發(fā)布時(shí)間：2018-04-25 17:25

  本文選題：人免疫缺陷病毒 + 結(jié)核��； 參考：《北京協(xié)和醫(yī)學(xué)院》2011年碩士論文

【摘要】：背景 HIV合并活動(dòng)性結(jié)核感染是HIV感染者死亡的重要原因之一。我國(guó)HIV感染人群中結(jié)核病的發(fā)病率高,造成了嚴(yán)重的疾病負(fù)擔(dān)。提高潛伏結(jié)核和活動(dòng)性結(jié)核的診斷準(zhǔn)確性,對(duì)控制HIV患者中結(jié)核病的治療和控制至關(guān)重要。結(jié)核分枝桿菌IFN-γ酶聯(lián)免疫斑點(diǎn)技術(shù)(Enzyme-Linked ImmunoSpot Assay, ELISPOT),在體外利用結(jié)核特異性抗原肽刺激外周血單個(gè)核細(xì)胞,通過(guò)酶聯(lián)顯色,計(jì)數(shù)釋放IFN-γ的細(xì)胞數(shù),是目前最敏感的檢測(cè)抗原特異性T細(xì)胞的方法之一。其在HIV感染人群及非HIV感染人群中診斷活動(dòng)性結(jié)核的準(zhǔn)確性已得到了證實(shí),對(duì)結(jié)核暴露的相關(guān)性也優(yōu)于TST,提示其診斷LTBI的準(zhǔn)確性?xún)?yōu)于TST。但結(jié)核分枝桿菌IFN-γ ELISPOT是否可以有效的監(jiān)測(cè)活動(dòng)性結(jié)核或潛伏結(jié)核的治療效果,是否可以預(yù)測(cè)活動(dòng)性結(jié)核的發(fā)生,目前尚無(wú)一致的結(jié)論。本實(shí)驗(yàn)旨在對(duì)活動(dòng)性結(jié)核和潛伏性結(jié)核患者進(jìn)行治療與隨訪,探討結(jié)核分枝桿菌IFN-γ ELISPOT對(duì)于結(jié)核治療監(jiān)測(cè)和預(yù)測(cè)活動(dòng)性結(jié)核的應(yīng)用價(jià)值。 目的 探討結(jié)核分枝桿菌IFN-γ ELISPOT在HIV感染人群中對(duì)結(jié)核治療監(jiān)測(cè)和預(yù)測(cè)活動(dòng)性結(jié)核的應(yīng)用價(jià)值。 方法 對(duì)2009年1月至2010年8月初次于深圳市東湖醫(yī)院艾滋病門(mén)診就診的病人進(jìn)行癥狀學(xué)篩查、結(jié)核特異性IFN-γ ELISPOT檢測(cè)(T-SPOT.TB)、TST、CD4細(xì)胞計(jì)數(shù)及胸部X線(xiàn)或CT檢查。對(duì)可疑活動(dòng)性結(jié)核的患者進(jìn)一步行痰涂片(至少連續(xù)三次)、痰培養(yǎng),必要時(shí)行肺組織穿刺活檢、抗酸染色及組織結(jié)核桿菌培養(yǎng)�？梢煞瓮饨Y(jié)核的患者進(jìn)一步行病變部位組織活檢及抗酸染色,以診斷或排除活動(dòng)性結(jié)核。從而評(píng)價(jià)T-SPOT.TB診斷活動(dòng)性結(jié)核的準(zhǔn)確性,以及外周血CD4+T細(xì)胞對(duì)T-SPOT.TB的影響。將排除活動(dòng)性結(jié)核的T-SPOT.TB陽(yáng)性的HIV感染者定義為潛伏性結(jié)核感染者,隨機(jī)分為兩組分別予INH6個(gè)月和INH+RFP3個(gè)月預(yù)防性抗結(jié)核治療,同時(shí)在治療前、療程結(jié)束和療程結(jié)束后3-6個(gè)月進(jìn)行T-SPOT.TB監(jiān)測(cè),觀察T-SPOT.TB結(jié)果在不同治療方案下的變化�；顒�(dòng)性結(jié)核感染者,也同樣給予正規(guī)抗結(jié)核治療,分別在0、3、6、9、12月隨訪T-SPOT.TB,觀察T-SPOT.TB結(jié)果隨著治療的變化,評(píng)價(jià)其用于治療監(jiān)測(cè)的價(jià)值。 結(jié)果 共篩查HIV感染者317例,其中2人因年齡小于18周歲,10人因T-SPOT.TB檢驗(yàn)結(jié)果不可判斷被排除。余下的305人中,32人病原學(xué)或臨床診斷為活動(dòng)性結(jié)核,273人經(jīng)癥狀學(xué)篩查和胸部X線(xiàn)片排除活動(dòng)性結(jié)核�；顒�(dòng)性結(jié)核患者的CD4+T細(xì)胞計(jì)數(shù)低于排除活動(dòng)性結(jié)核患者(median:96vs.222; Mann-Whitney U test, P0.01)。診斷為活動(dòng)性結(jié)核的32人中,24例T-SPOT.TB陽(yáng)性,余273例排除活動(dòng)性結(jié)核HIV感染者中,54例為T(mén)-SPOT.TB陽(yáng)性。T-SPOT.TB診斷HIV/ATB的靈敏度和特異度分別為75.0%(95%CI：56.6%-88.6%)和80.2%(95%CI：75.0%-84.8%)。在病原學(xué)診斷的HIV/ATB患者中,T-SPOT.TB的陽(yáng)性率升高為90.0%(95%CI：78.3%-98.8%)。比較T-SPOT和TST兩種檢測(cè)方法,T-SPOT.TB檢測(cè)HIV/ATB的陽(yáng)性率較高(McNema test,χ2=8.45, P0.05),且不受外周血CD4+T細(xì)胞計(jì)數(shù)水平的影響。在HIV/nonATB患者中,T-SPOT.TB與TST的陽(yáng)性率分別為19.8%(54/273,95%CI：15.2%-25.0%)和16.1%(41/255,95%CI：11.8%-21.2%),無(wú)統(tǒng)計(jì)學(xué)顯著性差異(McNemar test, χ2=2.2, P=0.14),但兩者一致性差(kappa=0.2790)。T-SPOT.TB與TST在HIV/nonATB患者中的陽(yáng)性率均隨著CD4+T細(xì)胞水平的降低而下降(χ2test for trend, p0.05).基線(xiàn)診斷為HIV/LTBI的54例患者中,22例完成了預(yù)防性抗結(jié)核治療和至少1次的隨訪。2例病人分別在預(yù)防性抗結(jié)核治療的第136和191天診斷為活動(dòng)性結(jié)核,余20例病人平均隨訪373.1+176.4天均未出現(xiàn)活動(dòng)性結(jié)核的表現(xiàn)。療程結(jié)束和療程結(jié)束后3-6個(gè)月,患者對(duì)ESAT-6(median:23vs.7; Wilcoxon signed rank, P=0.002)和CFP-10的應(yīng)答水平(median:24.5vs.5; Wilcoxon signed rank,P0.005)均較治療前降低,但療程結(jié)束后有僅31.6%的患者T-SPOT.TB轉(zhuǎn)陰,不同治療方案見(jiàn)無(wú)統(tǒng)計(jì)學(xué)顯著性差異。隊(duì)列中的34例活動(dòng)性結(jié)核,有27人接受了正規(guī)的抗結(jié)核治療,并完成了至少一次的隨訪�；�(xiàn)ESAT-6或CFP-10ELISPOT陽(yáng)性的患者,對(duì)ESAT-6(β=-0.1580, P=0.0001)或CFP-10的反應(yīng)水平(β=-0.1472,P=0.0012)均隨著治療而逐漸下降。但僅有25%的患者在最后一次隨訪時(shí),T-SPOT.TB已轉(zhuǎn)陰。 結(jié)論 在HIV感染人群中,T-SPOT.TB作為一種診斷活動(dòng)性結(jié)核的輔助手段,其靈敏度和特異度均優(yōu)于TST,且不受CD4+T細(xì)胞計(jì)數(shù)水平的影響。在廣泛接種BCG的國(guó)家,其診斷潛伏性結(jié)核的準(zhǔn)確度不受BCG的影響,優(yōu)于TST。不論是潛伏性結(jié)核或活動(dòng)性結(jié)核,ESAT-6和CFP-10的應(yīng)答水平均隨治療下降,為T(mén)-SPOT.TB用于ATB或LTBI的治療監(jiān)測(cè)提供了理論依據(jù),但僅有一小部分人群在隨訪結(jié)束時(shí)T-SPOT.TB轉(zhuǎn)陰,提示我們應(yīng)延長(zhǎng)隨訪時(shí)間和擴(kuò)大試驗(yàn)人群,明確T-SPOT.TB持續(xù)陽(yáng)性的原因。 背景 人乳頭狀瘤病毒感染是目前已知的與惡性腫瘤發(fā)生最為密切的病毒之一,目前已知與HPV感染有密切相關(guān)性的惡性腫瘤有宮頸癌、陰道癌、陰戶(hù)癌、陰莖癌及肛門(mén)癌,甚至在部分頭頸部腫瘤,尤其是扁桃體癌中同樣可以檢測(cè)到HPV的存在。HPV與HIV均可通過(guò)性行為傳播,在HIV感染的MSM人群中HPV合并感染率高,且HPV相關(guān)的癌前病變?cè)贖IV感染的MSM人群中更為常見(jiàn)。本實(shí)驗(yàn)旨在研究HIV感染MSM中肛周及口腔HPV感染情況及具體基因型,評(píng)估該人群肛門(mén)上皮內(nèi)瘤變、肛門(mén)癌及口腔部位腫瘤的潛在風(fēng)險(xiǎn)。 目的 調(diào)查HIV感染MSM肛周及口腔HPV感染情況及具體基因型,評(píng)估HPV感染的危險(xiǎn)因素,及該人群肛門(mén)上皮內(nèi)瘤變、肛門(mén)癌及口腔部位腫瘤的潛在風(fēng)險(xiǎn)。 方法 對(duì)2011年2月至2011年4月,深圳市第三人民醫(yī)院艾滋病門(mén)診HIV感染的MSM進(jìn)行肛周及皮膚視診、醋酸白實(shí)驗(yàn)及CD4+T細(xì)胞計(jì)數(shù),部分病人進(jìn)行肛周及口腔咽側(cè)壁HPV-DNA檢測(cè)。觀察該人群典型尖銳濕疣的發(fā)病率、HPV感染情況,并對(duì)年齡、吸煙、男性性伴侶總數(shù)、近半年男性性伴侶數(shù)、近半年性行為頻率、安全套使用頻率、包皮環(huán)切、藥物濫用史、性伴侶尖銳濕疣史以及目前CD4+T細(xì)胞計(jì)數(shù)、最低CD4+T細(xì)胞計(jì)數(shù)、HAART狀態(tài)等生殖器HPV感染危險(xiǎn)因素,以及口生殖器性行為、口交套等口腔HPV感染危險(xiǎn)因素進(jìn)行評(píng)估。 結(jié)果 共篩查HIV感染MSM138人,其中20人(14.5%)肛周有典型的尖銳濕疣,38人(27.5%)有可疑皮損,80人(58.0%)肛周無(wú)明顯皮膚改變。共62人進(jìn)行口腔及肛周的HPV-DNA檢查,13人有典型皮損,28人有可疑皮損,21人無(wú)明顯肛周皮膚改變,無(wú)人有口腔尖銳濕疣表現(xiàn)。肛周HPV-DNA檢測(cè)在三組人群中陽(yáng)性率分別為100.0%(13/13)、75.0%(21/28)、71.5%(15/21)；僅2例為口腔HPV-DNA陽(yáng)性,其口腔及肛周均無(wú)明顯皮膚改變。HPV-6、11、16、18四型在三組人群中感染率均較高。其它較常見(jiàn)的基因型有HPV45、52、58、53、66等。高危型陽(yáng)性率在三組人群中分別為69.2%(9/13)、67.9%(19/28)、57.14%(12/21)。HPV感染者中,63.3%為2種及以上基因型感染,僅36.7%為單基因型或未知基因型感染。對(duì)年齡、吸煙、男性性伴侶總數(shù)、近半年男性性伴侶數(shù)、近半年性行為頻率、安全套使用頻率、包皮環(huán)切、藥物濫用史、性伴侶尖銳濕疣史以及目前CD4+T細(xì)胞計(jì)數(shù)、最低CD4+T細(xì)胞計(jì)數(shù)、HAART狀態(tài)等因素,對(duì)肛周HPV感染或肛周尖銳濕疣的影響均無(wú)統(tǒng)計(jì)學(xué)顯著性。 結(jié)論 中國(guó)廣東省深圳市HIV感染的MSM人群中,有典型癥狀尖銳濕疣感染率為14.5%,有癥狀患者中HPV-DNA陽(yáng)性率為100%,而在無(wú)典型癥狀患者中HPV-DNA陽(yáng)性率在75%左右。除HPV-6、11、16、18外,HPV45、52、58、53、66等基因型也較為常見(jiàn)�；旌细腥韭矢��？谇患怃J濕疣發(fā)病率和口腔HPV感染率低。高危型HPV感染率高,提示需要對(duì)該人群進(jìn)行定期的肛門(mén)癌篩查,以及時(shí)診斷和治療。
[Abstract]:background
HIV combined active tuberculosis infection is one of the important causes of death of HIV infected people. The incidence of tuberculosis in HIV infected people in China is high, causing serious disease burden. It is important to improve the diagnostic accuracy of latent tuberculosis and active tuberculosis. It is very important to control the treatment and control of tuberculosis in HIV patients. IFN- gamma enzyme linked by Mycobacterium tuberculosis Enzyme-Linked ImmunoSpot Assay (ELISPOT), using TB specific antigen peptide to stimulate peripheral blood mononuclear cells in vitro, and count the number of IFN- gamma cells through enzyme linked color, is one of the most sensitive methods for detecting antigen specific T cells at present. It is disconnected in HIV infected people and non HIV infected people. The accuracy of dynamic tuberculosis has been confirmed, the correlation of tuberculosis exposure is also better than TST, suggesting that the accuracy of the diagnosis of LTBI is better than that of TST., but whether Mycobacterium tuberculosis IFN- gamma ELISPOT can effectively monitor the therapeutic effect of active tuberculosis or latent tuberculosis and whether it can predict the occurrence of active tuberculosis, there is no consistent conclusion at present. The purpose of this experiment is to treat and follow up the patients with active tuberculosis and latent tuberculosis, and to explore the application value of Mycobacterium tuberculosis IFN- gamma ELISPOT for the monitoring of tuberculosis treatment and prediction of active tuberculosis.
objective
Objective to investigate the application value of Mycobacterium tuberculosis IFN- gamma ELISPOT in monitoring and predicting active tuberculosis in patients with HIV infection.
Method
Symptomatic screening, tuberculosis specific IFN- gamma ELISPOT detection (T-SPOT.TB), TST, CD4 cell count and chest X - ray or CT examination were performed on patients in the AIDS clinic of Shenzhen hospital from January 2009 to early August 2010. Sputum smears (at least three consecutive times) for suspected active tuberculosis patients, sputum culture, necessary Pulmonary tissue biopsy, acid stain and Mycobacterium tuberculosis culture. Patients with suspected extrapulmonary tuberculosis were further performed biopsy and anti acid staining to diagnose or eliminate active tuberculosis. The accuracy of T-SPOT.TB diagnosis of active tuberculosis and the effect of CD4+ T cells in peripheral blood on T-SPOT.TB were evaluated. The T-SPOT.TB positive HIV infection in the nucleus was defined as latent tuberculosis infection, which were randomly divided into two groups for INH6 months and INH+RFP3 months for preventive anti tuberculosis treatment. At the same time, T-SPOT.TB monitoring was carried out at the end of the course of treatment and 3-6 months after the end of the course of treatment. The changes of T-SPOT.TB fruit were observed under different treatments. Active tuberculosis was observed. The infected people were also given regular anti tuberculosis treatment and were followed up for T-SPOT.TB at 0,3,6,9,12 months, and the results of T-SPOT.TB were observed with the change of treatment and the value of their use for treatment monitoring.
Result
A total of 317 cases of HIV infection were screened, of which 2 were aged less than 18 years old and 10 were unable to judge the results of T-SPOT.TB test. Among the remaining 305, 32 were pathogenic or clinically diagnosed as active tuberculosis, 273 were screened by symptomatic screening and chest X ray were excluded from active tuberculosis. The CD4+T cell count of active tuberculosis patients was lower than the exclusion. Patients with active tuberculosis (median:96vs.222; Mann-Whitney U test, P0.01). Among 32 patients diagnosed as active tuberculosis, 24 were T-SPOT.TB positive, and the other 273 excluded active tuberculosis HIV infection, and 54 were T-SPOT.TB positive.T-SPOT.TB diagnostic HIV/ATB sensitivity and specificity were 75% (95%CI:56.6%-88.6%) and 80.2% (95%CI:75.0%-84.8) (95%CI:75.0%-84.8). In the HIV/ATB patients diagnosed by etiology, the positive rate of T-SPOT.TB increased by 90% (95%CI:78.3%-98.8%). Compared with two methods of T-SPOT and TST, the positive rate of HIV/ATB was higher by T-SPOT.TB (McNema test, Chi 2=8.45, P0.05), and was not affected by the level of peripheral blood CD4+T cell counts. The positive rates were 19.8% (54/273,95%CI:15.2%-25.0%) and 16.1% (41/255,95%CI:11.8%-21.2%), and there was no statistically significant difference (McNemar test, Chi 2=2.2, P=0.14), but the positive rates of both kappa=0.2790.T-SPOT.TB and TST in HIV/nonATB patients were decreased with the decrease of CD4+T cell level. 05. Of the 54 patients with a baseline diagnosis of HIV/LTBI, 22 patients completed preventive anti tuberculosis treatment and at least 1 times of follow-up,.2 patients were diagnosed as active tuberculosis on 136th and 191st days of preventive anti tuberculosis treatment. The remaining 20 cases were followed up for 373.1+176.4 days without active tuberculosis. After the end of the course of treatment and the end of the course of treatment. 3-6 months, the patients' response to ESAT-6 (median:23vs.7; Wilcoxon signed rank, P=0.002) and CFP-10 (median:24.5vs.5; Wilcoxon signed rank, P0.005) were lower than before the treatment, but only 31.6% of the patients turned negative after the course of treatment. There were no statistically significant differences in different treatment cases. 34 cases of active tuberculosis in the queue, 27 people received regular anti tuberculosis treatment and completed at least one follow-up. The level of response to ESAT-6 (beta =-0.1580, P=0.0001) or CFP-10 (beta =-0.1472, P=0.0012) in both baseline ESAT-6 or CFP-10ELISPOT positive patients (beta =-0.1472, P=0.0012) gradually declined with treatment. But only 25% of the patients were in the last follow-up, and T-SPOT.TB had turned negative.
conclusion
The sensitivity and specificity of T-SPOT.TB, as a supplementary means for diagnosing active tuberculosis in HIV infected people, are superior to TST and are not affected by the level of CD4+T cells. The accuracy of the diagnosis of latent tuberculosis is not affected by BCG in the widely inoculated countries with BCG, which is superior to TST., whether it is latent tuberculosis or active tuberculosis, ESAT The response levels of both -6 and CFP-10 decreased with treatment, providing a theoretical basis for T-SPOT.TB for ATB or LTBI treatment monitoring, but only a small group of people turned negative at the end of follow-up at the end of the follow-up, suggesting that we should extend the follow-up time and expand the test population to make clear the reasons for the persistent positive of T-SPOT.TB.
background
Human papillomavirus (HPV) infection is one of the most closely related viruses known to occur at present. It is known that malignant tumors, which are closely related to HPV infection, are cervical, vaginal, vulva, penis and anal cancer, and even in some head and neck cancers, especially in tonsillar cancer, the presence of.HPV is also detected. And HIV can be transmitted through sexual behavior, with high incidence of HPV associated infection in HIV infected MSM population, and HPV related precancerous lesions are more common in HIV infected MSM population. The purpose of this study was to study the infection of perianal and HPV in HIV infected MSM and the specific genotypes, and to evaluate the intraepithelial neoplasia, anal and oral swollen in the human group. The potential risk of a tumor.
objective
To investigate the incidence of HPV infection in the perianal and oral MSM and the specific genotype of HIV, to assess the risk factors of HPV infection, and the potential risk of anus intraepithelial neoplasia, anal and oral tumor.
Method
From February 2011 to April 2011, the MSM of HIV infection in AIDS clinic of the third people's Hospital of Shenzhen city was treated with perianal and skin inspection, acetic acid white test and CD4+T cell count. Some patients were detected by HPV-DNA in perianal and oral pharyngeal wall. The incidence of typical condyloma acuminatum, HPV infection, age, smoking and male sex were observed. The total number of partners, the number of sexual partners in the near half of the year, the frequency of the condom use, the frequency of condom use, the circumcision, the history of drug abuse, the history of the condyloma acuminata, the current CD4+T cell count, the lowest CD4+T cell count, the risk factors for the HPV infection in the genitals, as well as the oral genital behavior, and the oral HPV infection, and the risk of HPV infection. Risk factors are evaluated.
Result
A total of MSM138 people were screened for HIV infection, of which 20 (14.5%) had typical condyloma acuminata, 38 (27.5%) had suspected skin lesions, 80 (58%) had no obvious skin changes in perianal. A total of 62 people performed HPV-DNA examination in oral and anal weeks, 13 had typical skin lesions, 28 had suspected skin lesions, 21 people had no obvious perianal skin changes, no one had oral condyloma appearance. The positive rate of perianal HPV-DNA detection in three groups was 100% (13/13), 75% (21/28), 71.5% (15/21); only 2 cases were oral HPV-DNA positive, and there were no obvious skin changes in the oral and anal weeks. The infection rate of.HPV-6,11,16,18 four was higher in the three groups. The other more common genotypes were HPV45,52,58,53,66, and the positive rate of high risk type. Among the three groups, 69.2% (9/13), 67.9% (19/28), 57.14% (12/21).HPV infection, 2 or more genotypes were infected, only 36.7% were monogenic or unknown genotypes. The history of substance abuse, the history of condyloma acuminatum, the current CD4+T cell count, the lowest CD4+T cell count, the HAART state and other factors, had no statistically significant effects on the perianal HPV infection or the perianal condyloma acuminata.
conclusion
Among the MSM population infected with HIV in Shenzhen, Guangdong, China, the infection rate of condyloma acuminata is 14.5%, and the positive rate of HPV-DNA in symptomatic patients is 100%, while the positive rate of HPV-DNA is about 75% in the patients with typical symptoms. Besides HPV-6,11,16,18, the HPV45,52,58,53,66 genotypes are also more common. The mixed infection rate is high. Morbidity and oral HPV infection rate are low. High risk HPV infection rate is high, suggesting the need for regular screening for anal cancer and timely diagnosis and treatment.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類(lèi)號(hào)】：R512.91;R378.911

【共引文獻(xiàn)】

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1 繆海鋒;T-SPOT試驗(yàn)在臨床結(jié)核診斷中的應(yīng)用價(jià)值研究[D];浙江大學(xué);2013年

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本文編號(hào)：1802267