Toxoplasmosis

Essentials of Diagnosis

• Infection confirmed by isolation of Toxoplasma gondii or identification of tachyzoites in tissue or body fluids

Primary infection

• Fever, malaise, headache, sore throat

• Lymphadenopathy

• Positive IgG and IgM serologic tests

Congenital infection

• After acute infection of seronegative mothers, CNS abnormalities and retinochoroiditis seen in offspring

Infection in immunocompromised persons

• Reactivation leads to encephalitis, retinochoroiditis, pneumonitis, myocarditis

• Positive IgG but negative IgM serologic tests

General Considerations

• T gondii, an obligate intracellular protozoan, is found worldwide in humans and in many species of mammals and birds

• Definitive hosts are cats

• Humans are infected after ingestion of cysts in raw or undercooked meat, ingestion of oocysts in food or water contaminated by cats, transplacental transmission of trophozoites or, rarely, direct inoculation of trophozoites via blood transfusion or organ transplantation

Demographics

• Toxoplasma seroprevalence

  • Varies widely

  • Has decreased in the United States to 20–30% or less

  • However, it is much higher in other countries in both the developed and developing worlds, where it may exceed 80%

• In the United States, T gondii is estimated to infect 1.1 million persons each year, with resultant chorioretinitis developing in 21,000 and vision loss in 4800

• In the United States, an estimated 400 to 4000 congenital infections occur yearly

Primary infection

• After ingestion, T gondii infection progresses from the gastrointestinal tract to lymphatics, and then dissemination

• Most acute infections are asymptomatic

• About 10–20% are symptomatic after an incubation period of 1–2 weeks

• Typically present as mild, febrile illnesses that resemble infectious mononucleosis

• Nontender cervical or diffuse lymphadenopathy may persist for weeks to months

• Systemic findings may include

  • Fever

  • Malaise

  • Headache

  • Sore throat

  • Rash

  • Myalgias

  • Hepatosplenomegaly

  • Atypical lymphocytosis

• Severe manifestations are rare and include

  • Pneumonitis

  • Meningoencephalitis

  • Hepatitis

  • Myocarditis

  • Polymyositis

  • Retinochoroiditis

Congenital infection

• Fetal infection follows maternal infection in 30–50% of cases, but this risk varies by trimester:

  • 10–25% during the first trimester

  • 30–50% during the second trimester

  • 60% or higher during the third trimester

• Early fetal infections commonly lead to

  • Spontaneous abortion

  • Stillbirths

  • Severe neonatal disease, including neurologic manifestations

• Systemic findings include

  • Fever or hypothermia

  • Jaundice

  • Vomiting

  • Diarrhea

  • Hepatosplenomegaly

  • Pneumonitis

  • Myocarditis

  • Rash

• Retinochoroiditis and other sight-threatening eye lesions may develop

  • Retinochoroiditis presents weeks to years after congenital infection, commonly in teenagers or young adults

  • Uveitis is also seen

  • Disease presents with pain, photophobia, and visual changes, usually without systemic symptoms

  • Signs and symptoms eventually improve, but visual defects may persist

  • Rarely, progression may result in glaucoma and blindness

Infection in the immunocompromised person

• Reactivated toxoplasmosis occurs in patients with AIDS, cancer, or those given immunosuppressive drugs

• Reactivation also can occur in those with hematologic malignancies or treated with immunosuppressive drugs

• Encephalitis, with multiple necrotizing brain lesions

  • Most common manifestation in patients with advanced AIDS

  • Usually presents subacutely with fever, headache, altered mental status, focal neurologic findings, and other evidence of brain lesions

• Chorioretinitis and pneumonitis are less common manifestations in patients with AIDS

  • Chorioretinitis presents with ocular pain and alterations in vision

  • Pneumonitis presents with fever, cough, and dyspnea

• Toxoplasmosis can develop in seronegative recipients of solid organ or bone marrow transplants due to reactivation or, more rarely, transmission of infection

Identification of parasites

• Organisms can be seen in tissue or body fluids, although they may be difficult to identify

• Special staining techniques can facilitate identification

• Demonstration of tachyzoites indicates acute infection

• Cysts may represent either acute or chronic infection

• Polymerase chain reaction (PCR) can be used for sensitive identification of organisms in amniotic fluid, blood, cerebrospinal fluid (CSF), aqueous humor, and bronchoalveolar lavage fluid

Serologic diagnosis

• IgG antibodies are seen within 1–2 weeks of infection, and usually persist for life

• IgM antibodies peak earlier than IgG and decline more rapidly, although they may persist for years

• In immunocompromised individuals in whom reactivation is suspected,

  • A positive IgG assay indicates distant infection, and thus the potential for reactivated disease

  • A negative IgG argues strongly against reactivation toxoplasmosis

  • With reactivation in immunocompromised persons, IgM tests are generally negative

During pregnancy and in newborns

• Positive IgG with negative IgM is highly suggestive of chronic infection, with no risk of congenital disease unless the mother is severely immunocompromised

• A positive IgM test is concerning for new infection because of the risk of congenital disease

• In newborns, positive IgM or IgA antibody tests are indicative of congenital infection, although the diagnosis is not ruled out by a negative test

• Positive IgG assays may represent transfer of maternal antibodies without infection of the infant, but persistence of positive IgG beyond 12 months of age is diagnostic of congenital infection

• PCR of blood, CSF, or urine can also be helpful for early diagnosis of congenital disease

In immunocompetent individuals

• Individuals with a suggestive clinical syndrome should be tested for IgG and IgM antibodies

• Seroconversion, a 16-fold rise in antibody titer, or an IgM titer greater than 1:64 are suggestive of acute infection, although false-positive results may occur

• Acute infection can also be diagnosed by detection of tachyzoites in tissue, culture of organisms, or PCR of blood or body fluids

• Histologic evaluation of lymph nodes can show characteristic morphology, with or without organisms

In immunodeficient individuals

• CT and MRI scans typically show multiple ring-enhancing cerebral lesions, most commonly involving the corticomedullary junction and basal ganglia

• MRI is the more sensitive imaging modality

• Standard therapy is the combination of pyrimethamine (200-mg loading dose, then 50–75 mg [1 mg/kg] orally once daily) plus sulfadiazine (1–1.5 g orally four times daily), with folinic acid (10–20 mg orally once daily) to prevent bone marrow suppression

• Clindamycin

  • A first-line alternative for sulfadiazine

  • Dosage: 600 mg orally four times daily

• Another alternative is TMP-SMZ

• Pyrimethamine is not used during the first trimester of pregnancy due to its teratogenicity

• Spiramycin

  • Standard therapy for acute toxoplasmosis during pregnancy

  • Dosage: 1 g orally three times daily until delivery)

  • Decrease the risk of fetal infection

  • Reduces the frequency of transmission to the fetus by about 60%

Prognosis

Primary infection

• Symptoms may fluctuate, but most patients recover spontaneously within at most a few months

Prevention

• Prevention of primary infection centers on avoidance of undercooked meat or contact with material contaminated by cat feces, particularly for seronegative pregnant women and immunocompromised persons

• Irradiation, cooking to 66°C, or freezing to –20°C kills tissue cysts

• Thorough cleaning of hands and surfaces is needed after contact with raw meat or areas contaminated by cats

• Oocysts passed in cat feces can remain infective for a year or more, but fresh oocysts are not infective for 48 hours

• For immunocompromised individuals, chemoprophylaxis to prevent primary or reactivated infection is warranted