 Introduction
Descriptions
Synonyms
Image Bank
Lecture Bank
Video Bank
Introduction
Medical
Veterinary
Environmental
Industrial
Agricultural
Introduction
Susceptibility
MIC Database
Procedures
Histopathology
Introduction
Abbreviations
Links
CME
Conference
 Highlights
Bibliography
Glossary
Good Books
Events
Calendar
Introduction
Our Mission
Editorial Board
Editorial Staff
Supporters
Contributors
Legal Stuff
Privacy Policy
Kudos
This page updated:
1/27/2007 9:23:00 AM
DoctorFungus - All Rights Reserved
© 2007 Copyright
& Privacy Policy
Site built and designed for doctorfungus by Webillustrated
|
 |
 |
|
You are here:
Mycoses >
|
Navigate this section from here:
|
|
Cryptococcosis
European blastomycosis, torulosis
Cryptococcosis refers to the infections produced by the ubiquitous encapsulated yeast Cryptococcus neoformans. The infection commonly starts following inhalation of the organism [462]. The primary infection may remain localized into the lungs or disseminate througout the body. Some authors have made the distinction between localized and disseminated cryptococcosis, based on the number of organs involved [1151]. However, cryptococcocal meningitis can only occur once the fungus has reach CNS tissue from the primary point of entry. Based on this, most authors consider any form of extra-pulmonary cryptococcosis to be a form of disseminated disease. Primary pulmonary infections have no diagnostic symptoms and usually are asymptomatic. However, a chronic form may develop producing a variety of lesions. The prostate may be a reservoir for relapse [157, 1296]. A positive serum cryptooccal antigen titer is highly suggestive of dissemination [1993]. Cryptococcosis is considered an opportunistic infections as it affects mainly immunosupressed individuals.
There are 37 species within the genus Cryptococcus, however the major human pathogen is Cryptococcus neoformans. A few cases of cryptococcosis cause by other species (C. albidus and C.laurentii) have been reported in the literature [1257, 1395]. Cryptococcus neoformans is an encapsulated round to oval yeastlike fungus measuring 4 to 6 microns. A characteristic polysaccharide capsule of variable thickness (1 to 30 microns) surrounds these yeasts. In its natural enviroment the capsule is thinner and the yeast smaller, while thicker capsules tend to be found from infected tissues. The polysaccharide capsule, the phenoloxidase enzyme of Cryptococcus neoformans, and the organism's ability to grow at 37°C, are its major virulence factors [447, 1760]. Recent data suggest that phospholipase enzymes may also be virulence factors [832].
Within the species Cryptococcus neoformans, there are major varieties with differing biological, ecological, and epidemiological characteristics. For many years, only , C. neoformans var. neoformans and C. neoformans var. gattii were described. However, based on molecular studies and genetic variation a new variety C. neoformans var. grubii has been incorporated to this list [760, 761, 2150].
| Characteristic |
var. neoformans |
var. gattii |
var. grubii |
Ecology
|
|
|
|
Environmental source |
Soil contaminated with pigeon droppings |
Eucalyptus tree and decaying wood forming hollows in living trees |
NA |
| Geographical distribution |
Worldwide
(predominant in Northern Europe) |
Tropical and subtropical areas
(Southern California, Africa, Australia and Southeast Asia) |
Worldwide |
| Sexual state |
Filobasidiella neoformans var. neoformans |
Filobasidiella neoformans var. bacillispora |
Filobasidiella neoformans var. neoformans |
| Biochemical properties |
|
|
|
Canavanine susceptibility |
Yes |
No |
Yes |
Glycine assimilation |
No |
Yes |
No |
Thymine assimilation |
Yes (orange color change) |
Yes (blue-green color change) |
No (no color change) |
Serotypes
(rabbit polyclonal antisera)1 |
D |
B and C |
A |
| Immunoflourescence binding pattern to the IgM monoclonal antibody 13F1 (Mab 13F1) |
Punctate |
NA |
Annular |
| Usual immune status of the infected host |
Immunocompromised |
Immunocompetent |
Immunocompromised |
1 There is also a serotype "AD" which is currently classified as a separate serotype and in none of the defined varieties
NA: not available
References
[760, 761, 2150]
Cryptococcus neoformans was first isolated from peach juice in Italy by Francesco Sanfelice in 1894. Almost at the same, two German physicians, Abraham Buschke and Otto Busee isolated the same fungus from sarcoma-like lesions. Sanfelice called this cryptogamic yeast Saccharomyces neoformans while Busse called it Saccharomyces hominis. The disease was then called saccharomycosis. One year later, a French pathologist, Fredinand Curtis, described a "vegetable parasite" belonging to the yeast species that caused skin and soft tissue tumours, some of them of myxomatous appearence. Accordingly, Curtis called the encapsulated yeast Megalococcus myxoides. Later on, in 1901, the French mycologist Jean-Paul Vuillemin reclassified the yeast isolated by Busse and Curtis in the Genus Cryptococcus (Greek kruptos, hidden) because of the abscense of endospores [390, 622].
Cryptococcal meningitis was first identified in 1905 by Von Hansemann, even though Curtis had made the observation of meningeal complication in his patient from 1895. Nevertheless, the disease was confused with blastomycosis and was called European blastomycosis. When American scientists first isolated the yeast, they confused the mucoid capsule with histolysis and named the fungus Torula histolytica. Consequently, CNS disease was initially and for long time called "Torula meningits" or "Torulopsis." It was Rhoda Behnam, the director of the first Medical Mycology lab at Columbia University in New York, who in 1934 finally made clear the differentiation of cryptococcosis from blastomycosis and defined the serological differences among the strains [622].
Cryptococcus neoformans grows easily in pigeon feces, however the birds are not naturally infected. Aerosolization and inhalation of the organism seem to be the most important mechanism of acquisition. Recent epidemiologic studies have confirmed the theory that primary infections occur during childhood and usually are asymptomatic [863]. Different from other airborne mycoses, environmental-related outbreaks have not been described. The disease occurs worldwide, with different serotypes occurring in different regions as mentioned in the previous table [1326]. Cryptococcus neoformans serotype A is responsible for the majority of human cases. An increase in the prevalence of serotype D has been recently noted in France [621].
Animals (including the dog, cat, fox, monkey, cattle, horse, goat, and, others) can naturally acquire cryptococcosis, however, animal-to-person transmission has not been ever demonstrated [1357]. Human-to-human transmision is also very rare. Indeed, this form of acquisition has only been reported in the setting of transplantation of contaminated tissue. The reported cases include a corneal transplant causing cryptococcal endophthalmitis in the recipient and a case that followed an accidental needle stick with contaminated blood [237, 848].
Prior to the AIDS epidemic, the true prevalence of cryptococcal infections in the United States was unknown because reporting was not required. However, the annual incidence had been estimated to be of one to two cases per 1 million inhabitants. Indeed, during the 12-year period from 1965 to 1977, 1,264 proven cases of cryptococcosis were reported [498].
Following the emergence of the HIV-related immunodeficiency syndrome, cryptococcal meningitis was rapidly recognized among the most frequent opportunistic infections in both the United States and rest of the world [441, 621, 1242, 2500]. Indeed, Currie et al. reported an annual prevalence of cryptococcosis of 6.1% to 8.5% among HIV-infected individuals in New York City. In other words, about the same number of cases (1,277) previously noted in a 12-year period in a whole country occurred in a single year in a single city [498]. Hajjeh et al. evaluated the annual incidence of cryptococcosis in four different cities in USA (Atlanta, Alabama, Houston and San Francisco). They found incidence rates ranging from 17 (San Francisco, 1994) to 66 (Atlanta, 1992) cases per 1,000 persons living with AIDS [968]. This disparity is thought to be related with the difference in the incidence of AIDS between these cities, as well as to the use of fluconazole prophylaxis, but not to any particular geographic variable. The same authors concurrently documented an incidence of 0.9 cases of cryptococcosis per 100,000 in the HIV-negative population [968].
- Risk Factors for Cryptococcosis
| Risk Factor |
Reference |
AIDS |
[441, 450, 968, 1242, 2500] |
Organ transplant |
[222, 968, 1088, 1312, 2113] |
Cancer (chronic lymphatic leukemia, Hodgkin's disease, chronic myelogenous leukemia, myeloma, lymphosarcoma, acute lymphoblastic leukemia in children, and others) |
[222, 588, 968, 1151, 1312] |
Sarcoidosis |
[222, 588, 968, 1657] |
Corticosteroid therapy |
[588, 968, 1312] |
Diabetes mellitus |
[222, 588, 968] |
Others: Chronic obstructive pulmonary disease or lung cancer, cirrhosis, rheumatoid arthritis, systemic lupus erythematous, pregnancy, and splenectomy |
[Casadevall, 1998 #10420 |
The occurrence of disseminated forms of cryptococcal diseases is clearly related to immune deficiencies of the T-cell lineages. Before the AIDS epidemic, most cases of cryptococcosis were related to cancer, especially lymphoreticular malignancies [1151, 1235]. Treatment with corticosteroids agents is an important association [968, 1357]. Sarcoidosis is another immunologic deficiency that has been linked to cryptococcal disease [588, 1657]. The very same risk factors have been found in a recent study focused on HIV-negative individuals [1715]. Interestingly, these authors also described nine cases of cryptococcosis where the only apparent risk factor was a history of splenectomy. In any event, AIDS now represent the most common risk factor for the development of cryptococcal disease [1242]. Extra-pulmonary cryptococcosis is the AIDS-defining illness in 5 to 7% of patients with AIDS [91, 450].
Another important form T-cell associated immunosuppression increasingly related to cryptococcosis is organ transplantion [1088, 1715, 2113]. Indeed, in the developed world, this condition may be replacing AIDS as the primary risk factor for cryptococcosis, due to the immune recovery that can be achieve with the new antiretroviral therapies [1088]. A recent report by Husain et al. found a 2.8% incidence in this population. The type of immunosuppressive therapy influence even the type of infection these patients may have. Patients receiving tacrolimus are less likely to suffer CNS cryptococcosis but seem more inclined to have skin, soft tissue, bone, and articular infections [1088]. If dissemination occurs, the fungus has a predilection for the central nervous system. As mentioned above, central nervous system cryptococcosis is the most frequent clinical presentation [441].
Finally, between 10 to 40% of patients with cryptococcal diseases lack any recognizable predisposing condition [222, 1333, 1715]. In few carefully evaluated cases selective lymphocytic abnormalities have been found [587, 889, 2047]. The disease is rare among children, however when it occurs, the predisposing conditions are very similar to those described for adults [1312, 1313, 1558].
Pulmonary disease represents the primary site of infection. Cryptococcosis of other sites follows dissemination from the lungs. Cryptococcocal meningitis represents the most frequent clinical manifestation of cryptococcosis [1275, 1326]. A variety of other clinical manifestations of dissemination are listed below.
| CATEGORIES |
NOTES |
| Pulmonary forms |
| Acute Infection |
Rarely diagnosed except in AIDS patients who may present with severe acute respiratory distress (ARDS) |
| Chronic Pulmonary |
May produce nodules or masses (usually in the upper lobes), cavities, segmental pneumonia, pleural effusion, or lymphadenopathy |
| Disseminated forms |
| Central Nervous system |
Meningitis that follows a subacute course is typical. Complications include papilledema, cranial nerve involvement, visual loss, and hydrocephalus.
Single or multiple intracerebral fungal masses may also occur, but are rare |
| Cutaneous |
Painless lesions that may appear as papules, pustules, plaques, ulcers, subcutaneous masses, or cellulitis |
| Others |
Endophthalmitis, chorioretinitis, conjunctivitis, sinusitis, otitis, sinusitis, myocarditis, pericarditis, endocarditis, gastroduodenitis, hepatitis, cholecystitis, peritonitis, renal abscesses, adrenal involvement, arthritis, osteomyelitis, lymphadenitis, breast masses. |
The diagnosis of any form of cryptococcal infection requires having a direct or indirect proof of the presence of Cryptococcus neoformans in a body fluid or tissue. Direct proof is obtained either by the visualization of the characteristic yeast once a body material is prepared with adequate stains or by isolation of the agent by culture. Indirect proof refers to the identification of specific components of the fungi.
Laboratory
Direct examination
Globose yeast cells are easily seen in most clinical materials, such as cerebrospinal fluid and pulmonary tissue mounted in 10% KOH or India ink. A capsule may or may not be present.
Isolation
Inoculate aspirates and tissue (processed in a tissue homogenizer) onto Sabouraud glucose agar, Inhibitory Mould agar, or Brain heart infusion agar and incubate at 30°C. Cryptococcus neoformans is sensitive to cycloheximide. Growth is usually present in 2-5 days. Spinal fluid should be processed by a filtration or centrifugation technique.
Serology
A number of serologic tests for cryptococcal disease have been described. Initial attempts were made to detect cryptocccal antibody, but this approach had poor sensitivity and specificity [2373]. In contrast, detection of cryptococcal antigens, particularly polysaccharide capsular antigen, proved more than 30 years ago to be particularly helpful [869].
Latex Agglutination Test (LAT)
- Principle: detect cryptococcal polysaccharide capsular antigen.
- Commercial LAT kits
| 1 |
Crypto-LA |
International Biologica Laboratories, Cranbury, NJ |
| 2 |
MYCO-Immune |
American Micro Scan, Mahwah, NJ |
| 3 |
IMMY |
Immuno-mycologics, Norman, OK |
| 4 |
CALAS |
Meridian Diagnostics Inc., Cincinnati, OH |
- Sensitivity & Specificity: In general, the sensitivity and specificity of commercially available latex-agglutination tests is very high. False-positive cases related to rheumatoid factor and other unknow factors were described 3 decades ago [221]. Our current list of known causes of false-positive reactions is:
- Rheumatoid factor [221]
- Cancer. Very low-titer false-positive reactions have been reported [1060].
- Infection due to Trichosporon spp. This organism produces the same polysaccharide in its capsule as is produced by the cryptococcus [1393, 1500].
- Infection due to Stomatococcus mucilaginosis As with Trichosporon infections, this organism produces a polysaccharide that cross-reacts with that of the cryptococcus [419].
- Infection due to Capnocytophaga canimorsus (formerly known as DF-2) Reported only once [2409], the cause of this cross-reaction is not known.
- Contamination during pipetting in the laboratory [1016]
- Soaps and disinfectants use for slide washing [258]
- Hydroxyethyly starch (HES) for intravascular volume replacement (fluid resucitation) [1540]
To avoid these reactions, one should pretreat specimens with proteolytic enzymes (pronase) and reduce the specimen by use of 2-β-mercaptoethanol or dithiothreitol [390, 888]. False-negative reactions are also occasionally noted and may be due to the prozone effect, infection with a poorly encapsulated strain, low organism burden, or problems with the test kit [390, 441, 499, 976]
Susceptibility testing
Reliable and standardized methods for determining susceptibility of C. neoformans have not been described. It is clear that true microbiological resitance can develop [47, 126, 500, 1835, 1939, 2451], and the basis of resistance is under investigation [1757].
For fluconazole, testing in yeast nitrogen base (YNB) with an inoculum of 104 CFU/ml yields more meaningful MICs than those obtained by the NCCLS M27 methodology [47, 834, 1118, 2451]. MICs greater than or equal to 16 micrograms/ml appear to correlate with failure of therapy. Detection of amphotericin B resistance is a challenge. Testing on agar or use of Antibiotic Medium 3 is helpful [1383, 1939]. Measurement of MFCs may be of value [1940]. Further work in this area is required.
The tissue reaction is initially a myxoid degeneration with the area of inflammation assuming a gelatinous appearance. Large numbers of round yeast cells are found in the mucoid matrix. As the lesion progresses, a granulomatous reaction ensues. Organisms decrease numerically and are usually found in giant cells and histiocytes. In old healed granulomata, the yeasts are usually dead with disintegrated capsules. They may be difficult to see in H & E stained slides. The yeasts are round, typically encapsulated, and 5-15 um in diameter. The blastoconidia are attached by a narrow neck. The capsules stain pink by the mucicarmine technique.
Special resource: You may also want to refer to the Infectious Disease Society of America-Mycoses Study Group (IDSA-MSG) Practice Guidelines for this disease. It is available at the IDSA website.
Localized pulmonary lesions in noncompromised patients have a good prognosis. They usually heal without treatment [1181].
Hematogenous spread to the central nervous system has a severe and often fatal course, especially in debilitated patients. The combination of amphotericin B with 5-fluorocytosine for 6 to 10 weeks is the best treatment option for CNS infection [222, 597]. An alternative option is the use of the previous combination for 2 weeks follows by fluconazole (400 mg/d) for at least 10 more weeks [1714, 2287]. The goal of therapy should be CSF sterilization. Monotherapy with 5-fluorocytosine is highly discouraged because resistance may develop frequently [2273]. Patients with mild to moderate severity culture-positive non-CNS infections can be treated with fluconazole or itraconazole for 6 to 12 months [576, 620, 1714]. If any of these agents cannot be used, amphotericin B is recommended until completing a total dose of 1-2 grams [1993].
AIDS patients with either pulmonary or CNS involvement should be treated as mentioned above.Until recently, it was recommended that AIDS patients be placed on a lifelong maintenance antifungal regimen, with fluconazole (200-400 mg/day), itraconazole (200 mg BID) or amphotericin B (1 mg/kg IV 1-3 times/week) [1836, 1992]. However, new highly active antiretroviral therapies (HAART) have had a major impact on the occurrence of opportunistic infections and cryptococcal meningitis does not seems to be an exception [1661, 1707, 1954]. A draft of the new version of USPHS/IDSA Guidelines for the prevention of opportunistic infection in persons infected with HIV considers the possibility of interrupting mantainance therapy in asymptomatic patients with sustained increased > 6 months of CD4+ lymphocytes. Data on this approach are still limited and close followup should be maintained if this approach is pursued.
Bony lesions and large (>3 cm) CNS lesions may be managed by surgical excision. Intrathecal or intraventricular amphotericin B is sometimes used as salvage therapy [1822].
However, despite all these therapeutic possibilities, cryptococcosis remains a considerable cause of morbidity and mortality both for HIV-positive and negative patients [1715].
PubMed
|
India Ink of CSF with C. neoformans
|
India Ink of CSF with C. neoformans
|
Gram Stain of tissue infected with C. neoformans
|
Mucicarmine stain of brain infected with C. neoformans
|
|
|
References
47. Aller, A. I., E. Martin-Mazuelos, F. Lozano, J. Gomez-Mateos, L. Steele-Moore, W. J. Holloway, M. J. Gutierrez, F. J. Recio, and A. Espinel-Ingroff. 2000. Correlation of fluconazole MICs with clinical outcome in cryptococcal infection. Antimicrob. Agents Chemother. 44:1544-1548.
91. Anonymous. 1996. HIV/AIDS Surveillance Report:U.S. HIV and AIDS cases reported through
126. Armengou, A., C. Porcar, J. Mascaro, and F. Garcia-Bragado. 1996. Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis. Clin. Infect. Dis. 23:1337-1338.
157. Bailly, M. P., A. Boibieux, F. Biron, I. Durieu, M. A. Piens, D. Peyramond, and J. L. Bertrand. 1991. Persistence of Cryptococcus neoformans in the prostate: Failure of fluconazole despite high doses (letter). J. Infect. Dis. 164:435-436.
221. Bennett, J. E., and J. W. Bailey. 1971. Control for rheumatoid factor in the latex test for cryptococcosis. Am J Clin Pathol. 56:360-5.
222. Bennett, J. E., W. E. Dismukes, R. J. Duma, G. Medoff, M. A. Sande, H. Gallis, J. Leonard, B. T. Fields, M. Bradshaw, H. Haywood, Z. A. McGee, T. R. Cate, C. G. Cobbs, J. F. Warner, and D. W. Alling. 1979. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N. Engl. J. Med. 301:126-131.
237. Beyt, B. E., and S. R. Waltman. 1978. Cryptococcal endophthalmitis after corneal transplantation. N Engl J Med. 298:825-826.
258. Blevins, L. B., J. Fenn, H. Segal, P. Newcomb-Gayman, and K. C. Carroll. 1995. False-positive cryptococcal antigen latex agglutination caused by disinfectants and soaps. J. Clin. Microbiol. 33:1674-1675.
390. Casadevall, A., and J. R. Perfect. 1998. Cryptococcus neoformans. ASM Press, Washington, D.C.
419. Chanock, S. J., P. Toltzis, and C. Wilson. 1993. Cross-reactivity between Stomatococcus mucilaginosus and latex agglutination for cryptococcal antigen. Lancet. 342:1119-20.
441. Chuck, S. L., and M. A. Sande. 1989. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N. Engl. J. Med. 321:794-799.
447. Clancy, C. J., M. H. Nguyen, R. Alandoerffer, M. Richardson, and J. R. Graybill. 1999. What makes Cryptococcus neoformans virulent? 37th Annual Meeting of the Infectious Diseases Society of America, Abstract No. 271.
450. Clark, R. A., D. Greer, W. Atkinson, G. T. Valainis, and N. Hyslop. 1990. Spectrum of Cryptococcus neoformans infection in 68 patients infected with human immunodeficiency virus. Rev Infect Dis. 12:768-77.
462. Collier, L., A. Balows, and M. Sussman. 1998. Topley & Wilson's Microbiology and Microbial Infections, 9th ed, vol. 4. Arnold, London, Sydney, Auckland, New York.
498. Currie, B. P., and A. Casadevall. 1994. Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. Clin. Infect. Dis. 19:1029-1033.
499. Currie, B. P., L. F. Freundlich, M. A. Soto, and A. Casadevall. 1993. False-negative cerebrospinal fluid cryptococcal latex agglutination tests for patients with culture-positive cryptoccal meningitis. J. Clin. Microbiol. 31:2519-2522.
500. Currie, B. P., M. Ghannoum, L. Bessen, and A. Casadevall. 1995. Decreased fluconazole susceptibility of a relapse Cryptococcus neoformans isolate after fluconazole treatment. Infect. Dis. Clin. Pract. 4:318-319.
576. Denning, D. W., R. M. Tucker, L. H. Hanson, J. R. Hamilton, and D. A. Stevens. 1989. Itraconazole therapy for cryptococcal meningitis and cryptococcosis. Arch. Intern. Med. 149:2301-2308.
587. Diamond, R. D., and J. E. Bennett. 1973. Disseminated cryptococcosis in man: decreased lymphocyte transformation in response to Cryptococcus neoformans. J Infect Dis. 127:694-7.
588. Diamond, R. D., and J. E. Bennett. 1974. Prognostic factors in cryptococcal meningitis: a study in 111 cases. Ann. Intern. Med. 80:176-181.
597. Dismukes, W. E., G. Cloud, H. A. Gallis, T. M. Kerkering, G. Medoff, P. C. Craven, L. G. Kaplowitz, J. F. Fisher, C. R. Gregg, C. A. Bowles, S. Shadomy, A. M. Stamm, R. B. Diasio, L. Kaufman, S.-J. Soong, W. C. Blackwelder, and National Institute of Allergy & Infectious Diseases Mycoses Study Group. 1987. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N. Engl. J. Med. 317:334-341.
620. Dromer, F., S. Mathoulin, B. Dupont, O. Brugiere, and L. Letenneur. 1996. Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. French Cryptococcosis Study Group. Clin Infect Dis. 22 Suppl 2:S154-60.
621. Dromer, F., S. Mathoulin, B. Dupont, A. Laporte, and French Cryptococcosis Study Group. 1996. Epidemiology of cryptococcosis in France: A 9-year survey (1985-1993). Clin. Infect. Dis. 23:82-90.
622. Drouhet, E. 1997. Milestones in the history of Cryptococcus and Cryptococcosis. J Mycologie Medicale. 7:10-27.
760. Franzot, S. P., B. C. Fries, W. Cleare, and A. Casadevall. 1998. Genetic relationship between Cryptococcus neoformans var. neoformans strains of serotypes A and D. J Clin Microbiol. 36:2200-2204.
761. Franzot, S. P., I. F. Salkin, and A. Casadevall. 1999. Cryptococcus neoformans var. grubii: Separate varietal status for Cryptococcus neoformans serotype A isolates. J Clin Microbiol. 37:838-840.
832. Ghannoum, M. A. 2000. Potential role of phospholipases in virulence and fungal pathogenesis. Clin Microbiol Rev. 13:122-143,CP3.
834. Ghannoum, M. A., A. S. Ibrahim, Y. Fu, M. C. Shafiq, J. E. Edwards, and R. S. Criddle. 1992. Susceptibility testing of Cryptococcus neoformans: a microdilution technique. J. Clin. Microbiol. 30:2881-2886.
848. Glaser, J. B., and A. Garden. 1985. Inoculation of cryptococcosis without transmission of the acquired immunodeficiency syndrome. N Engl J Med. 313:266.
863. Goldman, D. L., H. Khine, J. Abadi, D. J. Lindenberg, L. Pirofski, R. Niang, and A. Casadevall. 2001. Serologic evidence for Cryptococcus neoformans infection in early childhood. Pediatrics. 107:E66: NIL_10-NIL_15.
869. Goodman, J. S., L. Kaufman, and M. G. Koenig. 1971. Diagnosis of cryptococcal meningitis. Value of immunologic detection of cryptococcal antigen. N Engl J Med. 285:434-6.
888. Gray, L. D., and G. D. Roberts. 1988. Experience with the use of pronase to eliminate interference factors in the latex agglutination test for cryptococcal antigen. J Clin Microbiol. 26:2450-1.
889. Graybill, J. R., and R. H. Alford. 1974. Cell-mediated immunity in Cryptococcosis. Cell Immunol. 14:12-21.
968. Hajjeh, R. A., L. A. Conn, D. S. Stephens, W. Baughman, R. Hamill, E. Graviss, P. G. Pappas, C. Thomas, A. Reingold, G. Rothrock, L. C. Hutwagner, A. Schuchat, M. E. Brandt, and R. W. Pinner. 1999. Cryptococcosis: Population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. Cryptococcal Active Surveillance Group. J Infec Dis. 179:449-454.
976. Hamilton, J. R., A. Noble, D. W. Denning, and D. A. Stevens. 1991. Performance of cryptococcus antigen latex agglutination kits on serum and cerebrospinal fluid specimens of AIDS patients before and after pronase treatment. J Clin Microbiol. 29:333-9.
1016. Heelan, J. S., L. Corpus, and N. Kessimian. 1991. False-positive reactions in the latex agglutination test for Cryptococcus neoformans antigen. J Clin Microbiol. 29:1260-1.
1060. Hopfer, R. L., E. V. Perry, and V. Fainstein. 1982. Diagnostic value of cryptococcal antigen in the cerebrospinal fluid of patients with malignant disease. J Infect Dis. 145:915.
1088. Husain, S., M. M. Wagener, and N. Singh. 2001. Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcomes. Emerging Infectious Diseases. 7:375-380.
1118. Jessup, C. J., M. A. Pfaller, S. A. Messer, J. Zhang, M. Tumberland, E. K. Mbidde, and M. A. Ghannoum. 1998. Fluconazole susceptibility testing of Cryptococcus neoformans: Comparison of two broth microdilution methods and clinical correlates among isolates from Ugandan AIDS patients. J Clin Microbiol. 36:2874-2876.
1151. Kaplan, M. H., P. P. Rosen, and D. Armstrong. 1977. Cryptococcosis in a cancer hospital: clinical and pathological correlates in forty-six patients. Cancer. 39:2265-74.
1181. Kerkering, T. M., R. J. Duma, and S. Shadomy. 1981. The evolution of pulmonary cryptococcosis. Clinical implications from a study of 41 patients with and without compromising host factors. Ann. Intern. Med. 94:611-616.
1235. Korfel, A., H. D. Menssen, S. Schwartz, and E. Thiel. 1998. Cryptococcosis in Hodgkin's disease: description of two cases and review of the literature. Ann. Hematol. 76:283-6.
1242. Kovacs, J. A., A. A. Kovacs, P. M, W. C. Wright, G. V. J, C. U. Tuazon, E. P. Gelmann, H. C. Lane, R. Longfield, G. Overturb, A. M. Macher, A. S. Fauci, J. E. Parrillo, J. E. Bennett, and H. Masur. 1985. Cryptococcosis in the acquired immunodeficiency syndrome. Ann. Intern. Med. 103:533-538.
1257. Krumholz, R. A. 1972. Pulmonary cryptococcosis. A case due to Cryptococcus albidus. Am Rev Respir Dis. 105:421-4.
1275. Kwon-Chung, K. J., T. C. Sorrell, F. Dromer, E. Fung, and S. M. Levitz. 2000. Cryptococcosis: clinical and biological aspects. Med Mycol. 38:205-213.
1296. Larsen, R. A., S. Bozzette, J. A. McCutchan, J. Chiu, M. A. Leal, and D. D. Richman. 1989. Persistent Cryptococcus neoformans infection of the prostate after successful treatment of meningitis. California Collaborative Treatment Group. Ann. Intern. Med. 111:125-8.
1312. Leggiadro, R. J., F. F. Barrett, and W. T. Hughes. 1992. Extrapulmonary cryptococcosis in immunocompromised infants and children. Pediatr. Infect. Dis. J. 11:43-47.
1313. Leggiadro, R. J., M. W. Kline, and W. T. Hughes. 1991. Extrapulmonary cryptococcosis in children with acquired immunodeficiency syndrome. Pediatr. Infect. Dis. J. 10:658-662.
1326. Levitz, S. M. 1991. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis. 13:1163-9.
1333. Lewis, J. L., and S. Rabinovich. 1972. The wide spectrum of cryptococcal infections. Am J Med. 53:315-22.
1357. Littman, M. L., and J. E. Walter. 1968. Cryptococcosis: current status. Am J Med. 45:922-32.
1383. Lozano-Chiu, M., V. L. Paetznick, M. A. Ghannoum, and J. H. Rex. 1998. Detection of resistance to amphotericin B among Cryptococcus neoformans clinical isolates: Performance of three different media assessed by using E-Test and National Committee for Clinical Laboratory Standards M27-A methodologies. J. Clin. Microbiol. 36:2817-2822.
1393. Lyman, C. A., S. J. N. Devi, J. Nathanson, C. E. Frasch, P. A. Pizzo, and T. J. Walsh. 1995. Detection and quantitation of the glucuronoxylomannan-like polysaccharide antigen from clinical and nonclinical isolates of Trichosporon beigelii and implications for pathogenicity. J. Clin. Microbiol. 33:126-130.
1395. Lynch, J. P., 3rd, D. R. Schaberg, D. G. Kissner, and C. A. Kauffman. 1981. Cryptococcus laurentii lung abscess. Am Rev Respir Dis. 123:135-8.
1500. McManus, E. J., and J. M. Jones. 1985. Detection of a Trichosporon beigelii antigen cross-reactive with Cryptococcus neoformans capsular polysaccharide in serum from a patient with disseminated Trichosporon infection. J Clin Microbiol. 21:681-5.
1540. Millon, L., T. Barale, M.-C. Julliot, J. Martinez, and G. Mantion. 1995. Inteference by hydroxyethyl starch used for vascular filling in latex agglutination test for cryptococcal antigen. J. Clin. Microbiol. 33:1917-1919.
1558. Moncino, M. D., and L. T. Gutman. 1990. Severe systemic cryptococcal disease in a child: review of prognostic indicators predicting treatment failure and an approach to maintenance therapy with oral fluconazole. Pediatr. Infect. Dis. J. 9:363-368.
1657. Nottebart, H. C., R. F. McGehee, and J. P. Utz. 1973. Cryptococcosis complicating sarcoidosis. Am Rev Respir Dis. 107:1060-3.
1661. Nwokolo, N. C., M. Fisher, B. G. Gazzard, and M. R. Nelson. 2001. Cessation of secondary prophylaxis in patients with cryptococcosis. Aids. 15:1438-9.
1707. Palella, F. J., Jr., K. M. Delaney, A. C. Moorman, M. O. Loveless, J. Fuhrer, G. A. Satten, D. J. Aschman, S. D. Holmberg, and HIV Outpatient Study Investigators. 1998. Declining mortality and morbidity among patients with advanced human immunodeficiency virus infection. N. Engl. J. Med. 338:853-860.
1714. Pappas, P. G., J. Perfect, and R. A. Larsen. 1998. Cryptococcosis in HIV-negative patients: analysis of 306 cases. 36th Annual Meeting of the Infectious Diseases Society of America, Abstract No. Abstract No. 101.
1715. Pappas, P. G., J. R. Perfect, G. A. Cloud, R. A. Larsen, G. A. Pankey, D. J. Lancaster, H. Henderson, C. A. Kauffman, D. W. Haas, M. Saccente, R. J. Hamill, M. S. Holloway, R. M. Warren, and W. E. Dismukes. 2001. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis. 33:690-699.
1757. Perfect, J. R., and G. M. Cox. 1999. Drug resistance in Cryptococcus neoformans. Drug Resist Update. 2:259-269.
1760. Perfect, J. R., B. Wong, Y. C. Chang, K. J. Kwon-Chung, and P. R. Williamson. 1998. Cryptococcus neoformans: virulence and host defences. Med Mycol. 36:79-86.
1822. Polsky, B., M. R. Depman, J. W. M. Gold, J. H. Galicich, and D. Armstrong. 1986. Intraventricular therapy of cryptococcal meningitis via a subcutaneous reservoir. Am. J. Med. 81:24-28.
1835. Powderly, W. G., E. J. Keath, M. Sokol-Anderson, K. Robinson, D. Kitz, J. R. Little, and G. Kobayashsi. 1992. Amphotericin B-resistant Cryptococcus neoformans in a patient with AIDS. Infect. Dis. Clin. Pract. 1:314-316.
1836. Powderly, W. G., M. S. Saag, G. A. Cloud, P. Robinson, R. D. Meyer, J. M. Jacobson, J. R. Graybill, A. M. Sugar, V. J. McAuliffe, S. E. Follansbee, C. U. Tuazon, J. J. Stern, J. Feinberg, R. Hafner, and W. E. Dismukes. 1992. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 326:793-798.
1939. Rodero, L., S. Cordoba, P. Cahn, F. Hochenfellner, G. Davel, C. Canteros, S. Kaufman, and L. Guelfand. 2000. In vitro susceptibility studies of Cryptococcus neoformans isolated from patients with no clinical response to amphotericin B therapy. J Antimicrob Chemother. 45:239-242.
1940. Rodero, L., S. Cordoba, P. Cahn, M. Soria, M. Lucarini, G. Davel, S. Kaufman, C. Canteros, and L. Guelfand. 2000. Timed-kill curves for Cryptococcus neoformans isolated from patients with AIDS. Med Mycol. 38:201-207.
1954. Rollot, F., P. Bossi, R. Tubiana, E. Caumes, V. Zeller, C. Katlama, and F. Bricaire. 2001. Discontinuation of secondary prophylaxis against cryptococcosis in patients with AIDS receiving highly active antiretroviral therapy. Aids. 15:1448-1449.
1992. Saag, M. S., G. A. Cloud, J. R. Graybill, J. D. Sobel, C. U. Tuazon, P. C. Johnson, W. J. Fessel, B. L. Moskovitz, B. Wiesinger, D. Cosmatos, L. Riser, C. Thomas, R. Hafner, and W. E. Dismukes. 1999. A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. Clin Infect Dis. 28:291-296.
1993. Saag, M. S., R. J. Graybill, R. A. Larsen, P. G. Pappas, J. R. Perfect, W. G. Powderly, J. D. Sobel, W. E. Dismukes, and the Mycoses Study Group Cryptococcal Subproject. 2000. Practice guidelines for the management of cryptococcal disease. Clin. Infect. Dis. 30:710-718.
2047. Schimpff, S. C., and J. E. Bennett. 1975. Abnormalities in cell-mediated immunity in patients with Cryptococcus neoformans infection. J Allergy Clin Immunol. 55:430-41.
2113. Singh, N., T. Gayowski, M. M. Wagener, H. Doyle, and I. R. Marino. 1997. Invasive fungal infections in liver transplant recipients receiving tacrolimus as the primary immunosuppressive agent. Clin. Infect. Dis. 24:179-184.
2150. Steenbergen, J. N., and A. Casadevall. 2000. Prevalence of Cryptococcus neoformans var. neoformans (serotype D) and Cryptococcus neoformans var. grubii (serotype A) isolates in New York city. J Clin Microbiol. 38:1974-1976.
2273. Utz, J. P., B. S. Tynes, H. J. Shadomy, R. J. Duma, M. M. Kannan, and K. N. Mason. 1968. 5-Fluorocytosine in human cryptococcosis. Antimicrob. Agents Chemother. 8:344-6.
2287. Van der Horst, C. M., M. S. Saag, G. A. Cloud, R. J. Hamill, J. R. Graybill, J. D. Sobel, P. C. Johnson, C. U. Tuazon, T. Kerkering, B. L. Moskovitz, W. G. Powderly, W. E. Dismukes, and National Institue of Allergy and Infectious Diseases Mycoses Study Group AIDS Clinical Trials Group. 1997. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N. Engl. J. Med. 337:15-21.
2373. Walter, J. E., and R. D. Jones. 1968. Serodiagnosis of clinical cryptococcosis. Am Rev Respir Dis. 97:275-82.
2409. Westerink, M. A., D. Amsterdam, R. J. Petell, M. N. Stram, and M. A. Apicella. 1987. Septicemia due to DF-2. Cause of a false-positive cryptococcal latex agglutination result. Am J Med. 83:155-8.
2451. Witt, M. D., R. J. Lewis, R. A. Larsen, E. N. Milefchik, M. A. E. Leal, R. H. Haubrich, J. A. Richie, J. E. Edwards, Jr., and M. A. Ghannoum. 1996. Identification of patients with acute AIDS-associated cryptococcal meningitis who can be effectively treated with fluconazole: The role of antifungal susceptibility testing. Clin. Infect. Dis. 22:322-328.
2500. Zuger, A., E. Louie, S. R. Holzman, and S. M. Simberkoff. 1986. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Ann. Intern. Med. 104:234-240.
|