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TB Notes 1, 2000
Introduction
Where We've Been and Where We're Going: Perspectives from CDC's Partners in TB Control
Changes I've Seen
TB Control in New York City: A Recent History
Not by DOT Alone
Baltimore at the New Millennium
From Crickets to Condoms and Beyond
The Denver TB Program: Opportunity, Creativity, Persistence, and Luck
National Jewish: The 100-Year War Against TB
Earthquakes, Population Growth, and TB in Los Angeles County
TB in Alaska
CDC and the American Lung Association/ American Thoracic Society: an Enduring Public/Private Partnership
The Unusual Suspects
The Model TB Prevention and Control Centers: History and Purpose
My Perspective on TB Control over the Past Two to Three Decades
History of the IUATLD
Thoughts about the Future of TB Control in the United States
Where We've Been and Where We're Going: Perspectives from CDC
Early History of the CDC TB Division, 1944-1985
CDC Funding for TB Prevention and Control
Managed Care and TB Control - A New Era
Early Research Activities of the TB Control Division
The First TB Drug Clinical Trials
Current TB Drug Trials: The Tuberculosis Trials Consortium (TBTC)
TB Communications and Education
TB Control in the Information Age
Field Services Activities
TB's Public Health Heroes
Infection Control Issues
A Decade of Notable TB Outbreaks: A Selected Review
International Activities
The Role of CDC's Division of Quarantine in the Fight Against TB in the U.S.
The STOP TB Initiative, A Global Partnership
Seize the Moment - Personal Reflections
 
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This is an archived document. The links are no longer being updated.

TB Notes 1, 2000

My Perspective on TB Control over the Past Two to Three Decades

by Jeffrey Glassroth, MD
Prof of Medicine, Univ of Wisconsin Medical School
President, American Thoracic Society

In 1975 case rates for tuberculosis (TB) in the United States were in double digits per 100,000. Increasingly, those patients were individuals with serious social problems. A major concern at CDC that year was the screening for TB of newly arriving Vietnamese refugees; the treatment of active cases was provided, and notification to local health departments of latently infected individuals was undertaken. There was also concern about the quality of immigrant screening done overseas, but the major focus of "imported" TB was along the border with Mexico. Monitoring of TB drug resistance, particularly primary resistance (i.e., among persons not previously treated), was pursued and, reassuringly, indications were found that these rates were generally stable and low, particularly with respect to rifampin. A major treatment study was beginning and it would help to define the role of rifampin in so-called "short-course chemotherapy," meaning 9 months of daily treatment as opposed to the standard of 18-24 months that existed at the time. "TB Today!," an intensive educational program that provided essential knowledge to TB control staff from around the country, presented material on TB microbiology and diagnosis that emphasized the (then) state-of-the-art methods; a description of classical microbiologic techniques that had changed little in the near-century since Koch described the tubercle bacillus. Also taught in the course was a segment on optimizing the use and interpretation of the tuberculin skin test for identifying TB infection. A study was about to begin to assess the importance of skin test boosting when sequential tuberculin tests were applied. Much of what was underlying those efforts with tuberculin skin testing actually reflected concerns and frustrations with the use of isoniazid (INH) for treating latent TB infections, so-called TB prophylaxis. On the one hand prophylaxis was effective but, on the other hand, it came with a risk of side effects, most notably hepatitis. The challenge was to identify, via skin testing, the persons most likely to derive benefit from INH and least likely to be harmed by it; a classic benefit/risk "equation." BCG vaccination, though widely used outside the US, was rarely used here, because of perceived limited effectiveness and problems with skin test interpretation.

The intervening quarter century has seen remarkable changes with respect to TB but, in some ways, little has changed. A number of years ago, then–CDC Director Dr. James Mason urged that CDC's TB unit not think in terms of TB "control" but of "elimination." The name of the unit changed to reflect this new, more ambitious mission. Indeed, in the US, after some years of rising rates, TB rates are again falling and are a fraction of what they were 25 years ago. However, in many ways the challenges to TB elimination in the US are greater today than a quarter century ago. Worldwide, TB prevalence is increasing, and today over 40% of cases reported in the US are "imported" in the person of immigrants from high-prevalence countries. The worldwide TB burden is fueled by HIV infection, an entity unknown in 1975, which facilitates every aspect of the natural history of TB from transmission to disease. In recognition of this, and to more efficiently combat these interrelated public health problems, the TB division at CDC is now administratively "housed" with the HIV division. Moreover, CDC has dramatically increased its worldwide collaborations to assist in efforts at containing TB abroad.

Rifampin is now well entrenched as a cornerstone of treatment, and several related rifamycins have come into use. Short-course therapy has been further abbreviated to a standard of 6 months' duration by adding pyrazinamide during the first 2 months of treatment. Moreover, the proven efficacy of intermittent treatment has facilitated the widespread use of directly observed or supervised therapy ("DOT") as a means of improving adherence to treatment and is a major factor in treatment success. Unfortunately, drug resistance has become an additional issue contributing to treatment problems. Moreover, resistance is increasingly a problem with the rifamycins (almost unheard of 25 years ago), and outbreaks and sporadic cases of multidrug-resistant TB (MDR TB) represent a major concern for clinicians and public health officials alike.

Perhaps nowhere has change been more dramatic than in the area of diagnostics. Although skin testing is fundamentally unchanged, the microbiologic approach to TB diagnosis has been revolutionized by the application of molecular biologic techniques. Thus, laboratories are now capable of obtaining genetic material from small numbers of tubercle bacilli in specimens, amplifying or multiplying that material, and then testing the resulting "soup" for specific segments of DNA or RNA that are unique to TB. Refinements of these techniques also permit the identification of resistant strains in some cases and the tracking of outbreaks or mini-epidemics, and help us better understand the epidemiology of the disease as it currently exists. Such techniques hold the very real promise of rapid, highly sensitive, and specific diagnostic tests for TB disease. Powerful tools indeed!

Image 1: Laboratories are now capable of DNA fingerprinting: amplifying or multiplying genetic material and testing the material for segments of DNA or RNA that are unique to TB.

Preventive treatment of latent TB infection still emphasizes the use of INH. However, because of occasional concerns about resistance to INH, and also in an effort to reduce the time required to complete a course of preventive therapy, other regimens — particularly those using rifampin — have been increasingly used and shown to be effective (though more costly) alternatives to INH. Although additional studies have documented the limitations of BCG vaccination, there is increasing interest, in the US and abroad, that through the technical developments of recent years, more effective vaccines are feasible. Given the worldwide problems I have noted, application of a truly effective vaccine would be a logical strategy for dealing with this disease.

So what has happened in TB in the last 25 years? Lots of change and technologic development but fundamental challenges remain. Worldwide the number of cases is rising and treatment is becoming more difficult in some regions. In the US, numbers have declined but current cases often require more resources and sophistication to treat than they did even just a few years ago.

 


Released October 2008
Centers for Disease Control and Prevention
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