Cryptococcosis



Cryptococcosis


Stephanie H. Stovall

Steven C. Buckingham



Cryptococcosis is a mycosis that predominantly affects the lung, central nervous system (CNS), skin, and bone. Nineteen species of the genus Cryptococcus have been identified, but only C. neoformans is pathogenic in humans. This organism was identified in 1894, and its pathogenic role in human CNS disease was discovered shortly thereafter. The majority of infections caused by C. neoformans occur in immunocompromised individuals.


MICROBIOLOGY

Cryptococci are nonfermenting, round to oval, aerobic yeasts of irregular sizes, averaging 4 to 8 μm in diameter. Reproduction occurs by budding with a narrow neck between parent and daughter cells. C. neoformans is surrounded by an antiphagocytic polysaccharide capsule (Fig. 212.1). The five capsular serotypes of this organism are grouped into two varieties: C. neoformans variant neoformans (serotypes A, D, and AD) and C. neoformans variant gatii (serotypes B and C).


EPIDEMIOLOGY

The two varieties of C. neoformans have distinct epidemiologic and pathogenic characteristics. C. neoformans variant neoformans causes disseminated infections, especially in individuals with impaired cellular immunity, and has a particular tropism
for meninges. It is found in soil throughout the world, often in association with weathered bird droppings. C. neoformans variant gatii is associated with focal infections, particularly of the brain, in immunocompetent persons. It is endemic to regions of the world in which the red river gum tree, Eucalyptus camaldulensis, is found, including Australia, South America, Southeast Asia, and southern California. The remainder of this chapter will concern itself with C. neoformans variant neoformans unless otherwise stipulated.






FIGURE 212.1. India ink preparation of cerebrospinal fluid showing budding yeast with prominent capsule.

Cryptococcosis is most often found in patients with acquired immunodeficiency syndrome (AIDS). One study reported that 89% of cryptococcosis cases occur in persons infected with human immunodeficiency virus (HIV). Infection with C. neoformans occurred in 5% to 15% of adults with AIDS prior to the widespread use of highly active antiretroviral therapy (HAART). Since the advent of HAART, the incidence of cryptococcosis has decreased by more than 50% in the adult population. Cryptococcosis was unusual in HIV-infected children even prior to the routine use of HAART. Among 473 HIV-infected children followed from 1987 to 1995, only four developed cryptococcosis (average annual incidence, 0.10%). Cryptococcal infection occurs rarely in children who are immunocompromised for reasons other than HIV infection (e.g., cancer chemotherapy or systemic lupus erythematosus).


PATHOGENESIS

Cryptococci are inhaled and gain access to the body via the lower respiratory tract, where the initial host response relies on phagocytosis of the organisms. The principal virulence factor of C. neoformans is the polysaccharide capsule, which prevents phagocytosis and down-regulates the host immune response by stimulating suppressor T cells. Opsonization by anticapsular antibodies or complement facilitates ingestion of cryptococci by phagocytic cells. Neutrophils kill the ingested organisms effectively, but macrophages are ineffective unless they are activated by interferon-gamma from helper T cells. Natural killer cells also appear to play a role in the host response. If the initial host response fails to contain the infection, the pulmonary fungal burden will increase and hematogenous dissemination to other organs may occur subsequently.

Individuals with deficient cellular immunity can rapidly develop disseminated disease after infection with C. neoformans. The CNS is the organ system most frequently affected in disseminated disease. There is frequently minimal inflammatory response, especially in the immunocompromised individual; in fact, the cerebrospinal fluid (CSF) leukocyte count is often only minimally elevated. Cryptococci may also spread to extrapulmonary sites in presumably immunocompetent hosts; in these individuals, the immunologic response is characterized by formation of granulomas, termed cryptococcomas, which are composed of multinucleate giant cells.


CLINICAL MANIFESTATIONS

Initial pulmonary infection is typically asymptomatic in immunocompetent hosts, though immunocompromised patients may experience cough, hemoptysis, chest pain, and significant constitutional symptoms. Radiographic findings in symptomatic patients range from solitary or multiple pulmonary nodules to diffuse infiltrates.

The most common manifestation of cryptococcal disease is meningitis, especially in the immunocompromised host. Symptoms of cryptococcal meningitis include fever, headache, vomiting, and altered mentation. The onset of symptoms usually is insidious but can sometimes be acute, especially in immunocompromised patients. Classic meningeal signs, such as Kernig and Brudzinski signs, are seen in 50% of patients. Approximately one-third of patients will experience cranial nerve palsies, visual disturbances, or papilledema, and about 15% have seizures. About 10% of patients with meningitis have no neurologic symptoms whatsoever. Lumbar puncture typically reveals an elevated opening pressure and findings on CSF analysis of lymphocytic pleocytosis, elevated protein, and low glucose.

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Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on Cryptococcosis
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