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PubMedDate not supplied

Detection of HIV RNA levels in intraocular and cerebrospinal fluids in patients with AIDS-related cryptococcosis.

The objective of the present study was to evaluate human immunodeficiency virus (HIV) levels in the aqueous humor and vitreous fluid in patients with and those without ocular involvement due to AIDS-related cryptococcosis. We also assessed whether cryptococcosis infection in the central nervous system (CNS) was associated with elevated HIV levels in the cerebrospinal fluid (CSF). From 1993 to 2003, we obtained 16 CSF samples from 9 AIDS patients with cryptococcal meningitis and 7 AIDS patients without CNS opportunistic infection. Samples of intraocular fluids were obtained from all 9 patients with cryptococcal meningitis. Five cases presented with ocular involvement in patients with meningitis. By using the method of reverse transcriptase-polymerase chain reaction, we detected higher HIV loads in aqueous humor (27,244+/-4,123 copies/ml) and vitreous fluid (84,930+/-5,071 copies/ml) in patients with concomitant CNS and ocular involvement due to AIDS-related cryptococcosis (p<0.05). HIV levels in the vitreous fluid were correlated with levels in CSF (r=0.77). Mean HIV level in the CSF (209,761+/-18,787 copies/ml) was significantly elevated in AIDS patients with cryptococcoal meningitis (p<0.05). To our knowledge, this is the first report to study the level of HIV loads in the CSF and intraocular fluid simultaneously in AIDS patients with cryptococcosis. Our results revealed the intrathecal and intraocular HIV replication in patients with cryptococcosis.

AIDS-Related Opportunistic Infections↗
PubMed2003

Primary cutaneous cryptococcosis: a distinct clinical entity.

Cryptococcus neoformans is an encapsulated yeast responsible for disseminated meningitis in immunocompromised hosts. Controversies persist on the existence of primary cutaneous cryptococcosis (PCC) versus cutaneous cryptococcosis being only secondary to hematogenous dissemination. Thus, we reviewed cryptococcosis cases associated with skin lesions reported in the French National Registry. Patients with PCC (n=28) differed significantly from those with secondary cutaneous cryptococcosis (n=80) or other forms of the disease (n=1866) by living area (mostly rural), age (older), ratio of men to women (approximately 1:1), and the lack of underlying disease. Evidence of PCC included the absence of dissemination and, predominantly, a solitary skin lesion on unclothed areas presenting as a whitlow or phlegmon, a history of skin injury, participation in outdoor activities, or exposure to bird droppings, and isolation of C. neoformans serotype D. Therefore, PCC is a distinct epidemiological and clinical entity with a favorable prognosis even for immunocompromised hosts.

Adult↗
PubMed2006

Molecular analysis of 311 Cryptococcus neoformans isolates from a 30-month ECMM survey of cryptococcosis in Europe.

During a European Confederation of Medical Mycology (ECMM) prospective survey of cryptococcosis in Europe (from July 1997 to December 1999) 655 cases were reported from 17 countries; 565 of the completed questionnaires were evaluable. Cryptococcosis was associated with HIV infection in 77% of cases (range 57.5-94%). Assessment of the laboratory data highlighted the lack of defined standard procedures for the diagnosis of cryptococcosis: the antigen test was not usually used for screening, the disease was mainly recognised when meningitis occurred (65% of patients) and, with the exception of a few cases, the extent of the infection was not investigated. Cryptococcus neoformans was the etiological agent in all of the cases except for six caused by C. gattii and four by other Cryptococcus species. A total of 311 C. neoformans strains were serotyped by Crypto Check latex agglutination, genotyped by PCR-fingerprinting using the (GACA)4 oligonucleotide as a single primer, and their mating type was determined by PCR of the STE20 alleles. Serotype A was the most represented (51% of the isolates), followed by serotype D (30%) and serotype AD (19%). PCR-fingerprinting analysis significantly increased the percentage of hybrid strains to 30%, as 6% of the serotype A and 28% of the serotype D isolates were of the VN3 or VN4 hybrid genotype. In addition, the mating type determinations revealed the MATa serotype A allele in one haploid strain and 28 hybrids, and hybrid isolates with a single mating type (four Aalpha and two Dalpha) were also identified. This is the first prospective survey to be carried out in Europe which has attempted to investigate the epidemiology of cryptococcosis and the population structure of C. neoformans, and the results obtained thus far show the widespread involvement of AD hybrid strains in C. neoformans infections.

Adolescent↗
PubMed1989

Current concepts in cryptococcosis.

Cryptococcus neoformans has become an increasingly important pathogen. Cryptococcosis is an important cause of morbidity and mortality in immunocompromised hosts and is the second most common fungal infection complicating AIDS. In recent years, research has focused on the host defenses against Cryptococcus and has led to an improved understanding of the capsular virulence of the organism, the mechanisms of T-cell defenses, and the role of phagocytic cells in the fungistasis and killing of cryptocci. Amphotericin B with or without flucytosine has clearly improved treatment of cryptococcosis, but therapy is associated with significant toxicity. Current investigation is focused on the triazoles, which may offer improved therapy for cryptococcosis. In this report, we review recent developments in the understanding of the host defenses against Cryptococcocus and discuss current recommendations for the management of cryptococcosis.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Disseminated cryptococcosis with extensive cutaneous involvement in AIDS].

BACKGROUND: Diagnosis of an ulceratively decaying indolent papule in the skin of an AIDS patient. CASE REPORT: In a 36-year-old HIV-positive man with a CD4 lymphocyte count of 60/microliters, a diagnosis of disseminated cryptococcosis was established based on a biopsy of an ulceratively decaying indolent papule in the skin of the left side gluteal region. In additional papulopustular skin lesions of neck, upper arm, upper thigh, and rima ani, Cryptococcus neoformans var. neoformans was detected by specific culture. The Cryptococcus neoformans antigen titre in serum was 1:160. The extensive cryptococcal skin involvement was accompanied by symptoms of meningeal cryptococcosis like hearing at an abnormal sound volume, a sensation of high pressure in the head and a change of behaviour, but absence of cephalgia and stiff neck. Attention is drawn to the importance of biopsy for the differential diagnosis of the skin lesions and to the significance of a specific cultural detection of Cryptococcus neoformans in view of the therapy and epidemiology of this mycosis. Under a combination therapy, consisting of amphotericin B, flucytosine and fluconazole, a healing of the skin lesions and disappearance of the neurological symptoms followed by negative cultural and serological tests were seen. Specific comments on the epidemiology of cryptococcosis in AIDS are made. CONCLUSION: In case of doubt, papulopustular skin lesions of HIV-positive patients should be biopsied. Cryptococcosis should also be considered.

AIDS-Related Opportunistic Infections↗
PubMed1998

Cryptococcosis in Hodgkin's disease: description of two cases and review of the literature.

Systemic mycosis caused by Cryptococcus neoformans frequently becomes life threatening in patients with cellular immunodeficiencies. In contrast to AIDS patients, there are only a few reports of concurrent systemic cryptococcosis in patients with Hodgkin's disease (HD). Only two of 75 (2.7%) patients with HD who were consecutively admitted to our hospital in the past decade developed Cryptococcus neoformans infection. Both had stage IVB (Ann Arbor) HD with bone marrow involvement and absolute lymphopenia (< 1/nl). We have reviewed the literature and analyzed the data of 54 cases with concurrent cryptococcosis and HD. Presence of HD for > or = 12 months, stage IV disease, absolute lymphopenia (< 1/nl), and extensive pretreatment were the most common features among these patients and must be regarded as predisposing for acquiring a cryptococcal infection. In our patients antimycotic therapy was successful using liposomal amphotericin B (lipAmB) simultaneously with cytotoxic therapy for HD. Drug level measurements performed in one patient revealed a higher level of amphotericin B in CSF when the liposomal formulation was administered as compared with the level in CSF after administration of conventional amphotericin B. To our knowledge, this is the first report on antimycotic treatment of cryptococcosis with lipAmB in patients with HD. Regarding the favorable therapeutic index of lipAmB as compared with conventional amphotericin B, the drug should be considered as a less toxic and perhaps more effective alternative in the therapy of acute cryptococcosis, especially when cytotoxic treatment is administered simultaneously.

Adult↗
PubMed1984

Chronic pulmonary cryptococcosis in a Rattus rattus from Rabaul, Papua New Guinea.

A wild Rattus rattus trapped in Rabaul, East New Britain Province, Papua New Guinea, was noted to have chronic, cystic pulmonary cryptococcosis. R. rattus is common in settlements in Papua New Guinea whereas pigeons, which have been suspected as a possible source of human cryptococcosis, rarely nest in villages in this country. If R. rattus was susceptible to chronic pulmonary cryptococcosis, because of its habit of nesting in roofs, it could serve as a possible vector of human cryptococcosis in Papua New Guinea and perhaps in other countries as well.

Animals↗
PubMed2006

Computed tomography (CT) and positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG-PET) images of pulmonary cryptococcosis mimicking lung cancer.

BACKGROUND: The objective of this study was to clarify the clinical features of pulmonary cryptococcosis using chest computed tomography (CT) and positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG-PET), with a view to developing appropriate treatment. METHODS: We analyzed the clinical features, and chest CT and FDG-PET characteristics of six cases of pulmonary cryptococcosis that were treated by surgery. The patients comprised four males and two females, ranging in age from 28 to 79 years. RESULTS: All the patients were asymptomatic and had no extrapulmonary involvement. In all cases, chest CT showed nodular shadows. Spiculation and convergence of peripheral vessels were demonstrated in three cases, and pleural indentation in two cases. FDG-PET was performed in four of the cases, and showed accumulation of FDG in all of them. The standard uptake value (SUV) ranged from 0.93 to 4.85. Chest CT findings and accumulation of FDG made it difficult to distinguish pulmonary cryptococcosis from malignancies. Segmentectomy or wedge resection was performed in all cases for pathological diagnosis, and this revealed Cryptococcus fungal bodies. After surgical resection, no sign of relapse has been seen in any of the patients. CONCLUSIONS: Surgical resection is recommended for both diagnosis and treatment of pulmonary cryptococcosis.

Adult↗
PubMed2005

Clinical features and high-resolution CT findings of pulmonary cryptococcosis in non-AIDS patients.

The objective of this study was to clarify clinical and high-resolution computed tomography (HRCT) characteristics in non-AIDS patients with pulmonary cryptococcosis. We analyzed the medical records and HRCT scans in 22 patients with pulmonary cryptococcosis from 1988 to 2003. Thirteen patients (59%) were immunocompetent and nine (41%) were immunosuppressed, seven of whom had diabetes mellitus. No patients exhibited extrapulmonary involvement. Nineteen patients (86%) were asymptomatic. Radiography revealed incidental chest abnormality in all but two patients. The typical HRCT findings were solitary or multiple nodules in the subpleural area. Cavitation was present in 30% of the patients who had nodules. The most frequently applied and reliable diagnostic procedure was video-assisted thoracoscopic surgery (VATS). Treatment included antifungal therapy alone in 11 patients, surgery alone in eight including four treated by VATS, surgery plus antifungal therapy in two and none in one. Patients who underwent surgery alone did not develop any relapse. The majority of non-AIDS patients with pulmonary cryptococcosis present with incidental chest radiographic abnormalities. The most common HRCT findings are solitary or multiple nodules with or without cavitation in the subpleural areas of the lung. VATS is a useful tool for both diagnosis and treatment of isolated pulmonary cryptococcosis.

Adult↗
PubMed1988

Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome.

PURPOSE: Because of the increasing numbers of patients with acquired immunodeficiency syndrome (AIDS) who will require treatment for cryptococcosis and because of the problems associated with long-term administration of intravenous amphotericin B, an alternative therapeutic approach in the form of an efficacious and easily administered oral antifungal drug would be of great benefit. Fluconazole, a new triazole antifungal agent, represents such an alternative. We therefore conducted an open, non-randomized trial of oral fluconazole as maintenance suppressive therapy of disseminated cryptococcosis in patients with AIDS. PATIENTS AND METHODS: Twenty patients with AIDS, 19 of whom had cryptococcal meningitis, were studied. Patients were followed for up to 21 months. All patients received amphotericin B as primary therapy, from 20 to 257 days prior to entry (500 to 5,080 mg total dose). Eight also received flucytosine. After administration of amphotericin B for acute disseminated cryptococcosis, and prior to initiation of fluconazole therapy, Cryptococcus neoformans was isolated from the cerebrospinal fluid (CSF) in two patients and from the blood in one patient. Fluconazole was given once daily, in doses of 50 to 200 mg/day. RESULTS: Following initiation of fluconazole, results of CSF and blood cultures continued to be negative, except for the CSF culture in one patient who had a relapse in the 32nd week of therapy. Fluconazole therapy has been successfully continued in nine patients, for a median of 11 months (nine to 21 months). Seven patients died; five had no evidence of active cryptococcosis at the time of death. Two patients had a relapse, although the CSF culture showed growth of the fungus in only one patient. One patient was lost to follow-up after five months of therapy and one was unevaluable. Fluconazole had to be discontinued in only one patient in whom thrombocytopenia developed, and then resolved when the drug was stopped. CONCLUSION: We conclude that oral fluconazole represents a significant advance in the management of cryptococcal meningitis and should be useful in the long-term suppressive therapy of this opportunistic infection in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Pulmonary cryptococcosis.

Observation of an unusual pulmonary distribution of cryptococci in a patient at autopsy prompted a review of 36 patients with pulmonary cryptococcosis listed in the autopsy files of The Johns Hopkins Hospital. The patients ranged in age from 2 to 89 years (mean, 49 years), 19 were female, and 18 were black. All but three patients had underlying debilitating diseases, and 23 patients had received steroids and/or chemotherapy. In 25 patients (69 per cent) cryptococcosis was a major factor contributing to death, through pulmonary disease in ten, systemic involvement in seven, and central nervous system disease in eight. In 15 patients (42 per cent) cryptococcosis was diagnosed clinically. Four basic morphologic patterns were observed: 1) Seven patients (19 per cent) had one or more peripheral pulmonary granulomas. In three of these patients the granulomas were apparently quiescent, and no other lesions were found. 2) Nineteen patients (53 per cent) had what has been called granulomatous pneumonia, with intra-alveolar proliferating organisms and varying degrees of inflammatory response, which, when present, ranged from acute inflammation to diffuse intra-alveolar granulomas with giant cells. 3) In seven patients (19 per cent) organisms were present diffusely within alveolar capillaries and interstitial tissues, and reactions ranged from little or no inflammation with numerous organisms to few organisms with miliary granulomas. 4) In three patients (8 per cent) both intra-alveolar and intravascular organisms were present in massive numbers, and the primary route of infection was uncertain. Fatalities from pulmonary and generalized infection occurred in patients in each histologic group. The results show marked variability both in pathologic reaction to cryptococci and in the clinical appreciation and significance of pulmonary cryptococcosis.

Adolescent↗
PubMedDate not supplied

Cryptococcosis in a North Island brown kiwi (Apteryx australis mantelli) in New Zealand.

A case of disseminated cryptococcosis in a North Island kiwi (Apteryx australis mantelli) caused by Cryptococcus neoformans var. gattii (serotype B) is reported. This is the first case of cryptococcosis to be reported in a kiwi and is also the first isolation of C. neoformans var. gattii from a veterinary source in New Zealand. The kiwi is an example of a ratite bird and as such has a lower body temperature approximating that of a mammal. As a consequence, the kiwi and other ratitis (e.g. emus) would be expected to show an increased susceptibility to cryptococcosis compared with other birds. There has been only one other isolate of this variety of C. neoformans in New Zealand and this was isolated from the sputum of a human male with leukaemia who was from the Gisborne area of the North Island, a region adjacent to Hawkes Bay where the case of kiwi cryptococcosis occurred. Some months prior to the development of the infection in the bird, a mulch of Eucalyptus leaves/twigs had been spread throughout the kiwi enclosure and this is considered to have been the probable source of the yeast. Neither Eucalyptus camaldulensis nor Eucalyptus tereticornis were among the species from which the mulch material originated and it is suggested another species may be the environmental host(s) of C. neoformans var. gattii in New Zealand.

Animals↗
PubMed2001

Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.

We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.

Adolescent↗
PubMed2003

The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992-2000.

To examine trends in the incidence and epidemiology of cryptococcosis, active, population-based surveillance was conducted during 1992-2000 in 2 areas of the United States (the Atlanta, Georgia, and Houston, Texas, metropolitan areas; combined population, 7.4 million). A total of 1491 incident cases were detected, of which 1322 (89%) occurred in HIV-infected persons. The annual incidence of cryptococcosis per 1000 persons with AIDS decreased significantly during the study period, from 66 in 1992 to 7 in 2000 in the Atlanta area, and from 24 in 1993 to 2 in 1994 in the Houston area. Poisson regression analysis revealed that African American persons with AIDS were more likely than white persons with AIDS to develop disease. Less than one-third of all HIV-infected persons with cryptococcosis were receiving antiretroviral therapy before diagnosis. Our findings suggest that HIV-infected persons who continue to develop cryptococcosis in the era of highly active antiretroviral therapy (HAART) in the United States are those with limited access to health care. More efforts are needed to expand the availability of HAART and routine HIV care services to these persons.

AIDS-Related Opportunistic Infections↗
PubMed1995

Pulmonary cryptococcosis: localized and disseminated infections in 27 patients with AIDS.

We reviewed the records of 85 patients infected with both human immunodeficiency virus and Cryptococcus neoformans. Twenty-seven patients (32%) had pulmonary cryptococcosis. C. neoformans was cultured from bronchoalveolar lavage (BAL) or pleural fluid in 25 cases; the remaining two patients had cryptococcal antigen (CA) detected in BAL fluid and C. neoformans cultured from other sites. All but one of the 27 patients had detectable CA in serum. The CD4+ lymphocyte count was low in all cases (median, 24/mm3). Clinical manifestations of pulmonary cryptococcosis included fever (94%), cough (71%), dyspnea (7%), expectoration (4%), chest pain (2%), and hemoptysis (1%). Diffuse interstitial opacities (70.5%), focal interstitial abnormalities, alveolar opacities, adenopathies, cavitary lesions, and pleural effusions were evident. Outcome was poor (mean survival time, 23 weeks) despite treatment. Patients with localized pulmonary cryptococcosis appeared to have a higher CD4+ lymphocyte count, an earlier diagnosis, lower serum CA titers, fewer previous or concomitant infections, and a better prognosis than patients with disseminated cryptococcosis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Case report: cutaneous manifestations of cryptococcosis.

Cutaneous cryptococcosis usually is associated with concurrent systemic infection and actually may develop before clinical manifestations of cryptococcal meningitis become apparent. It is rare for a cryptococcal infection to be localized only to the skin. A case of cutaneous cryptococcosis is described in an immunocompromised patient who initially had a rash and a positive serum cryptococcal antigen titer, but no central nervous system involvement. The papular pustular skin lesions disappeared after 8 weeks of therapy with amphotericin B, which was stopped secondary to progressive azotemia. Less than 2 months after therapy, the skin lesions recurred, again without evidence of systemic disease. Treatment with oral fluconazole resulted in a gradual resolution of the cutaneous lesions. The pathogenesis of cryptococcosis is discussed, with emphasis on the management of cutaneous cryptococcosis.

Aged↗
PubMed2004

Hepatic cryptococcosis in a heart transplant recipient.

Cryptococcosis primarily occurs in patients with impaired immune response. While pulmonary and/or cerebral involvement are more often described, there is limited experience of its presence in other sites. We present a case of hepatic cryptococcosis with possible pulmonary involvement in a 54-year-old male heart transplant recipient. Two months after heart transplantation, he developed a persistent, moderate dyspnea with fever and signs of liver damage. Diagnosis was made with liver biopsy for a concurrent reactivation of chronic hepatitis B virus (HBV) infection already present before transplant. Along with a mild chronic HBV hepatitis with fibrosis, we observed sinusoidal dilation and groups of bright, rounded, colorless cells with a central nucleus suggestive of cryptococci. Periodic acid-Schiff stain clearly showed encapsulated yeasts, which supported the diagnosis. Cryptococcal antigen was positive in serum and negative in the cerebrospinal fluid. Computed tomography scan of the chest demonstrated a mild interstitial infiltrate. The patient promptly responded to reduction of immunosuppressive therapy and antifungal treatment with amphotericin B lipid complex and flucytosine followed by maintenance treatment with fluconazole. Cryptococcosis should always be considered in the differential diagnosis in immunocompromised hosts with dyspnea and signs of extrapulmonary involvement. Diagnosis of extrapulmonary and extraneural cryptococcosis is difficult and often fortuitous; a histopathological examination of tissues involved is probably warranted.

Cryptococcosis↗
PubMed2005

Cryptococcosis after living donor liver transplantation: report of three cases.

Cryptococcosis is the third most common invasive fungal infection in solid organ transplantation, which usually occurs more than 6 months after the primary operation. In our series of 180 consecutive adult living-donor liver transplantation recipients, three (1.5%) had cryptococcosis and one of these patients died. The serum cryptococcal antigen examination was positive in all three patients who suffered from cryptococcosis. The serum cryptococcal antigen test might contribute to the early detection and treatment of cryptococcosis.

Aged↗