Failure to Implement the Plan to Eliminate TB in the US: Implications in the Era of Declining Resources Sustaining Public Health Capacity in an Age of Austerity Forum on Microbial Threats Board on Global Health Institute of Medicine Randall Reves, MD, MSc Medical Director, Denver Metro Tuberculosis Control Denver Public Health Department Professor, Infectious Diseases University of Colorado Medical School and School of Public Health
2007: 19 y.o. student in ED with sepsis Acute abdominal pain UTI treatment with cipro. 6 mo. ago No known TB exposure Arrived from Nepal last year
19 y.o. student in ED Perforated colon at laparotomy Granulomatous inflammation Sputum AFB smear + Expired despite I.V. levofloxacin, amikacin, rifampin & antibiotics
News Alerts Colorado Springs Student From Nepal Dies From TB Woman Was International Student At CSU-Pueblo POSTED: 1:16 pm MDT June 11, 2007 COLORADO SPRINGS, Colo. -- Tuberculosis was confirmed as the cause of death of a patient who died at Colorado Springs' Memorial Hospital shortly after arriving at the emergency room on Friday. It was not known what type of TB killed the 19-year-old student from Nepal but officials held an afternoon news conference to discuss the case. Type of TB drug-susceptible M. tuberculosis. TB remains a potentially deadly disease for healthy young adults.
My introduction to TB in public health, EIS Field Services 1977-79 School and Community Transmission, Corinth MS HS senior Blue Chip prospect Lost weight over summer Hemoptysis at Aug. 76 football camp Physician diagnosed bronchitis in March 76 Cavitation and AFB + Reves et al, Am J Epidemiol 1981
Community Transmission of INH- Strep-PAS Resistant TB 1965-78 in Corinth MS 139 infected at school (19%) 4 secondary cases 2 fatalities one a student with acquired rifampin resistance ( MDR ) No known effective treatment for contacts Local HD overwhelmed 22 TB cases total
TB in a High School Student, Longmont, Boulder County, CO: 2012 Incident Command, PHP, multiple counties involved > $250 K direct cost Over 160 infected contacts by TST or IGRA Rifampin 4 mo. and INH+rifapentine 3 mo. > 90% completed LTBI treatment within 8 months Example of what can be done now with susceptible TB. Longmont Times Call, 1/21/2012
The one reference to TB in 2011 Ready or Not? Public interpretation: only MDR, not really that bad
American Journal of Epidemiology The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Number of suspected infectious respiratory-disease-related epidemic-assistance investigations (Epi-Aids), by etiology, Centers for Disease Control and Prevention, 1946 2005. Hadler S C et al. Am. J. Epidemiol. 2011;174:S36-S46 TB most common agent
TB is the mastodon in the room Year Event Deaths US TB cases MDR TB annual deaths* 1993 TB peak 25,107 407 1,639 2001 Al Qaeda 3,000 US 15,945 148 764 2003 SARS 800 global** 14,835 115 711 2011 Joplin tornado CO Lysteriosis Hurricane 140 30 56 10,521 105 4 XDR 505-915^ *Death certificate data 4.8% of reported cases in recent years **Global TB deaths estimated at well over one million per year ^Not available: 505 if 4.8%; 915 if 8.7%, proportion dead before treatment completed
Google Images No, not the band Mastodon
... this one
.. unlike the mastodon, TB thrives & the progeny are even worse Survey of 1,278 MDR case treated 2005-8 Resistance to at least one second-line drug in 44%, injectable 20%, FLQ 13% XDR in 6.7% - currently untreatable Range in 8 countries: 0.8% Philippines, 15% S Korea XDR TB MDR Dalton T, et al Lancet online August 30, 2012 http://dx.doi.org/10.1016/s0140-6736(12)60734-x
Latest global TB estimates - 2010 All forms of TB Greatest number of cases in Asia; greatest rates per capita in Africa Multidrug-resistant TB (MDR-TB) Estimated number of cases 8.8 million 650,000* Estimated number of deaths 1.1 million 150,000 Extensively drugresistant TB (XDR-TB) 50,000 30,000 HIV-associated TB 1.1 million 350,000 *Estimate: 16% treated
Transmission of MDR-TB in a worksite in AK, 2006 3 secondary cases detected by genotyping 29 (60%) of their contacts infected 2 were children with MDR TB
One patient with TB in the USA* Previously healthy elementary school teacher Coughing 3 months: pneumonia diagnosed Outpatient treatment failed Chest radiograph: left lung lesions, cavity Sputum: AFB on microscopic exam Culture: Mycobacterium tuberculosis Weeks later: resistance to INH, rifampin, EMB (MDR- TB) Exposure: none except limited travel to MX, Asia Curative TB treatment completed *Personal communication, colleague in CA. Manuscript in preparation.
What does MDR-TB mean? Hospitalization for weeks Weeks of inadequate treatment (pending lab results indicating drug-resistance) Daily treatment with IV medication for at least 4-6 mo., possible hearing loss At least 3-4 other types of pills causing nausea,depression, other effects for 18-24 mo. Directly observed treatment (DOT) Unable to work for months Often rejected by friends, co-workers, others Health department investigation at home, school, social setting with MDR implications
Modern Day Regimen for drug susceptible tuberculosis Nearly half a century old a combination of Isoniazid -1951 Rifampin - 1957 Pyrazinamide - 1952 Ethambutol - 1962 At least 6 months, ideally administered by directly observed therapy (DOT) Daily dose Contrast: 3-drug, single pill HIV Rx
Multidrug Resistance Multidrug-resistant (MDR) = Isoniazid and Rifampin +/- other drugs First-line Drugs Second-line Drugs Isoniazid Cycloserine - 1952 Rifampin Ethionamide - 1956 Rifapentine Levofloxacin Rifabutin Moxifloxacin 1990 s Ethambutol Gatifloxacin Pyrazinamide - 1952 p-aminosalicylic acid - 1944 Streptomycin - 1946 daily for 18-24 months! Amikacin/kanamycin - 83/ 58 Capreomycin 1960 s
U.S. Cost for TB: local/state/individual only* Drug Susceptible Total costs per individual DOT $4,000 Hospitalization (50% of patients) $19,000 Deaths due to TB each year in US 1,200 die before diagnosis or during treatment MDR-TB Total costs per individual $28,217 to $1,278,066 XDR-TB Over $600,000 excluding hospitalization Death rate over 40% in large patient series *No CDC or Ryan-White equivalent for TB drugs. MT had to pass a new state appropriation to treat a student MDR case.
We are being forced to use TB treatments abandoned 50 years ago
Evaluation of 185 contacts of teacher with MDR TB Teacher s Classroom: 21 of 31 (68%) infected (+TST); 10% risk for developing MDR-TB Other school contacts: 15 of 111 (14%) infected Treatment for MDR-TB infection (unproven benefit) Two medications daily for 12 months Started in 26 infected contacts Two full-time health department staff required for 1 yr No other TB cases developed so far
What should have happened? Prompt diagnosis & drug susceptibility results Safely return to work in 2-4 weeks Cure of TB with short-course 6 month regimen (why not 2 or 4 months?) Protection of contacts with 9 months treatment (why not 2-4 months?) Safe travel without exposure to MDR-TB Why not?
Key Recommendations by the IOM in 2000 Remain Valid, but Not Implemented Institute of Medicine Goal 1. Maintain control despite decline. 2. Accelerate decline by increasing targeted testing, Tx of LTBI. 3. Develop new Dx, Tx, & prevention tools. 4. Increase US involvement in global TB control. 5. Mobilize & sustain public support. Success Comments Yes No Yes/No Yes Yes/No Comments Continuing decline in since 1993. Decline decelerating. LTBI limited to PH, not expanded as required. Research expanded, implementation limited USAID TB $ $72 to $162 M in 6 yr. TB- HIV is 4% of PEPFAR. Success in mobilization modest.
Priorities for TB Support adequate TB control in the US Local - city, county State, federal support Invest in global TB control Improve infrastructure to effectively treat drugsusceptible TB with available regimens Significantly expand the laboratory infrastructure in high burden countries Pursue new tools Diagnostics for rapid detection, susceptibility Pursue better drugs and treatment regimens Pursue a better vaccine
US government s response Global TB - Lantos-Hyde Leadership Against HIV/AIDS, TB and Malaria Act enacted in 2008 Commits USG to Global Plan to Stop TB Authorizes $4 billion over 5 years for USAID's global TB program Domestic TB - Comprehensive TB Elimination Act enacted in 2008 Expands targeted TB detection and treatment among Foreignborn & minorities Authorizes new tools expansion at CDC and NIH Authorizes $220M for CDC's domestic TB program in FY2011 Instead CDCs TB budget of $145 M will be cut again this year
Hopeful News from 2010 We are beginning to see the winds of change, but what we really need is a storm. It is imperative that we transform the way we diagnose, treat, prevent, and control TB through biomedical research and public health measures to the same extent that we have done and will continue to do with HIV/AIDS. Anthony Fauci, MD Increasing collaboration between CDCs TB Trials Consortium and NIH ACTGs Promising new drugs but none approved
Conclusions: The failure to rapidly develop and implement new tools for diagnosis and treatment of TB and latent TB infection as recommended in 1987 has left local and state health departments: Inadequately prepared for MDR-TB Unprepared for XDR This is not a theoretical risk: MDR/XDR TB transmission does occur Potential for super-spreaders exists Should TB be a major focus for the Forum on Microbial Threats?