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Congenital Toxoplasmosis

Historical Perspective

• In 1908, Nicolle and Manceaux described the parasite in the blood, spleen and liver of a North African rodent–gundi (Ctenodactylus gundi), due to its similar appearance as leishmania they named it Leishmania gondii.
• In 1909, Nicolle and Manceaux renamed the parasite as T. gondii.
• In 1937, Sabin & Olitsky described that Toxoplasma was an obligate intracellular parasite and could be passed onto laboratory animals by intracranial, subcutaneous, intraperitoneal inoculation of brain homogenates (The slurry of tissues and cells which results when cell structure has been mechanically disrupted). They have also suggested that ingestion of Toxoplasma contaminated tissue can result in Toxoplasmosis.
• In 1937 to 1940, Wolf and Cowen have described necrotic and granulomatous lesions on autopsy of a 3 day old infant's brain infected with Toxoplasma. They have also reported that the mothers were asymptomatic but carried antibodies against Toxoplasma and the possibility of congenital transmission was expressed.
• In 1940, Pinkerton and Weinman reported the first fatal case of Toxoplasmosis in an adult.
• In 1948, Sabin and Feldman developed a serological test to identify infected individuals by using antibodies specific to Toxoplasma, called the Sabin Feldman Dye test. The serological test when used in large population studies showed a high proportion of humans and domestic animals carried antibodies against Toxoplasma.
• In 1965, Desmonts described that ingestion of under-cooked and uncooked meat plays a role in the pathogenesis of Toxoplasmosis.
• In 1970, Dubley described the life cycle of the parasite and established that the cats are the definitive hosts and any warm blooded animal can be an intermediate host.

Epidemiology, Demographics

• It is estimated that 25 to 30% of the world's population is infected with Toxoplasma.
• Toxoplasmosis affects 500 to 5000 new borns every year.
• In United States 22.5% of the population above the of 12 is estimated to be infected by Toxoplasma and affects 1.1 million people every year.
• In United States 89% of women in the childbearing age are susceptible to have an acute infection and at risk for transmitting the parasite to the baby if the primary infection occurs during the getational period.
• In countries such as North America, Northern Europe and in Sahelian countries of Africa low seroprevalences of 10% to 30% are observed. In countries of Central and Southern Europe, tropical African countries and Latin America the seroprevalence is around 30 to 50%. This shows the variation within the countries and as well as between the countries.

Race

• The prevalence of Toxoplasmosis is higher in non-Hispanic black population and Mexican Americans than non-Hispanic white population.

Age

• A decreasing trend in prevalence is reported in the population of U.S born persons aged between 12 to 49 years; with 14% between the years 1988 to 1994, and 9% in the years 1999 to 2004. This trend is attributed to the improvement of hygienic conditions, changes in farming systems, the consumption of frozen meat, and the feeding of cats with sterilized food.
• The similar decreasing trend of seroprevalence is been reported in France and Netherlands.

Developing Countries

• In countries with poor hygienic measures and using unfiltered surface water for consumption reported higher seroprevalence rates. In these countries the childhood population is at a higher risk of acquiring the infection, the mean age is reported to be 15 years.

Diagnosis

Laboratory Findings

Principles and methods used for the diagnosis of congenital toxoplasmosis:

Principle	Detection	Method	Findings supporting the diagnosis of Toxoplasmosis
Toxoplasma specific humoral responses	IgG, IgM, IgA	Dye test, ELISA, ELISA-like assays,ISAGA, immunofluorescence, agglutination	Positive IgM after 5 days of life and in the absence of blood transfusions Positive IgA after 10 days of life Persistence of Toxoplasma IgG beyond 1 year of age
	IgG, IgM, and IgA to specific Toxoplasma antigen	Western blot	Presence of specific bands only seen in the newborn or bands with higher intensity than maternal ones for IgG and/or IgM and/or IgA in a reference laboratory
Toxoplasma nucleic acid amplification	DNA	PCR	Positive result in any body fluid (e.g: amniotic fluid, cerebrospinal fluid, peripheral blood, urine)
Immunohistochemistry of Toxoplasma specific antigens in tissue	Antigens	Immunoperoxidase	Positive result in any tissue(e.g., brain or other fetal tissue)
Visualization by microscopy	Visual identification of tachyzoites and/or cysts	Stains such as hematoxylin/eosin, Giemsa	Positive identification in a reference laboratory
Isolation of Toxoplasma	Whole live parasite	Inoculation in peritoneal cavity of mice	Detection of live cysts from any body fluid or tissue that has been inoculated in mice in a reference laboratory
Brain imaging	Brain calcifications Hydrocephaly Microcephaly	Ultrasound, CT, brain MRI	Findings can be suggestive but are not diagnostic of congenital Toxoplasmosis since other etiologies may result in similar findings
Retinal exam	Inflammation in choroidal and retinal layers	Ophthalmological exam	Retinochoroidal lesions can be highly suggestive or, at times, diagnostic of congenital Toxoplasmosis

Table adopted from Laboratory Diagnosis of Congenital Toxoplasmosis