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Pulmonary Tuberculosis 肺結核

Pulmonary Tuberculosis 肺結核. 台中榮總 胸腔內科. 一個國家結核病已被控制的標準 ( WHO). 死亡率 : 每十萬人口2人以下 (台灣 5.80 人, 2003 年) 盛行率 : 20歲以上人口0.143%以下 (台灣 0.113% , 2002 年) 感染率 : 14歲兒童在1%以下 (台灣6歲兒童 0.43%,2002 年). Mycobacterium Tuberculosis 結核分枝桿菌. 細菌特性 Characters. Aerobic 嗜氧性

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Pulmonary Tuberculosis 肺結核

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  1. Pulmonary Tuberculosis肺結核 台中榮總 胸腔內科

  2. 一個國家結核病已被控制的標準(WHO) • 死亡率 : 每十萬人口2人以下 (台灣 5.80人,2003年) • 盛行率 : 20歲以上人口0.143%以下 (台灣 0.113%,2002年) • 感染率 : 14歲兒童在1%以下 (台灣6歲兒童 0.43%,2002年)

  3. Mycobacterium Tuberculosis結核分枝桿菌

  4. 細菌特性Characters • Aerobic嗜氧性 • 大小 0.5 x 3 um in size, Slow growing 生長緩慢- 每 25 to 32 hours 分裂一次 • Acid fastness 耐酸性,不易被強酸脫色，故又 稱耐酸菌 (mycolic acid & Lipoarabinomannan in cell wall) • 人体免疫反應為Cell-mediated immune response 需要2-12 weeks (103-104隻菌)

  5. Transmission 傳染途徑 • 結核病之傳染媒介為空氣中的飛沫Spread through air by droplet nuclei (<5μm) • 2-3 M. tuberculosis in each droplet • 傳染性肺結核病人講話、唱歌、咳嗽、或打噴 嚏時Cough, sneeze, speak or sing • Number of organisms 細菌數量, concentration 濃度, length of exposed time暴露時間, immune status of exposed host 宿主免疫

  6. Transmission 傳染途徑

  7. Limiting the Transmission 減少傳染 • Ventilation with fresh air 保持空氣新鮮通暢 • Ultraviolet irradiation 紫外線消毒 • Treating the infected patient with effective anti-TB chemotherapy 治療感染源 • Mask - filter function, fit tightly被動防護﹕口罩 • 卡介苗BCG

  8. Transmission

  9. After Infection .. • 受到結核菌感染後約六至八週，皮膚結核菌素 試驗由陰性轉為陽性 • 通常並不立即發病，新感染後每年約有2-4%的 發病機會，以後每年發病機會逐年遞減(共約10%) 。 • 結核病好發在肺部，而全身各器官，如骨、 腎、淋巴、腦、皮膚、生殖器官等，都會發病 • 一部分的肺結核病人發展成傳染性病人，再傳 染給別人。

  10. Pathogenesis 致病機轉 • 巨噬細胞Macrophage - first line immunity • DTH - delayed-type hypersensitivity; CD8+ Killing infected M • CMI - cell-mediated immunity; CD4+ M activation & intracellular killing • 乾酪性肉芽腫Caseating granuloma formation - 乾酪性壞死Caseous necrosis

  11. 細菌分布 • Actively growing extracellular organism (response for drug resistance), 存在於氧氣充足之空洞病灶(Cavity), 含菌量約 107- 109 • Slowly growing organisms inside macrophage at an acid pH, 存在於氧氣不足之Macrophage,含菌量約104 - 105 • Slowly growing organism at a neutral pH in solid caseous areas 存在於氧氣較少之封閉性乾酪病灶含菌量約104 - 105

  12. Host Factors 宿主免疫狀態 • Old age, adolescence, infants 年齡 • Malnutrition, DM, s/p gastrectomy • Pregnency, Steroid usage 賀爾蒙 • Silicosis 矽肺症 • Immunosuppressive drugs 免疫抑制劑 • Lymphoma, uremia • AIDS 愛滋病

  13. Diagnosis • 臨床表徵 • 胸部X光 • 結核菌素試劑 • 組織病理學檢查 • 臨床檢體之抹片、培養、鑑定 • 快速診斷法:如 BACTEC, PCR, serology

  14. Constitutional Fever 發燒(late afternoon) 食慾不振 Night sweats BW loss 體重減輕 Malaise, fatigue, etc.. Pulmonary Cough 咳嗽 Sputum (hemoptysis)吐痰, 喀血 Chest pain (pleuritic) Dyspnea, etc.. Clinical Manifestation臨床表徵

  15. Chest X-ray • 千變萬化 • Initial tuberculous complex • Reactivation • Advanced, mycetoma • Atelectasis, bronchiectasis • Miliary TB

  16. 肺結核 X光診斷定義 • 輕度肺結核 - 輕微散在之病灶，面積總和不超過一側肺之[前以第二肋軟骨聯合，後以第五胸椎体為準之水平線以上區域內]。 • 中度肺結核 - 合於以下三种情形之一1. 散在之病灶，面積總和不超過一側肺2. 融合塊狀病灶，總和不超過一側肺之1/33. 有空洞，直徑總和不超過 4cm • 重度肺結核 - 病灶超過中度範圍者。

  17. Primary TB

  18. Reactive TB

  19. Advanced TB

  20. Miliary TB

  21. 皮膚結核菌素試驗Tuberculin Skin Test • PPD - Purified protein derivative, 5TU 0.1cc • Intra-dermal injection • Delayed hypersensitivity • 6-8 weeks after infection • Max. induration - 48-72 hrs • False negative - 25% • False positive - BCG, NTM • 未接種卡介苗者反應≧10 mm者為陽性，＜10 mm者為陰性；已接種卡介苗者反應≧18 mm者為陽性，＜18 mm者為陰性

  22. Specimens Collection 標本收集 • Natural sputum >= 3 early morning samples • Induced sputum - by hypertonic saline, nebulizer(environmental control) • Gastric lavage - 50ml • Urine - morning voided midstream specimen • Digestion and decontamination

  23. Acid Fast Stain • AFB No. Report1-2/300 fields +/-1-9/100 fields 1+1-9/10 fields 2+1-9/field 3+>9/field 4+ • 抹片陽性者，每西西痰約有5000-10000隻以上的細菌 • 培養陽性者，每西西痰約有10-100隻以上的細菌 • Sensitivity 50-80%

  24. Culture • Lowenstein-Jensen (egg)(4-8weeks) • Middlebrook7H10, 7H11 (agar) (4-8weeks) • Middlebrook 7H12 (liquid)(2weeks) • Sensitivity 85%

  25. Rapid Tests 快速診斷 • BACTEC - radiometric or colorimetric growth detection, 1-3 weeks (BACTEC 460, MGIT 960) • Serologic test - ELISA, radioimmunoassay • Amplication of nucleic acid - 5-6 hours PCR - rRNA , pacuibacillary, extrapulmonaryTMA, LCR • DNA fingerprinting, RFLP (nosocomial outbreak, laboratory cross-contamination)

  26. Multiple Drug Resistant TB 抗葯性結核 • In Taiwan, The overall drug resistance rate : 23.1% • Resistant rates : SM 4.9% ; INH 9.2%; EMB 1.9%; RIF 1.9% • Multiple drug resistance : resistant to INH & RIF1.9% • Successful treatment : 53.8%

  27. 卡介苗 BCG (Bacillus Calmette-Guerin) • 卡介苗是一種活的牛型結核桿菌，經減毒後注 入人體，不會使人致病，但可產生對結核病的 抵抗力 。 • 卡介苗是一種預防工具，尤其是預防 粟粒性結核及死亡率非常高的結核性腦膜炎 。 對一般成人的肺結核無有效證據證明有預防效果 。 • 卡介苗目前在台灣的地位

  28. Mycobacteria Other Than Tuberculosis (MOTT) or NTM • M. Kansasii - INH, RIF, EMB • M. avium complex (MAC) - Klaricid, RIF, EMB, SM • Other slow growing NTM • Rapidly growing NTM - Klaricid, amikacin • Colonization of of chronic airway disease • Symptomatic patients with progression of CXR finding (esp. HIV(+) patients).

  29. 院內感染結核 • Inpatient medical or HIV ward 內科或愛滋病房 • Emergency departments 急診室 • Outpatient HIV clinic • Intensive care units 加護病房 • Autopsy rooms 解剖室 • Operating room 手術室 • Renal transplant unit 腎臟移植中心

  30. 院內感染結核 - 那些病人... • TB of lung, airways, or larynx • With cough or forceful expiratory measures • Failure to cover the mouth when coughing • Sputum smear AFS (+) • Absence of therapy, just started Tx, poor response • CXR - cavitation • Procedures inducing cough or aerosolization

  31. 院內感染結核相關因子 • Undiagnosed, untreated pulmonary TB • TB not suspected • Laboratory delay • Concomitant infection obscuring diagnosis • Delayed recognition of muti-drug resistant TB • Inadequate ventilation • Recirculation of contaminated air • Inadequate ventilation rate • No negative pressure

  32. 院內感染結核相關因子 • Malpractice of tuberculosis isolation • TB patients leaving the room • Door left open • Shared bathroom • Inadequate precautions for cough inducing procedure • Endotracheal intubation • Endotracheal suction • Bronchoscopy • Aerosol therapy

  33. 院內感染結核相關因子 • Lack of adequate respiratory protection • mask • Immunocompromised host • AIDS • s/p transplant • Tuberculosis abscess or skin ulcer • Autopsy

  34. 結核病治療的演進 • 19th 世紀中葉，結核病療養院 ﹕乾燥而新鮮 的空氣、適度運動及休養 • 塌陷治療(Collapse Therapy)，藉著人工氣胸 (Artificial Pneumo-thorax)、胸廓成形術 (Thoraco-plasty)、或合併肺葉切除，企圖將肺 內的空洞塌陷或切除，降低結核菌繁殖的速 度或減少結核菌的數目

  35. 結核病治療的演進 • 1944年 - 鏈黴素(Streptomycin) 開始結核病化學藥物治療的紀元 • 1949年 - 發現合併使用多種抗結核藥物來治 療結核病的重要性 • 1952年 - 發現Isoniazid • 1962年 - 發現每週２至３次間歇治療可達到 同樣的治療效果 • 1972年 - Rifampin 及 Isoniazid 之合併治療 ，可在１年以內即治癒結核病，短程治療成為 結核病治療的主流 。

  36. Chemotherapy of Tuberculosis • Active growing Intracellular Slow growing Extracellular Extracellular • Rifampin + + + • INH + + - • Streptomycin + - - • PZA - + -

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