Upload
others
View
16
Download
0
Embed Size (px)
Citation preview
Active TB disease
• Latent TB infection progresses to active TB in
– 感染後馬上發病 (primary progression)
– 5%感染後兩年內發病
– 5%感染兩年以後發病
• 90% 終身Latent TB
• Risk greater if cell-mediated immunity impaired
Chest Radiograph
• Abnormalities often seen in apical
or posterior segments of upper
lobe or superior segments of
lower lobe
• May have unusual appearance in
HIV-positive persons
• Cannot confirm diagnosis of TB
Arrow points to cavity in
patient's right upper lobe.
檢體採集
• Obtain 3 sputum specimens for smear examination and culture
• Persons unable to cough up sputum, induce
sputum, bronchoscopy or gastric aspiration
• Follow infection control precautions during
specimen collection
Smear Examination
• Strongly consider TB in patients with smears
containing acid-fast bacilli (AFB)
• Results should be available within 24 hours of
specimen collection
• Presumptive diagnosis of TB
What Does AFB Smear Tells Us?
IF positive, it is TB or NTM (Non-TB
Mycobacterium) infection.
If negative, no infection or infection but less
than 105 AFB/ml in the specimen
50% culture-positive are Smear-negative
Still it is the Most Widely Used Test Worldwide
And has had a Great Role in TB Diagnosis
1.A minimum of 100,000 tubercle bacilli per
millilitre of sputum are necessary to be seen on
microscopy.
2.Apparently only a few hundred bacilli per millilitre
of sputum are sufficient to be detected by culture.
BACTERIOLOGY
Cultures
• Use to confirm diagnosis of TB
• Culture all specimens, even if smear negative
• Results in 4 to 14 days when liquid medium
systems used
Colonies of M. tuberculosis growing on media
Different Culture Media
The Old Way
Egg-base. LJ, Ogawa, and Others
Agar-base. Middlebrook.
BACTEC 12B Radiometric
BACTEC 460 has become a “GOLD Standard”
for culture and Susceptibility testing
The New Way
Non-radiometric liquid culture systems
Latent TB infection
• Tuberculin skin test usually positive at 2-10
weeks
• Tubercle bacilli may remain dormant but viable
for many years
• No symptoms of active TB disease
• Not infectious
• Usually no progression in 90% of persons
Administering the Tuberculin Skin Test
• Inject intradermally 0.1 ml of 5
TU PPD tuberculin
• Produce wheal 6 mm to 10 mm
in diameter
• Do not recap, bend, or break
needles, or remove needles from syringes
• Follow universal precautions for infection control
Reading the Tuberculin Skin Test
• Read reaction 48-72 hours after injection
• Measure only induration
• Record reaction in millimeters
不同結核病患接觸者皮膚結核菌素測驗結果
塗片培養均陽性*
塗片陰性培養陽性
非開放性病人
無接觸對照組
Group
tested
374
228
221
709
感染數
244
61
39
157
No. of person tested
檢查人數
世界衛生組織資料 1976
%
65.2
26.8
17.7
22.1
Reactors
*P<0.0001(差異具統計學意義)
10-14歲兒童
Important!!!
Choose a right method!
• Active infection
– Acid fast stain
– Culture
– Molecular
detection
• In house PCR
• Genprobe
• Latent infection
– Tuberculin skin
test
g interfetron assay
– ELISPOT
– T SPOT
Hypocrites (460-
370 BC) and the
Kos School
• tuberculosis, or consumption.
• A morbid process characterized by
progressive debilitation, coughing,
hemoptysis, and suppurating lung
lesions.
The answer for a cure is in Nature
• The main goal of the doctor treating
tuberculosis was to avoid hindering
natural cures.
• Continual rest, a balanced diet, and
abstaining from anything in excess
including sex were considered crucial.
休養, 均衡飲食與禁慾
• Bloodletting to drain contaminated blood
from the infected lung,
• thoracic poultices,
• “sandacara” pollen (from Cupressaceae
plants),
• drinking wine to induce coughing and
suppurating from lung lesions,
• thoracentesis preformed with a sharp
knife to drain fluid from the lung.
In 1860, Hermann Brehmer from Germany
started the first center in Gobersdorf
• to cure tuberculosis by rest. • The mountain fresh air and over-feeding in
an establishment more like a luxury hotel than a hospital would strengthen the patient.
• Villemin, 1865, established that the disease
was infectious.
– An Army Doctor.
– Young solider in Barracks got TB.
– Rabbit experiment
Collapsing the lung
• In 1888, an Italian, Carlo Forlanini
preformed the first intentional
spontaneous pneumothorax using a
needle to puncture the pleual cavity and
then administering nitrogen.
結核菌
學名:Mycobacterium tuberculosis
1882年科霍發現結核菌
耐酸菌(acid-fast bacilli)
細胞壁富於脂質而會妨害色素通過, 因而不易染色, 一旦染色不易被強酸脫色, 故又稱耐酸菌
分裂速度慢(1次/20hrs)
潮濕陰暗處可存活 6-8 個月, 陽光直接照射 4-6
小時死亡, 煮沸5分鐘可殺死
結核病治療的里程碑
SM 1944 開始
治療進步但產生抗藥性
BMJ 1948 2:p769-782
PAS 1943 開始
# PAS + SM 避免了SM 抗藥性
# 確立TB 化學治療原則:多種藥物合併治療
INAH in 1951開始
兩階段治療的觀念
INH+PAS+SM
INH+PAS
抗結核藥物
• First-line Anti-tuberculosis Drugs
– Isoniazid (INH)
– Rifampin (RMP)
– Pyrazinamide (PZA)
– Ethambutol (EMB)
初次治療常規用藥
區分為初治或再治病人
• 新病人 (New case):不曾接受過抗結核藥治療或曾接受少於四週抗結核藥治療之病人。
• 再治病人(Retreatment case) – 復發 (Relapse):曾接受一個完整療程之抗結核藥治療並經
醫師宣告治癒而再次痰塗片或培養陽性之病人。
– 失落再治 (Treatment after default):中斷治療兩個月以上而再次痰塗片或培養陽性之病人。
– 失敗再治 (Treatment after failure):治療五個月後依然痰塗片或培養陽性的病人,或者治療前痰陰性、治療二個月後變成痰塗片或培養陽性的病人。
疾病管制局: 結核病診治指引
Drug Resistance of MTB for each Treatment
Category in Taiwan
0
10
20
30
40
50
60
70
Treatment failure Default Relapse New case *
MDR Any drug
Chiang CY,et al. Formos Med Assoc, 2004.
* Jen-Jyh Lee et al, Tzu Chi Med J, 2003.
結核病初次治療 *
• 標準治療
– 2HRZE/4HRE
– 每日一次口服
– 前 2 個月 INH+RMP+PZA+EMB
– 後 4 個月 INH+RMP+EMB
* 適用初治新案 (new case):不曾接受過抗結核藥治療或曾接受少於 4 週抗結核藥治療之病人。
如證實無 INH 或 RMP
抗藥, 則停用 EMB
•Rifater (each tab)
= INH 80mg
+ RMP 120mg
+ PZA 250mg
>=50kg 每日5錠
體重每減10kg 減1錠
Rifater (RFT) + EMB Rifinah (RFN) + EMB
•Rifinah300 (each tab)
= RMP 300mg + INH 150mg
•Rifinah150 (each tab)
= RMP 150mg + INH 100mg
>=50kg RFN300 每日2錠
<50kg RFN150 每日3錠
Fixed Drug Combination
若病人45kg, INH: 5*45=225, RIF: 10*45=450
3錠[RFN150] : INH 300, RIF 450
1錠[RFN150]+ 1錠[RFN300] : INH:250, RIF:450
也可 2.5錠INH 100*2.5=250, 3錠RIF 150*3=450
如果劑量過高, 容易副作用
若您是病人, 您會選哪種?
治療效果評估
• 門診評估症狀及病人服藥順從性:
– 治療第1個月至少應回診2次,以後每月至少1次。
• 結核菌檢查
– 痰抹片耐酸菌鏡檢及結核菌培養:
• 每個月至少檢查1次,直到連續2個月培養陰性;
• 治療滿6個月時再檢查1次。
– 菌種鑑定:
• 每次培養陽性均應作菌種鑑定。
• 藥物敏感性試驗:
– 第1次培養陽性的菌株,
– 治療滿3個月後仍培養陽性的菌株。
疾病管制局: 結核病診治指引, 2006 第二版
When to suspect MDR-TB?
Chavez AM, Blank R, Smith Fawzi MC, et al. Identifying early treatment failure on Category I therapy for pulmonary tuberculosis in Lima Ciudad, Peru. Int J Tuberc Lung Dis 2004; 8: 52-8.
Standards for Treatment
• Patients who have positive smears during the fifth month of treatment should be considered as treatment failures and have therapy modified appropriately.
• 治療第五個月仍痰陽性, 很可能治療失敗
• 需區分NTM非結核分枝桿菌之可能性
治療前評估 *
Never treat multidurg-resistant TB
(MDR-TB) without expert consultation
TB Case
標準初次
治療 照會專業醫師
Y
N
過去治療史
新案
•Return after default
•Relapse
•Failure
•Chronic case
WHO. Treatement of tuberculosis, 3nd ed. 2003. WHO/CDS/TB 2003.313
* 依過去治療史分類
初治 再治
Old WHO recommendations (before 2010)
Regimen Indications
4HREZ/2HR
(Category I) New cases
2SHREZ/1HREZ/5HRE
(Category II)
Retreatment cases
• Default • Relapse after cure
or completion
MDR-TB in Category I treatment failure
1. Becerra MC et al. Int J Tuberc Lung Dis. 2000; 4(2): 108-14.
2. Fitzwater SP et al. Clin Inf Dis 2010; 51(4):371–37.
3. Quy HT et al. Int J Tuberc Lung Dis 2003; 7: 631-636.
4. Gler MT et al. Int J Tuberc Lung Dis 2011; 15: 652-656.
Study Country
Proportion of MDR-
TB in Category I
treatment failure
Becerra et al.1 Peru 94%
Fitzwater et al.2 Peru 100%
Quy et al.3 Vietnam 80%
Gler et al.4 Philippines 83%