[Senate Hearing 110-258]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 110-258

    PROTECTING THE UNITED STATES FROM DRUG-RESISTANT TUBERCULOSIS: 
             REINVESTING IN CONTROL AND NEW TOOLS RESEARCH

=======================================================================

                                HEARING

                                 OF THE

                    COMMITTEE ON HEALTH, EDUCATION,
                          LABOR, AND PENSIONS

                          UNITED STATES SENATE

                       ONE HUNDRED TENTH CONGRESS

                             FIRST SESSION

                                   ON

 EXAMINING WAYS TO PROTECT THE UNITED STATES FROM THE RISING THREAT OF 
DRUG-RESISTANT TUBERCULOSIS, FOCUSING ON REINVESTING IN CONTROL AND NEW 
                             TOOLS RESEARCH

                               __________

                            OCTOBER 30, 2007

                               __________

 Printed for the use of the Committee on Health, Education, Labor, and 
                                Pensions


  Available via the World Wide Web: http://www.gpoaccess.gov/congress/
                                 senate



                  U.S. GOVERNMENT PRINTING OFFICE
38-733                    WASHINGTON : 2009
-----------------------------------------------------------------------
For sale by the Superintendent of Documents, U.S. Government Printing 
Office Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800; DC 
area (202) 512-1800 Fax: (202) 512-2104  Mail: Stop IDCC, Washington, DC 
20402-0001









          COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

               EDWARD M. KENNEDY, Massachusetts, Chairman

CHRISTOPHER J. DODD, Connecticut     MICHAEL B. ENZI, Wyoming,
TOM HARKIN, Iowa                     JUDD GREGG, New Hampshire
BARBARA A. MIKULSKI, Maryland        LAMAR ALEXANDER, Tennessee
JEFF BINGAMAN, New Mexico            RICHARD BURR, North Carolina
PATTY MURRAY, Washington             JOHNNY ISAKSON, Georgia
JACK REED, Rhode Island              LISA MURKOWSKI, Alaska
HILLARY RODHAM CLINTON, New York     ORRIN G. HATCH, Utah
BARACK OBAMA, Illinois               PAT ROBERTS, Kansas
BERNARD SANDERS (I), Vermont         WAYNE ALLARD, Colorado
SHERROD BROWN, Ohio                  TOM COBURN, M.D., Oklahoma

           J. Michael Myers, Staff Director and Chief Counsel
           Katherine Brunett McGuire, Minority Staff Director

                                  (ii)






                            C O N T E N T S

                               __________

                               STATEMENTS

                       TUESDAY, OCTOBER 30, 2007

                                                                   Page
Brown, Hon. Sherrod, a U.S. Senator from the State of Ohio, 
  opening statement..............................................     1
Enzi, Hon. Michael B., a U.S. Senator from the State of Wyoming, 
  opening statement..............................................     3
    Prepared statement...........................................     3
Coburn, Hon. Tom, a U.S. Senator from the State of Oklahoma, 
  statement......................................................     6
Allard, Hon. Wayne, a U.S. Senator from the State of Colorado, 
  statement......................................................     6
Castro, Kenneth G., M.D., Director, Division of Tuberculosis 
  Elimination, Center for Disease Control and Prevention, 
  Atlanta, GA....................................................     7
    Prepared statement...........................................     9
Burr, Hon. Richard, a U.S. Senator from the State of North 
  Carolina, statement............................................    18
Murkowski, Hon. Lisa, a U.S. Senator from the State of Alaska, 
  statement......................................................    20
Frieden, Thomas R., M.D., MPH, Commissioner, New York City 
  Department of Health and Mental Hygiene, New York, NY..........    26
    Prepared statement...........................................    28
Sadoff, Jerald C., M.D., President and CEO, AERAS Global TB 
  Vaccine Foundation, Rockville, MD..............................    32
Reves, Randall, M.D., Professor of Medicine, Infectious Diseases, 
  University of Colorado; Medical Director, Denver Metro 
  Tuberculosis Clinic; Chairman, Stop TB USA, Denver, CO.........    34
    Prepared statement...........................................    36

                          ADDITIONAL MATERIAL

Statements, articles, publications, letters, etc.:
    Questions of Senator Coburn for Kenneth G. Castro, M.D.......    46

                                 (iii)



 
    PROTECTING THE UNITED STATES FROM DRUG-RESISTANT TUBERCULOSIS: 
             REINVESTING IN CONTROL AND NEW TOOLS RESEARCH

                              ----------                              


                       TUESDAY, OCTOBER 30, 2007

                                       U.S. Senate,
       Committee on Health, Education, Labor, and Pensions,
                                                    Washington, DC.
    The committee met, pursuant to notice, at 10:04 a.m., in 
Room SD-430, Dirksen Senate Office Building, Hon. Sherrod 
Brown, presiding.
    Present: Senators Brown, Enzi, Burr, Murkowski, Allard, and 
Coburn.

                   Opening Statement of Senator Brown

    Senator Brown. The Senate Committee on Health, Education, 
Labor, and Pensions comes to order.
    I thank Senator Enzi for joining us today, and for his 
interest in tuberculosis. He and I had a discussion with some 
House members and the new president of the World Bank about 
tuberculosis and some other issues. And, I appreciate his 
interest.
    I also appreciate Senator Coburn's interest in TB. In his 
brief respite between the House and Senate one day, on a TB 
amendment I had in the House, he lobbied his roommate on behalf 
of our tuberculosis amendment and got his vote for it. And I 
appreciate Senator Coburn's long-time interest in public 
health.
    I just wanted to say first of all, I appreciate Dr. Castro 
being here, and others who have been so very involved in 
tuberculosis issues over the years, particularly Dr. Frieden, 
who's an old friend of mine and an old colleague and a long-
time colleague in working on these issues. And, I also want to 
mention Lee Reishman, who has done so much to advance the cause 
of public health. Lee has been sick for a while but will be 
back at work fairly soon. He is here in spirit and would be 
here in person, I think, if he could be.
    Some years ago, well, a long time ago, 30, almost 40 years, 
35 years ago, my physician in general practice father and I 
were driving down the street in my hometown of Mansfield, Ohio, 
a town of about 50,000, and we drove by a clinic, a building 
that looked like it was about to close. And I said to my 
father, ``What is that?'' And he said, ``It's a tuberculosis 
sanitorium. And we don't have TB in our town anymore. We used 
to have terribly difficult problems with TB and we don't need 
it anymore.''
    And I've obviously learned since then, that my father may 
have been correct in those days in Mansfield, Ohio, but it's a 
continuing worldwide problem to be sure, and a threat to public 
health in this country as we have learned. We know the toll 
that TB is taking on the health of people around the world. 
Globally, TB kills about 1.6 million people each year.
    It's the leading cause of death, especially in Africa, for 
people with HIV/AIDS. It's estimated that one-third of the 
world's population is infected with the TB bacteria, and that 
some 2 billion people have that bacteria in their bodies. It's 
estimated that 10 to 15 million Americans may carry the TB 
bacteria also.
    As our witnesses will describe, TB was never eradicated in 
our country and has emerged in a new and dangerous drug-
resistant form. What's different now from the TB of my 
childhood, is that now we have the more dangerous drug-
resistant forms of TB. Drug-resistant TB evolves when we fail 
to provide complete, consistent treatment regimens.
    We know it's a problem created by humankind, this drug-
resistant TB. It gained the spotlight earlier this year, as we 
all know, when Andrew Speaker boarded a plane and put his 
fellow passengers at risk. If any good came of that incident, 
and if any good is coming from the series of illnesses and a 
few deaths around the country now, with the public health 
problems that CDC is working so well and hard on, it's 
reminding us that in a globalized world, TB and other diseases 
like it are not only diseases of the poor and developing 
countries, but a risk to Americans, just sometimes a plane ride 
away. And once TB becomes drug-resistant, it becomes a 
tremendously costly and potentially deadly health threat, 
regardless of where you live.
    Less than a year ago, last December, the Advisory Council 
for the Elimination of TB, the expert group that advises the 
Secretary of Health and Human Services on TB issues, warned,

          ``If XDR, the excessively drug-resistant, the highest form, 
        if you will, of drug-resistant TB, the most insidious form, is 
        not addressed in the early stages before it becomes more 
        prevalent in our country, it will become a Trojan Horse that 
        will set back our country's ability to control TB for decades, 
        and set back our whole public health system.''

    As Dr. Frieden knows from what happened in New York 15 or 
so years ago.
    Because it's treatable and preventable, any new case of 
drug-
resistant TB represents a failure of all of us in the public 
health system somewhere, either here or in another country. 
Today, while the overall rate of TB cases in the United States 
continues to fall, the significant slowing of the decline rate 
from 6 percent per year, in the period 1993 to 2002, to 3 
percent per year in more recent, for 3-year period is of 
concern because of the history of TB in our country.
    In the 1970s and 1980s, after making much progress toward 
eliminating TB, but never actually reaching that goal, we began 
cutting the Nation's TB control infrastructure. Our weakened 
domestic TB capacity at the time, coupled with the HIV/AIDS 
epidemic, caused an unprecedented surge in the Nation's TB rate 
between 1985 and 1992. We need to make sure history doesn't 
repeat itself.
    Legislation I introduced with Senator Hutchison and 
Kennedy, the Comprehensive TB Elimination Act, would provide 
the resources necessary to respond to outbreaks of drug-
resistant TB in the United States and put the Nation back on 
the path toward eradicating TB. The bill has key provisions for 
enhancing research and demonstration projects to eliminate 
tuberculosis in our country. It increases research funding for 
new diagnostic and treatment tools, new vaccines, studies of 
at-risk populations, and research into the relationship between 
TB and HIV/AIDS.
    Our bill addresses a critical piece of the puzzle when it 
comes to combating TB domestically and globally, investment in 
new tools to diagnose, to treat, and to prevent TB. The reality 
is our TB diagnostic tests, drugs, and vaccines are all 
seriously outdated. And with the spread of drug-resistant TB, 
especially XDR TB, these tools are increasingly inadequate. The 
diagnostic tools that we have are more than 100 years old and 
aren't quick or sensitive enough to detect TB in all 
populations.
    The TB vaccine is more than 85 years old and is only 
effective in children. The Comprehensive TB Elimination Act 
will expand CDC and NIH research efforts and new tools, so that 
we can develop the diagnostic tests and the drugs and the 
vaccines that we need to effectively control TB globally and 
domestically.
    Today, we'll discuss how a combination of standard TB 
control, the directly observed treatment short-course and all 
that entails, and an investment in new diagnostic treatment and 
prevention tools can combat this disease.
    I'll also want to briefly mention legislation Senator Hatch 
and I will introduce tomorrow that focuses specifically on 
antimicrobial resistance. Drug resistance sets the clock back 
on our ability to combat a host of infections, increasing the 
threat these infections pose to human health, and dramatically, 
dramatically increasing the cost of treatment. Our 
legislation's intended to ensure that the United States takes 
action now to prevent intractable problems later.
    But today's hearing rightly focuses on a global killer with 
domestic implications. I look forward to our witnesses' 
testimony. And again, welcome Dr. Castro, and I'll call on 
Senator Enzi.
    Thank you.

                   Opening Statement of Senator Enzi

    Senator Enzi. Thank you, Mr. Chairman. And I want to 
congratulate you on an outstanding summary. I do have a full 
statement that I'd like to be a part of the record, but I think 
you pretty well covered that. And, so I would just ask for 
unanimous consent to have it in the record.
    Senator Brown. Without objection, so ordered.
    [The prepared statement of Senator Enzi follows:]

                   Prepared Statement of Senator Enzi

    Good morning, and thank you all for joining us today to 
address an extremely important and timely topic.
    It is absolutely critical that we as a Congress and as a 
nation realize that the fight against TB is BOTH an urgent U.S. 
issue, but also a GLOBAL threat of immense proportions.
    Hard as it may be to believe, each year approximately 9 
million people worldwide contract active TB, and about 2 
million of these die from the disease.
    Because of increased mobility world-wide, up to one-third 
of the world's population are now TB carriers--most of whom are 
latent carriers who are unaware of their condition. In other 
words, fully one-third of the world's population--nearly 2 
billion people--are infected with TB.
    It is difficult to draw clear lines of distinction with 
regard to the spread of TB between domestic and international 
settings. In the United States, the problem is also very 
severe. Here at home, nearly 14,000 cases of active TB were 
reported in 2006, with an estimated 10 to 15 million more 
carrying latent versions of the infection. In 2006, the TB rate 
in foreign-born persons in the United States was 9.5 times 
greater than that of U.S.-born persons.
    If these figures are not enough to wake us up and get us 
worried--we also face the emerging appearance of drug-resistant 
strains of tuberculosis--against which no current drug or 
combination of drugs can currently combat.
    Although the need is clearly very great, both globally and 
nationally, neither we as a nation, nor we as a global 
community, currently have adequate mechanisms, either 
clinically or from a public health management perspective, to 
combat this threat.
    Although it thankfully has not yet happened, the hazard 
posed by drug-resistant TB for a virtually unstoppable epidemic 
is a very real specter we must confront and combat--both 
nationally and globally.
    The case last spring of the Atlanta lawyer Andrew Speaker 
made international headlines and drew needed attention to this 
danger. Mr. Speaker, allegedly with full knowledge of his 
infection both by himself and health authorities, nevertheless 
managed to travel to, from, and through several countries 
internationally.
    Only very belatedly--and thankfully without tragic result--
were authorities able to catch up to the problem and deploy 
needed intervention and effective containment mechanisms.
    This case highlighted starkly not only our own shortcomings 
domestically, but the alarming absence of a global strategy to 
deal with this threat. As international travel becomes ever 
easier and greater in volume, so does the prospect of a 
horrendous disaster that could impact not only us here at home, 
but millions worldwide as well.
    Amplifying this threat is the fact that drug-resistant TB 
is not a clinical problem that stands alone. Even as we face 
this threat, similar and intertwined hazards, such as drug-
resistant AIDS strains and untreatable influenza viruses, 
challenge us as well.
    A very serious hole in our ability to fight tuberculosis 
exists globally, nationally, and at the State and local levels. 
It is the current lack of systems for the containment, up to 
and including isolation of infected persons, should an outbreak 
occur.
    I do realize that buzz words like ``quarantine'' and 
``isolation'' raise controversy and concern--some of which I 
share, and I do think we need to be careful in the terms we 
use--and the strategies we deploy.
    As everyone here knows, I am certainly no advocate of heavy 
handed government policies. However, in the face of a problem 
as severe as this, I do believe we need to face squarely the 
reality that, sometimes, urgent hazard does require equally 
urgent and stern measures to fight it.
    Although certainly not a direct answer to the problem of 
drug-resistant strains of TB, another TB-combating strategy 
worth close attention is the so-called DOTS approach. DOTS is 
short for ``Directly Observed Treatment, Short-Course'' action. 
The DOTS approach, which is gaining increasing international 
attention, focuses on a patient-centered strategy of closely 
supporting and monitoring the treatment of infected persons, 
both to assure they follow through on their own treatment and 
that the threat their infection poses to others is minimized.
    Whether here at home or globally, my view is that the fight 
to control and prevent TB is one that should focus on 
marshalling and better coordinating the resources not only of 
government agencies, both United States and abroad--but also 
better deploying and coordinating State efforts, local efforts, 
and private sector innovation. Also of immeasurable potential 
are the skills and resources deployable through charitable and 
corporate collaborations.
    The answer is not just more money--nor should it focus on 
top-down prescriptive legislative instructions, except where 
urgently and expressly needed.
    Senator Brown, who is chairing this hearing, deserves 
tremendous credit for pushing hard for committee attention and 
action to help prevent, control, and manage tuberculosis--
particularly drug-resistant strains of the disease.
    The TB legislation he has authored, with Senator Clinton, 
which focuses principally on U.S. domestic strategies, has 
undergone considerable discussion and modification since its 
introduction earlier this year--and I am pleased by the forward 
steps he has taken to address serious concerns about his 
original bill, both by the Administration, many on this 
committee, and others.
    We still have work to do on this bill, but I am hopeful--
cautiously hopeful--a bipartisan resolution can be reached 
before the bill is taken up for markup. This committee's strong 
track record of bipartisan collaboration--particularly on 
public health bills--is, I believe, one of our committee's 
proudest features.
    I think Senator Brown, Chairman Kennedy, and all of us on 
this committee, hope to avoid a repeat of what happened last 
summer, when this bill was rushed toward markup--only to be 
pulled when it became clear that outstanding concerns were too 
significant to be bridged in a collaborative, bipartisan 
manner.
    Much progress has been made since then, but I think we need 
to keep last summer's experience very much in mind as we again 
proceed to markup--which the Chairman indicates may be 
scheduled very soon. This challenge may prove a tall order--but 
one I and others on this side will attempt in good faith to 
achieve.
    One of the topmost concerns of many about the original 
Brown bill, including HHS, CDC, myself and others, was that it 
attempted to write a relatively detailed Federal prescription 
for fighting and preventing TB. Much more preferable is greater 
flexibility for the Federal authorities on the ground, and 
better collaboration with our non-Federal partners, whether 
they be States, local entities, charities, or corporate 
innovators.
    However, I do think most of us very much agree that the 
core directions of the Brown bill, both as introduced and as it 
has evolved, are ones of common concern and urgent need.
    These include efforts to better develop diagnostic and 
treatment tools, better testing of the safety and effectiveness 
of new treatments and vaccines, and a need for special 
attention to at-risk populations, and closer examination of 
improved public health intervention strategies. This last 
point--better intervention strategies--is of particular 
importance.
    This committee as we speak is aggressively engaged in 
examining the Andrew Speaker case of last spring.
    This investigation, which is being conducted on a fully 
bipartisan basis, is not yet complete. But its work is already 
making very clear that greater authority may be needed--
coordinated at both the Federal and State level--for rapid and 
firm containment of drug-resistant TB cases.
    One of our witnesses today, Dr. Frieden, from New York, 
will speak to the work his city and State have been doing to 
put in place such systems.
    I am hopeful that our committee's continuing investigation 
into the Speaker case and effective control of drug resistant 
outbreaks will give us useful guidance in this area.
    I regret that the anticipated markup schedule planned by 
the Majority does not better accommodate incorporation of this 
work in a coordinated manner. I hope that we work to ensure 
that all our legislative activity is adequately informed by 
investigative efforts.
    I do understand the importance of moving forward. This 
hearing, Senator Brown's legislation, and our HELP 
investigation are all steps toward a common goal of better 
attacking the challenge of TB--one I share.
    Senator Brown. Senator Coburn.

                      Statement of Senator Coburn

    Senator Coburn. First of all, let me thank you for your 
work on this subject and many others, on infectious disease. 
This is an important area that Congress needs to become more 
learned on. I appreciate those that are going to testify today 
and their efforts in resolving this.
    There is something Congress can do and we ought to be doing 
it. And I look forward to our testimonies today. I will be 
leaving probably before we have time for questioning, and would 
like unanimous consent to submit my questions to the record for 
later.
    Senator Brown. Of course. Without objection, so ordered. 
Thank you.
    Senator Allard.

                      Statement of Senator Allard

    Senator Allard. Mr. Chairman, I'll also be brief. I don't 
have any organized comments here that I will be making, or 
formal comments I'll be making, just would like to commend the 
committee for taking an interest in this particular subject 
area. It is important. And thank the panelists for taking time 
to be here to testify before this committee. We certainly 
appreciate you, Dr. Castro, being here from the Center for 
Disease Control and Prevention, Tuberculosis Research Facility 
at Colorado State University in Colorado.
    We also have testifying before us here, Dr. Randall Reves, 
Professor of Medicine and Infectious Disease, University of 
Colorado. I want to welcome him personally. He's the Medical 
Director of the Denver Metro Tuberculosis Clinic and Chairman 
of the Stop TB, USA. We are certainly pleased to see so much 
interest in Colorado on this emerging disease, partly because 
we've had an incident, involving an individual who traveled 
internationally with tuberculosis and raised a lot of issues, I 
think, with that particular incident.
    This is a very timely hearing and I want to thank all of 
you for being here, for your testimony. It's not always easy to 
get away from your daily jobs to be here and to give us your 
expertise. And we're looking forward to that. I have the same 
problem that Dr. Coburn has, which is that I have other events 
going on right now, so I may not be able to stay for the entire 
testimony, but I do have some questions I want to submit for 
the record.
    Thank you.
    Senator Brown. Thank you, Senator Allard.
    Since January 1993, Dr. Castro has served as the Director 
of the Division of Tuberculosis Elimination in the National 
Center for HIV, STD, and TB prevention in the Center for 
Disease Control and Prevention. In this role, Dr. Castro leads 
the team of technical experts devoted to TB elimination efforts 
in the United States. His division sponsors TB prevention 
control and research activities throughout the Nation. Dr. 
Castro has advanced the involvement by the United States 
international tuberculosis control efforts, serving as an 
expert advisor to the World Health Organization. He was 
promoted to the flag rank of Assistant Surgeon General in May 
2000. Dr. Castro will provide an overview of TB in the United 
States. Dr. Castro, thank you for your fine work over the last 
decade and a half, and welcome.

  STATEMENT OF DR. KENNETH G. CASTRO, M.D., ASSISTANT SURGEON 
GENERAL, USPHS, DIRECTOR, DIVISION OF TUBERCULOSIS ELIMINATION, 
CENTERS FOR DISEASE CONTROL AND PREVENTION, U.S. DEPARTMENT OF 
             HEALTH AND HUMAN SERVICES, ATLANTA, GA

    Dr. Castro. Thank you very much. Good morning, Chairman 
Brown, Ranking Member Enzi, and other distinguished members of 
the committee.
    It is my pleasure to be here today to discuss whether CDC's 
role in eliminating tuberculosis, including multidrug 
resistant- and extensively drug-resistant tuberculosis in the 
United States.
    This statement highlights what is necessary for the United 
States to work toward eliminating tuberculosis domestically, 
and to assist in global tuberculosis control.
    As the committee is already well-informed about the 
definitions of multidrug-resistant tuberculosis and 
extensively-drug resistant TB, I will go directly to my 
discussion of TB in the United States.
    For starters, I would like to observe that Senator Brown's 
father's comment is a very commonly held misconception. When 
you interview persons throughout this country, many think TB is 
a disease of the past, and we still have 40 new cases being 
diagnosed every day. So, by the end of today, there will have 
been another 40 new persons diagnosed with TB in this country.
    In 2006, States reported to see the lowest incidents of 
tuberculosis, with 13,779 persons diagnosed with tuberculosis 
in that year. Since the unprecedented tuberculosis resurgence 
in our country which peaked in 1992, the number of U.S.-TB 
cases reported on a yearly basis has decreased by 48 percent.
    However, this remarkable accomplishment is tempered by a 
slowing of the rate of decrease, as you've already observed, 
Senator, from 7.3 percent, annual percent decrease from 1993 
through 2000, to a slowing now to 3.8 percent between 2000 and 
2006.
    This may be a harbinger of the stagnation we're starting to 
see in our progress toward elimination, and several challenges 
to tuberculosis elimination remain, including: No. 1, the 
health disparities associated with tuberculosis. Racial and 
ethnic minorities continue to suffer from TB more than the 
majority of populations in the country. The rate of 
tuberculosis in U.S.-born blacks is 8 times higher than for 
U.S.-born whites.
    Second, foreign-born persons are adversely impacted. In 
fact, 57 percent of cases last year were in persons born 
outside this country, reflecting the global reality.
    Third, we continue to see sporadic outbreaks and clusters 
of tuberculosis which outstrip the local health departments' 
capacity to respond to these.
    Fourth, cases with consistent patterns of drug-resistance 
threaten our ability to control tuberculosis.
    And, fifth, there's a continued need to invest in the 
development of new tools--as you've already heard--to rapidly 
and reliably diagnose tuberculosis, provide safe and effective 
treatment, and ideally, vaccines.
    In the United States, cases of multidrug-resistant TB 
accounted for less than 1 percent of all persons reported in 
2006, and there were 48 persons with extensively drug-resistant 
TB identified between 1993 and 2006.
    While the total number of these persons is relatively 
small, their impact on U.S.-TB control programs can be 
devastating in terms of human capital and financial resources. 
For example, the average hospitalization cost of one person 
with XDR TB is averaging about $500,000.
    To eliminate tuberculosis, CDC and its partners must 
continue to ensure the United States has the essential elements 
of a strong TB control program. These include, No. 1, ensuring 
a strong Federal leadership, we have a Federal TB taskforce 
that coordinates activities between Federal agencies.
    Second, ensuing that State and local TV programs are 
adequately prepared to identify and treat patients, and in 
treating them, prevent the manufacturer of drug resistance.
    Third, invest in the research and development for improved 
drug treatment regimes, vaccines and diagnostics.
    Fourth, training of healthcare professionals to identify 
and treat this complex disease. And that's becoming an 
increasing challenge, there are fewer cases of tuberculosis, 
the proficiency in the medical profession keeps going down, and 
one of those things that CDC is doing is sponsoring four 
regional training and medical consultation centers, to make 
sure that there is access to the repository of expertise 
somewhere in the country.
    And last, we need to work with partners globally, to reduce 
the introduction of tuberculosis in the United States, and 
reduce the burden of the disease globally.
    Thank you for your time, and for your interest. And I will 
be happy to answer any questions. I have provided written 
testimony that has additional details, for the record.
    [The prepared statement of Dr. Castro follows:]
           Prepared Statement of RADM Kenneth G. Castro, M.D.
    Good morning, I am Dr. Kenneth Castro, Director of the Division of 
Tuberculosis (TB) Elimination, in the National Center for HIV/AIDS, 
Viral Hepatitis, STD, and TB Prevention, in the Coordinating Center for 
Infectious Diseases, in the Centers for Disease Control and Prevention 
(CDC) within the Department of Health and Human Services (HHS). 
Chairman Brown, Ranking Member Enzi and other distinguished members of 
the committee, it is my pleasure to be here to discuss with you CDC's 
role in eliminating tuberculosis, including multidrug-resistant and 
extensively drug-resistant tuberculosis, in the United States. This 
statement highlights what is necessary for the United States to work 
toward eliminating TB domestically and to assist in the Millennium 
Development goals for global TB control.
                        tb and drug resistant tb
    Tuberculosis is an airborne infectious disease that is spread from 
infectious persons when lung or throat secretions become aerosolized. 
In the late 19th and early 20th centuries, until the introduction of 
the antibiotic streptomycin in the 1940s, TB was one of the leading 
causes of death in the United States. TB may also mimic many other 
diseases in its clinical state. Currently, the World Health 
Organization (WHO) reports that one in three people in the world are 
infected with dormant or latent Mycobacterium tuberculosis, the 
bacteria that cause TB and nearly 9 million people develop active 
disease each year.
    The risk of transmitting any type of TB depends on several factors, 
including the extent of disease in the patient with TB, the duration of 
exposure, and ventilation. Most of the people who become infected with 
TB do so after prolonged, close contact with an infectious patient. 
People can also be infected, but remain healthy until the bacteria 
become active at a later time. This can happen when immunity is 
compromised, for example, by HIV, advancing age, immunosuppressive 
therapies and some medical conditions such as some autoimmune disorders 
and cancers.
    TB that is not resistant to drugs can be treated with a 6 to 9 
month course of ``first-line drugs'' (the most effective and safe), 
including isoniazid and rifampin; this treatment cures over 95 percent 
of patients. However, since people in many resource-poor countries lack 
access to appropriate treatment, about 1.6 million people die each year 
from TB.
    TB that is resistant to at least isoniazid and rifampin is called 
multidrug-resistant (MDR) TB. MDR TB requires treatment for 18-24 
months with ``second-line drugs'' that are less effective, often poorly 
tolerated by the patient, and far more costly. The cure rate for MDR TB 
is 70-80 percent under optimal conditions, but is usually closer to 50 
percent. Many countries with a high TB burden lack the laboratory 
capacity to test for MDR TB and, even when MDR-TB patients are 
identified, these countries often lack the resources to cover the cost 
of second-line drugs and the intensive support required to administer 
the drugs.
    Extensively drug-resistant TB (XDR TB) is a subset of MDR TB caused 
by strains of bacteria that are resistant to the most effective first- 
and second-line drugs. Reported mortality rates among persons with XDR 
TB are extremely high. Among non-immunocompromised persons, reports 
indicate that approximately 30 percent of patients can be cured, and 
more than half of those with XDR TB die within 5 years of diagnosis. 
Among immunocompromised persons, the illness is more severe, the 
mortality rate is even higher and death occurs within a shorter time.
    To date, 41 countries have confirmed cases of XDR TB; however, 
because many countries do not routinely test all isolates for 
resistance to second line drugs, the precise global incidence of XDR TB 
remains uncertain. Since drug resistance does occur, XDR TB could be 
much more widespread. Factors associated with development of drug 
resistant cases include the use of second-line drugs in suboptimal 
conditions, inconsistent TB case management, interruptions in drug 
availability due to supply management or resource limitations, patient 
non-adherence with drug treatments, and high HIV prevalence. The 
ability of the disease to develop resistance to therapies and for those 
infected with drug resistant strains to travel easily across borders 
makes worldwide TB control efforts critical. This is especially 
critical given the burden to the public health care system resulting 
from intense patient management and prolonged therapy.
                        tb in the united states
    CDC has reported the lowest number of TB cases in the United 
States, ever, at 13,779 new cases diagnosed during 2006. This 
represents a 2.1 percent decrease from the previous year. The case rate 
also decreased from 4.7 to 4.6 cases per 100,000, a decline of 3.1 
percent. Since the 1992 TB resurgence peak in the United States, the 
number of TB cases reported annually has decreased by 48 percent. The 
latest data show that deaths are also decreasing, from 657 deaths in 
2004 to 646 deaths in 2005. Despite these successes, the decreasing 
trend has slowed from an annual average decline of 7.3 percent for 1993 
through 2000 to an annual decline of 3.8 percent for 2000 through 2006. 
Challenges to TB control remain, including: (1) racial and ethnic 
minorities continue to suffer from TB more than majority populations; 
(2) foreign born persons are adversely impacted; (3) sporadic 
outbreaks/clusters which outstrip local capacity; (4) cases of drug 
resistance threaten our ability to control TB; and (5) need for new 
tools for rapid and reliable diagnosis, safe and effective treatments 
and vaccines.
    The United States still faces disparities in TB rates between 
racial and ethnic groups in U.S.-born persons. Current rates among non-
Hispanic Asians are 25.6 cases per 100,000; among Hispanics or Latinos, 
9.2 cases per 100,000; among black or African-Americans, 10.2 cases per 
100,000; and among non-Hispanic whites, 1.2 cases per 100,000. These 
case rates clearly indicate that additional efforts may be needed for 
these population groups.
    Despite decreasing TB incidence in the United States, the majority 
of reported TB cases are foreign-born. The percentage of TB cases in 
foreign-born persons in the United States increased from 22 percent of 
report cases in 1986 to 57 percent in 2006. Overall the number of TB 
cases among the foreign born remained stable, at about 7,000 to 8,000 a 
year from 1993 through 2006.
    Cases of MDR TB accounted for less than 1 percent of TB cases 
reported in 2006 (91 primary MDR cases out of 13,779). The proportion 
of cases of MDR TB among foreign-born persons has increased 
dramatically since the early 1990s, increasing from approximately 26 
percent of MDR TB cases in 1993 to approximately 76 percent of MDR TB 
cases from 1999 through 2006. And of the 48 cases of XDR TB identified 
from 1993 through 2006, more than half were among the foreign born. In 
addition, trends in XDR TB cases indicate that the problem in the 
United States is shifting to reflect the global epidemic. XDR TB cases 
that occurred from 1993-1999 were more likely to be in patients who 
were HIV co-infected and born in the United States. However, the 
majority of XDR TB cases that occurred from 2000-2006 were among 
foreign-born persons (75 percent of 11 cases).
    While the total number of MDR and XDR TB cases is relatively small, 
their impact on U.S.-TB control programs can be significant in terms of 
human capital and financial resources. For example, one patient with 
MDR or XDR TB requires a minimum of 18-24 months of treatment, and in-
patient costs alone for XDR TB can average $500,000 per case. Small 
programs are vulnerable in the event that an MDR or XDR TB case is 
identified in their jurisdiction. For example, this year, a case of MDR 
in Idaho nearly depleted the State's entire drug budget of 
approximately $40,000. States that are unable to carry out their TB 
programs could be more likely to face outbreaks. From 1999 to 2004 CDC 
investigated only one outbreak of MDR TB, involving three patients in a 
State jail. Since 2004, CDC has been called to investigate four State 
outbreaks of MDR TB, including one which involved international travel. 
The occurrence of MDR and XDR TB unveils longstanding limitations with 
available diagnostic tools.
   essential elements of an effective tb program in the united states
    Essential elements of an effective TB program in the United States 
include Federal leadership and policy guidelines development working in 
partnership with strong State and local TB control programs. Other 
elements include: research into new drugs, diagnostics and vaccines, 
prevention of the importation of disease, and work with other countries 
and organizations to control TB globally.
          strong federal leadership and guideline development
    At the Federal level, CDC serves several critical roles in 
controlling TB. CDC provides leadership and scientific support for TB 
control efforts both nationally and internationally. CDC monitors TB at 
the national level and develops standards for monitoring TB at the 
State level. CDC also utilizes expert panels and internal technical 
expertise to develop TB guidelines to be implemented with the help of 
other U.S. Government agencies and professional associations. These 
guidelines address factors such as core components of TB control 
programs, TB control in healthcare settings, use of diagnostic tests 
and recommended treatment regimens. The Federal TB Task Force 
established in 1991 facilitates coordination of activities between 
Federal agencies.
               strong state and local tb control programs
    The best defense against the development of drug resistant 
tuberculosis is a strong network of State and local public health 
programs and laboratories. If the United States does not protect its 
public health infrastructure, weaknesses in programs will enable 
additional MDR TB outbreaks--as seen in the 1980's and early 1990's. As 
with other infectious diseases, State, local, and territorial health 
departments support and augment the medical care system. These ``front 
line'' public health agencies are in direct contact with medical care 
providers and patients, providing important TB control services such as 
directly observed therapy (DOT, a proven method to improve adherence 
and thus prevent drug resistance), laboratory support, surveillance, 
contact tracing, and patient counseling. CDC provides about $100 
million annually in support to State, local and territorial health 
departments to prevent and control TB. Federal funding levels for TB 
control have been relatively stable, but many State and local 
governments have faced budget challenges in recent years. To better 
match TB funding to the current TB disease burden across the United 
States, CDC uses a funding formula to distribute a portion of available 
funds to States with higher disease burden and more complex cases to 
manage.
               improved ability to diagnose and treat tb
    Research to improve TB diagnostics and drug treatment regimens is 
critical to controlling TB worldwide. The most widely used diagnostic 
test for latent TB is over 100 years old. More rapid and sensitive 
tests are needed for the diagnosis of active TB and for MDR TB and XDR 
TB. The most common drugs used to treat TB are more than 40 years old. 
The global goals for a better TB treatment regimen include a shorter 
treatment length (2 months or less); high (99 percent) cure rate; and 
decreased side effects and fewer drug interactions, especially with HIV 
treatment medicines. In addition, development of a very short course 
(i.e., weeks), well tolerated treatment is greatly needed for latent TB 
infection.
Diagnostics
    CDC has supported efforts to improve surveillance and diagnosis of 
TB in the United States. These include the TB Genotyping Program, now 
active in 50 States, research to evaluate the use of nucleic acid 
amplification testing, and development of guidelines for use of 
QuantiFERON-TB-Gold to diagnose infection.
    However, new diagnostic tools are needed to identify TB infection 
and to determine the best course of action for treating both active and 
latent cases. Identification of rapid, highly accurate, point-of-care 
tests for TB diagnosis and identification of drug resistance would 
enable physicians to identify the correct regimen at the time of 
diagnosis. New point-of-contact tests have been developed to identify 
TB infection. However, further evaluation of these tests is needed.
    Improving testing for drug susceptibility is also critical. Current 
tests for drug susceptibility testing are conducted by growing colonies 
of TB bacilli and exposing them to various antibiotics. Since TB 
bacilli are notoriously slow-growing organisms, this process takes at 
least 1 month to complete. This process is also a difficult procedure 
to standardize, and maintaining the proficiency to perform these tests 
is challenging in laboratories that do not conduct them frequently.
    Newer molecular tests for drug susceptibility testing hold great 
promise for reducing the time for detecting resistance from months to 
days. However, such tests are not standardized and are only performed 
at a handful of laboratories in the United States. Commercial test kits 
have been developed, but have not been adequately field tested and are 
not licensed for use in the United States by the Food and Drug 
Administration (FDA).
New Treatment Regimens
    It has been over 30 years since the effectiveness of short-course 
(6 months) TB therapy was first introduced. Since then, only one new 
anti-TB drug class has appeared, and the utility of that class of drugs 
may be limited by their widespread use for other common conditions. For 
the first time in over 40 years, four new anti-TB drug candidates have 
entered clinical trials, and other candidate compounds are in earlier 
stages of development.
    CDC's TB Trials Consortium has a leading role in clinical 
tuberculosis research. Results from these consortium trials have formed 
the basis for the treatment guidelines developed by CDC and the 
American Thoracic Society, and in updating regimens for both HIV and 
non-HIV infected patients. This research will be increasingly important 
for the development of new drugs and regimens for drug-resistant TB. 
CDC has had primary responsibility for programmatically relevant TB 
drug and diagnostics research since the early 1960s. CDC also works 
closely with the National Institute for Allergy and Infectious Diseases 
which has the lead basic research on TB drugs and vaccines.
                    training of health care workers
    TB remains difficult to diagnose and treat, and because there are 
relatively few cases in the United States, many health care workers 
lack experience and proficiency in recognizing it. CDC supports 
Regional Training and Medical Consultation Centers to train health care 
workers in TB prevention and control, and to serve as consultants to 
community physicians and local and State TB programs. CDC also provides 
direct training and health communication tools for TB programs and 
health care workers.
                 preventing the importation of disease
    The United States works with partners worldwide in an effort to 
reduce the introduction of TB and drug-resistant TB into the United 
States. For example, CDC is involved with United States-Mexico Border 
activities to protect against the development of drug resistance. CDC 
supports TB prevention and control activities in the four States that 
border Mexico to ensure uninterrupted access to treatment throughout 
the entire course of therapy.
    In addition, the United States has strengthened the requirements 
for screening and treatment of refugees prior to their resettlement in 
the United States. These requirements are credited with a 14-fold 
reduction in reported TB cases in refugees from Thailand since 2005. 
CDC is also piloting a project to provide rapid notification to U.S.-TB 
control programs on the TB status of newly arriving immigrants and 
refugees.
    Finally, CDC also works to prevent the introduction of TB cases 
into the United States and the movement of infected individuals between 
States. When necessary, CDC can use isolation and quarantine strategies 
to restrict the movement of individuals who are traveling with TB. To 
this end, CDC maintains a close partnership with DHS and its agencies, 
and has worked hard over the past months to strengthen the link between 
public health and homeland security. The partnership between Customs 
and Border Protection and CDC is particularly vital, as CBP officers 
act as CDC's ``eyes and ears.'' It should be noted that State and local 
governments have primary responsibility for isolation and quarantine 
within their borders and conduct these activities in accordance with 
their respective laws and policies.
                        controlling tb globally
    Because we live in a global economy and because most cases of TB in 
the United States are among foreign-born persons, it is critical for 
the United States to assist in TB control globally. CDC provides 
leadership and technical assistance in infection control, epidemiology, 
surveillance (including drug resistance surveys), program and 
laboratory services development, monitoring and evaluation, operations 
research and training, improving diagnostic services, and identifying 
clinical factors important to TB outcomes. These efforts build upon 
CDC's successful program to control TB in the United States. CDC 
collaborates with U.S. partners to reduce TB in high-burden countries 
by developing guidelines, recommendations, and policies. Over the past 
3 years, CDC has been supporting TB control efforts in more than 25 
countries on 5 continents.
    In addition to working closely with Ministries of Health in other 
countries, CDC works with multilateral organizations including the 
World Health Organization and the International Union for TB and Lung 
Disease, foundations (including the Bill and Melinda Gates Foundation 
funded collaboration, such as the Foundation for Innovative Diagnostics 
(FIND)), and non-governmental organizations. CDC is a founding member 
of the Stop TB Partnership, a global effort of more than 500 
governmental and non-governmental organizations, housed by the WHO. 
Members of the Stop TB Partnership work towards achieving the 2006-2015 
Millennium Development Goals of reducing global TB deaths by 50 percent 
and the number of persons suffering from TB by 50 percent.
    Finally, as an implementing partner of the President's Emergency 
Plan for AIDS Relief (PEPFAR), CDC plays a critical role in efforts to 
address TB in the context of PEPFAR's HIV/AIDS prevention and treatment 
programs. Funding under these activities is tracked and accounted for 
under PEPFAR country operation plans.
                               conclusion
    To control TB, CDC and its partners must continue to ensure the 
United States has the essential elements of a strong TB control 
program. These include: (1) ensuring strong Federal leadership; (2) 
ensuring that State and local TB programs are adequately prepared to 
identify and treat TB patients to prevent drug resistant cases; (3) 
developing improved drug treatment regimens and diagnostics, (4) 
training health care professionals to identify and treat this complex 
disease; and (5) working with partners globally to reduce the 
introduction of TB into the United States and reducing the burden of 
disease globally.

    Senator Brown. Thank you, Dr. Castro.
    You had said it's $500,000 average cost for an excessively 
drug-resistant TB patient, could be $500,00 in a hospital. What 
is it for MDR TB, what is it for the most common forms of TB?
    Dr. Castro. Hospitalization costs, pardon me--alone. It 
excludes indirect costs, lost wages, that also contributes to 
the added cost.
    Senator Brown. When you said a few hundred times about MDR, 
can you give me something a little more specific in a range of 
20,000 to 50,000, or whatever the range is?
    Dr. Castro. Well, in the case of MDR, you could go up to 
about $2,500 for the treatment of someone, especially if they 
can be treated as outpatients, and don't require 
hospitalizations. Once they require hospitalization, and 
potential for surgery, the cost goes up.
    Senator Brown. So, MDR TB often is treated outpatient in 
our country, in the United States.
    Dr. Castro. Yes, if we can rely on the workforce of 
outreach workers that many Health Departments have, working 
with private physicians. You could do that--it is difficult, 
though. Some patients will require hospitalization, because of 
the extent of the disease, some may also require surgical 
intervention as a more extreme measure for their type of 
disease.
    Senator Brown. And there's not a quarantine issue on the 
MDR TB patients?
    Dr. Castro. No, what we do throughout the country is we 
rely on a system that facilitates the provision of treatment, 
the direct observation of treatment to ensure adherence, and in 
an experience that was published by New York City after 
following thousands of these persons, they showed that in 96 
percent of the cases, you can successfully treat tuberculosis 
by relying on these systems. In about 4 percent, you needed to 
resort to the more restrictive measures, because in spite of 
all attempts to provide treatment, persons were defaulting, and 
that's when you'd then need to resort to the judicial system, 
or restrict individuals. And those measures are available to 
us.
    But, fortunately, we don't need to rely on them often, 
because most people want to get better, and if you provide the 
patient-
centered approaches that would facilitate access to treatment, 
take care of the side effects that they will encounter with 
these medications, we will likely succeed.
    Senator Brown. Since the 1960s, I understand CDC has had 
the responsibility for TB, drug and diagnostic research. 
Describe, if you would, your role in what CDC does for 
research--drug and diagnostic research--and contrast that, so I 
can be a little clearer on what NIH's role is on all of this.
    Dr. Castro. Yes, thank you. In the 1960s a clinical trial 
for tuberculosis of the public health service was transferred 
to CDC. For years that was done on a shoestring budget.
    In the nineties when there were additional resources 
devoted to tuberculosis, we reconstituted the capacity to 
conduct clinical research. So, CDC sponsors a multicenter 
clinical-trials consortium that includes a few countries 
outside of the United States, but there are about 26 members of 
this consortium, most of them in the United States, and it 
enables us to implement the kind of clinical trials that you 
would have traditionally seen with NIH.
    The way we conduct this, however, is by working closely 
with NIH to avoid any duplication of effort. NIH continues to 
support the basic research that is going to be required for the 
field trials that we would then be engaged in, and we have 
Memorandums of Understanding between our agencies to make sure 
that we can conduct it in this fashion.
    Most recently, all of the evidence-based guidelines for TB 
treatment, have incorporated the findings of these type of 
research done over the last few years.
    Senator Brown. When we talk about TB diagnostic drugs, the 
diagnostic tests are pretty much 100 years old, the TB 
vaccine--which seems to be effective only in children--is 85 
years old; are we likely to see NIH come up with the basic 
science, and the basic scientific breakthrough separate from 
what the private sector is doing--which is pretty huge--and 
then CDC would be more likely to do the clinical trials of 
that? Is that the way it will work?
    Dr. Castro. That would be pretty much the way that you 
would see it operating, NIH supporting a lot of the basic 
science, and then we would come in and try to do the field 
trials to evaluate, how do these tests behave in the hands of 
clinicians in different parts of the country, and in the world?
    Senator Brown. Clinical trials also were conducted 
internationally, I assume?
    Dr. Castro. Yes, we have a site in Brazil, another one in 
Durbin, Uganda and in Spain. But those are all done through 
collaborations with U.S.-based academic institutions.
    Senator Brown. Thank you, Dr. Castro.
    Senator Coburn.
    Senator Coburn. Thank you.
    Dr. Castro, what is the total budget that the CDC is 
applying toward TB research, diagnosis and treatment?
    Dr. Castro. Our total budget for the clinical trials is 
hovering about $9 million, it used to be a little bit more, 
we've had to cut back on that.
    There's also another consortium to conduct epidemiologic 
and behavioral studies, and that is funded around $7 to $8 
million. So, put together, I'd say about $15 million out of the 
total budget is used for applied research, or the more 
programmatically-relevant research.
    Senator Coburn. OK. And outside of the research, how about 
treatment and coordination with State health departments and 
everything? In other words, I'm trying to look for a global 
number, what do we spend, CDC now, everything combined----
    Dr. Castro. Oh, everything combined?
    Senator Coburn. Treatment, research, trials, the whole 
works?
    Dr. Castro. One hundred and thirty-eight million.
    Senator Coburn. A hundred and thirty-eight million dollars.
    All right.
    I will submit the rest of my questions, I do want to enter 
into the record a statement that I have made recently, and it's 
going to be published in the Congressional Record, as well, 
just on disease-specific bills that we do, the Chairman knows 
that I'm supportive of efforts in this, but I have a great deal 
of problems when we start picking the disease and the amount of 
money, and take those decisions away from scientists and peer-
reviewed studies to tell us where we should do it.
    So, I'd just like unanimous consent to enter this into the 
record. My pledge is to work with the Chairman to accomplish 
his goals, and also my goal, of keeping decisionmaking on where 
we spend money, with the scientists and the professionals and 
not the politicians.

    [Editor's Note: The statement referenced above was not available at 
time of print.]

    Senator Brown. Thank you, Dr. Coburn. Since you are both, 
especially. So, thank you. Dr. Coburn--and Senator Coburn, 
Senator Burr and I--on the Energy and Commerce Committee in the 
House would hear people, particularly from NIH come in and 
lobby for their disease, if you will, and we pretty much agreed 
over the years, bipartisanly, that we shouldn't direct NIH to 
put this much money in this disease control, and this much 
money in this research and this much money in this research, 
but really letting those decisions be made there.
    In terms of the treatment, it's a bit of a different story. 
Certainly on the research, there's close to unanimity on that.
    Senator Allard is recognized.
    Senator Allard. Just briefly, would you describe the 
current tuberculosis research and development at CDC labs as it 
relates to clinical trials to evaluate safety and effectiveness 
of new drugs, diagnostics and vaccines for late-tuberculosis 
infections?
    Dr. Castro. Let me see if I understand--you want me to 
describe----?
    Senator Allard. The research that you're doing.
    Dr. Castro. Yes, we're now evaluating a new drug, for 
example, Moxifloxicillin is a drug that looks very promising in 
the mouse model, so much so that we might be able to reduce the 
total duration of treatment for persons with tuberculosis, and 
we're evaluating that for its safety and efficacy.
    We're also evaluating some of the newer tests that have 
been FDA licensed, yet need to be field-tested to see how well 
they behave in other settings at state-based laboratories. One 
of them is a Quanti-Feron gold test.
    There are a couple of other diagnostic tests that are being 
evaluated for FDA approval, and we're looking to evaluate them 
as they get used to test healthcare workers, who get routinely 
screened for tuberculosis.
    The relative advantage to some of these tests is that they 
would rely on a blood draw, rather than insert a needle in the 
forearm, have the person come back 48 to 72 hours later, we 
find that you lose many persons in this process who don't come 
back, you never have an accurate result. And there are other 
aspects that can yield false positive results, so those are 
some of the elements we're looking at.
    We're also looking at the program environment, how to 
better enhance--especially with PEPFAR--joint activities with 
HIV. How do we make sure that every person with TB gets 
routinely offered a test for HIV, since it will make a 
difference to them in their treatment, and vice versa. Every 
person with HIV ought to be screened for the presence of 
tuberculosis, because throughout the world, it's going to be 
the most common HIV-associated disease.
    This work is done by funding different sites that compete 
for those resources, and we developed the research protocols 
jointly with the investigators, subjected to external peer 
review processes, to make sure that there's a rigor applied to 
the type of research we do.
    CDC oversees this umbrella structure for the multisite 
trials, but we get people together, agree on a common protocol, 
that gets implemented in different parts of the country.
    Senator Allard. We've got a number of drugs that are 
immunosuppressive, we have a number of diseases that are 
immunosuppressive, and have you focused much on therapies, and 
what not, that may increase susceptibility to tuberculosis? HIV 
is one disease--are there other diseases, like leukemia, 
perhaps, is that immunosuppressive?
    Dr. Castro. Absolutely, thank you, Senator, this is an 
excellent question.
    What we have seen is that, with the advent of a lot of the 
new drugs that are being used, for example, for rheumatoid 
arthritis, we're seeing the occurrence of tuberculosis, because 
these drugs do immunosuppress some individuals. That has 
resulted in some policy guidelines to ensure that persons are 
routinely screened for the presence of tuberculosis, latent 
tuberculosis, before they get started on these drugs.
    The questions becomes, are you getting to them before they 
get so immune suppressed that the test becomes meaningless and 
could we rely on other, better and more reliable tests to get 
to those results.
    But, the bottom line is, as a result of these drugs being 
more commonly used, we've seen the need to issue policy 
guidelines, and in fact if you have listened to the adds on 
tuberculosis, they say be careful if you have had TB, make sure 
you see your physician before you use these drugs, it's a very 
well-recognized phenomenon.
    Other conditions that will facilitate progression from 
latent to active TB, in addition to HIV and these forms of 
drugs, as you pointed out, persons of cancer, immunosuppressive 
therapy for cancer--people who get placed on steroids for a 
long period of time could become immunosuppressed, also. 
Diabetes have been notoriously linked to tuberculosis--the low-
body weight and malnutrition could also contribute to disease 
progression.
    So, these are a variety of the underlying medical problems 
that will facilitate disease progression for someone who is 
latently infected with TB.
    I will remind you, Senator, of the figures cited by Senator 
Brown earlier--a third of the world's population is thought to 
be latently infected with the bacterium that causes 
tuberculosis.
    Senator Allard. Is there a high incidence of TB in new 
immigrants to the United States?
    Dr. Castro. Yes, sir. There is a relatively high incidence 
of tuberculosis in immigrants and what we have in place is a 
system to screen--we provide a medical evaluation before entry 
for every person who applies for an immigrant or refugee visa. 
That includes screening for tuberculosis.
    Most recently, we've updated those technical guidelines 
with another group at CDC, the Division of Global Migration and 
Quarantine, and are implementing some pilot projects to 
evaluate this enhanced screening process in a group of Burmese 
refugees that are slated for resettlement in the United States, 
a decision by the Department of State, so we're trying to make 
sure that we reduce the implication.
    Senator Allard. Can the statement be made that we're seeing 
a decrease in tuberculosis in domestic populations, but an 
increase caused by new immigrants coming to this country? Or 
sustaining, I mean it's sustaining our levels, with new 
immigrants.
    Dr. Castro. That would be an accurate statement. We are 
making progress against tuberculosis in the U.S.-born 
population, however, we don't see that yet in racial and ethnic 
minorities, there's still a gap where they have 8 times the 
risk of tuberculosis when you compare them with U.S.-born 
whites.
    And the problem there is that, as long as you have TB in 
the community and someone transmitting TB, TB won't pick who it 
infects. So, that's going to be part of our challenge.
    Senator Allard. It's also a zone overseas.
    Dr. Castro. Yes, there is microbacteria in bovis associated 
with unpasteurized milk, but at least in this country, you 
have--with the U.S. Department of Agriculture--a fairly 
effective bovine eradication program, where they test cattle, 
and will kill or sacrifice any cattle known to be infected. We 
also pasteurize all dairy products as a way to reduce the 
possibility of tuberculosis.
    Senator Allard. Thank you.
    Thank you, Mr. Chairman.
    Senator Brown. So, it's more a function of--are you 
implying, or suggesting, or saying it's more a function of 
poverty than it is any of those other factors?
    Dr. Castro. TB has notoriously preyed on the down and out 
in this very country, around the turn of the 20th Century, TB 
was a leading killer in the densely-populated urban 
environments. And, as we've made progress against it and 
improved those conditions, you're seeing less of it.
    But, throughout the world, the World Health Organization 
and the Stop TB Partnership have linked tuberculosis to poverty 
and to sustainable development, because it is the young adult 
of these populations who are succumbing to tuberculosis and 
that's the most productive part, unfortunately often, the down 
and out.
    Senator Brown. Senator Burr is recognized.
    Senator Burr. Thank you, Mr. Chairman.

                       Statement of Senator Burr

    Dr. Castro, welcome, thank you for the work you do.
    The current guidelines for air travel for persons affected 
by TB, as I understand it, are based on limited studies that 
were done over 10 years ago. What have we changed?
    Dr. Castro. Thank you. Those guidelines are based on 
studies that I was personally involved in where what we have 
seen is, during short commercial air travel, we have not 
documented evidence of transmission. The total number of such 
studies amount to about 7. There's not that many situations, 
and CDC often gets called upon to do these investigations. It's 
a big challenge to identify all of the passengers once they've 
dissipated, and get them tested.
    What we have learned through those studies is that 
transmission has been documented in long flights over 8 hours. 
That's the basis for the existing recommendations by WHO and by 
CDC, where we unequivocally State, No. 1, any person with 
active TB should not board a commercial aircraft; No. 2, if you 
have MDR TB, we want to see evidence that your cultures are 
negative, and what we're trying to do is improve the level of 
awareness.
    It is a challenge. All of us travel on a daily basis, and 
it would be unrealistic to expect that we would all be screened 
before boarding the aircraft by an x-ray, which is what you 
would almost need to have a foolproof system.
    So, we have the policy guidance in place, WHO, I 
understand, is going to try to update it to take into 
consideration the presence of XDR TB, because they were last 
printed in 2006 before the recognition of Extensively Drug 
Resistant Tuberculosis.
    Senator Burr. Dr. Castro, after the Speaker TB incident, 
Senator Gregg and I sent an extensive letter to Julie 
Gerberding at the CDC. We asked, specifically, what changes 
would need to be made in current Federal isolation and 
quarantine laws and regulations. This was precipitated by the 
revisions that were sought by CDC in the public comment period 
that ended in March 2006. What's the status of that effort, and 
more importantly, has anything changed since Senator Gregg and 
I wrote to the CDC?
    Dr. Castro. Yes, changes have been made, for example, we 
have improved the lines of communication between our Department 
and the Department of Homeland Security----
    Senator Burr. But, have any of the new regulations actually 
been put in place?
    Dr. Castro. Well, all States have State-specific laws for 
the prevention of tuberculosis transmission, as well as the 
implementation of worldwide agreed-upon standards for 
international health regulations which are a set of principles 
that not only try to reduce the importation of disease, but 
also plays upon our role as citizens of the world to reduce the 
exportation of disease.
    We can certainly get back to you with details about what's 
being done, because some of it is work in progress, but we----
    Senator Burr. Let me just say this--when I see an effort 
that was completed in 2006--March 1, 2006, CDC answer was, ``Is 
working to respond to more than 500 pages of comments from 
approximately 50 organizations and individuals regarding the 
proposed rule,'' but the proposed rule has not been finalized. 
We're a year and a half from then, we've had a major incident 
since then.
    Dr. Gerberding went on in the letter to say, ``CDC is 
working to clarify its quarantine authority to expressly 
address the movement of patients out of the country. 
Historically the use of quarantine has been devoted to keep 
people out of the United States and containing them from 
outside the country. This case represents the first time the 
CDC has had to address the issue of preventing a person from 
leaving the United States. Public health statutes were not 
designed to deal with this.''
    My only question is, have we changed anything that enables 
us to address these challenges any better than what was 
expressed to me in that letter earlier this year?
    Dr. Castro. I understand that the changes are being made, I 
don't have the specifics, but would be glad to provide them to 
you.
    Senator Burr. I would appreciate you doing that, because my 
concern is, if you wait as long to do that as you have to 
propose the final rule, which has not been proposed since March 
2006, this committee has something to worry about.
    Senator Burr. Let me switch, if I could, just very briefly, 
to the Speaker case. Testing was done in Atlanta that showed 
Mr. Speaker to be multi-drug resistant--excuse me, extensively 
drug-resistant. He was tested in Denver, and was determined to 
be multi-drug resistant. We had asked that CDC send the 
original samples to Denver to be tested, to see if, in fact, 
there was a different result. My understanding is that a sample 
went to Denver, and it was tested as multi-drug resistant. How 
much time, if any, are we spending looking at the testing side 
of it, to see if we've got some discrepancies in our methods 
and technologies, and is that something the committee should be 
concerned with?
    Dr. Castro. This is an area that is of concern to all of 
us. The testing for second-line drug resistance lacks the 
standardization--there are some national guidelines, CDC is a 
reference lab, and in fact, we follow those procedures.
    Unfortunately, you're looking at samples obtained in 
different States, and the discrepancy is based on two drugs. 
What you find is, whenever you read any chapter that describes 
MDR TB or now XDR TB, there's always a segment devoted to how 
to interpret, or what are the causes that could lead to 
discrepant lab results? It happens constantly, and it is a 
problem that we need to resolve, by having the research 
developed, the newer methods to test these.
    It takes 21 to 28 days to use the recommended measures to 
identify resistance to second line drugs----
    Senator Burr. Let me go back to my point. CDC was asked to 
take the original sample, the sample that they tested and found 
to be extensively drug resistant, send it to Denver, and have 
Denver re-test it. Was that ever done?
    Dr. Castro. Yes, I believe it was.
    And, now keep in mind that there are some technical 
challenges to this, because in a bacterial population, when you 
take a wire loop and you take a sample of that, you're taking a 
subpopulation, you usually don't take a swab of the whole petri 
dish, so to speak, with all of the bacteria growing. So, you 
could be sampling subpopulations that could have rise to 
discrepant results that are bona fide discrepancies, because 
you may be testing a subpopulation of bacteria.
    So, one has to be careful with over-interpreting those 
discrepancies, which happen all of the time. And, in fact if 
you were to ask any series of experts throughout the country, 
they would say, ``This is not news to us, this is what we deal 
with, every time we have a case of MDR TB,'' and I bring us 
back to, what that highlights is the existing and prevailing 
deficiencies in testing, that is relatively antiquated and 
needs to be updated. And, we need to make sure that we invest 
in the research to get us those tools that we can rely upon.
    Senator Burr. I thank the Chairman for his indulgence. And, 
what I think, as a member of the committee, I'm trying to get a 
better handle on, is what those tools are. And there's a point 
in time where CDC has to make a call based on where we are, 
where science is, and what we should change, versus continuing 
to use something that, I believe, Mr. Chairman, most people 
have expressed probably needs to be changed, based upon what we 
know today.
    My message back to CDC is, tell us what needs to be 
changed. But tell us now. Let's not wait 6 months, another 
year, another year and a half from the study, let's get the 
final rules out.
    Thank you, Mr. Chairman.
    Senator Brown. Thank you for your comments and your 
comments, Senator Burr.
    Senator Murkowski.

                     Statement of Senator Murkowski

    Senator Murkowski. Thank you, Mr. Chairman.
    Dr. Castro, I'm trying to figure out what's going on in 
Alaska. In 1945, about 20 percent of the deaths in the State 
were attributable to tuberculosis; we'd like to think that 
being 1 of the 50 States that our statistics, too, are 
improving. But, in fact, we had a higher number of those 
afflicted with tuberculosis in 2006 than we had in 2005. With 
our reported cases of TB in 2006, we're looking at 10.4 cases 
per 100,000, and when you compare this to the national average, 
which is 4.6 cases per 100,000, our statistics are terrible.
    In fact, in a newspaper article just this April in 
Anchorage, our largest city, the headline is ``TB Outbreak 
Again Amongst our Homeless Population.''
    Now, I understand the difficulties in, particularly with a 
homeless population, trying to track and provide for treatment, 
recognizing that the treatment can be a lengthy one, and you 
have a population that may or may not be checking in for the 
continued treatment.
    Can you give me some idea as to why in Alaska, we are not 
making better progress? Can you also speak to whether or not 
our numbers within our Alaska Native population are higher than 
our Caucasian numbers, or is it primarily with our homeless 
population? I understand that over 50 percent of all of the TB 
cases were among our homeless population, so I'm trying to 
understand what I'm dealing with in my State.
    Dr. Castro. Thank you, Senator. I'll need to get back and 
run some of the analyses of the information shared with us by 
the State of Alaska, but you're absolutely right--the rate of 
tuberculosis has been disturbingly higher in Alaska than in the 
rest of the country, and then--in fact, for that matter there 
are many other States that are above the average.
    One of the problems is, as you have pointed out, the 
occurrence of tuberculosis in the relatively marginalized 
populations. And, if you don't have the warm bodies to reach 
out and get them to complete therapy, you will have ongoing, 
unmitigated transmission.
    You will be hearing from Dr. Frieden in New York later, but 
New York implemented a very successful approach when we had the 
resurgence of tuberculosis, with outreach workers who were 
meeting homeless individuals under bridges in Queens and the 
city and the various boroughs, and getting them successfully to 
complete treatment. But that requires the infrastructure that--
what I was alluding to earlier, it is my understanding that the 
investment and infrastructure in Alaska has remained stable, 
not kept up with the cost of living increase, based on the 
information we get from our program consultants who interact.
    Also, the rates have been traditionally higher in the 
Native Americans, and it's an area of concern, and it relates 
back to the health disparities that I was alluding to earlier.
    Senator Murkowski. Is there any specific research going on 
within CDC as to this sub-population?
    Dr. Castro. No specific research, however CDC is ready to 
and has responded to requests by States for support during--the 
need to investigate clusters, unusual clusters or outbreaks in 
helpless populations.
    I can't recall having been, over the last couple of years, 
to Alaska, but certainly in Seattle we had last year a cluster 
of individuals who were homeless, mostly Native Americans also, 
several of whom who were also HIV-infected substance abusers, 
posing incredible challenges to getting them to get through the 
testing procedures that would diagnose them with TB, and 
subsequently to take the drugs for the time period that's 
required.
    Senator Murkowski. Is part of the problem the ethnicity, 
the genetic makeup of an Alaskan Native or, American Indian 
that makes them more susceptible? Or are you suggesting that 
they were not being as thorough with the treatment in these 
individuals because of certain issues like poverty and 
remoteness?
    Dr. Castro. I would have to agree with the second part of 
your statement, which is that I don't think that there is 
anything inherent to the Native populations, although we do 
know that over years, TB was rampant in the Inuit population, 
however, Dr. George Comstock who died just a few months ago 
demonstrated that in that very population, if you were able to 
implement widespread isoniazid preventive therapy after testing 
and screening out for active disease, you could actually reduce 
the rates quite significantly.
    I think what has happened is, you're dealing now with more 
remote populations where their contacts are not being promptly 
identified and screened, and you have unmitigated, ongoing 
transmission in these circles. And that's where we need to go 
back to the infrastructure of services that are going to be 
needed to get that done.
    With the added challenge in the case of Alaska that you 
have remote populations where you can only get to by propeller, 
you know, single-engine aircraft, and I'm aware that that poses 
a formidable challenge.
    Senator Murkowski. It kind of goes to what my colleague 
Senator Burr was saying, about not being allowed to fly if 
you've been diagnosed. If you can't fly to get out of one of 
our villages, you can't get to where the treatment is. So, 
we've got kind of a Catch-22 there.
    Mr. Chairman, this is an interesting discussion this 
morning, when you recognize that in this country--it's the 
poor, it's the homeless, it's those that are isolated for many 
different reasons, that we see this spread of this drug-
resistant tuberculosis, and they certainly are the ones with 
the least ability to advocate for their cause.
    So, thanks for having this hearing this morning.
    Senator Brown. Thank you, Senator Murkowski, thank you for 
your insights.
    I've got a couple of questions and comments about Senator 
Murkowski's questions, too--the 10-point--she had said it's 4.6 
nationally per 100,000, 10.4 in Alaska. And I appreciate your 
pointing out--as she did--the difficulty of doing the directly 
observed treatment in remote areas. You said something about 
Isoniazid protective therapy--is that different from the actual 
treatment of TB with Isoniazid?
    Dr. Castro. Thank you, Senator.
    Senator Brown. Or did I hear that right?
    Dr. Castro. It is different. Basically, what we have, in 
the tools to deal with tuberculosis is first and foremost, you 
have to find people who have TB in their respiratory system, 
because they're the ones who are, No. 1, sick, and No. 2, who 
are transmitting the disease in the community. By getting them 
cured, that's your best preventive measure.
    Then you have a second group that you need to target, those 
are the persons who have latent tuberculosis infection. We 
estimate that in the United States, we have anywhere from 9 to 
14 million such individuals. And these persons--if you target 
your approach to those of highest risk of developing TB, you 
give them isoniazid preventive therapy or treatment for latent 
tuberculosis with Isoniazid. That's a single drug, given for 9 
months, and it will prevent them, quite effectively, from 
developing active tuberculosis. That was the intervention that 
I was alluding to, used by Dr. Comstock in Alaska.
    Senator Brown. So, these patients, if you will, they're not 
really sick, but these patients will have--they will take a 
skin test, or whatever, and you will find that they have the 
tuberculosis bacterium in their bodies, you will then give them 
only one drug, instead of four, and for 9 months, instead of a 
different period, it will only be Isoniazid, and they then 
will, two things supposedly will happen--one they will not be 
sick themselves and they will not be able to transmit TB then, 
correct? That's the idea?
    Dr. Castro. That is correct, and in fact----
    Senator Brown. You're doing that in populations around the 
United States?
    Dr. Castro. Pardon me?
    Senator Brown. You're doing that in places around the 
United States?
    Dr. Castro. We try to, except that it's----
    Senator Brown. How do you decide on which of the 9 to 14 
million to do the isoniazid preventive therapy?
    Dr. Castro. Well, what we try to do is we go for the 
populations that are epidemiologically identified to be at 
highest risk for tuberculosis and promote what we call targeted 
screening. And, in fact, if you read our policy guidelines, 
decision to test should be accompanied by a decision to treat 
for every person that you find positive.
    What often happens is we have these relatively archaic 
testing systems of schoolchildren who don't necessarily carry a 
high risk for tuberculosis, and no one is doing anything about 
the results, not starting them on preventative therapy. And I'm 
pretty sure you're going to hear additional testimony by people 
in the States about the challenges that we confront. Because, 
what we're able to do with the resources now is control TB, but 
not go for that next layer to accelerate the rate of decline 
that would be required to achieve elimination over time. And 
that's a very important distinction.
    Let me also use this opportunity to state that one of the 
ongoing trials that CDC is sponsoring is looking at the 
potential use of two drugs, once weekly, because these drugs 
are longer-lasting, for a 3-month interval, and that would 
facilitate things, if they prove to be safe and effective in 
this particular setting. But it would be quite a promising 
finding if it turned out to be the case.
    Senator Brown. How many of the 9 to 14 million people 
carrying the bacteria in our country can you name? Can the 
public health system actually name by personal identity? Ten 
thousand, one hundred thousand, a million? How many do you 
actually know?
    Dr. Castro. We don't do surveillance for persons----
    Senator Brown. Well, I know you don't do general 
surveillance, but does the public health system know the answer 
to that? So, those are the ones, I would guess, that would be 
the prime candidates for Isoniazid protective therapy.
    Dr. Castro. Right.
    Senator Brown. I mean, you test school kids when they come 
in, you test people when they come to Doctor's offices, you 
don't screen everybody, you don't--I mean, I've been screened 
for TB, but only because I've been to a prison in Siberia, but 
you don't test people who typically look like me and dress like 
me, I understand, when you go into a doctor's office. But, you 
test people that are in higher risk populations, I assume. Is 
there a data bank that collects them, so you can--I mean, I'm 
not even suggesting the privacy issues around that--but so that 
you can look to them, perhaps, to do the isoniazid preventive 
therapy?
    Dr. Castro. Well, in local, our State-based health 
department, some have been able to conduct the targeted 
screening of particular foreign-born populations, for example, 
refugee groups that are seeking medical care, substance abusers 
known to have a high risk of TB--I've left out of the list, at 
the very top, the HIV-infected, they are at the top of the 
list, because if they happen to have latent TB, they have the 
extraordinary risk of progressing.
    But we don't have a data bank. And, now at the local State 
Department, I do believe that some will have those data, that 
they don't get reported to CDC, and you may want to ask the 
folks from the local State Department about how they handle 
that information.
    Senator Brown. Let me ask you another question about the 
isoniazid preventive therapy--if I go to the doctor, if I'm an 
immigrant, or I'm particularly from Asia, I would point out, in 
response to Senator Allard's question earlier, I would point 
out in your testimony which you--I don't believe you mention 
that, actually, in your testimony--rates among nonHispanic 
Asians are 25 per 100,000, Latinos are 9 per 100,000--so the 
immigrant population is almost three times Asians versus 
Latinos. I don't know if that's the assumption that everybody 
would make. African-Americans 10 per 100,000, and nonHispanic 
whites 1.2 per 100,000, as contrasted to the 10, as Senator 
Murkowski mentioned.
    If I'm one of those and I'm tested and I have the latent 
bacteria TB bacillus in my body, and you decide to prescribe 
Isoniazid protective therapy to me, and I'm not really very 
cooperative, I mean, I start taking it and I just don't take 
the treatment the way that I should, can I develop a drug 
resistance that, when I might get TB later, I all of a sudden 
have MDR TB, just from--my question suggests if we're not doing 
the Isoniazid, and I don't have any idea if we are, I didn't 
know about it before--but if we're not doing the isoniazid 
preventive therapy, well, does that create another avenue for a 
man-made MDR TB?
    Dr. Castro. Fortunately for us, the information shows that 
in persons who have latest tuberculosis, the bacterium are so 
dormant that you don't induce the selection of drug resistance 
by using Isoniazid.
    Now, the caveat here is that you need to have ruled out 
active tuberculosis in these persons. And once you've 
successfully accomplished that, and you're satisfied that they 
have latent TB, No. 1, they pose no threat to anyone else 
around them. And that's a common misconception, people call us 
all the time and say, ``Someone tested positive in their skin 
test, should I keep them out of work?'' The answer is no, they 
are not a threat to anyone else.
    Now, they should, ideally, take their drugs, if they don't 
take their drugs, or they interrupt treatment, they're not 
likely to result in drug resistance, based on studies that were 
published about four decades ago. And, it's obviously 
predicated on what I started out saying, you must have ruled 
out TB disease. Because once you have TB disease, using a 
single drug will, indeed, promote the selection of drug-
resistant strains.
    But, it's a different environment, set of bacteria being 
dormant, they're replicating in the body, and that's where 
you're going to be selecting for those mutants that occur 
sporadically.
    Senator Brown. And my last question, you had--in response 
to a question, I believe from Senator Coburn or Allard, I'm not 
sure, you said that diabetes is linked to tuberculosis, I had 
never heard that before, what does that mean?
    Dr. Castro. Persons with diabetes who are latently infected 
carry a higher risk of disease progression----
    Senator Brown. Never happens the other way?
    Dr. Castro. No.
    Senator Brown. Not people that--I, that's what I 
misunderstood.
    Dr. Castro. No.
    Senator Brown. All right. Thank you very much, Dr. Castro, 
for your testimony. I urge you to get back with Senator Burr on 
his concerns and questions and I know that Senator Allard and 
Senator Coburn were submitting questions for the record, too. I 
thank them, and I thank you very much for your service.
    Dr. Castro. Thank you, sir.
    Senator Brown. I'd like to call up the second panel, and as 
you get situated, I will introduce all three of you at once, 
and then begin with Dr. Frieden.
    Dr. Frieden has served as Commissioner of New York City 
Health Department since January 2002. One of the world's 
leading experts on TB control, Dr. Frieden was appointed NYC 
Health Commissioner after working in India for 5 years, where 
he assisted with national TB control efforts.
    Prior to his tenure in the Republic of India, Dr. Frieden 
was instrumental in stopping the tuberculosis epidemic in New 
York City. His investigations helped document and stop hospital 
spread of tuberculosis, and documented for the first time, the 
extent of drug-resistant TB. During his time as Director of the 
Bureau of Tuberculosis Control and Assistant Commissioner, from 
1992 to 1996, New York City reduced cases of multidrug-
resistant tuberculosis by 80 percent.
    Jerald Sadoff is President, Chief Executive Officer of the 
AERAS Global TB Vaccine Foundation. Prior to working at AERAS, 
Dr. Sadoff was at Merck where he was Executive Director of 
Clinical Development of Vaccines. Prior to Merck, he worked at 
Walter Reed Army Institute of Research, which has done some of 
the best medical research in world history that Walter Reed 
has. He attained the rank of Colonel in the U.S. Medical Corps. 
Well, Dr. Enzi's office had wanted Dr. Sadoff to provide the 
perspective of private companies in TB efforts.
    And Dr. Randall Reves is the Chairman of Stop TB USA, 
formerly the National Coalition for the Elimination of 
Tuberculosis. He's a Professor of Medicine at the Division of 
Infectious Diseases at the University of Colorado Health 
Sciences Center. Dr. Reves is Medical Director of the Denver 
Metro Tuberculosis Clinic of the Denver Public Health 
Department, he's a member of the National TB Control 
Association, of which he was President some 4 years ago. He 
will provide stories of his TB patients, as well as discuss all 
of the States perspective on TB control.
    Welcome all three of you--Dr. Frieden, if you would begin?

  STATEMENT OF THOMAS R. FRIEDEN, MD., MPH, COMMISSIONER, NEW 
YORK CITY DEPARTMENT OF HEALTH AND MENTAL HYGIENE, NEW YORK, NY

    Dr. Frieden. Thank you very much. Good morning Senator 
Brown, and thank you for your long-term commitment to the issue 
of tuberculosis control.
    Senator Enzi, members of the committee, Senator Burr, 
Murkowski, and Allard, I'm Tom Frieden. I'm Health Commissioner 
from New York City. Thank you for the opportunity to discuss TB 
control, an issue on which I've spent most or much of my 
career.
    In the 1990s, I ran the New York City Tuberculosis Control 
Program, and I took care of a man from India. He had 
extensively drug-resistant TBR XDR TB. I was his physician and 
it took about 2 years and well over $100,000. He nearly died, 
but we did cure him. It took medications, surgery, experimental 
drugs. The cost again, over $100,000.
    By chance, several years later, when I was working in 
India, I traveled to his home town where I helped start a DOTS 
or Directly Observed Treatment Shortcourse program. That 
program now is one of the most effective in the world. It has 
cared for more than 8 million patients, or nearly 8 million 
patients and prevented more than 1 million deaths. The cost to 
prevent a single case of drug-resistant TB is about $10 there.
    It's an indictment of all of us, I think, that more than 
1.5 million people will die from a disease this year, that is 
almost completely curable. TB isn't just a New York City 
problem or a U.S. problem, it's a global problem that can only 
be solved with a global approach. TB reminds us that we're all 
connected by the air we breathe. Until TB is controlled 
worldwide, it's continuing to cause avoidable suffering and 
death in developing countries, and an ongoing threat in 
developed countries like here in the United States.
    Fighting TB requires persistence on the part of patients, 
programs, and policymakers. TB control is a winnable battle. 
Drug-
resistant TB results from failure to implement effective TB 
control programs, programs that cost only a small fraction of 
what it costs to treat drug-resistant TB once it occurs. 
Protecting the United States from drug-resistant TB means 
developing and ensuring effective and continued implementation 
of both domestic and international programs. We'll never be 
able to build a moat around this country. We are connected to 
the world.
    Just as TB patients are tempted to stop medicines when 
symptoms are gone, governments are also tempted to de-fund TB 
control when it's no longer in the headlines. Doing so, 
unfortunately, will lead, both in the individual and in the 
governmental case, to interruption of treatment, development 
and spread of drug resistance, and to death.
    Rates go up, funding goes up, rates come down, funding 
comes down. I've got figures to show that in my chart. What 
you'll see is the control of TB in New York City with 
attention, and then a major decline in funding, both at the 
national and New York City level, our funding is down by 70 
percent from the Federal Government compared to 10 years ago.
    New York City's TB epidemic of the 1980s was in large part 
the result of Federal funding cuts, but TB control in 1990s led 
to declines of TB overall by 75 percent, U.S.-born cases by 
more than 90 percent, and multidrug-resistant TB by 95 percent. 
Our success wouldn't have been possible without CDC cooperative 
agreement, which provided financial and technical support. 
Incidentally, I'd note that the cooperative agreement process 
of CDC is a very successful model, and I hope Congress will 
consider expanding it to areas such as diabetes, cancer, 
tobacco, and heart disease, which are now the leading killers 
in this country.
    Today, the city again faces Federal funding cuts that 
threaten to undo this support and this success. This year, 
CDC's grant is worth less than one-third, in real terms, what 
it was 10 years ago. And yet, we still have far to go. New York 
City's rate is about 12 times the national goal for TB of one 
case per 100,000 people.
    Globally, we have to greatly improve lab capacity. New 
tools are needed, but we also have to make better use of 
existing tools, which are very accurate, inexpensive, and 
unavailable in most of the world. Treatment can cure more than 
95 percent of patients, and I urge you to support the global 
anti-TB drug facility with at least $15 million annually, and 
to provide funding for expanded assistance as outlined in the 
Stop TB Now Act.
    Good TB control is basically good management. It includes a 
standardized reporting system that documents the outcomes of 
every patient treated, and I think it's a model of effective 
care management. We need to build and maintain these systems 
nationally and globally.
    Currently, we do not have the tools to control TB in Sub-
Saharan Africa, but DOTS can prolong lives, prevent drug-
resistance, and blunt the increasing cases, and simple measures 
can prevent spread of TB in hospitals. Efforts to develop a 
more effective TB vaccine deserve support, but even if an 
effective vaccine is identified, effective treatment systems 
will be required for several decades.
    Substantial increases in funding are needed to strengthen 
State and local TB control programs. I urge you to enact and 
fully fund the Comprehensive TB Elimination Act, which would 
provide essential support to domestic TB control efforts and 
for needed research. There is an urgent need for substantially 
increased support for global TB control and I urge enactment 
and full funding of the Stop TB Now Act. Preventing TB and 
drug-resistant TB abroad will not only save millions of lives, 
but it is the only way to protect this country from the 
disease.
    Thank you.
    [The prepared statement of Dr. Frieden follows:]
           Prepared Statement of Thomas R. Frieden, M.D., MPH
    Good morning Senator Brown, Senator Enzi, and members of the 
committee. I am Dr. Tom Frieden, Health Commissioner for New York City. 
Thank you for this opportunity to discuss the important issue of TB 
control, a problem on which I have spent much of my career.
    When I ran the New York City TB control program, I spent mornings 
in our clinics caring for TB patients. For nearly 2 years in the mid-
1990s, I cared for a man from India with extensively drug-resistant 
(XDR) TB. He nearly died. But with intensive treatment, surgery, and 
experimental medicines, he was cured. The cost was well over $100,000. 
Several years later, I helped start a Directly Observed Treatment 
Shortcourse (DOTS) program in his hometown in India, along with 
programs that now cover all of India. The cost to prevent a case of 
drug-resistant TB there: about $10.
    As a Centers for Disease Control and Prevention (CDC) employee 
detailed to New York City in the 1990s, I documented and helped stop 
both hospital and community spread of multidrug-resistant TB (MDR TB). 
Cases had nearly tripled in a decade, and 1 in 5 patients had MDR TB. 
The attached chart (Attachment 1) illustrates the decline of new TB and 
MDR TB cases as the DOTS strategy was implemented in the city. After TB 
declined rapidly in New York City as a result of our efforts, I spent 5 
years in India on loan from the CDC to work with the World Health 
Organization helping India develop what is now one of the world's most 
effective TB control programs. India has now treated nearly 8 million 
patients and saved more than a million lives.
    Tuberculosis remains a serious disease that will be with us for a 
long time. It is an indictment of all of us that more than 1.5 million 
people will die this year from a disease that is nearly 100 percent 
curable. TB is not just a New York City problem, or a national problem, 
but a global problem that can only be solved with a global approach. TB 
reminds us that we all live in the same world community and we are all 
connected by the air we breathe. Until tuberculosis is controlled 
worldwide, it will continue to cause avoidable suffering and death in 
developing countries and will be a continuing threat in developed 
countries.
    The greatest enemy to TB control is complacency. Fighting TB is 
hard work that doesn't end. Our biggest need is persistence and energy, 
not only on the part of patients and our programs, but also 
policymakers. This is a winnable battle. We need sustained national and 
global political commitment to fight TB. The three critical issues for 
the future of tuberculosis control are sustained funding, technical 
rigor, and good management
    MDR and XDR TB are the result of failure to implement effective TB 
control programs--programs that cost a small fraction of the medical 
care and treatment costs for patients with MDR or XDR TB. No program 
can treat MDR/XDR TB faster than a bad program can create it, no matter 
how many resources are available. Protecting the United States from 
drug-resistant tuberculosis means developing and ensuring effective and 
continued implementation of both domestic and international TB control 
programs.
    As the overall caseload has fallen dramatically in New York City, 
non-U.S.-born patients now are more than 70 percent cases, compared to 
only 18 percent in 1992; nationally, as you have heard, the proportion 
is only slightly lower, and is growing. And increasingly, TB cases are 
found in the workplace and among business travelers, Wall Street 
executives, sales personnel, teachers, lawyers, and others.
    The story of the fall and rise and fall of TB in the United States 
provides valuable lessons for how to control a serious communicable 
disease--and how not to. Just as patients with tuberculosis are tempted 
to stop medicines when the symptoms are gone, so also governments are 
tempted to neglect tuberculosis control programs when TB is no longer 
in the headlines. But doing so will lead, both in the individual and in 
the governmental case, to interruption of treatment, development and 
spread of drug-resistant TB, and death.
    When TB is in the headlines, resources increase. Once those 
resources succeed in reducing the disease, we neglect the modest 
investment that needs to be maintained to prevent future epidemics--
epidemics that will cost lives and money. Rates go up, funding goes up; 
rates come down, funding comes down. The attached chart shows that 
CDC's tuberculosis control funding has declined steadily, in real 
dollars, over the past 15 years. New York City's funding has declined 
even faster.
    The TB and drug-resistant TB epidemic that began in the 1980s in 
New York City was in large part a result of the funding cuts to TB 
programs in the previous decade, further fueled by the rise in HIV/AIDS 
in the city. The TB epidemic ultimately cost the city's medical care 
system $1 billion. Today, New York City again faces Federal funding 
cuts that threaten to undermine the public health infrastructure that 
can maintain this success. In 2007, the city's CDC grant of about $13.8 
million is less than half its 1996 funding level of almost $30 million, 
and, after adjustment for inflation, is worth less than one third of 
that year's support. (Attachment 2) Although we successfully contained 
the epidemic, we still have far to go. The Healthy People 2010 
objective for tuberculosis is less than 1 case per 100,000 people; New 
York City had 12 cases per 100,000 people in 2006.
    New York City's success in controlling tuberculosis would not have 
been possible without the financial support from the Federal, State and 
local governments, and without the partnership with the CDC. Through a 
cooperative agreement with CDC, we not only received essential 
financial support but also important technical expertise. I would add 
that the cooperative agreement approach is a successful model, and I 
hope that Congress will expand its implementation to areas such as 
diabetes prevention and control, colon cancer prevention, tobacco 
control, and heart disease prevention, which are now the leading 
killers in this country.
    The key to the NYC TB program's success was using policies that had 
been rigorously proven to work, strong program management, and a focus 
on supporting the front lines--patients, laboratory workers, TB control 
and other health staff, and program managers. Support from public 
officials, hospital staff, and the academic community was also 
important
    Diagnosis: Rapid diagnosis of infectious tuberculosis by simple 
sputum smear for acid-fast bacilli remains an important tool, and more 
rapid molecular techniques hold promise. New techniques for diagnosing 
latent infection may be useful, but they are expensive: in New York 
City we have not applied these tests widely solely because we do not 
have sufficient funds. Globally, we need to greatly improve basic 
laboratory capacity, as part of a general health systems strengthening 
approach. It is key to start with simple smears, which diagnose the 
most seriously ill and infectious patients, and proceed to cultures, 
which are important to diagnose some patients, especially children and 
HIV-infected people, and then on to high-quality drug-susceptibility 
testing. While new tools are needed, it is unethical not to ensure 
effective use of existing tools--which are highly accurate, relatively 
inexpensive, but unavailable in most of the world.
    Treatment: Treatment can cure more than 95 percent of patients; 
direct observation of treatment, a component of the recommended five-
element DOTS strategy, is the standard of care. In the United States 
and globally, we need to strengthen our health care system, including 
TB care systems such as chest clinics. This means investing in 
education and training to improve the quality of laboratory and primary 
care services, building State and local public health laboratory 
capacity, and assuring that all drug-resistant patient isolates are 
tested for second-line drug susceptibility and isolates genotyped to 
identify outbreak patterns. We need new drugs, but we also need to 
ensure effective use of existing drugs worldwide. One of the highest 
priorities for global TB programs is an adequate supply of high quality 
drugs, as well as trained personnel to ensure an effective DOTS 
strategy. Hence I urge you to support the Global Anti-Tuberculosis Drug 
Facility with at least an annual allocation of $15 million and to 
provide funding for expanded technical assistance for TB control, as 
outlined in the ``Stop TB Now Act'' (S. 968/H.R. 1567.)
    Monitoring: Systematic monitoring of case detection and treatment 
outcomes is essential to effective service delivery. The proportion of 
patients diagnosed and treated effectively has increased greatly over 
the past decade but is still far short of global targets. New York 
City's program had a system of accountability that enabled us to tell 
policymakers the number of people we could--and did--cure for the 
dollars provided. Effective TB control includes a standardized 
reporting system which documents the outcomes of every patient and 
which is a model for effective care management.
    Good TB control is basically good management. That means supporting 
well-trained personnel for direct service and supervision, from those 
who provide or supervise DOT to lab technicians, to national program 
managers. Programs must have the ability to hire staff, purchase 
supplies, and contract for services efficiently without unnecessary 
administrative constraints.
    Strengthen Health Systems: We need to build and maintain a strong 
health care and public health infrastructure in order to implement good 
tuberculosis control. The global HIV epidemic has created increasing 
challenges for TB control, especially in sub-Saharan Africa. HIV 
exposes any weaknesses in TB control programs. We don't currently have 
the tools to control the epidemic of TB in high-HIV prevalence regions 
of sub-Saharan Africa, but we can prevent deaths and drug resistance by 
ensuring prompt and accurate diagnosis and treatment, including use of 
directly observed therapy. DOTS can prolong lives, prevent drug 
resistance, and blunt the increase in cases.
    Research: Efforts to develop more effective tuberculosis vaccines 
are underway, and deserve support. But even if a vaccine is identified, 
more effective treatment systems are likely to be required for decades. 
Other modes of tuberculosis control, such as treatment of latent 
infection, have a potentially important role in some contexts, such as 
infectious TB patients and patients co-infected with HIV. And we must 
face the tragic fact that at present we cannot control tuberculosis in 
sub-Saharan Africa with current technologies. We must explore ways to 
make improved care and control possible and prevent the spread of TB in 
hospitals.
    The current funding level for CDC's domestic TB activities is 
inadequate and represents a 27-percent decrease over the past decade 
when adjusted for inflation. Substantial increases in funding are 
needed to strengthen State and local TB control programs. I urge you to 
enact and fully fund S. 1551/H.R. 1532, the Comprehensive TB 
Elimination Act, which would provide essential support to domestic TB 
control efforts and for needed research for new diagnostic tools, 
drugs, and vaccines.
    Importantly, there is an urgent need for substantially increased 
support of global TB control programs. I also urge the enactment and 
full funding of the Stop TB Now Act, S. 968/H.R. 1567. Preventing TB 
and drug-resistant TB abroad will not only save millions of lives, but 
it is the only effective way to protect this country from the disease.
    Thank you for your support for tuberculosis control and for the 
opportunity to comment.




                                Summary
    Tuberculosis remains a serious disease and it will be with us for a 
long time. It is a global problem that can only be solved with a global 
approach. Until tuberculosis is controlled worldwide, it will continue 
to cause avoidable suffering and death in developing countries and will 
be a continuing threat in developed countries.
    Our greatest enemy is complacency. This is a winnable battle, but 
we need the political commitment and persistence for a sustained 
national and global approach to fighting TB. MDR and XDR TB result from 
failure to implement effective TB control programs--programs that cost 
a small fraction of the medical care and treatment costs for drug 
resistant TB patients. Protecting the United States from drug-resistant 
tuberculosis means developing and supporting--for the long-term--
effective domestic and international TB control programs.
    Government funding rises and falls with the rise and fall of TB 
rates; when government support falls, the public health infrastructure 
built to prevent TB is compromised, creating the potential for another 
epidemic.
    New York City was able to reduce TB cases by 75 percent, U.S.-born 
cases by 90 percent, and MDR TB cases by 95 percent since the last 
epidemic's peak in 1992. The key to the TB program's success has been 
using policies that had been rigorously proven to work, strong program 
management, and a focus on supporting the front lines--patients, 
laboratory workers, TB control and other health staff, and program 
managers.
    We need new diagnostic tools, but also wider use of effective 
existing tools--which are highly accurate, relatively inexpensive, but 
unavailable in most of the world. We need to:

     Develop new drugs, but we also need to assure an adequate 
supply of current high-quality drugs domestically and globally;
     Support directly observed treatment, which can save lives, 
reduce drug resistance, and save future health care treatment dollars;
     Ensure accountability for all programs and support the 
training and human resources necessary to get results;
     Support the public health infrastructure and strengthen 
the health care systems that these public health programs work with.

    I urge enactment of and full funding for S. 1551/H.R. 1532, the 
Comprehensive TB Elimination Act and the Stop TB Now Act, S. 968/H.R. 
1567 for a comprehensive approach to win the battle against TB. I also 
recommend at least $15 million for the Global Anti-Tuberculosis Drug 
Facility as well as substantially increased funding to international 
tuberculosis control in general. Preventing TB and drug-resistant TB 
abroad will not only save millions of lives, but it is the only 
effective way to protect this country from the disease.

    Senator Brown. Thank you, Dr. Frieden.
    Dr. Sadoff, welcome, nice to see you again. Thank you for 
being here.

 STATEMENT OF JERALD C. SADOFF, M.D., PRESIDENT AND CEO, AERAS 
          GLOBAL TB VACCINE FOUNDATION, ROCKVILLE, MD

    Dr. Sadoff. Senator Brown and other committee members, 
thank you for this opportunity to appear before you to discuss 
the state of tuberculosis vaccine development and to describe 
the work of the AERAS Global TB Vaccine Foundation, which is a 
public/private partnership focused on product development.
    We appreciate your interest in this critical matter and we 
look forward to working with you and other Senators in the 
future. Your role is crucial to ensuring adequate resources and 
incentives to accelerate vaccine development. We applaud your 
leadership in addressing the worldwide tuberculosis pandemic, 
which you point out infects 8 million people and kills 1.6 
million people a year. And of course of particular concern, the 
rising threats of drug-resistant tuberculosis and especially 
co-infection with HIV/AIDS.
    And in fact, tuberculosis, as you pointed out, is the cause 
of death of half the people with HIV/AIDS who die in Africa 
from HIV. New tools are urgently needed to diagnose, test, and 
prevent TB, including new and effective vaccine. And modeling 
studies show that without such vaccines, we can not eliminate 
TB from the world.
    We thank Senator Brown and others for highlighting the 
needs for these new tools, and bipartisan Comprehensive 
Tuberculosis Elimination Act. And as this bill makes clear, 
more resources and strategic focus are needed to spur the 
creation of 21st Century technologies to curb the pandemic.
    We also applaud Ranking Member Enzi and the full committee 
for the support of Senator Brown and Senator Brownback's 
creative, balanced, and forward-looking amendment to the FDA 
Revitalization Act. This measure holds promise of speeding the 
development of products to combat neglected diseases like TB.
    As recent experience shows, tuberculosis, like any 
infectious disease, is a problem that knows no borders. And the 
United States needs to significantly strengthen the efforts to 
halt its spread. The tools used in most places around the world 
are outdated and inadequate. Diagnostic tools currently used 
were invented 100 years ago, as you pointed out, antibiotics 
used to fight TB are over 50 years old, and the vaccine 
currently in use in countries outside the United States was 
invented 85 years ago and had very limited effectiveness, even 
in children. Clearly we need new solutions.
    One approach, important approach to developing these new 
tools is the product development partnership model, which 
bridges the gap between public sector's urgent need for these 
interventions and the private sector's technological expertise. 
Three such PDPs are engaged in the search for new tools to 
combat TB. The Global Alliance for TB Drug Development, the 
Foundation for Innovative New Diagnostics, and my organization, 
the AERAS Global TB Vaccine Foundation.
    AERAS's mission is to accelerate the development and 
delivery of safe, effective, affordable vaccines to prevent TB 
infection around the world. We are essentially a non-profit 
biotech company, guided by business principles, and seeking to 
be as efficient and flexible as a for-profit entity. I myself, 
am a hybrid of public and private experience, having spent more 
than 20 years, as you mentioned, creating vaccines at the 
Walter Reed Institute of Research, followed by over 7 years as 
Executive Director of Clinical Development of vaccines at 
Merck, before becoming the AERAS CEO in 2003.
    During my career, I've had the opportunity to be involved 
in the development of nine vaccines that are currently on the 
market today. Based on that experience, we operate AERAS on an 
industrial model, making tough decisions, weighing risks, 
resources, and time. My staff, most of whom have biotech or 
pharma experience, have quarterly benchmarks they must reach, 
directly tied to their compensation.
    However, unlike any individual pharmaceutical company, we 
are testing a portfolio of the world's most advanced TB vaccine 
candidates from a variety of sources, including several we have 
invented ourselves. AERAS collaborates with the best scientists 
around the world, whether in South Africa, India, Maryland, or 
Tennessee, whether with a small biotech, a large vaccine 
manufacturer, a leading academic researcher, or outstanding 
scientists in our own Government. This gives us an advantage 
over any single company and provides our funders with a central 
focus for TB vaccine development.
    My own pharmaceutical companies do more of this research. 
The private sector, where most vaccine product development 
expertise resides, has generally stayed on the sidelines 
because of the scientific challenges in an unpredictable 
market. Vaccines are among the most cost-effective and 
medically effective health interventions, but inventing them 
presents technical challenges that require significant 
investment. For profitable products, the public and private 
sectors have collaborated in a model where public sector 
agencies, such as National Institute of Health, finance basic 
research that industry translates into products by clinical 
trials, process development, manufacture, licensure, and 
marketing.
    This model breaks down for neglected diseases, such as TB. 
While the NIH continues to play a vital role in funding basic 
research and some early clinical development, its mandate does 
not generally include industrial-style product development. 
Biotech and pharmaceutical companies may have potential vaccine 
candidates or technologies that could help solve the TB 
problem, but they feel constrained by the need to maximize 
shareholder value.
    By taking on the expense and effort of early to late stage 
product development, PDPs like AERAS minimize risk and offer 
the private sector an opportunity to develop products that they 
would otherwise not be commercially viable. At the same time, 
our agreements with industry contain provisions to ensure the 
vaccine that emerges will be affordable and produced in 
adequate quantities.
    AERAS currently has six vaccine candidates in our pipeline, 
with clinical trials underway in the United States, Europe, 
Africa, Asia. The best of these vaccines are scheduled to enter 
proof of concept efficacy trials in 2009, enabling us to 
rationally select vaccines for subsequent large-scale trials in 
field sites, which we're developing in South Africa, India, 
Kenya, Uganda, and Cambodia. These trials will be conducted 
under the highest ethical standards, with vaccines that meet 
all FDA quality and safety requirements.
    I want to express appreciation for past financial support 
providing to AERAS by the CDC to develop field sites in India, 
and the cooperation we have received from the National 
Institute of Health. AERAS's programs have also attracted 
funding from the governments of the Netherlands and Denmark, as 
well as the Bill and Melinda Gates Foundation.
    I ask your sustained and increased leadership and 
commitment to research, and designing and testing new tools to 
fight TB needs more funding. Supporting the NIH basic research 
and CDC programs and directing resources for product 
development partnerships is the most effective way to develop 
new tools to defeat this horrible disease.
    I thank you for this opportunity to highlight the need for 
preventative TB vaccine and AERAS's efforts to develop such a 
vaccine. I look forward to answering any questions you may 
have.
    Senator Brown. Thank you, Dr. Sadoff, for your work.
    Dr. Reves.

   STATEMENT OF RANDALL REVES, M.D., PROFESSOR OF MEDICINE, 
INFECTIOUS DISEASES, UNIVERSITY OF COLORADO; MEDICAL DIRECTOR, 
   DENVER METRO TUBERCULOSIS CLINIC; CHAIRMAN, STOP TB USA, 
                           DENVER, CO

    Dr. Reves. My name is Randall Reves. I'm the Medical 
Director of the Denver Metro Tuberculosis Control Program, and 
a Professor in Infectious Diseases at the University of 
Colorado Health Sciences Center. I'm here representing the Stop 
TB USA Coalition, the American Thoracic Society, and 
importantly, my colleagues in the National TB Controllers 
Association.
    I want to thank Chairman Kennedy, Senator Brown, and 
Ranking Member Enzi, and the other Senators here today, 
including Senator Allard from Colorado, for holding this 
important hearing and for their leadership in global and 
domestic tuberculosis control.
    TB is an important issue, and I hope the hearing today will 
encourage the Senate to act favorably on legislation that will 
provide increased authority, resources, and coordination for TB 
control among Federal agencies.
    There are three points I want to make today in my 
presentation. No. 1, tuberculosis is still a problem in the 
United States. No. 2, we have tools to combat tuberculosis. But 
No. 3, we will never defeat TB until we develop and apply a new 
generation of diagnostic tools, TB drugs, and an effective 
vaccine.
    TB control, like all of public health, is ultimately 
delivered at the local health department level. This is the 
perspective that I bring to you today. To illustrate these 
points, I will tell you the story about a patient treated in 
our community. This is not someone you would recognize from 
news reports, but this patients' course would be familiar to 
many local health department staff in your own States.
    This young man arrived from Denver after several years in a 
refugee camp in Egypt. He completed and passed the mandatory 
refugee TB screening program before departing Egypt, but became 
quite ill during travel to the United States. He was promptly 
admitted to the hospital in Denver, in fact, he was admitted 
directly from Denver International Airport to the hospital.
    Preliminary tests were negative, but after 5 days, cultures 
grew tuberculosis. His doctors consulted with us at the Health 
Department and promptly initiated treatment for disseminated 
tuberculosis. He was brought to the TB clinic the day of 
hospital discharge by our outreach worker. We did this and we 
do this to ensure that the patient makes their first TB clinic 
visit and doesn't get lost in the transition.
    Several weeks later, test results revealed we were dealing 
with MDR TB, a strain resistant to isoniazid, rifampin, and 
streptomycin. Our public health workers, in doing the contact 
investigation, identified several other family members who also 
had active multidrug-resistant tuberculosis.
    This patient and his family members remained TB free after 
completing 2 years of daily multidrug-resistant treatment, each 
dose directly observed by our health department staff members. 
This was very expensive. But you see, we could not afford to 
have his treatment fail for him, for his family, or for our 
community. The man and his family members felt well within 
months, but we worked with them to ensure that they completed 
the necessary 18 months of treatment to prevent eventual 
relapse.
    This man is now a productive member of our community, 
holding a job, going to school, and supporting his family. This 
story illustrates how a public health emergency can, and should 
be, managed. However, imagine what could have happened if his 
TB disease had become highly infectious during travel. We were 
just lucky.
    If the hospital physicians had missed the diagnosis or 
delayed treatment, if the laboratory results had been 
inaccurate or slower in returning, if the patient was lost to 
follow up at discharge and never got into the clinic for 
treatment, if budget cuts meant we no longer had the staff to 
ensure curative treatment of the patient and his contacts, and 
if, even worse, the patient's treatment was inadequate his 
disease would then have become XDR TB.
    The effectiveness of your local health department is the 
only thing standing between you and XDR TB. Why do I say that? 
Because every MDR TB case is a potential XDR TB case if 
treatment fails. With over 100 new MDR TB cases in the United 
States each year, that means there are two diagnosed every week 
in either your local health department in your State or in a 
health department in my State. And it's incredibly important 
that these be managed correctly.
    We have a superb staff at the Denver TB Control Program, 
with expertise in clinical and public health management of TB. 
We have the experience of treating one MDR TB case each year, 
on average. I'm sure that you can imagine, however, that in a 
health department where MDR TB is not seen, that when one 
surfaces, it is a public health crisis.
    I hope you can appreciate from my local perspective, that 
TB remains a problem in the United States and that our current 
tools can be effective if we have the necessary resources to 
apply them.
    For the last point, I hope you're asking yourself, why we 
should have to treat this man's TB for 2 years. This is a 
throw-back to how we treated TB in the 1960s. In fact, we are 
now perfecting the obsolete treatments we abandoned over 30 
years ago. But why? Part of the answer lies in the nature of 
the TB bacterium. It mutates when inadequately treated. More 
importantly, we knew this, but we failed to respond. Globally, 
we failed to ensure the completion of curative treatment to 
prevent drug resistance and we allowed research for new and 
better drugs to grind to a halt.
    There is no scientific reason why we should not have a TB 
diagnosis confirmed or excluded within days. This can be done 
at selected places in the United States now, but nearly half of 
persons with culture-positive TB across the globe can not get a 
diagnosis because of reliance on ancient tests. Most patients 
with MDR TB and XDR TB, unlike the one who made it to Denver 
and survived, will die without a diagnosis ever being made.
    In 1993, AIDS was a chronic, progressive, infectious 
disease, for which treatment only delayed eventual death. Our 
national investment in clinical research changed that, and HIV 
can now be diagnosed rapidly and treatment is highly 
successful. In fact, there's one single-dose, daily treatment 
that involves three drugs that is highly effective for treating 
AIDS. These new HIV tools are now being implemented with 
governmental funding around the globe. In contrast, we have 
largely ignored TB research needs and millions are now paying 
for it.
    The good news is, that today, our existing tools can 
prevent the further development of drug-resistant strains if we 
apply them correctly. We have labor-intensive, but successful, 
public health strategies to prevent the spread of TB. We even 
know how to implement these in resource coordination's around 
the world. What is needed is the authority and resources to get 
the job done.
    The American Thoracic Society is pleased to support the 
legislation, the Comprehensive TB Elimination Act sponsored by 
Senators Brown, Hutchison, and Kennedy. This legislation 
responds to the public health threat that TB poses today and it 
seeks to ensure that the CDC, State and local health 
departments, and all health care providers are ready for the 
future. It would expand the resources and the authority of the 
CDC to more effectively apply today's TB diagnostic and 
treatment tools in the United States. The bill also expands 
CDC's authority to conduct the research needed to bring 
effective diagnostic and treatment tools into practice.
    Our public health system must be prepared to respond to the 
mutating TB germ. I thank the committee for this opportunity to 
testify on this important subject.
    [The prepared statement of Dr. Reves follows:]
               Prepared Statement of Randall Reves, M.D.
                              introduction
    My name is Randall Reves, M.D. and I am Director of the Denver 
Metro Tuberculosis Control Program and Associate Professor at the 
University of Colorado Health Sciences Center Department of 
Preventative Medicine and Biometrics. I am representing the National 
Tuberculosis Controller's Association (NTCA), the national association 
representing State tuberculosis control programs, the Stop TB USA 
Coalition (formerly the National Coalition for the Elimination of 
Tuberculosis), the U.S. partner of the global Stop TB Partnership, and 
the American Thoracic Society (ATS), a medical professional society 
that was founded over 100 years ago to foster the prevention, 
detection, treatment and cure of tuberculosis. The NTCA/Stop TB USA/ATS 
would like to thank Chairman Kennedy, Senator Brown and Ranking Member 
Enzi for holding this important hearing and for their leadership on 
global and domestic tuberculosis control. Tuberculosis is an important 
global and domestic public health threat that deserves the attention of 
Congress. I hope the hearing today will encourage the Senate to act 
favorably on legislation that will provide increased authority, 
resources and coordination for TB control efforts among key Federal 
agencies.
    There are three points I want to make. First, tuberculosis is a 
problem in the United States. Second, we have tools today to combat the 
spread of TB. Third, we will never defeat TB until we develop a new 
generation of diagnostic tools, a new generation of TB drugs and an 
effective vaccine.
                      the scope of the tb problem
    What is tuberculosis? Tuberculosis is an airborne infection caused 
by a bacterium, Mycobacterium tuberculosis. It primarily affects the 
lungs but can also affect other parts of the body, such as the brain, 
kidneys or spine. Tuberculosis is spread through coughs, sneezes, 
speech and close proximity to someone with active tuberculosis. People 
with active tuberculosis are most likely to spread it to other people 
they spend a lot of time with, such as family members or co-workers. It 
cannot be spread by touch or sharing utensils used by an infected 
person. The statistics for TB are alarming. TB is the second leading 
infectious disease killer in the world, taking at least 1.6 million 
lives per year.\1\
---------------------------------------------------------------------------
    \1\ Tuberculosis, World Health Organization (WHO) Factsheet No. 
104, March 2006.
---------------------------------------------------------------------------
    Until the Andrew Speaker case emerged earlier this year, many 
Americans thought TB was a disease of the past. The number of persons 
with newly diagnosed TB in the United States appears to be leveling off 
at just under 14,000 new cases and over 600 deaths each year. Although 
the number of TB cases in the United States continues to fall, the 
slowing of the decline rate, from 6.6 percent per year in the period 
1993-2002 to 3.1 percent per year in the period 2003-2006, is of 
concern because of the history of TB in the United States.\2\ In the 
1970s and early 1980s, the Nation let its guard down and began 
significantly reducing the TB control infrastructure. Consequently, the 
trend towards elimination was reversed and the Nation experienced an 
unprecedented resurgence of TB with a 20 percent increase in cases 
reported between 1985 and 1992.
---------------------------------------------------------------------------
    \2\ CDC. Reported Tuberculosis in the United States, 2006. Atlanta, 
GA.: U.S. Department of Health and Human Services, CDC, September 2007.
---------------------------------------------------------------------------
    That's the medical explanation and statistical background on TB in 
the United States. But what do we mean when we say TB is a domestic 
problem? It means that people in the United States are getting TB, 
including the drug resistant strains featured in the Andrew Speaker 
case earlier this year. It means even in the United States, where the 
TB incidence is much lower than the developing world, we are still 
vulnerable to outbreaks of multidrug-resistant (MDR) TB. As the Andrew 
Speaker story made clear, it only takes one infectious individual in 
close proximity to other people--in this case an intercontinental 
flight--to cause a public health alarm.
    While the Andrew Speaker story is alarming, the truly alarming news 
is that TB is mutating. Poor control of TB has lead to the development 
of drug resistant strains of TB. There are even strains of extremely 
drug resistant TB that are resistant to four or more of the drugs 
commonly used to treat TB. Without immediate attention to this problem, 
we may soon see strains of TB that are infectious, lethal and 
essentially impossible to cure.
    While the Andrew Speaker case got media attention, Mr. Speaker is 
far from the typical case of TB found in the United States. Let me 
share with you a more typical example of a TB case found in the United 
States. A couple of years ago, I treated a young man with tuberculosis 
from Egypt. The man most likely became infected with TB while living in 
a refugee camp. Despite completing and passing the mandatory TB 
screening program prior to entering the United States, he was 
hospitalized for pulmonary symptoms shortly after arriving in the 
United States. Based on his symptoms and case history, he was presumed 
to have TB and was put on antibiotic treatment. He responded well to 
treatment. A few weeks after treatment was initiated and he was 
discharged from the hospital, test results came back indicating the man 
had drug-resistant TB with resistance to isoniazid, rifampin and 
streptomycin--the three first line drugs used to treat TB. He survived 
because initial treatment included drugs with MDR TB activity.
    The patient remained free of TB after completing 2 years of daily 
treatment with health care workers delivering and observing ingestion 
of each dose. Public health workers also did standard contact follow up 
and identified other members of his family that had MDR TB. They also 
were located and treated successfully. This man is now a productive 
member of our society holding a job and supporting a family.
    This case illustrates many of the strengths and weaknesses of the 
current tools used to detect, treat and cure TB. And let me tell you 
that Denver is one of the best run TB programs in the United States. We 
are experts in both the medical and public health aspects of TB. Any 
potential flaws in how a case is handled in Denver are going to be 
magnified in programs with less expertise.
    Refugee camps are well recognized as being hot beds for developing 
drug-resistant strains of TB. However, applying standard public health 
practices for TB in refugee camps could significantly reduce this 
problem. Identifying cases under a microscope, screening for HIV and 
providing the standard course of anti-TB drugs can be done cheaply and 
with a minimum financial investment. Instead, the lack of TB control 
measures in Egypt meant that my patient and several of his family 
members developed MDR TB, significantly increasing the cost of treating 
the disease and posing significantly higher health risks for everyone 
they came in contact with.
    How this man passed the initial screening test prior to entering 
the United States, I don't know, but I would suspect the reason, in 
part, is due to the lack of fast, cheap tests capable of effectively 
screening for TB.
    While my patient from Egypt responded well to the initial 
treatment, it was weeks after he was discharged from the hospital that 
we found out he had MDR TB. We were able to keep track of Mr. X and 
alter his treatment accordingly, and provide follow up for 2 years to 
ensure he completed his treatment. What if during that 2-week 
timeframe, he got ``lost'' and could not be followed up with? Then a 
super-germ would be circulating throughout the community potentially 
infecting others. Diagnostic tests that can detect TB in hours or 
days--not weeks--are needed to accurately detect TB and its level of 
drug susceptibility.
    What if, due to cuts in public health funding, we did not have the 
staff to follow up with my patient's contacts? Then we would have 
failed to identify his family members who also had MDR TB, again 
putting the community at risk.
               the need for better diagnostics and drugs
    Why did it take 2 years to successfully treat his TB? While we 
should be pleased that the Denver public health system was able visit 
him daily for 2 years to ensure he completed his antibiotic treatment, 
think of the staff time and organizational effort involved in a 2-year 
treatment plan. Drugs with shorter treatment times and novel 
antibiotics to treat TB are desperately needed.
    When the first highly successful treatment for TB with INH-
streptomycin-PAS was introduced in the 1950s, we failed to ensure that 
all patients completed the 2-year course of treatment, allowing the 
bacteria to become resistant. Most experts at the time believed that 
drug-resistance was harmless since many patients improved clinically 
despite persistence of positive sputum cultures. The ``mutant'' 
bacteria were believed incapable of being transmitted to others. That 
theory held for 20 years until 1977 when I, as a new CDC trainee 
stationed in Mississippi, pursued the investigation of a high school 
outbreak of INH-streptomycin-PAS resistant TB in Alcorn County. These 
bacteria had spread to 150 students and faculty resulting in five 
active TB cases. The source was a smoldering community outbreak with a 
total of 22 active TB cases that began when the public health system 
failed to ensure treatment for patients diagnosed up to 12 years 
earlier.
    We moved on to the next wonder drug and cured most of the drug-
resistant TB cases in Alcorn County using the new wonder drug, 
rifampin, in combination with ethambutol. At least two patients lapsed 
from treatment and the bacilli added rifampin resistance to their 
existing repertoire of drug resistance genes, killing one previously 
healthy young woman. This shot across the bow by an organism, later 
named MDR TB, was largely ignored for the next two decades as we 
allowed local, State and national tuberculosis control capacity to 
deteriorate to the point that successful completion of the new 6-month 
TB treatment in many areas became the exception, rather than the rule.
    The end result was extensive, deadly outbreaks of TB in New York 
City, Miami and other cities in the 1980s and 1990s and MDR strains 
resistant to more than six drugs were found to be readily transmitted. 
Patients with HIV/AIDS in New York City died within weeks, usually 
before the drug resistance was detected. We had no new TB drugs to use 
but learned by experience, not by research, that new fluoroquinolone 
antibiotics could be used successfully in combination treatment lasting 
18-24 months. For patients with MDR TB this meant going back to 
treatments we abandoned two decades ago, including lung surgery. We 
learned to stop complaining about patients who were not compliant, and 
became committed to ensuring curative treatment. Many programs adopted 
the approach touted decades earlier by John Sbabaro in Denver, 
insisting that a health care provider Directly Observe the ingestion of 
each dose of Treatment (DOT).
    There is no scientific reason that we should not have a TB 
diagnosis confirmed or excluded within days. This can be done in 
selected places in the United States now, but nearly half of all 
persons with culture-positive TB across the globe cannot get a 
diagnosis because of reliance on the sputum AFB smear, a 100-year-old 
test. Most patients with MDR TB and XDR TB will die after treatment 
failure without a culture and/or drug susceptibility test ever being 
done. There are promising diagnostic tools that will need evaluation in 
field studies before successful implementation.
    In 1993, AIDS was a chronic progressive infectious disease for 
which treatment only delayed the inevitable progress to death. Because 
of our national investment in clinical research, HIV infection can now 
be diagnosed within weeks of onset, and AIDS can now be successfully 
treated with one triple-drug pill taken daily. These new tools for HIV 
are also being implemented, with governmental funding, around the 
globe. We have largely ignored TB research and needs, and millions are 
now paying for it.
                     domestic tb control challenges
    The fiscal year 2007 funding level of $137.4 million for the 
Centers for Disease Control and Prevention's Division of Tuberculosis 
Elimination actually represents a 27 percent decrease over the past 
decade when adjusted for inflation. To effectively address TB in the 
United States and appropriately develop both domestic and global 
preparedness and outbreak response capacity for drug-resistant TB, 
additional resources are urgently required.
    In order to prevent the spread of drug resistant TB in the United 
States and to put the Nation back on the path to eliminating the 
disease in the United States, domestic TB control capacity, and 
treatment, and prevention systems must be strengthened to ensure 
diagnosis, and treatment. The following are some additional specific 
steps that must be taken:

     Improve strategies to identify and treat latent TB 
infection and reach at-risk populations.
     Intensify TB control activities among persons who 
regularly cross the United States-Mexico border.
     Intensify efforts to prevent, detect, and treat TB among 
foreign-born persons in the United States.
     Expand United States-provided leadership and intensify 
technical assistance activities to address the global TB crisis.
                               conclusion
    The slowing of the decline in the overall national TB rate and the 
inability to effectively address persistent disparities in TB rates 
between U.S.-born and foreign-born persons and between minority 
populations threatens progress toward the goal of eliminating TB in the 
United States.
    The good news is that today, appropriately applying our existing 
tools can prevent the further development of drug resistant strains of 
TB. We have successful--but labor intensive--public health strategies 
to prevent the spread of TB. We even know how to make TB control 
programs work in the most resource-poor nations in the world. What is 
needed is the authority and resources to get the job done.
    The American Thoracic Society is pleased to support the 
legislation--the Comprehensive TB Elimination Act--sponsored by Senator 
Sherrod Brown of Ohio, Senator Kay Bailey Hutchison of Texas, and 
Senator Edward Kennedy of Massachusetts. This legislation responds to 
both the real and immediate public health threat that TB poses today as 
well as looking to the future to ensure that the Centers for Disease 
Control and State and local public health departments and all health 
care providers are ready for the future.
    It responds to today's needs by expanding the resources and 
authority of the CDC to more effectively apply today's diagnostic and 
treatment tools to identify and effectively treat TB in the United 
States. The legislation also gives CDC expanded authority to conduct 
research to develop more effective diagnostic and treatment tools 
particularly a new generation of anti-TB drugs--to ensure that our 
public health system is prepared to effectively respond to a mutating 
TB germ.
    I thank the committee for this opportunity to testify on this 
important subject.

    Senator Brown. Thank you, Dr. Reves.
    Dr. Reves, earlier, I think Dr. Castro mentioned--and I 
really appreciate your comments about drug resistance and your 
statement that every TB case is potentially a multidrug-
resistant case, and what that means to patients and doctors and 
the whole public health system and policymakers--Dr. Castro had 
talked about the difficulty of having people who really do know 
how to treat tuberculosis, how to recognize it, how to diagnose 
it, how to treat it--are you seeing as a representative here, 
in some sense, of the States and of public health authorities 
all over the States, all over the communities of this country, 
is it a significant long-term problem that we don't train 
doctors and nurses and other public health officials well 
enough to recognize TB? Talk about that as a problem, and what 
we need to do about it.
    Dr. Reves. Well, it is a major problem, and the health 
department sector where I work, we really rely upon physicians 
in practice--whether that be the emergency room, the hospital, 
other clinics and so forth--to diagnose at least two-thirds of 
the cases that they then refer to us, report to us, and refer 
for treatment. So, it is a challenge, because you have 
physicians who haven't seen a case of TB in 5 or 10 years. And 
how do we provide them with some sort of an ongoing continuing 
education reminder, and a small enough piece that it doesn't 
consume their whole day? Nobody needs to go to the 3-day 
National Jewish course if they're not going to see a TB case in 
5 years. But, they need to be reminded and to think about 
tuberculosis.
    One of the things we've done in Denver is working with some 
of our community-based groups--there's an Asian-Pacific 
Islander Health Education Project involving a number of 
different community groups, and at their health fairs, they 
talk about TB, they've gotten past the stigma about it. And 
it's helpful, I think, if a patient goes into their doctor who 
hasn't seen TB in 5 years and say, ``Well, you know, I'm from 
Thailand, I'm from India, I'm from Korea, I'm from Mexico--
could these symptoms be due to tuberculosis?''
    Senator Brown. Thank you, and continue to do some thinking 
about that, and all of you, really give this committee your 
input about how we can help to prepare the public health sector 
better.
    Dr. Frieden, you mentioned the sort of analogy of when 
patients stop taking their medicine, it's not too far different 
from when government stops doing things, because the patient 
quits coughing in the second month, that they can now stop, and 
they feel better, or they feel worse when they're taking the 
medicine, feel better when it stops--the analogy that 
government stops funding when TB starts to look better. Do you 
see similarities between the current domestic TB situation and 
what you saw in New York a decade and a half ago?
    Dr. Frieden. A decade and a half ago, what was happening is 
that we had ignored warning signs in the poorer communities of 
New York City, where rates were quite high. Funding was 
reduced, and programs were reduced, and there was an 
inappropriate focus on things that didn't make a big difference 
in TB control. We lost sight that the priority is to cure 
patients with infectious disease, and once you've got that 
underway, you can then start preventing TB in people who have 
infection but aren't sick. And there were simply insufficient 
resources.
    What happened then, there was intense media interest, there 
was a crisis mentality, there was a big increase in funding at 
the local level, at the State level, at the Federal level, and 
TB is a very rewarding disease to treat as a physician or as a 
public health officer, because it responds to good management. 
You do the right things, and in just about everywhere in the 
world, it goes away. You can cure the vast majority of 
patients, you can bring rates down. That's what we saw. So, as 
I mentioned, our rate of multidrug-resistant tuberculosis is 95 
percent less than it was at the peak of our epidemic.
    U.S.-born cases are down by 91 percent, and overall cases 
are down by 75 percent. It used to be that only about 18 
percent of our cases were among the foreign-born, now it's 70 
percent among the foreign-born.
    What we're seeing now is the erosion of the public health 
infrastructure. Funding for CDC has not kept up with inflation, 
it's down by 27 percent in constant dollars, funding in New 
York City is down by 70 percent from the Federal Government. We 
do our best to continue to control the disease, but we're 
ignoring warning signs that could be a serious problem.
    At the same time, we have to recognize that there is a huge 
problem globally, and we can't just put our head in the sand. 
Unless we can address that problem, we're never going to 
control TB in this country. I can't stop those 70 percent of 
cases that are coming into New York City--they feel fine when 
they come in--but 1 year, 5 years, 10 years, 20 years later, 
they break down with active tuberculosis having been infected 
overseas.
    We don't want to keep people out. These are people who, in 
the vast majority of cases are here legally, they're part of 
our society, they're contributing, they're working, they 
actually use fewer health services than many other people, but 
they may have a higher risk of having active tuberculosis.
    One of the most effective ways we can protect our own 
country is by improving tuberculosis control globally, so that 
they don't have drug-resistant tuberculosis, they don't have 
multidrug, or XDR TB, they don't have TB at all, because the 
disease is controllable.
    Senator Brown. Thank you, thank you, Dr. Frieden.
    Dr. Sadoff, unfair question perhaps, but predict when we're 
going to see a vaccine, when we're going to see a new, improved 
diagnostic tool. Share with us where the emphasis and the 
resources have been on those two--are we putting more public/
private emphasis on vaccines, or on diagnostic tools and what 
do you predict in the next few years, if you could?
    Dr. Sadoff. Thank you. Well, we think that others working 
on diagnostics are going to come up with better diagnostics, 
actually in the next 2 years, with something that might be very 
effective in the next 3 to 5 years. There's a couple of drugs 
that look very promising that could be available 3 to 5 years 
from now, and we think that a new vaccine will be available at 
around 2015--late 2014, 2015. As I said in my testimony, we've 
got 6 candidates that we're narrowing down with small trials, 
so that we can pick the best to go into very large-scale 
trials, which should start mid-2010, and then we should have 
licensure of 2014, 2015.
    I know it sounds like a long time, and I agree completely 
that we have to do everything we can to control TB with the 
tools we have now, but I also believe that if we're not 
forward-thinking on new tools, we'll really never get control 
of this disease worldwide and even in the United States.
    And that's because the synergy between immunosuppression, 
that was brought up by one of the Senators, and TB is making TB 
go completely out of control worldwide. The synergy between the 
HIV epidemic and the TB epidemic is overwhelming our standard 
control measures around the world. And that doesn't mean we 
shouldn't do everything we can to use everything we can right 
now, but I really believe without new tools, we're going to be 
overwhelmed.
    Senator Brown. In 2 years, you said 2 years diagnostic--
good diagnostic tool, 3 to 5 years really something good, and 
2014 or 2015 vaccine. I've worked in this town a long time--
I've never seen a witness give that specific a prediction on 
anything, especially on the Federal budget, but thank you for 
that. We will----
    Dr. Sadoff. We work on timelines.
    Senator Brown. No, I appreciate the way you've thought 
about that, the way you laid that out, with the people, with 
the researchers working in your operation and all of that. 
Thank you.
    Senator Burr.
    Senator Burr. I also should say, I don't believe this 
Congress or any Congress can change the ebb and flow of what we 
throw at any given disease, Dr. Frieden--I think it's inherent 
in the institution. When there's pressure and concern and fear, 
the investment goes up. When that fear goes away, the 
investment goes down. Some of us don't like it, but that's the 
reality of the institution.
    Dr. Reves, you talked about needing new tools and drugs, 
let me just ask you quite candidly--what, if anything, could 
the CDC be doing today that would improve our ability to better 
educate health professionals and the public, respond to TB 
outbreaks, prepare, all of the above?
    Dr. Reves. Well, there's, in terms of training, there are 
these regional training centers and those are doing their best 
now. I think we--clearly we can expand that. We do our best to 
try to get out to our community to educate our physicians, but 
there's a limited amount of time that we have for that.
    In terms of treatment tools, what's required is studies 
that enroll around 1,000 or maybe 1,500 patients during the 
course of treatment and follow up for a couple of years 
afterwards. We're at the phase now at the CDC clinical trial 
group of really looking at short-term treatment to find out, 
does this look like a promising drug to take into a long-term 
regimen? So, if we had more sites that we could enroll in those 
studies--we have sites in Uganda, South Africa, Brazil and 
Barcelona, that also contribute--if we could expand to some 
additional sites and enroll those studies more rapidly, get to 
the answers more quickly, then go onto the next study to find 
out how these really work in combination with other drugs, we 
could get there a lot quicker. And, I think that's a key thing, 
if we could really expand that clinical trials network.
    And, in terms of the diagnostics, there's a lot of 
promising things out there, but what you have to do is go out 
and put them in the clinic, and find out--how does this really 
work? When we have a group of refugees coming in from Burma. If 
we apply this test, compared to our previous test--how well 
does it actually pick up active tuberculosis in a timely 
fashion?
    Senator Burr. Clearly we have an implementation problem. We 
have an aversion to the risk, because we're trying to do 
something different. I mean, we've been doing it for 100 years, 
there's a great comfort level.
    Dr. Frieden, you talked about the need to educate 
healthcare providers and communities. What strategies would you 
suggest we consider to effectively do that education?
    Dr. Frieden. I think there are two different aspects of 
that question, in this country, and then a different issue 
globally.
    In this country, as Dr. Reves pointed out, many physicians 
won't see a case of TB for the next 5 years, so----
    Senator Burr. Some have never seen a case of TB.
    Dr. Frieden. That's right. And, so you basically need to 
keep it simple. If someone's coughing or has fever, think of 
the diagnosis, because we really rely on the general healthcare 
system to make the diagnosis.
    Senator Burr. But let me ask you--who can effectively do 
that?
    Dr. Frieden. Who can give that education? I think there are 
a lot of possibilities. In New York City, we do quite a bit of 
outreach to physicians through actually office visits, 
patterned after the pharmaceutical detailing-type visit. We do 
continuing medical education----
    Senator Burr. But New York City is a place where there are 
12 or 13 now, per 100,000 so you--people in New York City are 
way more aware of it than they are in Charlotte, I would think, 
or in Asheville--in more rural areas.
    Dr. Frieden. Somewhat. Though, we also have challenges, for 
example, with some of our physicians who may have been trained 
elsewhere, and they have a different approach to diagnosing and 
treating TB. So, one of the things that we find very useful, is 
first off, we have to maintain the care system in the public 
health world. We run TB clinics, as do the public hospital 
system. Those clinics need support--they need support in the 
short-term and in the long-term, TB is going to be with us for 
a long time. They need to provide excellent care, so that 
doctors can refer the patients to us when they've found them, 
or we can do the follow up of those around the patient to see 
if there are people who have become infected, and make sure 
they get preventative treatment so they don't become tomorrow's 
case.
    At the same time, there's a lot that we can do around each 
case. So, anytime a case is diagnosed, or even suspected, it's 
reported to us, we reach out to the doctor or the hospital or 
the health center, and we can use that as a teachable moment.
    Senator Burr. Is there a Federal template that every 
community health agency in the country can easily access to 
learn how to educate the medical community on TB?
    Dr. Frieden. There are good Federal materials on education 
about tuberculosis and we work with our own partners on this. I 
think educating physicians, both in training and afterwards, is 
an area where we've worked hard, and I would have to say, 
frankly, we haven't always gotten the results we'd like to get.
    Senator Burr. I guess the question I'm asking is, the CDC 
is connected to public health, I keep reminding everybody of 
the prevention side. Isn't that the best avenue for us to have 
some type of standardized educational process--not just limited 
to TB, but it might include other infectious disease areas that 
we've got concerns about down the road?
    Dr. Frieden. Absolutely, I think there are many ways in 
which Federal, State and local public health agencies can 
really enrich the quality of healthcare. We spend $2 trillion a 
year on health care in this country, and yet we don't prevent a 
lot of preventable diseases.
    Senator Burr. Well, when you've got a system that only 
triggers when you get sick, you understand exactly how flawed 
our healthcare system is in this country.
    We're going to get called out for votes, I just want to ask 
one more question and let the Chairman have the rest of the 
time.
    Dr. Sadoff, we've created a new mechanism to try to help 
finance private companies in the advanced development of drugs, 
vaccines, and antivirals, as it relates to the threat of 
bioterrorism. It seems like what you've designed is extremely 
similar, you've just done it from the private side--private 
companies, private dollars, foundations, commitments to take 
products through, what I call, the Valley of Death--in between 
the initial funding from NIH, to the end where they're actually 
in the FDA approval process.
    Is there anything that you'd like to expand on your model 
that would help us to better understand it?
    Dr. Sadoff. Thank you for the question. Yes, that Valley of 
Death is a good description of it, because not only is it very 
difficult and requires tremendous levels of expertise and 
experience, but for scientists that are used to excitement, 
it's quite boring. And, it's something where you take a novel, 
exciting idea, and then make it into something that's routine, 
that works in millions of cases, where you can make millions of 
doses of something. That process is not something that is very 
well appreciated outside of industry, where that's what they 
actually do.
    Our model, then, tries to capture that process, and those 
processes which take the novel ideas, and the creative spirit 
that scientists use to generate these novel concepts, and then 
make them into something practical. And that requires--as I 
said in my testimony--three things: a balance between 
resources, risk, and time. Time is critical because 1.7 million 
people are dying every day. And you can shorten time by taking 
more risk and using more resources. But you have to do that in 
a balanced way, because you can use too many resources--there's 
only limited resources, and there's limited risk. And that 
balance is what's absolutely critical to the industrial model.
    We've tried to capture that by having people from industry 
that have that experience, including people like myself, work 
with industry to provide--or work with academics, or even work 
with the government--to try and provide whatever is necessary 
that they're missing--whether it be money and resources, 
experience, field sites, technical expertise. Biotechs don't 
have the same expertise as a big pharma does in manufacturing, 
but they may have more of an entrepreneurial spirit.
    So, there's a balance for each one. That's what we try and 
create. And I think that this model, with funding from 
philanthropy and with funding from government, can help channel 
and help develop that type of expertise which really exists 
primarily currently in industry, but there's plenty of industry 
people very dedicated to doing good for the world in this type 
of a model, and that's what we're trying to capture.
    Senator Burr. Well, let me thank all three of our doctors 
for, No. 1, your experience, and No. 2, your passion for this 
infectious disease, and the belief that it's unacceptable for 
us not to make progress, because this is achievable if we all 
head in the same direction.
    I thank you, Mr. Chairman.
    Senator Brown. Thank you, Senator Burr.
    And thank you all, Dr. Reves, Dr. Sadoff, Dr. Frieden, 
thank you for being here today, but especially thank you for 
your commitment, as Senator Burr said.
    And, any of you that have thoughts--and that includes 
anybody in the audience, too, that has thoughts about improving 
the legislation we're working on, any of the bills we've talked 
about today--feel free to share those thoughts with Roberta 
Downey, who is sitting behind me, in our office, or anyone with 
committee staff on either side of the aisle. Because, I think 
this is an issue that we want to do it right and work on this 
long-term the way that we should.
    So, I thank all of the witnesses, thank you Dr. Castro, 
too.
    The committee is adjourned.
    [Additional material follows.]

                          ADDITIONAL MATERIAL

            Questions of Senator Coburn for Dr. Castro, CDC
    Question 1. Dr. Castro, Senator Brown's bill calls for a 
comprehensive plan to address TB prevention, control, and treatment. 
Does CDC have the authority to do that sort of planning today? Why have 
they not?

    Question 2. Dr. Castro, what does Senator Brown's legislation 
include that you cannot already do?

    Question 3. Can you comment on the effect that passing one disease-
specific bill has on the other disease prevention efforts that are 
ongoing at CDC? Are resources and efforts diverted from some when we 
pass bills about our favorites?

    Question 4. Dr. Castro, I understand that CDC provides $100 million 
to support local and State efforts to prevent TB. Can you outline for 
me the metrics that are used to evaluate how effectively these dollars 
are being used?

    Question 5. How does CDC justify spending $1.7 million on Hollywood 
liaison programs, $10 million in furniture, $45 million in conferences, 
and syphilis prevention funds on a porn star's presentation (http://
coburn.senate.gov/ffm/index.cfm?Fuse
Action=OversightAction.Home&ContentRecord--id=bf7e1789-802a-23ad-42e1-
57d542e77901) when the threat of TB is very real and very imminent?

    Question 6. The Federal deficit is estimated to be $163 billion 
this year. The national debt is $9.1 trillion. The CDC already provides 
$100 million to States and local entities. Dr. Castro, your testimony 
mentions that many State and local governments have faced budget 
challenges in recent years and that's why CDC needs more funding to 
help them. New York has a $3.2 billion budget surplus this year, and 
the Federal Government has a $163 billion deficit. If you were a CEO, 
which budget would you pull from to get both governments out of the red 
ink next year?

    [Editor's Note: Responses to the above questions were not available 
at time of print.]

    [Whereupon, at 11:43 a.m., the hearing was adjourned.]

