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PubMed1999

Heat shock protein 70 (hsp70) as a major target of the antibody response in patients with pulmonary cryptococcosis.

Cryptococcus neoformans causes infection in individuals with defective T cell function, such as AIDS, as well as without underlying disease. It has been suggested that humoral as well as cellular immunity might play an important role in the immune response to C. neoformans infection. We have recently shown, using immunoblotting, that the 70-kD hsp family of C. neoformans was the major target molecule of the humoral response in murine pulmonary cryptococcosis. In this study we also used immunoblotting to define the antibody responses in the sera of 24 patients with pulmonary cryptococcosis: 21 proven and three suspected diagnoses. Anti-C. neoformans hsp70 antibody was detected in 16 of 24 (66.7%) patients with pulmonary cryptococcosis. Fourteen of 17 (82.3%) patients with high antigen titres (> or = 1:8) and two of seven (28.6%) patients with low titres (< or = 1:4) had detectable levels of anti-hsp70 antibody. Sera from patients positive for anti-hsp70 antibody showed high titres in the Eiken latex agglutination test for the detection of serum cryptococcal antigen. Our results indicate that the 70-kD hsp family from C. neoformans appears to be a major target molecule of the humoral response, not only in murine pulmonary cryptococcosis, but also in human patients with pulmonary cryptococcosis.

Adult↗
PubMed2003

Vertebral cryptococcosis simulating tuberculosis.

Infection with the fungus Cryptococcus neoformans is seen predominantly in two forms: (a) pulmonary and (b) cerebromeningeal. Skeletal cryptococcosis is uncommon. There have been only occasional case reports of thoracic vertebral cryptococcosis presenting as cord compression. A young female had cervical lymphadenopathy diagnosed as tuberculosis by fine needle aspiration cytology (FNAC) and was on antitubercular therapy (ATT) for 5 months. She developed rapidly progressive paraparesis and imaging demonstrated a destructive vertebral body lesion involving T2-3 with a paraspinal abscess producing cord compression. A costotransversectomy with excision of the diseased bone and bone grafting was done. Histopathological examination revealed cryptococcosis. The patient was put on antifungal medication, but expired 2 weeks after surgery. Radiological, magnetic resonance imaging and surgical finding of vertebral cryptococcosis can mimic tuberculosis. The definite diagnosis of cryptococcosis depends upon microscopic identification of the organism. A high index of suspicion leading to early surgical confirmation and institution of anti fungal therapy is necessary to reduce the mortality and morbidity.

Adult↗
PubMed2003

Primary cutaneous cryptococcosis in immunocompetent and immunocompromised hosts.

A case of primary cutaneous cryptococcal infection is presented and cases of primary cutaneous cryptococcosis in normal and immunocompromised hosts are reviewed. Cutaneous cryptococcosis can occur from local inoculation or dissemination from a distant site of infection. Risk factors associated with development of primary cutaneous cryptococcosis are those which affect cell-mediated immunity, such as corticosteroid usage, solid organ transplantation, sarcoidosis and immunosuppression. The cutaneous manifestations of cryptococcosis are protean and may mimic other cutaneous diseases. Patients with a diagnosis of cryptococcosis from a skin biopsy or culture should undergo evaluation to exclude disseminated disease and an evaluation of cell-mediated immunity. Although some patients do well without antifungal therapy, these patients cannot be discerned prospectively and therefore antifungal therapy appears warranted in all patients with localized disease. Choice of therapy depends on the extent of disease and immunocompetence of the host.

Adult↗
PubMed2005

Cryptococcosis: the 1981-2000 epidemic.

The annual incidence of cryptococcosis during 1981-2000 was determined in subscribers of a large integrated health care program in Northern California and in those among them who were HIV positive. The incidence of cryptococcosis had been measured in this setting in the previous decade. The 20-year incidence per million person-years was 19.0 in males and 2.6 in females. In males, annual incidence rose sharply but irregularly from 1981 to 1992, then decreased irregularly. In females, trends were less marked, with maximum incidence in 1997. In HIV-positive patients cryptococcosis incidence was highest in 1981-85 and decreased thereafter in men. In women, maximum incidence occurred in 1986-90 and was followed by a decrease. Cryptococcosis was rare in the non-predisposed. Thus, cryptococcosis incidence increased markedly in men early in the AIDS epidemic, and began to decrease in both male and female HIV-positive patients well before highly active antiretroviral therapy became available.

AIDS-Related Opportunistic Infections↗
PubMed1970

Cryptococcosis of the central nervous system. Epidemiological, clinical, and therapeutic features.

(1) A survey of cryptococcal infections of the nervous system in Queensland, Australia, revealed the nine year prevalence rate for the Australian aboriginal to be some 17 times greater than that of the white population. Uncommon in the first decade of life, the disease was developed by 79% of 29 patients between 20 and 59 years, males being affected twice as commonly as females. (2) Cryptococcosis appears to be more common in Australia than in the United Kingdom, and in Queensland the nine year incidence of neurological cryptococcosis was 4·7 per 100,000 in the tropical north compared with 1·8 per 100,000 in the southern parts of the State. Because of this, and since 20 of the 29 patients were regarded as having outdoor occupations, it is suggested that a high environmental exposure to the fungus may be associated with an animal reservoir and with dry, dusty conditions. It is also possible that geographical and occupational factors rather than racial predisposition account for the high incidence of the disease in the Australian aborigine. However, individual resistance and susceptibility are probably also important factors, since the clinical disease appears to be positively correlated with certain other diseases, or with steroid therapy, which would impair the immune responses of the body. (3) Headache is the outstanding symptom of neurological cryptococcosis and fever or evidence of meningeal reaction, though often present, may be absent. An awareness of the possibility of neurological cryptococcosis in the differential diagnosis of various intracranial disorders should lead to identification of the encapsulated C. neoformans in the cerebrospinal fluid. Although in eight of 26 patients the lumbar cerebrospinal fluid was sterile on repeated examination, in five cases C. neoformans was found on direct examination of cerebrospinal fluid obtained by ventricular puncture. The remaining three died before further investigations could be performed. (4) Before the introduction of amphotericin B, neurological cryptococcosis was almost invariably fatal. At the present time, the infection can be eradicated in some 80% of patients. Intravenous administration of amphotericin B is generally adequate, but the intrathecal route should be used for cases in relapse or in critically ill patients. In addition to the toxic effects of the drug, the possibility of later deterioration in the patient's condition due to meningeal reaction-for example, occult hydrocephalus-merits consideration and appropriate neurosurgical treatment.

Adolescent↗
PubMed1992

CSF in 85 patients with AIDS and CNS cryptococcosis.

In an eight years time period (July 1984-June 1992) CSF samples of 40718 patients were studied, and 610 were from patients with AIDS clinically diagnosed and immunologically confirmed through HIV antibodies detection. Among opportunistic infections detected in them 85 were CNS cryptococcosis. For the purpose of this study the CSF of these 85 patients are the AIDS group of CNS cryptococcosis. For comparison, CSF data from 50 patients with CNS cryptococcosis but without AIDS were taken (non-AIDS group); in this group, 22 patients were immunosuppressed after renal transplant. In AIDS group, the more frequent CSF findings were: yeast presence at direct exam (Fuchs-Rosenthal cell counting chamber), growing of the yeast in cultures, and gamma globulins increase. In non-AIDS group were more frequent: hypercytosis, neutrophil cells presence, and total protein increase. Differences between the two groups are discussed taking into account CNS/CSF immune changes induced by HIV infection. It is concluded that in CNS cryptococcosis of patients with AIDS the CSF evidenced more extensive signs of the fungal opportunistic infection than signs of inflammatory response to the infection. The latter were more prominent among patients of the non-AIDS group of CNS cryptococcosis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Prevalence of HTLV-I antibody in pulmonary cryptococcosis.

A retrospective study was done to determine the prevalence of anti-HTLV-I antibodies in patients with pulmonary cryptococcosis. None of the 19 patients with pulmonary cryptococcosis had underlying immunodeficiency. Anti-HTLV-I antibody was present in 6 (32%) of 19 patients with pulmonary cryptococcosis, a significantly higher prevalence than found in patients with bronchial asthma (4 (7%) of 58) (p less than 0.01, chi-square test). No statistical difference was noted when anti-HTLV-I antibody seropositivity was compared to that of patients with pulmonary tuberculosis (16% (17/105)), lung cancer (17% (22/129)) and pneumonia (9% (6/64)). A reduced cellular immunity as shown by lymphopenia, the CD4/CD8 ratio, and purified protein derivative skin test was found in only 1 (5%) of 19, 2 (12%) of 17, and 6 (33%) of 18 patients, respectively. These results do not explain the susceptibility to pulmonary cryptococcosis in HTLV-I carriers. This is the first report of high prevalence of pulmonary cryptococcosis in HTLV-I carriers and it raises the question whether HTLV-I carriers are more susceptible to opportunistic infections and other malignancies probably due to subtle immunological abnormalities.

Adolescent↗
PubMed2003

[Clinical and mycological features of cryptococcosis].

Cryptococcosis is the third most common deep mycosis in Japan. Cryptococcus neoformans is known to grow in pyres of pigeon feces. Chicken feces in Thailand were tested for whether C. neoformans could be isolated, because there is considerable prevalence of cryptococcal meningitis in patients with HIV in that country. We isolated C. neoformans from chicken feces in as many as at 70 % of the villages tested. Chicken as well as pigeon feces were believed to be an origin of infection. We have studied the relation between in vitro virulence and thickness of polysaccharide capsules. Strains with thicker capsules such as YC-11 or YC-5 showed more resistance to macrophage phagocytosis than strains with thinner capsules like YC-27 or YC-13. This finding was consistent with the cytokine dynamic state in mice cryptococcosis. Th1 was dominant in infections with thinner capsule strains, although Th2 was relatively dominant in those with thick capsules. The clinical features of 104 cases with pulmonary cryptococcosis were summarized. Radiological findings of pulmonary cryptococcosis varied depending on the time course of the disease and on immunological status. There were no specific symptoms and signs except for positive glucronoxylomannan. Those in azole class were the most commonly prescribed antifungals. New generation antifungals voriconazole and intravenous itraconazole showed potent clinical efficacy in pulmonary cryptococcosis.

Animals↗
PubMed2000

Changing scenario of cryptococcosis in a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: With the increase in the number of patients of AIDS, the incidence of cryptococcosis is on the rise in India. It was therefore considered important to evaluate the predisposing factors, laboratory investigations and outcome of patients with cryptococcosis in this changed scenario. METHODS: We assessed 58 patients with cryptococcosis retrospectively over a five year period (January 1995-December 1999) at the Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. RESULTS: The annual incidence of cryptococcosis in PGIMER, Chandigarh has increased about 15 fold from 1970-1982 (pre AIDS era) to 1995-1999 (present series). Of the 47 patients studied for predisposing factors, 36 patients were identified with predisposing factors, HIV infection (57.4%) was the commonest followed by haematologic malignancies (6.3%) and renal transplant (4.2%). Forty one patients were diagnosed by isolation of the organism as well as antigen detection in cerebrospinal fluid/serum, 9 by isolation alone and 8 by antigen detection alone. Quantitative antigen titres were done in 38 patients and a significantly higher (P < 0.01) antigen titre (> 512) was observed in HIV positive patients as compared to HIV negative patients. All isolates tested were of Cryptococcous neoformans var neoformans biotype and no resistance to antifungal agents was noted. Twenty of 41 patients receiving treatment improved. The results were compared with other studies available from India. INTERPRETATION & CONCLUSION: The incidence of cryptococcosis is on the rise in this part of north India and this can be attributed to an increase in AIDS cases.

Adult↗
PubMed2000

[Study on pulmonary cryptococcosis disclosed by chest radiographic screening in Nagasaki Prefecture].

We conducted a retrospective investigation of 20 cases of pulmonary cryptococcosis discovered by chest radiographic screening in Nagasaki Prefecture among 2,011,577 persons over a period of 9 years, Apr. 1989-Mar. 1998. Eight males and 12 females between 15 and 72 years of age(mean: 46.6 years) were diagnosed as having pulmonary cryptococcosis. The mean detectability of pulmonary cryptococcosis by screening was 0.99 per 10(5) persons: 1.30 for residents, 0.51 for school children and 0.80 for workers. Chest radiography showed shadows of solitary nodules in 9 patients, multiple nodules in 4, infiltration in 4 and others in 3. Cavities were noted in 7. However, it was difficult to distinguish between pulmonary cryptococcosis from pulmonary tuberculosis and pulmonary cancer based on radiographic data alone. Final diagnoses for 11 and 3 patients, respectively, were made using TBLB or BAL, and lung biopsy. Sixteen patients each underwent an Eiken-Latex agglutination test (serum cryptococcus antigen test) and 15 (93.8%) had positive results. The serum antigen level thus appears to be a useful indicator in the supplementary serological diagnosis of pulmonary cryptococcosis.

Adolescent↗
PubMed2004

Cryptococcosis in patients with hematologic malignancies. A report from GIMEMA-infection.

BACKGROUND AND OBJECTIVES: Cryptococcosis is an important cause of morbidity and death in immunocompromised patients. The aim of this study was to evaluate clinical and laboratory characteristics, and outcome of patients with cryptococcosis complicating hematologic diseases. DESIGN AND METHODS: This was a retrospective study, conducted over a ten-year period (1993-2002) in 21 hematology divisions, in tertiary care or university hospitals. RESULTS: This study evaluated 17 patients with hematologic diseases who developed cryptococcosis. Possible risk factors recognized before the onset of the infection were: administration of steroids for the underlying malignancy (6 patients), diabetes mellitus (4 patients), cutaneous lesions (2 patients) and autoimmune disease, hepatic cirrhosis, chronic renal failure and exposure to pigeons (1 patient each). Five patients received prophylaxis, consisting of fluconazole in 2 cases. Fever, neurological and respiratory signs developed according to the primary sites of infection (5 blood, 5 central nervous system, 4 lung, and 1 each in gut, skin and mouth). Diagnosis was made by positive microbiological culture, antigen detection in serum or cerebrospinal fluid, or polymerase chain reaction. All patients started specific treatment (fluconazole, 7 patients; amphotericin-B deoxycolate or liposomal amphotericin-B, 10 patients). Two patients died from cryptococcosis within 30 days after diagnosis. INTERPRETATION AND CONCLUSIONS: Cryptococcosis in patients with hematologic malignancies is a rare complication. In neutropenic patients, it is less fatal than other fungal infections (i.e. aspergillosis or candidemia). Specific treatment, started promptly, positively influences the outcome.

Adolescent↗
PubMed2005

[Case of primary pulmonary cryptococcosis accompanied by severe back pain].

We report a case of primary pulmonary cryptococcosis. A 43-year-old male, without any significant underlying disease or immunological abnormalities, was admitted to our hospital with a complaint of sudden onset of severe back pain. His chest-X-ray and computed tomography revealed infiltrative shadows in the left lower lung without any signs of pleural effusion. Through transbronchial biopsy, cryptococcosis was obtained. Cryptococcal antigen also tested positive, we diagnosed this case as primary pulmonary cryptococcosis. And started anti-fungal therapy (fluconazole) consisting of parenteral and oral fluconazole. As soon as anti-fungal therapy was started, both the chest X-ray findings and cryptococcal antigen showed general improvement. Furthermore, subjective symptoms subsided immediately after treatment, During follow up through the outpatient clinic, his symptomatic complaint and chest roentgenogram shows improvements. This case was noteworthy for two reasons: 1) In cases with chest X-rays showing infiltrative shadows but lacking any underlying diseases, pulmonary cryptococcosis should be considered. 2) Sudden onset of back pain is a rare but a possible primary symptom of pulmonary cryptococcosis.

Administration, Oral↗
PubMed2005

[Surgical treatment of primary pulmonary cryptococcosis].

OBJECTIVE: To assess the clinical feature, diagnosis and treatment of primary pulmonary cryptococcosis. METHODS: From 1996 to 2004, 11 patients with primary pulmonary cryptococcosis were surgical treated and confirmed by histologic study. At the same period, 2715 patients with pulmonary abnormalities received surgery. Their clinical data were retrospectively reviewed. RESULTS: Sixty-four percent (7/11) of the patients were symptomatic at the time of diagnosis. All 11 cases were misdiagnosed as lung cancer or inflammatory or tuberculosis by X-ray and CT scan before surgery. Three cases received fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) scan and their primary pulmonary lesions showed FDG avid. All 11 patients were treated by antibiotics and antituberculosis therapy but no responses appeared. Primary pulmonary cryptococcosis was diagnosed by ultrasound-guided fine needle aspiration biopsy in only 2 cases, but antifungal therapy was not effective. All 11 patients underwent thoracotomy and their pulmonary cryptococcosis were resected. Only 1 patient with multiple nodules received antifungal therapy postoperatively. No recurrence was found in any patients. CONCLUSIONS: Primary pulmonary cryptococcosis is non-specific and can be confused with lung cancer, tuberculosis, etc. The pulmonary abnormalities should be resected unless the diagnosis is established. Antifungal therapy is not necessary in patients whose abnormality has been resected thoroughly.

Adult↗
PubMed1993

[Clinical evaluation of diagnosis and treatment in three cases of primary pulmonary cryptococcosis].

Pulmonary cryptococcosis has been considered as a disease associated with depressed immune function of the host. However, it may develop in healthy individuals without any underlying disease. Recently, we experienced three cases of primary pulmonary cryptococcosis. Case 1. A 30-year-old woman in the sixth week postpartum developed cough and low-grade fever. Chest X-ray showed infiltrative shadows in right S2 and left S6. A diagnosis of pulmonary cryptococcosis was made from transbronchial brushings and histological examination. Case 2. A 51-year-old man was noted to have abnormal shadows on chest X-ray film at a regular medical checkup. Chest X-ray examination showed a small nodular density in left S9. A diagnosis of pulmonary cryptococcosis was made from percutaneous pulmonary paracentesis. Case 3. A 58-year-old man was noted to have an abnormal shadow on chest X-ray film at a regular medical checkup. Chest X-ray examination showed a nodular density in right S8. A diagnosis of pulmonary cryptococcosis was made from transbronchial brushings and histological examination. All three cases showed no impairment in their immune functions. These cases are described with a discussion of the literature.

Adult↗
PubMed1993

[A case report--pulmonary cryptococcosis associated with systemic lupus erythematosus and review of 44 cases in Japan].

A case of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) associated with pulmonary cryptococcosis which was successfully treated with fluconazole (FCZ) and flucytosine (5-FC) is described. A 63-year-old woman who had been treated with steroid for SLE and low dose methotrexate (MTX) for RA was admitted to Jichi Medical School Hospital because of abnormal shadow in the chest X-ray film. Physical examination revealed no abnormality. A chest CT film showed multiple nodular shadows localized in the right lower lobe. An ultrasonically guided trans-cutaneous lung biopsy performed on 10th hospital day established a diagnosis of pulmonary cryptococcosis. Following the treatment with FCZ and 5-FC for a month, her abnormal lung shadows improved and serum cryptococcal antigen level was decreased. A survey of the literature from 1955 to 1990 revealed 44 cases of SLE associated with cryptococcosis in Japan, in addition to our case, most of whom were on corticosteroid therapy. The majority of patients were young women, representing the usual population of patients with SLE. 34 of these patients had cryptococcal meningitis; 22, pulmonary cryptococcosis; 6, sepsis; 6 cutaneous cryptococcosis. Twenty patients died. Deep fungal infections should be considered whenever patients with SLE have fever of unknown origin, diffuse pulmonary infiltrates, or unexplained CNS symptoms.

Arthritis, Rheumatoid↗
PubMed1996

[Pleural cryptococcosis in patients with human immunodeficiency virus infection].

Four cases of pleural cryptococcosis as the form of onset of cryptococcosis in patients with human immunodeficiency virus (HIV) infection are reported. In two out of the four cases cryptococci were simultaneously isolated in other localizations (blood and meninges). In the two remaining patients the pleura was the only site of the disease, with serum determination of the cryptococci antigen being negative in one. The four patients evolved favourably, with three being exclusively treated with fluconazol. Pleuritis is an infrequent manifestation in cryptococcosis although it may be the form of onset and the only localization of the disease. Only 10 cases have been reported in patients with HIV infection. The present four cases represent 11% of the authors' series of cryptococcosis in AIDS patients. The diagnostic possibility of cryptococcosis should be considered in patients with human immunodeficiency virus infection presenting pleural effusion.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Clinical and serologic evaluation of cats with cryptococcosis.

OBJECTIVE: To evaluate the long-term clinical outcomes and serologic changes in cryptococcal antigen and antibody titers in cats with confirmed Cryptococcus neoformans infection. DESIGN: Prospective case series. ANIMALS: 47 cats with cryptococcosis. PROCEDURE: Cats included in this study were determined to have cryptococcosis on the basis of identification of C neoformans on histologic or cytologic examination, isolation of C neoformans in culture, or positive serologic test results for cryptococcal antigens. Information concerning the signalment, history, physical examination findings, FeLV and feline immunodeficiency virus status, serologic testing, treatment, and outcome for each cat was requested on a survey form. Follow-up measurements of serum cryptococcal antigen and antibody titers were requested for all surviving cats. RESULTS: Signalment and clinical signs of cats with cryptococcosis reported here were consistent with previous reports. Treatment consisted primarily of azole antifungal drugs. All cats were seronegative for cryptococcal antibody titers, whether tested initially or at follow-up examination. All but 1 cat tested were seropositive for cryptococcal antigens when initially tested. Cats with and without clinical signs of C neoformans infection were seropositive for cryptococcal antigens months to years after initial diagnosis of cryptococcosis. CLINICAL IMPLICATIONS: The results of this study indicate that serum titers to cryptococcal antigens in cats can persist with or without clinical signs for months to years after an initial diagnosis of cryptococcosis is made. Repeated evaluation of serum cryptococcal antigen titers is advised during the treatment of cats to monitor progress, evaluate prognosis, and guide cessation of treatment.

Animals↗
PubMed2006

Microglial cells from psychologically stressed mice as an accelerator of cerebral cryptococcosis.

Severe stress decreases the resistance of hosts exposed to microbial infections. As compared with two groups of control mice (normal mice, food-and-water-deprived mice [FWD mice]), restraint-stressed mice (RST mice) were shown to be greatly susceptible to intracerebral growth of Cryptococcus neoformans. The susceptibility of FWD mice to cerebral cryptococcosis increased to the level shown in RST mice, when these groups of mice were inoculated with microglial cells from the brains of RST mice. However, the susceptibility of FWD mice to cerebral cryptococcosis was not influenced by the adoptive transfer of microglial cells from normal mice or FWD mice. Microglial cells from RST mice produced CC-chemokine ligand-2 (CCL-2/monocyte chemoattractant protein 1), but not microglial cells from FWD mice. The resistance of RST mice to cerebral cryptococcosis was improved to the extent shown in FWD mice, when they were treated with anti-CCL-2 antibody. However, the susceptibility of normal mice and FWD mice to cerebral cryptococcosis increased to that shown in RST mice, when they were treated with rCCL-2. Microglial cells from RST mice were discriminated from the same cell preparations derived from FWD mice by their abilities to produce CCL-2, to phagocytize C. neoformans cells and to express Toll-like receptor 2. These results indicate that the resistance of RST mice to cerebral cryptococcosis is diminished by CCL-2 produced by microglial cells that are influenced by restraint stress.

Animals↗