Diagnosis of Pulmonary Tuberculosis

1. Diagnosis of Pulmonary Tuberculosis Presenter: 4A Ri范綱志 Sep. 29,2008

2. Why diagnosis important? • Diagnosis of tuberculosis in most cases • clinical diagnosis based upon the clinical presentation (hx & PE) • In 15-20% of p’t with suspected TB • lab confirmation never obtained • Early diagnosis and initiation of effective therapy • reducing morbidity and mortality from TB • minimize the spread of infection

3. Outline • Screening for prior infection • Tuberculin skin test • Diagnosis of pulmonary TB • Medical history • Physical examination • Chest radiograph • Bacteriologic exam

4. Screening for prior infectionTuberculin skin test 篩出感染者

5. Screening for prior infection • Whom to screen • High prevalence and high risk population (HIV) • How to screen • Mantoux tuberculin test (ie, purified protein derivative or PPD, tuberculin skin test) • How to interpret • Determine maximum diameter of induration by palpation

6. Mantoux Tuberculin Test • Preferred method of testing for TB infection in adults and children • Tuberculin skin testing useful for • Examining person who is not ill but may be infected • Determining how many people in group are infected • Examining person who has symptoms of TB

7. Mantoux test • Inject intradermally 0.1 mlof 5TU PPD tuberculin • Produce wheal 6 mm to 10mm in diameter • Represent DTH (delayed type hypersensitivity)

8. Reading of Mantoux test • Read reaction 48-72 hours after injection • Measure only induration • Record reaction in mm

9. Classifying the tuberculin reaction • >5 mm is classified as positive in • HIV-positive persons • Recent contacts of TB case • Persons with fibrotic changes on CXR consistent with old healed TB • Patients with organ transplants and other immunosuppressed patients

10. Classifying the tuberculin reaction • >10 mm is classified as positive in • Recent arrivals from high-prevalence countries • Injection drug users • Residents and employees of high-risk settings • Mycobacteriology laboratory personnel • Persons with clinical conditions that place them at high risk • Children <4 years, or children and adolescents exposed to adults in high-risk categories

11. Classifying the tuberculin reaction • >15 mm is classified as positive in • Persons with no known risk factors for TB

12. Factors may affect TST • False negative • Faulty application • Anergy • Acute TB (2-10 wks to convert) • Very young age (< 6 months old) • Live-virus vaccination • Overwhelming TB disease • False positive • BCG vaccination (usually <10mm by adulthood) • Nontuberculous mycobacteria infection

13. Boosting • Some people with LTBI may have negative skin test reaction when tested years after infection • Initial skin test may stimulate (boost) ability to react to tuberculin • Positive reactions to subsequent tests may be misinterpreted as a new infection

14. Two-Step Testing • Use two-step testing for initial skin testing of adults who will be retested within 1-3 weeks • If first test (+), consider the person infected • If first test (-), give second test 1-3 weeks later • If second test (+), consider person infected • If second test (-), consider person uninfected

15. Screening for prior infection • 台灣早年結核病盛行率高 • 50年前20歲以上成人 • 80% TST 為陽性 • 年齡越大,TST對結核病的診斷幫助越小

16. Diagnosis of Pulmonary TB

17. Diagnosis of disease • Medical history • Physical examination • Chest radiograph • Bacteriologic exam • AFS • Culture

18. Medical History

19. Medical History • Symptoms of disease • History of TB exposure, infection, or disease • Past TB treatment • Demographic risk factors for TB • Medical conditions that increase risk for TB disease

20. Medical History • High prevalence population • More likely to be exposed to and infected with bacillus • Immigrant from high prevalence area • Resident or worker in jail • Long term care facility • Close contact to p’t with active TB

21. Medical History • High risk population • More likely to progress from infection to active TB • HIV (+) or other immunodeficiency • CRF • DM • IVDA • Alcoholics • Malnourished • Malignancy • Gastrectomy

22. Physical Examination

23. Physical Examination • Productive, prolonged cough • duration of ~3 weeks‏ • Chest pain • Hemoptysis • Fever/Chills • Night sweats • Appetite loss • Weight loss • Easily fatigued

24. Chest radiography

25. Chest radiography • Classical radiograph appearance • Infiltration • Cavitation • Fibrosis with traction • Enlargement of hilar and mediastinal lymph node • In reactivaiton TB • Classically fibrocavitary apical disease • Primary TB • Middle or lower lobe consolidation

26. Chest radiography • Abnormalities often seen in apical or posterior segments of upper lobe or superior segments of lower lobe • May have unusual appearance inHIV-positive persons • Cannot confirm diagnosis of TB!! cavity in patient‘s RUL classic" for adult-type, reactivation tuberculosis

27. Classic adult TB CXR • PA view • diffuse parenchymal disease with multiple cavities and bulla formation on the left • Sputum smear was positive for AFB

28. Chest radiography • No chest X-ray pattern is absolutely typical of TB • 10-15% of culture-positive TB patients not diagnosed by X-ray • 40% of patients diagnosed as having TB on the basis of x-ray alone do not have active TB

29. X-ray-based evaluation causes over-diagnosis of TB Over- diagnosis NTI, Ind J Tuberc, 1974

30. Bacteriologic Exam

31. Specimen Collection • Obtain 3 sputum specimens for smearexamination and culture • Persons unable to cough up sputum • inducesputum • bronchoscopy • gastric aspiration • Follow infection control precautions during specimen collection

32. Three Specimens • Three specimens optimal • Spot specimen on first visit; sputum container given to patient • Early morning collection by patient on next day • Spot specimen during second visit

33. Three sputum smears are optimal

34. Number of sputum samples required • overall diagnostic yield for sputum examination related to • the quantity of sputum (at least 5 mL) • the quality of sputum • multiple samples obtained at different times to the laboratory for processing • 3 samples obtained at least eight hours apart with at least one sample obtained in the early morning

35. Number of sputum samples required • several studies have suggested that only two samples may be sufficient to capture the majority of cases: • Retrospective study • Nelson, SM, Deike, MA, Cartwright, CP. Value of examining multiple sputum specimens in the diagnosis of pulmonary tuberculosis. J Clin Microbiol 1998; 36:467. • overall, 92 percent of cases would have been detected with two specimens • Craft, DW, Jones, MC, Blanchet, CN, et al. Value of examining three acid-fact bacillus sputum smears for the removal of patients suspected of having tuberculosis from the "airborn precautions" category. J Clin Microbiol 2000; 38:4285. • a third sputum smear was of no additional value

36. 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 • Not specific for M. tuberculosis

37. AFB Smear • Sensitivity: 40-70% • Specificity: 90%

38. AFB smear AFB (shown in red) are tubercle bacilli

39. Number of bacilli seen Result reported None per 100 oil immersion fields Negative 1-9 per 100 oil immersion fields Scanty, report exact number 10-99 per 100 oil immersion fields 1+ 1-10 per oil immersion field 2+ > 10 per oil immersion field 3+ Reporting on AFBMicroscopy

40. HIV Negative 70 60 Early HIV 50 40 Late HIV 30 20 10 0 Proportion of patients with pulmonary TB who have positive AFB smears AFB positivity in TB patients

41. Open tuberculosis • A tuberculous ulceration or other form of tuberculosis in which tubercle bacilli are present in the excretions or secretions. • Pulmonary tuberculosis, especially with cavitation. • 開放性結核就是在病人咳出的痰液中有結核桿菌的存在

42. Cultures • Gold standard for TB diagnosis • 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

43. Cultures • Sensitivity: 80-85% • Specificity: 98% • Times needed: • Solid medium • 4-8 wks • Liquid medium • 2 wks

44. AFB smear vs. Cultures • AFB smear • 可檢測到每ml標本有5000-10000隻細菌 • 染色陰性並不能排除結核病 • Rapid diagnosis • Cultures • 每ml標本只需有10-100隻細菌便可檢測到 • More sensitive • Allows drug susceptivity test

45. Microscopy is more objective and reliable than X-ray Inter-observer agreement

46. Microscopy is a more specific test than X-ray for TB diagnosis Specificity

47. Cough 3 weeks If 1 positive, X-ray and evaluation AFB X 3 If 2/3 positive: Anti-TB Rx Ifnegative: Broad-spectrum antibiotic 10-14 days If symptoms persist, repeat AFB smears, X-ray If consistent with TB Anti-TB Treatment Diagnosis of Pulmonary TB

48. Diagnosis of pulmonary TB

49. Recommended Diagnostic Approach

50. Take Home Message • 診斷結核病必須綜合 • 臨床表現 • Non-specific symptoms • 放射學變化 • Often over diagnosis • 實驗室細菌學診斷 • AFB smear • Rapid diagnosis, presumptive diagnosis • Culture • Gold standard, more sensitive • 只要強烈懷疑TB可先開始進行抗結核治療