Clinical Presentation and Diagnosis of Tuberculosis

1. Clinical Presentation and Diagnosis of Tuberculosis Your name Institution/organization Meeting Date International Standards 1-5

2. Clinical Presentation and Diagnosis of TB Objectives:At the end of this presentation, participants will be able to: • Describe the signs/symptoms and risk factors that should raise suspicion for the diagnosis of TB • Understand the importance of sputum smear microscopy, as well as the need to obtain specimens for microbiologic examination from extrapulmonary sites • Recognize that CXR alone is not sufficient for the diagnosis of TB • List criteria used for the diagnosis of smear-negative TB

3. Clinical Presentation and Diagnosis of TB Overview: • General considerations • Signs and symptoms • Role of AFB smear • Radiographic presentation • AFB smear-negative diagnosis International Standards 1, 2, 3, 4, and 5

4. Standards for Diagnosis

5. Fundamental Principles • Rapid, accurate diagnosis is essential for individual and public health • Despite technical advances, clinical acumen with a high index of suspicion remains vital to the diagnosis of TB.  Think TB

6. “Classic” TB Clinical Presentation • Insidious onset and chronic course • Chest symptoms • Cough (usually productive) • Hemoptysis • Chest pain (usually pleuritic) • Nonspecific constitutional symptoms (more common in children and HIV) • Extrapulmonary symptoms (if involved)

7. Nonspecific Systemic Symptoms • Fever in 65-80% of cases • Chills/night sweats • Fatigue/malaise • Anorexia/weight loss • However, 10-20% of TB cases have no symptoms at the time of diagnosis

8. Diagnosis of TB in HIV Cannot rely on “typical” indicators of TB • Fever and weight loss are important symptoms • Cough is less common • Chest radiographic pattern more variable • More extrapulmonary and disseminated TB • Differential diagnosis is broader

9. Standard 1: Prolonged Cough All persons with otherwise unexplained productive cough lasting two-three weeks or more should be evaluated for tuberculosis

10. Prolonged Cough Think TB: Prolonged Cough(2-3 weeks) • Cough may not be specific for TB, however, long duration raises likelihood of TB diagnosis • Criterion for suspecting TB in most national and international guidelines • Percentage of AFB smear-positive sputum increases with increasing duration of cough  Will not identify all TB cases; use best clinical judgment

11. Clinical Presentation: Risk Factors Risk for Recent Infection • Contact with active TB case • Occupational risk – e.g. healthcare worker • Crowded conditions – e.g. jails, institutional residences • Recent stay in a healthcare facility

12. Clinical Presentation: Risk Factors Risk of Progression to Active TB • HIV infection • Abnormal CXR suggestive of prior TB (with inadequate treatment) • Children (less than 5 years of age) • Underlying medical conditions • Immunosuppressive therapy • Malnutrition • Diabetes, renal failure, and other conditions • Injection drug use (?)

13. Clinical Presentation: Physical Examination • May be normal in mild–moderate disease • Chest: rales, rhonchi; absent breath sounds and dullness to percussion if pleural fluid is present • Extrapulmonary (site specific): adenopathy, skin lesions, bone tenderness, neck stiffness, etc.  The physical examination is nonspecific, but it is helpful to identify extrapulmonary sites of involvement

14. Standard 2: Sputum Microscopy All patients (adults, adolescents, and children who are capable of producing sputum) suspected of having pulmonary TB should have at least two sputum specimens obtainedfor microscopic examination. When possible, at least one early morning specimen should be obtained.

15. Sputum Microscopy • To prove a diagnosis of TB, every effort must be made to identify the causative agent • TheAFB smearin high-prevalence areas is: • Highly specific for TB • Most rapid method for determining TB diagnosis • Identifies those at greatest risk of dying from TB • Identifies those most likely to transmit disease

16. Performance of Sputum Microscopy Average yield of single earlymorning specimen: 86.4% Average yield of single spot specimen: 73.9% Mase SR, Int J tuberc Lung Dis 2007;11(5): 485-95

17. Can this be TB? 54-year-old man with three months of focal low-back pain

18. Can this be TB? Extrapulmonary • “Pott’s disease” • Signs and symptoms of extrapulmonary TB are site specific • Sampling of extrapulmonary sites for smear, culture, and histopathology may confirm diagnosis 54-year-old man with three months of focal low-back pain

19. Standard 3: Extrapulmonary Specimens For all patients (adults, adolescents, and children) suspected of having extrapulmonary TB, appropriate specimens from the suspected sites of involvement should be obtained for microscopy, and, where facilities and resources are available, for culture and histopathological examination.

20. Example of Extrapulmonary Sites • Incidence/site may vary  TB can involve any organ • More common in HIV/TB Both, 9% Extrapulmonary, 21% Pleural, 17% Lymphatic, 43% Other, 13% Pulmonary, 70% Bone/joint, 11% Genitourinary, 5% TB Cases by Form of Disease, United States, CDC, 2006 Peritoneal, 5% Meningeal, 6%

21. Extrapulmonary Tuberculosis

22. Radiographic Presentation of TB

23. Standard 4: Evaluation of Abnormal CXR All persons with chest radiographic findings suggestive of tuberculosis should have sputum specimens submitted for microbiological examination. ISTC Training Modules 2008

24. Can this be TB?

25. Can this be TB? Distribution • Apical / posterior segments of upper lobes • Superior segments of lower lobes • Isolated anterior segment involvement is unusual Typical Pattern: Reactivation, Post-primary TB

26. Reactivation/Post-primary TB Patterns of disease • Air-space consolidation • Cavitation, cavitary nodule • Miliary • Fibro-nodular densities • Nodule (Tuberculoma) • Pleural effusions

27. Can this be TB?

28. Can this be TB? • Distribution: Any lobe involved (slight lower lobe predominance) • Air-space consolidation • Cavitation is uncommon (< 10%) • Adenopathy is common (esp. in children and HIV) • Miliary pattern Atypical pattern: Primary TB

29. Can this be TB?

30. Can this be TB? Miliary TB

31. Can this be TB?

32. Can this be TB? Findings suggestive of prior TB • Ca+ granuloma – Ghon lesion • Ca+ granuloma and hilar node calcification – Ranke complex • Apical pleural thickening • Fibrosis and volume loss

33. Evaluation of Abnormal CXR Study from India: 2229 outpatients evaluated by CXR/culture • Of 227 cases deemed TB by CXR alone • 36% had negative sputum cultures for TB • Of 162 culture-positive cases of TB • 20% would have been missed based on CXR alone CXR alone is not enough Nagpaul DR, Proceedings of the 9th Eastern Region Tuberculosis Conference and 29th National Conference on Tuberculosis and Chest Diseases. 1974 Delhi, as cited in Toman’s tuberculosis. Case detection, treatment and monitoring, 2nd Edition: World Health Organization, 2004

34. Standard 5: Smear-negative Diagnosis (1 of 2) The diagnosis of sputum smear-negative pulmonary tuberculosis should be based on the following criteria: • At least two negative sputum smears (including at least one early morning specimen) • Chest radiography findings consistent with tuberculosis • Lack of response to a trial of broad-spectrum antimicrobial agents (1 of 2)

35. Standard 5: Smear-negative Diagnosis (2 of 2) (Continued) • For such patients, if facilities for culture are available, sputum cultures should be obtained. In persons with known or suspected HIV infection, the diagnostic evaluation should be expedited. • [Note: Because the fluoroquinolones are active against M. tuberculosis complex, and thus may cause transient improvement in persons with tuberculosis, they should be avoided.] (2 of 2) ISTC Training Modules 2008

36. TB Diagnostic Algorithm:HIV Negative or Low-Prevalence Area No Yes All Pulmonary TB Suspects Sputum AFB Microscopy Any smear + At least 2 smears - Rx: Non-anti TB antibiotics Improvement? Repeat AFB Any smear + All smears - CXR & medical officer’s judgment Yes TB No TB

37. TB Diagnostic Algorithm: High HIV Prevalence Seriously Ill TB Suspects Immediate referral possible Immediate referral not possible Antibiotic treatment, Sputum AFB and Culture, HIV test, CXR Antibiotic treatment, ? PCP treatment, Sputum AFB and Culture, HIV test, CXR Other Diagnosis, No TB Yes TB AFB Positive AFB Negative Treat for TB HIV care if positive Improvement 3-5 d No improvement 3-5 d Reassess for other HIV assoc. disease Reassess for TB, HIV care if HIV+ TB treatment, HIV care if HIV+ No TB

38. TB Diagnostic Algorithm: High HIV Prevalence Ambulatory TB Suspects AFB smears, HIV test AFB Positive AFB Negative Treat for TB, CPT HIV care if positive AFB smears/culture, CXR, clinical evaluation TB likely TB not likely Reassess for TB No or poor response Treat for bacterial infection and/or PCP HIV care if positive, CPT CPT = cotrimoxazole prophylaxis Response

39. Clinical Presentation and Diagnosis of TB Additional points: • Symptoms/severity: none to overwhelming • Tempo of illness: ranges from indolent to fast • TB can involve any organ or tissue • Signs/symptoms may be both local and systemic • Consider HIV testing in the diagnostic evaluation TB is capable of presenting in many ways

40. Clinical Presentation and Diagnosis of TB Summary: • A prolonged duration of cough should raise TB suspicion and trigger a diagnostic evaluation • TB risk factors and exposure increase level of suspicion • AFB smear in high-prevalence areas is highly specific and most rapid tool for diagnosing TB • Radiographic patterns may help in TB diagnosis if suspicion high and AFB smear is negative, but a radiograph alone is not enough to make diagnosis

41. Summary: ISTC Standards Covered* Standard 1: Unexplained productive cough lasting 2-3 weeks or more should be evaluated for tuberculosis. Standard 2: All TB suspects should have at least 2 sputum specimens obtained for microscopic examination (at least one early morning specimen if possible). Standard 3: Specimens from suspected extrapulmonary TB sites should be obtained for microscopy, and if possible, for culture and histopathological exam. * Abbreviated versions

42. Summary: ISTC Standards Covered* Standard 4: All persons with chest radiographic findings suggestive of TB should have sputum specimens submitted for microbiological examination. Standard 5: The diagnosis of smear-negative pulmonary TB should be based on the following: at least two negative sputum smears (including at least one early morning specimen); CXR finding consistent with TB; and lack of response to broad-spectrum antibiotics (avoid fluoroquinolones). Obtain cultures as available.  Think TB * Abbreviated versions

43. Alternate Slides

44. Purpose of ISTC

45. ISTC: Key Points • 17 Standards • Differ from existing guidelines:standards present what should be done, whereas, guidelines describe how the action is to be accomplished • Evidence-based, living document • Developed in tandem with Patients’ Charter for Tuberculosis Care • Handbook for using the International Standards for Tuberculosis Care

46. ISTC: Key Points • Audience: all health care practitioners, public and private • Scope:diagnosis, treatment, and public health responsibilities; intended to complement local and national guidelines • Rationale:sound tuberculosis control requires the effective engagement of all providers in providing high quality care and in collaborating with TB control programs

47. Questions

48. Clinical Presentation and Diagnosis of TB 1.A 32 year-old man complains of cough and malaise for the past three weeks. His wife is currently being treated for active tuberculosis. Of the following choices, your first step would be: Begin an empiric trial of treatment with a fluoroquinolone antibiotic for a possible community-acquired pneumonia Obtain a chest film to confirm your suspicion for TB which will make sputum testing unnecessary Obtain three sputum specimens for AFB microscopy (including at least one early morning specimen) Both answers A and C

49. Clinical Presentation and Diagnosis of TB 2.In high prevalence areas, the AFB sputum microscopy smear: Is highly specific for TB Identifies those at greatest risk of dying from TB Identifies those most likely to transmit disease All of the above

50. Clinical Presentation and Diagnosis of TB 3.A 54 year-old woman complains of cough, fever, and unexpected weight loss over the past month. She admits smoking 10 cigarettes per day for over 20 years. Three sputum smears were negative for AFB. You would consider each of the following except: An empiric trial of antibiotics (non-fluoroquinolone) Obtaining a chest film for further evaluation A trial of bronchodilator medication alone and follow-up in 3 months Sending sputum specimens for AFB culture