The American Experience with TB Elimination

Reaching the Goal of TB Elimination by 2035 March 3, 2015 The American Experience with TB Elimination John Jereb, M.D. Medical officer Division of Tuberculosis Elimination National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention Overview of Presentation History BCG, or treatment of latent M. tuberculosis infection? Epidemiologic trends Strategy going forward

Leading Causes of Death in the United States, 1900, 2010 Jones, DS, et al., N Engl J Med. 2012 Jun 21;366(25):2333-8. CONSUMPTION PRIMARILY A NERVE DISEASE Read before the Illinois State Medical Society, May, 1893. BY J. J. M. ANGEAR, B. S.,M.A.,M.D., Professor of Physiology, Nervous and Mental Disease in College of Physicians and Surgeons, Keokuk, Iowa. Professor of Physiology and Pathology in United States Dental College Surgeon of the Columbian Accident Company Attending Physician National Temperance Hospital Member American Medical Association Illinois State Medical Society Chicago Medical Society Chicago Pathological Society Chicago Academy of Sciences Ex-Preside J. J. M. ANGEAR, B.S.,M.A.,M.D JAMA. 1893;XX(20):558-560.

New York City TB Surveillance Biggs, The Administrative Control of Tuberculosis, 1907 TB Death Rate, 1880 1929 1880 1901 1904 1907 1910 1913 1916 1919 1922 1925 1928 2.5 2 1.5 1908 Mantoux Skin Test 1918-1919 Influenza Epidemic Hundreds 1 Mortality Rate 0.5 1883 First Morbidity Surveillance 0

Framingham Demonstration Study, 1917 1923 1 st medical survey of an entire population Many children tuberculin tested Radiograph first systematically used as a diagnostic tool Expert consultation made available to local practitioners Sevenfold increase in the number of cases reported in 1 year National Tuberculosis Christmas Seal Program Establish state societies Secure TB divisions in local health depts. Education Employment of nurses to conduct surveys Operation of clinics, dispensaries Financial aid for patients in institutions Relief for families and patients Source: The History of Medicine Division. Prints and Photographs Collection. 31 January 2013. <http://ihm.nlm.nih.gov/images/c04908>

Source: The History of Medicine Division. Prints and Photographs Collection. 31 January 2013. <http://www.nlm.nih.gov/hmd/ihm/> U.S. Library of Congress Website: Available at http://www.loc.gov/pictures/

U.S. Library of Congress Website: Available at http://www.loc.gov/pictures/ U.S. Library of Congress Website: Available at http://www.loc.gov/pictures/

TB Case Rates and Death Rate, 1930 2013 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 120 100 Antibiotic Era Case Rate (Active/Inactive) 1979 Case-based reporting 1993 Expanded casebased reporting 80 1992 TB Resurgence 60 Mortality Rate 40 Case Rate (Active Only) 20 1944 Federal TB Program USPHS 0

Incidence of Tuberculosis among Initial Reactors to Tuberculin Puerto Rico, 1949 1951 Comstock GW, Livesay VT, Woolpert SF: The Prognosis of positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 99:134, 1974 Clinical Studies of Treatment of Latent M. tuberculosis Infection 1952 INH is introduced 1954 Lincoln (Bellevue Hosp, NYC) notes that children with TB treated with INH do not develop meningitis 1955 USPHS cooperative study of the effects of INH on primary TB in children 1956-1961 Controlled chemoprophylaxis trials (12 trials; 7 countries; 100,000 participants) 1970 IUAT trial among persons with fibrotic lesions (7 European countries; 28,000 participants) 1992 Controlled trial of three regimens among persons with silicosis (Hong Kong; 679 participants) 1993-1998 TB prevention trials among persons with HIV infection (7 trials; 7 countries; 7,000 participants; included SCMD regimens)

U.S.: Treatment for TB Prevention 1965 ATS recommends INH preventive therapy for persons with Evidence of old, healed, untreated TB Recent tuberculin skin test (TST) conversion < 3 years of age with TST positive result 1967 Extend to all with TST 10 mm 1974 Exclude persons > 35 years of age 1983 Add clinical and laboratory monitoring 1998 Test high risk groups 2000 Targeted Testing 2011 3-month, 12-dose DOT combination regimen ARPE Report, United States, 2006-2010 Investigation of Sputum AFB Smear Positive TB (data as of 2/1/2013) Year 2006 2007 2008 2009 2010 Jurisdictions Reporting (N) 56 59 53 55 56 Cases for investigation (N) 4649 4776 4084 3668 3820 Cases with No Contacts (N) 365 335 281 205 173 Contacts Identified (N) 75410 75463 68344 66628 68219 Contacts Evaluated (N) 60010 61842 56253 52259 56253 TB Disease (N) 437 505 427 341 489 Latent TB Infection (N) 13584 14296 12411 10453 11236 Started LTBI Treatment (N) 9767 10109 9190 7053 8082 Completed LTBI Treatment (N) 6412 6889 5887 4754 5475

ARPE Report, United States, 2006-2010 Investigation of Sputum AFB Smear Positive TB (data as of 2/1/2013) Year 2006 2007 2008 2009 2010 Jurisdictions Reporting (%) 82 87 78 81 82 Contacts Identified (%) 92 93 93 94 96 No Contacts Identified (%) 8 7 7 6 4 Contact per Case (N, avg.) 16.2 15.8 16.7 18.2 17.9 Contacts Evaluated (%) 80 82 82 78 82 TB Disease Rate (%) 0.58 0.67 0.76 0.65 0.90 Latent TB Infection (%) 23 23 22 20 20 LTBI Treatment Initiated (%) 72 71 74 67 72 LTBI Treatment Completed (%) 66 68 64 67 68 Cumulative TB Rate 33 months from enrollment MITT Sterling et al. Log-rank P-value: 0.06

Tolerability MITT population Outcome Treatment completion Permanent drug d/cany reason 9H 3HP P-value N=3,745 N=3,986 2,585 (69.0%) 3,362 (82.0%) < 0.0001 1,160 (31.0%) 624 (18.0%) < 0.0001 Permanent drug d/cdue to an adverse 135 (3.6%) 188 (4.7%) 0.004 event Death 39 (1.0%) 31 (0.8%) 0.22 30,000 Reported TB Cases United States, 1982 2013* 25,000 No. of Cases 20,000 15,000 10,000 5,000 0 *Updated as of June 11, 2014. Year

TB Case Rates,* United States, 2013 D.C. < 3.0 (2013 national average) *Cases per 100,000. **Information as of June 11, 2014 >3.0 TB Hot Topics, from Surveillance Foreign born Homelessness Incarceration HIV/AIDS Completion of Therapy

The 22 TB High Burden Countries, 2013 Afghanistan Bangladesh Brazil Cambodia China DRC Ethiopia India Indonesia Kenya Mozambique Myanmar/Burma Nigeria Pakistan Philippines Russian Federation South Africa Tanzania Thailand Uganda Viet Nam Zimbabwe Division of Tuberculosis Elimination National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Top 10 Countries of Birth of Foreign-born Persons Reported with TB, United States, 2013 1. Mexico 2. Philippines 3. India 4. Viet Nam 5. China 6. Guatemala 7. Haiti 8. Ethiopia 9. Honduras 10.Myanmar Division of Tuberculosis Elimination National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

19,000 Number of TB Cases in U.S.-born vs. Foreign-born Persons United States, 1993 2013* 17,000 15,000 13,000 No. of Cases 11,000 9,000 7,000 5,000 3,000 1,000-1,000 U.S.-born Foreign-born *Updated as of June 11, 2014. No. of Cases Trends in TB Cases in Foreign-born Persons United States, 1992 2013* Percentage 9,000 70 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1,000 0 60 50 40 30 20 10 0 Number of Cases Percentage of Total Cases *Updated as of June 11, 2014.

Percentage of TB Cases Among Foreign-born Persons, United States* 2003 2013 DC DC *Updated as of June 11, 2014. >50% 25% 49% <25% TB Cases Reported as Homeless in the 12 Months Prior to Diagnosis, Age 15, United States, 1993-2013* 1,600 1,400 1,200 1,000 800 600 400 200 0 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% Number of Cases Percent of Total Cases *Updated as of June 11, 2014. Note: Homeless within past 12 months of TB diagnosis

TB Cases by Residence in Correctional Facilities, Age 15, United States, 1993-2013* 1,200 1,000 800 600 400 200 0 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% Number of Cases Percent of Total Cases *Updated as of June 11, 2014. Note: Resident of correctional facility at time of TB diagnosis Estimated HIV Coinfection in Persons Reported with TB, United States, 1993 2013* 70 60 50 % Coinfection 40 30 20 10 0 25-44 Years Old All Ages *Updated as of June 11, 2014. Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group

Percentage 100 90 80 70 60 50 40 30 20 10 0 Completion of TB Therapy United States, 1993 2011* Completed in one year or less Completed * Updated as of June 11, 2014. Data available through 2011 only. Note: Includes persons alive at diagnosis, with initial drug regimen of one or more drugs prescribed, who did not die during therapy. Excludes persons with initial isolate rifampin resistant, or patient with meningeal disease, or pediatric patient (aged <15) with miliary disease or positive blood culture. Framework: Elements of National Elimination Strategy Ending Neglect: The Elimination of Tuberculosis in the United States Institute of Medicine Report published in 2000 CDC response includes 6 goals that are elements of elimination strategy in United States

Goal I: Maintain Control 5 components: detection of TB cases; treatment of TB cases; investigation of contacts; treatment of infected contacts; infection control Importance of oversight and support by health department to ensure patients complete treatment DOT and incentives and enablers: effective, but resource intensive and difficult to sustain Alternatives, e.g., video or e-dot Loss of expert personnel, especially experienced public health nurses Goal II: Accelerate the Decline 3 components: addressing LTBI; regionalizing; genotyping and outbreak detection and response Genotyping is useful, but different applications based on incidence Low incidence not as valuable for outbreak detection, may be more useful for detecting false positives Methods with better resolution needed in some situations (WGS) Insufficient surge capacity to respond to outbreaks

Latent M. tuberculosis infection (LTBI) Problem is vast, and a major initiatives are needed Registry and a surveillance system Scale up of testing to targeted populations More focused guidance on who to target Eliminate wasteful testing of low-risk persons Specific funding for IGRAs, especially for foreign-born Scale up of short course LTBI treatment (3HP, 4R) Communication, outreach Engagement of affected communities and their medical providers Goal III: New tools Shorter treatment regimens for TB and LTBI Point-of-care diagnostics LTBI test that predicts who will get TB disease Vaccine

Goal IV: Global TB Focus on screening of immigrants in the United States Overseas priorities Expansion of screening for TB disease to populations beyond permanent immigrants and refugees Addition of LTBI testing and treatment to current overseas screening program Goal V: Mobilize and Sustain Support Need better messages simple, clear and memorable Need more active champions and advocates Focus on the affected communities

Goal VI: Track Progress Use standard national indicators Sometimes not as relevant to low-incidence states Flexible program evaluation Thank You! Questions?

TB Case Rates by Age Group and Sex, United States, 2013* Cases per 100,000 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 Under 5 5-14 15-24 25-44 45-64 65 Male Female *Updated as of June 11, 2014 35.0 30.0 25.0 TB Case Rates by Race/Ethnicity* United States, 2003 2013** Cases per 100,000 20.0 15.0 10.0 5.0 0.0 White Asian 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Native Hawaiian or Other Pacific Islander *All races are non-hispanic. **Updated as of June 11, 2014. American Indian or Alaska Native Black or African American Hispanic or Latino

Reported TB Cases by Race/Ethnicity* United States, 2013 Hispanic or Latino 29% Black or African American 22% American Indian or Alaska Native 1% Native Hawaiian or Other Pacific Islander 1% White 15% Asian 32%. *All races are non-hispanic. Persons reporting two or more races accounted for less than 2% of all cases Budget Appropriated FY 2014: $142,256,000 Appropriated FY 2015: $142,256,000 Ceiling FY 2014: $138,721,979 Ceiling FY 2015: $138,729,667 Level funding