Toxoplasma gondii

• Protozoan parasite associated with cats and raw beef mostly known for causing opportunistic infections and congenital infections

Microbiology

• Protozoan parasite
• Organized into twelve haplotypes

Epidemiology

• Zoonotic disease with worldwide distribution
• Modes of transmission
  • Ingesting tissue cysts in meat, or oocytes in food or water
  • Solid-organ transplantation, especially heart
  • Vertical or transplacental transmission
  • Case reports of lab-acquired needlestick transmission
  • Theoretical risk with blood transfusion
• Seroprevalence around 10-18% in Canada 12
  • As high as 60% in Nunavut, however 3
• There are large parts of South and Central America, as well as Pacific Islands, that have very high seroprevalence 4

Life Cycle

• The only definitive hosts are in the Felidae family, essentially housecats and their relatives
• Intermediate hosts are many, and include birds and rodents
• An infected cat sheds oocytes into the environment (for 1 to 3 weeks), where they spend 1 to 5 days sporulating
  • Each sporulated oocyst contains two sporocysts, and each sporocyst contains four sporozoites
• Intermediate hosts ingest the sporozoites, where they mature into tachyzoites
• Tachyzoites migrate to brain and muscle, where they encyst and become bradyzoites
• Bradyzoites are ingested by a cat, completing the life cycle

Pathophysiology

• Following ingestion, bradyzoites and sporozoites invade the small intestinal mucosa and develop into tachyzoites within the gut epithelium
• There, they insert themselves into monocytes and other nucleated cells
• Infected cells travel throughout the body, carrying the tachyzoite with them
• Infection triggers a Th-1 response

Clinical Presentation

Immunocompetent

• Asymptomatic in 80% of primary infections
• Symptoms, when they occur, can involve fever, cervical lymphadenopathy, myalgias, and weakness/fatigue
  • May mimic infectious mononucleosis
• Can also cause chorioretinitis
• Severity of illness depends in part on genotype, with strain II in North America and Europe being less severe
  • Rarely, unusual strains may cause pneumonitis, myocarditis, meningoencephalitis, or polymyositis, and can lead to death

Immunocompromised

• May be from primary infection or, more commonly, reactivation
• Unlike in immunocompetent people, it is always a serious infection in the immunocompromised
• Major risk factor is cellular immunodeficiency, as in HIV and some immunosuppressive medications
  • In HIV, beware with CD4 < 100
• Typically presents with CNS involvement as encephalitis
  • Symptoms include fever, headache, lethargy, incoordination, ataxia, hemiparesis, loss of memory, dementia, or seizures
• Can also present with pneumonitis, chorioretinitis, or myocarditis, and rarely involves essentially any other organ

Pregnancy

• As with other immunocompetent people, it is largely asymptomatic
• Only half of women can identify a significant risk factor 5
• Can cause fetal loss
• Risk of transmission to fetus is with parasitemia associated with primary infection, so women who are seropositive are not at risk of having a child with congenital infection

Congenital

• Can be acquired during maternal parasitemia associated with primary infection
  • Risk of transplacental infection of fetus is lowest in first trimester and highest in third
• 85% of infected babies are asymptomatic at birth; 15% symptomatic
  • Symptom severity increases is highest in first trimester and lowest in third
• Classic triad of chorioretinitis (most common), intraparenchymal cerebral calcifications, and hydrocephalus
• Others: thrombocytopenia, hepatitis, hepatosplenomegaly

Diagnosis

• Immunocompetent or pregnant women with primary infection: IgG/IgM serology, possibly with avidity testing for pregnant women
• Fetus, to rule out congenital infection following maternal primary infection: PCR of amniotic fluid
• Newborn, to rule out congenital infection: PCR of placenta or cord, or serology
• Immunocompromised patient, to diagnose cerebral or disseminated disease: PCR of blood, CSF, BAL, or tissue
• Patient with chorioretinitis: Parallel serologies from aqueous humour and serum, or PCR of aqueous humour

Serology

• IgM titres plateau within 1 month, and IgG within 2-3 months
• IgM is still detectable for months or years after infection
• IgM avidity testing can help to assess how recently the infection was acquired
  • Provides a measure of how tightly the antibodies bind, which is highest in early infection
  • A high avidity ratio (weak binding) suggests that the infection was acquired at least 4 months prior

Management

• First-line is a combination of pyrimethamine and sulfadiazine
  • Pyrimethamine (with folinic acid) is the backbone
  • The second agent is typically sulfadiazine, which can be replaced with clindamycin if needed
• Alternatives
  • TMP-SMX
  • Atovaquone

Dosing

• Encephalitis: pyrimethamine 200 mg load followed by 50-75 mg/day
• Infection during pregnancy: pyrimethamine 100 mg daily for 2 days followed by 25 to 50 mg/day

= HIV

• Pyrimethamine 200 mg PO once, followed by dose based on body weight:
  • Body weight ≤60 kg: pyrimethamine 50 mg PO daily + sulfadiazine 1000 mg PO q6h + leucovorin 10–25 mg PO daily (can increase to 50 mg daily or BID)
  • Body weight >60 kg: pyrimethamine 75 mg PO daily + sulfadiazine 1500 mg PO q6h + leucovorin 10–25 mg PO daily (can increase to 50 mg daily or BID)
• Alternatives
  • Pyrimethamine (leucovorin)c plus clindamycin 600 mg IV or PO q6h
  • TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg) (IV or PO) BID
  • Atovaquone 1500 mg PO BID + pyrimethamine (leucovorin)
  • Atovaquone 1500 mg PO BID + sulfadiazine
  • Atovaquone 1500 mg PO BID

Prevention

• Cats: hand hygiene after handling cat, use gloves and wash hands when handling litter, wash litter tray with hot >60ºC water, keep litter out of kitchen
• Soil: use gloves for gardening, wash hands after soil contact
• Water: avoid tap water in highly endemic countries, avoid ingestion of lake and river water
• Food: avoid raw oysters/clams/mussels, wash all vegetables/fruits/herbs, cook meat well down

Further Reading

• Epidemiology of and Diagnostic Strategies for Toxoplasmosis. Clin Microbiol Rev. 2012;25(2):264. doi: [10.1128/CMR.05013-11]