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

2. ISTC Training Modules 2008 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. ISTC Training Modules 2008 Clinical Presentation and Diagnosis of TB International Standards 1, 2, 3, 4, and 5 Overview: General considerations Signs and symptoms Role of AFB smear Radiographic presentation AFB smear-negative diagnosis

4. ISTC Training Modules 2008 Standards for Diagnosis

5. ISTC Training Modules 2008 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 Fundamental Principles

6. ISTC Training Modules 2008 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. ISTC Training Modules 2008 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. ISTC Training Modules 2008 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. ISTC Training Modules 2008 Standard 1: Prolonged Cough All persons with otherwise unexplained productive cough lasting two-three weeks or more should be evaluated for tuberculosis

10. ISTC Training Modules 2008 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. ISTC Training Modules 2008 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. ISTC Training Modules 2008 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. ISTC Training Modules 2008 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. ISTC Training Modules 2008 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 obtained for microscopic examination. When possible, at least one early morning specimen should be obtained.

15. ISTC Training Modules 2008 Sputum Microscopy To prove a diagnosis of TB, every effort must be made to identify the causative agent The AFB smear in 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. ISTC Training Modules 2008 Mase SR, Int J tuberc Lung Dis 2007;11(5): 485-95 Average yield of single early morning specimen: 86.4% Average yield of single spot specimen: 73.9% Specimen Number Incremental Yield of smear specimens (of all smear positive) Incremental Sensitivity of smear specimens (compared with culture) 185.8%53.8% 211.9%11.1% 32.4%3.1% Total100%68.0% Performance of Sputum Microscopy

17. ISTC Training Modules 2008 54-year-old man with three months of focal low-back pain Can this be TB? Extrapulmonary Potts disease Signs and symptoms of extrapulmonary TB are site specific Sampling of extrapulmonary sites for smear, culture, and histopathology may confirm diagnosis

18. ISTC Training Modules 2008 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.

19. ISTC Training Modules 2008 Pulmonary, 70% Extrapulmonary, 21% Both, 9% Pleural, 17% Lymphatic, 43% Bone/joint, 11% Genitourinary, 5% Meningeal, 6% Other, 13% TB Cases by Form of Disease, United States, CDC, 2006 Peritoneal, 5% Clinical Presentation: Extrapulmonary Incidence/site may vary TB can involve any organ More common in HIV/TB

20. ISTC Training Modules 2008 Extrapulmonary Tuberculosis

21. ISTC Training Modules 2008 Radiographic Presentation of TB

22. ISTC Training Modules 2008 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

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

24. ISTC Training Modules 2008 Reactivation/Post-primary TB Patterns of disease Air-space consolidation Cavitation, cavitary nodule Miliary Fibro-nodular densities Nodule (Tuberculoma) Pleural effusions

25. ISTC Training Modules 2008 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

26. ISTC Training Modules 2008 Can this be TB? Miliary TB

27. ISTC Training Modules 2008 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

28. ISTC Training Modules 2008 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 Tomans tuberculosis. Case detection, treatment and monitoring, 2 nd Edition: World Health Organization, 2004

29. ISTC Training Modules 2008 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 Standard 5: Smear-negative Diagnosis (1 of 2)

30. ISTC Training Modules 2008 (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.] Standard 5: Smear-negative Diagnosis ISTC Training Modules 2008 (2 of 2)

31. ISTC Training Modules 2008 TB Diagnostic Algorithm: HIV Negative or Low-Prevalence Area All Pulmonary TB Suspects Sputum AFB Microscopy Rx: Non-anti TB antibiotics Improvement? Repeat AFB Any smear +All smears - CXR & medical officers judgment Yes TB No TB No Any smear +At least 2 smears - Yes

32. ISTC Training Modules 2008 Seriously Ill TB Suspects Immediate referral possible No improvement 3-5 d Antibiotic treatment, Sputum AFB and Culture, HIV test, CXR AFB Positive Yes TB Immediate referral not possible Antibiotic treatment, ? PCP treatment, Sputum AFB and Culture, HIV test, CXR AFB Negative Improvement 3-5 d TB treatment, HIV care if HIV+ Reassess for TB, HIV care if HIV+ No TB Reassess for other HIV assoc. disease Treat for TB HIV care if positive Other Diagnosis, No TB TB Diagnostic Algorithm: High HIV Prevalence

33. ISTC Training Modules 2008 TB Diagnostic Algorithm: High HIV Prevalence Ambulatory TB Suspects AFB smears, HIV test AFB PositiveAFB Negative Treat for bacterial infection and/or PCP HIV care if positive, CPT TB likely Reassess for TB Treat for TB, CPT HIV care if positive AFB smears/culture, CXR, clinical evaluation TB not likely No or poor response Response CPT = cotrimoxazole prophylaxis

34. ISTC Training Modules 2008 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

35. ISTC Training Modules 2008 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

36. ISTC Training Modules 2008 * Abbreviated versions 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.

37. ISTC Training Modules 2008 Summary: ISTC Standards Covered* * Abbreviated versions 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

38. ISTC Training Modules 2008 Alternate Slides

39. ISTC Training Modules 2008 Purpose of ISTC

40. ISTC Training Modules 2008 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

41. ISTC Training Modules 2008 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 ISTC: Key Points

42. ISTC Training Modules 2008 Questions

43. ISTC Training Modules 2008 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: A.Begin an empiric trial of treatment with a fluoroquinolone antibiotic for a possible community- acquired pneumonia B.Obtain a chest film to confirm your suspicion for TB which will make sputum testing unnecessary C.Obtain three sputum specimens for AFB microscopy (including at least one early morning specimen) D.Both answers A and C

44. ISTC Training Modules 2008 Clinical Presentation and Diagnosis of TB 2. In high prevalence areas, the AFB sputum microscopy smear: A.Is highly specific for TB B.Identifies those at greatest risk of dying from TB C.Identifies those most likely to transmit disease D.All of the above

45. ISTC Training Modules 2008 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: A.An empiric trial of antibiotics (non-fluoroquinolone) B.Obtaining a chest film for further evaluation C.A trial of bronchodilator medication alone and follow-up in 3 months D.Sending sputum specimens for AFB culture