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1、Pneumonia in HIV, approached by specific diseases 通过特定疾病考察 HIV感染肺炎,Causes of Pulmonary Disease Associated with Human Immunodeficiency Virus Infection 与人类HIV感染有关的肺部疾病的病因,Mandell, Douglas, and Bennetts Principals and Practice of Infectious Disease. Sixth edition. 传染性疾病的要点与实践：第六版,最常见病因 细菌 肺炎链球菌 流感嗜学血杆菌
2、 未发现微生物，但对抗细菌药物有反应 分枝杆菌 结核分枝杆菌 真菌 肺囊虫肺炎 不常见但在某些场合可具有重要临床意义 细菌 绿脓杆菌 金黄色葡萄球菌 肠杆菌科 军团菌 奴卡菌 马红球菌 分枝杆菌 坎沙西分枝杆菌 鸟型分枝杆菌复合物 真菌 新型隐球菌 荚膜组织胞浆菌 厌酷球孢子 曲霉菌 皮炎芽生菌 马尔尼菲青霉菌,病毒 流感病毒 巨细胞病毒 单纯疱疹病毒 腺病毒 呼吸道合胞病毒 副流感病毒 寄生虫 刚地弓形虫 粪类圆线虫 微孢子虫 微小隐孢子虫 非感染性 卡波济肉瘤 非何杰金淋巴瘤 肺癌 原发肺动脉高压 充血性心力衰竭 淋巴细胞性（或淋巴样）间质肺炎 肺气肿 阿巴卡韦过敏,Distributio
3、n of AIDS cases by five opportunistic infections in Thailand, (Data as of September 1984-March 2004) 泰国按5种机会性感染分类的AIDS病例组成情况， （1984年9月-2004年3月数据）,3.3%,14.7%,4.6%,25.6%,18.7%,Bureau of Epidemiology, CDC , MOPH,Mycobacterium Infection - Mycobacterium tuberculosis (M. TB) - Mycobacterium avium Complex
4、(MAC) Fungal Infection - Pneumocystis jirovecii - Cryptococcus neoformans Bacterial Infection - Nocardia spp. - Rhodococcus equi - Miscellaneous,Key Opportunistic Organisms for Pneumonia in HIV+ Patients HIV阳性患者肺炎主要机会性致病性微生物,分枝杆菌感染 - 结核分枝杆菌 (M. TB) - 鸟分枝杆菌复合物 (MAC) 真菌感染 - 肺囊虫肺炎 - 新型隐球菌 细菌感染 - 诺卡氏菌 -
5、 马红球菌 - 其它细菌,Mycobacterium tuberculosis 结核分枝杆菌 (M. TB),结核-HIV的联合流行分布,Impact of TB on HIV,leading AIDS-related OI enhance HIV replication might accelerate the natural progression of HIV infection drug interaction between RMP vs. ARV,结核对HIV的影响,结核是首要的艾滋病相关机会性感染 结核可增强HIV复制 结核有可能加速HIV感染的自然病程 利福平与抗逆转录药物的相
6、互作用,Impact of HIV on TB,high rate of primary TB and reactivation increase incidence of extrapulmonary and disseminated TB increase incidence of paradoxical reaction might need longer treatment course more adverse drug reactions increase incidence of MDR-TB high mortality rate,HIV对结核的影响,原发结核的高发病率和再激活
7、 增加肺外结核和播散性结核的发病率 增加异常反应的发生率 可能需要延长疗程 增加药物不良反应 增加耐多药性结核病的发生率 高死亡率,Clinical manifestations of active TB in early versus late HIV infection HIV感染早期和晚期活动性结核的临床表现,For practical purposes , early and late may be defined as CD4+cell counts 300 cells/mm and 300 个细胞/mm a和 200个细胞/mm,a,a,Radiographic Pictures
8、of TB/HIV,CD4 300 - patchy or nodular infiltration - location in apical or subapicoposterior segment of upper lobe or superior segment of lower lobe - dry, thick wall cavitation (50%), air-fluid level is uncommon - lymphadenopathy is unusual - pleural effusion could be found,“Typical radiographic pa
9、ttern of PTB”,结核/HIV的放射学检查图象,CD4 300 - 斑片或结节浸润影 - 定位于肺尖或上叶尖下后段或下叶上段 - 干性厚壁空洞 (50%)，气液平不常见 - 淋巴腺病不常见 - 可见胸膜渗出,“肺结核的典型放射线表现”,Radiographic Pictures of TB/HIV,CD4 200 - alveolar infiltration, diffuse interstitial infiltration, or mixed infiltration - location in any segments or lobes - common enlarged l
10、ymphadenopathy - common extrapulmonary involvement - normal CXR (14-20%) in advanced AIDS (CD450),“Non-specific radiographic pattern”,结核/HIV的放射学检查图象,CD4 200 - 肺泡浸润，弥漫间质浸润或混合浸润 - 定位于任何肺段或肺叶 - 一般化增大的淋巴结 - 一般化的肺外受累 - 晚期艾滋病患者(CD450)可有正常的X线表现 (14-20%),“非特异放射线表现”,AFB stain; acid-fast bacilli 抗酸杆菌染色； 抗酸杆菌,
11、Gram stain; ghost bacilli 革兰氏染色； 血影杆菌,H&E stain 苏木素和伊红染色,AFB stain 抗酸杆菌染色,Mycobacterium avium Complex 鸟分枝杆菌综合症 (MAC),MAC infection in Non-HIV,Prior history of underlying lung pathology Middle-age to old man Typical radiographic pictures - upper lobe fibronodular lesion, associated with pleural thick
12、ening - cavitations tend to be higher than tuberculosis (60-90% vs. 50%) and more likely to be thin-wall, quite large - pleural effusion is common,“Pulmonary disease”,非HIV感染者的MAC感染,有基础肺疾病史 从中年到老年均可发生 典型放射线表现 - 上叶纤维结节病灶，与胸膜增厚有关 - 空洞的发生比结核多（分别为60-90%和50%），更多见大的薄壁空洞 - 胸膜渗出常见,“肺部疾病”,MAC infection in a 5
13、2-year-old COPD man, with history of prolong fever, weight loss, cough, intermittent hemoptysis, and dyspnea 某52岁慢阻肺患者的MAC感染，持续发热，体重下降，咳嗽，间断性咯血和呼吸困难,Mandell, Douglas, and Bennetts Principals and Practice of Infectious Disease. Sixth edition.,MAC infection in AIDS-patients,CD4 50 The most common orga
14、ns involved; - spleen, liver, intestines, colon, lymph nodes, bone marrow The less common organs involved; - lung (10%), adrenal glands, stomach, central nervous system (CNS) Radiographic pictures, simulating TB; - alveolar/interstitial infiltration - nodules/cavitations are uncommon - adenopathy is
15、 not dominant,“Disseminated disease”,艾滋病患者的MAC感染,CD4 50 最常受累的器官： - 脾，肝，小肠，结肠，淋巴结，骨髓 最少受累的器官： - 肺 (10%)，肾上腺，胃，中枢神经系统 (CNS) 放射线表现类似于结核： - 肺泡/间质浸润 - 结节/空洞不常见 - 腺病不是主要的,“播散性疾病”,Pneumocystis jirovecii (carinii) （卡氏）肺囊虫肺炎,您可以预防卡氏肺囊虫肺炎： HIV感染者指南,PCP in Non-HIV,Immunocompromised host at risk for Pneumocysto
16、sis - hematological malignancies and solid tumors - solid organ/bone marrow transplant recipients - collagen vascular disorders - use of cytotoxic/immunosuppressive therapy especial corticosteroids Insidious onset of progressive dyspnea on exertion, fever, + dry cough and cyanosis in 1-2 weeks,非HIV感
17、染者的卡氏肺囊虫肺炎,免疫受损宿主易发生肺囊虫肺炎 - 血液系统恶变和实体肿瘤 - 实体器官/骨髓移植接受者 - 胶原血管异常 - 使用细胞毒/免疫抑制治疗，尤其是皮质激素 缓慢发作的劳力性进展性呼吸困难，发热， +干咳，紫绀（1-2周）,Radiographic Pictures of PCP,Typical pattern: - normal CXR (10-39%) in early disease - diffuse bilateral infiltration (ground-glass appearance) Atypical pattern: - thin-wall cyst,
18、bleb - - risk for pneumothorax - unilateral infiltration, nodules, cavitations lymphadenopathy, pleural effusion,卡氏肺囊虫肺炎放射线表现,典型表现: - 早期疾病可有正常胸部X线表现 (10-39%) - 弥漫性双侧浸润（毛玻璃样表现） 非典型表现: - 薄壁囊，气泡 - - 发生气胸风险 - 单侧浸润，结节，空洞，淋巴腺病，胸膜渗出,PCP in AIDS-patients,CD4 200 Disease burden is higher but severity is less
19、 Symptoms; lasting from weeks to months Extrapulmonary pneumocystosis; in advanced AIDS without PCP prophylasis or only aerosolized pentamidine CXR; cavitations, lymphadenopathy and pleural effusion are unusual,“Cavity, adenopathy and pleural effusion are unusual”,艾滋病患者卡氏肺囊虫肺炎,CD4 200 疾病负荷更高，但严重度较小
20、症状：持续数周到数月 肺外肺囊虫肺炎：可见于不做PCP预防治疗或仅做戊烷脒雾化治疗的进展期艾滋病患者 胸部X线表现：空洞、淋巴腺病、胸膜渗出不常见,“空洞、腺病和胸膜渗出不常见”,GMS stain; cluster of round or cup shaped cysts GMS染色； 成堆的圆形或杯状囊,H frothy eosinophilic honeycombed material filling alveolar space 苏木素和伊红染色； 空泡化嗜酸粒蜂窝样物质充填于肺泡间隙,Cryptococcal neoformans 新型隐球菌,Cryptococcal Infecti
21、on in Non-HIV,Susceptible hosts Symptoms range; - asymptomatic colonization of the airway to life- threatening pneumonia (depend on immune status) Radiographic characteristics include; - well-defined noncalcified single/multiple nodules, mass-like infiltration or dry thin-wall cavitations The two co
22、mmon sites are lung and CNS,非HIV感染者的新型隐球菌感染,易感宿主 症状范围： - 从气道的无症状聚集到威胁生命的肺炎都可能发生（取决于免疫状态） 放射线特点包括： - 分界清楚的非钙化单发/多发结节，肿块样浸润或干性薄壁空洞 两个常见部位为肺和中枢神经系统,Mandell, Douglas, and Bennetts Principals and Practice of Infectious Disease. Sixth edition.,HIV感染 淋巴增生异常 肉瘤 皮质激素治疗 高-IgM综合征 高-IgE综合征 单克隆抗体（如英利昔单抗） 系统性红斑狼疮
23、* HIV阴性CD4+ T淋巴细胞减少症 糖尿病# 器官移植* 腹膜透析 肝硬化 * 免疫抑制治疗可能导致易感性。 # 糖尿病长期以来就被认为是新型隐球菌感染的危险因素。但由于糖尿病是一个很常见的疾病，因此不能确定糖尿病就是新型隐球菌感染的危险因素。 摘自 Casadevall A, Perfect JR.新型隐球菌，华盛顿：ASM Press；1998:410,表261-1：已知或可能与新型隐球菌感染有关的情形,Mandell, Douglas, and Bennetts Principals and Practice of Infectious Disease. Sixth edition
24、.,Cryptococcal Infection in AIDS-patients,CD4 100 More CNS and extrapulmonary infections For CNS infection; - high rate of +india ink, +Cryptococcal Ag, +blood culture, and few CSF inflammatory cells For lung infection (only 5-25% of cases); - coinfection have been reported with TB, PCP, Nocardiosis
25、,“Limited pneumonia is uncommon and coinfection is considered”,艾滋病患者的新型隐球菌感染,CD4 100 更多的中枢神经系统和肺外感染 中枢神经系统感染： - 高阳性率的印度墨汁染色，新型隐球菌抗原，血培养和脑脊液炎性细胞 肺感染（发生率只有5-25%）： - 曾见于结核、卡氏肺囊虫肺炎、诺卡菌病的联合感染,“限制性肺炎不常见，此时要考虑联合感染”,Cryptococcal Pneumonia in AIDS-patients,Radiographic pictures; - diffuse bilateral interstit
26、ial infiltration (mimic PCP) - focal/nodular infiltration, consolidation, dry thin-wall cavitations - lymphadenopathy - pleural involvement is unusual,“Radiographic patterns often mimic PCP”,艾滋病患者的新型隐球菌肺炎,放射线表现： - 弥漫双侧间质浸润（酷似卡氏肺囊虫肺炎） - 局灶/结节浸润，实变，干性薄壁空洞 - 淋巴腺病 - 胸膜受累不常见,“放射线表现常酷似卡氏肺囊虫肺炎”,AFB stain;
27、encapsulated yeast cells and acid-fast bacilli 抗酸杆菌染色; 包囊化酵母细胞和抗酸杆菌,Wright stain; encapsulated yeast cells 莱特染色； 包囊化酵母细胞,Nocardia spp. 诺卡氏菌,Nocardiosis,Preexisting immunocompromised host; - alcoholism - diabetes mellitus - organ transplantation/lymphoreticular neoplasm - long-term corticosteroid usa
28、ge - chronic lung disease - AIDS 3 forms; 1. progressive cutaneous/lymphocutaneous disease 2. pulmonary disease 3. disseminated infection: CNS, eye, skin, bone&joint, heart, lung and kidney,诺卡菌病,存在免疫受损的宿主： - 酗酒 - 糖尿病 - 器官移植/淋巴网状系统肿瘤 - 长期应用皮质激素 - 慢性肺疾病 - 艾滋病 3种形式： 1. 进展性皮肤/淋巴皮肤疾病 2. 呼吸疾病 3. 播散感染：中枢神经
29、系统，眼，皮肤，骨/关节，心脏，肺和肾,Nocardiosis,Radiographic pictures; - irregular nodules, mass-like condolidation, abscesses, reticulonodular infiltration - pleural effusion/empyema - contiguous extension to deep structures and surface Nocardiosis in AIDS-patients; - CD4 200 - Overall incidence in AIDS-patient is
30、 low!,“Clinical clues to suspected nocardiosis” spread to contiguous structures, especially soft tissue swelling or external fistulas, and to CNS,诺卡菌病,放射线表现; - 不规则结节，肿块样实变，脓肿，网状结节浸润 - 胸膜渗出/积脓 - 向深部结构和体表连续进展 艾滋病患者的诺卡菌病： - CD4 200 - 在艾滋病患者中整体发病率较低！,“诺卡菌病的临床线索” 扩散到连续性组织结构，尤其是组织肿胀或扩散到外部瘘管和中枢神经系统,Gram st
31、ain; gram+ branching filament 革兰氏染色； 革兰 + 分支细丝,Modified acid fast stain; acid-fast branching filament 改良抗酸染色； 抗酸分支细丝,Rhodococcus equi 马红球菌,Rhodococcus equi,Two thirds of cases have occurred in AIDS-patient - CD4 100 - Overall incidence in AIDS-patients is low! Radiographic pictures; - nodules, thick
32、-wall cavitations (sometimes air-fluid level), necrotizing pneumonia (resembles TB or nocardiosis) - lymphadenopathy, pleural effusion/empyema Extrapulmonary infection: frequently a late manifestation of the initial pulmonary infection,马红球菌,此病的三分之二病例发生在艾滋病患者中 - CD4 100 - 在艾滋病患者中整体发病率较低！ 放射线表现： - 结节，厚壁空洞（有时有气液平），坏死性肺炎（可与结核或诺卡菌病相似） - 淋巴腺病，胸膜渗出/积脓 肺外感染：经常是肺初始感染的晚期表现,Gram stain; gram+ coccobacilli 革兰氏染色； 革兰 + 球杆菌,Modified acid fast stain; acid-fast coccobacilli 改良抗酸染色； 抗酸球杆菌,Thank you 谢谢,