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人类免疫缺陷病毒与分枝杆菌合并感染的临床研究

发布时间:2018-08-03 13:49
【摘要】:第一部分艾滋病合并结核病的流行病学调查 目的:了解不同人群HIV感染率及结核病患病率。 方法:对24326例非结核病患者及7448例结核病患者进行HIV筛查;对住院的67217例HIV阴性患者、995例HIV阳性患者及2037例行cARV治疗前基线检查的HIV感染者进行结核病筛查及诊断。收集艾滋病合并机会性感染患者病例资料,对其机会性感染进行统计分析。 结果:本院非结核病人群HIV感染率为0.18%,结核病人群HIV感染率为0.48%,结核病人群HIV感染率明显高于非结核病人群(P=0.000)。本院非艾滋病人群结核病患病率为0.11%,行cARV治疗前基线检查的HIV感染人群结核病患病率为6.38%,住院艾滋病患者结核病患病率为21.01%,HIV感染人群结核病患病率明显高于非艾滋病人群(21.01%vs0.11%,P=0.000;6.38%vs0.11%,P=0.000)。结核病是艾滋病最重要的机会性感染之一,占38.0%。 结论:结核人群HIV感染率显著高于非结核病人群;HIV感染者活动性结核病患病率显著高于非HIV感染人群,结核病是艾滋病最常见的机会性感染。对HIV人群筛查结核病,对结核病人群筛查HIV有助于提高艾滋病及结核病的防治水平。 第二部分艾滋病合并结核病的临床特征 目的:总结并分析艾滋病合并结核病的临床症状、结核病类型特点及其与CD4+T淋巴细胞的关系。 方法:收集375例艾滋病合并结核病的病例资料及1013例HIV阴性结核病的病例资料,分析艾滋病合并结核病的临床症状、结核类型,并与HIV阴性结核病相比较。 结果:HIV阳性结核病患者最常见的症状为发热、乏力、纳差、咳嗽及消瘦,分别占85.6%、68.4%、65.6%、52.6%及50.2%。HIV阳性结核病仍以肺结核为多见(51.2%),肺外结核及栗粒性结核明显多于HIV阴性结核病(21.2%vs5.3%,P=0.000;13.3%vs1.7%,P=0.000)。HIV阳性结核病最常见的肺外结核类型为淋巴结结核,占48.1%。HIV阳性结核病中,肺外结核的CD4+T淋巴细胞计数较高,为146(34-246)个/ul,粟粒性结核的CD4+T淋巴细胞计数最低,为26(10-73)个/ul。肺外结核的CD4+T淋巴细胞计数显著高于肺结核(P=0.040)和粟粒性结核(P=0.001)。 结论:HIV感染合并结核病的临床表现多种多样,HIV感染早期,HIV阳性结核病患者的临床表现与HIV阴性结核病患者相似。随着免疫缺陷加重,CD4+T淋巴细胞明显减少,艾滋病患者的结核病变累及多个器官和系统,肺外结核及粟粒性结核增多,患者发热、盗汗、消瘦等全身中毒症状更明显。 第三部分艾滋病合并结核病的诊断方法比较 目的:探讨影像学、免疫学、细菌学、纤维支气管镜检查与血沉对艾滋病合并结核病的诊断价值。 方法:收集艾滋病合并结核病患者影像学结果、分析艾滋病合并结核病患者的影像学特点,并与HIV阴性结核病比较。对HIV阴性结核病及艾滋病合并结核病患者的血液进行血沉、免疫学检测(IGRA、TST及结核蛋白芯片检测),痰液、分泌物等标本进行分枝杆菌培养、分型鉴定及药物敏感性试验。对研究对象进行纤维支气管镜检查及肺泡灌洗,分析纤维支气管镜的镜下表现及分枝杆菌检出率。 结果:艾滋病合并结核病的影像学特点为病变多为弥漫性(57.3%),纵膈淋巴结肿大多见(51.6%),多位于双肺(54.0%)的全叶(46.0%)或上叶(25.0%)。IGRA、TST及结核蛋白芯片对艾滋病合并结核病的敏感性分别为78.3%、16.7%及34.7%,IGRA的敏感性显著高于TST及结核蛋白芯片(78.3%vs16.7%,P=0.005及78.3%vs34.7%, P=0.000)。TST及结核蛋白芯片的敏感性随CD4+T淋巴细胞计数下降而逐渐下降,而IGRA敏感性受CD4+T淋巴细胞计数影响较小,CD4+T淋巴细胞计数50个/u1时,IGRA的敏感性显著高于TST及结核蛋白芯片(分别为76.6%vs14.3%, P=0.001;76.6%vs25.0%, P=0.000)。IGRA的阳性结果提示HIV感染者结核潜伏性感染率为32.6%,艾滋病合并结核病的结核分枝杆菌检出率为20.3%,显著低于HIV阴性结核病的48.0%(P=0.000)。HIV阳性患者的结核分枝杆菌耐药率为25.0%,与HIV阴性患者的25.2%无显著性差异。行纤维支气管镜检查患者的结核分枝杆菌检出率显著高于未行纤维支气管镜检查的艾滋病合并肺结核病患者(51.2%vs17.7%,P=0.000)。HIV阳性结核病患者、HIV感染者及HIV阴性结核病患者的血沉依次为84(49-117)mm/h、53(20-83)mm/h及24(13-41)mm/h,三组之间差异有显著性(P=0.000)。 结论:艾滋病合并结核病的临床表现不一。需根据病史、症状体征、影像学检查、免疫学检测、血沉及病原学检查,有的患者尚须进行诊断性治疗等综合措施,才能作出正确诊断。IGRA受免疫功能缺陷影响较小,对HIV阳性结核病有较大的诊断价值。HIV阳性结核病人群病原检出率显著低于HIV阴性结核病人群。淋巴结脓液及支气管肺泡灌洗液的结核分枝杆菌检出率较高。从艾滋病患者分离到的结核分枝杆菌多耐药及耐多药菌株相对较多。纤维支气管镜对疑难病人有较大诊断价值。支气管肺泡灌洗液作细菌培养及TB-DNA检测可提高结核分枝杆菌检出率。 第四部分HIV、TB及HBV/HCV合并感染的研究 目的:了解HIV、TB及HBV/HCV合并感染的流行情况并分析多重感染的临床特征、抗结核治疗的肝损率及病死率。 方法:根据HBsAg及抗-HCV结果,将361例HIV阳性结核病患者分为HIV/TB组、HIV/TB/HBV组、HIV/TB/HCV组,并随机选取1013例HIV阴性结核病患者作为对照组,对研究对象随访一年,比较各组患者结核病类型、抗结核治疗时肝功能异常率和病死率。 结果:HIV阳性人群肝炎病毒感染率为32.4%,明显高于HIV阴性人群的8.9%(P=0.000)。HIV阳性患者的肺外结核及播散性结核分别为21.1%及26.9%,均明显高于HIV阴性患者的5.2%及18.3%(P=0.000及P=0.001),其中HIV/TB/HBV组播散性结核最多,为44.4%。HIV阳性患者药物性肝损率为4.2%,明显高于HIV阴性患者的1.0%(P=0.000),其中HIV/TB/HBV组药物性肝损率最高,为18.5%。HBV-DNA1.0×105copy/ml的患者抗结核治疗出现肝功能异常比率为68.4%,HBV-DNA阴性或1.0×105copy/ml的患者为21.1%,两者具有统计学差异(P=0.000)。HCV-RNA1.0×105copy/ml的患者抗结核治疗出现肝功能异常率为42.9%, HCV-RNA阴性或1.0×105copy/ml的患者为10.0%,两者具有统计学差异(P=0.006)。HIV阳性结核病患者病死率为13.6%,明显高于HIV阴性结核病患者的0.9%(P=0.000)。HIV/TB/病毒性肝炎组的病死率为19.7%,明显高于HIV/TB组的10.7%(P=0.019)。 结论:HIV阳性结核病人群有较高的HBV和/或HCV感染率。HIV及HBV/HCV合并感染显著增加结核病患者抗结核治疗的肝损率。HBV及HCV复制水平与抗结核治疗肝功能损害密切相关。HIV、TB及HBV/HCV合并感染人群病死率高。在抗结核治疗前,对患者作HIV、HBV及HCV筛查,有助于发现上述疾病的混合感染者;对HIV、TB及HBV合并感染者作含3TC及TDF方案的cART治疗,对HIV、TB及HCV合并感染者作抗HCV治疗,有助于降低肝损率及病死率。 第五部分艾滋病合并非结核分枝杆菌病的研究 目的:分析艾滋病合并非结核分枝杆菌病的患病率及临床特征,为其诊断及治疗提供参考依据。 方法:收集武汉大学中南医院艾滋病合并非结核分枝杆菌病病例资料19例,总结并分析其患病率、临床表现、影像学特点、细菌检出率及耐药性,并与艾滋病合并结核病进行比较。 结果:艾滋病合并非结核分枝杆菌病最常见的症状为发热(94.7%)、纳差(89.5%)、乏力(89.5%)、消瘦(84.2%)、胸闷(78.9%)、咳嗽(73.7%)。影像学特点为病变多为弥漫性(88.2%),实变影(52.9%)、纵膈淋巴结肿大(64.7%)较常见。艾滋病合并非结核分枝杆菌病的细菌检出率为21.1%。HIV阳性非结核分枝杆菌对四种一线抗结核药(INH、RFP、EMB、Sm)及两种二线抗结核药(Km、Ofx)均不敏感。 结论:艾滋病合并NTM病的临床症状与艾滋病合并结核病相似,易导致误诊和漏诊,NTM病与结核病的治疗药物有区别,明确诊断需根据病史、临床表现、细菌培养及菌种鉴定。HIV阳性人群NTM病的患病率显著高于HIV阴性人群。HIV阳性患者感染的NTM对INH、RPF、EMB、Sm、Km及Ofx均不敏感。本地区艾滋病合并NTM病的诊断、治疗及预防工作亟待加强。
[Abstract]:Part one epidemiological investigation of AIDS complicated with tuberculosis
Objective: To investigate the prevalence of HIV infection and the prevalence of tuberculosis in different populations.
Methods: 24326 cases of non TB patients and 7448 cases of tuberculosis were screened by HIV, 67217 cases of HIV negative patients in hospital, 995 cases of HIV positive patients and 2037 cases of HIV infected with cARV before cARV were screened and diagnosed. The data of AIDS patients with opportunistic infection were collected and the opportunistic infection was collected. Carry out statistical analysis.
Results: the rate of HIV infection in non TB patients was 0.18%, the rate of HIV infection in tuberculosis population was 0.48%, the rate of HIV infection in tuberculosis population was significantly higher than that of non tuberculosis population (P=0.000). The prevalence rate of tuberculosis in non AIDS population in our hospital was 0.11%, and the prevalence rate of tuberculosis in HIV infected people before cARV treatment was 6.38%. The prevalence rate of tuberculosis was 21.01%. The prevalence rate of tuberculosis in HIV infected people was significantly higher than that of non AIDS (21.01%vs0.11%, P=0.000; 6.38%vs0.11%, P=0.000). Tuberculosis was one of the most important opportunistic infections of AIDS, accounting for 38.0%..
Conclusion: the rate of HIV infection in the tuberculosis population is significantly higher than that of non tuberculosis people; the prevalence rate of active tuberculosis in HIV infected people is significantly higher than that of non HIV infected people. Tuberculosis is the most common opportunistic infection of AIDS. Screening of TB for HIV population and screening HIV in the population are helpful to improve the prevention and treatment of AIDS and tuberculosis.
The second part is the clinical characteristics of AIDS complicated with tuberculosis.
Objective: To summarize and analyze the clinical symptoms, tuberculosis types and their relationship with CD4 + T lymphocytes in AIDS patients with tuberculosis.
Methods: the data of 375 cases of AIDS with tuberculosis and 1013 cases of HIV negative TB cases were collected, and the clinical symptoms and tuberculosis types of AIDS combined with tuberculosis were analyzed and compared with those of HIV negative tuberculosis.
Results: the most common symptoms of HIV positive TB patients were fever, fatigue, tolerance, cough and emaciation, accounting for 85.6%, 68.4%, 65.6%, 52.6% and 50.2%.HIV positive tuberculosis still more common (51.2%), and extrapulmonary tuberculosis and chestnut tuberculosis were more than HIV negative tuberculosis (21.2%vs5.3%, P=0.000; 13.3%vs1.7%, P=0.000).HIV positive nodules. The most common type of extrapulmonary tuberculosis in nuclear disease is lymph node tuberculosis. In 48.1%.HIV positive tuberculosis, the CD4+T lymphocyte count of extrapulmonary tuberculosis is higher, 146 (34-246) /ul, and the CD4+T lymphocyte count of miliary tuberculosis is the lowest, and the CD4 +T lymphocyte count of 26 (10-73) /ul. pulmonary tuberculosis is significantly higher than that of pulmonary tuberculosis (P=0.040) and miliary sex Tuberculosis (P=0.001).
Conclusion: the clinical manifestations of HIV infection with tuberculosis are varied. The clinical manifestations of HIV positive TB patients in the early stage of HIV infection are similar to those with HIV negative tuberculosis. With the aggravation of the immunodeficiency, the CD4+T lymphocyte is obviously reduced, the tuberculosis of AIDS patients is involved in multiple organs and systems, and the increase of tuberculosis and miliary tuberculosis in the lung is increased. Fever, night sweats, emaciation and other symptoms of systemic poisoning were more obvious.
The third part is the diagnosis of AIDS complicated with tuberculosis.
Objective: To explore the diagnostic value of imaging, immunology, bacteriology, fiberoptic bronchoscopy and erythrocyte sedimentation rate (ESR) in AIDS complicated with tuberculosis.
Methods: to collect the imaging results of AIDS patients with tuberculosis, analyze the imaging characteristics of AIDS patients with tuberculosis, and compare with HIV negative tuberculosis. Blood sedimentation for HIV negative TB and AIDS patients with tuberculosis, immunological detection (IGRA, TST and TB chip detection), sputum, secretions and so on. Mycobacterium culture, typing identification and drug sensitivity test were carried out. Fiberoptic bronchoscopy and alveolar lavage were performed on the subjects. The findings of fiberoptic bronchoscopy and the detection rate of Mycobacterium were analyzed.
Results: the imaging features of AIDS combined with tuberculosis were mostly diffuse (57.3%), and the enlargement of the mediastinal lymph nodes (51.6%) was mostly located in the whole lobe (46%) or upper lobe (25%).IGRA of double lung (54%), and the sensitivity of TST and tuberculosis protein chip to AIDS combined with tuberculosis was 78.3%, 16.7% and 34.7% respectively, and the sensitivity of IGRA was significantly higher than that of T. The sensitivity of ST and tuberculin chip (78.3%vs16.7%, P=0.005, 78.3%vs34.7%, P=0.000).TST and tuberculosis protein chip decreased with the decrease of CD4+T lymphocyte count, but IGRA sensitivity was less affected by CD4+T lymphocyte count. When CD4+T lymphocyte count was 50 /u1, the sensitivity of IGRA was significantly higher than that of tuberculosis protein chip. The positive results of 76.6%vs14.3%, P=0.001, 76.6%vs25.0%, P=0.000).IGRA showed that the latent infection rate of tuberculosis in HIV infected persons was 32.6%, the detection rate of Mycobacterium tuberculosis in AIDS combined with tuberculosis was 20.3%, which was significantly lower than that of 48% (P=0.000).HIV positive patients with HIV negative tuberculosis (P=0.000), and the resistance rate of Mycobacterium tuberculosis was 25%, and HIV negative. There was no significant difference in the 25.2% of the patients with sex. The detection rate of Mycobacterium tuberculosis in the patients with fiberoptic bronchoscopy was significantly higher than that of the AIDS patients with pulmonary tuberculosis (51.2%vs17.7%, P=0.000).HIV positive tuberculosis. The erythrocyte sedimentation rate of HIV infected and HIV negative TB patients was 84 (49-117) mm/h, 53 (20-83) mm/h and 24 (13-41) mm/h, there was a significant difference between the three groups (P=0.000).
Conclusion: the clinical manifestation of AIDS combined with tuberculosis is different. It should be based on the medical history, symptoms and signs, imaging examination, immunological examination, erythrocyte sedimentation and pathogenic examination. Some patients still have to carry out comprehensive measures such as diagnostic treatment to make correct diagnosis of.IGRA, which is less affected by the immune function, and has a greater diagnosis of HIV positive tuberculosis. The detection rate of pathogenic bacteria in.HIV positive TB patients was significantly lower than that of HIV negative tuberculosis. The detection rate of Mycobacterium tuberculosis in lymph node and bronchoalveolar lavage fluid was higher. The multi drug resistance and multi drug resistant strains isolated from AIDS patients were relatively more. The fiberoptic bronchoscopy has a greater diagnosis for the difficult patients. Value. Bronchoalveolar lavage fluid for bacterial culture and TB-DNA detection can improve the detection rate of Mycobacterium tuberculosis.
The study of fourth parts of HIV, TB and HBV/HCV infection
Objective: To investigate the prevalence of HIV, TB and HBV/HCV co-infection and analyze the clinical features of multiple infections, the liver lesion rate and mortality of anti-tuberculosis treatment.
Methods: according to the results of HBsAg and anti -HCV, 361 cases of HIV positive tuberculosis were divided into HIV/TB group, HIV/TB/HBV group and HIV/TB/HCV group, and 1013 cases of HIV negative TB patients were randomly selected as the control group. The subjects were followed up for one year, and compared the type of tuberculosis, the abnormal rate of liver function and the fatality rate of anti tuberculosis treatment.
Results: the infection rate of hepatitis virus in HIV positive group was 32.4%, which was significantly higher than that of 8.9% (P=0.000).HIV positive patients with HIV negative population (21.1% and 26.9% respectively), which were significantly higher than 5.2% and 18.3% (P=0.000 and P=0.001) of HIV negative patients (P=0.000 and P=0.001). Among them, HIV/TB/HBV multicast dispersive tuberculosis was the most 44.4%.HIV positive patients. The drug induced liver damage rate was 4.2%, which was significantly higher than 1% (P=0.000) of HIV negative patients. The drug induced liver damage rate in HIV/TB/HBV group was the highest. The rate of abnormal liver function was 68.4% in the patients with 18.5%.HBV-DNA1.0 x 105copy/ml and 21.1% for HBV-DNA negative or 1 x 105copy/ml patients. The difference was statistically significant (P=0.000).HCV-RNA1. The rate of abnormal liver function was 42.9% in the patients with.0 * 105copy/ml and 10% in HCV-RNA negative or 1 x 105copy/ml patients. The mortality rate was 13.6% in.HIV positive tuberculosis patients (P=0.006), and the mortality rate of 0.9% (P=0.000).HIV/TB/ viral hepatitis group was 19.7%, which was significantly higher than that of HIV negative TB patients. It was significantly higher than 10.7% (P=0.019) in group HIV/TB.
Conclusion: HIV positive tuberculosis patients have higher HBV and / or HCV infection rate.HIV and HBV/HCV combined infection significantly increase the liver damage rate of tuberculosis patients,.HBV and HCV replication level closely related to the anti tuberculosis treatment of liver function damage.HIV, TB and HBV/HCV combined infected people with high mortality rate. Before the anti tuberculosis treatment, the patient was made HIV. HBV and HCV screening can help to detect the mixed infection of the above diseases; cART therapy containing 3TC and TDF schemes for those with HIV, TB and HBV infection, and anti HCV therapy for the HIV, TB and HCV combined infection can help to reduce the rate of liver damage and mortality.
The fifth part is the study of AIDS combined with non tuberculous mycobacterial disease.
Objective: To analyze the prevalence and clinical characteristics of non-tuberculous mycobacteriosis in AIDS patients, and to provide reference for its diagnosis and treatment.
Methods: 19 cases of AIDS combined with non tuberculosis mycobacterium tuberculosis cases in Zhongnan Hospital of Wuhan University were collected and analyzed. The prevalence, clinical manifestations, imaging features, bacterial detection rate and drug resistance were analyzed and compared with AIDS combined with tuberculosis.
Results: the most common symptoms of AIDS combined with non tuberculous Mycobacterium were fever (94.7%), poor (89.5%), fatigue (89.5%), emaciation (84.2%), chest tightness (78.9%), and cough (73.7%). The imaging features were mostly diffuse (88.2%), real change (52.9%), and mediastinal lymph node enlargement (64.7%) more common. AIDS combined with non tuberculosis mycobacterium tuberculosis. The detection rate of bacteria was 21.1%. HIV-positive non-tuberculous Mycobacterium was not sensitive to four first-line anti-tuberculosis drugs (INH, RFP, EMB, Sm) and two second-line anti-tuberculosis drugs (Km, Ofx).
Conclusion: the clinical symptoms of AIDS combined with NTM disease are similar to AIDS combined with tuberculosis. It is easy to cause misdiagnosis and missed diagnosis. There is a difference between NTM's and TB treatment drugs. The definite diagnosis should be based on the medical history, clinical manifestation, bacterial culture and identification of.HIV positive population, the incidence of NTM's disease is significantly higher than that of.HIV positive patients with HIV negative population. NTM is not sensitive to INH, RPF, EMB, Sm, Km and Ofx. The diagnosis, treatment and prevention of AIDS with NTM disease in this area need to be strengthened.
【学位授予单位】:武汉大学
【学位级别】:博士
【学位授予年份】:2014
【分类号】:R512.91

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