1. Tuberculosis in the 21 st Century Scott Lindquist MD MPH Tuberculosis Medical Consultant Washington State DOH and Kitsap County Health Officer

2. Feedback Poll A.Balanced B.Overblown C.Confusing D.None of the above In my opinion, the recent media coverage of the case of drug resistant tuberculosis involving international travel was:

3. In the World One out of every three persons has been infected with tuberculosis.... Our story begins....

4. Person

5. Reported TB Cases by Race/Ethnicity* United States, 2005 Hispanic or Latino (29%) Black or African-American (28%) Asian (23%) White (18%) American Indian or Alaska Native (1%) Native Hawaiian or Other Pacific Islander (<1%) *All races are non-Hispanic. Persons reporting two or more races accounted for less than 1% of all cases.

6. *Updated as of March 29, 2006. 19991998 >65 Age Group (years) 0 5 10 15 20 19931994199519961997200020012002200320042005 <1515–2425–4445–64 TB Case Rates* by Age Group United States, 1993–2005 Cases per 100,000

7. Estimated HIV Coinfection in Persons Reported with TB: United States, 1993–2004* *Updated as of March 29, 2006. Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group. % Coinfection 0 10 20 30 199319951997199920012003 All AgesAged 25–44

8. % with Test Results *Updated as of March 29, 2006. Note: Includes TB patients with positive, negative, or indeterminate HIV test results and persons from California reported with AIDS. (HIV test results are not reported from California) Reporting of HIV Test Results in Persons with TB by Age Group: United States, 1993– 2004* 0 20 40 60 80 199319941995199619971998199920002001200220032004 All AgesAged 25–44

9. Adult TB Cases  by Homeless Status* 1994-2001  Adult TB case = TB in person aged >18 years * Homeless within year prior to TB diagnosis Homeless 0 2 4 6 8 10 19941995199619971998199920002001 %

10. Adult TB Cases  by Correctional Facility Status,* 1993-2001  Adult TB case = TB in person aged >18 years old * Resident of correctional facility at the time of TB diagnosis % Correctional Facility 199319941995199619971998199920002001 0 2 4 6 8 10

11. Selected Risk Factors: Ten-Year Period, WA 1993-2005 0 10 20 30 40 50 1994-19951996-19971998-19992000-20012002-20032004-2005 % of Cases Unemployed Homeless Alcohol Previous Diagnosis

12. Place

13. TB Case Rates*: United States, 2005 < 3.5 (year 2000 target) 3.6–4.8 > 4.8 (national average) D.C. *Cases per 100,000.

14. TB Low-Incidence States,* 1990–2000 * <3.5 TB cases per 100,00 population (Year 2000 target) Number of Low- Incidence States 0 5 10 15 20 25 19901991199219931994199519961997199819992000

15. Countries of Birth of Foreign-born Persons Reported with TB: US, 2005 Mexico (25%) Philippines (11%) Vietnam (8%) India (7%) China (5%) Haiti (3%) Guatemala (3%) Other Countries (38%)

16. Trends in TB Cases in Foreign-born Persons: US, 1986–2005* No. of CasesPercentage *Updated as of March 29, 2006. 0 2,000 4,000 6,000 8,000 10,000 8687888990919293949596979899000102030405 0 10 20 30 40 50 60 No. of CasesPercentage of Total Cases

17. 59% 63% 60% 70% 72% 69% 66% 68% 67% 73% 61% 0% 15% 30% 45% 60% 75% 90% 19961997199819992000200120022003200420052006 Proportion of Foreign-born Cases: WA, 1996-2006

18. Drug Resistance

19. Drug Resistance Definitions Primary drug resistance  Applies to previously untreated patients who are found to have drug- resistant organisms, presumably because they have been infected from an outside source of resistant Mycobacterium tuberculosis. Acquired drug resistance  Applies to patients who initially have drug- susceptible bacteria that become drug- resistant due to inadequate, inappropriate, or irregular treatment or, more importantly, because of non-adherence in drug taking.

20. Multidrug-Resistant Tuberculosis (MDR) Resistance to at least two of the best anti- TB drugs, isoniazid and rifampicin. These drugs are considered first line agents.

21. Extensively Drug Resistant TB (XDR TB) This is a rare type of multidrug-resistant tuberculosis. It is resistant to almost all drugs used to treat TB, including all first line agents and the best second-line agents: fluoroquinolones and at least one of three injectable agents (amikacin, kanamycin, or capreomycin). There have been only 49 cases in the US since 1993.

22. Primary Isoniazid Resistance in U.S.-Born vs. Foreign-Born Persons: US, 1993–2005* *Updated as of March 29, 2006. Note: Based on initial isolates from persons with no prior history of TB. % Resistant 0 2 4 6 8 10 12 14 1993199519971999200120032005 U.S.-bornForeign-born

23. Primary Anti-TB Drug Resistance: WA, 1996-2006 Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin. 0% 5% 10% 15% 19961997199819992000200120022003200420052006 INHMDR TB

24. Primary MDR TB: US, 1993–2005* *Updated as of March 29, 2006. Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin. No. of Cases Percentage 0 100 200 300 400 500 93949596979899000102030405 0 1 2 3 No. of CasesPercentage

25. Primary MDR TB: WA,1996-2006 Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin. No. of Cases 1.1% 2.0% 0.0% 1.0% 2.0% 0.4% 0.0% 0.4% 1.1% 2.0% 0 5 10 15 20 19961997199819992000200120022003200420052006 0% 10% 20% 30% 40% 50% No. of MDR cases % of Total

26. Primary MDR TB in US-born vs. Foreign- born Persons with TB, 1993-2001 Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin. % Primary MDR TB 0 1 2 3 199319941995199619971998199920002001 US-bornForeign-born

27. New Diagnostics Quantiferon MTD testing Universal genotyping

28. Commonly Asked TST Questions (1 of 2) How do you know and ensure that the medical community using the TST is properly trained? Can you place a TST on a Thursday and read on a Monday? Who needs a two-step test and why? What is the boosted response?

29. Commonly Asked TST Questions (2 of 2) What if the longitudinal reading of the TST is 12mm and the horizontal (official reading) is 8mm? Is that considered positive? Can I accept a negative reading if the patient said there was absolutely no reaction and there is no reaction on day four after the test? We switched products from tubersol to aplisol, and I noticed more “positives.” We retested with tubersol, and all were negative. Which test do I believe?

30. The Answer Quantiferon  Blood-based testing method

31. MTD Mycobacterium Tuberculosis Direct Test (MTD) Nucleic acid amplification Sensitivity 85.7%–97.8% Criteria for use:  Smear-positive cases  Highly suspicious cases  If it will change treatment

32. Universal Genotyping All TB cultures from WA state now sent to CDC for genotyping “fingerprinting” Spoligotyping MIRU pattern Goal is to detect clusters

33. No. Cases Homeless TB Cases in King County by Treatment Start Date 2002 Treatment Start Date 2003 2004 0 1 2 3 4 5 6 7 8 JanMarMayJulSepNovJanMarMayJulySeptNovJanMarMayJulySept Non-outbreak RFLP Outbreak RFLP No known epi link (RFLP pending) Second RFLP cluster Epi-link (RFLP pending) Clinical case

34. Treatment DOT (consistency is key)  Latent TB infection nine months  Pulmonary six months  Meningitis 12 months  Adenopathy six months  Bone/Joint 12 months Monthly weight check

35. Treatment Evaluation HIV screen Hep B and C (if risk factors) AST ALT Bilirubin A.Phos. Creatinine Platelets Vision testing (if Ethambutol used > 2 mo.)

36. Ongoing Diagnostic Monitoring Monthly sputum collection (until two negative smears). Look for smear positive cases after initial two months of therapy. Liver function tests if abnormalities on screening or risk factors for hepatitis.

37. DOT or Not to DOT Strongly recommended. Patient centered approach is more successful.  Social service support  Treatment incentives and enablers  Housing assistance  Substance abuse treatment

38. TB Case #1:“Doc, can he fly home?” 17-year-old male exchange student from Azerbaijan. BCG at birth. One month of cough, hemoptysis, weight loss, and acute chest pain. He presents to your office...now what do you do?

39. Feedback Poll What is your first step? A. Place a PPD and order a chest radiograph B. Place this patient in an N-95 mask C. Start four drug therapy D. All of the above

40. Results PPD 19 mm Cavitary right upper lobe on radiograph AFB smears all negative

41. The Rest of the Story Sputum MTD was positive Repeat of the AFB at state lab was positive INH, Rifampin, PZA and Ethambutol started Patient instructed not to fly home Held from last two days of high school Contact investigation begun Host family asks to have him removed from home....

42. Further Dilemmas Where can he go? When can he fly home? How certain are you that this is not XDR?

43. Feedback Poll Can he fly home? A.Yes B.No

44. Contact Dr. Lindquist You can call Dr. Lindquist with your TB-related questions at: 360-337-5237 206-718-2664 Or contact him by e-mail at: lindqs@health.co.kitsap.wa.us