Everything you always wanted to know about TB…but were afraid to inhale?

1. Everything you always wanted to know about TB…but were afraid to inhale? Kevin Schwartzman MD, MPH Respiratory Division, MUHC kevin.schwartzman@mcgill.ca RVH Internal Medicine Resident Core Teaching March 30, 2010

2. Learner Objectives--1 • To describe basic concepts in tuberculosis epidemiology • To recognize the spectrum of clinical and radiographic manifestations of active TB, in different patient populations • To describe the essential pathophysiology of latent and active TB • To identify and understand the rationale for evidence-based diagnostic strategies for active and latent TB

3. Learner Objectives--2 • To describe standard treatment for active and latent TB • To identify indications, contraindications, and potential complications of this treatment • To identify key concepts in TB control, within and outside the hospital

4. Overview--1 • Case presentations • Epidemiology • Pathophysiology and natural history • Active TB: • Diagnosis • Treatment, including special considerations • Infection control

5. Overview--2 • Latent TB: • Diagnosis • Tuberculin skin test, interferon-gamma release assays • Treatment priorities • Treatment regimens • Special situations • Key concepts in TB control

6. Jad Davenport, “Mural outside tuberculosis clinic, Dhaka” World Lung Foundation (http://worldlungfoundation.org)

7. Jad Davenport. “TB flourishes in crowded Dhaka shantytowns” World Lung Foundation (http://worldlungfoundation.org)

8. Pierre Virot, “A TB patient is examined by the doctor, Ghana” World Lung Foundation (http://worldlungfoundation.org)

9. www.nytimes.com On May 24, 2007, Andrew Speaker, a 31 year-old lawyer from Atlanta, landed at Trudeau Airport on a flight from Prague, with a diagnosis of extensively drug-resistant (XDR) tuberculosis. He drove a rented car across the US border, and was apprehended. He had smear-negative TB, later determined not to be XDR.

10. Case 1 • 35 y.o. Inuit female • Referred to MGH after trauma • Smoker, no other past history • No respiratory or constitutional symptoms • Previously exposed to brother with active TB • Apparently did not receive treatment for latent infection

12. Next steps?

13. Case 1 • Underwent bronchoscopy • BAL cytology negative • BAL smear-negative for AFB • Discharged to the North with instructions for follow-up CXRs and clinical follow-up/other tests depending on results • BAL ultimately culture-negative • Apparently lost to follow-up until she developed left arm and shoulder pain in February 2010

16. Case 1 • What would you recommend now?

17. Case 1 • Bronchoscopy: some mucosal abnormalities seen on left side • BAL AFB smear negative • BUT necrotizing granulomatous inflammation and AFB seen on biopsy specimens • Patient is staying at Northern Module • What would you recommend now?

18. Case 2 • 32 y.o. male refugee claimant from Congo, arrived in Canada < 1 week previously • Admitted to medical ward because of extensive herpes zoster in left V1 distribution, with probable bacterial superinfection • Wife known HIV-positive, no respiratory issues • Patient found to be HIV-positive with CD4 70 • Complains of minor hemoptysis

20. Case 2 • What investigations (if any) would you now arrange? • Would you isolate this patient? • What treatment (if any) would you recommend?

21. Case 3 • 50 year-old female respiratory therapist, Quebec-born, completely asymptomatic • Smoker, treated for type 2 diabetes with oral hypoglycemic agent • Referred for tuberculin skin test measuring 13 mm, done 1 week after assisting at bronchoscopy of patient whose BAL was 4+ smear-positive for AFB, and laryngeal lesions were seen • What other information would you like?

22. Case 3 • Received BCG vaccination in primary school, at about age 8 (~1968) • Had tuberculin skin test results of 0 mm in 2005 and 2006, 2 mm in 2009. • What do you think? • What are the next steps?

23. “I thought TB had disappeared” • 2007: WHO estimated 9.3 million new cases, vs. 8.3 million cases in 2000 and 6 million cases in 1990 • 55% in Asia, 31% in Africa • Overall global incidence 137 per 100,000 annually, down from peak 142 in 2004 • 1.3 million deaths in HIV-negative individuals, 450,000 deaths in HIV-positive individuals (~25% of all deaths in HIV-infected persons) • 1/3 of world population believed to have latent TB infection http://www.who.int/tb/publications/global_report/2009/en/index.html

28. Major Determinants • Basic elements of TB control e.g. diagnosis, consistent and appropriate treatment • Health system infrastructure e.g. national control programs, public vs. private providers etc. • General socioeconomic and health status, tobacco, alcohol • HIV • Drug resistance • Obviously all these are interrelated

29. Bates et al, Arch Int Med 2007

30. HIV • Strongest known risk factor for TB disease • Increases risk of progression/reactivation of latent TB infection by 100-fold or more • To date, impact on global epidemiology most evident in sub-Saharan Africa, but concern re unknown magnitude of HIV-TB coinfection notably in India

32. Drug Resistance • In 2007, the estimated number of cases of multi-drug resistant TB was 511,000 • 3.1% of all new TB cases and 19% of retreatment cases were multi-drug resistant • Defined as resistance to isoniazid AND rifampin, with or without resistance to other antibiotics • A marker of treatment program quality • Poor prognosis, treatment complexity and expense

34. WHO, Anti-Tuberculosis Drug Resistance in the World, 2008

35. WHO, Anti-Tuberculosis Drug Resistance in the World, 2008

36. TB in Canada Ellis et al, Public Health Agency of Canada

42. Drug Resistance in 2007 Of 1,188 Canadian cases with drug resistance data: • 94 (8%) mono-resistance to first line drugs (82 INH), plus 6 INH/ethambutol • 10 (0.8%) MDR-TB • 1 (0.08%) XDR-TB

43. Montreal • 123 reported active TB cases in 2007; maximum was 209 in 1994 • Corresponding decrease in incidence from 11.6 to 6.4 per 100,000 • Consistently ~80% of cases involve foreign-born persons DSP Montréal-Centre, Bureau de surveillance épidémiologique http://www.santepub-mtl.qc.ca/Mi/surveillance/mado/archives/90-2005/incidence90-2007.pdf

44. Pathophysiology Active Tuberculosis Case Finding (Passive or Active) Effective Drug Treatment Patient Behaviour (e.g. Cover Mouth) Airborne Droplets Respiratory Isolation Progression or Reactivation Ventilation and Air Filtration Ultraviolet Light BCG Vaccination Diagnosis and Treatment of Latent TB Inhalation by Others Antiretroviral Therapy for HIV Latent Infection

45. Long and Schwartzman, Transmission and Pathogenesis of TB, Chapter 3, Canadian Tuberculosis Standards 2007

46. Clinical Manifestations • Pulmonary disease: 2/3 of cases in Canada • Pleural TB and thoracic nodal disease ~ 10% • Most common extrapulmonary site is peripheral lymph nodes (~12%) • Patients often asymptomatic when they have less extensive disease (e.g. immigration screening) • Most frequent symptom: cough, usually for weeks to months—in symptomatic patients, virtually always present (even if not the symptom that precipitated the visit)

47. Clinical Manifestations • Other frequent symptoms: sputum, fever, malaise, loss of weight/appetite, night sweats, hemoptysis • Symptoms generally not very specific, hence the importance of the clinical and epidemiologic context • Timing of cough often used to estimate period of contagion • Physical exam generally not helpful; may show cachexia, fever, sometimes adenopathy

48. Questions to Ask • Place of birth, year of immigration (risk highest in years immediately after arrival) • Known history of TB disease, latent TB, exposure • Recent travel • Visitors from abroad • HIV issues • Other past medical history

49. Chest Radiograph • The key first step in investigation • A normal chest X-ray usually excludes the diagnosis of pulmonary TB, except in some HIV-infected persons • Reactivation disease: usually upper zone airspace disease (infiltrate; “fluffy” appearance), may have cavities • Involvement of other areas of lung, or contralateral lung, suggests bronchogenic spread, and a higher bacterial load/potential for contagion • Beware of judging active vs. inactive TB on a CXR

50. Gary Hampton, “Paula Fujiwara of the IUATLD talks to the mother of a TB patient…” World Lung Foundation (http://worldlungfoundation.org)