Cryptococcosis gattii: A literature review
DOI:
https://doi.org/10.33448/rsd-v14i8.49248Keywords:
Cryptococcosis, Cryptococcal infections, Cryptococcus gattii infection.Abstract
Introduction: Cryptococcus gattii causes an invasive fungal infection with a high morbidity and mortality rate. Its prevalence is estimated at 11% to 33% of cryptococcosis cases globally, and it can affect both immunocompetent and immunosuppressed patients. This article aims to present a review of Cryptococcosis gattii. Method: This study consists of a literature review of articles found in the indexing platforms PubMed and Scielo, published in the last 15 years. All selected articles answered the guiding question and passed the inclusion and exclusion criteria. Results and Discussion: C. gattii is widely found in wooded regions and has been isolated from house dust in the Amazon. Although most studies show that the disease affects immunocompetent patients, recent evidence points to potential genetic and immunological factors predisposing to infection. The pathogen is typically acquired through the respiratory tract, with the lungs being the organ initially affected. Mortality and sequelae of central nervous system cryptococcosis due to C. gattii remain high. Conclusion: C. gattii is a highly prevalent pathogen with significant case fatality rates. This pathology should always be considered in the differential diagnosis of patients with chronic pulmonary conditions, regardless of their level of immunocompetence. Studies considering new therapeutic regimens are encouraged.
References
Akins, P. T., & Jian, B. (2019). The Frozen Brain State of Cryptococcus gattii: A Globe-Trotting, Tropical, Neurotropic Fungus. Neurocritical care, 30(2), 272–279. https://doi.org/10.1007/s12028-018-0538-4
Alanio, A., Vernel-Pauillac, F., Sturny-Leclère, A., & Dromer, F. (2015). Cryptococcus neoformans host adaptation: toward biological evidence of dormancy. mBio, 6(2), e02580-14. https://doi.org/10.1128/mBio.02580-14
Baddley, J. W., Schain, D. C., Gupte, A. A., Lodhi, S. A., Kayler, L. K., Frade, J. P., Lockhart, S. R., Chiller, T., Bynon, J. S., Jr, & Bower, W. A. (2011). Transmission of Cryptococcus neoformans by Organ Transplantation. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 52(4), e94–e98. https://doi.org/10.1093/cid/ciq216
Baddley, J. W., Chen, S. C., Huisingh, C., Benedict, K., DeBess, E. E., Galanis, E., Jackson, B. R., MacDougall, L., Marsden-Haug, N., Oltean, H., Perfect, J. R., Phillips, P., Sorrell, T. C., & Pappas, P. G. (2021). MSG07: An International Cohort Study Comparing Epidemiology and Outcomes of Patients With Cryptococcus neoformans or Cryptococcus gattii Infections. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73(7), 1133–1141. https://doi.org/10.1093/cid/ciab268
Beardsley, J., Dao, A., Keighley, C., Garnham, K., Halliday, C., Chen, S. C., & Sorrell, T. C. (2022). What's New in Cryptococcus gattii: From Bench to Bedside and Beyond. Journal of fungi (Basel, Switzerland), 9(1), 41. https://doi.org/10.3390/jof9010041
Bielska, E., & May, R. C. (2016). What makes Cryptococcus gattii a pathogen?. FEMS yeast research, 16(1), fov106. https://doi.org/10.1093/femsyr/fov106
Billmyre, R. B., Applen Clancey, S., Li, L. X., Doering, T. L., & Heitman, J. (2020). 5-fluorocytosine resistance is associated with hypermutation and alterations in capsule biosynthesis in Cryptococcus. Nature communications, 11(1), 127. https://doi.org/10.1038/s41467-019-13890-z
Brito-Santos, F., Barbosa, G. G., Trilles, L., Nishikawa, M. M., Wanke, B., Meyer, W., Carvalho-Costa, F. A., & Lazéra, M.dosS. (2015). Environmental isolation of Cryptococcus gattii VGII from indoor dust from typical wooden houses in the deep Amazonas of the Rio Negro basin. PloS one, 10(2), e0115866. https://doi.org/10.1371/journal.pone.0115866
Brito-Santos, F., Trilles, L., Firacative, C., Wanke, B., Carvalho-Costa, F. A., Nishikawa, M. M., Campos, J. P., Junqueira, A. C. V., Souza, A. C., Lazéra, M. D. S., & Meyer, W. (2020). Indoor Dust as a Source of Virulent Strains of the Agents of Cryptococcosis in the Rio Negro Micro-Region of the Brazilian Amazon. Microorganisms, 8(5), 682. https://doi.org/10.3390/microorganisms8050682
Brown, G. D., Denning, D. W., Gow, N. A., Levitz, S. M., Netea, M. G., & White, T. C. (2012). Hidden killers: human fungal infections. Science translational medicine, 4(165), 165rv13. https://doi.org/10.1126/scitranslmed.3004404
Byrnes, E. J., 3rd, Bartlett, K. H., Perfect, J. R., & Heitman, J. (2011). Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals. Microbes and infection, 13(11), 895–907. https://doi.org/10.1016/j.micinf.2011.05.009
Casarin, S. T. et al. (2020). Tipos de revisão de literatura: considerações das editoras do Journal of Nursing and Health. Journal of Nursing and Health. 10 (5). https://periodicos.ufpel.edu.br/index.php/enfermagem/article/view/19924.
Chang, C. C., Sorrell, T. C., & Chen, S. C. (2015). Pulmonary Cryptococcosis. Seminars in respiratory and critical care medicine, 36(5), 681–691. https://doi.org/10.1055/s-0035-1562895
Chastain, D. B., Rao, A., Yaseyyedi, A., Henao-Martínez, A. F., Borges, T., & Franco-Paredes, C. (2022). Cerebral Cryptococcomas: A Systematic Scoping Review of Available Evidence to Facilitate Diagnosis and Treatment. Pathogens (Basel, Switzerland), 11(2), 205. https://doi.org/10.3390/pathogens11020205
Chau, T. T., Mai, N. H., Phu, N. H., Nghia, H. D., Chuong, L. V., Sinh, D. X., Duong, V. A., Diep, P. T., Campbell, J. I., Baker, S., Hien, T. T., Lalloo, D. G., Farrar, J. J., & Day, J. N. (2010). A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam - high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease. BMC infectious diseases, 10, 199. https://doi.org/10.1186/1471-2334-10-199
Chen, S. C., Slavin, M. A., Heath, C. H., Playford, E. G., Byth, K., Marriott, D., Kidd, S. E., Bak, N., Currie, B., Hajkowicz, K., Korman, T. M., McBride, W. J., Meyer, W., Murray, R., Sorrell, T. C., & Australia and New Zealand Mycoses Interest Group (ANZMIG)-Cryptococcus Study (2012). Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 55(6), 789–798. https://doi.org/10.1093/cid/cis529
Chen, S. C., Korman, T. M., Slavin, M. A., Marriott, D., Byth, K., Bak, N., Currie, B. J., Hajkowicz, K., Heath, C. H., Kidd, S., McBride, W. J., Meyer, W., Murray, R., Playford, E. G., Sorrell, T. C., & Australia and New Zealand Mycoses Interest Group (ANZMIG) Cryptococcus Study (2013). Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 57(4), 543–551. https://doi.org/10.1093/cid/cit341
Chen, S. C., Meyer, W., & Sorrell, T. C. (2014). Cryptococcus gattii infections. Clinical microbiology reviews, 27(4), 980–1024. https://doi.org/10.1128/CMR.00126-13
Chen, S. C., Sorrell, T. C., Chang, C. C., Paige, E. K., Bryant, P. A., & Slavin, M. A. (2014b). Consensus guidelines for the treatment of yeast infections in the haematology, oncology and intensive care setting, 2014. Internal medicine journal, 44(12b), 1315–1332. https://doi.org/10.1111/imj.12597
Cogliati M. (2013). Global Molecular Epidemiology of Cryptococcus neoformans and Cryptococcus gattii: An Atlas of the Molecular Types. Scientifica, 2013, 675213. https://doi.org/10.1155/2013/675213
Crum-Cianflone, N. F., Lam, P. V., Ross-Walker, S., Rosen, L. B., & Holland, S. M. (2017). Autoantibodies to Granulocyte-Macrophage Colony-Stimulating Factor Associated With Severe and Unusual Manifestations of Cryptococcus gattii Infections. Open forum infectious diseases, 4(4), ofx211. https://doi.org/10.1093/ofid/ofx211
Dao, A., Kim, H. Y., Garnham, K., Kidd, S., Sati, H., Perfect, J., Sorrell, T. C., Harrison, T., Rickerts, V., Gigante, V., Alastruey-Izquierdo, A., Alffenaar, J. W., Morrissey, C. O., Chen, S. C., & Beardsley, J. (2024). Cryptococcosis-a systematic review to inform the World Health Organization Fungal Priority Pathogens List. Medical mycology, 62(6), myae043. https://doi.org/10.1093/mmy/myae043
DeCS 2024. (2024). São Paulo: BIREME / PAHO / WHO. https://decs.bvsalud.org/en/
do Carmo, F. N., de Camargo Fenley, J., Garcia, M. T., Rossoni, R. D., Junqueira, J. C., de Barros, P. P., & Scorzoni, L. (2022). Cryptococcus spp. and Cryptococcosis: focusing on the infection in Brazil. Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology], 53(3), 1321–1337. https://doi.org/10.1007/s42770-022-00744-y
Espinel-Ingroff, A., & Kidd, S. E. (2015). Current trends in the prevalence of Cryptococcus gattii in the United States and Canada. Infection and drug resistance, 8, 89–97. https://doi.org/10.2147/IDR.S57686
Fisher, J. F., Valencia-Rey, P. A., & Davis, W. B. (2016). Pulmonary Cryptococcosis in the Immunocompetent Patient-Many Questions, Some Answers. Open forum infectious diseases, 3(3), ofw167. https://doi.org/10.1093/ofid/ofw167
Francisco, E. C., de Jong, A. W., & Hagen, F. (2021). Cryptococcosis and Cryptococcus. Mycopathologia, 186(5), 729–731. https://doi.org/10.1007/s11046-021-00577-7
Garrett, L., Marr, K., West, S., & Allada, G. (2011). 74-year-old man from the pacific northwest with fever and a lung mass. Chest, 140(3), 814–817. https://doi.org/10.1378/chest.10-2964
Hagen, F., Ceresini, P. C., Polacheck, I., Ma, H., van Nieuwerburgh, F., Gabaldón, T., Kagan, S., Pursall, E. R., Hoogveld, H. L., van Iersel, L. J., Klau, G. W., Kelk, S. M., Stougie, L., Bartlett, K. H., Voelz, K., Pryszcz, L. P., Castañeda, E., Lazera, M., Meyer, W., Deforce, D., … Boekhout, T. (2013). Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest. PloS one, 8(8), e71148. https://doi.org/10.1371/journal.pone.0071148
Hagen, F., Khayhan, K., Theelen, B., Kolecka, A., Polacheck, I., Sionov, E., Falk, R., Parnmen, S., Lumbsch, H. T., & Boekhout, T. (2015). Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex. Fungal genetics and biology : FG & B, 78, 16–48. https://doi.org/10.1016/j.fgb.2015.02.009
Harris, J. R., Lockhart, S. R., Debess, E., Marsden-Haug, N., Goldoft, M., Wohrle, R., Lee, S., Smelser, C., Park, B., & Chiller, T. (2011). Cryptococcus gattii in the United States: clinical aspects of infection with an emerging pathogen. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 53(12), 1188–1195. https://doi.org/10.1093/cid/cir723
Howard-Jones, A. R., Sparks, R., Pham, D., Halliday, C., Beardsley, J., & Chen, S. C. (2022). Pulmonary Cryptococcosis. Journal of fungi (Basel, Switzerland), 8(11), 1156. https://doi.org/10.3390/jof8111156
Hurtado, J. C., Castillo, P., Fernandes, F., Navarro, M., Lovane, L., Casas, I., Quintó, L., Marco, F., Jordao, D., Ismail, M. R., Lorenzoni, C., Martinez-Palhares, A. E., Ferreira, L., Lacerda, M., Monteiro, W., Sanz, A., Letang, E., Marimon, L., Jesri, S., Cossa, A., … Martínez, M. J. (2019). Mortality due to Cryptococcus neoformans and Cryptococcus gattii in low-income settings: an autopsy study. Scientific reports, 9(1), 7493. https://doi.org/10.1038/s41598-019-43941-w
Iyer, K. R., Revie, N. M., Fu, C., Robbins, N., & Cowen, L. E. (2021). Treatment strategies for cryptococcal infection: challenges, advances and future outlook. Nature reviews. Microbiology, 19(7), 454–466. https://doi.org/10.1038/s41579-021-00511-0
Jarvis, J. N., Lawrence, D. S., Meya, D. B., Kagimu, E., Kasibante, J., Mpoza, E., Rutakingirwa, M. K., Ssebambulidde, K., Tugume, L., Rhein, J., Boulware, D. R., Mwandumba, H. C., Moyo, M., Mzinganjira, H., Kanyama, C., Hosseinipour, M. C., Chawinga, C., Meintjes, G., Schutz, C., Comins, K., … Ambition Study Group (2022). Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. The New England journal of medicine, 386(12), 1109–1120. https://doi.org/10.1056/NEJMoa2111904
Kabanda, T., Siedner, M. J., Klausner, J. D., Muzoora, C., & Boulware, D. R. (2014). Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 58(1), 113–116. https://doi.org/10.1093/cid/cit641
Koche, J.C. (2020). Fundamentos de metologia científica. Editora Vozes.
Kuo, C. Y., Wang, S. Y., Shih, H. P., Tu, K. H., Huang, W. C., Ding, J. Y., Lin, C. H., Yeh, C. F., Ho, M. W., Chang, S. C., He, C. Y., Chen, H. K., Ho, C. H., Lee, C. H., Chi, C. Y., & Ku, C. L. (2017). Disseminated Cryptococcosis Due to Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Absence of Pulmonary Alveolar Proteinosis. Journal of clinical immunology, 37(2), 143–152. https://doi.org/10.1007/s10875-016-0364-4
Kwon-Chung, K. J., Fraser, J. A., Doering, T. L., Wang, Z., Janbon, G., Idnurm, A., & Bahn, Y. S. (2014). Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis. Cold Spring Harbor perspectives in medicine, 4(7), a019760. https://doi.org/10.1101/cshperspect.a019760
Kwon-Chung, K. J., Bennett, J. E., Wickes, B. L., Meyer, W., Cuomo, C. A., Wollenburg, K. R., Bicanic, T. A., Castañeda, E., Chang, Y. C., Chen, J., Cogliati, M., Dromer, F., Ellis, D., Filler, S. G., Fisher, M. C., Harrison, T. S., Holland, S. M., Kohno, S., Kronstad, J. W., Lazera, M., … Casadevall, A. (2017). The Case for Adopting the "Species Complex" Nomenclature for the Etiologic Agents of Cryptococcosis. mSphere, 2(1), e00357-16. https://doi.org/10.1128/mSphere.00357-16
Lahiri, S., Manjunath, N., Bhat, M., Hagen, F., Bahubali, V. H., Palaniappan, M., Maji, S., & Chandrashekar, N. (2020). Clinical insights and epidemiology of central nervous system infection due to Cryptococcus neoformans/gattii species complexes: A prospective study from South India. Medical mycology, 58(5), 600–608. https://doi.org/10.1093/mmy/myz097
Lee, G. A., Arthur, I., Merritt, A., & Leung, M. (2019). Molecular types of Cryptococcus neoformans and Cryptococcus gattii in Western Australia and correlation with antifungal susceptibility. Medical mycology, 57(8), 1004–1010. https://doi.org/10.1093/mmy/myy161
Limper, A. H., Knox, K. S., Sarosi, G. A., Ampel, N. M., Bennett, J. E., Catanzaro, A., Davies, S. F., Dismukes, W. E., Hage, C. A., Marr, K. A., Mody, C. H., Perfect, J. R., Stevens, D. A., & American Thoracic Society Fungal Working Group (2011). An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. American journal of respiratory and critical care medicine, 183(1), 96–128. https://doi.org/10.1164/rccm.2008-740ST
Lizarazo, J., & Castañeda, E. (2022). Central Nervous System Cryptococcosis due to Cryptococcus gattii in the Tropics. Current tropical medicine reports, 9(1), 1–7. https://doi.org/10.1007/s40475-022-00253-w
Maziarz, E. K., & Perfect, J. R. (2016). Cryptococcosis. Infectious disease clinics of North America, 30(1), 179–206. https://doi.org/10.1016/j.idc.2015.10.006
May, R. C., Stone, N. R., Wiesner, D. L., Bicanic, T., & Nielsen, K. (2016). Cryptococcus: from environmental saprophyte to global pathogen. Nature reviews. Microbiology, 14(2), 106–117. https://doi.org/10.1038/nrmicro.2015.6
McMullan, B. J., Sorrell, T. C., & Chen, S. C. (2013). Cryptococcus gattii infections: contemporary aspects of epidemiology, clinical manifestations and management of infection. Future microbiology, 8(12), 1613–1631. https://doi.org/10.2217/fmb.13.123
Nakao, M., Fujita, K., Arakawa, S., Hayashi, S., Tomita, S., Sato, H., & Muramatsu, H. (2021). Treatment of Cryptococcus gattii Infection Using Voriconazole. Internal medicine (Tokyo, Japan), 60(22), 3635–3638. https://doi.org/10.2169/internalmedicine.5866-20
Pereira A. S. et al. (2018). Metodologia da pesquisa científica. [free e-book]. Editora UAB/NTE/UFSM.
Phillips, P., Galanis, E., MacDougall, L., Chong, M. Y., Balshaw, R., Cook, V. J., Bowie, W., Steiner, T., Hoang, L., Morshed, M., Ghesquiere, W., Forrest, D. M., Roscoe, D., Doyle, P., Kibsey, P. C., Connolly, T., Mirzanejad, Y., Thompson, D., & British Columbia Cryptococcus gattii Study Group (2015). Longitudinal clinical findings and outcome among patients with Cryptococcus gattii infection in British Columbia. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 60(9), 1368–1376. https://doi.org/10.1093/cid/civ041
Rother, E. T. (2007). Revisão sistemática x revisão narrativa. Acta Paul. Enferm. 20 (2). https://doi.org/10.1590/S0103-21002007000200001.
Saijo, T., Chen, J., Chen, S. C., Rosen, L. B., Yi, J., Sorrell, T. C., Bennett, J. E., Holland, S. M., Browne, S. K., & Kwon-Chung, K. J. (2014). Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients. mBio, 5(2), e00912–e914. https://doi.org/10.1128/mBio.00912-14
Sionov, E., Lee, H., Chang, Y. C., & Kwon-Chung, K. J. (2010). Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. PLoS pathogens, 6(4), e1000848. https://doi.org/10.1371/journal.ppat.1000848
Smith, R. M., Mba-Jonas, A., Tourdjman, M., Schimek, T., DeBess, E., Marsden-Haug, N., & Harris, J. R. (2014). Treatment and outcomes among patients with Cryptococcus gattii infections in the United States Pacific Northwest. PloS one, 9(2), e88875. https://doi.org/10.1371/journal.pone.0088875
Snyder, H. (2019). Literature review as a research methodology: An overview and guidelines. Journal of business research, 104, 333-339.
Souto, A. C., Bonfietti, L. X., Ferreira-Paim, K., Trilles, L., Martins, M., Ribeiro-Alves, M., Pham, C. D., Martins, L., Dos Santos, W., Chang, M., Brito-Santos, F., Santos, D. C., Fortes, S., Lockhart, S. R., Wanke, B., Melhem, M. S., Lazéra, M. S., & Meyer, W. (2016). Population Genetic Analysis Reveals a High Genetic Diversity in the Brazilian Cryptococcus gattii VGII Population and Shifts the Global Origin from the Amazon Rainforest to the Semi-arid Desert in the Northeast of Brazil. PLoS neglected tropical diseases, 10(8), e0004885. https://doi.org/10.1371/journal.pntd.0004885
Springer, D. J., & Chaturvedi, V. (2010). Projecting global occurrence of Cryptococcus gattii. Emerging infectious diseases, 16(1), 14–20. https://doi.org/10.3201/eid1601.090369
Suwatanapongched, T., Sangsatra, W., Boonsarngsuk, V., Watcharananan, S. P., & Incharoen, P. (2013). Clinical and radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients and their outcomes after treatment. Diagnostic and interventional radiology (Ankara, Turkey), 19(6), 438–446. https://doi.org/10.5152/dir.2013.13049
Thornton, C. S., Larios, O., Grossman, J., Griener, T. P., & Vaughan, S. (2019). Pulmonary Cryptococcus infections as a manifestation of idiopathic CD4 lymphocytopenia: case report and literature review. BMC infectious diseases, 19(1), 862. https://doi.org/10.1186/s12879-019-4453-x
Vijayan, T., Chiller, T., & Klausner, J. D. (2013). Sensitivity and specificity of a new cryptococcal antigen lateral flow assay in serum and cerebrospinal fluid. MLO: medical laboratory observer, 45(3), 16–20.
WHO. (2022). Fungal Priority Pathogens List to Guide Research, Development and Public Health Action. World Health Organization; Geneva, Switzerland. pp. 1–48.
Wu, H. H., Chen, Y. X., & Fang, S. Y. (2020). Pleural effusion in an immunocompetent host with cryptococcal pneumonia: A case report. World journal of clinical cases, 8(7), 1295–1300. https://doi.org/10.12998/wjcc.v8.i7.1295
Xue, X., Deng, H., Zhao, L., Zang, X., Asuquo, I. P., Meng, M., Ma, X., Qin, C., Meng, Y., Wu, C., Gao, J., & Pan, L. (2020). Cryptococcosis caused by cryptococcus gattii: 2 case reports and literature review. Medicine, 99(50), e23213. https://doi.org/10.1097/MD.0000000000023213
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