CRYPTOCOCCOSIS
Cryptococcosis is caused by the closely related, budding, yeastlike fungi Cryptococcus neoformans and Cryptococcus gattii. Cryptococcus is a uniphasic fungus that does not exist in a mycelial form. Cryptococcus neoformans has a worldwide distribution in rotting vegetation as well as in soil contaminated by pigeon excreta. However, pigeon exposure does not play an important role in the epidemiology of this infection. It is likely that both humans and pigeons get exposed to this fungus through exposure to rotting vegetation, and the latter act as carriers of the fungus in their gastrointestinal tracts. Most infections in immunocompromised hosts are caused by C. neoformans. C. gattii has been associated with certain varieties of Eucalyptus trees in Australia and other parts of the world and with other tree varieties in Vancouver Island in Canada. Almost all C. gattii infections are seen in immunocompetent hosts.
Cryptococcus spp. probably
gain entry into the body through the lungs, by inhalation of the basidiospore
form of this fungus. Basidiospores are smaller than the yeast form that
facilitates deposition in the alveoli and terminal bronchioles after
inhalation. From the lungs, the fungus can disseminate to all organs. Although
the lung is the initial site of infection, it is the second most clinically
relevant site of infection after the central nervous system (CNS). After
inhalation, C. neoformans causes a small focal granulomatous
pneumonitis; the vast majority of these are clinically and radiographically silent.
However, in a manner similar to tuberculosis, these foci of yeasts can persist
in a latent stage and cause active infection later if the host immune system
becomes compromised.
The thick polysaccharide capsule of C. neoformans has
antiphagocytic properties and is an important virulence determinant. In the
laboratory, the capsule can be visualized as a clear area in a suspension of
India ink when examined under a microscope. Another important virulence factor
is the enzyme phenol oxidase, which is also unique to C. neoformans and
can be used for laboratory identification.
Some immunocompetent patients can have symptomatic
infection, which may be related to infection with a large inoculum or a
virulent strain. These patients usually present with cough, sputum, chest pain,
fever, weight loss, and hemoptysis. Chest radiographic findings can vary widely,
including solitary or multiple nodules, pneumonic infiltrates, hilar and
mediastinal adenopathy, and pleural effusion. Diagnosis is made by
visualization of the characteristic encapsulated yeast forms in sputum,
bronchoalveolar lavage, or tissue specimens and culture of the organism from
these same specimens. Serum cryptococcal antigen is rarely positive and
suggests disseminated disease and a need for sampling the cerebrospinal fluid.
Immunocompromised patients represent the majority of
cases with cryptococcosis. Reactivation of latent infection is the most likely
mechanism of infection, but new infections are also possible. Underlying
conditions include HIV infection, malignancies, stem cell and organ transplantation, chronic
liver, kidney or lung disease, diabetes, sarcoidosis, sickle cell disease,
treatment with systemic corticosteroids, or tumor necrosis factor antagonists.
In non–HIV-infected patients, symptoms and radiographs resemble the disease
seen in immunocompetent patients, but dyspnea and disseminated disease are more
common.
In HIV-infected patents, the pulmonary infection is
more acute and severe, and the majority of these patients have CNS involvement.
These patients usually have interstitial infiltrates, but alveolar infiltrates,
mass lesions, adenopathy, and pleural effusions are also seen. Co-infection
with other opportunistic pathogens has been described in HIV-infected patients.
Diagnosis relies on microscopy and culture of respiratory secretions or tissue.
Serum cryptococcal antigen results are positive in the majority of these
patients. CNS involvement should always be assessed in these patients.
TREATMENT
With the exception of immunocompetent asymptomatic
patients with a negative serum cryptococcal antigen result, treatment of
cryptococcosis is indicated. Asymptomatic patients with positive serum antigen
test results should be treated as having mild to moderate disease to prevent
symptomatic systemic dissemination. For mild to moderate pulmonary disease in
immuno- competent patients, oral fluconazole or itraconazole for 6 to 12 months
is indicated. In patients with extensive multiorgan disease or CNS involvement,
intravenous amphotericin B and flucytosine is indicated as induction therapy for
2 to 3 weeks followed by oral fluconazole. The same treatment approach is
recommended for all immunocompromised patients with cryptococcal infection
because the induction therapy is fungicidal. Prognosis is generally good with
current treatment of cryptococcosis.
