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Tuberculosis in the 21 st Century

Tuberculosis in the 21 st Century. Scott Lindquist MD MPH Tuberculosis Medical Consultant Washington State DOH and Kitsap County Health Officer. In my opinion, the recent media coverage of the case of drug resistant tuberculosis involving international travel was:. A. Balanced

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Tuberculosis in the 21 st Century

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

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

  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 American Indian or Alaska Native (1%) White (18%) Asian (23%) Native Hawaiian or Other Pacific Islander (<1%) Hispanic or Latino (29%) Black or African-American (28%) *All races are non-Hispanic. Persons reporting two or more races accounted for less than 1% of all cases.

  6. TB Case Rates* by Age Group United States, 1993–2005 20 15 Cases per 100,000 10 5 0 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 <15 15–24 25–44 45–64 >65 Age Group (years) *Updated as of March 29, 2006.

  7. 30 20 % Coinfection 10 0 1993 1995 1997 1999 2001 2003 All Ages Aged 25–44 Estimated HIV Coinfection in PersonsReported 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.

  8. 80 60 40 20 0 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 All Ages Aged 25–44 Reporting of HIV Test Results in Persons with TB by Age Group: United States, 1993–2004* % 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)

  9. 10 8 6 Homeless 4 2 0 1994 1995 1996 1997 1998 1999 2000 2001 Adult TB Cases by Homeless Status*1994-2001 % Adult TB case = TB in person aged >18 years * Homeless within year prior to TB diagnosis

  10. 10 8 6 % Correctional Facility 4 2 0 1993 1994 1995 1996 1997 1998 1999 2000 2001 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

  11. Selected Risk Factors:Ten-Year Period, WA 1993-2005 Unemployed Homeless 50 Alcohol Previous Diagnosis 40 30 % of Cases 20 10 0 1994-1995 1996-1997 1998-1999 2000-2001 2002-2003 2004-2005

  12. Place

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

  14. TB Low-Incidence States,* 1990–2000 25 20 Number of Low-Incidence States 15 10 5 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 * <3.5 TB cases per 100,00 population (Year 2000 target)

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

  16. Trends in TB Cases in Foreign-born Persons:US, 1986–2005* No. of Cases Percentage 10,000 60 50 8,000 40 6,000 30 4,000 20 2,000 10 0 0 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 No. of Cases Percentage of Total Cases *Updated as of March 29, 2006.

  17. 90% 73% 72% 70% 69% 61% 68% 67% 66% 75% 63% 60% 59% 60% 45% 30% 15% 0% 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 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* 14 12 10 8 % Resistant 6 4 2 0 1993 1995 1997 1999 2001 2003 2005 U.S.-born Foreign-born *Updated as of March 29, 2006. Note: Based on initial isolates from persons with no prior history of TB.

  23. Primary Anti-TB Drug Resistance: WA, 1996-2006 15% INH MDR TB 10% 5% 0% 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 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.

  24. Primary MDR TB: US, 1993–2005* No. of Cases Percentage 500 3 400 2 300 200 1 100 0 0 93 94 95 96 97 98 99 00 01 02 03 04 05 No. of Cases Percentage *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.

  25. Primary MDR TB: WA,1996-2006 20 50% No. of MDR cases % of Total 40% 15 30% 10 No. of Cases 20% 5 10% 2.0% 2.0% 2.0% 2.0% 0.4% 1.1% 1.1% 0.4% 1.0% 0.0% 0.0% 0 0% 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 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.

  26. Primary MDR TB in US-born vs. Foreign-born Persons with TB, 1993-2001 3 % Primary MDR TB 2 1 0 1993 1994 1995 1996 1997 1998 1999 2000 2001 US-born Foreign-born Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin.

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

  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

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