What is toxoplasmosis?

Toxoplasmosis Overview

Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii, an obligate intracellular parasite with worldwide distribution that infects approximately one-third of the human population and can cause devastating consequences for fetuses, immunocompromised patients, and occasionally immunocompetent individuals. 1

The Causative Organism

• Toxoplasma gondii is an apicomplexan protozoan parasite capable of infecting any nucleated cell in any warm-blooded animal 2
• The parasite has three main clonal lineages (types 1,2, and 3) in North America and Europe, with atypical strains frequently reported in the Americas 1
• Members of the cat family (Felidae) serve as the definitive hosts, while humans and other warm-blooded animals are intermediate hosts 1

Routes of Transmission

The primary routes of human infection are oral ingestion of oocysts or tissue cysts, with oocysts being the predominant transmission route in the United States (78% of pregnant women with acute infection showed serologic evidence of oocyst transmission). 1

Major Transmission Pathways:

• Contaminated soil/cat feces: Touching mouth after gardening, cleaning cat litter boxes, or consuming unwashed fruits/vegetables contaminated with oocysts from cat feces 1
• Undercooked meat: Eating inadequately cooked meat (especially pork, lamb, or venison) containing tissue cysts, or cross-contamination from raw meat to kitchen surfaces 1
• Other routes: Drinking unpasteurized milk or contaminated water, organ transplantation, blood transfusion (rare), or laboratory accidents 1, 3
• Vertical transmission: Transplacental transmission from acutely infected mother to fetus during pregnancy 1, 4

Critical Food Safety Parameters:

• Freezing below -20°C (-4°F) for at least 48 hours inactivates tissue cysts 1
• Thorough cooking to 63°C (145°F) for whole cut meat, 71°C (160°F) for ground meat, and 74°C (165°F) for poultry kills the parasite 1
• Microwave cooking and chilling at 5°C for 5 days are insufficient to kill tissue cysts 1

Epidemiology in the United States

• The seroprevalence among women of childbearing age (15-44 years) has declined dramatically: 15% (1988-1994), 11% (1999-2004), and 9.1% (2009-2010) 1
• Among US-born women specifically, rates dropped from 13% to 6% over the same period 1
• Approximately 91% of US women of childbearing age remain susceptible to Toxoplasma infection 1
• People born outside the United States have significantly higher seroprevalence (25.1% vs 9.6%) 1
• Hispanic individuals have higher rates than non-Hispanic whites (15.8% vs 10.2%) 1

Disease Burden:

• Toxoplasmosis is the second leading cause of death and fourth leading cause of hospitalizations from foodborne illnesses in the United States 1
• Over an 11-year period (2000-2010), 789 toxoplasmosis-associated deaths occurred, with cumulative productivity loss of $815 million 1
• An estimated 400-4,000 cases of congenital toxoplasmosis occur annually in the United States 5

Clinical Manifestations

In Immunocompetent Adults:

• Most infections (approximately 50%) are asymptomatic and do not exhibit conventional risk factors 1, 6
• When symptomatic, acute infection may present as a febrile illness resembling mononucleosis 1

Congenital Toxoplasmosis:

Recent US data from the National Reference Laboratory showed that 85% of 164 infants with congenital toxoplasmosis were severely affected: 92% had chorioretinitis, 80% had intracranial calcifications, 68% had hydrocephalus, and 62% had all three manifestations. 1

• The risk of maternal-fetal transmission in untreated women is 29% overall (95% CI: 25-33%) 1
• Transmission risk increases dramatically with gestational age: 2-6% in first trimester, 44% at 26 weeks, and 71% at 37 weeks 1, 4
• However, disease severity is inversely related to gestational age—early infection causes the most severe fetal damage, including miscarriage 4
• Most infected newborns are asymptomatic at birth but develop late sequelae including retinitis, visual impairment, and neurologic damage 4

Three Mechanisms of Congenital Transmission:

1. Primary acute infection in a previously seronegative mother during pregnancy or within 3 months before conception 1
2. Reactivation in a previously immune but severely immunocompromised pregnant woman 1, 4
3. Reinfection with a new, more virulent strain in a previously immune mother 1, 4

In Immunocompromised Patients:

• In HIV-infected individuals, toxoplasmosis causes severe manifestations including encephalitis, pneumonitis, hepatitis, and cardiomyopathy 3
• CNS toxoplasmic encephalitis is uncommon in HIV-infected children (<1% of pediatric AIDS cases), with most cases representing congenital infection 1
• Transmission through blood transfusion is particularly concerning for immunocompromised recipients 3

Risk Factors for Acute Infection

Approximately 61% of women who gave birth to infants with congenital toxoplasmosis had no exposure to cat litter or raw meat, and 52% had no acute febrile illness during pregnancy, indicating that conventional risk factors are absent in many cases. 1

Documented Risk Factors in US Studies:

• Eating raw ground beef, rare lamb, or locally produced cured/dried/smoked meat 1
• Working with meat 1
• Eating raw oysters, clams, or mussels (novel risk factor) 1
• Drinking unpasteurized raw goat milk 1
• Having ≥3 kittens in the household 1
• Drinking untreated water (major source of community outbreaks in Canada and Brazil) 1

Prevention Strategies

Primary Prevention:

• Cook meat to safe temperatures: 63°C (145°F) for whole cuts, 71°C (160°F) for ground meat, 74°C (165°F) for poultry 1
• Freeze meat below -20°C (-4°F) for at least 48 hours before consumption 1
• Peel or thoroughly wash all fruits and vegetables before eating 5
• Clean cooking surfaces and utensils after contact with raw meat 5
• Pregnant women should avoid changing cat litter or use gloves and wash hands thoroughly afterward 5
• Do not feed raw or undercooked meat to cats and keep cats indoors 5
• Avoid drinking unpasteurized milk or untreated water 1

Secondary Prevention (Prenatal Treatment):

• Early antibiotic treatment within 3 weeks of maternal seroconversion can reduce transmission risk by 52% 4
• Prompt initiation of prenatal treatment decreases mother-to-child transmission and ameliorates severity of clinical manifestations 1
• Treatment should begin as soon as acute maternal infection is suspected, ideally confirmed by reference laboratory testing 1

Diagnostic Considerations

• Serologic tests include Toxoplasma IgG, IgM, IgA, IgE, IgG-avidity, and differential agglutination 1
• IgM positivity alone does not confirm recent infection, as it can persist for months to years 4
• Serial testing is needed to confirm acute versus chronic infection; single-point testing is often insufficient 4
• Samples should be sent to a reference laboratory when clinical suspicion exists to avoid delays in diagnosis and treatment 1
• Fetal ultrasound should monitor for ventriculomegaly, hydrocephalus, intracranial calcifications, or growth restriction 4

Treatment Considerations

• Pyrimethamine-based regimens are standard for toxoplasmosis treatment 7
• Concurrent administration of folinic acid (leucovorin) is strongly recommended when treating toxoplasmosis in all patients to prevent hematologic toxicity 7
• In patients receiving high-dose treatment, semiweekly blood counts including platelet counts should be performed 7
• Congenitally infected children should be treated beginning in utero and continuing through the first year of life 6
• In HIV-infected children, lifelong suppression is indicated following treatment for toxoplasmosis to prevent recurrence 1

Common Adverse Effects:

• Anorexia and vomiting (minimized by taking medication with meals) 7
• Megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia at doses used for toxoplasmosis treatment 7
• Hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis, particularly when combined with sulfonamides 7

Critical Drug Interactions:

• Concomitant use with other antifolate drugs (sulfonamides, trimethoprim-sulfamethoxazole, proguanil, zidovudine, methotrexate) increases risk of bone marrow suppression 7
• Mild hepatotoxicity reported when lorazepam and pyrimethamine are administered together 7

Special Populations

Pregnancy:

• Pyrimethamine is Pregnancy Category C and should only be used if potential benefit justifies potential risk to the fetus 7
• The drug has shown teratogenic effects in animal studies (cleft palate, microphthalmia, meningocele) at doses 2.5-5 times the human treatment dose 7
• Women of childbearing potential taking pyrimethamine should be warned against becoming pregnant 7

Immunocompromised Patients:

• In HIV patients with brain mass and negative toxoplasma serology, proceed directly to brain biopsy rather than empiric anti-toxoplasma therapy, as primary CNS lymphoma is more likely 8
• Provide PCP prophylaxis if CD4 count <200 cells/µL 8
• Initiate or optimize antiretroviral therapy immediately regardless of diagnosis 8