Epidemiology & Social
Epidemiology of HIV-associated cryptococcosis in France (1985–2001): comparison of the pre- and post-HAART eras
Dromer, Françoisea; Mathoulin-Pélissier, Simoneb; Fontanet, Arnaudc; Ronin, Olivierd; Dupont, Bertrandd; Lortholary, Oliviera,d; on behalf of the French Cryptococcosis Study Group
From the aCentre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, Institut Pasteur, Paris, bService de Biostatistique, Institut Bergonié, Bordeaux, cUnité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, and dService de Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, Paris, France. *See Appendix.
Correspondence to F. Dromer, Centre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Received: 3 July 2003; revised: 15 September 2003; accepted: 29 September 2003.
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.
Cryptocococcosis is the most common life-threatening systemic fungal infection occurring in HIV-infected patients, and extrapulmonary cryptococcosis is an AIDS-defining illness. The most frequent clinical presentation is disseminated meningoencephalitis which is rapidly fatal in the absence of antifungal treatment [1–4].
Excellent reviews on the epidemiology of the infection were published in the early 1990s [5–7]. Up to 1996, the prevalence of cryptococcosis among HIV-patients varied from < 1 to 10% in Western countries [8–13] as opposed to almost a third of HIV-infected individuals in sub-Saharian Africa and Southeast Asia [14,15] where it is associated with high mortality [16,17].
Before 1996, the decline in the frequency of some opportunistic fungal infections was attributed to increased prophylactic usage of drugs active against various pathogens [12,18–20]. Since the introduction of highly active antiretroviral therapy (HAART), the nationwide AIDS surveillance programmes implemented in Western countries have reported sharp decreases in the incidences of AIDS cases and the estimated number of deaths among AIDS patients, while the number of persons living with AIDS has increased [21–24]. Concomitant decreases of the incidences of several opportunistic infections, especially Pneumocystis carinii pneumonia, Mycobacterium avium complex, cytomegalovirus and even Cryptococcus neoformans have been ascribed to the introduction of HAART in these countries [25–30].
Data collected by our national surveillance program enabled us to analyse the modifications of cryptococcosis epidemiology in France and to identify demographic factors associated with an increased risk of cryptococcosis in the post-HAART era.
Materials and methods
In 1985, the National Reference Center for Mycoses (NRCM)  instigated a nationwide survey on cryptococcosis in France through a passive system of data collection with the voluntary participation of clinicians and biologists comprising the French Cryptococcosis Study Group. We previously assessed the completeness of our data collection system by capture–recapture analysis . We have now analysed the cases diagnosed in France from 1 January 1985 to 31 December 2001 and sent to the NRCM before 30 June 2002 (without adjustment of reported cases for reporting delays).
Cases diagnosed by culture of C. neoformans from a specimen from any site, by antigen detection in cerebrospinal fluid (CSF) and/or serum samples, and/or by histopathological findings consistent with cryptococcosis were considered to be cryptococcosis. Recurrence was considered only if it occurred > 6 months after the previous episode or it was the first episode reported to the NRCM. The isolate had been identified as C. neoformans in each participating laboratory and was sent to the NRCM for serotyping .
Data collection and evaluation
Data were recorded on a standardized form by the treating clinician and/or the biologist and mailed to the NRCM. The one-page questionnaire, unchanged since 1990 , included demographic characteristics, and epidemiological and mycological data.
Our classification of HIV-infected patients was based on that established by the Centers for Disease Control and Prevention (CDC) in 1993  and on criteria used by the French Government Agency for Disease control and Prevention (Institut de Veille Sanitaire) . Thus, five exposure categories were established: homosexuality/bisexuality, injecting drug use, heterosexuality, contamination by blood or blood products, and others (including combinations of the previous categories, mother-to-child transmission, and unknown risk factors). Depending on the stage of HIV infection, extrapulmonary cryptococcosis was considered to be an AIDS-defining illness (sometimes revealing HIV infection) or not. Patients also were classified according to their continent of birth: Europe, Africa, or others (including North, Central and South America, Caribbean Islands, and Asia).
Cases were classified as cryptococcal meningitis (C. neoformans-positive CSF assessed by direct examination, antigen testing or culture) or as extrameningeal cryptococcosis.
Two periods were defined: pre-HAART (1985–1996) and post-HAART (1997–2001); HAART was introduced in France in mid-1996.
In accordance with French law, the NRCM database was approved by the National Commission on Informatics and Freedom (Commission Nationale de l'Informatique et des Libertés). All variables were coded. Epi-Info software (version 6.04c, 1997, CDC, Atlanta, Georgia, USA, and World Health Organization, Geneva, Switzerland) was used to record data. For the analyses of cryptococcosis, all reported cases were used, whereas only the first recorded episode was considered for the analysis of patients. Percentages were compared using chi-square or Fisher's exact tests. Means were compared with Student's t test or analysis of variance. A logistic regression was constructed for multivariate analysis. All variables that were clinically relevant or statistically significant in the univariate analysis (P < 0.25) were entered simultaneously into the full model . These results are reported as odds ratios (OR) and their 95% confidence intervals (CI). A negative binomial regression model was constructed to evaluate the evolution of the incidence of cryptococcosis among HIV-positive subjects after the introduction of HAART. Estimates of the total number of HIV-positive subjects per year in France were obtained from Angela Downs (EuroHIV, Institut de Veille Sanitaire; personal communication, 2003). Analyses were performed using Stata computer package version 7 (Stata Statistical Software, Stata Corporation, College Station, Texas, USA).
Trends in the occurrence of cryptococcosis in France
Among the 2125 cases recorded from 135 cities around the country, 1644 were diagnosed in HIV-infected individuals (including 184 cases recorded as recurrences of which 46 were a first notification). The total number of cases paralleled that recorded for HIV-positive patients with a steady rise until 1995, a sharp decrease in 1996 and 1997 and a plateau thereafter (Fig. 1). Using recent data from the Institut de Veille Sanitaire , we found that the annual percentage of cryptococcosis cases among the new AIDS cases was stable over time (mean, 3.5 ± 0.3%).
Cases of cryptococcosis were recorded throughout the country but mostly in three regions: Paris and its suburbs (54% of all cases), the Mediterranean area (15%) and the Southwest (11%), which correspond to the highest densities of HIV-positive individuals. No seasonal fluctuation was observed in the numbers of cases recorded.
Characteristics of the population diagnosed with cryptococcosis
HIV-infected patients were significantly younger and more often born in Africa than HIV-negative patients (Table 1). The percentage of males of all ages was significantly higher for HIV-positive than HIV-negative patients (male : female ratio, 6.8 versus 1.7; P < 0.001) and increased significantly with age among males. The sex ratio according to the HIV seropositivity or -negativity was similar for African patients (male : female ratio, 2.5) while it differed significantly for European patients (male : female ratio, 10 versus 1.7, P < 0.001). Females were significantly younger than males only in the HIV-infected population [median age in years (range), 33 (8–80) versus 36 (9–84); P < 0.001].
HIV-negative patients risk factors for cryptococcosis included solid organ transplantation (mostly kidney, 17.4%), haematological malignancies (lymphomas, chronic lymphoid leukaemia, myeloma and other dysglobulinaemias) and solid cancers (36.8%), miscellaneous underlying diseases (systemic inflammatory diseases, sarcoidosis, idiopathic CD4 lymphocytopenia, cirrhosis, diabetes mellitus, or pre-existing pulmonary diseases such as tuberculosis, asthma or cystic fibrosis; 20.4%), and no underlying disease (25.4%) but a clinical history compatible with primary cutaneous cryptococcosis for some patients .
Among the 19 children diagnosed with cryptococcosis (≤ 15 years old, 10 boys and nine girls) with a median age of 11 years [3–15], six were HIV-infected, four had malignancies (lymphomas, myeloid leukaemia), two had hyper-IgM syndrome. Five children including three with primary cutaneous cryptococcosis had no identified risk factor.
Characteristics of the fungal infection
Cryptococcal meningitis was diagnosed in 74% of the HIV-positive patients and the infection was disseminated in 46% of them [based on positive cultures of blood (31%), urine (17%), bronchoalveolar lavage (14%) or skin (2.5%) samples]. Among the HIV- negative patients, 51% had cryptococcal meningitis and the infection was disseminated in 41% of them [based on positive cultures of blood (22.5%), urine (15%), bronchoalveolar lavage (11%) or skin (7%) samples]. For patients with no positive CSF culture (i.e., negative culture or not done), blood, urine, broncholaveolar lavage and skin cultures were positive for respectively 29%, 14%, 32% and 5% of HIV-positive patients, and for 19.5%, 9%, 35% and 33.5% of HIV-negative patients. It should be noted however, that differences were observed in clinical practices (diagnostic procedures, extent of work-up) according to HIV status and the region of diagnosis (data not shown).
The isolates recovered from 1190 patients with cryptococcosis were available for serotyping. Rare isolates were identified as variety gattii serotype B (11 isolates including four from HIV-positive patients), 22.5% were serotype D and serotype A predominated (76.5%).
Influence of HAART introduction on the epidemiology of cryptococcosis in France
Demographic characteristics of HIV-infected patients diagnosed with cryptococcosis were analysed over time. We defined two periods according to the year of cryptococcosis diagnosis, i.e., the pre-HAART (n = 1352) and post-HAART (n = 292) eras (Table 2). The incidence of cryptococcosis among HIV-positive individuals decreased by 46% during the post-HAART period (P < 0.001).
The number of cases recorded for male homosexuals declined sharply and the diminution was somewhat less for male and female injecting drug users, while the number of cases recorded of persons exposed through heterosexual contacts remained stable (Fig. 2). Compared to the pre-HAART era, significantly higher post-HAART percentages were observed for African-born patients whose cryptococcosis revealed HIV infection (13% versus 30%; P < 0.001), patients with no previous AIDS-defining diagnosis (40.7% versus 58.5% for both sexes; P < 0.001), and heterosexual HIV transmission for both sexes (19.3% versus 47.6%; P < 0.001). The types of cryptococcal disease, the percentages of serotype D isolates and the median CD4 counts did not change over time. According to our multivariate analysis, African origin (OR, 2.07; 95% CI, 1.35–3.14; P = 0.001), ‘older’ age (35–45 years: OR, 2.04; 95% CI, 1.42–2.93; P < 0.001; and > 45 years-old: OR, 1.93; 95% CI, 1.23–3.03; P = 0.004), heterosexual HIV contamination (OR, 2.39; 95% CI, 1.64–3.47; P < 0.001), no previous HIV-infection diagnosis (OR, 1.6; 95% CI, 1.03–2.49; P = 0.035) or no previous AIDS-defining diagnosis (OR, 1.66; 95% CI, 1.14–2.42; P = 0.008) were variables independently associated with the post-HAART era.
Among patients with cryptococcosis whose HIV status was known, 14.6% were seronegative during the pre-HAART era as opposed to 26.1% during the post-HAART era (P < 0.001). However, none of the characteristics of the HIV-negative population (sex ratio, age, ethnic origin, risk factors, serotype of the isolate) changed over time (data not shown).
Because cryptococcosis is not a notifiable disease anywhere, only specific surveillance programs can provide accurate data on the trends in its epidemiology. The NRCM instigated such a program in 1985, at the beginning of the AIDS epidemic, when clinical advice was increasingly sought for this unusual fungal infection. Since then, clinicians and microbiologists have voluntarily reported their cases. Given that the system did not change since we assessed its exhaustivity at approximately 50% in 1996 , we assumed that the following years also provided accurate data.
Over the 17-year study, 2125 patients were diagnosed with cryptococcosis in France (population, 59 million). The number of cryptococcosis cases recorded for HIV-infected patients increased until 1995, declined abruptly over 1996 and 1997 and then levelled off, in parallel with the incidence of AIDS cases recorded in France . This evolution differs from that observed in four areas of the USA, where decreased incidences of cryptococcosis started in 1994, first attributed to the use of fluconazole  and later to HAART .
We observed that the characteristics of the HIV-infected patients with cryptococcosis changed after the introduction of HAART. The decreased incidence essentially occurred among European male homosexuals, leading to a significant increase of the relative percentages of African-born patients and patients contracting HIV through heterosexual contacts, a finding not elucidated in the recent American analysis made by Mirza et al. . In both the French and the American-AIDS surveillance programs however [21,22], the numbers of AIDS cases attributed to heterosexual transmission have stabilized or even increased in the recent years, while the other exposure groups (male homosexuals and intravenous drug users of both sexes) declined, and the number of patients with poorer access to care increased.
Other demographic characteristics of the patients also changed. The median age of the HIV-infected patients with cryptococcosis increased during the post-HAART era, a finding in agreement with what has been observed for the entire AIDS population in France. Cryptococcosis revealed the HIV infection for a higher percentage of patients diagnosed in France during the post-HAART era. Indeed, it was the AIDS-defining illness for 57% of the 221 males and 66% of the 53 females patients during the post-HAART era, values significantly higher than those observed during the pre-HAART era in France (39.5% of the 961 males and 49% of the 124 females) and during the 1992–2000 survey in the USA (39% of 179 patients) . The reason for the difference between the two countries is not clear but could reflect the divergence in the approaches to HIV infection management. In addition, various socio-demographic conditions account for an increased risk of developing cryptococcosis in these two countries. Thus, cryptococcosis continues to occur but primarily in patients availing themselves less to routine medical care and to HAART (i.e., African-born individuals and women in France), often because of reticence or ignorance, considering themselves not at risk for HIV infection, or in patients with poor access to care in the USA (i.e., African–American individuals) .
Although the HIV-infected population diagnosed with cryptococcosis changed over time, the HIV-negative population did not, thereby suggesting the absence of a new source of immunosuppression predisposing to cryptococcosis during the study period. Analysis of our data showed that diagnostic procedures differed according to the patient's HIV status and the region of diagnosis. Although this was never explicitly stated, it is probable that it represents a bias in all recent or earlier studies conducted for surveillance purposes and not therapeutic issues [8,16,20,29,30,37]. It is also likely that patient management is influenced by other events, such as local clinical trials, publications of multicenter trial results and practical guidelines [38–41]. Thus, the features that distinguish patients with cryptococcosis according to their HIV status can only be determined accurately in a specifically designed investigation, such as the CryptoA/D study currently under analysis .
In conclusion, cryptococcosis represents an important worldwide cause of morbidity and mortality for HIV-infected patients, which tends to decline in countries where HAART is available but remains high elsewhere. A surveillance system such as that implemented by the French Cryptococcosis Study Group provides important information on the evolution of this opportunistic fungal infection and the efficacy of antiretroviral therapies that pertinently complements findings obtained through other surveillance programs.
1. Kwon-Chung KJ, Bennett JE. Cryptococcosis.
In Medical Mycology
. Edited by Kwon-Chung KJ, Bennett JE. Philadelphia: Lea & Febiger; 1992:397–446.
2. Heyderman RS, Gangaidzo IT, Hakim JG, Mielke J, Taziwa A, Musvaire P, et al. Cryptococcal meningitis in human immunodeficiency virus-infected patients in Harare, Zimbabwe. Clin Infect Dis
3. Mwaba P, Mwansa J, Chintu C, Pobee J, Scarborough M, Portsmouth S, et al. Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions. Postgrad Med J
4. Dupont B, Crewe Brown HH, Westermann K, Martins MD, Rex JH, Lortholary O, et al. Mycoses in AIDS. Med. Mycol
5. Levitz SM. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis
6. Hajjeh RA, Brandt ME, Pinner RW. Emergence of cryptococcal disease: epidemiologic perspectives 100 years after its discovery. Epidemiol Rev
7. Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS–100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev
8. Knight FR, Mackenzie DW, Evans BG, Porter K, Barrett NJ, White GC. Increasing incidence of cryptococcosis in the United Kingdom. J Infect
9. Dromer F, Mathoulin S, Dupont B, Laporte A, the French Cryptococcosis Study Group. Epidemiology of cryptococcosis in France: 9-year survey (1985-1993). Clin Infect Dis
10. Bacellar H, Muñoz A, Hoover DR, Phair JP, Besley DR, Kingsley LA, et al. Incidence of clinical AIDS conditions in a cohort of homosexual men with CD4+ cell counts < 100/mm3. J Infect Dis
11. Currie BP, Casadevall A. Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. Clin Infect Dis
12. Sorvillo F, Beall G, Turner PA, Beer VL, Kovacs AA, Kerndt PR. Incidence and factors associated with extrapulmonary cryptococcosis among persons with HIV infection in Los Angeles County. AIDS
13. Burckhardt B, Sendi P, Pfluger D, Zimmerli W, Nüesch R, Bucher HC, et al. Rare AIDS-defining diseases in the Swiss HIV cohort study. Eur J Clin Microbiol Infect Dis
14. Tansuphasawadikul S, Amornkul PN, Tanchanpong C, Limpakarnjanarat K, Kaewkungwal J, Likanonsakul S, et al. Clinical presentation of hospitalized adult patients with HIV infection and AIDS in Bangkok, Thailand. J Acquir Immune Defic Syndr
15. Hakim JG, Gangaidzo IT, Heyderman RS, Mielke J, Mushangi E, Taziwa A, et al. Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS
16. Moosa MY, Coovadia YM. Cryptococcal meningitis in Durban, South Africa: a comparison of clinical features, laboratory findings, and outcome for human immunodeficiency virus (HIV)-positive and HIV-negative patients. Clin Infect Dis
17. Corbett EL, Churchyard GJ, Charalambos S, Samb B, Moloi V, Clayton TC, et al. Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus. Clin Infect Dis
18. McNeil JI, Kan VL. Decline in the incidence of cryptococcosis among HIV-infected patients [letter]. J Acquir Immune Defic Syndr Hum Retrovirol
19. McKinsey DS, Wheat LJ, Cloud GA, Pierce M, Black JR, Bamberger DM, et al. Itraconazole prophylaxis for fungal infection in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. Clin Infect Dis
20. Hajjeh RA, Conn LA, Stephens DS, Baughman W, Hamill R, Graviss E, et al. Cryptococcosis: population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. J Infect Dis
21. Centers for Disease Control and Prevention. Update: AIDS–United States, 2000. MMWR
22. Institut de Veille Sanitaire. Surveillance du Sida en France. Situation au 31 mars 2002. Bull Epidémiol Hebd
23. Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. Lancet
24. ven Elden LJR, Walenkamp AME, Lipovsky MM, Reiss P, Meis JFGM, de Marie S, et al. Declining number of patients with cryptococcosis in the Netherlands in the era of highly active antiretroviral therapy [letter]. AIDS
25. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med
26. Antinori S, Galimberti L, Magni C, Casella A, Vago L, Mainini F, et al. Cryptococcus neoformans infection in a cohort of Italian AIDS patients: natural history, early prognostic parameters and autopsy findings. Eur J Clin Microbiol Infect Dis
27. Leonard MK, Larsen N, Drechsler H, Blumberg H, Lennox JL, Arellano M, et al. Increased survival of persons with tuberculosis and human immunodeficiency virus infection, 1991–2000. Clin Infect Dis
28. Kaplan JE, Hanson D, Dworkin MS, Frederick T, Bertolli J, Lindegren ML, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis
29. Mirza SA, Phelan M, Rimland D, Graviss E, Hamill R, Brandt ME, et al. The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992–2000. Clin Infect Dis
30. Chen S, and the Australasian Society for Infectious Diseases (ASID) Mycoses Interest Group. Cryptococcosis in Australasia and the treatment of cryptococcal and other fungal infections with liposomal amphotericin B. J Antimicrob Chemother
31. Dromer F, Guého E, Ronin O, Dupont B. Serotyping of Cryptococcus neoformans by using a monoclonal antibody specific for capsular polysaccharide. J Clin Microbiol
32. Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR
33. Ancelle-Park R. Expanded AIDS case definition. Lancet
34. Hosmer DW, Lemeshow S. Applied Logistic Regression
. New York: John Wiley Sons; 1989.
35. Neuville S, Dromer F, Morin O, Dupont B, Ronin O, Lortholary O, et al. Primary cutaneous cryptococcosis, a distinct clinical entity. Clin Infect Dis
36. Hajjeh R. The changing epidemiology of cryptococcosis: implication for public health. Fifth International Conference on Cryptococcus and cryptococcosis.
Adelaide, Australia, March 2002 [abstract S8.1].
37. Chen S, Sorrell T, Nimmo G, Speed B, Currie B, Ellis D, et al. Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Clin Infect Dis
38. Dupont B, Drouhet E. Cryptococcal meningitis and fluconazole. Ann Intern Med
39. Saag MS, Powderly WG, Cloud GA, Robinson P, Grieco MH, Sharkey PK, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. N Engl J Med
40. van der Horst CM, Saag MS, Cloud GA, Hamill RJ, Graybill JR, Sobel JD, et al. Treatment of cryptococcal meningitis associated with acquired immunodeficiency syndrome. N Engl J Med
41. Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, et al. Practice guidelines for the management of cryptococcal disease. Clin Infect Dis
42. Kwon-Chung KJ, Sorrell TC, Dromer F, Fung E, Levitz SM. Cryptococcosis: clinical and biological aspects. Med Mycol
The French Cryptococcosis Study Group includes clinicians and biologists from various hospitals in France. The following members actively participated in data collection for this study: H. Chardon (Aix- en-Provence), H. Greze (Albi), O. Chrétien (Alençon), B. Carme, M.P. Hayette, G. Nevez (Amiens), J.P. Bouchara, D. Chabasse (Angers), M. Martin (Angoulême), S. Blanc (Annecy), V. Blanc (Antibes), F. Leturdu, M. Pulik (Argenteuil), B. Hautefort (Arles), J. Fruit (Arras), I. Cahitte (Asnières), F. Giacomini, M.P. Le Pennec (Aulnay-sous-Bois), H. Lefrand (Avignon), M. Larrouy (Bayonne), X. Doat, J. Larfouilloux (Beaune), J.P. Faller (Belfort), T. Barale, R. Piarroux, G. Reboux (Besançon), A. Dayan (Blois), C. Bouges-Michel, O. Launay (Bobigny), G. Delzanig, I. Poilane (Bondy), C. Boisseau, B. Couprie, A. Texier, F.X. Weill (Bordeaux), M.E. Bougnoux (Boulogne-Billancourt), H. de Montclos (Bourg-en-Bresse), M. Gavignet (Bourges), O. Masure, E. Moalic, D. Quinio (Brest), G. Otterbein (Brie-sur-Marne), C. Lefort (Brives), C. Duhamel (Caen), C. Bidault (Chalon-sur-Saône), O. Rogeaux (Chambéry), M. Zaigel (Chartres), C. Allard (Cherbourg), E. Laurens (Cholet), Y. Guibert, V. Hervé, P. Soler (Clamart), M. Cambon (Clermont-Ferrand), R. Roué (Clichy), Y. Boussougant, G. Galeazzi, S. Lasry (Colombes), C. Malbrunot (Corbeil-Essonne), F. Cordier (Creil), S. Bretagne, G. Belkacem, M. Geslin, P. Lesprit, A. Marmorat-Khuong (Créteil), X. Lhoste (Dax), M. Berthelot, C. Bessin, J.P. Gaillard (Dieppe), A. Bonin, P. Camerlynck, J. Lopez (Dijon), G. Grise (Elboeuf), M. Gauthier (Evry), J.M. Chevalier, P. Lafay, X. Poullain (Flers), E. Counillon (Fréjus), I. Bouchard (Fresnes), C. Nauciel (Garches), F. Poujade (Gonesse), R. Grillot, B. Lebeau, A. Thomas (Grenoble), F. Botterel, P. Bourée, S. Romand (Kremlin-Bicêtre), A. Lagarde (Lagny), X. Gosset (Lannion), M. Auberger (Laval), M.A. Dessailly-Chanson (La Roche-sur-Yon), J. Vincent (La Rochelle), O. Eloy (Le Chesnay), M.L. Grillot (Le Havre), E. Boyer (Le Mans), A. Capbern (Libourne), B. Bouteille, M.L. Darde (Limoges), Y. Lermercier (Longjumeau), E. Dannaoui, M.A. Piens, M. Rabodnirina (Lyon), G. Janin (Macon), L. Berardi (Mantes-la-Jolie), A. Blancard, L. Collet, A. Michel-N'Guyen, A. Penaud (Marseille), M. Bietrix, M. Nezri (Martigues), A. Eme, A. Fiacre (Meaux), C. Chandesris (Montargis), M. Piquet (Montfermeil), P. Rispail (Montpellier), V. Gettler (Montreuil), M.F. Penner, A. Trévoux (Mulhouse), M.F. Biava, L. Kures (Nancy), O. Morin (Nantes), M. Felz, S. Kernbaum (Neuilly-sur-Seine), X. Lenon (Nevers), Y. Le Fichoux, M. Gari-Toussaint (Nice), A. Delage (Nîmes), X. Romaru (Niort), J.P. Barthez, D.M. Poisson (Orléans), X. Méion (Pau), Y. Giudicelli (Poissy), J.L. Jacquemin, C. Kauffmann-Lacroix (Poitiers), A. Blanchard, X. Thibault (Pontoise), F. Pateyron (Provins), J.M. Pinon, D. Toubas (Reims), S. Chevrier, C. Guigen (Rennes), P. Brasseur, L. Favenec (Rouen), J.M.P. Lafaye (Royan), G. Sirondelle (Rozoy-sur-Serre), M. Janvier (Saint-Cloud), N. Godineau, S. Hamane (Saint-Denis), G. Dorche, H. Raberin (Saint-Etienne), S. Fegueux (Saint-Germain-en-Laye), A. Gregory (Saint-Julien-en-Genevois), X. Cavallo, M.C. Debord, R. Roué (Saint-Mandé), M. Simoneau (Saint-Maurice), J.Y. Leberre (Saint-Nazaire), P. Malherbe (Saint-Quentin), S. Liebeau (Saumur), M. Gauthron (Sens), H. Koenig, J. Waller (Strasbourg), P. Cahen (Suresnes), L. Kures (Toul), Y. Muzellec (Toulon), M.T. Baixench, M.D. Linas, P. Luydlin, J.F. Magnaval, P. Recco, J.P. Seguela (Toulouse), C. Coignard, F. de Keyser, M. Vinocour (Tourcoing), F. Declosets, M. Ferly-Therizol, R. Lenoble (Tours), F. Moreau-Benaoudia (Troyes), J. Verger (Tulle), M.A. Piens (Valence), E. Mazars (Valenciennes), O. Eloy (Versailles), D. Fortineau, D. Matthieu, F. Salida (Villejuif), J. Breuil, S. Dellion, O. Patey (Villeneuve-Saint-Georges); and in Paris, C. Chochillon (Hôpital Bichat), V. Lavarde (Hôpital Broussais), C. Bizet, A. Buré, B. Pangon (Hôpital Claude-Bernard), M.T. Baixench, J. Dupouy-Camet, A. Paugham, F. Robert-Gangeux (Hôpital Cochin), N. Desplaces (Hôpital de la Croix-Saint-Simon), J. Prost, F. Raymond, M. Segonds (Hôpital des Diaconesses), M. Cornet, V. Lavarde (Hôpital Européen Georges Pompidou), D. Basset, M. Cornet, P. Lagrange (Hôpital de l'Hôtel-Dieu), M.C. Escande (Institut Curie), C. Lamer, Y. Pean (Institut Mutualiste Montsouris), N. Fortineau (Hôpital Laënnec), C. Dematons (Hôpital Lariboisière), S. Challier, C. Hennequin (Hôpital Necker), C. Aznar, J. Fleury (Hôpital Pasteur), I. Abeille, E. Bart-Delabesse, J. Carrière, A. Datry, M. Gentilini, V. Zeller (Hôpital La Pitié-Salpêtrière), A.M. Deluol (Hôpital Rothschild), G. Buot (Fondation Rothschild), J.L. Poirot (Hôpital Saint-Antoine), A. Marmorat (Hôpital Saint-Joseph), C. Lacroix, F. Derouin, M. Feuilhade-Chauvin, F. Traore (Hôpital Saint-Louis), J. de Recondo (Hôpital Sainte-Anne), G. Ponsot (Hôpital Saint-Vincent-de-Paul), P. Roux, G. Kac (Hôpital Tenon), X. Crozas (Hôpital Trousseau), M. Arborio (Hôpital du Val de Grâce).
This article has been cited 61 time(s).
Brazilian Journal of Infectious DiseasesStrategies to reduce mortality and morbidity due to AIDS-related cryptococcal meningitis in Latin AmericaBrazilian Journal of Infectious Diseases
Plos OneEpidemiology of Cryptococcal Meningitis in the US: 1997-2009Plos One
Qjm-An International Journal of MedicineCryptococcosis in sarcoidosis: cryptOsarc, a comparative study of 18 casesQjm-An International Journal of Medicine
Prevention of cryptococcosis in HIV-infected patients with limited access to highly active antiretroviral therapy: evidence for primary azole prophylaxis
HIV Medicine, 6(4):
Cryptococcosis in HIV-infected individuals
HIV and the central nervous system
Revue Neurologique, 162(1):
Medical MycologyThe weapon potential of human pathogenic fungiMedical Mycology
Clinical Infectious Diseases
Cryptococcus gattii infection: Characteristics and epidemiology of cases identified in a South African province with high HIV seroprevalence, 2002-2004
Clinical Infectious Diseases, 43(8):
Plos MedicineDeterminants of disease presentation and outcome during cryptococcosis: The CryptoA/D studyPlos Medicine
Journal of Clinical MicrobiologyUse of a suspension array for rapid identification of the varieties and genotypes of the Cryptococcus neoformans species complexJournal of Clinical Microbiology
Antimicrobial Agents and ChemotherapyEfficacy of amphotericin B in combination with flucytosine against flucytosine-susceptible or flucytosine-resistant isolates of Cryptococcus neoformans during disseminated murine cryptococcosisAntimicrobial Agents and Chemotherapy
Medical MycologyCryptococcus gattii: in vitro susceptibility to the new antifungal albaconazole versus fluconazole and voriconazoleMedical Mycology
Medical MycologyFungal diseases: an evolving public health challengeMedical Mycology
Revista DO Instituto De Medicina Tropical De Sao PauloHistopathology, Serology and Cultures in the Diagnosis of CryptococcosisRevista DO Instituto De Medicina Tropical De Sao Paulo
Eukaryotic CellBiosynthesis and immunogenicity of glucosylceramide in Cryptococcus neoformans and other human pathogensEukaryotic Cell
Cadernos De Saude Publica
Profiles of multiple causes of death related to HIV/AIDS in the cities of Sao Paulo and Santos, Brazil, 2001
Cadernos De Saude Publica, 23(3):
Results of nine years of the clinical and epidemiological survey on cryptococcosis in Colombia, 1997-2005
International Journal of Infectious DiseasesColitis as a manifestation of infliximab-associated disseminated cryptococcosisInternational Journal of Infectious Diseases
Current Molecular Medicine
The cellular responses induced by the capsular polysaccharide of Cryptococcus neoformans differ depending on the presence or absence of specific protective antibodies
Current Molecular Medicine, 5(4):
Original Research: Risk Factors for Mortality from Primary Cryptococcosis in Patients with HIV
Postgraduate Medicine, 121(2):
Acta Medica Portuguesa
Acta Medica Portuguesa, 21(3):
American Journal of Pathology
Capsule structure changes associated with Cryptococcus neoformans crossing of the blood-brain barrier
American Journal of Pathology, 166(2):
Infectious Disease Clinics of North AmericaCryptococcosisInfectious Disease Clinics of North America
Clinical Infectious DiseasesManagement of cryptococcal meningitis in AIDS: The need for specific studies in developing countriesClinical Infectious Diseases
PeptidesIn vitro activity of the synthetic lipopeptide PAL-Lys-Lys-NH2 alone and in combination with antifungal agents against clinical isolates of Cryptococcus neoformansPeptides
Cochrane Database of Systematic ReviewsAntifungal interventions for the primary prevention of cryptococcal disease in adults with HIVCochrane Database of Systematic Reviews
Antimicrobial Agents and ChemotherapyResults obtained with various antifungal susceptibility testing methods do not predict early clinical outcome in patients with cryptococcosisAntimicrobial Agents and Chemotherapy
Cadernos De Saude Publica
Impact of highly active antiretroviral therapy (HAART) on the incidence of opportunistic infections, hospitalizations and mortality among children and adolescents living with HIV/AIDS in Belo Horizonte, Minas Gerais State, Brazil
Cadernos De Saude Publica, 23():
Plos OneCryptococcal Neuroradiological Lesions Correlate with Severity during Cryptococcal Meningoencephalitis in HIV-Positive Patients in the HAART EraPlos One
Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France
Expert Opinion on PharmacotherapyCryptococcal disease and HIV infectionExpert Opinion on Pharmacotherapy
Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy
MycopathologiaEpidemiological profile of cryptococcal meningitis patients in Rio Grande do Sul, BrazilMycopathologia
HIV MedicineAIDS-associated cryptococcosis: a comparison of epidemiology, clinical features and outcome in the pre- and post- HAART eras. Experience of a single centre in ItalyHIV Medicine
Seminars in Respiratory and Critical Care Medicine
Seminars in Respiratory and Critical Care Medicine, 25(2):
Journal of InfectionTreatment of cryptococcal meningitis in Peruvian AIDS Patients using amphotericin B and fluconazoleJournal of Infection
Clinical Infectious DiseasesCryptococcosis in Solid Organ Transplant Recipients: Current State of the ScienceClinical Infectious Diseases
Revista DO Instituto De Medicina Tropical De Sao Paulo
Clinical and epidemiological features of 123 cases of cryptococcosis in MATO Grosso Do Sul, Brazil
Revista DO Instituto De Medicina Tropical De Sao Paulo, 50(2):
Population-based surveillance for cryptococcosis in an antiretroviral-naive South African province with a high HIV seroprevalence
Journal of Infectious DiseasesIgM(+) Memory B Cell Expression Predicts HIV-Associated Cryptococcosis StatusJournal of Infectious Diseases
Journal of Antimicrobial ChemotherapyA multicentre pharmacoepidemiological study of therapeutic practices in invasive fungal infections in France during 1998-1999Journal of Antimicrobial Chemotherapy
Journal De Mycologie MedicaleImmune reconstitution syndrome in systemic mycoses in HIV infected patientsJournal De Mycologie Medicale
ProteomicsA proteomic-based approach for the identification of immunodominant Cryptococcus neoformans proteinsProteomics
Immunotherapy for fungal infections with special emphasis on central nervous system infections
Neurology India, 55(3):
Current HIV Research
Inpatient care of the HIV infected patient in the highly active antiretroviral therapy (HAART) era
Current HIV Research, 3(2):
Pulmonary cryptococcosis - Comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients
Samj South African Medical Journal
Cryptococcosis in Gauteng: Implications for monitoring of HIV treatment programmes
Samj South African Medical Journal, 98(6):
Journal De Mycologie MedicaleSystemic mycosis in patients without evidence of immunosuppressionJournal De Mycologie Medicale
Statistical Methods in Medical ResearchEvaluation of change in CD4+cell counts in AIDS clinical trialsStatistical Methods in Medical Research
Jornal Brasileiro De Pneumologia
Chapter 3-Pulmonary cryptococcosis
Jornal Brasileiro De Pneumologia, 35():
The diverse roles of autophagy in medically important fungi
Cadernos De Saude Publica
Cryptococcal meningitis in Rio de Janeiro State, Brazil, 1994-2004
Cadernos De Saude Publica, 24():
Journal of Antimicrobial ChemotherapyImpact of highly active antiretroviral therapy on incidence and management of human immunodeficiency virus-related opportunistic infectionsJournal of Antimicrobial Chemotherapy
Fems Yeast ResearchMolecular analysis of 311 Cryptococcus neoformans isolates from a 30-month ECMM survey of cryptococcosis in EuropeFems Yeast Research
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and EndodontologyRare mycoses of the oral cavity: a literature epidemiologic reviewOral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology
Journal of Research in Medical Sciences
Isolation of Cryptococcus neoformans and other opportunistic fungi from pigeon droppings
Journal of Research in Medical Sciences, 18(1):
Cryptococcus neoformans Meningoencephalitis in a Patient with Idiopathic CD4(+) T Lymphocytopenia
Collegium Antropologicum, 37(2):
DrugsCryptococcal Infections: Changing Epidemiology and Implications for TherapyDrugs
JAIDS Journal of Acquired Immune Deficiency SyndromesPrevalence, Determinants of Positivity, and Clinical Utility of Cryptococcal Antigenemia in Cambodian HIV-Infected PatientsJAIDS Journal of Acquired Immune Deficiency Syndromes
cryptococcosis; epidemiology; HAART; Cryptococcus neoformans; HIV; AIDS
© 2004 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Highlight selected keywords in the article text.
Data is temporarily unavailable. Please try again soon.