Tuberculosis (TB) is an infectious disease(感染) usually caused by the bacterium Mycobacterium tuberculosis(結核桿菌) (MTB).[1]Tuberculosis generally affects the lungs(肺), but can also affect other parts of the body. Most infections do not have symptoms, known as latent tuberculosis. About 10% of latent infections progress to active disease which, if left untreated, kills about half of those infected. The classic symptoms of active TB are a chronic cough(咳嗽) with blood-containing(咳血) sputum, fever(发热), night sweats, and weight loss(减肥).[1] The historical term "consumption" came about due to the weight loss.[2] Infection of other organs can cause a wide range of symptoms.[3]
"’结核病’’’（{{lang|en|Tuberculosis}}，又稱’’’TB’’’）為一種[[結核桿菌]]（’’{{lang|la|Mycobacterium tuberculosis}}’’，MTB）感染所引起的疾病<ref name=WHO2015Fact/>。结核通常造成 [[肺]]部感染, 但也会感染身体的其他部分。大多數感染者沒有症狀，此型態感染稱為{{le|潛伏結核感染|Latent tuberculosis}}<!-- <ref name=WHO2015Fact/> -->。如果此時沒有適當治療，10%的潛伏感染患者會惡化為活性結核病（Active tuberculosis），致死率可高達一半<!-- <ref name=WHO2015Fact/> -->。結核病的典型症狀包含慢性[[咳嗽]]、[[咳血]]、[[發燒]]、{{le|夜間盜汗|night sweats}}，以及[[體重減輕]]<ref name=Cha1998>{{cite book|title=The Chambers Dictionary.|year=1998|publisher=Allied Chambers India Ltd.|location=New Delhi|isbn=978-81-86062-25-8|pages=352|url=https://books.google.com/books?id=pz2ORay2HWoC&pg=RA1-PA352}}</ref>。感染其他器官則可能導致其他症狀<ref name=ID10>{{cite book|last=Dolin|first=[edited by] Gerald L. Mandell, John E. Bennett, Raphael|title=Mandell, Douglas, and Bennett’s principles and practice of infectious diseases|year=2010|publisher=Churchill Livingstone/Elsevier|location=Philadelphia, PA|isbn=978-0-443-06839-3|pages=Chapter 250|edition=7th}}</ref>。
Tuberculosis is spread through the air when people who have active TB in their lungs cough, spit, speak, or sneeze.[1][4] People with latent TB do not spread the disease. Active infection occurs more often in people with HIV/AIDS(艾滋病) and in those who smoke.[1]Diagnosis of active TB is based on chest X-rays, as well as microscopic examination and culture of body fluids. Diagnosis of latent TB relies on the tuberculin skin test(结核菌素试验) (TST) or blood tests.[5]
結核病屬於{{le|飛沫傳播|Airborne disease|飛沫傳染性疾病}}。意即病原體會藉由活性結核患者咳嗽、打噴嚏，或說話過程中所產生的飛沫散佈<ref name=WHO2015Fact/><ref name=CDC2012B>{{cite web|title=Basic TB Facts|url=http://www.cdc.gov/tb/topic/basics/default.htm|website=CDC|accessdate=11 February 2016|date=March 13, 2012}}</ref>；而潛伏性結核病患者則不會散布疾病<!-- <ref name=WHO2015Fact/> -->。活性結核常發生於[[愛滋病]]患者及抽菸者<ref name=WHO2015Fact/> ，需藉由{{le|胸部X光|chest X-rays}}、[[顯微鏡|顯微鏡檢]]，及體液培養來進行診斷<!-- <ref name=AP/> --> 。潛伏結合患者則可利用[[結核菌素試驗]]或血液檢查來診斷<ref name=AP>{{cite journal|author=Konstantinos A |year=2010|title=Testing for tuberculosis |journal=Australian Prescriber |volume= 33 |issue=1 |pages=12–18 |url= http://www.australianprescriber.com/magazine/33/1/12/18/}}</ref>。
Prevention of TB involves screening those at high risk, early detection and treatment of cases, and vaccination(疫苗接種) with thebacillus Calmette-Guérin(卡介苗) vaccine.[6][7][8] Those at high risk include household, workplace, and social contacts of people with active TB.[8] Treatment requires the use of multiple antibiotics(抗细菌药) over a long period of time.[1] Antibiotic resistance(抗生素抗藥性) is a growing problem with increasing rates of multiple drug-resistant tuberculosis (MDR-TB).[1]
One-third of the world’s population is thought to be infected with TB.[1] New infections occur in about 1% of the population each year.[9] In 2014, there were 9.6 million cases of active TB which resulted in 1.5 million deaths. More than 95% of deaths occurred indeveloping countries(发展中国家). The number of new cases each year has decreased since 2000.[1] About 80% of people in many Asian and African countries test positive while 5–10% of people in the United States population tests positive by the tuberculin test.[10] Tuberculosis has been present in humans since ancient times(古代史).[11]
預防可透過篩檢高風險者、早期診斷和治療，以及接種[[卡介苗]]等方法達成<ref>{{cite journal|last1=Hawn|first1=TR|last2=Day|first2=TA|last3=Scriba|first3=TJ|last4=Hatherill|first4=M|last5=Hanekom|first5=WA|last6=Evans|first6=TG|last7=Churchyard|first7=GJ|last8=Kublin|first8=JG|last9=Bekker|first9=LG|last10=Self|first10=SG|title=Tuberculosis vaccines and prevention of infection.|journal=Microbiology and molecular biology reviews: MMBR|date=December 2014|volume=78|issue=4|pages=650–71|pmid=25428938|doi=10.1128/MMBR.00021-14|pmc=4248657}}</ref><ref>{{cite book|last1=Harris|first1=Randall E.|title=Epidemiology of chronic disease: global perspectives|date=2013|publisher=Jones & Bartlett Learning|location=Burlington, MA|isbn=9780763780470|page=682|ref=https://books.google.ca/books?id=KJLEIvX4wzoC&pg=PA682}}</ref><ref name=TBCon2008>{{cite book|last1=Organization|first1=World Health|title=Implementing the WHO Stop TB Strategy: a handbook for national TB control programmes|date=2008|publisher=World Health Organization|location=Geneva|isbn=9789241546676|page=179|url=https://books.google.ca/books?id=EUZXFCrlUaEC&pg=PA179}}</ref>。高風險者包含生活環境中與活性結核病患者密切接觸的人<ref name=TBCon2008/>。治療通常搭配不同的[[抗細菌藥|抗生素]]組合做一段時間的治療<ref name=WHO2015Fact/> 。近年帶有[[抗生素抗藥性]]的結核桿菌(MDR-TB)日益增加<ref name=WHO2015Fact/>。
世界上大約有三分之一的人口患有肺結核<ref name=WHO2015Fact/><!-- Quote = About one-third of the world’s population has latent TB -->。全球每年大約有1%的人口新感染該病<ref name=WHO2002>{{cite web|title=Tuberculosis|url=http://www.who.int/mediacentre/factsheets/who104/en/print.html|work=World Health Organization|year=2002}}</ref> ，2014年全球有960萬名活性結核病患者，150萬例死亡，死亡者當中有95%是來自[[發展中國家]]。自2000年起，全球新病例數已逐年下降<ref name=WHO2015Fact>{{cite web|title=Tuberculosis Fact sheet N°104|url=http://www.who.int/mediacentre/factsheets/fs104/en/|website=WHO|accessdate=11 February 2016|date=October 2015}}</ref>
在許多亞洲與非洲國家，大約有80%的人肺結核檢驗結果為陽性，而在美國的人口中約有5-10%的人肺結核檢驗為陽性<ref name=Robbins>{{cite book |vauthors=Kumar V, Abbas AK, Fausto N, Mitchell RN |year=2007 |title=Robbins Basic Pathology |edition=8th |p
ublisher=Saunders Elsevier |pages=516–522 |isbn=978-1-4160-2973-1}}</ref> Tuberculosis has been present in humans since [[Ancient history|ancient times]]。結核病在[[古代史]]中就有紀載<ref name=Lancet11>{{cite journal|last=Lawn|first=SD|author2=Zumla, AI |title=Tuberculosis|journal=Lancet|date=2 July 2011|volume=378|issue=9785|pages=57–72|pmid=21420161|doi=10.1016/S0140-6736(10)62173-3}}</ref>。
The main symptoms of variants and stages of tuberculosis are given,[12] with many symptoms overlapping with other variants, while others are more (but not entirely) specific for certain variants. Multiple variants may be present simultaneously.
Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis).[3] Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, although extrapulmonary TB may coexist with pulmonary TB.[3]
General signs and symptoms include fever(发热), chills(發冷), night sweats, loss of appetite, weight loss(减肥), and fatigue(疲倦).[3] Significant nail clubbing may also occur.[13]
==臨床體徵與症狀==
[[File:Tuberculosis symptoms.svg|thumb|upright=1.5|結核病不同變種與階段的主要症狀如下[12]。<ref>{{cite web|url=http://www.emedicinehealth.com/tuberculosis/page3_em.htm|title=Tuberculosis Symptoms|publisher=[[eMedicine]]Health|author=Schiffman G|date=15 January 2009}}</ref> 許多變種的主要症狀相互重疊，而又有一些變種有其獨特（但並不一定是完全獨特）的症狀，幾個變種的症狀也可同時表現出來。]]
結核病可以在全身的任何一個部位發病，但最常發病於肺（即被稱為肺結核）[3]。<ref name=ID10/> 肺外結核病（即在肺以外的器官發生的結核病）可能與肺結核共同存在[3]。<ref name=ID10/>
結核病一般的臨床體徵與症狀包括[[發熱]]、[[發冷]]、[[盜汗]]、[[食慾不振]]、[[體重減輕]]以及[[疲倦]][3]。<ref name=ID10/> 結核病患者也可能出現明顯的[[杵狀指甲]]症狀[13]。<ref name=Pet2005/>
Pulmonary
If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases).[11][14]Symptoms may include chest pain and a prolonged cough producing sputum. About 25% of people may not have any symptoms (i.e. they remain "asymptomatic").[11] Occasionally, people may cough up blood(咳血) in small amounts, and in very rare cases, the infection may erode into the pulmonary artery(肺動脈) or a Rasmussen’s aneurysm, resulting in massive bleeding.[3][15] Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones.[3] The reason for this difference is not clear.[10] It may be due either to better air flow,[10] or to poor lymph(淋巴) drainage within the upper lungs.[3]
===肺結核===
活性結核病最常見於肺部（占約90%的病例）[11][14]。<ref name=Lancet11/><ref>{{cite book|last=Behera|first=D.|title=Textbook of Pulmonary Medicine|year=2010|publisher=Jaypee Brothers Medical Publishers|location=New Delhi|isbn=978-81-8448-749-7|pages=457|url=https://books.google.com/books?id=0TbJjd9eTp0C&pg=PA457|edition=2nd}}</ref> 肺結核的症狀可能包含{{le|胸痛|Chest pain}}和長時間帶痰咳嗽， !-- <ref name=Lancet11/> --> 而約有25%的人可能不會表現任何症狀（即「無症狀的」）[11]。 <ref name=Lancet11/> 偶爾，人們可能小量的[[咳血]]，在極為罕見的病例中，感染可能侵蝕到[[肺動脈]]和{{le|雷斯莫森氏動脈瘤|Rasmussen’s aneurysm}}，導致大量出血[3][15]。<ref name=ID10/><ref>{{cite journal|last1=Halezeroğlu|first1=S|last2=Okur|first2=E|title=Thoracic surgery for haemoptysis in the context of tuberculosis: what is the best management approach?|journal=Journal of Thoracic Disease|date=March 2014|volume=6|issue=3|pages=182–5|pmid=24624281|doi=10.3978/j.issn.2072-1439.2013.12.25}}</ref> 肺結核可能演變成慢性疾病，並導致上肺葉產生大疤痕。 !-- <ref name=ID10/> --> 上肺葉比下肺葉更易受到肺結核的影響[3]，<ref name=ID10/> 但這個差別的原因目前還未明[10]。<ref name="Robbins" /> 可能的解釋為上肺葉的空氣流通較佳[10]，<ref name="Robbins" /> 或其[[淋巴]]引流能力較差[3]。<ref name=ID10/>
Extrapulmonary
In 15–20% of active cases, the infection spreads outside the lungs, causing other kinds of TB.[16] These are collectively denoted as "extrapulmonary tuberculosis".[17] Extrapulmonary TB occurs more commonly in immunosuppressed(免疫抑制) persons and young children. In those with HIV, this occurs in more than 50% of cases.[17] Notable extrapulmonary infection sites include the pleura(胸膜腔) (in tuberculous pleurisy), the central nervous system(中樞神經系統) (in tuberculous meningitis(脑膜炎)), the lymphatic system(淋巴系統) (in scrofula of the neck), the genitourinary system (inurogenital tuberculosis), and the bones and joints (in Pott disease of the spine), among others. When it spreads to the bones, it is also known as "osseous tuberculosis",[18] a form of osteomyelitis.[10] Sometimes, bursting of a tubercular abscess through skin results in tuberculous ulcer.[19] An ulcer originating from nearby infected lymph nodes is painless, slowly enlarging and has an appearance of "wash leather".[20] A potentially more serious, widespread form of TB is called "disseminated tuberculosis", also known as miliary tuberculosis.[3] Miliary TB makes up about 10% of extrapulmonary cases.[21]
===肺外結核病===
在15％至20%的活性結核病案例中，結核桿菌感染可傳播至肺外，引起其他種類的結核病[16]。<ref>{{cite book|last=Jindal|first=editor-in-chief SK|title=Textbook of Pulmonary and Critical Care Medicine|publisher=Jaypee Brothers Medical Publishers|location=New Delhi|isbn=978-93-5025-073-0|pages=549|url=https://books.google.com/books?id=EvGTw3wn-zEC&pg=PA549|year=2011}}</ref> 這些病症被歸類為「肺外結核病」[17]。 <ref name=Extra2005>{{cite journal|pmid=16300038|year=2005|vauthors=Golden MP, Vikram HR |title=Extrapulmonary tuberculosis: an overview|volume=72|issue=9|pages=1761–8|journal=American Family Physician }}</ref> 肺外結核病常發生於存在[[免疫抑制]]的個體或幼兒，50％以上患有肺結核的HIV病毒攜帶者均患有肺外結核病[17]。<ref name=Extra2005/> 肺外結核病常發病於[[胸膜腔]]（結核性胸膜炎）、[[中樞神經系統]]（結核性[[腦膜炎]]）、[[淋巴系統]]（即頸部{{le|淋巴結核|Scofula}}，又稱瘰癧）、泌尿生殖道系統（即{{le|尿殖道結核|urogenital tuberculosis}}），以及骨與筋腱（即{{le|博特氏病|Pott disease}}；脊柱結核性彎曲）等部位。當結核病發病於骨骼時，也被稱為「骨結核病」[18]， <ref>{{cite book|last=Kabra|first=[edited by] Vimlesh Seth, S.K.|title=Essentials of tuberculosis in children|year=2006|publisher=Jaypee Bros. Medical Publishers|location=New Delhi|isbn=978-81-8061-709-6|pages=249|url=https://books.google.com/books?id=HkH0YbyBHDQC&pg=PA249|edition=3rd}}</ref> 即一種骨髓炎[10]。 <ref name="Robbins" /> 有時結核性膿腫破出皮膚導致結核性潰瘍[19]。<ref>{{cite book|title=Manual of Surgery|year=2008|publisher=Kaplan Publishing|isbn=9781427797995|pages=75}}</ref> 由周圍感染的淋巴結產生的潰瘍常表現為無痛、緩慢擴大以及看起來像水洗過的皮革的特性。<ref>{{cite book|la
st=Burkitt|first=H. George|title=Essential Surgery: Problems, Diagnosis & Management 4th ed|year=2007|isbn=9780443103452|pages=34}}</ref> 彌散性結核病是一種更具危險性、更易擴散的結核病，也被稱為{{le|粟粒狀結核|Milliary tuberculosis}}][3]，<ref name=ID10/> 粟粒狀結核占肺外結核病例的10％[21]。<ref name=Gho2008/>
另外在台灣較常見的肺外結核為淋巴結核和骨結核，而結核性腦膜炎為其次，肺外結核的發生率比肺結核低。[中1] 而在中国大陆，以1996年至1999年上海市的流行病學研究為例，肺外结核發病案例以周围淋巴结结核为主,占38.3%,余依次为骨关节结核(19.9%)、泌尿生殖系统结核(16.7%)及肠、腹膜结核(9.1%)和脑神经结核(6.4%)。男女之比为1:1.35[中2]。
Mycobacteria
Main article: Mycobacterium tuberculosis(結核桿菌)
Scanning electron micrograph(扫描电子显微镜) of M. tuberculosis
The main cause of TB is Mycobacterium tuberculosis(結核桿菌), a small, aerobic(好氧生物), nonmotile bacillus(芽孢桿菌屬).[3] The highlipid(脂類) content of this pathogen accounts for many of its unique clinical characteristics.[22] It divides(细胞分裂) every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour.[23] Mycobacteria have an outer membrane(細菌結構) lipid bilayer.[24] If a Gram stain(革蘭氏染色) is performed, MTB either stains very weakly "Gram-positive" or does not retain dye as a result of the high lipid and mycolic acid content of its cell wall.[25] MTB can withstand weak disinfectants(消毒) and survive in a dry state(内生孢子) for weeks. In nature, the bacterium can grow only within the cells of a host(宿主) organism, but M. tuberculosiscan be cultured in the laboratory(In vitro).[26]
Using histological(组织学) stains on expectorated(吐痰) samples from phlegm(痰) (also called "sputum"), scientists can identify MTB under a microscope. Since MTB retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus.[10][25]The most common acid-fast staining techniques are the Ziehl–Neelsen stain[27] and the Kinyoun stain, which dye acid-fast bacilli a bright red that stands out against a blue background.[28] Auramine-rhodamine staining[29] and fluorescence microscopy(熒光顯微鏡)[30] are also used.
==病因==
===分枝桿菌屬===
{{main|結核桿菌}}
[[File:Mycobacterium tuberculosis.jpg|thumb|[[Scanning electron micrograph]] of ’’M. tuberculosis’’]]
[[結核桿菌]]是主要引起結核病的致病原，它是一個小型、[[好氧]]、不具活動性的細菌，屬於[[芽孢桿菌屬]]<ref name=ID10/>。結核桿菌的生長速度與其他細菌相比非常緩慢，細胞每16至20小時才[[分裂]]一次，而其他細菌一般則不到半小時即分裂一次<ref>{{cite book|last=Jindal|first=editor-in-chief SK|title=Textbook of Pulmonary and Critical Care Medicine|publisher=Jaypee Brothers Medical Publishers|location=New Delhi|isbn=978-93-5025-073-0|pages=525|url=https://books.google.com/books?id=rAT1bdnDakAC&pg=PA525|year=2011}}</ref> 。結核桿菌還有一個特殊的雙層脂質[[細菌結構|外膜]]<ref name=Niederweis2010>{{cite journal |vauthors=Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H |title=Mycobacterial outer membranes: in search of proteins |journal=Trends in Microbiology |volume=18 |issue=3 |pages=109–16 |date=March 2010 |pmid=20060722 |pmc=2931330 |doi=10.1016/j.tim.2009.12.005 }}</ref>。細胞壁富含脂質是分枝桿菌屬特有的臨床特徵<ref>{{cite book |author=Southwick F |title=Infectious Diseases: A Clinical Short Course, 2nd ed. |publisher=McGraw-Hill Medical Publishing Division |date=10 December 2007 |pages=104, 313–4 |chapter=Chapter 4: Pulmonary Infections |isbn=0-07-147722-5}}</ref>，使用一般的[[革蘭氏染色鑑定]]，會出現不明顯的陽性反應或無法被染上色的現象，原因就是其細胞壁中富含脂質以及[[黴菌酸（分枝菌酸）]]（一種脂肪酸）<ref name=Madison_2001>{{cite journal |author=Madison B |title=Application of stains in clinical microbiology |journal=Biotechnic & Histochemistry |volume=76 |issue=3 |pages=119–25 |year=2001 |pmid=11475314 |doi=10.1080/714028138}}</ref> 。結核桿菌可以抵抗弱[[消毒劑]]並且可以用[[內生孢子]]的方式存活數星期。在自然界，結核桿菌只能生長於[[宿主]]個體的細胞中，但在實驗室中則可在[[試管內]]培養<ref name=Parish_1999>{{cite journal |author1=Parish T. |author2=Stoker N. |title=Mycobacteria: bugs and bugbears (two steps forward and one step back) |journal=Molecular Biotechnology |volume=13 |issue=3 |pages=191–200 |year=1999| pmid=10934532 |doi = 10.1385/MB:13:3:191}}</ref>。
醫檢師可利用[[組織]]染色法處理[[痰液]]檢體，便可用顯微鏡鑑別出結核桿菌。因為結核桿菌染色後不會被酸性溶劑沖洗掉，分類上又被稱為{{link-en|抗酸性桿菌|Acid-fast bacillus}}<ref name=Robbins/><ref name="Madison_2001"/>。目前最常用的耐酸染色法是{{link-en|齐尔-尼尔森（Ziehl–Neelsen）染色|Ziehl–Neelsen stain}}及{{link-en|金氏（Kinyoun）染色|Kinyoun stain}}，兩染色法在顯微鏡下所見的背景為藍色，而結核桿菌則是呈現紅色<ref name=Stain2000>{{cite book |title=Medical Laboratory Science: Theory and Practice |publisher=Tata McGraw-Hill |location=New Delhi |year=2000 |pages=473 |isbn=0-07-463223-X |url=https://books.google.com/books?id=lciNs3VQPLoC&pg=PA473}}</ref><ref>{{cite web|title=Acid-Fast Stain Protocols|url=http://www.microbelibrary.org/component/resource/laboratory-test/2870-acid-fast-stain-protocols|accessdate=26 March 2016|date=21 August 2013}}</ref>。另外也可使用{{link-en|金胺-若丹明（Auramine-rhodamine ）染色法|Auramine-rhodamine stain}}，並在[[螢光顯微鏡]]下觀察<ref name=Kommareddi_1984>{{cite journal|author1=Kommareddi S. |author2=Abramowsky C. |author3=Swinehart G. |author4=Hrabak L. |title=Nontuberculous mycobacterial infections: comparison of the fluorescent auramine-O and Ziehl-Neelsen techniques in tissue diagnosis|journal=Human Pathology|volume=15|issue=11|pages=1085–1089|year=1984|pmid=6208117|doi=10.1016/S0046-8177(84)80253-1}}</ref><ref>{{cite book|last1=van Lettow|first1=Monique|last2=Whalen|first2=Christopher|title=Nutrition and health in developing countries|year=2008|publisher=Humana Press|location=Totowa, N.J. (Richard D. Semba and Martin W. Bloem, eds.)|isbn=978-1-934115-24-4|pages=291|url=https://books.google.com/books?id=RhH6uSQy7a4C&pg=PA291|edition=2nd}}</ref>。
The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria(分枝杆菌属): M. bovis, M. africanum, M. canetti, andM. microti.[31] M. africanum is not widespread, but it is a significant cause of tuberculosis in parts of Africa.[32][33] M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk(巴斯德消毒法) has almost completely eliminated this as a public health problem in developed countries.[10][34] M. canetti is rare and seems to be limited to the Horn of Africa(非洲之角), although a few cases have been seen in African emigrants.[35][36] M. microti is also rare and is seen almost only in immunodeficient people, although its prevalence(患病率) may be significantly underestimated.[37]
Other known pathogenic mycobacteria include M. leprae(麻风杆菌), M. avium, and M. kansasii. The latter two species are classified as "nontuberculous mycobacteria" (NTM). NTM cause neither TB nor leprosy(麻风病), but they do cause pulmonary diseases that resemble TB.[38]
结核分枝杆菌复合群(MTBC)包括其他四种可引起结核病的[[分枝桿菌屬]]的細菌：[[牛分枝桿菌]]、[[非洲分枝桿菌]]、[[卡氏分枝桿菌]]及[[田鼠分枝桿菌]]<ref>{{cite journal |author=van Soolingen D. |title=A novel pathogenic taxon of the Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa |journal=International Journal of Systematic Bacteriology |volume=47 |issue=4 |pages=1236–45 |year=1997 |pmid=9336935 |doi=10.1099/00207713-47-4-1236 |name-list-format=vanc |display-authors=1 |last2=Hoogenboezem |first2=T. |last3=De Haas |first3=P.E.W.|last4=Hermans |first4=P.W.M. |last5=Koedam |first5=M.A. |last6=Teppema |first6=K.S. |last7=Brennan |first7=P.J.|last8=Besra |first8=G.S.|last9=Portaels |first9=F.}}</ref>。 "非洲分枝桿菌"分佈不廣，但卻是導致非洲結核病感染的重要因素<ref>{{cite journal |author=Niemann S. |title=Mycobacterium africanum Subtype II Is Associated with Two Distinct Genotypes and Is a Major Cause of Human Tuberculosis in Kampala, Uganda |journal=Journal of Clinical Microbiology |volume=40 |issue=9 |pages=3398–405 |year=2002 |pmid=12202584 |pmc=130701 |doi=10.1128/JCM.40.9.3398-3405.2002 |name-list-format=vanc |display-authors=1 |last2=Rusch-Gerdes |first2=S.|last3=Joloba |first3=M.L.|last4=Whalen |first4=C.C.|last5=Guwatudde |first5=D.|last6=Ellner |first6=J.J.|last7=Eisenach |first7=K.|last8=Fumokong |first8=N. |last9=Johnson |first9=J.L.}}</ref><ref>{{cite journal |author=Niobe-Eyangoh S.N.|title=Genetic Biodiversity of Mycobacterium tuberculosis Complex Strains from Patients with Pulmonary Tuberculosis in Cameroon |journal=Journal of Clinical Microbiology |volume=41 |issue=6 |pages=2547–53 |year=2003 |pmid=12791879 |pmc=156567 |doi=10.1128/JCM.41.6.2547-2553.2003 |name-list-format=vanc |display-authors=1 |last2=Kuaban |first2=C. |last3=Sorlin |first3=
P. |last4=Cunin |first4=P. |last5=Thonnon |first5=J. |last6=Sola |first6=C. |last7=Rastogi |first7=N. |last8=Vincent |first8=V. |last9=Gutierrez |first9=M.C.}}</ref>。"牛分枝桿菌"曾是導致結核病感染的常見因素，但因[[巴式消毒法]]在牛奶生產中的使用，在發達國家已幾乎不再出現牛分枝桿菌導致結核病感染的病例<ref name=Robbins/><ref>{{cite journal |vauthors=Thoen C, Lobue P, de Kantor I |title=The importance of ’’Mycobacterium bovis’’ as a zoonosis |journal=Veterinary Microbiology |volume=112 |issue=2–4 |pages=339–45 |year=2006 |pmid=16387455 |doi=10.1016/j.vetmic.2005.11.047}}</ref> 。"卡式分枝桿菌"較為罕見，且似乎僅出現於[[非洲之角（東北非洲）]]，但也有少數幾例病例出現於非洲裔移民中<ref>{{cite book|last=Acton|first=Q. Ashton|title=Mycobacterium Infections: New Insights for the Healthcare Professional|year=2011|publisher=ScholarlyEditions|isbn=978-1-4649-0122-5|pages=1968|url=https://books.google.com/books?id=g2iFfV6uEuAC&pg=PA1968}}</ref><ref>{{cite journal|last=Pfyffer|first=GE|author2=Auckenthaler, R |author3=van Embden, JD|author4=van Soolingen, D|title=Mycobacterium canettii, the smooth variant of M. tuberculosis, isolated from a Swiss patient exposed in Africa|journal=Emerging Infectious Diseases|date=Oct–Dec 1998|volume=4|issue=4|pages=631–4|pmid=9866740|pmc=2640258|doi=10.3201/eid0404.980414}}</ref> 。"田鼠分枝桿菌"也較為罕見，且幾乎僅出現於免疫不全人群，但其[[盛行率]]可能被嚴重低估<ref>{{cite journal|last=Panteix|first=G|author2=Gutierrez, MC |author3=Boschiroli, ML |author4=Rouviere, M |author5=Plaidy, A |author6=Pressac, D |author7=Porcheret, H |author8=Chyderiotis, G |author9=Ponsada, M |author10=Van Oortegem, K |author11=Salloum, S |author12=Cabuzel, S |author13=Bañuls, AL |author14=Van de Perre, P |author15=Godreuil, S |title=Pulmonary tuberculosis due to Mycobacterium microti: a study of six recent cases in
France|journal=Journal of Medical Microbiology|date=August 2010|volume=59|issue=Pt 8|pages=984–9|pmid=20488936|doi=10.1099/jmm.0.019372-0}}</ref>
其他致病分枝桿菌屬細菌包括[[痲瘋桿菌]]、{{link-en|鳥分枝桿菌|Mycobacterium avium complex}}及{{link-en|堪塞斯分枝桿菌|Mycobacterium kansasii}}。後兩者被歸為
{{link-en|非结核性分枝杆菌(NTM)|Nontuberculous mycobacteria}}。非结核性分枝杆菌既不能引起結核病也不能引起[[痲瘋病]]，但其感染會導致相似於結核病的肺部疾病<ref name=ALA_1997>{{cite journal |title=Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association |journal=American Journal of Respiratory and Critical Care Medicine |volume=156 |issue=2 Pt 2 |pages=S1–25 |year=1997 |pmid = 9279284 |author=American Thoracic Society |doi=10.1164/ajrccm.156.2.atsstatement }}</ref>。
Risk factors
Main article: Risk factors for tuberculosis
A number of factors make people more susceptible to TB infections. The most important risk factor globally is HIV; 13% of all people with TB are infected by the virus.[39] This is a particular problem in sub-Saharan Africa(撒哈拉以南非洲), where rates of HIV are high.[40][41] Of people without HIV who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes;[13] in contrast, 30% of those coinfected with HIV develop the active disease.[13]
===危險因子===
{{main|肺結核的危險因子}}
有許多因子會讓人更容易罹患肺結核。目前全球最重要的一項危險因子是HIV病毒；在罹患肺結核的病人中，有13%是HIV病毒感染的患者[39]<ref name=WHO2011>{{cite web|title=The sixteenth global report on tuberculosis|author=World Health Organization|url=http://www.who.int/tb/publications/global_report/2011/gtbr11_executive_summary.pdf|year=2011}}</ref>。 該問題在[[撒哈拉以南非洲|漠南非洲]]尤其顯著，因為這個區域愛滋病罹患率相當高<ref>{{cite web|author=World Health Organization|url=http://www.who.int/tb/publications/global_report/en/index.html|title=Global tuberculosis control–surveillance, planning, financing WHO Report 2006|accessdate=13 October 2006}}</ref><ref>{{cite journal|last=Chaisson|first=RE|author2=Martinson, NA |title=Tuberculosis in Africa—combating an HIV-driven crisis|journal=The New England Journal of Medicine|date=13 March 2008|volume=358|issue=11|pages=1089–92|pmid=18337598|doi=10.1056/NEJMp0800809}}</ref>。 未感染HIV的肺結核患者中，有約5～10%日後發展為活動性肺結核[13] <ref name=Pet2005>{{cite book|last1=Gibson|first1=Peter G. (ed.)|last2=Abramson|first2=Michael (ed.)|last3=Wood-Baker|first3=Richard (ed.)|last4=Volmink|first4=Jimmy (ed.)|last5=Hensley|first5=Michael (ed.)|last6=Costabel|first6=Ulrich (ed.)|title=Evidence-Based Respiratory Medicine|date=2005|publisher=BMJ Books|isbn=978-0-7279-1605-1|page=321|edition=1st|url=http://www.wiley.com/WileyCDA/WileyTitle/productCd-072791605X.html}}</ref>； 相比之下，同時感染HIV的肺結核患者日後有30％發展為活動性肺結核[13]<ref name=Pet2005/>。
Tuberculosis is closely linked to both overcrowding and malnutrition(營養不良), making it one of the principal diseases of poverty.[11] Those at high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather (e.g. prisons and homeless shelters), medically underprivileged and resource-poor communities, high-risk ethnic minorities, children in close contact with high-risk category patients, and health-care providers serving these patients.[42]
肺結核與擁擠環境、[[營養不良]]相關，這些特性使其成為{{le|貧窮病|disease of proverty}}之一<ref name=Lancet11/>。 其他高風險因子則包含注射毒品、人口聚集場所居民及工作人員（如收容所及監獄）、醫療衛生較差區域、某些特定種族、與病患長期接觸的孩童，以及醫療照護人員等等 <ref name=Griffith_1996>{{cite journal |vauthors=Griffith D, Kerr C | title=Tuberculosis: disease of the past, disease of the present | journal=Journal of Perianesthesia Nursing | volume=11 | issue=4 | pages=240–5 | year=1996 | pmid=8964016 | doi=10.1016/S1089-9472(96)80023-2 }}</ref>。
Chronic lung disease is another significant risk factor. Silicosis increases the risk about 30-fold.[43] Those who smoke cigarettes(香煙) have nearly twice the risk of TB compared to nonsmokers.[44]
慢性肺部疾病是另一種重要的危險因子。{{link-en|矽肺症|Silicosis}}提高了大約30倍的風險 [43]。[[吸煙者|香煙]]相於沒有吸煙的族群，有大約兩倍罹患肺結核的風險<ref>{{cite journal|last=van Zyl Smit|first=RN|author2=Pai, M |author3=Yew, WW |author4=Leung, CC |author5=Zumla, A |author6=Bateman, ED |author7=Dheda, K |title=Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD| journal=European Respiratory Journal |date=January 2010|volume=35|issue=1|pages=27–33|pmid=20044459|quote=These analyses indicate that smokers are almost twice as likely to be infected with TB and to progress to active disease (RR of about 1.5 for latent TB infection (LTBI) and RR of ∼2.0 for TB disease). Smokers are also twice as likely to die from TB (RR of about 2.0 for TB mortality), but data are difficult to interpret because of heterogeneity in the results across studies.|doi=10.1183/09031936.00072909}}</ref>。
Other disease states can also increase the risk of developing tuberculosis. These include alcoholism(酗酒)[11] and diabetes mellitus(糖尿病) (three-fold increase).[45]
另外還有一些疾病也會提高肺結核的風險，包含[[酗酒]]、[[糖尿病]] (提高約3倍的患病機率) <ref>{{cite journal|last=Restrepo|first=BI|title=Convergence of the tuberculosis and diabetes epidemics: renewal of old acquaintances|journal=Clinical Infectious Diseases |date=15 August 2007|volume=45|issue=4|pages=436–8|pmid=17638190|doi=10.1086/519939|pmc=2900315}}</ref>。
Certain medications, such as corticosteroids(皮質類固醇) and infliximab (an anti-αTNF monoclonal antibody), are becoming increasingly important risk factors, especially in thedeveloped world(已開發國家).[11]
某些藥物逐漸成為重要的風險因子，尤其是在[[已開發國家]]。例如[[皮質類固醇]] 和 {{link-en|Infliximab|Infliximab}} (一種抗αTNF的單株抗體)<ref name=Lancet11/>。
Genetic susceptibility also exists,[46] for which the overall importance remains undefined.[11]
{{link-en|遺傳易感性|Genetic susceptibility}} 也是危險因子之一，然而其重要性目前仍未確立<ref>{{cite journal|last=Möller|first=M|author2=Hoal, EG |title=Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis|journal=Tuberculosis |date=March 2010|volume=90|issue=2|pages=71–83|pmid=20206579|doi=10.1016/j.tube.2010.02.002}}</ref><ref name=Lancet11/>。
Transmission
When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol(气溶胶) droplets 0.5 to 5.0 µm(微米) in diameter. A single sneeze can release up to 40,000 droplets.[47] Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection).[48]
People with prolonged, frequent, or close contact with people with TB are at particularly high risk of becoming infected, with an estimated 22% infection rate.[49] A person with active but untreated tuberculosis may infect 10–15 (or more) other people per year.[50] Transmission should occur from only people with active TB – those with latent infection are not thought to be contagious.[10] The probability of transmission from one person to another depends upon several factors, including the number of infectious droplets expelled by the carrier, the effectiveness of ventilation, the duration of exposure, the virulence(病毒性) of the M. tuberculosis strain, the level of immunity in the uninfected person, and others.[51] The cascade of person-to-person spread can be circumvented by segregating those with active ("overt") TB and putting them on anti-TB drug regimens. After about two weeks of effective treatment, subjects with nonresistant(抗生素抗藥性) active infections generally do not remain contagious to others.[49] If someone does become infected, it typically takes three to four weeks before the newly infected person becomes infectious enough to transmit the disease to others.[52]
==發病機制==
[[File:TB poster.jpg|thumb|Public health campaigns in the 1920s tried to halt the spread of TB.]]
===傳染途徑===
當患有開放性肺結核的患咳嗽、打噴嚏、說話、唱歌或吐痰，患者會釋放出具有傳染性、直徑0.5至5.0µm([[微米]])的懸浮粒子，並與空氣形成[[氣溶膠]]。每個噴嚏可釋放出高達40,000顆懸浮粒子<ref name=Cole_1998>{{cite journal |vauthors=Cole E, Cook C |title=Characterization of infectious aerosols in health care facilities: an aid to effective engineering controls and preventive strategies |journal=Am J Infect Control |volume=26 |issue=4 |pages=453–64 |year=1998 |pmid=9721404|doi = 10.1016/S0196-6553(98)70046-X}}</ref>。由於肺結核的感染劑量非常低(吸入少於十個細菌即有可能造成感染)，每一顆懸浮粒子都可能造成傳染<ref>{{cite journal |vauthors=Nicas M, Nazaroff WW, Hubbard A |title=Toward understanding the risk of secondary airborne infection: emission of respirable pathogens |journal=J Occup Environ Hyg |volume=2 |issue=3 |pages=143–54 |year=2005 |pmid=15764538|doi = 10.1080/15459620590918466}}</ref>。
與肺結核患者長期、頻繁或親密接觸者皆有非常高的感染風險，感染率約為22%<ref name=Ahmed_2011>{{cite journal |vauthors=Ahmed N, Hasnain S |title=Molecular epidemiology of tuberculosis in India: Moving forward with a systems biology approach |journal=Tuberculosis |volume=91 |issue=5 |pages=407–3 |year=2011|pmid = 21514230|doi = 10.1016/j.tube.2011.03.006}}</ref>。未經治療的開放性肺結核患者每年會傳染10至15人(或更多)<ref name="WHO2012data"/> 肺結核只由開放性患者傳染給其他人（也就是说所有「活動性」患者也具感染性），而潛伏結核感染患者與非開放性肺結核患者一般並不被認為具有感染性<ref name=Robbins/>。多個因素同時影響個體之間的傳染機率，其中包括病患噴出飛沫的懸浮粒子數量、通風情況、暴露於感染源的持續時間、結核分枝桿菌[[分型|菌株]]的[[病毒性|致病性]]，以及個體的免疫力等等<ref name=CDCcourse>{{cite web|publisher=[[Centers for Disease Control and Prevention]] (CDC), Division of Tuberculosis Elimination|url=http://www.cdc.gov/tb/education/corecurr/pdf/corecurr_all.pdf|title=Core Curriculum on Tuberculosis: What the Clinician Should Know|page=24|edition=5th|year=2011}}</ref> 。人與人間的傳染可以藉由隔離具有傳染性肺結核的患者和給予抗結核的藥物治療來避免。大約在兩個星期有效的治療後，沒有[[抗生素抗藥性]]之患者一般不會傳染給其他者<ref name="Ahmed_2011"/> 。人被傳染後通常需要3至4周的時間，才會具有足夠傳染力去傳染別人<ref>{{cite web | url=http://www.mayoclinic.com/health/tuberculosis/DS00372/DSECTION=3|title=Causes of Tuberculosis|accessdate=19
October 2007|date=21 December 2006|publisher=[[Mayo Clinic]]}}</ref>。
Pathogenesis
About 90% of those infected with M. tuberculosis have asymptomatic, latent TB infections (sometimes called LTBI),[53] with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease.[54] In those with HIV, the risk of developing active TB increases to nearly 10% a year.[54] If effective treatment is not given, the death rate for active TB cases is up to 66%.[50]
===病因===
[[File:Tuberculous epididymitis Low Power.jpg|thumb|經[[蘇木精-伊紅染色|蘇木精-伊紅（H&E）染色後光學顯微鏡下的結核性附睪炎]]
大約90％的結核桿菌感染者是{{link-en|無症狀|asymptomatic}} 、潛伏的（也被稱為潛伏結核感染，LTBI)<ref name=Book90>{{cite book|last=Skolnik|first=Richard|title=Global health 101|year=2011|publisher=Jones & Bartlett Learning|location=Burlington, MA|isbn=978-0-7637-9751-5|pages=253|url=https://books.google.com/books?id=sBQRpj4uWmYC&pg=PA253|edition=2nd}}</ref>， 只有10％的感染者的一生中某個時段會發展成開放性結核病<ref name=Arch2009>{{cite book|last=editors|first=Arch G. Mainous III, Claire Pomeroy,|title=Management of antimicrobials in infectious diseases: impact of antibiotic resistance.|year=2009|publisher=Humana Press|location=Totowa, N.J.|isbn=978-1-60327-238-4|pages=74|url=https://books.google.com/books?id=hwVFAPLYznsC&pg=PA74|edition=2nd rev.}}</ref>。而HIV感染者中有潛伏結核感染的發展為開放性結核病的幾率可增加至每年10％<ref name=Arch2009/>。若未經有效治療，開放性結核病的死亡率可達66％<ref name=WHO2012data>{{cite web|url=http://www.who.int/mediacentre/factsheets/fs104/en/index.html|title=Tuberculosis Fact sheet N°104|publisher=[[World Health Organization]]|date=November 2010|accessdate=26 July 2011}}</ref>。
TB infection begins when the mycobacteria reach the pulmonary alveoli(肺泡), where they invade and replicate within endosomes(核内体)of alveolar macrophages(巨噬细胞).[10][55] Macrophages identify the bacterium as foreign and attempt to eliminate it by phagocytosis(吞噬作用). During this process, the bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. The phagosome then combines with a lysosome to create a phagolysosome. In the phagolysosome, the cell attempts to usereactive oxygen species(活性氧类) and acid to kill the bacterium. However, M. tuberculosis has a thick, waxy mycolic acid capsule that protects it from these toxic substances. M. tuberculosis is able to reproduce inside the macrophage and will eventually kill the immune cell.
肺結核感染始於結核桿菌感染[[肺泡]]，結核桿菌可侵入肺泡並在其[[巨噬細胞]]的[[核內體]]中複製<ref name=Robbins/><ref name=Houben>{{cite journal |vauthors=Houben E, Nguyen L, Pieters J | title=Interaction of pathogenic mycobacteria with the host immune system | journal=Curr Opin Microbiol | volume=9 | issue=1 | pages=76–85 | year=2006 | pmid=16406837 | doi=10.1016/j.mib.2005.12.014 }}</ref>。巨噬細胞辨認結核桿菌為異己並嘗試以[[吞噬作用]]清除。在此過程中，結核桿菌被巨噬細胞包裹并暫時儲存於吞噬體中，即一種膜連型囊泡。之後吞噬體與溶酶體結合，形成吞噬溶酶體。在吞噬溶酶體中細胞嘗試使用[[活性氧類]]及酸來殺死細菌，但結核桿菌有一層蠟狀的厚層{{link-en|黴菌酸|mycolic acid}}構成的囊狀結構，以此保護其自身免於毒性物質的侵害。因此結核桿菌可以在巨噬細胞里複製并最終殺死巨噬細胞。
The primary site of infection in the lungs, known as the "Ghon focus", is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe(肺).[10] Tuberculosis of the lungs may also occur via infection from the blood stream. This is known as a Simon focus and is typically found in the top of the lung.[56] This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones.[10][57] All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the heart(心臟), skeletal muscles(骨骼肌), pancreas(胰脏), or thyroid(甲状腺).[58]
原發性肺結核在肺部好發的部位稱為「[[肺结核原发病灶（Ghon氏病灶）]]」，通常位於[[肺|下葉]]的上半部或是上葉的[[肺|下半部]]<ref name=Robbins/>。結核菌也可能透過血液循環而感染到肺部，通常會感染道肺部的頂部這被稱作「[[Simon氏病灶]]」<ref>{{cite book|last=Khan|title=Essence Of Paediatrics|year=2011|publisher=Elsevier India|isbn=978-81-312-2804-3|pages=401|url=https://books.google.com/books?id=gERCc6KTxwoC&pg=PA401}}</ref>。 血液循環也可能把感染帶到身體其他遠端部位，例如週邊淋巴結、腎臟、腦部和骨骼<ref name=Robbins/><ref name=Herrmann_2005>{{cite journal |vauthors=Herrmann J, Lagrange P |title=Dendritic cells and ’’Mycobacterium tuberculosis’’: which is the Trojan horse? |journal=Pathol Biol (Paris) |volume=53 |issue=1 |pages=35–40 |year=2005|pmid = 15620608 |doi=10.1016/j.patbio.2004.01.004}}</ref>。全身所有部位都有機會被結核菌感染，但是[[心臟]]、[[骨骼肌]]、[[胰臟]]以及[[甲狀腺]]較少受到侵犯，其機制至今未明<ref>{{cite journal |vauthors=Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D |pmc=1090580 |title=Tuberculous dilated cardiomyopathy: an under-recognized entity? |journal=BMC Infect Dis |volume=5 |issue=1 |page=29 |year=2005 |pmid=15857515 |doi=10.1186/1471-2334-5-29}}</ref>。
[[File:Carswell-Tubercle.jpg|thumb|left|upright=90%|{{link-en|Robert Carswell|Robert Carswell (pathologist)}}製作的結節核示意圖<ref name="GoodCooper1835">{{cite book|author1=John Mason Good|author2=Samuel Cooper|author3=Augustus Sidney Doane|title=The Study of Medicine|url=https://books.google.com/books?id=K906AQAAMAAJ&pg=PA32|year=1835|publisher=Harper|page=32}}</ref>]]
Tuberculosis is classified as one of the granulomatous inflammatory diseases. Macrophages(巨噬细胞), T lymphocytes(T细胞), B lymphocytes(B细胞), and fibroblasts(成纤维细胞) aggregate to form granulomas, with lymphocytes(淋巴细胞) surrounding the infected macrophages. When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. The granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system.[60] However, more recent evidence suggests that the bacteria use the granulomas to avoid destruction by the host’s immune system. Macrophages and dendritic cells(樹狀細胞) in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed.[61] Bacteria inside the granuloma can become dormant, resulting in latent infection. Another feature of the granuloma s is the development of abnormal cell death (necrosis(壞死)) in the center of tubercles. To the naked eye, this has the texture of soft, white cheese and is termed caseous necrosis.[60]
結核病被歸類為一種{{link-en|肉芽腫性|granuloma}}炎症。[[巨噬細胞]]、[[T細胞]]、[[B細胞]]以及[[纖維母細胞]]<!-- 及其他細胞 --> 聚集為[[肉芽腫]]，且[[淋巴細胞]]會圍繞受感染的巨噬細胞。其他巨噬細胞會在肺泡囊融合為一個多核的細胞以攻擊受感染的巨噬細胞。肉芽腫的形成可以避免結核桿菌散播，也提供一個局部環境讓免疫系統的細胞之間交互作用<ref name=Grosset />。然而，最近的證據顯示結核桿菌利用肉芽腫避免被宿主免疫系統破壞。巨噬細胞和[[樹狀細胞]]在肉芽腫中無法發揮對淋巴球[[抗原呈現|呈現抗原 ]]的功能，這即導致免疫反應被抑制<ref>{{cite journal | author=Bozzano F | title=Immunology of tuberculosis | journal=Mediterr J Hematol Infect Dis | volume=6 | issue=1 | page=e2014027 | year=2014 | pmid=24804000 | doi=10.4084/MJHID.2014.027 | pmc=4010607 }}</ref>。肉芽腫中的細菌可能休眠，造成潛伏感染。肉芽腫的另一個特色是會造成[[結節]]中心的不正常的細胞[[壞死]]。在肉眼觀察下，這樣的病灶會呈現質地軟類似白色乳酪的壞死，稱為[[乾酪性壞死]]。<ref name=Grosset>{{cite journal |author=Grosset J |title=Mycobacterium tuberculosis in the Extracellular Compartment: an Underestimated Adversary |journal=Antimicrob Agents Chemother |volume=47 |issue=3 |pages=833–6 |year=2003|pmid = 12604509|doi = 10.1128/AAC.47.3.833-836.2003 |pmc=149338}}</ref>。
If TB bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues.[62] This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis.[63] People with this disseminated TB have a high fatality rate even with treatment (about 30%).[21][64]
當結核菌從受感染的組織進入血流，它們可以在身體散佈，並在組織中形成許多細小的白色節結<ref>{{cite book|last=Crowley|first=Leonard V.|title=An introduction to human disease: pathology and pathophysiology correlations|year=2010|publisher=Jones and Bartlett|location=Sudbury, Mass.|isbn=978-0-7637-6591-0|pages=374|url=https://books.google.com/books?id=TEiuWP4z_QIC&pg=PA374|edition=8th}}</ref>。這種嚴重的結核病稱做粟粒狀結核病，最好發的族群是年幼孩童和人類免疫缺陷病毒患者<ref>{{cite book|last=Anthony|first=Harries|title=TB/HIV a Clinical Manual.|year=2005|publisher=World Health Organization|location=Geneva|isbn=978-92-4-154634-8|pages=75|url=https://books.google.com/books?id=8dfhwKaCSxkC&pg=PA75|edition=2nd }}</ref>。罹患這種瀰漫型的結核病，即使經過治療也有很高的死亡率 (大約30%)<ref name=Gho2008>{{cite book|last=Ghosh|first=editors-in-chief, Thomas M. Habermann, Amit K.|title=Mayo Clinic internal medicine: concise textbook|year=2008|publisher=Mayo Clinic Scientific Press|location=Rochester, MN|isbn=978-1-4200-6749-1|pages=789|url=https://books.google.com/books?id=YJtodBwNxokC&pg=PA789}}</ref><ref>{{cite journal|last=Jacob|first=JT |author2=Mehta, AK |author3=Leonard, MK|title=Acute forms of tuberculosis in adults|journal=The American Journal of Medicine|date=January 2009|volume=122|issue=1|pages=12–7|pmid=19114163|doi=10.1016/j.amjmed.2008.09.018}}</ref>。
In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and fibrosis(纤维化).[60]Affected tissue is replaced by scarring and cavities filled with caseous necrotic material. During active disease, some of these cavities are joined to the air passages bronchi(支氣管) and this material can be coughed up. It contains living bacteria, so can spread the infection. Treatment with appropriate antibiotics(抗细菌药) kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.[60]
在大多數的患者中，感染病程起起伏伏。組織的破壞和壞死通常以癒合和[[纖維化]]作結 <ref name=Grosset/>。受侵犯的組織通常會被疤痕或填滿乾酪性壞死的空腔所取代。在開放性肺結核的時期，一些空腔與空氣行經的[[支氣管]]相連，內含的物質就會被咳出來，也包含了結核菌的活體，於是透過這種方式傳播。適當的[[抗細菌藥|抗生素]]治療可以殺死細菌，並讓癒合得以進行。當痊癒時，受感染的區域最終會被疤痕組織取代<ref name=Grosset/>。
Main article: Tuberculosis diagnosis
==診斷==
{{main|{{le|結核病診斷|Tuberculosis diagnosis}}}}
Active tuberculosis
===活動性結核病（開放性結核病）===
Diagnosing active tuberculosis based only on signs and symptoms is difficult,[65] as is diagnosing the disease in those who are immunosuppressed.[66] A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks.[66] A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation.[66] Interferon-γ release assays and tuberculin skin tests are of little use in the developing world.[67][68] IGRA have similar limitations in those with HIV.[68][69]
依據臨床表現和症狀下活動性結核病的診斷是不容易的<ref name=DiagP2011>{{cite journal|last=Bento|first=J |author2=Silva, AS |author3=Rodrigues, F |author4=Duarte, R|title=[Diagnostic tools in tuberculosis]|journal=[[Acta Médica Portuguesa]]|date=Jan–Feb 2011|volume=24|issue=1|pages=145–54|pmid=21672452}}</ref>，如同在免疫低下的個案診斷這類疾病<ref name=Clinic2009>{{cite journal|last=Escalante|first=P|title=In the clinic. Tuberculosis|journal=Annals of Internal Medicine|date=2 June 2009|volume=150|issue=11|pages=ITC61–614; quiz ITV616|pmid=19487708|doi=10.7326/0003-4819-150-11-200906020-01006}}</ref>。當肺部症狀或{{link-en|全身癥狀|constitutional symptoms}}持續超過兩週時，結核病的診斷就應該被考慮<ref name=Clinic2009/>。初步檢查典型包含了{{link-en|胸部X光|Chest radiograph}}、多套針對{{link-en|抗酸菌|Acid-fast}}的{{link-en|痰液培養|sputum culture}}<ref name=Clinic2009/>。丙型干擾素檢驗與結核菌素皮膚測試在開發中國家有一點角色<ref>{{cite journal|last=Metcalfe|first=JZ |author2=Everett, CK |author3=Steingart, KR |author4=Cattamanchi, A |author5=Huang, L |author6=Hopewell, PC |author7=Pai, M|title=Interferon-γ release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis|journal=The Journal of Infectious Diseases|date=15 November 2011|volume=204 Suppl 4|pages=S1120–9|pmid=21996694|doi=10.1093/infdis/jir410|pmc=3192542|issue=suppl_4}}</ref><ref name="Sester 100–11">{{cite journal|last=Sester|first=M |author2=Sotgiu, G |author3=Lange, C |author4=Giehl, C |author5=Girardi, E |author6=Migliori, GB |author7=Bossink, A |author8=Dheda, K |author9=Diel, R |author10=Dominguez, J |author11=Lipman, M |author12=Nemeth, J |author13=Ravn, P |author14=Winkler, S |author15=Huitric, E |author16=Sandgren, A |author17=Manissero, D |title=Interferon-γ release assays for the diag
nosis of active tuberculosis: a systematic review and meta-analysis|journal=The European Respiratory Journal|date=January 2011|volume=37|issue=1|pages=100–11|pmid=20847080|doi=10.1183/09031936.00114810}}</ref>。丙型干擾素檢驗有些侷限，如同它在人類免疫缺陷病毒的角色一般<ref name="Sester 100–11"/><ref>{{cite journal|last=Chen|first=J|author2=Zhang, R |author3=Wang, J |author4=Liu, L |author5=Zheng, Y |author6=Shen, Y |author7=Qi, T |author8=Lu, H |title=Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis|journal=PLoS ONE|year=2011|volume=6|issue=11|pages=e26827|pmid=22069472|doi=10.1371/journal.pone.0026827|pmc=3206065|editor1-last=Vermund|editor1-first=Sten H}} {{open access}}</ref>。
A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample (e.g., sputum, pus(膿), or a tissue(组织 (生物学))biopsy(活體組織切片)). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture.[70] Thus, treatment is often begun before cultures are confirmed.[71]
要在檢體（痰、[[膿]]或[[活體組織切片]]）上確認到結核菌，才算是確定診斷患有結核病。然而因為結核桿菌生長速度緩慢，培養困難，來自血液或痰液的培養需要2至6週的時間<ref>{{cite book|last=Diseases|first=Special Programme for Research & Training in Tropical|title=Diagnostics for tuberculosis: global demand and market potential.|year=2006|publisher=World Health Organization on behalf of the Special Programme for Research and Training in Tropical Diseases|location=Geneva|isbn=978-92-4-156330-7|pages=36|url=https://books.google.com/books?id=CFPpcCef4yQC&pg=PA36}}</ref>，所以治療往往在培養結果確認之前就開始了<ref name=NICE2011/>。因細菌學檢查後，檢體內有結核菌，此時病人具傳染性，為結核病防治的對象（稱為傳染性結核病或開放性結核病）。痰細菌學檢查一般採用塗片抗酸菌染色及結核菌培養二種方式，痰塗片可偵測出痰中細菌量大的病人；至於痰中細菌量小的病患，即痰塗片陰性者，可藉由痰培養發現細菌。經過研究顯示，同樣是培養陽性的病患，塗片陽性者的傳染性是塗片陰性者二倍以上。<ref name=":1">{{Cite web|url=http://www.cdc.gov.tw/diseaseinfo.aspx?treeid=8d54c504e820735b&nowtreeid=dec84a2f0c6fac5b&tid=BAB48CF8772C3B05|title=傳染病介紹 結核病|accessdate=2016-07-10|author=|date=|publisher=衛生福利部疾病管制署}}</ref>。
Nucleic acid amplification tests and adenosine deaminase(腺苷脫氨酶) testing may allow rapid diagnosis of TB.[65] These tests, however, are not routinely recommended, as they rarely alter how a person is treated.[71] Blood tests to detect antibodies are not specific or sensitive(靈敏度和特異度), so they are not recommended.[72]
{{link-en|核酸扩增试验|Nucleic acid amplification test}}及[[腺苷脱氨酶检测]]檢驗可以提供結核病快速診斷<ref name=DiagP2011/>。不過因為這些檢驗方式鮮少改變病人的治療計畫，所以不是例行性的建議檢驗項目<ref name=NICE2011/>。檢驗血中的抗體因為[[靈敏度和特異度]]不出色，所以也不是建議的檢驗項目<ref>{{cite journal|last=Steingart|first=KR|coauthors=Flores, LL, Dendukuri, N, Schiller, I, Laal, S, Ramsay, A, Hopewell, PC, Pai, M|title=Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis|journal=PLoS medicine|date=August 2011|volume=8|issue=8|pages=e1001062|pmid=21857806|doi=10.1371/journal.pmed.1001062|pmc=3153457|editor1-last=Evans|editor1-first=Carlton}}</ref>。
Latent tuberculosis
Main article: Latent tuberculosis
===潛伏結核病（非開放性結核病）===
{{main|{{le|非開放性結核病|Latent tuberculosis}}}}
[[File:Mantoux tuberculin skin test.jpg|thumb|[[結核菌素試驗]]]]
Mantoux tuberculin skin test(结核菌素试验)
[[結核菌素試驗]]
The Mantoux tuberculin skin test(结核菌素试验) is often used to screen people at high risk for TB.[66] Those who have been previously immunized may have a false-positive test result.[73] The test may be falsely negative in those with sarcoidosis(结节病), Hodgkin’s lymphoma(霍奇金淋巴瘤), malnutrition(營養不良), and most notably, active tuberculosis.[10] Interferon gamma release assays (IGRAs), on a blood sample, are recommended in those who are positive to the Mantoux test.[71] These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive(第一型及第二型錯誤) results.[74] However, they are affected by M. szulgai, M. marinum, and M. kansasii.[75] IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone.[76]
[[結核菌素試驗]] 通常應用於篩檢結核病的高危險群<ref name=Clinic2009/>。先前接受過疫苗的人可能會有偽陽性的檢驗結果<ref name=Rothel_2005>{{cite journal|vauthors=Rothel J, Andersen P |title=Diagnosis of latent ’’Mycobacterium tuberculosis’’ infection: is the demise of the Mantoux test imminent?|journal=Expert Rev Anti Infect Ther |volume=3 |issue=6 |pages=981–93 |year=2005|pmid = 16307510|doi = 10.1586/14787210.3.6.981}}</ref>。罹患 [[結節病]]、[[霍奇金淋巴瘤]]或是[[營養不良]]的人，以及最需要注意的活動性結核病患者，可能會有偽陰性的檢驗結果<ref name=Robbins/>。抽血做{{link-en|丙型干擾素檢驗|Interferon gamma release assays}}（IGRAs）建議應用於結核菌素試驗陽性的個案<ref name=NICE2011>{{NICE|117|Tuberculosis|2011}}</ref>。丙型干擾素檢驗不會因為先前接種過疫苗或是大部分{{link-en|非結核性分枝桿菌|Nontuberculous mycobacteria}}而產生{{link-en|偽陽性|第一型及第二型錯誤}}<ref>{{cite journal|vauthors=Pai M, Zwerling A, Menzies D |title=Systematic Review: T-Cell–based Assays for the Diagnosis of Latent Tuberculosis Infection: An Update |journal=Ann. Intern. Med. |volume=149 |issue=3 |pages=1–9 |year=2008 |pmid=18593687 |pmc=2951987|doi=10.7326/0003-4819-149-3-200808050-00241}}</ref>。然而可能會受到M. szulgai、M. marinum 以及 M. kansasii干擾<ref>{{cite book|last=Jindal|first=editor-in-chief SK|title=Textbook of Pulmonary and Critical Care Medicine|publisher=Jaypee Brothers Medical Publishers|location=New Delhi|isbn=978-93-5025-073-0|pages=544|url=https://books.google.com/books?id=rAT1bdnDakAC&pg=PA544|year=2011}}</ref> 。丙型干擾素檢驗合併皮膚測試可以提高敏感度，然而單獨使用丙型干擾素檢驗的敏感度確比皮膚試驗還要低<ref>{{cite journal|last=Amicosante|first=M|author2=Ciccozzi, M |author3=Markova, R |title=Rational use of immunodiagnostic tools for tuberculosis infection: guidelines and cost effectiveness s
tudies|journal=The new microbiologica|date=April 2010|volume=33|issue=2|pages=93–107|pmid=20518271}}</ref>。
Tuberculosis prevention and control efforts rely primarily on the vaccination of infants and the detection and appropriate treatment of active cases.[11] The World Health Organization(世界卫生组织) has achieved some success with improved treatment regimens, and a small decrease in case numbers.[11]
==預防==
肺結核的預防與控制主要依靠在嬰兒時期的疫苗注射及對於感染病例的檢測及適當治療[11]。[[世界衛生組織]]已藉著改善治療方法達到些許成效，並使感染人數有小幅度的下降[11]。
Vaccines
Main articles: Tuberculosis vaccines and BCG vaccine(卡介苗)
The only available vaccine(疫苗) as of 2011 is Bacillus Calmette-Guérin(卡介苗) (BCG).[77] In children it decreases the risk of getting the infection by 20% and the risk of infection turning into disease by nearly 60%.[78]
===疫苗===
{{main|肺結核疫苗}}及{{main|卡介苗}}
直到2011年為止，仍只有卡介苗作為被使用的疫苗[77]。在接種疫苗的孩童中，卡介苗可降低20%的被感染風險值並降低將近60%的感染後發病風險值[78]。
It is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated(疫苗接種).[11] The immunity it induces decreases after about ten years.[11] As tuberculosis is uncommon in most of Canada, the United Kingdom, and the United States, BCG is administered only to those people at high risk.[79][80][81] Part of the reasoning against the use of the vaccine is that it makes the tuberculin skin test(结核菌素试验) falsely positive, reducing the test’s use in screening.[81] A number of new vaccines are currently in development.[11]
卡介苗是全世界被運用的最廣泛的疫苗，有超過90%的孩童有[[疫苗接種]] [11]。卡介苗的免疫作用在大約10年後會逐漸下降[11]。當肺結核在加拿大、英國及美國不再普遍，卡介苗只會被使用在肺結核高風險的群眾上[79][80][81]。反對使用卡介苗的部分因素是因為它會造成[[結核菌素試驗]]產生偽陽性的結果，減少此試驗的使用[81]。目前有許多新的肺結核疫苗正在研發當中[11]。
Public health
The World Health Organization declared TB a "global health emergency" in 1993,[11] and in 2006, the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between its launch and 2015.[82] A number of targets they have set are not likely to be achieved by 2015, mostly due to the increase in HIV-associated tuberculosis and the emergence of multiple drug-resistant tuberculosis.[11] A tuberculosis classification system developed by the American Thoracic Society(美国胸腔学会) is used primarily in public health programs.[83]
===公共衛生===
世界衛生組織在1993年時宣布肺結核疫情進入全球性的緊急狀態[11]，在2006年the Stop TB Partnership發起了{{le|全球結核病防治計畫|Global Plan to Stop Tuberculosis}}，希望能在2006年到2015年之間救治一千四百萬條生命[82]。在2015年，由於許多HIV感染的肺結核患者增加及多重抗藥性結核病所造成的影響，使它們許多目標未達成[11]。[[美國胸腔協會]]制定的{{le|結核病分級標準 |tuberculosis classification}}已被廣泛運用在公共衛生計畫當中。 [83]
Main article: Tuberculosis management
Treatment of TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective.[84] The two antibiotics most commonly used are isoniazid(异烟肼) and rifampicin(利福平), and treatments can be prolonged, taking several months.[51] Latent TB treatment usually employs a single antibiotic,[85] while active TB disease is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance(抗生素抗藥性).[11] People with latent infections are also treated to prevent them from progressing to active TB disease later in life.[85] Directly observed therapy, i.e., having a health care provider watch the person take their medications, is recommended by the WHO in an effort to reduce the number of people not appropriately taking antibiotics.[86] The evidence to support this practice over people simply taking their medications independently is poor.[87] Methods to remind people of the importance of treatment do, however, appear effective.[88]
==治療==
結核病的治療通常使用[[抗細菌藥|抗生素]]，但由於結核分枝桿菌細胞壁成分和構造較為特殊，藥物較難進入病原體中，因此難以發揮藥效[84]。目前最常用的抗生素為[[异烟肼]]（Isoniazid）及[[利福平]]（Rifampin），且通常需服藥長達數月[51]。潛伏性結核病通常可給予單一抗生素治療，而活動性肺結核則最好同時合併使用多種抗生素治療，以減少結核菌產生[[抗生素抗藥性|抗藥性]]的風險[11]。除活動性結核病患者外，潛伏性結核病患者也建議進行治療，以避免在未來惡化為活動性結核病[85]。結核病的治療需要長期不間斷的服藥，自行中斷服藥或忘記服藥容易導致治療失敗。因此[[世界衛生組織]]建議實施「{{le|都治計畫|Directly observed therapy}}」（DOTs），即由醫療照護人員親自定期送藥，監督患者確實服藥[86]。中華民國衛生福利部的資料顯示，實施都治計畫能有效降低治療失落率，與對照組比較起來也能明顯提升治療成功率[中1]。
New onset
The recommended treatment of new-onset pulmonary tuberculosis, as of 2010, is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide(吡嗪酰胺), and ethambutol(乙胺丁醇) for the first two months, and only rifampicin and isoniazid for the last four months.[11] Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative.[11]
==首次發病==
截至2010年，肺結核首次發病的建議療法是六個月的抗生素綜合治療，首兩個月使用[[利福平]]、[[異煙肼]]（Isoniazid）、[[吡嗪酰胺]]（Pyrazinamide）及乙胺丁醇（Ethambutol）；最後四個月只使用利福平和異煙肼[11]。如果對異煙肼的抗藥性高，乙胺丁醇可以被用做最後四個月的取代[11]。
Recurrent disease
If tuberculosis recurs, testing to determine to which antibiotics it is sensitive is important before determining treatment.[11] If multiple drug-resistant TB is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended.[11]
==復發==
如果肺結核復發，在選擇治療方法前測試細菌對哪些抗生素有敏感性很重要[11]。如果檢驗出細菌對多種藥物有抗藥性，建議使用最少四種有效的抗生素進行18到24個月的療程[11]。
Medication resistance
Primary resistance occurs when a person becomes infected with a resistant strain of TB. A person with fully susceptible MTB may develop secondary (acquired) resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately (lack of compliance), or using low-quality medication.[89] Drug-resistant TB is a serious public health issue in many developing countries, as its treatment is longer and requires more expensive drugs. MDR-TB is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB(广泛耐药结核) is also resistant to three or more of the six classes of second-line drugs.[90] Totally drug-resistant TB is resistant to all currently used drugs.[91] It was first observed in 2003 in Italy,[92] but not widely reported until 2012,[91][93] and has also been found in Iran and India.[94][95] Bedaquiline is tentatively supported for use in multiple drug-resistant TB.[96]
XDR-TB is a term sometimes used to define extensively resistant TB, and constitutes one in ten cases of MDR-TB. Cases of XDR TB have been identified in more than 90% of countries.[94]
===抗藥性====
原發性抗藥性肺結核發生在受具抗藥性肺結核菌株感染的人中。帶有易受觸動的結核分枝桿菌的人可能在治療過程中因治療不足、沒有正確按醫囑服藥或藥物品質低劣而得到多發性肺結核[89]。抗藥性肺結核在很多發展中國家是一個嚴重的公共衛生議題，因為這延長療程及需要較昂貴藥物。
多重抗藥性結核病（MDR-TB）的定義是結核菌同時對兩種最有效的第一線藥物利福平(rifampicin)和異煙肼(isoniazid)具抗藥性。[[广泛耐药结核]]是指同時對三種以上或六類第二線藥物具抗藥性[90]。完全抗藥性肺結核是指對所有用作治療的藥物具抗藥性[91]。它於2003年在義大利[92]首次被發現，也在伊朗和印度[94][95]有案例，不過到2012年才有廣泛報告[91][93]。Bedaquiline 暫時受到認受作為治療多重抗藥性結核病的藥物[96]。
在每十宗多重抗藥性結核病裡，就有一例是廣泛耐藥結核。廣泛耐藥結核在超過九成國家中有病例[94]。