Most cases of Toxoplasma infection are subclinical in individuals with normal immune systems, and usually disease is self-limiting. Lymphadenopathy is the manifestation recognized most frequently, and the location most often is cervical, followed by axillary and then inguinal sites, although any group of lymph nodes may be involved. Adenopathy may occur more commonly at single sites in adults, but is more likely to occur at multiple sites in children. Usually, the lymph nodes are firm and movable and initially may be tender. They do not suppurate, and typically the lymph nodes are 1 to 2 cm in size, but they may be as large as 6 cm. Most cases of lymphadenopathy resolve over the course of 1 to 2 months.

Occasionally, disease may persist beyond 6 months. Adenopathy may be recurrent. The differential diagnosis of toxoplasmic lymphadenopathy includes lymphoma, leukemia, and other malignancies, infectious mononucleosis (Epstein-Barr virus), cytomegalovirus (CMV) infection, human immunodeficiency virus (HIV) infection, cat-scratch disease, bacterial lymphadenitis, atypical mycobacterial infection, tuberculosis, tularemia, and sarcoidosis. Other clinical presentations include an infectious mononucleosis–like illness with fever, malaise, and myalgia, although sore throat and hepatosplenomegaly are not typical with Toxoplasma infection.

Ocular disease may be associated with acute acquired infection in normal hosts but is associated more typically with congenital disease and reactivated disease. Although it is rare, severe systemic disease, including encephalitis, has been reported in apparently normal children (see further discussion later in this section). Other reported manifestations have included maculopapular rash, hepatitis, pneumonitis, myositis, myocarditis, pericarditis, and meningitis. Infection in immunologically
normal hosts usually is self-limited. Severe disease more typically occurs in patients with a deficient immune system.

Toxoplasmosis in immunocompromised hosts may result from acute or reactivated infection. Disseminated infection may occur with fever and involvement of any and all organs, including brain, heart, and lung. It may result from primary infection in patients who are receiving immunosuppressive therapy (e.g., organ or bone marrow transplant recipients), in patients who have malignant disease (especially reticuloendothelial) and are undergoing chemotherapy, or in patients with acquired or congenital immunodeficiencies. Primary infection can occur also in transplant recipients via an infected organ or bone marrow or through blood transfusion. Diagnosing disseminated toxoplasmosis in such patients may be difficult because signs and symptoms are not specific to toxoplasmosis. However, the condition should be considered as a diagnostic possibility because the infection is rapidly fulminant. Early treatment can improve the outcome. Reactivation of latent infection may occur in the setting of altered immunity, such as immunosuppressive therapy after a transplant or decreasing immune function in a patient with acquired immunodeficiency syndrome (AIDS). Clinical findings include any of the following: retinal disease, encephalitis, pneumonitis, myocarditis, or multiorgan disease.

Toxoplasma encephalitis (TE) is a common opportunistic infection in adult patients with AIDS (10% to 50% of those seropositive for Toxoplasma with CD4 counts of fewer than 100 cells/μL), and typically it results from reactivation of infection in the setting of poor cellular immunity. In contrast to its incidence in adults, TE is uncommon in children with AIDS, most likely because of the low incidence of T. gondii infection. TE may present with fever, headache, and focal neurologic signs. Disturbances of consciousness, confusion, motor impairment, seizures, impaired coordination, and focal weakness can occur. Usually, the course is subacute, but it may be fulminant and rapidly fatal. Generally, focal hypodense mass lesions with contrast enhancement are seen. Magnetic resonance imaging with enhancement is thought to be more sensitive in detecting lesions than is computed tomography. Often, lesions are found in the basal ganglia and corticomedullary junction of the cerebral hemispheres. Usually, multiple lesions are found, but a solitary lesion can occur. Marked edema often is present. In patients with disseminated toxoplasmosis in the brain, contrast enhancement may be absent. An image finding that is highly suggestive but only present in approximately 25% of cases is the asymmetric (eccentric) target sign. This lesion is characterized by a ring of contrast enhancement with a small eccentric nodule along the wall, giving it a target-like shape. In developing countries, where neuroimaging and other sophisticated techniques may not be readily available, HIV-positive individuals with suspected intracranial masses should be empirically treated for TE. The main differential diagnosis of TE is primary central nervous system (CNS) lymphoma, especially in the presence of a single lesion. Other possibilities include progressive multifocal leukoencephalopathy, bacterial abscess, cryptococcosis, cytomegalovirus infection, tuberculosis, and focal viral encephalitis. Patients with TE may have coexisting intracranial diseases. Another CNS manifestation of toxoplasmosis is myelopathy, which has been reported in patients with AIDS.

Although TE is rare in individuals with intact immune systems, a report reviewing TE in children found that 9 of 32 reported cases occurred in children who had no known immunodeficiencies. In eight of these immunocompetent children, TE occurred with primary infection (one unknown).

Pulmonary toxoplasmosis may be seen in patients with AIDS with decreasing CD4 cell counts (typically, fewer than 100 cells/μL) or other immunosuppressed patients (primarily reported in adults). The clinical picture of pulmonary toxoplasmosis is similar to that of pneumocystis, although usually the course is more rapid. Patients present with fever, cough, and dyspnea. Often, diffuse bilateral interstitial pneumonitis is seen on chest radiography (although variously a miliary pattern, multiple nodules, lobar infiltrates, and pleural effusions have been described). Often, patients have a high lactate dehydrogenase level. The organism may be found in a bronchoalveolar lavage aspirate and in biopsy specimen, or in both, using appropriate histologic staining techniques. Thorascopic or open lung biopsy may be required to make a diagnosis in some cases.

The risk of fetal infection with T. gondii increases, but the severity of disease decreases, with the gestational age at which acute maternal infection occurs. The onset of fetal infection by T. gondii also is delayed after an acute maternal infection. The rate of maternal-fetal transmission may be as low as 1% or less with maternal infection in the periconceptional period and can approach 90% or greater with maternal infection in late gestation. Average transmission rates are approximately 15% or less overall for the first trimester (rate rapidly increases after 10 weeks of gestation), 30% for the second trimester, and 60% for the third trimester and are a function of the increasing efficiency of the placenta. Studies of twins have shown that monozygotic twins have nearly identical infection rates but dizygotic twins do not, further underscoring the importance of the placenta in fetal infection.

Although rare, there have been case reports of congenital T. gondii infection when maternal infection was documented before conception. There has also been a case report of congenital infection that was thought to result from maternal reinfection during pregnancy. Congenital infection following chronic maternal infection is a more frequent occurrence in the setting of maternal immunosuppression, such as women receiving cytotoxic or corticosteroid therapy or women with HIV infection. In these women, symptoms of reactivated maternal toxoplasmosis may be absent, and the fetal transmission risk as a function of the degree of maternal immunosuppression is not known.

In the absence of treatment of the fetus with combination anti-Toxoplasma drugs, most fetuses infected early in pregnancy die in utero or in the neonatal period or have severe neurologic and ophthalmologic disease. Those infected in the second and third trimesters typically have mild or subclinical disease. The delay in maternal-fetal transmission appears to diminish with increasing gestational age. Although most fetal infections are likely to occur within several weeks, a delay of more than 3 months has been described.

Most newborn infants with congenital Toxoplasma infection have subclinical infection with no overt disease at birth, but indirect ophthalmoscopy may reveal ocular disease, and examination of the cerebrospinal fluid (CSF) and intracranial radiographic imaging may reveal abnormalities of the CNS. The New England Newborn Screening Program measures Toxoplasma-specific IgM on all newborn infants in Massachusetts and New Hampshire. Over a 6.5-year period beginning in 1986, 52 infants with congenital Toxoplasma infection were identified from 635,000 infants screened. Fifty of the 52 infants had normal routine newborn examinations, but after their T. gondii infection was identified through serologic screening, 48 had further testing that revealed abnormalities of either the CNS or the retina in 19 (40%). Most often, ocular lesions consisted of unilateral macular retinal scars, and CNS lesions were characterized by small, focal cerebral calcifications and mild to moderate elevations of CSF protein.

The principal clinical findings for infants and children with symptomatic congenital toxoplasmosis were described by Eichenwald in 1960. Such children were classified as having disease limited to the CNS and eyes (108 of 152) or more generalized (systemic) disease (44 of 152). The latter group evinced a lower incidence of CNS and ocular disease and a higher incidence of hepatosplenomegaly, lymphadenopathy, jaundice, and anemia. For all 152 infants, the incidences of neurologic and ocular abnormalities were as follows: intracranial calcifications, 37%; abnormal CSF profiles, 63%; chorioretinitis, 86%; convulsions, 41%; and hydrocephalus, 20%. Examples of brain and retinal lesions are shown in Figure 222.2.

Toxoplasma is the most common cause of infectious chorioretinitis in immunocompetent children. In the past, ocular toxoplasmosis was thought to be primarily a sequela of congenital infection; however, more recent data suggest it may more frequently follow postnatally acquired infection. For example, Southern Brazil has a very high seroprevalence rate, and most Toxoplasma infections are thought to be acquired postnatally, yet 18% of the population has chorioretinal scars. Similarly, 20 of 97 (21%) individuals infected during a 1995 waterborne outbreak of toxoplasmosis in British Columbia went on to develop Toxoplasmic chorioretinitis. Strain or host differences or inoculum size may account for the high rate of acquired chorioretinitis in some settings. Usually, chorioretinal disease associated with acquired toxoplasmosis involves one eye. Disease associated with reactivation from congenital infection may be bilateral, although many cases are unilateral.