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BACKGROUND AND CLINICAL INFORMATION: Head

Infectious agent: Toxoplasma gondii is an intracellular parasite, remarkably, can invade and multiply inside most mammalian cell types nonselectively. It can circumvent the immune responses and allow it to survive indefinitely in the host.

Life cycle: The definitive host is domestic cats. The sexual phase of the life cycle is in cats. Cysts are excreted in the feces of cat. Other animals, including human, are incidental hosts. Human acquires infection either by eating not thoroughly cook parasite infested meat or from contaminated feces of cat. Tachyzoites (cell-invasive proliferating form), and tissue cysts (containing bradyzoites, may contain up to 3000 bradyzoites each) are found in human tissue. Oocysts are only found in cats.

Incidence: A large number of people worldwide are infected by Toxoplasma, but most of these cases are subclinical. Most frequently seen in immunosuppressed host and comprised one of the commonest opportunistic infection of the CNS.

Clinical spectrum: most human infections with T. gondii are asymptomatic. Both immunocompetent and immunocompromised hosts can be affected. Abscess formation in common in HIV infected patients. Usually the have a necrotic center surrounded by granulomatous lesions. Less frequently, toxoplasmosis may present as an encephalitis with microglial nodules in both gray and white matter accompanied by gliosis. The leptomeninges may also be involved. When the nervous system is infected, the specrtum includes:

Meningoencephalitis during primary infection in an immunocompetent host
Encephalitis and retinochoroiditis as a result of transplacental infection of the fetus
Retinochoroiditis associated with primary infection or reactivation of an earlier infection
Intracerebral mass lesions or encephalitis in immunocompromised hosts. Anatomic locations: Multiple bilateral abscesses appearing as ring-enhancing lesions in the brain.

Clinical features, congenital type:

Ranges from asymptomatic or subclinical infection to severe, necrotizing encephalitis and systemic infection. The typical triad includes hydrocephlus, cerebral calcification, and retinochoroiditis (blindness). The CNS appears to be preferentailly infected. Despite widespread parasitemia, encephalitis may be the only manifestation. Combination of encephalitis and generalized systemic involvement are also seen.
It may progress slowly so that it is not noted at birth but causes mental deterioration in an infant who seems normal at birth. Signs of infection at birth usually indicate severe infection that has already caused significant neurologic damage.
The principal clinical findings include convulsions, retinochoroiditis, abnormal CSF, and anemia. Because of the ventriculitis, the hypothalamus is frequently involved and, therefore, hypothalamic dysfunctions including wide fluctuations of body temperature is common.
Retinochoroiditis is very common in infants with symptomatic congenital toxoplasmosis. They are typically bilateral. Very early infection will result in microphthalmos. Nystagmus is frequent. Iris and capillary muscle dysufnction, strabismus, and cataract are also seen. Fundoscopic examination reveals lesions most commonly in the posterior portion of the eyes and the macular region is frequently affected.
The sequalae of congenital toxoplasma encephalitis include hydrocephalus, microcephaly, seizure disorders, severe psychomotor retardation.
Pathogenesis: Immunity to Toxoplasma depends primarily on cellular immunity, which in the neonate is immature and not transferable between mother and fetus. When a pregnant woman is ingected, there will be parasitemia. Tachyzoites can cross the placenta and infect the fetus. There is wide dissemination of the organisms with multiple manifestation including pneumonia, myocarditis, myositis, hepatitis, and encephalitis.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head

Organism: Toxoplasma within cysts may resemble Leishmania, Trypanosoma, Sarcocystis, or Besnoitia resemble Histoplasma, Pneumocystis. Because of the persistence of the cysts, demonstration of cysts in the absence of tissue reactions does not prove that an active infection is taking place. [Figure]

Primary infection in immunocompetent host: most patients are asymptomatic. The most frequent manifestation is lymphadenopathy. Rarely, a fatal infection can occur. Extrneural involvement is more severe than congenital toxoplasmosis. CNS pathology includes nonspecific changes such as gliosis. Both cysts and tachyzoites can be seen. Indolent, localized, necrotizing granulomatous reaction may be seen. Extensive necrosis that is typically seen in immunocompromised patients is not a prominant.

Infection in immunocompromised host: typically, there are necrotic foci of variable size, often being large, and characteristically surrounded by acute inflammatory cell infiltration. Some are also surrounded by granulomatous reation. The demarcation of the necrotic foci from the surrounding tissue is variable from poor to chronic abscess like. Viable cysts are typically seen in the peripheral and viable tissue. Dead cyst appearing as bright large pink balls are frequently noted in the necrotic foci. These balls are suggestive but not diagnosis for toxoplasma infection. Immunostaining is very helpful for identification of cysts.

Congenital retinochoroiditis: primary lesions usually begin in the retina, characteristically near the posterior pole of the eye, with vitreous and choroid pathology being secondary phenomena. There is inflammation, disorganization and disruption of the retinal layers with undermining and destruction of retinal supporting and neural tissues. Retinal cells may be displaced. In the later stage, there is fibrosis and gliosis.

Congenital toxoplasmic encephalomyelitis:

Acute or subacute form: This is characterized by multiple granulomatous inflammatory lesions with necrotic cores. They are found through out the brain but predominantly in periventricular areas and in the meninges, where inflammation may be severe. Perivascular inflammatory cell infiltrations are also noted. The gray and white matter as well as the nerve roots can all be affected. Vasculitis with intimal proliferation, thrombosis, and tachyzoites in intimal endothelial cells may also be seen.

Chronic form: This is characterized by cortical atrophy and ventricular dilatation that may be asociated with cystic cavities. Porencephaly and schizencephaly may be present. Calcified foci may be found throughout the brain, particularly around the ventricles.

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Background Histopathology & Immunohistochemistry