Tuberculosis Elimination

Transcription

1 Tuberculosis Elimination Where We ve Been, Where We re Going Mark Lobato, MD New England TB Consultant Division of Tuberculosis Elimination Centers for Disease Control and Prevention

2 Disclosures / Disclaimer No financial conflicts of interest Off-label usage of FDA-approved medications This presentation is that of the author and does not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention

3 Where we ve been What's past is prologue. William Shakespeare

4 130 years of progress Recognition TB is infectious Microscopy for MTB identification TST for the diagnosis of LTBI CXR for the diagnosis of TB Vaccine Chemotherapy

5 Reported TB Cases United States, * No. of cases * As of March 23, 2012

6 Ending Neglect Loss of infrastructure Nosocomial transmission HIV epidemic Immigration

7 U.S. Response to TB Resurgence MDR-TB Action Plan & New Resources Improved Case Finding & Training Updated Diagnostic Labs & TB Genotyping Rebuilt Research Capacity Updated Infection Control & Rx Recommendations DOT & Improved Rx Completion 2HRZE/4HR

8 Cycle of concern

9 Wherever you are, there you are "Great things are done by a series of small things brought together." Vincent Van Gogh

10 Mycobacterial tuberculosis in the United States 2011 TB cases LTBI 10,521 TB cases >50,000 TB suspects ~100,000 contacts 11 million infected 312 million Americans who breathe

11 Reported TB Cases Connecticut, No. of cases

12 TB prevention & control strategy Effective TB Programs Clinical Expertise Laboratory Support Research

13 Available elements Surveillance Treatment Effective drugs DOT Case management Contact investigations LTBI Genotyping Prevent nosocomial transmission Lab capacity NAAT Automated culture systems IGRAs

14 Waning TB Control Capacity Less TB control funds and positions Increased cases per case-manager More complex cases Decreased expertise of private providers Endangered medical safety net Overcome by daily pressures 14

15 Perceived barriers to TB prevention BCG sometimes interferes with TST Some patients won t take INH for 9 months Overstated concerns about hepatotoxicity No time devoted to test Most reimbursements are low or non-existent Public health may communicates poorly No way I track test results and treatment Year 2000 guidelines change too often C. Jackson. Engaging the private sector in TB prevention.

16 Case example 62 y/o Vietnamese male with untreated LTBI History of inactive hepatitis B Receiving chemotherapy for colon adenoma Developed hemoptysis and thought to have lung metastasis Bronchoscopy lavage grew M. tuberculosis

17 Prior TB testing among foreign-born TB patients in CT based on entry status, Had prior TST Characteristic No. Total % OR p-value Documented Ref. Undocumented Guh A. Inter J TB Lung Dis 2011; 15:1044 9

18 Soon-to-have elements Short-course treatment regimens LTBI: 12 doses of weekly therapy TB: 4 months of therapy? Rapid POC testing Xpert MTB/Rif Advocacy STOP TB USA Congressional TB Elimination Caucus

19 Criteria for screening Disease has serious consequences Screening population has higher prevalence of detectable preclinical stage Screening test has a low rate of false positive results and high accuracy for detecting preclinical stage Treatment is more effective before symptom onset and is not too toxic

20 Prevalence: LTBI vs. Diabetes LTBI Diabetes 2 0 All Blacks Mex-Amer. NHANES: Bennett D. AJRCCM 2008;177 CDC. National Diabetes Factsheet, 2011

21 TB in U.S.-born and foreign-born persons by time in the U.S., 2011 Origin Time in U. S. (yrs) Cases n (%) Case Rate U.S. born 3,929 (37.5) 1.5 * Foreign born Total 6,546 (62.5) 17.3 * >1 to > * CDC. Trends in Tuberculosis United States. MMWR 2012; 61:181-5 Cain KP, et al. AJRCCM 2007;175:75-9

22 Screening persons from high vs. medium TB incidence countries Recent entrants VN, RP, Africa Persons from Mexico Population screened 10,000 10,000 Estimated TB case rate (10 5 ) Cases prevented annually * *Assumes 82% treated, 93% treatment efficacy Adapted from K. Cain

23 Lifetime risk for reactivation TB (%) TST=10-14 mm Age (y) Nonconversion Conversion Immunosuppress Old TB HIV Adapted from Horsburgh N Engl J Med 2004;350:2064

24 Priority candidates for LTBI treatment Immunocompromised / immunosuppressed Immigrants and refugees with old TB Children with a LTBI risk Risk for recent infection with M. tuberculosis Contacts Converters Adults with TB risk and a medical or social risk

25 TB risk reduction in adults Recent (<5 years) arrival from or travel (>1 month) to high prevalence areas of the world Medical conditions (diabetes, TNF-α blockers) HCWs Social risk factors homelessness alcohol or drug use incarceration Exposure Risks Medical/Social Risks Prevention opportunities

26 Screening Test

27 Testing persons at risk: LTBI vs. Diabetes LTBI Diabetes Tested NHANES: Bennett D. AJRCCM 2008;177 CDC. National Diabetes Factsheet, 2011

28 TST has low Positive Predictive Value Connecticut foreign born = 487,120 persons * Assume 19% prevalence ** for LTBI TST sensitivity 77%; specificity 59% *** PPV = a / (a + b) = 36% The majority of TST results are false positive TST+ TST- LTBI(+) LTBI (-) a = 71,265 b = 128,454 c = 21,287 d = 266,114 *U.S. Census Bureau, 2010 **Bennett D. AJRCCM 2008;177 ***Pai M. Ann Intern Med 2008 ;149

29 Improving pretest probability Army recruits Assessed using risk factors and TST + IGRA Risk questionnaire reduced testing by >90% Targeted testing necessary to reduce false positive test results Mancuso JD et al. Clin Infect Dis. 2011;53:

30 Impact and yield of screening by risk assessment Tennessee, Screen for TB Risk TST Placed TST Result TST + Start LTBI Treat Complete LTBI Treat* Cases Preve nted Tests to Prevent One Case Foreign born 28,322 (17) 21,680 (77) 17,699 (82) 5,759 (33) 3,269 (57) 1416/2484 (57) High risk, US 85,342 (51) 69,652 (82) 57,860 (83) 2,933 (5) 1,334 (45) 474/980 (48) ,702 2,120 Low risk 54,583 (32) 33,868 (62) 27,150 (80) 398 (1) 177 (44) 63/136 (46) 3 9,834 *As of 2005 Adapted from: Cain K. Am J Respir Crit Care Med 2012;186:273-9.

31 Treatment

32 Preventive care: LTBI vs. Diabetes LTBI Diabetes 10 0 Prevention NHANES: Bennett D. AJRCCM 2008;177 CDC. National Diabetes Factsheet, 2011

33 Where is testing and treatment occurring? 37,857 patients started on LTBI treatment (2002) 79% public health clinic 6.4% immigrant /refugee clinic 6.1% correctional 2.0% private Conclusions: LTBI treatment is started primarily in public sector Extrapolated to U.S: 4,000-11,000 cases prevented Sterling, et al. Am J Respir Crit Care Med 2006;173

34 LTBI treatment regimens Drugs Duration Interval Minimum doses Isoniazid 9 months Daily 270 Twice weekly* 76 Isoniazid 6 months Daily 180 Isoniazid and Rifapentine Twice weekly* 52 3 months Once weekly* 12 Rifampin 4 months Daily 120 * Dosing by DOT

35 Completion of therapy for LTBI INH vs. 3HP Study Year N Population Percent Horsburgh NA public & private clinics 48% Hirsch.Moverman NYC 56% Jasmer TB clinics in U.S. 57% * Menzies Montreal pulmonary clinic 62% Reichler Contacts in U.S. 51% CDC ARPE Contacts to smear + 67% CDC ARPE Contacts to smear - 69% PREVENT INH PREVENT 3HP US, Canada, Brazil, Spain contacts, converters, HIV 69% 82% * 6 months INH

36 Where we re going The future belongs to those who believe in the beauty of their dreams. Eleanor Roosevelt

37 Elements in the pipeline Vaccine Rapid diagnostic and drug susceptibility tests Global TB elimination

38 New drugs, better early bactericidal activity Diacon AH. Lancet 2012 Jul 20. [Epub ahead of print]

39 Range of incidence projections Doubling the rate of treatment of LTBI

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41 Community-based TB preventive services Establish public health partnerships Provide TB and public health education Deliver TB preventive services

42 TB is a primary care issue 6 steps to TB prevention 1. Assess for TB risk factors 2. If risk present, perform IGRA or TST 3. If test is positive, rule out TB disease 4. If no TB disease, evaluate for LTBI therapy 5. If a candidate, start therapy 6. If therapy started, ensure completion

43 Case management of TB preventive services King County, WA Immigrants and refugees seeking primary care Case management model house calls: INH delivery; phone follow up TB education health referrals information on housing, schools, employment social support Culturally competent outreach workers Straddle medical model and community beliefs

44 Initiation of INH Bosnian Somali Russian Julie Wallace. Stamping out TB. 2001

45 Completion of therapy Bosnian Somali Russian Julie Wallace. Stamping out TB

46 Community-based TB preventive services Boston, MA A nurse coordinator Provider teams became the TB expert resources for the health centers Collaboration between HCs and HD Consensus policies for TB screening Identify obstacles and accomplishments

47 Findings 187 high-risk persons referred to the clinic Almost twice as likely to complete treatment 73% vs. 39% No difference in adverse medication events John Bernardo, MD: Unpublished data

48 XDR TB is a significant threat to the major gains made in global TB control World Health Organization

49 Budget cutter

50 Advocates of change

51 A world free of TB Are we willing to pay the price? Photo: David Rochkind

52 Thank You!