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TB Notes 1, 2000
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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TB Notes 1, 2000

Early Research Activities of the TB Control Division

By George W. Comstock, MD, DrPH, FACE
Alumni Centennial Professor of Epidemiology
Johns Hopkins University
School of Hygiene and Public Health

Herman E. Hilleboe was the first Chief of the Tuberculosis Control Division of the United States Public Health Service, with Carroll E. Palmer as director of the Field Studies Section, the unit responsible for most of the Division's research. This review is based largely on perusal of the 70 Tuberculosis Control Issues, published during the first week of every month as special issues of Public Health Reports. This arrangement continued from March 1, 1946, to December 7, 1951, when Public Health Reports changed to a monthly schedule.

The Student Nurse Study was initiated by Palmer, and was supported by the National Tuberculosis Association until the foundation of the Tuberculosis Control Division. During the period from 1943 to 1949, some 22,000 student nurses in 76 schools were given tuberculin tests every six months by a specially trained team. On one of these occasions, approximately 10,000 nurses were also given chest radiographs. Comparison of skin test and radiographic findings showed that many pulmonary calcifications were due to histoplasmosis, that histoplasmosis was concentrated in certain areas of this country, and that many positive tuberculin reactions were due to nontuberculous mycobacteria.

Confirmation of these results came from a research unit established in 1945 in Kansas City, Missouri, to study the epidemiology of histoplasmosis. Two little-known findings deserve emphasis. In two midwestern counties, there was remarkable local variability in the frequency of histoplasmin reactions among cattle. Farms with histoplasmin-positive cattle were interspersed irregularly among those with no reactors. (This marked small-area variability was later found in Maryland among high school students, suggesting that risk factors for endemic and outbreak histoplasmosis are different.)

Studies of tuberculin, histoplasmin, and various nontuberculous mycobacterial antigens reached their peak with the testing of more than a million US Navy recruits from 1958 to 1969. A detailed report of the results of the first half-million tests delineated the extent of these infections in cities, counties, and states. Other important findings were as follows: a) in any area with nontuberculous mycobacterial infections, the larger the tuberculin reaction, the greater the probability that its cause was tubercle bacilli; b) the risk of developing TB after infection was high among underweight persons and low among the obese; c) there was a suggestion that nontuberculous mycobacterial infections conferred some resistance against TB; and d) there was also a suggestion that social stress increased the risk of developing TB.

A major purpose of the Muscogee County (GA) Tuberculosis Study, started in 1946, was to evaluate the role of mass chest x-ray surveys in TB control. The prospectus and a description of the coverage of the survey and prevalence of TB were included in the first two papers published on this study. Calculation of participation rates was made possible by the population denominator provided by a private census. Basic factors associated with participation and the prevalence among participants were described, as well as reasons for not taking part in the survey. Subsequent papers, building on this foundation, were able to provide information on the incidence of TB among tuberculin reactors and the risks of reactivation among persons with inactive TB, information that has been used to the present time.

The first report of the BCG trials in Muscogee County and Russell County (AL) appeared in 1951. The school children vaccinated in 1947 were retested 6 months later, and many controls and vaccinees were tested with tuberculin again in 1950. Both groups had had less than 5-mm induration to the 100-TU dose of PPD tuberculin in 1947. Although 46% of the vaccinees had 5 or more mm of induration to 5 TU of PPD-tuberculin 6 months later, only 24% of them had reactions this large in 1950; at that time, only 3% of controls had similar reactions. Subsequent follow-up of persons in these trials produced findings that were completely unexpected at the time of their initiation. In contrast to the belief that most TB occurred very shortly after infection and that those who survived this short-term risk were relatively safe thereafter, approximately 80% of TB developed among the initially positive reactors who continued to be at risk. This finding dashed an early hope, namely that the source of a new case of TB ought to be readily found among recent contacts. An unpublished finding involved the first 56 cases among survey participants who did not have a known case in the household. Some 13,000 possible contacts were identified (relatives, friends, workers in the same factory, school mates, etc.). Approximately 11,000 were examined, with the identification of only one possible but unlikely source case. The facts that so little TB developed among nonreactors (those eligible for vaccination) and that BCG appeared to cause harm among school children and to afford very little protection to older persons were major considerations in the hesitancy to advise BCG vaccination in the United States. Over a 23-year period, there were slightly but significantly more cancer cases among vaccinees than controls, most markedly for tumors of the lymphoid tissues.

Many other studies were carried out by the Field Studies Section during this period. There were numerous reports relevant to mass chest x-ray surveys, then in their heyday, dealing with topics such as x-ray generators, fluorescent screens, films, protection of personnel, and the feasibility of taking photofluorograms without having participants disrobe. The development of standardized fungal antigens, notably histoplasmin, was also an important endeavor. Finally, and far from least important, was the publication of Carroll Palmer's ideas for research that could be done in conjunction with the mass tuberculin testing and BCG vaccination then underway in the International Tuberculosis Campaign.

(Editor's note: Dr. George Comstock conducted the trials in Georgia from 1946 to 1955. He continued to make major contributions to the knowledge of TB and measures to prevent the development of TB. After retirement from the PHS he became the Alumni Centennial Professor of Epidemiology at Johns Hopkins University. Dr. David Sencer, a medical officer, was then assigned to Georgia to continue Dr. Comstock's work. He subsequently rose through the CDC ranks to become the Director of CDC, serving from 1966 to 1977.)


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