發(fā)布時(shí)間：2018-08-03 13:49

【摘要】：第一部分艾滋病合并結(jié)核病的流行病學(xué)調(diào)查 目的：了解不同人群HIV感染率及結(jié)核病患病率。 方法：對(duì)24326例非結(jié)核病患者及7448例結(jié)核病患者進(jìn)行HIV篩查；對(duì)住院的67217例HIV陰性患者、995例HIV陽(yáng)性患者及2037例行cARV治療前基線檢查的HIV感染者進(jìn)行結(jié)核病篩查及診斷。收集艾滋病合并機(jī)會(huì)性感染患者病例資料,對(duì)其機(jī)會(huì)性感染進(jìn)行統(tǒng)計(jì)分析。 結(jié)果：本院非結(jié)核病人群HIV感染率為0.18%,結(jié)核病人群HIV感染率為0.48%,結(jié)核病人群HIV感染率明顯高于非結(jié)核病人群(P=0.000)。本院非艾滋病人群結(jié)核病患病率為0.11%,行cARV治療前基線檢查的HIV感染人群結(jié)核病患病率為6.38%,住院艾滋病患者結(jié)核病患病率為21.01%,HIV感染人群結(jié)核病患病率明顯高于非艾滋病人群(21.01%vs0.11%,P=0.000；6.38%vs0.11%,P=0.000)。結(jié)核病是艾滋病最重要的機(jī)會(huì)性感染之一,占38.0%。 結(jié)論：結(jié)核人群HIV感染率顯著高于非結(jié)核病人群；HIV感染者活動(dòng)性結(jié)核病患病率顯著高于非HIV感染人群,結(jié)核病是艾滋病最常見(jiàn)的機(jī)會(huì)性感染。對(duì)HIV人群篩查結(jié)核病,對(duì)結(jié)核病人群篩查HIV有助于提高艾滋病及結(jié)核病的防治水平。 第二部分艾滋病合并結(jié)核病的臨床特征 目的：總結(jié)并分析艾滋病合并結(jié)核病的臨床癥狀、結(jié)核病類型特點(diǎn)及其與CD4+T淋巴細(xì)胞的關(guān)系。 方法：收集375例艾滋病合并結(jié)核病的病例資料及1013例HIV陰性結(jié)核病的病例資料,分析艾滋病合并結(jié)核病的臨床癥狀、結(jié)核類型,并與HIV陰性結(jié)核病相比較。 結(jié)果：HIV陽(yáng)性結(jié)核病患者最常見(jiàn)的癥狀為發(fā)熱、乏力、納差、咳嗽及消瘦,分別占85.6%、68.4%、65.6%、52.6%及50.2%。HIV陽(yáng)性結(jié)核病仍以肺結(jié)核為多見(jiàn)(51.2%),肺外結(jié)核及栗粒性結(jié)核明顯多于HIV陰性結(jié)核病(21.2%vs5.3%,P=0.000；13.3%vs1.7%,P=0.000)。HIV陽(yáng)性結(jié)核病最常見(jiàn)的肺外結(jié)核類型為淋巴結(jié)結(jié)核,占48.1%。HIV陽(yáng)性結(jié)核病中,肺外結(jié)核的CD4+T淋巴細(xì)胞計(jì)數(shù)較高,為146(34-246)個(gè)/ul,粟粒性結(jié)核的CD4+T淋巴細(xì)胞計(jì)數(shù)最低,為26(10-73)個(gè)/ul。肺外結(jié)核的CD4+T淋巴細(xì)胞計(jì)數(shù)顯著高于肺結(jié)核(P=0.040)和粟粒性結(jié)核(P=0.001)。 結(jié)論：HIV感染合并結(jié)核病的臨床表現(xiàn)多種多樣,HIV感染早期,HIV陽(yáng)性結(jié)核病患者的臨床表現(xiàn)與HIV陰性結(jié)核病患者相似。隨著免疫缺陷加重,CD4+T淋巴細(xì)胞明顯減少,艾滋病患者的結(jié)核病變累及多個(gè)器官和系統(tǒng),肺外結(jié)核及粟粒性結(jié)核增多,患者發(fā)熱、盜汗、消瘦等全身中毒癥狀更明顯。 第三部分艾滋病合并結(jié)核病的診斷方法比較 目的：探討影像學(xué)、免疫學(xué)、細(xì)菌學(xué)、纖維支氣管鏡檢查與血沉對(duì)艾滋病合并結(jié)核病的診斷價(jià)值。 方法：收集艾滋病合并結(jié)核病患者影像學(xué)結(jié)果、分析艾滋病合并結(jié)核病患者的影像學(xué)特點(diǎn),并與HIV陰性結(jié)核病比較。對(duì)HIV陰性結(jié)核病及艾滋病合并結(jié)核病患者的血液進(jìn)行血沉、免疫學(xué)檢測(cè)(IGRA、TST及結(jié)核蛋白芯片檢測(cè)),痰液、分泌物等標(biāo)本進(jìn)行分枝桿菌培養(yǎng)、分型鑒定及藥物敏感性試驗(yàn)。對(duì)研究對(duì)象進(jìn)行纖維支氣管鏡檢查及肺泡灌洗,分析纖維支氣管鏡的鏡下表現(xiàn)及分枝桿菌檢出率。 結(jié)果：艾滋病合并結(jié)核病的影像學(xué)特點(diǎn)為病變多為彌漫性(57.3%),縱膈淋巴結(jié)腫大多見(jiàn)(51.6%),多位于雙肺(54.0%)的全葉(46.0%)或上葉(25.0%)。IGRA、TST及結(jié)核蛋白芯片對(duì)艾滋病合并結(jié)核病的敏感性分別為78.3%、16.7%及34.7%,IGRA的敏感性顯著高于TST及結(jié)核蛋白芯片(78.3%vs16.7%,P=0.005及78.3%vs34.7%, P=0.000)。TST及結(jié)核蛋白芯片的敏感性隨CD4+T淋巴細(xì)胞計(jì)數(shù)下降而逐漸下降,而IGRA敏感性受CD4+T淋巴細(xì)胞計(jì)數(shù)影響較小,CD4+T淋巴細(xì)胞計(jì)數(shù)50個(gè)/u1時(shí),IGRA的敏感性顯著高于TST及結(jié)核蛋白芯片(分別為76.6%vs14.3%, P=0.001;76.6%vs25.0%, P=0.000)。IGRA的陽(yáng)性結(jié)果提示HIV感染者結(jié)核潛伏性感染率為32.6%,艾滋病合并結(jié)核病的結(jié)核分枝桿菌檢出率為20.3%,顯著低于HIV陰性結(jié)核病的48.0%(P=0.000)。HIV陽(yáng)性患者的結(jié)核分枝桿菌耐藥率為25.0%,與HIV陰性患者的25.2%無(wú)顯著性差異。行纖維支氣管鏡檢查患者的結(jié)核分枝桿菌檢出率顯著高于未行纖維支氣管鏡檢查的艾滋病合并肺結(jié)核病患者(51.2%vs17.7%,P=0.000)。HIV陽(yáng)性結(jié)核病患者、HIV感染者及HIV陰性結(jié)核病患者的血沉依次為84(49-117)mm/h、53(20-83)mm/h及24(13-41)mm/h,三組之間差異有顯著性(P=0.000)。 結(jié)論：艾滋病合并結(jié)核病的臨床表現(xiàn)不一。需根據(jù)病史、癥狀體征、影像學(xué)檢查、免疫學(xué)檢測(cè)、血沉及病原學(xué)檢查,有的患者尚須進(jìn)行診斷性治療等綜合措施,才能作出正確診斷。IGRA受免疫功能缺陷影響較小,對(duì)HIV陽(yáng)性結(jié)核病有較大的診斷價(jià)值。HIV陽(yáng)性結(jié)核病人群病原檢出率顯著低于HIV陰性結(jié)核病人群。淋巴結(jié)膿液及支氣管肺泡灌洗液的結(jié)核分枝桿菌檢出率較高。從艾滋病患者分離到的結(jié)核分枝桿菌多耐藥及耐多藥菌株相對(duì)較多。纖維支氣管鏡對(duì)疑難病人有較大診斷價(jià)值。支氣管肺泡灌洗液作細(xì)菌培養(yǎng)及TB-DNA檢測(cè)可提高結(jié)核分枝桿菌檢出率。 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合并感染的流行情況并分析多重感染的臨床特征、抗結(jié)核治療的肝損率及病死率。 方法：根據(jù)HBsAg及抗-HCV結(jié)果,將361例HIV陽(yáng)性結(jié)核病患者分為HIV/TB組、HIV/TB/HBV組、HIV/TB/HCV組,并隨機(jī)選取1013例HIV陰性結(jié)核病患者作為對(duì)照組,對(duì)研究對(duì)象隨訪一年,比較各組患者結(jié)核病類型、抗結(jié)核治療時(shí)肝功能異常率和病死率。 結(jié)果：HIV陽(yáng)性人群肝炎病毒感染率為32.4%,明顯高于HIV陰性人群的8.9%(P=0.000)。HIV陽(yáng)性患者的肺外結(jié)核及播散性結(jié)核分別為21.1%及26.9%,均明顯高于HIV陰性患者的5.2%及18.3%(P=0.000及P=0.001),其中HIV/TB/HBV組播散性結(jié)核最多,為44.4%。HIV陽(yáng)性患者藥物性肝損率為4.2%,明顯高于HIV陰性患者的1.0%(P=0.000),其中HIV/TB/HBV組藥物性肝損率最高,為18.5%。HBV-DNA1.0×105copy/ml的患者抗結(jié)核治療出現(xiàn)肝功能異常比率為68.4%,HBV-DNA陰性或1.0×105copy/ml的患者為21.1%,兩者具有統(tǒng)計(jì)學(xué)差異(P=0.000)。HCV-RNA1.0×105copy/ml的患者抗結(jié)核治療出現(xiàn)肝功能異常率為42.9%, HCV-RNA陰性或1.0×105copy/ml的患者為10.0%,兩者具有統(tǒng)計(jì)學(xué)差異(P=0.006)。HIV陽(yáng)性結(jié)核病患者病死率為13.6%,明顯高于HIV陰性結(jié)核病患者的0.9%(P=0.000)。HIV/TB/病毒性肝炎組的病死率為19.7%,明顯高于HIV/TB組的10.7%(P=0.019)。 結(jié)論：HIV陽(yáng)性結(jié)核病人群有較高的HBV和/或HCV感染率。HIV及HBV/HCV合并感染顯著增加結(jié)核病患者抗結(jié)核治療的肝損率。HBV及HCV復(fù)制水平與抗結(jié)核治療肝功能損害密切相關(guān)。HIV、TB及HBV/HCV合并感染人群病死率高。在抗結(jié)核治療前,對(duì)患者作HIV、HBV及HCV篩查,有助于發(fā)現(xiàn)上述疾病的混合感染者；對(duì)HIV、TB及HBV合并感染者作含3TC及TDF方案的cART治療,對(duì)HIV、TB及HCV合并感染者作抗HCV治療,有助于降低肝損率及病死率。 第五部分艾滋病合并非結(jié)核分枝桿菌病的研究 目的：分析艾滋病合并非結(jié)核分枝桿菌病的患病率及臨床特征,為其診斷及治療提供參考依據(jù)。 方法：收集武漢大學(xué)中南醫(yī)院艾滋病合并非結(jié)核分枝桿菌病病例資料19例,總結(jié)并分析其患病率、臨床表現(xiàn)、影像學(xué)特點(diǎn)、細(xì)菌檢出率及耐藥性,并與艾滋病合并結(jié)核病進(jìn)行比較。 結(jié)果：艾滋病合并非結(jié)核分枝桿菌病最常見(jiàn)的癥狀為發(fā)熱(94.7%)、納差(89.5%)、乏力(89.5%)、消瘦(84.2%)、胸悶(78.9%)、咳嗽(73.7%)。影像學(xué)特點(diǎn)為病變多為彌漫性(88.2%),實(shí)變影(52.9%)、縱膈淋巴結(jié)腫大(64.7%)較常見(jiàn)。艾滋病合并非結(jié)核分枝桿菌病的細(xì)菌檢出率為21.1%。HIV陽(yáng)性非結(jié)核分枝桿菌對(duì)四種一線抗結(jié)核藥(INH、RFP、EMB、Sm)及兩種二線抗結(jié)核藥(Km、Ofx)均不敏感。 結(jié)論：艾滋病合并NTM病的臨床癥狀與艾滋病合并結(jié)核病相似,易導(dǎo)致誤診和漏診,NTM病與結(jié)核病的治療藥物有區(qū)別,明確診斷需根據(jù)病史、臨床表現(xiàn)、細(xì)菌培養(yǎng)及菌種鑒定。HIV陽(yáng)性人群NTM病的患病率顯著高于HIV陰性人群。HIV陽(yáng)性患者感染的NTM對(duì)INH、RPF、EMB、Sm、Km及Ofx均不敏感。本地區(qū)艾滋病合并NTM病的診斷、治療及預(yù)防工作亟待加強(qiáng)。
[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.
【學(xué)位授予單位】：武漢大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R512.91

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