CDC's Response to Ending Neglect
GOAL IV: Increase involvement in global efforts
Increase U.S. involvement in international TB control activities
to reduce the global burden of TB.
TB cannot be eliminated in the United States without a considerable
reduction in the global burden of TB.9 In 2001, approximately
50% of newly diagnosed U.S. TB patients were born outside the United
States.7 Most of these patients acquired their TB infections
in countries such as Mexico, the Philippines, Vietnam, India, China,
and Korea but did not have clinical disease when they entered the
United States. Subsequently, for reasons not sufficiently understood,
their immune systems were unable to keep the infections in check
and they developed active TB. Within the next several years, it
is expected that more than half of the new TB patients diagnosed
each year in the United States will be foreign-born persons.
The global community is fighting TB on several fronts. Based on
the pioneering work of the IUATLD, WHO has developed a specific
strategy for TB control in low-income countries. Thestrategy, called
"directly observed treatment, short-course" (DOTS), combines
five elements: 1) the political commitment of the government to
support TB control programs, 2) bacteriologically-based diagnosis,
with AFB-smear microscopy of sputum specimens of patients with symptoms
of TB, 3) standardized treatment with rifampin-based (short-course)
regimens given under direct supervision, 4) a reliable supply of
quality drugs and diagnostic supplies, and 5) individualized reporting
of treatment outcome coupled with program monitoring and supervision.
DOTS coverage has expanded greatly during the past decade, but inadequacies
in diagnostic and treatment tools limited its easy applicability.
A global partnership, Stop TB was created to help coordinate the
efforts of governments, nongovernmental agencies, and donor agencies
in global TB control. Working through the Stop TB Partnership, CDC
has contributed to DOTS expansion and also addressed the recalcitrant
problems of MDR TB and HIV-associated TB.
Although MDR TB has come under control in the United States, it
appears to be a much more serious problem internationally. In 1999,
the estimated proportion of multidrug resistance in new TB patients
was 1.6% in the United States but reached as high as 10% in Latvia
and Russia (see graph). Rates of TB and drug-resistant TB have been
increasing at an alarming rate in Russia, fueled by 1) lack of continuous
access to quality drugs, 2) the country's inability to support the
TB diagnosis and treatment infrastructure, 3) high levels of TB
transmission in prisons, 4) limited TB control policies and reluctance
to adopt the WHO-recommended DOTS strategy, and 5) increasing levels
of HIV infection.
At the request of the USAID mission in Moscow, WHO, CDC, and USAID
are implementing DOTS programs in the Orel and Vladimir oblasts
(territorial administrative divisions) and strengthening the DOTS
program started by WHO in Ivanovo oblast in 1995. As part of the
implementation of DOTS-Plus (WHO's strategy for managing MDR TB
in low-resource settings) in the Ivanovo oblast, CDC 1) developed
a diagnostic and treatment protocol that has become the basis for
the Russian DOTS programs, 2) posted CDC public health advisors
to 3-month temporary assignments to help implement DOTS and DOTS-Plus
strategies, 3) helped establish a national TB surveillance system,
and 4) conducted epidemiologic studies of risk factors for development
of MDR TB. CDC has also provided laboratory training, quality assurance
for drug sensitivity testing, and consultation. As a result of these
actions, cure rates in Ivanovo oblast have risen from 61% to 75%;
in the initial cohort in Orel, the cure rate was 83%.
CDC has also been involved in activities to strengthen TB laboratory
services in low-income countries. Throughout much of the world AFB
microscopy is the basis for diagnosis and control of TB, but there
is currently no practical guidance for national programs in monitoring
and promoting quality testing at the clinic level. CDC and its Stop
TB partners are developing international guidelines on national
external quality assessment programs for microscopy. CDC has also
developed several products that are focused on providing training
to the laboratory technician performing AFB microscopy at the local
level in middle- and low-income countries.
CDC is also engaged in WHO-sponsored international efforts to evaluate
the effectiveness of treatment strategies for MDR TB in low-resource
settings and to conduct large-scale purchases of MDR TB drugs that
will lower prices to a fraction of current levels. CDC is a charter
member of an MDR TB working group and serves as one of five international
agencies that review MDR TB treatment protocols submitted by national
TB programs for potential participation in WHO's MDR TB treatment
Efforts to address TB-HIV coinfection include the implementation
of the BOTUSA Project in Botswana. In 1995, at the invitation of
the Ministry of Health, CDC established a TB-HIV field site in Botswana,
a country with high HIV prevalence and high TB case rates. The field
site is collaborating with the Botswana Ministry of Health, WHO,
and other countries on the provision of TB preventive therapy to
persons with HIV infection and the development of methods to improve
TB diagnosis in low-resource settings. The BOTUSA site serves as
a base for regional USAID-funded TB activities throughout southern
Africa, including an assessment of drug quality and the implementation
of a computer-based TB surveillance system. Research projects have
addressed 1) causes of illness in patients with suspected TB whose
initial diagnostic evaluation was negative, 2) use of molecular
epidemiology techniques to identify risk factors for TB transmission,
3) absorption of TB drugs in patients coinfected with TB and HIV,
4) TB drug resistance, 5) patients' knowledge and attitudes about
HIV and TB testing, 6) acceptability of preventive therapy, and
7) TB patients' risk behaviors for HIV transmission. BOTUSA is working
with the national AIDS and TB programs to explore the use of preventive
therapy postnatally in HIV-positive women and to identify other
populations for TB preventive therapy.
In collaboration with WHO and other international partners,
provide leadership in public health advocacy for TB prevention and
- Increase collaboration with the Stop TB Partnership at both
the global and regional levels.
- Working with the USAID-funded TB Technical Advisors Consortium,
increase the pool of skilled persons who can provide technical
assistance to TB control programs.
- Support the educational programs of IUATLD.
- Contribute to the development of technical guidelines and recommendations
through participation on international working groups (e.g., Green
Light Committee, WHO Scientific and Technical Group for TB, Regional
WHO Advisory Committees).
- Provide technical assistance to USAID for activities related
to TB control.
- Coordinate with NIH in international TB control and research.
Provide technical support and build capacity for implementation
of DOTS, especially in those countries that contribute significantly
to the U.S. TB burden.
- Contribute technical support and capacity-building assistance
to strengthen epidemiologically-based DOTS implementation in 3
to 5 countries from which a high volume of U.S. TB cases originate
and in several of the other 22 high-TB burden countries identified
- Conduct operational studies to enhance the implementation
- Improve TB surveillance.
- Provide training in program management, epidemiologic methods,
and operations research.
- Assist in program reviews (WHO, IUATLD, USAID).
- In collaboration with the Stop TB Partnership, develop technical
guidelines and training products that strengthen laboratory services
in high-burden countries.
In collaboration with WHO and other partners, develop models
for the diagnosis and treatment of MDR TB in countries with high
rates of drug resistance.
- Expand and enhance the Latvian model center (see page 50).
- Provide assistance to the MDR TB project in Peru funded by
the Bill and Melinda Gates Foundation.
- Implement DOTS-Plus in Ivanovo, Russia.
Provide technical, programmatic, and research support aimed
at reducing the incidence of TB as an opportunistic disease in high
- Through collaboration with CDC's Global AIDS Program (GAP),
provide technical assistance for TB surveillance in countries
with high rates of HIV-associated TB.
- Through collaboration with GAP, provide technical assistance
for enhanced TB laboratory capability in countries with high rates
of HIV-associated TB.
- Through BOTUSA and other GAP-supported programs, conduct operational
research to improve the diagnosis and treatment of HIV-associated
- Conduct large-scale feasibility studies of various regimens
for the treatment of latent TB infection in HIV-infected persons.
Center of Excellence
for the Management of MDR TB in the Baltics
Latvia has one of the highest rates of drug resistance in
the world. In 1999, 10% of new TB patients had MDR TB; this
compares with 1.6% in the United States and <1% in most
African countries. The high rates of MDR TB are attributed
to poor treatment programs and drug shortages that occurred
in the early 1990s after the fall of the Soviet Union.
In 1999, with fiscal support from the U.S. Department of
State, CDC and USAID signed a Memorandum of Agreement to 1)
develop a Center of Excellence for the diagnosis and management
of MDR TB in Latvia, and 2) disseminate lessons learned to
Estonia, Lithuania, and other republics of the former Soviet
Union where TB control efforts have been compromised by drug
resistance. The Center was designed to develop local expertise
and facilities that can provide world-class diagnosis and
treatment of MDR TB and to use locally trained experts and
facilities to train persons from other countries in the region.
The project builds on a foundation of basic TB and MDR TB
treatment programs that are being supported by the Latvian
government with financial and technical support from the World
Bank and the Nordic countries.
Since the signing of the agreement, the Center has made substantial
progress in three focus areas:
1) building expertise among Latvian physicians by strengthening
clinical practice and management,
2) designing and implementing infection-control measures,
3) organizing MDR TB training for physicians from elsewhere
in the region.
In September 1999, the Center initiated a study of risk factors
for primary and acquired MDR TB; findings will facilitate
early targeting of patients with likely MDR TB for more rapid
diagnosis and possible presumptive treatment. The training
component began in March 2000 with a course for Latvian physicians
who manage MDR TB patients. By use of videoconferencing, the
Center also conducts regular meetings in which Latvian physicians
present and discuss difficult management issues with U.S.-based
experts. Finally, the Center has started development of an
MDR TB data management system that will facilitate case management
and treatment outcome studies, the results of which can be
used to improve clinical practice. The data system can also
serve as a model for a WHO consortium of countries conducting
pilot projects in MDR TB management.
Infection-control efforts are designed to respond to evidence
of ongoing transmission of MDR TB to staff and patients. The
Center is developing an infection-control plan that includes
the installation of air-cleaning equipment. A plan to ensure
more rapid laboratory diagnosis of drug resistance is also
being developed so that MDR TB patients can be segregated
from other patients and treated more quickly.
Regional training, the final component of the project, began
in January 2001 with the training of the first group of physicians
from Russia. The 3-week course, which was taught by CDC's
Latvian collaborators in Russian, was an expanded version
of the initial MDR TB course staged for Latvian physicians
in March 2000 and included extensive opportunities for discussion
of case management.
In 2000, the U.S. government launched the Leadership and
Investment in Fighting an Epidemic (LIFE) initiative with
a $100 million increase in U.S. support to 14 countries in
Africa and India. CDC received $35 million of the initial
funds and through its newly formed Global AIDS Program is
working closely with USAID to implement this initiative. CDC's
objectives are to 1) reduce HIV transmission through primary
prevention of sexual, mother-to-child, and bloodborne transmission,
2) develop programs to improve community and home-based care
and treatment of HIV infection, other sexually transmitted
infections, and opportunistic infections, and 3) strengthen
the capacity of countries to collect and use surveillance
data and to manage national HIV/AIDS programs. Improving TB
prevention and control efforts is an important component of
the project, and CDC staff have been involved in 1) developing
project blueprints consisting of "best practices,"
2) participating in site visits, and 3) convening experts
to provide input into the selection of countries for initial
efforts and the proposed content for country-specific projects;
initial TB efforts have focused on six countries.