John Jereb, M.D.Medical officer

The American Experiencewith TB Elimination

Division of Tuberculosis Elimination

National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention

Reaching the Goal of TB Elimination by 2035March 3, 2015

Overview of Presentation

� History

� BCG, or treatment of latent MM. 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 DISEASERead 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

0

0.5

1

1.5

2

2.51880 1901 1904 1907 1910 1913 1916 1919 1922 1925 1928

Hu

nd

red

s

1908Mantoux Skin Test

Mortality Rate

1918 - 1919Influenza Epidemic

1883First Morbidity

Surveillance

Framingham Demonstration Study, 1917–1923

• 1st 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 patientsSource: 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

Case Rate(Active Only)

Antibiotic Era

1992 TB Resurgence

1979Case-based reporting

1993 Expanded case-based reporting

Mortality Rate

Case Rate (Active/Inactive)

1944Federal TB Program USPHS

0

20

40

60

80

100

1201930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010

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

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)

H is introduced

Clinical Studies of Treatment ofLatent M. tuberculosis Infection

U.S.: Treatment for TB Prevention1965 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 mm1974 Exclude persons > 35 years of age1983 Add clinical and laboratory monitoring 1998 Test high risk groups2000 Targeted Testing2011 3-month, 12-dose DOT combination regimen

ARPE Report, United States, 2006-2010

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

Investigation of Sputum AFB Smear Positive TB (data as of 2/1/2013)

ARPE Report, United States, 2006-2010

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

Investigation of Sputum AFB Smear Positive TB (data as of 2/1/2013)

Cumulative TB Rate33 months from enrollment—MITT

Log-rank P-value: 0.06Sterling et al.

TolerabilityMITT population

Outcome 9HN=3,745

3HPN=3,986

P-value

Treatment completion

2,585 (69.0%) 3,362 (82.0%) < 0.0001

Permanent drug d/c-any reason

1,160 (31.0%) 624 (18.0%) < 0.0001

Permanent drug d/c-due to an adverse event

135 (3.6%) 188 (4.7%) 0.004

Death 39 (1.0%) 31 (0.8%) 0.22

Reported TB Cases United States, 1982–2013*

*Updated as of June 11, 2014.

0

5,000

10,000

15,000

20,000

25,000

30,000

No.

of C

ases

Year

TB Case Rates,* United States, 2013

*Cases per 100,000.

**Information as of June 11, 2014

< 3.0 (2013 national average)

>3.0

D.C.

TB Hot Topics, from Surveillance

• Foreign born

• Homelessness

• Incarceration

• HIV/AIDS

• Completion of Therapy

• Afghanistan

• Bangladesh

• Brazil

• Cambodia

• China

• DRC

• Ethiopia

• India

• Indonesia

• Kenya

• Mozambique

• Myanmar/Burma

• Nigeria

• Pakistan

• Philippines

The 22 TB High Burden Countries, 2013

Division of Tuberculosis Elimination

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

• Russian Federation

• South Africa

• Tanzania

• Thailand

• Uganda

• Viet Nam

• Zimbabwe

Top 10 Countries of Birth of Foreign-born Persons Reported with TB, United States, 2013

Division of Tuberculosis Elimination

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

1. Mexico

2. Philippines

3. India

4. Viet Nam

5. China

6. Guatemala

7. Haiti

8. Ethiopia

9. Honduras

10.Myanmar

Number of TB Cases inU.S.-born vs. Foreign-born Persons

United States, 1993–2013*

*Updated as of June 11, 2014.

No.

of C

ases

-1,000

1,000

3,000

5,000

7,000

9,000

11,000

13,000

15,000

17,000

19,000

U.S.-born Foreign-born

Trends in TB Cases in Foreign-born PersonsUnited States, 1992 – 2013*

*Updated as of June 11, 2014.

No. of Cases Percentage

0

10

20

30

40

50

60

70

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

Number of Cases Percentage of Total Cases

>50%25%–49%<25%

2003 2013

DC

*Updated as of June 11, 2014.

Percentage of TB Cases Among Foreign-born Persons, United States*

DC

TB Cases Reported as Homeless in the 12 Months Prior to Diagnosis,

Age ≥15, United States, 1993-2013*

*Updated as of June 11, 2014.

Note: Homeless within past 12 months of TB diagnosis

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

8.0%

0

200

400

600

800

1,000

1,200

1,400

1,600

Number of Cases Percent of Total Cases

TB Cases by Residence in Correctional Facilities, Age ≥15, United States, 1993-2013*

*Updated as of June 11, 2014.

Note: Resident of correctional facility at time of TB diagnosis

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

0

200

400

600

800

1,000

1,200

Number of Cases Percent of Total Cases

Estimated HIV Coinfection in Persons Reported with TB, United States, 1993 – 2013*

*Updated as of June 11, 2014.

Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group

% C

oin

fect

ion

0

10

20

30

40

50

60

70

25-44 Years Old All Ages

Completion of TB TherapyUnited States, 1993 – 2011*

* 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.

Perc

enta

ge

0

10

20

30

40

50

60

70

80

90

100

Completed in one year or less Completed

� 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

Framework: Elements of National Elimination Strategy

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*

Cas

es p

er 1

00,0

00

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

Under 5 5 - 14 15 - 24 25 - 44 45 - 64 ≥65

Male Female

*Updated as of June 11, 2014

TB Case Rates by Race/Ethnicity* United States, 2003–2013**

*All races are non-Hispanic.

**Updated as of June 11, 2014.

Cas

es p

er 1

00,0

00

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

White American Indian or Alaska Native

Asian Black or African American

Native Hawaiian or Other Pacific Islander Hispanic or Latino

Reported TB Cases by Race/Ethnicity*United States, 2013

. *All races are non-Hispanic. Persons reporting two or more races accounted for less than 2% of all cases

Black or African American

22%

American Indian or Alaska Native

1%

Asian32%White

15%

Native Hawaiian or Other Pacific

Islander1%

Hispanic or Latino29%

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