antibody positivity rates to T gondii infection as high as 80%.^[14] The development of toxoplasmosis among immunocompetent patients does not seem to vary from region to region; however, the prevalence of immunocompromised patients is higher in some nations as a function of both HIV/AIDS infection and also organ transplantation and immunomodulatory medication prescribing.

Mortality/Morbidity

The incidence of toxoplasmosis (including CNS disease) in patients with AIDS has declined dramatically in the recent past likely due to the evolution of highly active antiretroviral therapy (HAART) and the routine use of prophylaxis against Pneumocystis jiroveci and T gondii. The incidence of CNS toxoplasmosis decreased from 5.4 per 1000 person-years between 1990 and 1992 to 2.2 per 1000 in 1996 to 1998.^[15] The routine use of cotrimoxazole prophylaxis both in the United States and internationally has also likely significantly decreased the incidence of CNS toxoplasmosis.

Depending on the location and severity of toxoplasmic chorioretinitis, infection can result in permanent retinal scarring and loss of visual acuity. Recurrent episodes are common, resulting in multiple areas of retinal scarring and functional loss. Toxoplasmic encephalitis and brain abscess can result in permanent neurologic sequelae depending on the location of the lesion and the extent of local damage and inflammation.

Race

While there do exist differences in the seroprevalence of infection among different ethnic groups, these differences likely reflect the regionality of infection rather than a particular susceptibility to infection.

Sex

Although toxoplasmosis is well studied in women of childbearing age because of its detrimental effects on the fetus, no difference in prevalence between the sexes is reported.

Age

No difference in seroprevalence based on age has been noted; however, with the exception of T gondii chorioretinitis, older individuals are more likely to manifest clinically evident reactivation of Tgondii infection. Congenitally acquired Tgondii chorioretinitis is more likely to recur in those older than 40 years.^[7]