Toxoplasma gondii

Causative agent of toxoplasmosis

■ Toxoplasma gondii is the causative agent of a zoonosis that occurs worldwide with high prevalences (up to 80% depending on region and age). Humans are infected by ingesting oocysts excreted by the definitive hosts (cats) or by eating unprocessed meat containing Toxoplasma cysts. If a women contracts toxoplasmosis for the first time during pregnancy, diaplacental transmission of the pathogen to the fetus is possible with potential severe consequences (for example malformations, eye damage, clinical symptoms during childhood). There is, however, no risk to the fetus from mothers who had been infected before their first pregnancy and have produced serum antibodies (about 35-45 %). Latent infections can be activated by immunodeficiencies (e.g., in AIDS patients) and may result in cerebral or generalized symptomatic toxoplasmosis. Serological surveillance in pregnant women is important to prevent prenatal infections. ■

Occurrence. T. gondii occurs worldwide. The low level of host specificity of this organism explains its ready ability to infect a wide spectrum of warmblooded vertebrate species (for example humans, sheep, pigs, cattle, horses, dogs, cats, wild mammals, bird species). It is estimated that approximately one-third of the world population is infected with T. gondii, although prevalences vary widely depending on age and region. According to a seroepide-miological study in Switzerland (published in 1995) of 4000 persons aged one to 70, an average of 52 % was infected with seroprevalence rates in different age groups as follows: one to nine years: 24%, 20-39 years: 43%, and 40-70 years: 69%. Of 9000 pregnant women, 46% were infected. Women of childbearing age groups in other European countries showed either lower or higher seroprevalences. High prevalences were also observed in various animal species (see Epidemiology p. 514).

Parasite. Various strains of T. gondii differ in virulence and certain biological and genetic characteristics. The life cycle of T. gondii includes various stages:

■ Tachyzoites (endozoites) (Fig. 9.12a, b) are proliferative forms that reproduce rapidly within a parasitophorous vacuole in nucleate host cells by means of endodyogeny (endodyogeny: formation of two daughter cells from a mother cell by endogenous budding). The tachyzoites are sickleshaped (toxon: bow) cells about 4-7 im long and 2-4 mm wide. An apical complex is located at the anterior pole, consisting of serveal components, including the conoid (a conical structure of spirally arranged microtubuli), a pole ring complex, the rhoptries, and micronemes (Fig. 9.12b). The apical complex

— Toxoplasma gondii

— Toxoplasma gondii

Sporozoite Ultrastructure

Fig. 9.12 a Tachyzoites, b ultrastructure of a tachyzoite, c cyst with bradyzoites.

Fig. 9.12 a Tachyzoites, b ultrastructure of a tachyzoite, c cyst with bradyzoites.

contributes to parasite penetration into host cells. The nucleus is located in the posterior half of the cell. More recent investigations have revealed that Toxoplasma and several other apicomplexan protozoa (e.g., Plasmodium, Sar-cocystis) contain, in addition to the chromosomal and mitochondrial genomes, a further genome consisting of circular DNA (35 kb) localized in a special organelle called the apicoplast. This organelle, usually located anterior to the nucleus and close to the Golgi apparatus, is surrounded by several membranes and possesses outer and inner membrane complexes. There is evidence that the apicoplast has evolved from the plastids of endosymbiontic green or red algae. The function of the apicoplast remains uncertain but is indispensable for the host cell and may be a new and specific target for chemotherapy. Tachyzoites also multiply in experimental animals and cell cultures. This stage is highly labile outside of a host and usually does not survive the stomach passage following ingestion.

■ Bradyzoites (cystozoites) are stages produced by slow reproduction within the cysts (4-8 x 2-4 im). The cysts develop intracellularly in various tissues (see below), have a relatively resistant wall, grow as large as 150 im, and can contain up to several thousand bradyzoites (Fig. 9.12c). They have a long lifespan in the host. Humans and animals can be infected by peroral ingestion of meat containing cysts (Fig. 9.13).

■ Oocysts are rounded and encysted stages of the organism, surrounded by a resistant cyst wall, and are approx. 9 x 14 im in size. They are the final product of a sexual reproductive cycle in the intestinal epithelia of Felidae. They contain a zygote and are shed in feces (Fig. 9.13). Sporulation takes place

within two to four days, producing two sporocysts with four sporozoites each. Sporulated oocysts are infective for humans and animals.

Life cycle. The developmental cycle of T. gondii involves three phases: intestinal, external, and extraintestinal (Fig. 9.13).

■ The intestinal phase with production of sexual forms (gamogony) takes only place in enterocytes of definitive hosts. Only domestic cats, and several other felid species of little epidemiological significance, can function as definitive hosts for T. gondii. Only extraintestinal development is seen in intermediate hosts (pigs, sheep, and many other animal species) as well as in dead-end hosts (humans). Following primary infection of a cat with Toxoplasma cysts in raw meat, asexual reproductive forms at first develop in the small intestine epithelium, with sexually differentiated stages and oocysts following later. The oocysts are shed in feces after a prepatent period of three to nine days. When cats are infected with sporulated oocysts, the prepatent period is extended to 20-35 days because in these cases the intestinal development of Toxoplasma is preceded by an extraintestinal asexual reproduction (see below). Oocyst shedding lasts for only a few days to a maximum of three weeks, but can be highly intensive (up to 600 million oocysts per eat during the patent period!).

■ External phase. Oocysts excreted in cat feces sporulate at room temperature within two to four days, rendering them infective. Kept moist, they remain infective for up to five years and are not killed by standard disinfectant agents. They die within a few minutes at temperatures exceeding 55 °C.

■ Extraintestinal phase. This phase follows a peroral infection with oocysts or cysts and is observed in intermediate hosts (dogs, sheep, pigs, other vertebrates, birds) and dead-end hosts (humans), as well as in the definitive hosts (cats). Starting from the intestine, the Toxoplasma organisms travel in blood or lymph to various organs and multiply in nucleate host cells, especially in the reticulohistiocytic system, in musculature, and in the CNS. Repeated endodyogenic cycles produce as many as 32 individual daughter cells in the expanding host cell before it bursts. The tachyzoites thus released attack neighboring cells.

These processes result in focal necroses and inflammatory reactions in affected tissues. Generalization of the infection can lead to colonization of the placenta and, about three to four weeks later, infection of the fetus. Cysts that elicit no inflammatory reactions in the near vicinity are produced early in the course of the infection. Such cysts (tissue cysts) are found above all in the CNS, in the skeletal and heart muscles as well as in the retina, the uterine wall, and other organs. They can remain viable for years without causing noticeable damage to the host.

— Toxoplasma gondii: Life Cycle -

— Toxoplasma gondii: Life Cycle -

Toxoplasma Cell Stages

Fig. 9.13 a Development in the definitive host (cat): intestinal phase with production of sexual forms: 1 Toxoplasma that has penetrated into a small intestine epithelial cell; 2 asexual reproductive stage with merozoites (can continue for several generations). The arrow indicates that an extraintestinal cycle precedes the enteral cycle when a cat is infected with oocysts; 3 production of sexual forms (gamogony) and formation of the zygote; 4 oocyst.

b External phase with sporogony: 5 unsporulated oocyst, shed in cat feces; 6 sporulated oocyst with two sporocysts each containing four sporozoites. c Development in an intermediate host (mammals, birds, humans): extraintestinal phase with only asexual multiplication of parasites; 7 sporozoite released in organism following oral ingestion of oocysts; 8a human infection; 8b infection of various animal species; 9 asexual reproductive stages (tachyzoites) in a somatic cell; 10 free tachyzoite; 11 cyst with bradyzoites in musculature; 12a infection of a dog with Toxoplasma cysts in animal meat; 12b infection of a human with Toxoplasma cysts; 13 infection of cat with infective stages of cysts in meat or with oocysts.

Immunity. Various Toxoplasma antigens induce humoral and cellular immune responses which, following a primary infection, result in antibody production and inhibition of tachyzoite multiplication. Toxoplasmas then "escape" from the immune defense system by encysting (immunoevasion). This enables them to persist in a latent state for many years in immunocom-petent hosts, at the same time maintaining an immune status that confers protection from new infections due to the continuous presentation of antigens.

The relevant immune defense mechanisms include mainly cellular mechanisms and production of IFNy. Bradyzoites can also migrate out of cysts (without cyst rupture), are then, however, locally inactivated in immunocompetent persons, sometimes leading to formation of satellite cysts. In cases of cellular immune deficiency, this control system is lacking and the latent infection progresses to become an acute, manifest toxoplasmosis. Similarly, latent Toxoplasma infections in AIDS patients are usually activated and turn symptomatic when the CD4+ cell count falls below 200/il.

Pathogenicity and clinical manifestations. Focal necrotic, inflammatory and immunopathological processes are the basis of the pathogenesis and varied clinical manifestations observed in toxoplasmosis. Cases are differentiated as to time of acquisition, i.e., postnatal and prenatal infections.

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Responses

  • edda
    Who does toxoplasma affect?
    5 years ago
  • Markku
    What is the causative agent of taxoplasma gondili?
    5 years ago
  • sara
    How is toxoplasmosis related to microbiology?
    4 years ago

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