Toxoplasmosis

Essentials

• The most common latent protozoan infection in humans
• The infection is usually dangerous only in pregnancy or in an immunocompromised patient.
• The transmission is usually from cat faeces, soil, or inadequately cooked meat.
• Symptomatic disease is the consequence of a primary infection or the reactivation of a latent infection.

Causative agent

• Toxoplasma gondii is a parasitic protozoon belonging to sporozoa (Coccidia).
• Toxoplasma exists in three forms, all of which may infect humans: oocyst, tissue cyst and tachyzoite.

Epidemiology

• There are considerable geographic differences. The reasons are explained by differences in the cat population, climatic conditions, farming methods, hygiene, and cultural habits in regard to cooking food.
• In many countries the majority of fertile-aged women are IgG-seronegative and thus at risk for primary toxoplasma infection during pregnancy.
• For more information, see data from ECDC http://www.ecdc.europa.eu/en/toxoplasmosis, CDC http://www.cdc.gov/parasites/toxoplasmosis/epi.html and WHO http://www.who.int/bulletin/volumes/91/7/12-111732.pdf, as well as the results of a recent systematic review and meta-analysis http://www.nature.com/articles/s41598-020-69078-9.

Transmission

• The primary host of Toxoplasma gondii is the cat. Seroprevalence is higher in older cats than in younger ones. Feeding cats with raw food is also for them a risk factor for acquiring toxoplasma infection.
  1. Oocysts are excreted in feline faeces as the organism replicates in the cat's small intestine during an acute toxoplasm infection.
     • The oocysts remain infective in the nature even for months and may contaminate drinking water, soil or human food.
  2. Tachyzoites are rapidly replicated in the cells of the host during an acute toxoplasm infection (either primary infection or activation of a latent infection) and are spread to different organs via blood circulation.
     • A mother's primary toxoplasm infection during pregnancy may be vertically transmitted through the placenta to the foetus by tachyzoites. The risk of transmission is 30% on the average.
     • Primary infection in the mother poses a danger to the foetus, but a reactivation does not.
     • In rare cases, a tachyzoite infection may also be spread through blood transfusion or by a puncture injury.
  3. Tissue cysts are formed by the immune response of the host after a toxoplasm infection. They are found in the skeletal muscles, in the heart muscle and in the brain. They represent the latent form of a toxoplasm infection.
     • Transmission of tissue cysts may take place through uncooked or inadequately cooked meat Food and Environmental Risk Factors for Acute Toxoplasmosis in Pregnancy or, in rare cases, through organ transplantation.

Global importance

• The most common protozoan infection in humans. Prevalence correlates e.g. with the level of environmental and food hygiene and with climatic conditions.
• Symptomatic disease is a consequence of either a primary infection or the activation of a latent infection.
• The infection is usually dangerous only during pregnancy or in immunocompromised patients.
• Infection is usually spread through food - inadequately cooked meat or unwashed/unpeeled vegetables or fruits - originally contaminated by soil (feline faeces).

Symptoms

• Acquired infection is usually asymptomatic in a basically healthy patient.
• The incubation period of a symptomatic infection is 10-14 (-21) days.
• When symptoms exist, lymphadenopathy is the most common manifestation. Toxoplasma infection is the cause in 3-7% of cases of clinically significant lymphadenopathy.
• Fever, fatigue, night sweats, sore throat and muscle pain are the most common symptoms.
• Hepatosplenomegaly and maculopapular rash may also occur.
• Atypical lymphocytes may be found in the peripheral blood.
• In immunocompromised patients, the clinical manifestations are often severe. Patients may develop encephalitis, pneumonia or myocarditis, and the infection may be fatal. The clinical picture may sometimes be severe even in immunocompetent patients.
• Congenital toxoplasmosis is a generalized infection with symptoms of CNS inflammation.
  • The disease results from primary infection of the mother during pregnancy. The risk of transmission from mother to foetus is 10% in the first trimester and 70% in the third trimester of pregnancy.
  • Infection early in pregnancy usually results in severe disease.
  • The disease is chronic and causes visual and/or CNS defects with the years in 85-90% of the patients.
• In chronic active toxoplasmosis, symptoms and signs persist for months or even years. In these patients the parasite or its DNA can be detected in blood.
• Retinochoroiditis is the most common lesion in ocular toxoplasmosis (pictures 1 and 2). Toxoplasmic eye disease has also been reported in association with acute infection.

Diagnosis

• The diagnosis of primary infection is usually serological.
  • Toxoplasma-specific IgG and IgM antibodies are first determined from one serum sample (1-2 ml).
  • According to the result of the IgM test the avidity of IgG may be determined, and in infants, if needed, also IgA (special test, not available in all laboratories).
• Toxoplasma nucleic acid detection tests from the blood, cerebrospinal fluid, amniotic fluid or tissues can be performed if there are special indications. Serological testing is always the first-line examination.
• Diagnosis of congenital toxoplasmosis after birth usually requires several serum samples.

Treatment and prognosis , Management of Toxoplasmic Encephalitis in HIV-Infected Adults

• Toxoplasmosis will usually resolve spontaneously after the symptomatic period that may last from a few days to a few weeks. Treatment is indicated in
  • patients with severe infection
  • immunocompromised patients
  • pregnant women with primary infection
  • infants with congenital toxoplasma infection.
• Toxoplasmosis during pregnancy should always be treated in specialized care setting.
  • If toxoplasma nucleic acid detection test in the amniotic fluid is negative, the treatment consists of azithromycin 500 mg × 1 on 3 consecutive days. This is repeated during the following weeks at least 3 times.
  • If the infection has spread into the uterus (PCR +), a triple treatment is introduced: sulphadiazine (3 g/day), pyrimethamine (25 mg/day) and folinic acid (5 mg twice per week) in 3 weeks. Subsequently, azithromycin 500 mg × 1 is given as 3-day courses during the following 3 weeks. These cycles are alternated until delivery. The treatment prevents approximately 40-50% of infections.
• Pyrimethamine use is associated with risk of severe adverse effects (bone marrow toxicity).
• Pregnancy need not be interrupted if repeated foetal ultrasound is normal, toxoplasma-PCR from amniotic fluid is negative and antiparasitic treatment is given.
• The option of terminating the pregnancy should be restricted only to those primary infections where the foetus is diagnosed to be infected (PCR from amniotic fluid positive for toxoplasma) and ultrasonography reveals abnormal findings.
• The same drugs are used as alternating therapy in the treatment of congenital toxoplasmosis with doses suitable for a newborn infant.

Prevention