1. Case Finding and Diagnosis Module 5 – March 2010

2. Project Partners Funded by the Health Resources and Services Administration (HRSA)

3.  Case Finding  Steps in Diagnosing TB Medical History Bacteriologic Examination Drug Susceptibility Testing Radiographic Exam Sputum smear-negative patient Module Overview International Standards 1, 2, 3, 4, 5, and 18

4. Learning Objectives At the end of this presentation, participants will be able to:  List the steps involved in diagnosing tuberculosis  Describe the role of sputum smear microscopy in the diagnosis of tuberculosis  Recognize the role of culture and drug sensitivity testing in the diagnosis and management of tuberculosis

5. Case Finding  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 tuberculosis  THINK TB

6. Where can you conduct case finding activities?

7. Opportunities for Case Finding  TB Chest Clinics  Hospitals (Public)  Public Health Clinics  Voluntary Counselling and Testing (VCT) clinics  Prevention of Mother to Child Transmission (PMTCT) clinics  Correctional facilities (prisons, jails)  Drug Rehab Centres  HIV Care facilities  Private medical clinics  Occupational Health facilities  Long term care facilities and shelters

8. Steps in Diagnosing TB  Medical History  Bacteriologic examination  TB Culture and Drug Susceptibility Testing  Radiographic exam  Other examinations based on site(s)/location(s) involved

9. Medical History  Known exposure to a person with infectious pulmonary TB  Symptoms of TB disease and onset  Previous treatment for latent TB infection or active TB disease  Risk factors for developing TB disease  Other medical conditions that might affect treatment approach

10. What are the signs and symptoms of tuberculosis?

11. Standard 1: Prolonged Cough All persons with otherwise unexplained productive cough lasting two-three weeks or more should be evaluated for tuberculosis International Standards for Tuberculosis Care, 2009

12. Prolonged Cough Think TB: Prolonged Cough (2 - 3 weeks)  Cough may not be specific for TB, however, long duration raises the likelihood of TB diagnosis  This is common criterion for suspecting TB in most national and international guidelines  The likelihood of AFB smear-positive sputum increases with increasing duration of cough  Will not catch all TB cases; use best clinical judgment

13. “Classic” TB Clinical Presentation  Subtle onset and chronic course  Chest symptoms Cough (usually productive) Hemoptysis Chest pain (usually pleuritic)  Nonspecific constitutional symptoms  Extrapulmonary symptoms (if involved)

14. Typical Systemic Symptoms  Fever in 65-80% of cases  Night sweats  Fatigue/malaise  Anorexia/weight loss  10-20% of TB cases have no symptoms at the time of diagnosis

15. Clinical Presentation Physical Examination (PE):  May be normal in mild–moderate disease  Lungs: 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 PE is most useful when assessing for non-pulmonary sites of TB

16. Bacteriologic Examination

17. All patients suspected of having pulmonary TB who can produce sputum should have at least two sputum specimens obtained for microscopic examination in a quality-assured laboratory. When possible, at least one early morning specimen should be obtained. Standard 2: Sputum Microscopy International Standards for Tuberculosis Care, 2009

18. Sputum Microscopy  To confirm 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

19. 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% Performance of Sputum Microscopy Specimen Number Incremental Yield (of all smear positive) Incremental Sensitivity (of all culture positive) 185.8%53.8% 211.9%11.1% 32.4%3.1% Total100%68.0%

20. Culture & Drug Susceptibility Testing Obtaining culture and drug susceptibility testing (DST) offers significant advantages in the diagnosis and management of TB:  Increases case detection  Earlier diagnosis  Identification of drug resistance

21. Culture: Advantages  Higher sensitivity than smear microscopy (culture can make diagnosis despite fewer bacilli in specimen)  If TB disease is suspected and sputum smears are negative, culture may provide diagnosis  Allows for identification of mycobacterial species  Allows for drug susceptibility testing

22. Culture: Disadvantages  Cost  Technical complexity  May take weeks to get results  Requires ongoing quality assurance  Therefore, culture testing is more likely to be found in major referral centers. Avoid delaying appropriate TB treatment in suspicious cases while awaiting results.

23. Case 1 A 32 year old man presents to the clinic with complaint of cough x 1 month. He is not severely ill and can be evaluated in an ambulatory setting. Questions:  What other history do you ask him about?  What other signs will you look for during your examination to aide in diagnosis?

24. Case 1 (2) Patient gives further history of feeling poorly for several months now; reports weight loss (about 3-4kg) and cough has gotten progressively worse. Patient denies smoking. His brother was treated for tuberculosis last year. Patient was not evaluated for TB at that time. Question:  What laboratory tests would do you order?

25. Case 1 (3) Among the results you receive, one of two sputum smears is positive for acid fast bacilli (AFB) on direct microscopy. Question:  What would you do next?

26. Case 1 Summary If smear result is from a Lab with EQA:  Obtain chest X-ray, order TB culture and initiate TB treatment

27. Standard 3: Extrapulmonary Specimens For all patients suspected of having extrapulmonary TB, appropriate specimens from the suspected sites of involvement should be obtained for microscopy, culture, and histopathological examination. International Standards for Tuberculosis Care, 2009

28. Pulmonary, 70% Extrapulmonary, 21% Both, 9% Pleural, 18% Lymphatic, 42% Bone/joint, 11% Genitourinary, 5% Meningeal, 6% Other, 12% TB Cases by Form of Disease, United States, CDC, 2005 Peritoneal, 6% Clinical Presentation: Extrapulmonary  Incidence/site may vary  TB can involve any organ  More common in HIV/TB (co-infection)

29. Extrapulmonary Tuberculosis

30. Radiographic Examination

31. Standard 4: Evaluation of Abnormal CXR All persons with chest radiographic findings suggestive of tuberculosis should have sputum specimens submitted for microbiological examination. International Standards for Tuberculosis Care, 2009

32. 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, 2 nd Edition: World Health Organization, 2004

33. Chest Radiography Purpose:  Provides additional evidence to aid in diagnosis of TB disease when only 1 sputum smear is positive in settings without an EQC laboratory  Check for lung abnormalities in people who have symptoms of TB; especially in those with HIV co-infection  Evaluate and rule out TB disease in persons with a newly positive tuberculin skin test (Mantoux)  Chest X-ray alone cannot confirm TB disease

34. Chest Radiography (2) Chest X-ray findings suggestive of active PTB disease include:  Acute upper lobe pneumonia  Unresolving pneumonia  Cavitation, cavitary lesion  Pleurisy, pleural effusion  Lung infiltrate, especially in upper lung zones  Intrathoracic adenopathy International Standards for Tuberculosis Care, 2009

35. Chest Radiography (3) Chest X-ray findings suggestive of previous or presumed inactive PTB include:  Apical fibrosis  Upper lobe fibronodular abnormality  Pleural (fibro) calcification  Upper lung zone bronchiectasis  Thoracoplasty or partial pneumonectomy  Healed primary lesion (Ghon focus/complex)

36. Can this be TB?

37. Can this be TB? Miliary TB

38. 54-year-old man with three months of focal low-back pain Can this be TB?

39. 54-year-old man with three months of focal low-back pain 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

40. Sputum Smear-Negative Patient Criteria for diagnosis:  Have sputum that is smear-negative but culture- positive for M. tuberculosis OR  Decision by a clinician to treat with a full course of anti-TB therapy; AND  Chest X-ray consistent with TB; AND either: Laboratory or strong clinical suspicion of HIV infection Lack of response to broad-spectrum (non- fluoroquinolone) antibiotic (if HIV-negative or unknown)

41. Standard 5: Smear-negative Diagnosis The diagnosis of sputum smear-negative PTB should be based on the following criteria:  At least two negative sputum smears (including at least one early morning specimen)  Chest radiographic findings consistent with TB  Lack of response to a trial of broad-spectrum anti-microbial agents (avoid use of fluoroquinolones) For such patients sputum cultures should be obtained. International Standards for Tuberculosis Care, 2009

42. Standard 5: Smear-negative Diagnosis (2)  In persons who are seriously ill or have known or suspected HIV infection, the diagnostic evaluation should be expedited and if clinical evidence strongly suggests TB, a course of antituberculosis treatment should be initiated International Standards for Tuberculosis Care, 2009

43. TB Diagnostic Algorithm: HIV-Negative or Low Prevalence Area Yes TB * Any smear + Repeat AFB smear Order TB culture > 1 smear +or TB culture +All smears - CXR & medical officer’s judgment Yes TB * No Rx: Non-anti TB antibiotics Improvement? No TB > 2 smears - Yes Sputum AFB Microscopy Assess for HIV All Pulmonary TB Suspects

44. TB Diagnostic Algorithm: HIV-Positive and High Prevalence Ambulatory HIV+ TB Suspect AFB smears/culture; DST AFB Positive * AFB 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 Clinical evaluation; CXR; TST; may repeat AFB smears/culture TB not likely No or poor response Response CPT = cotrimoxazole prophylaxis Reassess if symptoms recur

45. Clinical Presentation and Diagnosis of TB Remember:  Symptoms/severity can range from 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

46. Can this be TB?

47.  Distribution: Any lobe involved (slight lower lobe predominance)  Air-space consolidation  Cavitation is uncommon (< 10%)  Adenopathy is common (especially in children and HIV)  Miliary pattern Atypical pattern: Primary TB

48. ISTC Standard 18 All providers of care for patients with TB should ensure that persons who are in close contact with patients who have infectious TB are evaluated and managed in line with international recommendations. The determination of priorities for contact investigation is based on the likelihood that a contact: 1.Has undiagnosed TB 2.Is at high risk of developing TB if infected 3.Is at risk of having severe TB if the disease develops 4.Is at high risk of having been infected by the index case

49. ISTC Standard 18 (2) The highest priority contacts for evaluation are:  Persons with symptoms suggestive of tuberculosis  Children aged <5 years  Contacts with known or suspected immunocompromise, particularly HIV infection  Contacts of patients with MDR/XDR tuberculosis  Other close contacts are a lower priority group

50. Contact Investigation  There is a high likelihood that a person with smear-positive PTB will transmit tuberculosis. Therefore, prompt and thorough contact investigation is essential for the control of TB  Contact investigations should start with the persons most likely to be infected (those who most frequently come in contact with the person who has infectious TB)

51. Contact Investigation (2)  Actively seeking out and evaluating contacts to persons with smear- positive PTB is an important TB control strategy for two reasons: It identifies persons with previously undetected tuberculosis, allowing initiation of treatment and halting further transmission It identifies persons with TB infection who would benefit from isoniazid preventive therapy (IPT) to prevent future TB reactivation

52. Case Finding 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

53. * 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, culture, and histopathological exam.

54. Summary: ISTC Standards Covered* (2) 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 PTB 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. Seriously ill or HIV + patients should have an expedited diagnostic evaluation and if there is strong clinical evidence, treatment should be initiated. * Abbreviated versions

55. Summary: ISTC Standards Covered* (3) Standard 18: All providers of care for patients with TB should ensure that persons who are in close contact with patients who have infectious TB are evaluated and managed in line with international recommendations. The highest priority contacts for evaluation are:  Persons with symptoms suggestive of tuberculosis  Children aged <5 years  Contacts with known or suspected immunocompromise, particularly HIV infection  Contacts of patients with MDR/XDR tuberculosis  Other close contacts are a lower priority group * Abbreviated versions

56.  Think TB

57. Additional Cases

58. Can this be TB?

59. Distribution  Apical / posterior segments of upper lobes  Superior segments of lower lobes  Isolated anterior segment involvement is unusual (think M. avium complex or other disease) Typical Pattern: Reactivation, Post-primary TB

60. Reactivation/Post-primary TB Patterns of disease  Air-space consolidation  Cavitation, cavitary nodule  Endobronchial spread  Miliary  Bronchostenosis  Tuberculoma  Pleural effusions

61. Can this be TB?

62. Findings suggestive of prior TB  Ca+ granuloma – Ghon lesion  Ca+ granuloma and hilar node calcification – Ranke complex  Apical pleural thickening  Fibrosis and volume loss