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October 20, 2006
Dear Colleagues:
Several of us from CDC attended the first meeting of the
Global XDR TB Task Force meeting, convened by the World Health
Organization (WHO) in Geneva, Switzerland, October 9-10, 2006.
This meeting was convened to develop a rapid response to the
emerging problem of extensively drug-resistant tuberculosis
(XDR TB).*
Please recall the original publication on XDR TB in the March
24, 2006 Morbidity and Mortality Weekly Report entitled
“Emergence of Mycobacterium tuberculosis with Extensive
Resistance to Second-Line Drugs -- Worldwide, 2000 –
2004” (PDF).
This report provided an alert that XDR TB has emerged worldwide
as a threat to public health and TB control, raising concerns
of a future epidemic of virtually untreatable TB, and documented
the known occurrence of XDR TB globally, as well as here in
the United States—with U.S. patients with XDR TB being
64% more likely to die during treatment than patients with
multidrug-resistant (MDR) TB. We also reported that new anti-TB
drug regimens, better diagnostic tests, and international
standards for second line drug-susceptibility testing are
urgently needed for effective detection and treatment of MDR
and XDR TB.
CDC is collaborating with national and international health
agencies to provide leadership, technical support, and capacity
building to ensure proper action is taken to limit the development
and spread of XDR TB. CDC also participated in an expert consultation
held in Johannesburg, South Africa, September 7-8, 2006, organized
by the South African Medical Research Council (MRC) and WHO.
This consultation was convened because of concerns raised
by recent reports from KwaZulu-Natal (KZN) province in South
Africa, describing a recent outbreak of XDR TB in an HIV-infected
population, characterized by alarmingly high mortality rates.
Of 544 patients found with culture-positive TB, 221 had MDR
TB. Of these 221 MDR TB cases, 53 were described by local
investigators as XDR TB. Of these 53 patients, 44 were tested
for HIV and all were positive; 52 of 53 patients died, on
average within 25 days -- including those benefiting from
antiretroviral drugs. Investigators from the University of
KZN have also documented the existence of this same XDR TB
strain in 28 healthcare institutions throughout KZN province.
Additionally, we learned of anecdotal reports from medical
authorities who care for gold miners describing patients experiencing
unexplained high death rates from TB in neighboring parts
of South Africa. These different data from South Africa likely
represent the “tip of the iceberg” of highly drug-resistant
TB predominantly affecting HIV-infected individuals, and likely
present in other regions of the world.
XDR TB poses a grave public health threat, especially in
populations with high rates of HIV and where there are few
health care resources. Recommendations outlined by the WHO
Global Task Force on XDR TB include:
- Preventing XDR TB through strengthening TB and HIV
control
- Management of XDR TB suspects in high and low HIV prevalence
settings:
Accelerate access to rapid tests for rifampicin resistance,
to improve case detection of all patients suspected of multidrug-resistant
TB (MDR TB) so that they can be given treatment that is
as effective as possible. Rapid diagnosis is potentially
life saving to those who are HIV positive.
Program management of XDR TB and treatment design in HIV
negative and positive people:
- Adhere to WHO Guidelines for the Programmatic Management
of Drug Resistant TB;
- Improve MDR TB management conditions;
- Enable access to all MDR TB second-line drugs, under
proper conditions;
- Ensure all patients with HIV are adequately treated
for TB and started on appropriate antiretroviral therapy.
- Laboratory XDR TB definition:
XDR TB is defined as resistance to at least rifampicin and
isoniazid from among the first line anti-TB drugs (which
is the definition of MDR TB) in addition to resistance to
any fluoroquinolone, and to at least one of three injectable
second-line anti-TB drugs used in TB treatment (capreomycin,
kanamycin, and amikacin).
- Infection control and protection of health care workers
with emphasis on high HIV prevalence settings.
- Immediate XDR TB surveillance activities and needs:
Strengthen laboratory capacity to diagnose, manage and survey
drug resistance; Commence rapid surveys of drug-resistant
TB so that the extent and size of the XDR TB epidemic, and
its association with HIV, can be determined.
- Advocacy, communication and social mobilization:
- Initiate information-sharing strategies that promote
effective prevention, treatment, control of XDR TB at
global and national levels and also in high HIV prevalence
settings;
- Strengthen communication with affected communities
and individuals;
- Develop a fully-budgeted plan with the resources and
funding required to address XDR TB, including through
necessary improvements in overall TB control and HIV
care in the immediate and medium term;
- Initiate resource mobilization.
Many of the lessons-learned from the MDR TB outbreaks in
the United States in the 1990s are being brought to bear to
address this urgent situation. This includes expertise in
rapid outbreak response, surveillance, building laboratory
capacity, and infection control, all while keeping a focus
on overall TB program strengthening as the crucial element
to prevent the development and transmission of MDR and XDR
TB. Our country has accrued more than 10 years of experience
addressing drug-resistance in resource-limited settings and
contributed substantively to development of the DOTS-Plus
strategy and global policy on MDR TB. This puts us in an unparalleled
position to respond to the current crisis; we will rely on
national partners such as the National TB Controllers Association
and the National Coalition for the Elimination of Tuberculosis,
American Thoracic Society, Infectious Diseases Society of
America, and Staff from the Division of Tuberculosis Elimination
(DTBE) and the Global AIDS Program (GAP) to continue and expand
work with colleagues in WHO, U.S. Agency for International
Development, South Africa MRC, and with other international
partners to provide technical assistance, share expertise,
and mobilize financial and technical resources to respond
to action items to address XDR TB.
In addition to providing our expertise and technical assistance
to our international partners, we must also ensure that our
domestic programs are capable of diagnosing, treating, and
preventing TB, including XDR TB. The hard work by many in
state and local health department programs has resulted in
a decline in TB trends, including in 2005 the lowest reported
number of persons diagnosed with TB disease in the United
States. However, that very success makes us vulnerable to
the complacency and neglect that come with fewer persons suffering
with TB. In the 1970s and early 1980s, the nation let its
guard down and TB control efforts were neglected. The country
became complacent about TB, and many states and cities redirected
TB prevention and control funds to other programs. Consequently,
the trend toward elimination was reversed and the nation experienced
an unprecedented resurgence of TB, with a 20% increase in
TB cases reported between 1985 and 1992. Many of these were
in persons with difficult-to-treat MDR TB, and in persons
coinfected with HIV.
Listed below are some very important areas of focus and need
for U.S. TB programs to prevent the emergence of additional
XDR TB and to eliminate TB in the United States.
Maintaining Control: By strengthening current TB control,
treatment, and prevention systems, we ensure the ability
to diagnose and provide proper treatment to people with
active TB disease and, thus, prevent spread to others; this
will also prevent the emergence of MDR TB and XDR TB.
Accelerating the Decline: By finding better methods of
identifying and treating latent TB infection and improving
strategies for reaching at-risk populations, we will speed
our progress toward elimination.
Developing New Tools for Diagnosis, Treatment, and Prevention:
Through research to develop more effective methods of testing
for latent TB infection, better drugs to treat latent TB
infection and active TB disease, and an effective TB vaccine,
we will find vital ways to stop the transmission of TB.
Engaging in Global TB Prevention and Control: In providing
leadership, contributing technical support, and forming
international partnerships, we improve global health. Worldwide
control of TB is in the nation’s best interest.
Mobilizing Support for TB Elimination: By reaching leaders
of high-risk groups, we can work together to eliminate a
disease that burdens their communities.
Monitoring Progress: By assessing the impact of our elimination
efforts, we can continually monitor our progress and identify
and address any lapses in our efforts.
This recently described problem of XDR TB constitutes an
urgent global health reality, instead of an urgent health
threat -- and is deserving of commensurate attention and action.
Furthermore, the experience and expertise gained in our country
from having to respond in the early 1990s to the HIV-associated
resurgent TB and MDR TB will hopefully shed light and provide
relevant lessons. We may need to call upon you to provide
the necessary response, and will keep you informed of progress
and new developments as these occur.
Sincerely yours,
Kenneth G. Castro, M.D.
Assistant Surgeon General
Director, Division of Tuberculosis Elimination
National Center for HIV, STD and TB Prevention
Coordinating Center for Infectious Disease
* Extensively drug resistant tuberculosis (XDR TB) was originally
defined as the presence of Mycobacterium tuberculosis isolates
resistant to at least isoniazid and rifampin (MDR TB), plus
additional resistance to at least three of the six classes
of second-line drugs used to treat persons with MDR TB. These
forms of tuberculosis are both more difficult and expensive
to treat. XDR TB is of particular concern among persons with
HIV infection or other conditions that weaken the host’s
immunity. These persons are more likely to develop TB disease
once they become infected with Mycobacterium tuberculosis, and
have been associated with a higher risk of death. The greatest
concern is that XDR TB leaves some patients virtually untreatable
with currently available drugs.
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