本文選題：農(nóng)村地區(qū) + 結(jié)核病��； 參考：《復(fù)旦大學(xué)》2012年碩士論文

【摘要】：結(jié)核病(tuberculosis TB)主要是由于感染結(jié)核分枝桿菌(Mycobacterium tuberculosis M. TB)引起的一種嚴(yán)重危害人民健康的呼吸道傳染病,被列為我國(guó)重大傳染病之一。由于耐藥結(jié)核病的出現(xiàn)、結(jié)核病控制措施的減弱以及艾滋病(HIV/AIDS)的流行,在20世紀(jì)80年代結(jié)核病重新復(fù)發(fā)流行,1993年WHO宣布全球結(jié)核病處于緊急狀態(tài)。WHO估計(jì)每年有800萬(wàn)人患結(jié)核病,每年有200萬(wàn)人死于結(jié)核病。我國(guó)自1991年起實(shí)施直接監(jiān)督短程化療法(directly observed treatment short-course, DOTC),從2001年開始,全面推行了現(xiàn)代結(jié)核病控制策略,10年間全國(guó)共發(fā)現(xiàn)并治療肺結(jié)核患者829萬(wàn)例,其中涂陽(yáng)肺結(jié)核患者450萬(wàn)例,避免了4000多萬(wàn)健康人感染結(jié)核菌。2010年全國(guó)涂陽(yáng)肺結(jié)核患病率降至66/10萬(wàn),比2000年下降了61%。 然而我國(guó)結(jié)核病防治工作還面臨著諸多新的問(wèn)題與挑戰(zhàn)。我國(guó)仍是全球22個(gè)結(jié)核病高負(fù)擔(dān)國(guó)家之一,WHO評(píng)估,目前我國(guó)結(jié)核病年發(fā)病人數(shù)約為130萬(wàn),占全球發(fā)病人數(shù)的14%,位居全球第二位。近年來(lái),我國(guó)每年報(bào)告肺結(jié)核發(fā)病人數(shù)約100萬(wàn),始終位居全國(guó)甲乙類傳染病的前列；耐多藥肺結(jié)核危害日益凸顯,每年新發(fā)患者人數(shù)約12萬(wàn),未來(lái)數(shù)年內(nèi)可能出現(xiàn)以耐藥菌為主的結(jié)核病流行態(tài)勢(shì)；結(jié)核菌/艾滋病病毒雙重感染患者人數(shù)持續(xù)增加,防治工作亟待加強(qiáng)；中西部地區(qū)、農(nóng)村地區(qū)結(jié)核病防治形勢(shì)嚴(yán)峻。我國(guó)現(xiàn)行結(jié)核病防治服務(wù)體系和防治能力還不能滿足新形勢(shì)下防治工作的需要,防治基礎(chǔ)設(shè)施建設(shè)滯后,基層防治力量薄弱,流動(dòng)人口患者治療管理難度加大,公眾對(duì)結(jié)核病危害的認(rèn)識(shí)不足,防治任務(wù)尤其是農(nóng)村地區(qū)仍然十分艱巨,需要長(zhǎng)期不懈的努力。 本研究以臺(tái)州市農(nóng)業(yè)縣-仙居縣實(shí)施結(jié)核病DOTC控制項(xiàng)目縣為研究現(xiàn)場(chǎng),采用現(xiàn)場(chǎng)流行病學(xué)和分子生物學(xué)技術(shù)方法對(duì)當(dāng)?shù)乜h級(jí)疾控中心結(jié)核病防治所2011年4月～2012年3月登記的所有痰培養(yǎng)陽(yáng)性的結(jié)核病患者進(jìn)行系統(tǒng)的研究,通過(guò)收集患者的基本信息,采集患者的痰液進(jìn)行抗酸染色鏡檢,對(duì)所有痰標(biāo)本分離培養(yǎng)結(jié)核菌,以比例法對(duì)分離的M.TB進(jìn)行兩種一線抗結(jié)核菌藥物敏感試驗(yàn)(RFP和INH),采用15位點(diǎn)MIRU-VNTR基因分型方法對(duì)所有的M.TB進(jìn)行基因分型,用BioNumerics軟件對(duì)結(jié)果進(jìn)行聚類分析,同時(shí)用多重PCR方法檢測(cè)RD105片段是否缺失來(lái)區(qū)分北京基因型和非北京基因型菌株,掌握臺(tái)州市農(nóng)村地區(qū)M.TB的流行菌株和藥物敏感情況,以及該地區(qū)的M.TB的基因多態(tài)性。分析臺(tái)州市農(nóng)村地區(qū)結(jié)核病的基本特征及可能傳播途徑,為臺(tái)州市農(nóng)村地區(qū)的結(jié)核病預(yù)防與控制提供科學(xué)依據(jù)。 主要結(jié)果和結(jié)論如下 1.結(jié)核病基本流行特征 本次納入研究對(duì)象共89人,男性67人,占75.3%,女性22人,占24.7%。結(jié)核患者的平均年齡為51.4±18.2歲,最大88歲,最小15歲,中位數(shù)為52歲,其中30-60年齡段人數(shù)最多,為44人,占49.4%,其次是≥60年齡段31人,占34.8%。職業(yè)以農(nóng)民為最多,73人,占82%,非農(nóng)民16人,占18%。初治患者78人,占87.6%,復(fù)治患者11人,占12.4%。本地病例79人,占88.8%,外地病例10人占11.2%。痰涂片陽(yáng)性的47例,占51.7%,陰性42例,占48.3%。 2.結(jié)核患者結(jié)核桿菌分離及耐藥情況 從所有患者中共分離到M. TB80株,占89.9%；鳥-胞內(nèi)分枝桿菌8株,占9.0%；堪薩斯分枝桿菌1株,占1.1%。80株M.TB菌中對(duì)INH或RFP單一耐藥有7株,占8.8%,均為初治患者；對(duì)INH和RFP均耐藥率有6株,占7.5%,其中3例為復(fù)治患者。11例復(fù)治患者中4例分離出鳥-胞內(nèi)分枝桿菌,7例分離出M.TB有3例耐多藥。 3.不同治療史患者M(jìn).TB藥敏結(jié)果比較 80例分離出M.TB的結(jié)核病患者中初治患者74例,占92.5%；復(fù)治患者6例,占7.5%。74例初治患者中對(duì)INH和RFP均敏感的有64例,占86.5%(95%CI76.5%-93.3%),對(duì)藥物耐藥的有10例,占13.5%(95%CI6.7%-23.5%)；6例復(fù)治患者中對(duì)INH和RFP均敏感的有3例,占50.0%(95%CI11.8%-88.2%),對(duì)藥物耐藥的有3例,占50.0%(95%CI11.8%-88.2%)。初治患者和復(fù)治患者在總耐藥率方面(敏感vs耐藥)無(wú)顯著性差異(7=3.08,P=0.0510.05),初治患者和復(fù)治患者在耐藥類型(單耐藥vs耐多藥)方面無(wú)顯著性差異(χ2=4.55,P=0.1020.05)。 4.M.TB不同基因型鑒定及藥敏結(jié)果比較 80株M.TB中北京基因型菌株39株,占48.7%；非北京基因型菌株41株,占51.3%。39株北京基因型菌株中對(duì)INH和RFP均敏感的有33例,占84.6%(95%CI69.5%-94.1%),對(duì)藥物耐藥的有6例,占15.4%(95%CI5.9%-30.1%)；41株非北京基因型菌株中對(duì)INH和RFP均敏感的有34例,占82.9%(95%CI67.9%-92.8%),對(duì)藥物耐藥的有7例,占17.1%(95%CI7.2%～32.1%)。北京基因型和非北京基因型菌株在總耐藥率方面(全敏感vs耐藥)無(wú)顯著性差異(χ2=0.04,P=0.8380.05),北京基因型和非北京基因型菌株在耐藥類型方面(單耐藥vs耐多藥)也無(wú)顯著性差異(χ2=1.93,P=0.3800.05) 5.耐藥結(jié)核病影響因素分析 單因素logistic分析發(fā)現(xiàn)復(fù)治與MDR-TB人群分布有關(guān)(P0.05),年齡、性別、職業(yè)、戶籍、治療史、痰涂片、菌株基因型等因素與單耐藥病人人群分布均無(wú)明顯的關(guān)聯(lián)。多因素logistic研究分析發(fā)現(xiàn)結(jié)核病人的既往治療史與耐多藥病人的人群分布有關(guān),復(fù)治的結(jié)核病人是發(fā)生耐多藥結(jié)核病的主要人群(復(fù)治/初治：OR:15.854;95%CI:1.866～134.677)。 6.M.TB基因分型情況 采用15個(gè)MIRU-VNTR位點(diǎn)對(duì)80株M.TB的分辨力最高的是MIRU26(HGI=0.865),分辨力最低的是ETRC (HGI=0.165), HGI0.5的有10個(gè)位點(diǎn)。 15位點(diǎn)MIRU-VNTR基因分型結(jié)果顯示80株M.TB共得到78個(gè)基因型,76株有獨(dú)立基因型,另外4株兩兩成簇,成簇率為2.5%。經(jīng)Bionumberics5.0軟件聚類分析,可78個(gè)基因型分為8個(gè)基因群(Ⅰ群、Ⅱ群、Ⅲ群、Ⅳ群、V群、Ⅵ群、Ⅶ群、Ⅷ群)。分別為Ⅰ群占8.75%,含7個(gè)基因型；Ⅱ群占11.25%,含8個(gè)基因型；Ⅲ群占55.0%,含43個(gè)基因型；Ⅳ群占6.25%,含5個(gè)基因型；V群占2.5%,含2個(gè)基因型；Ⅵ群占8.75%,含7個(gè)基因型；Ⅶ群占5.0%,含4個(gè)基因型；Ⅷ群占2.5%,含2個(gè)基因型。 臺(tái)州市農(nóng)村地區(qū)結(jié)核病呈低水平流行,M.TB的耐藥率低于全國(guó)水平,初治患者和復(fù)治患者在總耐藥率方面無(wú)顯著性差異,M.TB中以非北京基因型為優(yōu)勢(shì)菌,北京基因型呈低流行,北京基因型和非北京基因型菌株在總耐藥率方面無(wú)顯著性差異,15位點(diǎn)MIRU-VNTR基因分型結(jié)果顯示菌株間成簇率低,基因多態(tài)性明顯,說(shuō)明該地區(qū)的結(jié)核病以獨(dú)立感染或內(nèi)源性復(fù)燃為主,近期傳播少。
[Abstract]:Tuberculosis (tuberculosis TB) is mainly caused by the infection of Mycobacterium tuberculosis (Mycobacterium tuberculosis M. TB), a kind of respiratory infectious disease which seriously endangers the people's health. It is listed as one of the major infectious diseases in our country. Because of the emergence of drug-resistant tuberculosis, the reduction of tuberculosis control measures and the epidemic of AIDS (HIV/AIDS), in 20 In 80s, tuberculosis was relapsed. In 1993, WHO announced that global tuberculosis was in a state of emergency,.WHO estimated that 8 million people had TB each year, and 2 million people died of tuberculosis each year. China has implemented direct supervision short course therapy (directly observed treatment short-course, DOTC) since 1991. Since 2001, it has been carried out in an all-round way. In the past 10 years, 8 million 290 thousand cases of tuberculosis patients were found and treated in the country, of which 4 million 500 thousand cases were smear positive tuberculosis patients, which prevented about 40000000 healthy people from infection of TB bacteria to 66/10 million in.2010, and decreased 61%. than in 2000.
However, our country is still facing a lot of new problems and challenges in the prevention and control of tuberculosis. China is still one of the 22 countries with high tuberculosis burden in the world, WHO assessment. At present, the number of TB patients in our country is about 1 million 300 thousand, accounting for 14% of the global number of people in the world. In recent years, the number of tuberculosis cases in China has been reported to be about 1 million every year. In the end, it is the forefront of infectious diseases of class A and B in the country; the number of multi drug resistant tuberculosis is becoming more and more serious, the number of new patients is about 120 thousand every year, and the epidemic situation of tuberculosis which is mainly resistant bacteria may appear in the next few years; the number of TB / AIDS virus double infection patients continues to increase, and the prevention and control work needs to be strengthened urgently; the central and western regions, rural areas The situation of tuberculosis prevention and control in the region is severe. The current system of tuberculosis control and prevention and control in our country can not meet the needs of the prevention and control work under the new situation, the construction of the prevention and control infrastructure is lagging behind, the prevention and control force at the grass-roots level is weak, the treatment management of the patients with the floating population is more difficult, the public is not aware of the harm of tuberculosis, and the prevention and control task is especially important. Rural areas are still very arduous and require long-term and unremitting efforts.
In this study, the tuberculosis DOTC control project county in Taizhou agricultural county Xianju county was used as the research site. The field epidemiology and molecular biological techniques were used to systematically study all the tuberculosis patients who were registered in the tuberculosis control center of the county CDC from April 2011 to March 2012. The basic information of the patients was collected from the sputum of the patients, and all the sputum specimens were isolated and cultured. Two kinds of first-line anti tuberculosis drug sensitivity tests (RFP and INH) were carried out by the proportional method, and all M.TB was classified by the 15 locus MIRU-VNTR genotyping method, and the results were obtained by BioNumerics software. The cluster analysis was carried out, and the multiple PCR method was used to detect whether the RD105 fragment was missing to distinguish the Beijing genotypes and non Beijing genotypes. The epidemic strains and drug sensitivity of M.TB in rural areas of Taizhou and the genetic polymorphism of M.TB in this area were used to analyze the basic characteristics and possible transmission of tuberculosis in rural areas of Taizhou. To provide scientific basis for tuberculosis prevention and control in rural areas of Taizhou.
The main results and conclusions are as follows
1. basic epidemic characteristics of tuberculosis
The study included 89 people, 67 men, 75.3% and 22 women. The average age of 24.7%. tuberculosis patients was 51.4 + 18.2 years old, the largest was 88 years, the smallest 15 years old, and the median of 52 years old. 30-60 age groups were the largest, 44, 49.4%, and the largest of the 34.8%. occupations. People accounted for 78 of the first 18%. patients, accounting for 87.6%, and 11 of the retreated patients, accounting for 79 local cases, accounting for 88.8%. 10 people in the field accounted for 47 cases of 11.2%. sputum smear positive, accounting for 51.7% and negative in 42 cases, accounting for 48.3%..
2. tuberculosis bacilli isolation and drug resistance
M. TB80 strains were isolated from all patients, accounting for 89.9%, 8 strains of Mycobacterium tumefaciens, 9%, 1 strains of Mycobacterium in Kansas, 7 strains of INH or RFP in 1.1%.80 strains, 8.8% of them, and 6 of INH and RFP, 7.5% of them, and 4 of the retreated patients were isolated from the retreated patients. Mycobacterium bacilli isolated from 7 cases of M.TB, 3 cases were multi drug resistant.
Comparison of M.TB drug sensitivity results in 3. patients with different history of treatment
In 80 cases of M.TB tuberculosis, 74 were first treated, 92.5% were treated, 6 were retreated, 64 were sensitive to INH and RFP in the first 7.5%.74 cases, 86.5% (95%CI76.5%-93.3%), 10 of drug resistance, 13.5% (95%CI6.7%-23.5%); 3 cases were sensitive to INH and RFP in 6 patients, accounting for 50% (95%CI11.8%-). 88.2%) there were 3 cases of drug resistance, accounting for 50% (95%CI11.8%-88.2%). There was no significant difference between the initial and retreated patients (7=3.08, P=0.0510.05) in the total drug resistance rate (7=3.08, P=0.0510.05). There was no significant difference between the first treated and retreated patients (P=0.1020.05) in the drug resistance type (single drug resistant vs multidrug resistance).
Identification of different genotypes and comparison of drug sensitivity results of 4.M.TB
There were 39 strains of Beijing genotypes and 41 strains of non Beijing genotypes, 33 of which were sensitive to INH and RFP in Beijing genotypes, 84.6% (95%CI69.5%-94.1%), 6 of drug resistance and 15.4% (95%CI5.9%-30.1%), and 34 of non Beijing genotype strains susceptible to INH and RFP in 34, 34, and 34, respectively. 82.9% (95%CI67.9%-92.8%), 7 cases of drug resistance, accounting for 17.1% (95%CI7.2% to 32.1%). There was no significant difference between Beijing genotypes and non Beijing genotypes (all sensitive vs resistance) (x 2=0.04, P=0.8380.05), and Beijing genotypes and non Beijing genotype strains (single drug resistant vs MDR) were also not significant Sexual differences (x 2=1.93, P=0.3800.05)
Analysis of the influencing factors of 5. drug resistant tuberculosis
Single factor Logistic analysis found that retreatment was associated with the distribution of MDR-TB population (P0.05). Age, sex, occupation, household registration, treatment history, sputum smear, and strain genotypes were not associated with the distribution of single drug resistant patients. Multiple factor Logistic analysis found that the history of tuberculosis patients was associated with the distribution of multidrug resistant patients. Retreated TB patients are the main group of patients with multidrug-resistant tuberculosis (retreatment / initial treatment: OR:15.854; 95%CI:1.866 to 134.677).
6.M.TB genotyping
The highest resolution of 15 MIRU-VNTR loci for 80 M.TB was MIRU26 (HGI=0.865), the lowest resolution was ETRC (HGI=0.165), and HGI0.5 had 10 loci.
The results of 15 loci MIRU-VNTR genotyping showed that 80 strains of M.TB had 78 genotypes, 76 had independent genotypes, and 4 other 22 were clustered. The cluster rate was 2.5%. by Bionumberics5.0 software cluster analysis, and 78 genotypes were divided into 8 gene groups (group I, group II, group III, IV group, V group, VI group, VII group, VIII group). The group I accounted for 8.75% and 7 Genotypes; II group accounted for 11.25%, containing 8 genotypes; III group accounted for 55% and 43 genotypes; IV group accounted for 6.25% and 5 genotypes; V group accounted for 2.5% and 2 genotypes; VI group accounted for 8.75%, 7 genotypes, VII group 5%, containing 4 genotypes; VIII group accounted 2.5%, containing 2 genotypes.
The prevalence of tuberculosis in the rural areas of Taizhou was low. The resistance rate of M.TB was lower than the national level. There was no significant difference in the total drug resistance rate between the first treated and retreated patients. In M.TB, the non Beijing genotypes were the dominant bacteria, the Beijing genotype was low, and the Beijing genotype and the non Beijing genotype had no significant difference in the total resistance rate. The results of MIRU-VNTR genotyping at 15 loci showed that the rate of clustering among the strains was low and the gene polymorphism was obvious, indicating that the region was mainly infected by independent infection or endogenous reburning, and the recent transmission was less.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R52;R181.3

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