本文選題：結(jié)核分支桿菌 + 卡介苗接種�。� 參考：《中國人民解放軍軍事醫(yī)學科學院》2009年碩士論文

【摘要】： 據(jù)世界衛(wèi)生組織統(tǒng)計,全球有超過三分之一的人口感染了結(jié)核分支桿菌(M. tuberculosis ,MTB),每年有200萬人因結(jié)核病死亡。第4次全國結(jié)核病流調(diào)結(jié)果顯示,我國有5.5億人曾感染MTB,人群感染率為44.5%,現(xiàn)有活動性結(jié)核患者500萬,每年新發(fā)132萬結(jié)核病人。新發(fā)結(jié)核病例,大部分由于內(nèi)源性復發(fā),而不是外源性感染。因此,如何發(fā)現(xiàn)結(jié)核潛感染者,如何預測結(jié)核潛感染者的預后,并對那些活動性結(jié)核病危險性最大的潛感染者實施預防性抗癆治療,是當今國際上結(jié)核病控制的重要戰(zhàn)略和研究重點。 研究不同狀態(tài)結(jié)核病感染和卡介苗(Bacille Calmette-Guerin, BCG)接種對結(jié)核免疫應(yīng)答的影響,涉及結(jié)核病免疫預防和治療、結(jié)核疫苗研發(fā)、結(jié)核病血清學診斷、結(jié)核病流行病學監(jiān)測和結(jié)核病臨床治療諸領(lǐng)域,不僅具有重要的學術(shù)研究價值,而且對于結(jié)核病流行病學調(diào)研及臨床治療亦具有重要的實際意義。 結(jié)核菌能合成約4000種蛋白,其中多數(shù)蛋白具有免疫原性,加上多糖和脂多糖抗原,結(jié)核抗原種類、數(shù)量眾多。本研究基于結(jié)核病臨床治療和實驗室診斷現(xiàn)狀,采用國內(nèi)外已廣泛應(yīng)用于結(jié)核病血清學診斷的3種分支桿菌抗原,調(diào)查結(jié)核菌臨床感染者(結(jié)核病患者)、結(jié)核菌亞臨床感染者(潛感染者)和BCG接種者相應(yīng)抗體應(yīng)答水平及其變化特點。這3種結(jié)核分支桿菌抗原是:部分純化蛋白衍生物(Purified protein derivation, PPD)、脂阿拉伯甘露聚糖(lipoarabinomannan, LAM)和38 kDa蛋白。 新兵是一個身體素質(zhì)高、年齡相對集中(18-19歲)、且以男性為主的群體。盡管入伍時經(jīng)過嚴格體檢,但新兵入伍半年后,仍有少數(shù)人被診斷為結(jié)核病。由于軍隊的生活和工作環(huán)境高度集中,任何散在的結(jié)核病例均有可能引發(fā)結(jié)核病暴發(fā)流行,對我軍戰(zhàn)斗力造成嚴重危害。如何有效發(fā)現(xiàn)和預防士兵結(jié)核病,是一個非�，F(xiàn)實和緊迫的課題,其關(guān)鍵是如何發(fā)現(xiàn)新兵中的活動性結(jié)核病的潛感染者,并及早給予預防性抗癆治療。目前檢測結(jié)核潛感染的方法主要有結(jié)核菌素皮膚試驗(tuberculin skin test, TST)和r-干擾素釋放試驗(IGRAS)。TST用于檢測結(jié)核潛感染已有很長的歷史,但其特異性差,特別是在結(jié)核病高發(fā)地區(qū)。IGRAS是近年來開發(fā)的檢測結(jié)核潛感染新技術(shù),用于檢測結(jié)核潛感染不受卡介苗(BCG)接種的影響。但是,該方法不能區(qū)分活動性結(jié)核病與結(jié)核潛感染,檢測結(jié)果(致敏T-細胞r-干擾素釋放量)與潛感染者的預后無關(guān),且受MTB感染時間制約。 本研究根據(jù)新兵TST結(jié)果,對TST陰性新兵接種BCG后體液免疫的變化進行了監(jiān)測;對TST強陽性新兵結(jié)核特異性抗體水平進行了調(diào)查;對TST強陽性和38 kDa蛋白抗體陽性的新兵進行了隨訪和信訪,同時對各類結(jié)核病患者相應(yīng)抗體應(yīng)答水平及其變化進行了觀察,并探討結(jié)核病患者、高危結(jié)核潛感染者和BCG接種者的區(qū)別方法。本研究采用的3種結(jié)核分支桿菌抗原是:部分純化蛋白衍生物(PPD)、脂阿拉伯甘露聚糖(LAM)和38 kDa蛋白。 本研究首先對無卡痕、TST試驗陰性新兵在接種BCG疫苗后對3種抗原的抗體應(yīng)答進行了連續(xù)監(jiān)測,發(fā)現(xiàn):種卡新兵對抗原LAM和38 kDa蛋白不產(chǎn)生抗體應(yīng)答;種卡后新兵血清PPD抗體水平持續(xù)升高,3個月達高峰,種卡后6個月PPD抗體滴度仍顯著高于種卡前。結(jié)果表明,種卡1年內(nèi),PPD抗體血清學檢測不適用于結(jié)核病的診斷,而采用抗LAM和抗38 kDa蛋白抗體檢測通常不受種卡影響。 10395名新兵TST試驗結(jié)果表明,有卡痕和無卡痕新兵TST試驗陽性率分別為70.2%和24.9%,差異非常顯著(P0.001);TST試驗強陽性率的有卡痕(3.3%)和無卡痕新兵(2.5%)之間的差異亦有顯著性(P0.05),但TST試驗不能區(qū)分結(jié)核潛感染者和BCG接種者。 對TST強陽性新兵抗體應(yīng)答特征進行調(diào)查和隨訪結(jié)果表明,TST強陽性新兵LAM抗體檢測均為陰性,38 kDa蛋白抗體有6例陽性,其中5例為無卡痕新兵。3個月隨訪發(fā)現(xiàn),6例TST強陽性且38 kDa蛋白抗體陽性新兵中,有3例具有結(jié)核體征,且均為無卡痕新兵。1年信訪結(jié)果發(fā)現(xiàn),無結(jié)核體征TST強陽性、38 kDa蛋白抗體陽性新兵健康狀況良好,而3例有結(jié)核體征新兵中,1年內(nèi)有2例診斷為結(jié)核性胸膜炎,另1例因工作調(diào)動失去聯(lián)系。上述結(jié)果表明:TST強陽性且38 kDa蛋白抗體陽性可用作新兵結(jié)核菌潛感染的指標;本研究結(jié)果提示:對TST強陽性且38 kDa蛋白抗體陽性新兵給予預防性抗癆治療,是降低士兵結(jié)核病發(fā)病率和減少部隊結(jié)核病暴發(fā)流行最有效、最經(jīng)濟的防疫措施。結(jié)核菌潛感染新兵抗LAM抗體應(yīng)答呈陰性;PPD抗體應(yīng)答不能用于結(jié)核菌潛感染鑒別。 對接受化療的結(jié)核病患者的免疫應(yīng)答調(diào)查表明:在化療作用下,結(jié)核患者PPD抗體應(yīng)答呈現(xiàn)3種模式。模式1患者占66.6%,多為菌陽病人,患者接受化療后,PPD抗體水平持續(xù)增高,平均在化療后1.8月抗體水平達到最高值,滴度升至化療前的2～3倍,然后緩慢降低。模式2患者中復治病例比率高,接受化療后血清PPD抗體從較高濃度逐漸降低。模式3患者多為病灶小、痰菌陰性、化療前抗體水平低的初治結(jié)核患者,接受化療后PPD抗體水平無變化。臨床資料表明,化療后抗體水平顯著升高的患者療效好。 總之,本研究比較了臨床活動性結(jié)核病人、結(jié)核菌潛感染者和BCG接種者的抗體應(yīng)答特征,明確了新兵、兒童和新學員人群的結(jié)核病血清學診斷方法;明確了新兵結(jié)核潛感染的診斷方法;提出了士兵結(jié)核病預防措施;對結(jié)核病患者抗體應(yīng)答特點及其與療效的關(guān)系進行了初步探討。
[Abstract]:According to the World Health Organization , more than a third of the world ' s population has been infected with M . tuberculosis , and 2 million people die each year due to tuberculosis . The fourth national tuberculosis epidemic has shown that more than 500 million people in China have been infected , with a population infection rate of 44.5 % . New tuberculosis cases , mostly due to endogenous recurrence , are not exogenous infections . Therefore , it is important to find out how to predict the prognosis of patients with latent tuberculosis , and to implement preventive anti - tuberculosis treatment for those who have the greatest risk of active tuberculosis .



To study the effect of tuberculosis infection and BCG vaccination on the immune response of tuberculosis , and to the field of tuberculosis immune prevention and treatment , tuberculosis vaccine development , tuberculosis serologic diagnosis , tuberculosis epidemic monitoring and tuberculosis clinical treatment , not only has important academic research value , but also has important practical significance for the investigation of tuberculosis epidemiology and clinical treatment .



Mycobacterium tuberculosis can synthesize about 4000 kinds of proteins , most of them have immunogenicity , combined with polysaccharide and lipopolysaccharide antigen , tuberculosis antigen kinds and quantity . This study is based on the present situation of tuberculosis clinical treatment and laboratory diagnosis .



It is a very realistic and urgent task to detect the latent infection of tuberculosis , and it is a very realistic and urgent task to detect the latent infection of tuberculosis .



In this study , the changes of humoral immunity after BCG vaccination were monitored by new recruits , and the specific antibody level of anti - tuberculosis positive and 38 kDa protein antibodies was investigated .



The results showed that PPD antibody serologic test was not suitable for the diagnosis of tuberculosis after BCG vaccination . The results showed that PPD antibody serologic test was not suitable for the diagnosis of tuberculosis after BCG vaccination . The results showed that PPD antibody serologic test was not suitable for the diagnosis of tuberculosis in 1 year , but the detection of anti - LAM and anti - 38 kDa protein antibody was not normally affected by seed card .



The results of the 10395 new recruits showed that the positive rates were 70.2 % and 24 . 9 % , respectively , and the difference was very significant ( P 0 . 001 ) . There was also a significant difference between the positive rate of positive rate ( 3.3 % ) and the new recruits ( 2.5 % ) .



The results showed that the positive and 38 kDa protein antibody positive recruits were positive and the 38 kDa protein antibody positive recruits were the most effective and economical epidemic prevention measures . The results showed that the positive and 38 kDa protein antibody positive recruits were the most effective and economical epidemic prevention measures . The PPD antibody response could not be used for the identification of anti - LAM antibody response .



The results showed that PPD antibody response in patients with tuberculosis was 66.6 % .



In conclusion , this study compared the antibody response characteristics of patients with clinically active tuberculosis , Mycobacterium tuberculosis latent infection and BCG vaccination , defined the diagnostic methods of tuberculosis serologic in the population of recruits , children and new students , defined the diagnosis methods of new recruits ' TB latent infection , proposed the preventive measures of soldiers tuberculosis , and discussed the relationship between antibody response characteristics and curative effect of tuberculosis patients .

【學位授予單位】：中國人民解放軍軍事醫(yī)學科學院
【學位級別】：碩士
【學位授予年份】：2009
【分類號】：R52;R186

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