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20 mm

Figure 26.21 Filobasidiella (Cryptococcus) neoformans in the Spinal Fluid of an Individual with Cryptococcal Meningitis India ink has been added to the fluid to outline the organism's capsule.

26.4 Fungal Diseases of the Nervous System 683

ficient in immunocompromised individuals, however. In some cases, the organisms continue to multiply, enter the bloodstream, and are then distributed throughout the body. The capsule is essential to pathogenicity, since non-encapsulated strains do not cause disease. Capsular material inhibits phagocytosis and migration of leukocytes. It also diffuses from the organism and neutralizes opsonins. Progressive infection and dissemination are much more likely to occur when a person's cell-mediated immunity is impaired, particularly in AIDS and certain cancers. Macrophage activation by immune lymphocytes, lacking in many immunodeficiencies, is essential for rapid phagocytic killing of C. neoformans. Meningoencephalitis is the most common infection outside of the lung, but organisms spread by the bloodstream can also infect skin, bones, or other body tissues. In meningoencephalitis, the organisms typically cause thickening ofthe meninges, sometimes impeding the flow of cerebrospinal fluid, thereby increasing the pressure within the brain. They also invade the brain tissue, producing multiple abscesses. ■ opsonins, pp. 383,399

Epidemiology

Cryptococcus neoformans is distributed worldwide in soil and vegetation but is especially numerous in soil where pigeon droppings accumulate. Infection is contracted by inhaling contaminated dust. For every case of cryptococcal meningoencephalitis, millions of people are infected by the organism without harm. Symptomatic infection is often the first indication of AIDS. Person-to-person transmission of the disease does not occur.

Prevention and Treatment

There is no vaccine or other preventive measure available. Treatment with the antibiotic amphotericin B is often effective, particularly if given concurrently with flucytosine (5-fluorocytosine) or newer oral antifungal medicines such as itraconazole. Amphotericin B must be given intravenously and the dose carefully regulated to minimize the toxic effects of the antibiotic, mainly against the kidneys. Since amphotericin B does not reliably cross the blood-brain barrier, it is often necessary to administer it through a plastic tube inserted through the skull into a lateral ventricle of the brain. Except in AIDS patients, treatment is successful in about 70% of cases. AIDS patients respond poorly to treatment, most likely because they lack T-cell-dependent killing of C. neoformans that normally assists the action of the antifungal medications. Unless their T-cell function can be restored by treatment, AIDS patients are rarely cured of their infection and must remain on antifungal medication for life. ■ antifungal medicines, p. 526

The main features of cryptococcal meningoencephalitis are summarized in table 26.9.

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