Toxoplasmosis

Disease caused by the parasitic protozoan Toxoplasma gondii that is prevalent worldwide and is found in many different intermediate hosts (fish, amphibians, reptiles, birds and mammals). Approximately 33% of domestic animals and humans worldwide present subclinical toxoplasmosis. Cats (and other felines) are the definitive hosts (where the parasite completes its cycle).

Life cycle

Extraintestinal or parenteral cycle

Occurs in intermediate hosts and in cats. Parasites ingested in the form of sporulated oocysts (sporozoites) or from infected tissues (bradyzoites) invade the mesenteric lymph nodes and from there spread to a wide variety of cells in which they multiply (tachyzoites). These parasitized cells break down and the released parasites invade new cells. As antibody synthesis increases, tachyzoites transform into bradyzoites and form cysts, which can remain in the host for its entire life, since they are immune to antibodies and are less susceptible to being destroyed by proteolytic enzymes. They are mainly located in muscle, nervous tissue and viscera.

Entero-epithelial or intestinal cycle

Only cats. A preliminary stage of entero-epithelial replication starts when a cat ingests tissue containing bradyzoites (or sporulated oocysts). This is followed by a gametocyte stage (zygote), eventually leading to oocyst formation.

After ingestion of cysts with bradyzoites, oocysts are shed in the faeces within 3-10 days. Shedding continues for 1-2 weeks. If the cat ingests tachyzoites, it may take 19 days for oocysts to be shed. If infection is due to sporulated oocysts, the prepatent period usually lasts more than 20 days, and oocyst shedding lasts for several weeks.

Only 16%-20% of cats that ingest tachyzoites or sporulated oocysts shed oocysts in their faeces. Nearly all (97%) of cats that ingest tissue cysts (bradyzoites) are oocyst shedders. Oocysts shed in faeces sporulate to an infective stage within 1 and 5 days, depending on ambient temperature, and under appropriate conditions remain viable in the environment for more than 18 months.

Symptoms

After infection by T. gondii, the animal usually becomes a clinically silent carrier. The degree of involvement will depend on the age of the animal, its immune status, the virulence of the parasite, and the form of infection. Clinical symptoms are caused by cellular necrosis (rupture of cells infected with tachyzoites) associated with delayed hypersensitivity reactions in the host and an immune response mediated by the formation of immune complexes (vasculitis).
The first organ involved in the initial phase of infection is usually the liver, accompanied by lymph and lung tissue. As the immune system develops antibodies, the infection enters a chronic subclinical phase, although it can be reactivated if the host become immunoexpressed.

1. Definitive host
   In general, multiplication of the parasite does not cause clinical signs, except in kittens a few weeks old, which may present diarrhoea.
2. Intermediate hosts
   Prenatal infection: due to intrauterine infection in pregnant females not previously exposed to the parasite. Kittens may be stillborn or die before weaning due to inflammation of the liver, lungs, and central nervous system. Female dogs miscarry, and the puppies that survive have diarrhoea, respiratory disorders, ataxia, and lesions in the central nervous system. Humans are most susceptible to the parasite in the third trimester of pregnancy.

Infections early in pregnancy cause infertility and miscarriage, while in late infections the child may be born with neurological manifestations. Only 30%-40% of infections during pregnancy are transmitted to the foetus.

• Acute postnatal infection: presents as a rapidly progressing disseminated infection that affects healthy adult individuals who ingest large quantities of oocysts or bradyzoites, and also affects newborns, or immunoexpressed individuals. In these cases, the parasite causes severe pulmonary symptoms, fever and gastrointestinal symptoms. It usually causes hepatitis, myositis, and sometimes myocarditis, and can cause death. Dogs (particularly older animals) can present neurological symptoms similar to those caused by Neospora caninum.
• Chronic postnatal infection: due to mild exposure to the parasite or reactivation of a latent infection due to immunodepression. In the latter case, lesions usually appear in the central nervous system and eyes.

Interpretation of laboratory tests

General Tests

• Complete blood count. Acute infection - Variable, normal or non-regenerative anaemia. Leucocytosis, neutrophilia, lymphocytosis, monocytosis and eosinophilia. In cats, the disease may progress to leucopaenia with absolute lymphopaenia, neutropaenia, eosinopaenia and monocytopaenia. Leucocytosis often occurs during the recovery phase.
• Biochemistry. Increased GPT and GOT due to hepatic and muscular necrosis, accompanied in cats by increased TBIL due to cholangiohepatitis and secondary hepatic lipidosis. In dogs, ALP is also increased due to hepatic necrosis/
  Increased lipase and amylase if the pancreas is affected, and increased CPK due to muscle necrosis.
• Serum proteins. In acute infection, usually hypoproteinaemia and hypoalbuminaemia. Hyperglobulinaemia is common in chronic infection in cats.

Specific tests

• Serology. Determination of immunoglobulins by IIF, ELISA or agglutination (MAT: modified agglutination test).
• Symptomatic dogs or cats. Elevated IgG titres (>= 1/1024 on IIF) in cats are associated with active infection. If the titre is negative, low or moderate, a new titration is required within 2 weeks. Significant subsequent increases (four times the initial value) indicate an active infection. IgM in addition to IgG can also be determined. Elevated IgM together with low or negative IgG indicates a recent infection (IgM appears 7-10 days post-infection and decreased at 3 weeks while IgG appears at 2 weeks and can remain elevated indefinitely). Negative or very low IgM with moderately elevated IgG indicates chronic infection that probably does not cause toxoplasmosis. Presence of the disease could be confirmed with new IgG determination after 2 weeks. Negative IgM and IgG values indicate that the animal has not been exposed to the parasite.
• Asymptomatic cats (screening). Negative IgM titres with positive IgG in a single test or stable IgG levels in two consecutive tests performed 2 weeks apart indicate chronic infection. These cats are highly unlikely to be shedding oocysts and equally unlikely to become ill from re-exposure to the parasite and start shedding oocysts.
  A negative IgM titre with negative IgG in a single analysis or a negative IgG titre in two consecutive analyses performed two weeks apart indicates that that the animal has not been exposed to the parasite, so the cat is at risk of infection.
• Coprological examination. This is the most reliable method of determining whether there is a risk of the parasite being transmitted from the cat to humans. The infected cat will generally only shed oocysts during the first 5-14 days following primary infection, and serum antibody levels are not detectable during this time.
• PCR in blood and biological fluids. PCR is used to identify T. gondii in biological samples. Its clinical usefulness is questionable, because presence of the parasite does not always guarantee that it is responsible for the pathology.
• Analysis of cerebrospinal fluid and aqueous humour. In dogs and cats with toxoplasma-induced encephalomyelitis and uveitis, increased protein and leukocytes are observed in the CSF and aqueous humour, respectively. In some cases specific antibodies can be found.
• Cytology/biopsy. In certain cases, and during the acute phase of the disease, the parasite can be detected in body fluids (pleural and peritoneal fluid in animals with ascites or pleural effusion, and more rarely in blood, urine and CSF).

Health measures

• In addition to ingestion of oocysts, the most common source of infection for humans is meat containing T. gondii tissue cysts.
• Oocysts recently shed in faeces are not infectious until they sporulate (1 to 5 days). The sand in the litter box should be changed every 1-2 days.
• Cats should be prevented from eating raw meat or small prey as far as possible.
• Pregnant women and immunoexpressed individuals should not handle the cat’s litter box. They should avoid coming into contact with unknown cats
• Only eat well-cooked meat, wash hands after handling raw meat.
• Reduce gardening as much as possible (contact with soil contaminated by oocysts).

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