How can TB elimination models inform program strategies today?

Modeling by the CDC and the NCHHSTP Epidemiologic and Economic Modeling

Agreement (NEEMA) Grantees

Suzanne Marks, MPH, MA

CDC/Division of Tuberculosis Elimination

NTCA Conference, Atlanta, Georgia

April 19, 2017

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

Division of Tuberculosis Elimination

What is a model?

• A system of mathematical equations that describes or projects the past, present, or future

• Answers questions that cannot otherwise be addressed (for practical, ethical, or financial reasons), by making sense of incomplete data from disparate sources (ref. 1)

• Lists inputs and assumptions explicitly (ref. 1)

What do we need to know?

• What is the current trend in TB cases, given existing activities and resources?

• What would happen if we changed resources and activities?

• Projected outcomes, overall and by population:

– TB and latent TB infection (LTBI) cases and rates

– Time to TB elimination

– Intervention costs

– Cost effectiveness: costs per TB case averted or per quality-adjusted life year

What have we learned so far from CDC and NEEMA modeling?

Estimated 145,000 to 319,000 TB Cases Averted During 1995–2014 (ref. 2)

Estimated societal benefits of averted TB cases 1995–2014 were $3.1 to $6.7 billion, excluding deaths;

$6.7 to $14.5 billion, including deaths (ref. 2)

$6.7

$14.5

$3.1

$6.7

$3.4

$7.3

-

2

4

6

8

10

12

14

16

Societal Costs w/o Deaths Societal Costs Inc. Deaths

Billi

ons

Scenario 1 Scenario 2 Model

$12.9

$27.7

$9.3

$19.9

$9.6

$20.5

-

5

10

15

20

25

30

Societal Costs w/o Deaths Societal Costs Inc. Deaths

Billions

Scenario 1 Scenario 2 Model

If TB Elimination had occurred in 1994, estimated societal benefits of averted TB cases 1995–2014

would have been $9.3 billion to $27.7 billion (ref. 3)

NCHHSTP Epidemic and Economic Modeling Agreement (NEEMA)

• 5 year cooperative agreement, beginning in FY2014, with CDC/NCHHSTP

• To model epidemiologic and economic outputs and outcomes of HIV, hepatitis, STDs, TB, and for school-age populations

• 3 grantees (Emory/Johns Hopkins, Harvard, UCSF) funded through awards each year

TB NEEMA Principal Investigators and Collaborating Organizations

Emory Coalition for Applied Modeling

for Prevention (CAMP)/Johns

Hopkins University (JHU)

Harvard University Prevention Policy

Modeling Lab (PPML)

University of CA at San Francisco (UCSF)

Consortium to AssessPrevention Economics

(CAPE)

CDC and Collaborators

Eli Rosenberg Joshua Salomon Jim Kahn/Paul Volberding

Suzanne Marks

David Dowdy Andrew Hill

Center for Global Health/Division of Global HIV & TB

TB Epidemiologic Studies Consortium (TBESC)

National TB Controllers Association (NTCA)

With current resources and activities, TB elimination is not projected to occur before 2100• In 2020, Yelk-Woodruff (ref. 4) projects:

– 78% of cases will be foreign-born (FB), with 22% of FB from Mexico, 11% from Philippines, 9% from India, 7% from Vietnam, and 5% from China

– Combined with projected 2020 US population (ref. 5), implies a TB case rate of 24/M

• In 2025, Shrestha (ref. 6) projects TB case rates at:

– 52/M in California

– 36/M in New York

– 29/M in Texas

– 25/M in Florida

• In 2050, Menzies (ref. 7) projects a TB case rate of 14/M, or ~ 5,600 cases

• In 2050, Goodell (ref. 8) projects:

– ~ 1100 TB cases in California in 2050

• Barry (ref. 9) estimates that TB elimination in California would require a 14% annual rate of decline, compared with the 4% current rate

What would be the impact on TB elimination of interventions to improve TB disease control?

• Increased use of rapid TB diagnostics– Menzies (ref. 7) projected impact: reduces TB transmission and

consequently TB case rate by 1.1/M compared with current trends, from 14.4/M in 2050 to 13.3/M

– Medicare allowable fee: nucleic acid amplification (NAA) testing or XpertMTB/RIF is ~ $59 per test (ref. 10)

– Estimated cost effectiveness:

• NAA testing was found cost saving in persons with HIV, homelessness, or substance abuse (ref. 11)

• Modeling of the Xpert MTB/RIF test found it cost effective (ref. 12)

• Better TB treatment (increased completion)– Menzies (ref. 7) projected impact: decreases TB case rate by 0.7/M, from

14.4/M to 13.7/M in 2050

• More accurate and effective outbreak detection and response – Impact: Mindra (ref. 13) found that 76% of TB outbreaks from 2009-2015

were first identified through genotype data

TB elimination will require LTBI testing and treatment to prevent reactivation to TB

• NHANES 2011-2012 Estimated LTBI prevalence by IGRA: ~5% of the US population aged ≥ 6 years (ref. 14):

– 3% of US-born (USB) (ref. 14)

– 16% of FB (ref. 14)

• 27% of Indian-born (ref. 15)

• 26% of Chinese-born (ref. 15)

• 24% of Filipino-born (ref. 15)

• 19% of Vietnamese-born (ref. 15)

• 15% of Mexican-born (ref. 15)

– Shrestha (ref. 6) estimates FB LTBI prevalence at 20%-45% in CA, 15%-40% in NY, 10%-30% in both TX and FL

• In 2015 based on NHANES prevalence and Census Bureau US population (ref. 16) estimates, LTBI prevalence = 14M using TST positivity (6M using positivity by both TST and IGRA and 15M using IGRA alone)

– LTBI case rate of 47,000/M (21,000/M to 50,000/M)

• In 2050, Menzies (ref. 7) projects LTBI prevalence at 1.9% overall, 0.4% in USB, 7.2% in FB, and annual LTBI incidence of 12,900 cases

What would be the impact on TB elimination of interventions for LTBI testing and treatment?

LTBI Tests and Treatments

• LTBI tests: interferon gamma release assay (IGRA) vs. tuberculin skin test (TST)– Projected impact: varies by test and population

– Medicare allowable fee: $9 for TST, $85 for QuantiFERON Gold-in-tube (QFT-GIT), and $102 for T-spot (ref. 10)

– Linas estimated cost-effectiveness:

• In persons having close contact to TB, persons with HIV, and FB, QFT (ref. 17)

• in FB with no medical risks, IGRA (ref. 18)

• LTBI treatments: 3 months of isoniazid (H) and rifapentine (P) by directly observed therapy (DOT) or self-administered (SAT)– Projected impact: 3HP/DOT equal efficacy to 9H/SAT (ref. 19), and higher

adherence: 80%-90% vs. 60%-70% for 9H (ref. 20)

– Holland and Shepardson estimated cost-effectiveness:

• 3HP/SAT, 3HP/DOT, and 4R are cost effective vs. 9H/SAT (ref. 21, 22)

Populations for LTBI Testing and Treatment

• Linas projected impact: Number Needed to Test (NNT) and treat with isoniazid to prevent one TB case (ref. 17):

– persons with HIV (67-71),

– persons with close contact to infectious TB (69-110),

– recent (within 5 years) immigrants (104-110),

– FB (301-450),

– persons with homelessness (411-436),

– injection drug users (525-555),

– prisoners (618-655)

• Linas estimated cost effectiveness: greatest in persons with close contact, persons with HIV, and FB (ref. 18)

Targeted LTBI Testing and Treatment (TTT) of Legal Immigrants and Refugees Prior to Arrival

• Menzies projected impact: reduces TB case rate by 4/M compared with current activities, from 14.4/M to 10.4/M in 2050 (ref. 7)

• Wingate estimated cost: ~ $2.8 million annually (in 2011 $) to conduct TTT of Chinese student-visa applicants and ~ $440,000 for Indian student-visa applicants (ref. 23)

• Wingate estimated cost effectiveness: above student-visa intervention is cost-effective and cost saving to the US, but imposes additional costs on students and on public health departments to follow up (ref. 23)

Increasing TTT of US Residents

• Projected impact:

– Menzies estimates that doubling of TTT of all high risk populations and treatment with 3HP reduces the TB case rate by 3.2/M, from 14.4/M to 11.2/M in 2050 (ref. 7)

– Goodell estimates that during 2017-2065 (ref. 8):

• doubling TTT of FB would avert 18,000 cases

• quadrupling TTT of FB would avert 35,000 cases

• increasing TTT of FB 10 times would avert 50,000 cases

Menzies estimates (ref. 7)

NEEMA Ongoing Projects

• Evaluation of the impact and cost of interventions:

– Expansion of TTT of FB persons in the US

– Modeling TB interventions in Mexico, Philippines, Vietnam, India, China

• Modeling the impact of US Preventive Services Task Force (USPSTF) recommendations for primary care clinicians to conduct TTT

• Comparing and contrasting models to create a single unified model for US TB elimination

Summary (1)• With current resources and activities, TB elimination is not

projected to occur before 2100

• Additional interventions to improve TB control are projected to have minimal impact on achieving TB elimination

• Achieving TB elimination will require improvements in LTBI testing and treatment

• TTT for LTBI in persons with medical risks, TB contact, or who are FB are estimated to be most cost effective

• IGRA LTBI diagnostics, combined with 3HP, are estimated to be most cost effective vs. TST with 9H

Summary (2)

• TTT of legal immigrants and refugees prior to US arrival is projected to have moderate impact and is cost effective for student-visa applicants

• TTT of all FB US residents is projected to have moderate impact

• Combining interventions has the greatest potential to accelerate TB elimination, but will require large increases in resources to implement them

References1. CDC Draft White paper on Infectious Disease Modeling at CDC, March 7, 2017

2. Castro KG, Marks SM, Chen MP, Hill AN, Becerra JE, Miramontes R, Winston CA, Navin TR, Pratt RH, Young KH, LoBue PA. Estimating tuberculosis cases and their economic costs averted in the United States over the past two decades. International Journal of Tuberculosis and Lung Disease. 2016; 20(7):926–933.

3. Castro KG, Marks SM, Hill AN, Chen MP, Miramontes R, Winston CA, LoBue PA. In Reply: The cost of the failure to eliminate tuberculosis in the United States. International Journal of Tuberculosis and Lung Disease. 2017; 21(1):120–126.

4. Woodruff RSY, Winston CA, Miramontes R (2013) Predicting U.S. Tuberculosis Case Counts through 2020. PLoS ONE 8(6).

5. US Census Bureau. 2014 National Population Projections. https://www.census.gov/population/projections/data/national/2014/downloadablefiles.html

6. Shrestha S, Hill A, Marks SM, Dowdy DW. Comparing drivers and dynamics of tuberculosis in California, Florida, New York, and Texas. American Journal of Respiratory and Critical Care Medicine. 2017. In press.

7. Menzies NA, Cohen T, Yaesoubi R, Galer K, Wolf E, Marks SM, Hill AN, Salomon JA. The Future of TB in the United States. Poster presentation at the International Union Against Tuberculosis and Lung Disease/North America Region (IUATLD/NAR) Annual Conference. Denver, CO, February 2016. Updated analyses and paper submitted for publication 2017.

8. Goodell AJ, Shete PB, Breman R, McCabe D, Porco TC, Barry PM, Flood J, Marks SM, Hill A, Cattamanchi A, Kahn JG. Prospects for Elimination: An individual-based model to assess tuberculosis control strategies in California. Poster presentation at IUATLD/NAR Annual Conference, May 2016. Updated analyses and paper drafted in 2017.

9. Barry PM, Kay AW, Flood JM, Watt J. Getting to Zero: Tuberculosis Elimination in California. Infectious Disease Epidemiology. Current Epidemiology Reports. 2016. DOI 10.10007/s40471-016-0076-6.

10. Centers for Medicare and Medicaid. 2017 Clinical Lab Fee Schedule. https://www.cms.gov/medicare/medicare-fee-for-service-payment/clinicallabfeesched/ for CPT code 87556, accessed 4/3/2017.

11. Marks SM, Cronin W, Venkatappa T, Maltas G, Chon S, Sharnprapai S, Gaeddert M, Tapia J, Dorman SE, Etkind S, Crosby C, Blumberg HM, Bernardo J. The health-system benefits and cost-effectiveness of using Mycobacterium tuberculosis direct nucleic acid amplification testing to diagnose tuberculosis disease in the United States. Clin Infect Dis. 2013 Aug;57(4):532-42.

References12. Choi HW, Miele K, Dowdy D, Shah M. Cost-effectiveness of Xpert MTB/RIF for diagnosing pulmonary tuberculosis in the

United States. International Journal of Tuberculosis and Lung Disease. 2013;17 (10):1328-1335.

13. Mindra G, Wortham JM, Haddad MB, Powell KM. Tuberculosis Outbreaks in the United States, 2009-2015. Public Health Reports. 2017;132(2):157-163.

14. Miramontes R, Hill AN, Yelk Woodruff RS, Lambert LA, Navin TR, Castro KG, LoBue PA. Tuberculosis Infection in the United States: Prevalence Estimates from the National Health and Nutrition Examination Survey, 2011-2012. PLoS One. 2016; 10(11): e0140881.

15. Woodruff RSY, Hill A, Miramontes R. Tuberculosis Infection among Foreign-born Persons by Country of Birth, United States, 2011-2012. Poster presentation at the 2016 IUATLD/North America conference. Denver, CO. February 2016. Data from NHANES.

16. US Census Bureau Fact Finder https://factfinder.census.gov/faces/nav/jsf/pages/index.xhtml

17. Linas BP, Wong AY, Freedberg KA, Horsburgh CR. Priorities for Screening and Treatment of Latent Tuberculosis Infection in the United States. American Journal of Respiratory and Critical Care Medicine. 2011; 184:590–601.

18. Linas BP, Tasillo A, Menzies NA, Horsburgh CR, Marks SM, Salomon JA. The cost-effectiveness of testing and treatment for latent tuberculosis infection among foreign-born persons in the U.S. Poster presentation at the American Thoracic Society International Conference. San Francisco, CA, May 18, 2016. Updated analyses.

19. Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Dukes Hamilton C, et al. for the TB Trials Consortium PREVENT TB Study Team. Three Months of Rifapentine and Isoniazid for Latent Tuberculosis Infection. New England Journal of Medicine. 2011;365:2155-66.

20. Young KH, Ehman M, Reves R, Maddox BLP, Khan A, Chorba TL, Jereb J. Tuberculosis Contact Investigations — United States, 2003–2012. CDC MMWR 2015;64: 1369-1374.

21. Shepardson D, Marks SM, Chesson H, Kerrigan A, Holland DP, Scott N, Tian X, Borisov AS, Shang N, Heilig CM, Sterling TR, Villarino ME, Mac Kenzie WR. Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States. Int J Tuberc Lung Dis. 2013; 17(12):1531-7.

22. Holland DP, Sanders GD, Hamilton CD, Stout JE. Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection. Am J Respir Crit Care Med. 2009; 179(11):1055-60.

23. Wingate LT, Coleman MS, Posey DL, Zhou W, Olson CK, Maskery B, Cetron MS, Painter JA. Cost-Effectiveness of Screening and Treating Foreign-Born Students for Tuberculosis before Entering the United States. Cost-Effectiveness of Screening and Treating Foreign-Born Students for Tuberculosis before Entering the United States. PLoS ONE. 2015; 10(4): e0124116.

Acknowledgements

• Emory CAMP/JHU: Sourya Shrestha, Monica Trigg

• Harvard University PPML: Ted Cohen, Ken Freedberg, Kara Galer, Bob Horsburgh, Benjamin Linas, Nick Menzies, Abriana Tasillo, Emory Wold, Reza Yaesoubi, others

• UCSF/CAPE: Haleh Ashki, Adithya Cattamanchi, Wei Chang, Alex Goodell, Mohsen Malekinejad, Devon McCabe, Andrea Parriott, Priya Shete, Amanda Viitanen, CA DPH

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

For more information please contact:

Suzanne Marks

Division of Tuberculosis Elimination/Data Management, Evaluation, and Statistics Branch

Mailstop E-10

1600 Clifton Road NE, Atlanta, GA 30333

smarks@cdc.gov

CDC Info Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348

Visit: www.cdc.gov | Contact CDC at: 1-800-CDC-INFO or www.cdc.gov/info

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

Division of Tuberculosis Elimination