肺孢子虫肺炎 (PCP) 是儿童、青少年和成人最常见的艾滋病定义性疾病之一。[1]Palella FJ, Delaney KM, Moorman FC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338:853-860.http://content.nejm.org/cgi/content/abstract/338/13/853http://www.ncbi.nlm.nih.gov/pubmed/9516219?tool=bestpractice.com它仍是HIV感染患者住院期间最常见的艾滋病相关死亡原因。在纽约市一家三级医院(拥有艾滋病护理计划的综合门诊),从2004年至2008年,4.8%(10/208)的艾滋病相关的死亡是由于PCP。[2]Kim JH, Psevdos G Jr, Gonzalez E, et al. All-cause mortality in hospitalized HIV-infected patients at an acute tertiary care hospital with a comprehensive outpatient HIV care program in New York City in the era of highly active antiretroviral therapy (HAART). Infection. 2013;41:545-551.http://www.ncbi.nlm.nih.gov/pubmed/23264096?tool=bestpractice.com使用高活性抗逆转录病毒疗法(HAART)和常规PCP预防有助于降低总患病数。[3]Murray JF, Nadel JA, Mason RJ. Murray and Nadels Textbook of respiratory medicine. 4th ed. 2005, Philadelphia, PA: Elsevier Saunders.EuroSIDA 研究随访了一个包括超过 8500 例 HIV 阳性欧洲患者的队列,发现 PCP 的发生率从 1995 年 3 月前的 4.9 例每 100 人-年下降到 1998 年 3 月后的 0.3 例 100 人-年。[4]Weverling GJ, Mocroft A, Ledergerber B, et al. Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection. EuroSIDA Study Group. Lancet. 1999;353:1293-1298.http://www.ncbi.nlm.nih.gov/pubmed/10218526?tool=bestpractice.com 在 HIV 阳性成人中,发生 PCP 的最重要危险因素为 CD4 细胞计数<200 个细胞/μL,CD4 细胞计数低于此水平的程度越高,发病风险越高。[5]Phair J, Munoz A, Detels R, et al. The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group. N Engl J Med. 1990 Jan 18;322(3):161-5.http://www.ncbi.nlm.nih.gov/pubmed/1967190?tool=bestpractice.com[6]Stansell JD, Osmond DH, Charlebois E, et al. Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group. Am J Respir Crit Care Med. 1997;155:60-66.http://www.ncbi.nlm.nih.gov/pubmed/9001290?tool=bestpractice.com如果患者通过进行HAART而维持CD4细胞计数增加超过200个细胞/μl,其他感染PCP的风险会下降。
目前,PCP病例多发生在不知道自身感染HIV、未进行HIV治疗、因不遵守或不耐受而未使用HAART或PCP预防的患者。[7]Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the U.S. in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000;30(suppl 1): 5S-14S.http://www.ncbi.nlm.nih.gov/pubmed/10770911?tool=bestpractice.com[8]Pulvirenti J, Herrera P, Venkataraman P, et al. Pneumocystis carinii pneumonia in HIV-infected patients in the HAART era. AIDS Patient Care STDS. 2003:17:261-265.http://www.ncbi.nlm.nih.gov/pubmed/12880489?tool=bestpractice.com[9]Lundberg BE, Davidson AJ, Burman WJ. Epidemiology of Pneumocystis carinii pneumonia in an era of effective prophylaxis: the relative contribution of non-adherence and drug failure. AIDS. 2000;14:2559-2566.http://www.ncbi.nlm.nih.gov/pubmed/11101068?tool=bestpractice.com[10]Huang L, Hecht FM. Why does Pneumocystis carinii pneumonia still occur? AIDS. 2000;14:2611-2612.http://www.ncbi.nlm.nih.gov/pubmed/11101076?tool=bestpractice.com在 2000 和 2013 年之间,一项欧洲研究报告称,诊断 HIV 前有金罗维氏肺囊虫肺炎 (PJP) 发作史的患者的年龄和比例有所增高(分别从 34 增高到 44 岁和从 48% 增高到 67%)。[11]López-Sánchez C, Falcó V, Burgos J, et al. Epidemiology and long-term survival in HIV-infected patients with Pneumocystis jirovecii pneumonia in the HAART era:experience in a university hospital and review of the literature. Medicine (Baltimore). 2015;94:e681.http://journals.lww.com/md-journal/Fulltext/2015/03040/Epidemiology_and_Long_Term_Survival_in.14.aspxhttp://www.ncbi.nlm.nih.gov/pubmed/25816039?tool=bestpractice.com
在美国,HIV感染的患病率可能被低估,因此,PCP首次发病率也可能被低估,特别是缺乏医疗护理的人群。[12]Centers for Disease Control and Prevention (CDC). HIV prevalence estimates: United States, 2006. MMWR Morb Mortal Wkly Rep. 2008;57:1073-1076.http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5739a2.htmhttp://www.ncbi.nlm.nih.gov/pubmed/18830210?tool=bestpractice.com另一类PCP的高危患者是来自发展中国家的HIV阳性的难民,这些人群可能很难将PCP与肺结核感染或二重感染区分。[13]Fisk DT, Meshnick, S, Kazanjian PH. Pneumocystis carinii pneumonia in patients in the developing world who have acquired immunodeficiency syndrome. Clin Infect Dis. 2003;36:70-78.http://www.ncbi.nlm.nih.gov/pubmed/12491205?tool=bestpractice.comPCP的发病率因地域不同而有差异,但世界上的有些地区呈低流行。[14]Taylor SM, Meshnick SR, Worodria W, et al. Low prevalence of Pneumocystis jirovecii lung colonization in Ugandan HIV-infected patients hospitalized with non-Pneumocystis pneumonia. Diagn Microbiol Infect Dis. 2012;72:139-143.http://www.ncbi.nlm.nih.gov/pubmed/22153850?tool=bestpractice.com
在儿童患者中,PCP的总发病率已较HIV感染初期时代有所下降,部分原因是由于改善了产前HIV抗体测试和进行HIV治疗预防垂直传播,此外,也由于进行了HAART。[7]Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the U.S. in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000;30(suppl 1): 5S-14S.http://www.ncbi.nlm.nih.gov/pubmed/10770911?tool=bestpractice.com在一项围产期艾滋病的协同传输的研究中,HAART治疗前后,HIV阳性的儿童PCP发病率从5.2例每100人年下降至0.3例每100人年。[15]Nesheim SR Kopogiannis BG, Soe SM, et al. Trends in opportunistic infections in the pre- and post-highly active antiretroviral therapy eras among HIV-infected children in the Perinatal AIDS Collaborative Transmission Study, 1986-2004. Pediatrics. 2007;120:100-109.http://www.ncbi.nlm.nih.gov/pubmed/17606567?tool=bestpractice.comHIV阳性的儿童中,PCP在3-6个月大的婴儿中发生率最高。6岁以下的儿童发生PCP的危险因素与CD4细胞计数无关但与CD4百分比有关。大于6个月的儿童,发生PCP危险因素与成人相似,与CD4细胞计数有关。[16]Kovacs A, Frederick T, Church J, et al. CD4 T-lymphocyte counts and Pneumocystis carinii pneumonia in pediatric HIV infection. JAMA. 1991;265:1698-1703.http://www.ncbi.nlm.nih.gov/pubmed/1672169?tool=bestpractice.com[17]Morris A, Lundgren JD, Masur H, et al. Current epidemiology of Pneumocystis pneumonia. Emerg Infect Dis. 2004;10:1713-1720.http://www.ncbi.nlm.nih.gov/pubmed/15504255?tool=bestpractice.com[18]Kaplan JE, Masur H, Holmes KK. Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. 2002;51(RR-8):1-52.
在HIV阴性的患者中,PCP的总体发病率低,几乎只发生在由其他原因造成的免疫功能低下的患者。[19]Falagas ME, Manta KG, Betsi GI, et al. Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review. Clin Rheumatol. 2007;26:663-670.http://www.ncbi.nlm.nih.gov/pubmed/17186117?tool=bestpractice.com[20]Gilmartin GS, Koziel H. Pneumocystis carinii pneumonia in adult non-HIV disorders. J Intensive Care Med. 2002;17:283-301.[21]Pareja JGR, Garland R, Koziel H. Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. Chest. 1998;113:1215-1224.http://www.ncbi.nlm.nih.gov/pubmed/9596297?tool=bestpractice.com[22]Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc. 1996;71:5-13.[23]Fillatre P, Decaux O, Jouneau S, et al. Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV-negative patients. Am J Med. 2014;127:1242.http://www.ncbi.nlm.nih.gov/pubmed/25058862?tool=bestpractice.com[24]Bienvenu AL, Traore K, Plekhanova I, et al. Pneumocystis pneumonia suspected cases in 604 non-HIV and HIV patients. Int J Infect Dis. 2016;46:11-17.http://www.ncbi.nlm.nih.gov/pubmed/27021532?tool=bestpractice.com[25]Ling C, Qian S, Wang Q, et al. Pneumocystis pneumonia in non-HIV children: a 10-year retrospective study. Clin Respir J. 2016 Feb 15 [Epub ahead of print].http://www.ncbi.nlm.nih.gov/pubmed/26878193?tool=bestpractice.com在英国和法国(分别从 2000 到 2010 年和 2005 到 2013 年),HIV 阳性患者中的 PCP 发病率减少,但在同期 HIV 阴性的患者中增加。[26]Maini R, Henderson KL, Sheridan EA, et al. Increasing Pneumocystis Pneumonia, England, UK, 2000-2010. Emerg Infect Dis. 2013;19:386-392.http://wwwnc.cdc.gov/eid/article/19/3/12-1151_article.htmhttp://www.ncbi.nlm.nih.gov/pubmed/23622345?tool=bestpractice.com在这类人群中,PCP 主要发生在器官移植受者 (7%-43%)、血液系统恶性肿瘤患者 (23%-39%)、恶性实体肿瘤患者 (18%-27%) 和炎症性疾病患者 (11%-27%)。[20]Gilmartin GS, Koziel H. Pneumocystis carinii pneumonia in adult non-HIV disorders. J Intensive Care Med. 2002;17:283-301.[21]Pareja JGR, Garland R, Koziel H. Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. Chest. 1998;113:1215-1224.http://www.ncbi.nlm.nih.gov/pubmed/9596297?tool=bestpractice.com[23]Fillatre P, Decaux O, Jouneau S, et al. Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV-negative patients. Am J Med. 2014;127:1242.http://www.ncbi.nlm.nih.gov/pubmed/25058862?tool=bestpractice.com[24]Bienvenu AL, Traore K, Plekhanova I, et al. Pneumocystis pneumonia suspected cases in 604 non-HIV and HIV patients. Int J Infect Dis. 2016;46:11-17.http://www.ncbi.nlm.nih.gov/pubmed/27021532?tool=bestpractice.comPCP在使用肿瘤坏死因子-α拮抗剂或抗CD20单克隆抗体利妥昔单抗的患者中有报道。[27]Harigai M, Koike R, Miyasaka M, et al. Pneumocystis pneumonia associated with infliximab in Japan. N Engl J Med. 2007;357:1874-1876.http://www.ncbi.nlm.nih.gov/pubmed/17978303?tool=bestpractice.com[28]Imaizumi K, Sugishita M, Usui M, et al. Pulmonary infectious complications associated with anti-TNFalpha therapy (infliximab) for rheumatoid arthritis. Intern Med. 2006;45: 685-688.http://www.ncbi.nlm.nih.gov/pubmed/16778341?tool=bestpractice.com[29]Kalyoncu U, Karadag O, Akdogan A, et al. Pneumocystis carinii pneumonia in a rheumatoid arthritis patient treated with adalimumab. Scand J Infect Dis. 2007;39:475-478.http://www.ncbi.nlm.nih.gov/pubmed/17464877?tool=bestpractice.com[30]Lahiff C, Khiaron OB, Nolan N, et al. Pneumocystis carinii pneumonia in a patient on etanercept for psoriatic arthritis. Ir J Med Sci. 2007;176:309-311.http://www.ncbi.nlm.nih.gov/pubmed/17906888?tool=bestpractice.com[31]Mori S, Imamura S, Fiyofiji C, et al. Pneumocystis jiroveci pneumonia in a patient with rheumatoid arthritis as a complication of treatment with infliximab, anti-tumor necrosis factor alpha neutralizing antibody. Mod Rheumatol. 2006;16:58-62.http://www.ncbi.nlm.nih.gov/pubmed/16622728?tool=bestpractice.com[32]Martin-Garrido I, Carmona EM, Specks U, et al. Pneumocystis pneumonia in patients treated with rituximab. 2013;144:258-265.http://www.ncbi.nlm.nih.gov/pubmed/23258406?tool=bestpractice.comPCP在HIV阴性人群中发病多呈现暴发性过程,较HIV阳性的患者具有更高的发病率和死亡率。[24]Bienvenu AL, Traore K, Plekhanova I, et al. Pneumocystis pneumonia suspected cases in 604 non-HIV and HIV patients. Int J Infect Dis. 2016;46:11-17.http://www.ncbi.nlm.nih.gov/pubmed/27021532?tool=bestpractice.com[33]Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med. 1984 May;100(5):663-71.http://www.ncbi.nlm.nih.gov/pubmed/6231873?tool=bestpractice.com[34]Mansharamani NG, Garland R, Delaney G, et al. Management and outcome patterns for adult Pneumocystis carinii pneumonia, 1985 to 1995: comparison of HIV-associated cases to other immunocompromised states. Chest. 2000;118:704-711.http://www.ncbi.nlm.nih.gov/pubmed/10988192?tool=bestpractice.com