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Epidemiology of cryptococcosis in France: a 9-year survey (1985-1993). French Cryptococcosis Study Group.

We analyzed the data collected during a nationwide survey of cryptococcosis (1985-1993). We first checked the quality of the survey. The stability of its completeness (approximately 50%) and its representativity were assessed by the capture-recapture method after we cross-checked our data on cryptococcosis (as a presenting manifestation of AIDS) against those of the national registry of AIDS. Of the 1,057 cases of cryptococcosis (1,013 patients), 827 (86%) involved patients with AIDS. The increasing number of cases of human immunodeficiency virus (HIV)-related cryptococcosis over time paralleled the AIDS epidemic except for a higher male-to-female ratio. Malignancies (32%), organ transplantation (19%), and corticosteroid therapy (33%) were the main predisposing conditions in 163 patients without AIDS. Cryptococcal meningitis more frequently occurred in patients with AIDS than in HIV-negative patients (P < 10(-6)). Among the 413 isolates available for serotyping, 410 were Cryptococcus neoformans variety neoformans (including 20.5% of serotype D). Three isolates of the variety gattii (serotype B) were recovered from patients without AIDS.

AIDS-Related Opportunistic Infections↗

[Chronic pulmonary cryptococcosis. A case contribution for diagnosis of cryptococcosis in man from a pathologic-anatomic viewpoint].

Routine use of differential nutrients for isolating cryptococcus neoformans (Staib-Agar) during post-mortem examination revealed previously unsuspected chronic pulmonary cryptococcosis in a 64-year-old woman. Cause of recurrent pleural effusions over three years were probably sub-pleural cryptococcomas. In on-target and specific search for the cryptococcosis pathogen, the lung deserves special attention as a probable gateway.

Autopsy↗

Cutaneous cryptococcosis as the first symptom of a disseminated cryptococcosis in a patient with lymphogranulomatosis X.

A 63-year-old patient, known to have suffered from lymphogranulomatosis X for 4 years is reported, in whom a cutaneous cryptococcosis appeared as first sign of a disseminated cryptococcosis. Despite systemic therapy with amphotericin B, the patient died after a period of 2 months. Differential diagnosis of skin tumours of immunosuppressed patients includes rare skin mycoses, and both histological and mycological examinations should be performed.

Cryptococcosis↗

[Disseminated cryptococcosis in 2 AIDS patients. A contribution to cryptococcosis diagnosis in AIDS].

In two AIDS patients (homosexual men) microscopical demonstration of Cryptococcus neoformans in samples obtained by puncture of the liver (n = 1) and additionally of the spleen (n = 1) led to the diagnosis of systemic cryptococcosis. Using the India ink method capsulated Cryptococcus neoformans cells could also be detected in cerebrospinal fluid (CSF) and urine. Concomitant culture of the fungus from tracheal secretion, CSF, urine and faeces confirmed the diagnosis of a disseminated infection; the identification and germ count of C. neoformans was achieved by means of the differential-selective medium Guizotia-abyssinica-creatinine agar. The C. neoformans antigen titres in serum and CSF corresponded to the stage of the mycosis as detected by microscopy and culture. After a six-week course of treatment with amphotericin B and flucytosine (Ancotil), the fungus could no longer be isolated from the materials examined in one patient. Mycological monitoring aiming at the detection of C. neoformans in the tracheal secretions by means of the mentioned differential-selective medium is therefore recommended as a prophylactic measure in AIDS patients and persons at risk.

Acquired Immunodeficiency Syndrome↗

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.

We retrospectively analyzed clinical outcome of meningeal and extrameningeal cryptococcosis in HIV-negative patients treated with amphotericin B (43 patients) or fluconazole (40 patients). Amphotericin B and fluconazole were prescribed equally to patients with neoplastic diseases and no risk factor, but organ transplant recipients and patients with other diseases were mostly given fluconazole and amphotericin B, respectively. Patients with more severe infections (i.e., meningitis, neurological disorders, or higher levels of antigen in cerebrospinal fluid) were more frequently treated with amphotericin B. A cure rate of > 70% was achieved regardless of the initial treatment and the severity of the infection. A Cox regression analysis showed that age of > 60 years, neoplastic disease, abnormal mental status, disseminated infection at the time of diagnosis, and therapeutic failure were independent predictors of death. Although fluconazole appears to be as effective as amphotericin B, only a prospective multicenter study will determine the best treatment regimen for patients with cryptococcal meningitis who do not have AIDS.

Adult↗

Proven pulmonary cryptococcosis due to capsule-deficient Cryptococcus neoformans does not differ clinically from proven pulmonary cryptococcosis due to capsule-intact Cr. neoformans.

We compared the clinical manifestations, laboratory and radiologic findings, and outcomes of eight patients with proven pulmonary cryptococcosis (PC) caused by capsule-deficient Cryptococcus neoformans with those of six patients with PC caused by capsule-intact Cr. neoformans. The presentations and outcomes did not differ significantly between the groups.

Adult↗

[Fatal cryptococcosis in a bird fancier. A clinical case report on pathology, diagnosis and epidemiology of cryptococcosis].

In a 69 year-old female patient who had been a pet bird enthusiast, cryptococcosis of the central nervous system was surprisingly established as cause of death at postmortem. Clinically, a diagnosis of cirrhosis of the liver associated with atypical coma hepaticum had been suspected. Apart from damage due to alcohol abuse, no other underlying disease could be found. The fecal matter of a budgerigar (Melopsittacus undulatus) has been suggested as the probable source of infection. Using Guizotia abyssinica creatinine agar, Cryptococcus neoformans could be isolated from dry fecal matter collected from the bird cage. In a pet shop in the neighbourhood of the patient's home, fecal matter from various pet bird species was collected. Using the same method, examination also revealed the presence of Cr. neoformans. Contrastingly, masses of pigeon manure found in the garret of the patient's house did not contain Cr. neoformans. The epidemiological significance of the fecal matter of pet birds as a habitat for Cr. neoformans is discussed.

Aged↗

Immunosuppression in experimental cryptococcosis in rats: modification of macrophage functions by T suppressor cells. Macrophages functions in cryptococcosis.

The influence of lymphocytes on the modulation of macrophage functions in altered immune states induced by Cryptococcus neoformans infection in rats has been investigated. In this report we observed a decrease of 'in vitro' phagocytic activity by peritoneal cells (PC) from rats that received T suppressor cells induced by cryptococcal infection, against both the same microorganism that stimulated this suppressor population (p less than 0.05) and another non-pathogenic primary yeast (Candida tropicalis), (p less than 0.02). The microbicide function of the PC from these animals present a significant decrease in challenge by C. tropicalis (p less than 0.002) when compared with PC from animals transferred with T normal cells. The transference of T suppressor cells induced by cryptococcal infection in animals immunized with human serum albumin-complete Freund's adjuvant (HSA-CFA) produces a significant alteration of the phagocytosis to HSA-human red cells (HSA-HRC) when compared with the phagocytosis observed in animals that received T normal cells or the phagocytosis of normal animals (p less than 0.001). We could also observe that the DTH to HSA studied during 30 days was negative in rats transferred with PC sensitizated with HSA and treated with suppressor T cells, when compared with the DTH response of animals transferred with PC-HSA cocultured with normal cells (p less than 0.05 21st day). The data presented in this paper illustrated that following infection of rats with C. neoformans there is a change in some population of accessory cells behavior reflected by the modification of several functions, such as phagocytosis, lytic activity and antigen presentation.

Animals↗

[Lung pathology of cryptococcosis].

To elucidate the relationship between the clinical manifestations and pathologic findings of the lung in patients with cryptococcosis, we reviewed 14 autopsied cases of cryptococcosis. Five patients had pulmonary cryptococcosis and 9 had disseminated cryptococcosis. Patients with pulmonary cryptococcosis showed granulomatous reactions of the lung, such as fibrocaseous cryptococcoma (n = 2), discrete granuloma (n = 2), and granulomatous pneumonia (n = 1). Patients with disseminated cryptococcosis showed intracapillary/interstitial involvement (n = 2), mucoid pneumonia (n = 3), histiocytic pneumonia (n = 1), and granulomatous pneumonia (n = 3). There was a distinct difference between pulmonary cryptococcosis and disseminated cryptococcosis in lung pathology. Intracapillary/interstitial involvement and mucoid pneumonia were fatal because of extensive hematogeneous dissemination to other organs. Hilar lymph node involvement of cryptococcosis was found in all of the nine patients with disseminated cryptococcosis and in one of the five patients with pulmonary cryptococcosis. Pleural involvement of cryptococcosis was found in six of the nine patients with disseminated cryptococcosis. We conclude that the clinical manifestations of cryptococcosis are closely associated with the variety of lung pathology of cryptococcosis. Clinicians should understand the morphologic features to cope with patients with cryptococcosis.

Adult↗

Incidence and factors associated with extrapulmonary cryptococcosis among persons with HIV infection in Los Angeles County.

OBJECTIVE: To determine the incidence and factors associated with extrapulmonary cryptococcosis among a cohort of persons with HIV in Los Angeles County. DESIGN: Records-based cohort study. METHODS: Data were analysed from a cohort of 3836 persons aged > or = 13 years with HIV infection enrolled from four outpatient facilities in Los Angeles from 1990 to 1995. The potential association between cryptococcosis and demographic risk behavior and clinical factors was assessed. Possible seasonal clustering was evaluated and an estimate of survival following cryptococcosis was calculated. Multivariate analysis was performed using a Cox proportional hazards approach. RESULTS: Cryptococcosis was identified in 112 patients (2.9%) representing a crude incidence rate of 1.7 cases per 100 person-years experience. The rate of cryptococcosis was higher among men than women (1.9 and 0.6, respectively; P < 0.01) and in Hispanics than in whites (2.3 and 1.2, respectively, P < 0.01). A significant trend of decreasing cryptococcosis was observed with increasing age (P < 0.01). Cryptococcosis increased with declining CD4+ lymphocyte count, with risk being greatest at CD4+ cell counts below 100 x 10(6)/l (P < 0.001). In bivariate analysis persons with a history of antifungal medication had a marginally lower rate of cryptococcosis, but this difference was not statistically significant. The rate of cryptococcosis was significantly higher in fall and winter months [rate ratio (RR), 1.45; 95% confidence interval (CI), 1.0-2.3; P = 0.05]. After controlling for other variables, cryptococcosis was more common in men than women (adjusted RR, 3.2; 95% CI, 1.0-10.4) and in Hispanics than whites (adjusted RR, 1.6; 95% CI, 0.9-2.7). Both CD4+ count and age continued to be strongly associated with the occurrence of cryptococcosis. After controlling for other factors a substantial protective effect was observed for antifungal therapy (adjusted RR, 0.48; 95% CI, 0.29-0.79). CONCLUSION: Our data suggest that HIV-infected men, Hispanics, persons aged under 45 years and those with CD4+ counts under 100 x 10(6)/l have an increased risk of extrapulmonary cryptococcosis. A fall-winter seasonality in the occurrence of cryptococcosis may exist. Significant primary protection against cryptococcal disease is afforded by antifungal therapy. These results may provide insight into possible routes of transmission and sources of cryptococcal infection and help guide both primary prophylaxis and early recognition and diagnosis in persons likely to be at increased risk.

AIDS-Related Opportunistic Infections↗

Surveillance of cryptococcosis in Alabama, 1992-1994.

PURPOSE: Although cryptococcosis is a significant opportunistic infection among patients with human immunodeficiency virus (HIV), there is conflicting information on rates of cryptococcosis among HIV-positive and HIV-negative patients. Precise state-wide epidemiologic data for cryptococcosis are not available in Alabama. METHODS: We conducted an active laboratory and hospital medical record-based surveillance for cryptococcosis in Alabama from October 1, 1992 to September 30, 1994. A case of cryptococcosis was defined as a patient's initial episode of cryptococcal disease and based on either a positive culture for C. neoformans from any normally sterile site, a positive latex agglutination serologic test for cryptococcal antigen in CSF or serum, or histopathologic findings consistent with C. neoformans. RESULTS: Over the two year period, 153 cases were identified. The diagnosis was based on positive culture (37%), positive antigen (24%), positive autopsy culture (2%), and histopathologic findings (4%). Further, 33% of the total cases were diagnosed from combined positive culture, antigen, or histopathology. Of the total 153 cases, 55% were in HIV-positive patients and 44% were in HIV-negative individuals and one case (1%) had an unknown HIV status. The overall annual incidence rate of cryptococcosis was 1.89 cases per 100,000 population. The incidence was 1638.7 per 100,000 in the HIV-positive population and 0.84 per 100,000 in the HIV-negative population. CONCLUSION: The first Alabama statewide active surveillance system for cryptococcosis confirms previous observations that rates of cryptococcosis are consistently higher in HIV-infected individuals than in their HIV-negative counterparts. In Alabama, cryptococcosis occurs more commonly in urban residents and in men. Cryptococcosis in HIV-positive persons is more likely to occur in the 20 to 44 year age group, whereas cryptococcosis in HIV-negative persons is more likely to occur in those greater than 45 years old.

AIDS-Related Opportunistic Infections↗

Prospects for preventing cryptococcosis in persons infected with human immunodeficiency virus.

Cryptococcosis is a major cause of illness and death among persons infected with human immunodeficiency virus (HIV). Its management must include both initial and maintenance treatment. Although most authorities favor an initial period of therapy with amphotericin B for acute cryptococcosis, the triazoles play a role in both the management of acute disease and subsequent maintenance therapy. AIDS surveillance data collected by the Centers for Disease Control and Prevention document the occurrence of cryptococcosis in more than 17,000 (6.2%) of adults with AIDS in the United States, although this figure is known to be an underestimate. The risk of cryptococcosis among HIV-infected persons is highest at CD4+ lymphocyte counts of < 100/microL. Although cryptococcosis is especially frequent among AIDS patients who are black, male, or injection drug users, the explanations for these patterns remain unclear. Whether geographic differences in rates of cryptococcosis result from variations in the environmental distribution of Cryptococcus neoformans as well as in the distribution of HIV infection is also unclear. Although exposure to pigeon feces is the best known of the putative exposure-related risk factors, proof is lacking that avian excreta are the primary environmental source of the organism in most cases of cryptococcosis. Prophylaxis with triazoles can prevent cryptococcosis and may be considered for adults and adolescents with CD4+ counts of < 50/microL. However, it is uncertain whether prophylaxis will affect survival, be cost-effective, or have an adverse impact on the susceptibility of a variety of fungi to antifungal drugs. Vaccines and monoclonal antibodies designed to prevent or modify cryptococcosis in HIV-infected persons are in the experimental stage.

Adult↗

Pulmonary cryptococcosis associated with HIV-1 infection in Rwanda: a retrospective study of 37 cases.

OBJECTIVES: To study the demographic, clinical, radiographic and diagnostic features, the clinical course and therapeutic response of pulmonary cryptococcosis in HIV-1-infected patients. DESIGN: Retrospective review. SETTING: The Department of Medicine of an urban reference hospital in Central Africa. METHODS: All the records of HIV-1-infected patients with pulmonary cryptococcosis were reviewed retrospectively with regard to the parameters described above. RESULTS: Over a 3-year period, pulmonary cryptococcosis was diagnosed in 37 HIV-1-infected Rwandan patients (21 men, 16 women; mean age, 35 years; range, 26-55 years). Twenty-nine patients (78%) had primary pulmonary cryptococcosis. Cough (94%), weight loss (65%), fever (51%), dyspnoea (46%), thoracic pain (30%), headache (13%) and haemoptysis (8%) were the predominant clinical findings. A diffuse interstitial infiltrate on chest radiograph was observed in 76% of the patients, an alveolar pattern in 19%, mediastinal and/or hilar adenopathy in 11%, nodules and pleural effusion each in 5%. Bronchoalveolar lavage, with a yield of 82%, was found to be the most sensitive diagnostic procedure. Screening of cryptococcal antigen in the serum failed to detect cases of primary pulmonary cryptococcosis. Twelve patients with primary pulmonary cryptococcosis treated with itraconazole as acute and maintenance therapy were all protected against disseminated cryptococcal disease; seven out of 10 (70%) of those who did not receive a specific anticryptococcal drug developed disseminated cryptococcal disease. CONCLUSION: Pulmonary cryptococcosis is not a rare complication of HIV-1 infection in Rwanda. Its clinical and radiographic patterns are non-specific and bronchoalveolar lavage is the procedure of choice for its diagnosis. The natural history of untreated primary pulmonary cryptococcosis is disseminated cryptococcal disease. Itraconazole is highly effective in the prevention of disseminated cryptococcal disease in patients with primary pulmonary cryptococcosis.

AIDS-Related Opportunistic Infections↗

Direct determination of cryptococcal antigen in transthoracic needle aspirate for diagnosis of pulmonary cryptococcosis.

Pulmonary cryptococcosis causes significant morbidity and mortality in immunocompromised patients. Definitive diagnosis of pulmonary cryptococcosis is usually difficult. The use of direct determination of cryptococcal antigen in transthoracic needle aspirate to diagnose pulmonary cryptococcosis was investigated. Over a 2-year period, we studied a total of 41 patients with respiratory symptoms and pulmonary infiltrates of unknown etiology who were suspected of having pulmonary cryptococcosis. Twenty-two patients were immunocompetent patients and 19 patients were immunocompromised. A diagnosis of pulmonary cryptococcosis was based on cytological examination, culture for Cryptococcus neoformans, histopathologic examination, and clinical response to antifungal therapy. All patients underwent chest ultrasound and ultrasound-guided percutaneous transthoracic needle aspiration to obtain specimens for cryptococcal antigen determination. The presence of cryptococcal antigen was determined by the latex agglutination system (CALAS; Meridian Diagnostics, Cincinnati, Ohio). An antigen titer equal to or greater than 1:8 was considered positive. The specimens were also sent for cytological examination, fungal culture, and/or histopathologic examination. A final diagnosis of pulmonary cryptococcosis was made in eight patients. Direct determinations of cryptococcal antigen in lung aspirate were positive in all eight patients with pulmonary cryptococcosis (100% sensitivity, 97% specificity, a positive predictive value of 89%, and negative value of 100%), and there was only one false-positive in noncryptococcosis patients. The diagnostic accuracy was 97.5%. Serum cryptococcal antigen was positive in only three patients with pulmonary cryptococcosis (sensitivity, 37.5%). This study showed that direct measurement of cryptococcal antigen in lung aspirate can be a rapid and useful test for diagnosis of pulmonary cryptococcosis.

Adolescent↗

Pulmonary cryptococcosis: manifestations in the era of acquired immunodeficiency syndrome.

To examine the clinical manifestations, treatment, and outcome of pulmonary cryptococcosis, we reviewed the medical records of all patients treated for Cryptococcus neoformans infection at our hospital from January 1988 through September 1998. Sixty-three patients were included in the analysis, 10 (16%) of whom had acquired immunodeficiency syndrome (AIDS). Thirty-four of the 53 non-AIDS patients, including 19 men and 15 women had pulmonary cryptococcosis, including 31 with isolated pulmonary cryptococcosis and three with disseminated disease. Of the 10 AIDS patients, seven presented with disseminated cryptococcosis (including one patient with lung involvement) and one had isolated cryptococcal lung disease. The age (mean +/- SD) of the 34 non-AIDS patients with pulmonary cryptococcosis was 52.1 +/- 15.2 years (range, 19-75 yr). Cough was the most common symptom (58%). Diabetes mellitus (12%) and malignancy (12%) were two major underlying diseases. Nodules and masses were the predominant manifestations of pulmonary cryptococcosis in non-AIDS patients (79%). The most frequently used diagnostic modality for pulmonary cryptococcosis was biopsy with/without aspiration under ultrasound guidance (56%). Antifungal therapy (20/34) was the most common treatment for non-AIDS patients, followed by surgical resections with antifungal therapy (9), surgical resections alone (3), and no treatment (2). Antifungal therapy and/or resection yielded excellent outcomes (total recovery, 27; improvement, 4). Of the 18 patients who underwent lumbar puncture, only two had positive cerebrospinal fluid (CSF) cultures for C. neoformans, both had symptoms and signs of increased intracranial pressure. There was no clinical evidence of meningitis in the other 32 patients. Our findings indicate that pulmonary cryptococcosis in non-AIDS patients tends to be a more localized and benign process than in AIDS patients. Ultrasound-guided lung biopsy or aspiration is an effective tool for diagnosis. CSF examination may not be mandatory as an initial routine procedure for pulmonary cryptococcosis in non-AIDS patients.

AIDS-Related Opportunistic Infections↗

Epidemiology of HIV-associated cryptococcosis in France (1985-2001): comparison of the pre- and post-HAART eras.

OBJECTIVE: To analyse the epidemiological evolution of cryptococcosis in France after the introduction of highly active antiretroviral therapy (HAART). DESIGN: Retrospective study of cryptococcosis cases recorded at the National Reference Center for Mycoses in France since 1985. METHODS: Using the national surveillance data, we reviewed 1644 cases of HIV-associated cryptococcosis diagnosed in France (population, 59 million) between 1985 and 2001 and compared them to 335 cases recorded in HIV-negative patients. RESULTS: The total number of cryptococcosis cases evolved in parallel to that recorded for HIV-infected patients. Changes occurring after HAART introduction were analysed. A negative binomial regression model established a 46% decrease of the incidence of cryptococcosis during the post-HAART era (1997-2001, n = 292) compared to the pre-HAART era (1985-1996, n = 1352). According to multivariate analysis, African origin, older age, heterosexual HIV contamination, no previous AIDS-defining illness, and no previous HIV infection diagnosis were variables independently associated with an increased risk of cryptococcosis during the post-HAART era. During the same period, the characteristics of the HIV-negative population did not change. CONCLUSIONS: Our analysis of the national surveillance identified demographic factors associated with an increased risk of cryptococcosis in the post-HAART era suggesting that failure to consult and considering oneself not at risk were determinant in the current epidemiology of HIV-related cryptococcosis in France.

AIDS-Related Opportunistic Infections↗