新型隐球菌是一种分布在世界各地的真菌。它常和鸟粪相关(特别是鸽子粪),并已从几个品种的树的中心木质中分离到该病原体。[1]Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006;20:507-544.http://www.ncbi.nlm.nih.gov/pubmed/16984867?tool=bestpractice.com[2]Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am. 2002;16:837-874.http://www.ncbi.nlm.nih.gov/pubmed/12512184?tool=bestpractice.com[4]Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008;29:141-150.http://www.ncbi.nlm.nih.gov/pubmed/18365996?tool=bestpractice.com
>95% 的隐球菌病是由新型隐球菌格鲁比(血清 A 型)引起的。[1]Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006;20:507-544.http://www.ncbi.nlm.nih.gov/pubmed/16984867?tool=bestpractice.com新型隐球菌新型变种(血清 D 型)多在欧洲国家(如丹麦、德国、意大利、法国和瑞士)、澳大利亚和美国引起疾病。格特隐球菌(血清 B 型和 C 型)主要在热带及亚热带地区(如澳大利亚,巴布新几内亚,东南亚,中非和南南)引发疾病,因为某些桉树树种可生长在这些地方。但是,格特隐球菌曾在加拿大温哥华岛引起隐球菌病感染的爆发,已被隔离。[5]Kidd SE, Hagen F, Tscharke RL, et al. A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci USA. 2004;101:17258-17263.http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15572442http://www.ncbi.nlm.nih.gov/pubmed/15572442?tool=bestpractice.com[6]Lui G, Lee N, Ip M, et al. Cryptococcosis in apparently immunocompetent patients. QJM. 2006;99:143-151.http://qjmed.oxfordjournals.org/cgi/content/full/99/3/143http://www.ncbi.nlm.nih.gov/pubmed/16504989?tool=bestpractice.com
接触隐球菌属是相当常见的,有证据表明大多数人到5岁时已接触过该真菌。[7]Goldman DL, Khine H, Abadi J, et al. Serologic evidence for Cryptococcus neoformans infection in early childhood. Pediatrics. 2001;107:E66.http://pediatrics.aappublications.org/cgi/content/full/107/5/e66http://www.ncbi.nlm.nih.gov/pubmed/11331716?tool=bestpractice.com在 HIV 阴性患者中,隐球菌病的年发病率接近每 10 万人 0.2-0.9 例,具体发病率取决于所研究的地理地区。[8]Hajjeh RA, Conn LA, Stephens DS, et al. Cryptococcosis: population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. J Infect Dis. 1999;179:449-454.http://jid.oxfordjournals.org/content/179/2/449.fullhttp://www.ncbi.nlm.nih.gov/pubmed/9878030?tool=bestpractice.comHIV感染在世界范围内和>80%的隐球菌病相关。在发达国家,高效的抗逆转录病毒治疗 (highly active antiretroviral treatment, HAART) 降低了隐球菌病的发生率,现在大多数新病例见于最近诊断的 HIV 患者中。[9]Dromer F, Mathoulin-Pelissier S, Fontanet A, et al. Epidemiology of HIV-associate cryptococcosis in France (1985-2001): comparison of the pre-and post-HAART eras. AIDS. 2004;18:555-562.http://www.ncbi.nlm.nih.gov/pubmed/15090810?tool=bestpractice.com[10]Friedman GD, Jeffrey Fessel W, Udaltsova NV, et al. Cryptococcosis: the 1981-2000 epidemic. Mycoses. 2005;48:122-125.http://www.ncbi.nlm.nih.gov/pubmed/15743430?tool=bestpractice.com[11]Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. November 2016. http://aidsinfo.nih.gov (last accessed 19 December 2016).https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf此外,CD4 细胞计数<100 个细胞/μL 的患者倾向于具有更高风险。[11]Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. November 2016. http://aidsinfo.nih.gov (last accessed 19 December 2016).https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf一项报告估计,隐球菌脑膜炎每年约引起 62.4 万人死亡。[4]Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008;29:141-150.http://www.ncbi.nlm.nih.gov/pubmed/18365996?tool=bestpractice.com[12]Park BJ, Wannemuehler KA, Marston BJ, et al. Refocusing on a re-emergent disease: the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. In: Program and abstracts of the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the Infectious Disease Society of America (IDSA) 46th Annual Meeting; October 25-28, 1998; Washington, DC.无论是HIV阳性还是HIV阴性患者,男性在隐球菌病中占的比例更高。[9]Dromer F, Mathoulin-Pelissier S, Fontanet A, et al. Epidemiology of HIV-associate cryptococcosis in France (1985-2001): comparison of the pre-and post-HAART eras. AIDS. 2004;18:555-562.http://www.ncbi.nlm.nih.gov/pubmed/15090810?tool=bestpractice.com[13]Dromer F, Mathoulin-Pelissier S, Launay O, et al; the French Cryptococcis Study Group. Determinants of disease presentation and outcome during cryptococcosis. PLoS Med. 2007;4:e21.http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17284154http://www.ncbi.nlm.nih.gov/pubmed/17284154?tool=bestpractice.com隐球菌病在儿童中相当少见,即使是AIDS患者。
在免疫功能受损的患者中,大部分感染是由新型隐球菌引起的,而格特隐球菌更多见于 HIV 阴性人群中。[1]Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006;20:507-544.http://www.ncbi.nlm.nih.gov/pubmed/16984867?tool=bestpractice.com[4]Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008;29:141-150.http://www.ncbi.nlm.nih.gov/pubmed/18365996?tool=bestpractice.com[5]Kidd SE, Hagen F, Tscharke RL, et al. A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci USA. 2004;101:17258-17263.http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15572442http://www.ncbi.nlm.nih.gov/pubmed/15572442?tool=bestpractice.com[6]Lui G, Lee N, Ip M, et al. Cryptococcosis in apparently immunocompetent patients. QJM. 2006;99:143-151.http://qjmed.oxfordjournals.org/cgi/content/full/99/3/143http://www.ncbi.nlm.nih.gov/pubmed/16504989?tool=bestpractice.com[14]MacDougall L, Kidd SE, Galanis E, et al. Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. Emerg Infect Dis. 2007;13:42-50.http://wwwnc.cdc.gov/eid/article/13/1/06-0827_articlehttp://www.ncbi.nlm.nih.gov/pubmed/17370514?tool=bestpractice.com隐球菌病在实体器官移植患者中是第三大侵袭性真菌感染。[1]Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006;20:507-544.http://www.ncbi.nlm.nih.gov/pubmed/16984867?tool=bestpractice.com[4]Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008;29:141-150.http://www.ncbi.nlm.nih.gov/pubmed/18365996?tool=bestpractice.com[15]Vilchez RA, Fung J, Kusne S. Cryptococcosis in organ transplant recipients: an overview. Am J Transplant. 2002;2:575-580.http://onlinelibrary.wiley.com/doi/10.1034/j.1600-6143.2002.20701.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/12201357?tool=bestpractice.com[16]Pappas PG, Kaufmann C, Alexander B, et al. Prospective surveillance of invasive fungal infections (IfIs) among organ transplant recipients (OTRs) in the US 2001-2006. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September, 2007; Chicago, IL.