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Clinical, Epidemiological and Outcome Features of Patients with Cryptococcosis in Uberaba, Minas Gerais, Brazil

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Abstract

Nearly one million of cryptococcosis cases occur yearly around the world, involving mainly HIV-infected patients who are not receiving antiretroviral therapy (ART) or present poor adherence. This study aims to evaluate epidemiological, clinical and outcome aspects of patients with cryptococcosis from 1998–2010. Patients were prospectively recruited, and their medical and laboratory records were reviewed. A total of 131 cases were included, and of these, 119 (90.83%) had AIDS, 4 received a renal transplant, 2 presented systemic lupus erythematosus and 6 (4.6%) were apparently immunocompetent. Ninety-one (69.46%) were men, and the median age was 38.7 years. Cryptococcal meningitis (CM) was diagnosed in 103 (78.62%), whereas 28 (21.38%) had cryptococcal infection in other sites. Of patients with CM, 94 (91.26%) had AIDS being cryptococcosis the first defining illness in 61 (64.9%), while 37 (60.65%) of them presented simultaneously both diagnosis. Headache, altered mental status, papilledema and seizures at admission were significatively associated with a poor outcome. Of 163 different isolates, 155 (95.09%) were Cryptococcus neoformans and eight (4.88%) Cryptococcus gattii. Antifungal therapy was warranted in 8 (87.4%) patients with CM, but 46 (51.1%) died during the first days or weeks. Of 28 patients without CM, 21 (75%) received treatment, but 6 (28.6%) died. The poor outcome among this case series was similar to that reported from other developing countries, but it is paradoxal in Brazil where the ART is at free disposal in the public health services. Despite, at least 60–70% of patients present advanced immunosuppression when they receive the AIDS diagnosis.

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References

  1. Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006;20:507–44.

    Article  PubMed  Google Scholar 

  2. Jarvis JN, Harrison TS. HIV-associated cryptococcal meningitis. AIDS. 2007;21:2119–29.

    Article  PubMed  Google Scholar 

  3. Hung JJ, Ou LS, Lee WI, Huang JL. Central nervous system infections in patients with systemic lupus erythematosus. J Rheumatol. 2005;32(1):40–3.

    PubMed  Google Scholar 

  4. Davis JA, Horn DL, Marr KA, Fishman JA. Central nervous system involvement in cryptococcal infection in individuals after solid organ transplantation or with AIDS. Transpl Infect Dis. 2009;11(5):432–7.

    Article  PubMed  CAS  Google Scholar 

  5. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23(4):525–30.

    Article  PubMed  Google Scholar 

  6. French N, Gray K, Watera C, Nakiyingi J, Lugada E, Moore M, Lalloo D, Whitworth JA, Gilks CF. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS. 2002;16(7):1031–8.

    Article  PubMed  Google Scholar 

  7. Kambugu A, Meya DB, Rhein J, O’Brien M, Janoff EN, Ronald AR, Kamya MR, Mayanja-Kizza H, Sande MA, Bohjanen PR, Boulware DR. Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy. Clin Infect Dis. 2008;46:1694–701.

    Article  PubMed  CAS  Google Scholar 

  8. Lortholary O, Poizat G, Zeller V, Neuville S, Boibieux A, Alvarez M, Dellamonica P, Botterel F, Dromer F, Chêne G. Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy. AIDS. 2006;20:2183–91.

    Article  PubMed  Google Scholar 

  9. Pappas PG. Cryptococcosis in the developing world: an elephant in the parlor. Clin Infect Dis. 2010;50(3):345–6.

    Article  PubMed  Google Scholar 

  10. Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am. 2002;16(4):837–74.

    Article  PubMed  Google Scholar 

  11. Steele KT, Thakur R, Nthobatsang R, Steenhoff AP, Bisson GP. In-hospital mortality of HIV-infected cryptococcal meningitis patients with C. gattii, C. neoformans infection in Gaborone, Botswana. Med Mycol. 2010;48(8):1112–5.

    Article  PubMed  Google Scholar 

  12. MacDougall L, Kidd SE, Galanis E, Mak S, Leslie MJ, Cieslak PR, Kronstad JW, Morshed MG, Bartlett KH. Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. Emerg Infect Dis. 2007;13:42–50.

    Article  PubMed  Google Scholar 

  13. Byrnes EJ 3rd, Marr KA. The outbreak of Cryptococcus gattii in Western North America: epidemiology and clinical issues. Curr Infect Dis Rep. 2011;13(3):256–61.

    Article  PubMed  Google Scholar 

  14. Viviani MA, Cogliati M, Esposto MC, Lemmer K, Tintelnot K, Colom Valiente MF, Swinne D, Velegraki A. Velho R; European Confederation of Medical Mycology (ECMM) Cryptococcosis Working Group. Molecular analysis of 311 Cryptococcus neoformans isolates from a 30-month ECMM survey of cryptococcosis in Europe. FEMS Yeast Res. 2006;6:614–9.

    Article  PubMed  CAS  Google Scholar 

  15. Okamoto K, Hatakeyama S, Itoyama S, Nukui Y, Yoshino Y, Kitazawa T, Yotsuyanagi H, Ikeda R, Sugita T, Koike K. Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007. Emerg Infect Dis. 2010;16(7):1155–7.

    Article  PubMed  Google Scholar 

  16. Nicol AM, Hurrell C, McDowall W, Bartlett K, Elmieh N. Communicating the risks of a new, emerging pathogen: the case of Cryptococcus gattii. Risk Anal. 2008;28(2):373–86.

    Article  PubMed  Google Scholar 

  17. Dixit A, Carroll SF, Qureshi ST. Cryptococcus gattii: An Emerging Cause of Fungal Disease in North America. Interdiscip Perspect Infect Dis. 2009. doi:10.1155/2009/84045.

  18. Brouwer AE, Rajanuwong A, Chierakul W, Griffin GE, Larsen RA, White NJ, Harrison TS. Combination antifungal therapies for HIV-associated cryptococcal meningitis, a randomised trial. Lancet. 2004;29;363(9423):1764–7.

    Article  Google Scholar 

  19. Kwon-chung KJ, Polacheck I, Bennett JE. Improved diagnostic medium for separation of Cryptococcus neoformans var neoformans (serotypes A and D) and Cryptococcus neoformans var gattii (serotypes B and C). J Clin Microbiol. 1982;15(3):535–7.

    PubMed  CAS  Google Scholar 

  20. Ministério da Saúde do Brasil. Dados e pesquisa em DSTs e Aids. Coordenação do programa nacional de DST/Aids. Brasília, DF; 2002.

  21. Pappalardo MC, Melhem MS. Cryptococcosis: a review of the Brazilian experience for the disease. Rev Inst Med Trop Sao Paulo. 2003;45(6):299–305.

    Article  PubMed  Google Scholar 

  22. Kisenge PR, Hawkins AT, Maro VP, McHele JP, Swai NS, Mueller A, Houpt ER. Low CD4 count plus coma predicts cryptococcal meningitis in Tanzania. BMC Infect Dis. 2007;7:39.

    Article  PubMed  Google Scholar 

  23. van Elden LJ, Walenkamp AM, Lipovsky MM, Reiss P, Meis JF, de Marie S, Dankert J, Hoepelman AI. Declining number of patients with cryptococcosis in the Netherlands in the era of highly active antiretroviral therapy. AIDS. 2000;1;14(17):2787–8.

    Article  Google Scholar 

  24. Mirza SA, Phelan M, Rimland D, Graviss E, Hamill R, Brandt ME, Gardner T, Sattah M, de Leon GP, Baughman W, Hajjeh RA. The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992–2000. Clin Infect Dis. 2003;1536(6):789–94.

    Article  Google Scholar 

  25. Dromer F, Mathoulin-Pélissier S, Launay O, Lortholary O, French Cryptococcosis Study Group. Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. PLoS Med. 2007;4(2):e21.

    Article  PubMed  Google Scholar 

  26. Graybill JR, Sobel J, Saag M, van Der Horst C, Powderly W, Cloud G, Riser L, Hamill R, Dismukes W, The NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. Clin Infect Dis. 2000;30(1):47–54.

    Article  PubMed  CAS  Google Scholar 

  27. Charlier C, Dromer F, Lévêque C, Chartier L, Cordoliani YS, Fontanet A, Launay O, Lortholary O, French Cryptococcosis Study Group. Cryptococcal neuroradiological lesions correlate with severity during cryptococcal meningoencephalitis in HIV-positive patients in the HAART era. PLoS One. 2008;3(4):e1950.

    Article  PubMed  Google Scholar 

  28. Bicanic T, Muzoora C, Brouwer AE, Meintjes G, Longley N, Taseera K, Rebe K, Loyse A, Jarvis J, Bekker LG, Wood R, Limmathurotsakul D, Chierakul W, Stepniewska K, White NJ, Jaffar S, Harrison TS. Independent association between rate of clearance of infection and clinical outcome of HIV-associated cryptococcal meningitis: analysis of a combined cohort of 262 patients. Clin Infect Dis. 2009;49(5):702–9.

    Article  PubMed  CAS  Google Scholar 

  29. Monaco LS, Silva Nieto F, Warley E, Cervelli MR. Criptococosis meníngea asociada al SIDA en el Hospital Diego Paroissien en el periodo 1996/1999. Rev Argent Microbiol. 2001;33(2):118–21.

    PubMed  CAS  Google Scholar 

  30. Darze C, Lucena R, Gomes I, Melo A. Clinical and laboratory characteristics of 104 cryptococcal meningoencephalitis cases. Rev Soc Bras Med Trop. 2000;33(1):21–6.

    Article  PubMed  CAS  Google Scholar 

  31. Correa Mdo P, Severo LC, Oliveira Fde M, Irion K, Londero AT. The spectrum of computerized tomography (CT) findings in central nervous system (CNS) infection due to Cryptococcus neoformans var gattii in immunocompetent children. Rev Inst Med Trop Sao Paulo. 2002;44:283–7.

    PubMed  Google Scholar 

  32. Trilles L, Lazéra Mdos S, Wanke B, Oliveira RV, Barbosa GG, Nishikawa MM, Morales BP, Meyer W. Regional pattern of the molecular types of Cryptococcus neoformans and Cryptococcus gattii in Brazil. Mem Inst Oswaldo Cruz. 2008;103(5):455–62.

    Article  PubMed  CAS  Google Scholar 

  33. Santos WR, Meyer W, Wanke B, Costa SP, Trilles L, Nascimento JL, Medeiros R, Morales BP, Bezerra Cde C, Macêdo RC, Ferreira SO, Barbosa GG, Perez MA, Nishikawa MM, Lazéra Mdos S. Primary endemic Cryptococcosis gattii by molecular type VGII in the state of Pará, Brazil. Mem Inst Oswaldo Cruz. 2008;103(8):813–8.

    Article  PubMed  Google Scholar 

  34. Rozenbaum R, Gonçalves AJ, Wanke B, Vieira W. Cryptococcus neoformans var gattii in a Brazilian AIDS patient. Mycopathologia. 1999;112:33–4.

    Article  Google Scholar 

  35. Severo LC, Mattos-Oliveira F, Londero T. Cryptococcosis due to Cryptococcus neoformans var gattii in Brazilian patients with Aids. Report of three cases. Rev Iberoamer Micol. 1999;16:152–4.

    CAS  Google Scholar 

  36. Lindenberg Ade S, Chang MR, Paniago AM, Lazéra Mdos S, Moncada PM, Bonfim GF, Nogueira SA, Wanke B. Clinical and epidemiological features of 123 cases of cryptococcosis in Mato Grosso do Sul, Brazil. Rev Inst Med Trop São Paulo. 2008;50(2):75–8.

    PubMed  Google Scholar 

  37. Macdougall L, Fyfe M, Romney M, Starr M, Galanis E. Risk Factors for Cryptococcus gattii Infection, British Columbia, Canada. Emerg Infect Dis. 2011;17(2):193–9.

    PubMed  Google Scholar 

  38. Morgan J, McCarthy KM, Gould S, Fan K, Arthington-Skaggs B, Iqbal N, Stamey K, Hajjeh RA, Brandt ME, Gauteng Cryptococcal Surveillance Initiative Group. Cryptococcus gattii infection: characteristics and epidemiology of cases identified in a South African province with high HIV seroprevalence, 2002–2004. Clin Infect Dis. 2006;1543(8):1077–80.

    Article  Google Scholar 

  39. Chaturvedi S, Dyavaiah M, Larsen RA, Chaturvedi V. Cryptococcus gattii in AIDS patients, southern California. Emerg Infect Dis. 2005;11(11):1686–92.

    Article  PubMed  CAS  Google Scholar 

  40. Litvintseva AP, Thakur R, Reller LB, Mitchell TG. Prevalence of clinical isolates of Cryptococcus gattii serotype C among patients with AIDS in Sub-Saharan Africa. J Infect Dis. 2005;1;192(5):888–92.

    Article  Google Scholar 

  41. Lui G, Lee N, Ip M, Choi KW, Tso YK, Lam E, Chau S, Lai R, Cockram CS. Cryptococcosis in apparently immunocompetent patients. Q J Med. 2006;99:143–51.

    Article  CAS  Google Scholar 

  42. Chen S, Sorrell T, Nimmo G, Speed B, Currie B, Ellis D, Marriott D, Pfeiffer T, Parr D, Byth K. Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group. Clin Infect Dis. 2000;31(2):499–508.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank to Miss Angela Azor for the technical assistance and Fundação de Amparo a Pesquisa de Minas Gerais (FAPEMIG) for the financial support. Grant number: PQ 1813-09.

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Authors and Affiliations

  1. Infectious Diseases Department, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil

    Delio José Mora, Eduardo Rodrigues da Cunha Colombo, Kennio Ferreira-Paim, Leonardo Eurípedes Andrade-Silva, Gabriel Antonio Nogueira Nascentes & Mario León Silva-Vergara

  2. Medicina Tropical, Caixa Postal 118, Uberaba, Minas Gerais, CEP 38001-170, Brazil

    Mario León Silva-Vergara

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  1. Delio José Mora
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Correspondence to Mario León Silva-Vergara.

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Mora, D.J., da Cunha Colombo, E.R., Ferreira-Paim, K. et al. Clinical, Epidemiological and Outcome Features of Patients with Cryptococcosis in Uberaba, Minas Gerais, Brazil. Mycopathologia 173, 321–327 (2012). https://doi.org/10.1007/s11046-011-9504-9

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