Page 100 - AIDSBK23C

Page 100

CRYPTOCOCCUS NEOFORMANS INFECTIONS

Cryptococcosis is a leading cause for fungal disease in persons infected with HIV. There
are four serotypes based on the capsular polysaccharide, glucuronoxylomannan (GXM): C.
neoformans var. grubii, C. neoformans var gattii, and C. neoformans var. neoformans. C. gattii
has been classified as a separate species. The organism C neoformans var. neoformans is
cosmopolitan, and bird droppings tend to play a major role in its distribution to urban settings.
In contrast, C neoformans var. gattii tends to occur in tropical and subtropical locations and is
found in decaying vegetation, particularly from eucalyptus trees. [450]
Non neoformans species of Cryptococcus are rarely reported as causes for infection, but
can cause disease in immunocompromised hosts, and most cases are due to Cryptococcus
laurentii and Cryptococcus albidus. Other occasional pathogens include Cryptococcus curvatus,
Cryptococcus humicolus, and Cryptococcus uniguttulatus. Clinical manifestations resemble
those of C neoformans infections. The most common sites of infection are the bloodstream
and CNS, followed by pulmonary sites and the skin, eyes, and gastrointestinal tract.[451]
Cryptococcus is a basidiomycetous yeast that exists in the environment in the sexual form
and produces hyphae with terminal basidiospores (chains of unbudded yeast). When the 3
micron basidiospores break off they become aerosolized and may be inhaled into the alveoli. An
infection is asymptomatic in most persons, but in persons with severe cell-mediated
immunodeficiency, the organism may enter the circulation and survive in vivo in a haploid,
asexual state, leading to disseminated disease. Cryptococcus may survive within human because
of a polysaccharide capsule that allows it to evade phagocytosis. In addition, a phenol oxidase
enzyme uses catecholamines as substrate to produce melanin, which accumulates in the cell wall,
and synthesis of catecholamines for neurotransmitters may predispose to involvement of the
central nervous system.[450]
About 6 to 10% of HIV-infected persons not on prophylactic therapy or antiretroviral
therapy have been shown to develop cryptococcal meningitis in developed nations. More than
three-fourths of cases occur when the CD4 count is less than 50/µL. Most infections are
acquired via the respiratory tract, where the major host defense mechanism is complement-
mediated phagocytosis by macrophages, with help from both CD4 and CD8 cells to inhibit
proliferation of cryptococcal organisms. Cryptococcosis may represent either primary infection
or reactivation of prior infection.[452] Though cryptococcosis is a major complication in adults
with advanced HIV infection, cryptococcal infections in children are relatively uncommon, with
a frequency of less than 1%.[453]
Involvement of the central nervous system and lung by Cryptococcus neoformans in
AIDS is similar to non-AIDS cases. In cases with dissemination, C neoformans has a wide
distribution, appearing in decreasing frequency in: lymph node, spleen, genitourinary tract, liver,
adrenal, and bone marrow tissue. Cutaneous dissemination may be seen in about 10% of cases,
appearing as molluscum-appearing skin lesions, and as osseous involvement in approximately
5% of cases. Cryptococcus neoformans is infrequently identified in gastrointestinal tract (Table
5).[450]
The most common clinical presentation of cryptococcosis is meningitis, seen in over 70%
of infections. The onset and course of cryptococcal meningitis can be rapid and severe, though
symptoms may develop over days to weeks. Sometimes only headache and altered mental status
are present. One of the best clinical means of diagnosis is examination of cerebrospinal fluid