American Journal of Respiratory and Critical Care Medicine

As tuberculosis transmission decreases, case rates decline and an increasing proportion of cases arises from the pool of persons with latent infection. Elimination of tuberculosis will require preventing disease from developing in infected persons. From 1994 to 1996 the Atlanta TB Prevention Coalition conducted a community-based tuberculin screening and isoniazid preventive therapy project among high-risk inner-city residents of Atlanta, Georgia. We established screening centers in outpatient waiting areas of the public hospital serving inner-city residents, the city jail, clinics serving the homeless, and with outreach teams in neighborhoods frequented by drug users. All services were provided free. A total of 7,246 persons participated in tuberculin testing; 4,701 (65%) adhered with skin test reading, 809 (17%) had a positive test, 409 (50%) fit current guidelines for isoniazid preventive therapy, 84 (20%) we intended to treat completed therapy. The major limitations of this community-based tuberculin screening and preventive therapy project were the low proportion of infected individuals who were eligible for isoniazid preventive therapy and the poor adherence with a complete regimen among those we intended to treat. For community-based programs to be efficacious, preventive therapy regimens that are of shorter duration and safe for older persons will need to be implemented.

Preventive therapy for persons with tuberculosis infection to prevent progression to disease has been advocated since antibiotics effective against tuberculosis became available (1). Early reports described community-based programs as well as clinical trials of preventive therapy for case contacts and institutionalized persons (2– 4). In 1965, the U.S. Public Health Service in collaboration with the District of Columbia Department of Public Health conducted an intensive tuberculin screening and isoniazid preventive therapy project in inner-city Washington, DC (2). At that time the District's tuberculosis incidence rate was among the highest in the country at 67 cases/100,000 persons. Khoury and coworkers report a tremendous effort to reach a high-risk population by going from house to house offering tuberculin testing and delivering isoniazid tablets to the homes of those placed on preventive therapy. However, they concluded that only approximately 13% of the estimated tuberculin reactors in the population completed preventive therapy, and that their study “did not indicate that chemoprophylaxis among reactors should become a city-wide policy.”

With the number and rate of tuberculosis cases in the United States declining to the lowest point ever in 1997 (5), the national goal of eliminating tuberculosis has again become a focus (6). Typically, once tuberculosis control programs effectively decrease transmission of Mycobacterium tuberculosis by early detection and treatment of cases, case rates decline and an increasing proportion of cases arises from the pool of persons with latent infection (7). Elimination will require the prevention of new cases from developing among the 10 to 15 million people in the United States estimated to have tuberculosis infection (8), and community-based tuberculin screening and preventive therapy programs may be an important aspect of a tuberculosis elimination program.

From 1994 through 1996 the Atlanta TB Prevention Coalition conducted a demonstration tuberculosis prevention project designed to diagnosis and treat with isoniazid high-risk persons with tuberculosis infection in Atlanta, Georgia. In 1993 Atlanta had one of the highest tuberculosis incidence rates, 68 cases/100,000 persons, among United States cities with a population of greater than 250,000. We targeted populations for screening and preventive therapy on the basis of the local epidemiology of tuberculosis and national guidelines developed by the American Thoracic Society and the Centers for Disease Control and Prevention (ATS/CDC) (9). We chose sites for the screening on the basis of information regarding access to health care from interviews conducted with 151 patients with tuberculosis disease in Atlanta from autumn 1993 through winter 1994 (10). Three-fourths of these patients reported having no regular source of medical care. Potential public health sites where patients had received some health services and could have been offered tuberculosis prevention services within the 5 yr prior to their tuberculosis diagnosis were correctional facilities (44%), the public hospital emergency room (28%), one of several county sexually transmitted disease clinics (19%), and one of many homeless shelters (12%). Seventy-one percent of the patients reported either alcohol (55%), crack cocaine (42%), or injection drug (26%) abuse. Only 3% were foreign-born.

To evaluate the effectiveness of a tuberculin screening and isoniazid preventive therapy program designed for this high-risk, inner-city population, we assessed the proportion of participants who returned to have their tuberculin skin test read once one had been placed, the proportion with a positive tuberculin skin test among those who had their test read, and the proportion who completed isoniazid preventive therapy among those we intended to treat. For each of these three outcomes, we also determined risk factors associated with the outcomes, and we used these findings to make recommendations for future tuberculin screening and preventive therapy programs.


After consultation with members of the Atlanta TB Prevention Coalition, we established tuberculin screening centers (1) in outpatient waiting rooms at Grady Memorial Hospital, an urban public hospital serving inner-city residents (Grady Memorial Hospital); (2) at the city pretrial detention center (jail); (3) in clinics on mobile vans run by a community-based organization serving the homeless populations at shelters and soup kitchens (homeless clinics); and (4) with a street outreach team doing acquired immunodeficiency syndrome (AIDS) risk reduction education and counseling with the illicit drug-using community (STARR team). Members of the coalition included the Fulton and Dekalb county health department tuberculosis programs, the two programs where the majority of Atlanta's tuberculosis patients received care; Grady Health System, the administrators of the public hospital; the American Lung Association of Georgia; Mercy Mobile Health Care, an independent health care for the homeless project; Emory and Morehouse Schools of Medicine; and the Georgia Division of Public Health. The project was approved by the Human Investigations Committee at Emory University School of Medicine.

For each of the sites, we met first with the chief administrator of that program (i.e., the director of emergency services at the public hospital emergency care center; the commissioner of the city jail) to elicit their permission to establish a tuberculin screening program. We then had several meetings with personnel from each site, to educate them about tuberculosis and to jointly determine a way to integrate the tuberculin screening project and our staff into their operations.

Data Collection

A standard questionnaire was used to collect information on each participant in the project. These data included name, age, gender, race/ ethnicity, country of origin, years of education completed, whether homeless within the last year (defined as having spent at least one night on the street or in a shelter), whether abusing alcohol (defined by the CAGE questionnaire [11]), or using injection drugs or crack cocaine in the last year, self-reported previous tuberculin skin test, self-reported having known someone with active tuberculosis, and study site where enrolled.

Tuberculin Skin Testing

Tuberculin skin testing was performed using the Mantoux method, giving an intradermal injection of 0.1 ml of purified protein derivative (PPD) (Parke-Davis, Morris Plains, NJ) in the volar surface of the forearm and raising a 6- to 10-mm wheal (12). The reaction was read 48 to 72 h after the injection by measuring the diameter of induration across the forearm. Participants who returned for reading after 72 h but within 1 wk and whose induration was ⩾ 10 mm were managed as described subsequently; all others returning for reading after 72 h had testing repeated.

Follow-up of Tuberculin Skin Tests

For any participant whose tuberculin test measured ⩾ 10 mm, a chest radiograph was recommended and an assessment for human immunodeficiency virus (HIV) risk behaviors, specifically intravenous drug use and sexual intercourse without barrier protection, was made. When HIV testing was indicated because of high-risk behaviors, the staff provided pretest counseling, obtained informed consent, and collected serum for the ELISA test and confirmatory Western blot, at the site where tuberculin testing had been done. Chest radiographs were available at the public hospital, and participants screened at the homeless clinics or by the STARR team were provided with directions and transportation tokens to get to the hospital. Incarcerated individuals screened at the jail who were tuberculin skin test positive were transported by the jail staff to the public hospital for chest radiographs. Participants known to be HIV-seropositive at the time of screening were referred for chest radiographs and preventive therapy when the tuberculin test measured ⩾ 5 mm.

Preventive Therapy

Isoniazid preventive therapy was recommended to participants with a positive tuberculin test based on current ATS/CDC guidelines (9). Participants placed on preventive therapy started treatment the same day that their chest radiograph was taken and reviewed if they had an indication for preventive treatment. Those who had HIV testing were given an appointment to return for results in 1 wk; if they had not previously started preventive therapy but had indications for treatment based on the HIV serology, isoniazid was started at that time. Preventive therapy was self-administered. A special clinic was set up in the hospital for participants to have a monthly check-up and pick up their medication. All patients ⩾ 18 yr of age had an aspartate transaminase test (AST) performed monthly. If the AST increased to greater than three to five times normal, isoniazid was held until the AST returned to baseline and the patient was restarted on isoniazid with weekly monitoring of AST until AST remained stable for more than 4 wk, after which monthly monitoring was resumed, or, if the AST increased again, isoniazid was discontinued. For patients who could not tolerate isoniazid due to AST elevations or side effects, rifampin 600 mg daily was used for preventive treatment.

Cost to Participants

All services (tuberculin skin tests, AST and HIV tests, chest radiographs, isoniazid [or rifampin] tablets, and clinic visits) were provided free of charge.

Outcome Data Collection

For each participant who had a tuberculin skin test placed, staff used the standard questionnaire to record whether the participant returned for skin test reading, the results of induration in millimeters, whether a chest radiograph and/or HIV serology was ordered, the results of each if done, whether the participant met criteria for preventive therapy, and if so, whether treatment was started, the number of preventive therapy clinic visits kept, and whether therapy was completed.

Data Analysis

We calculated frequencies for each risk factor among the participants (age, gender, race/ethnicity, country of origin, years of education completed, alcohol and drug abuse [as defined previously], homelessness [as defined previously], self-reported history of tuberculin testing, or exposure to a person with active tuberculosis), for study site where enrolled, and for each of the outcomes (tuberculin skin test read, tuberculin skin test positive, isoniazid preventive therapy completed). A chi-square test and Cornfield 95% confidence intervals were determined to measure associations between the risk factors and each of the three outcomes. To control for confounding from the various risk factors, logistic regression models were run and adjusted odds ratios (OR) and confidence intervals (CI) were determined (13). A p value of ⩽ 0.05 was considered statistically significant. Data analysis was performed using SAS software (SAS Institute, Cary, NC).


From July 1, 1994 through September 30, 1996 the screening project enrolled 7,246 persons who underwent tuberculin skin testing. The enrollment at each site was as follows: the jail 1,863 (26%), homeless clinics 2,918 (40%), Grady Memorial Hospital 2,111 (29%), STARR team 251 (3%). Of the participants, 6,927 (96%) were born in the United States and 319 (4%) were foreign born; 2,719 (37.5%) were female and 4,527 (62.5%) male. The mean age was 35 yr, with a range of < 1 to 88 yr; 4,383 (61%) were between 25 and 44 yr of age. Six thousand three hundred twenty-one (87%) were racial and/or ethnic minorities: 5,994 (79%) African-American, 261 (4%) non-black Hispanic, 33 (< 1%) Asian, and 925 (13%) white. Three thousand two hundred eighteen (44%) acknowledged abusing alcohol or drugs within the previous year, and 2,065 (28%) acknowledged being homeless within the previous year. Four thousand eight hundred seventy (67%) had not completed their high school education. Three hundred eighty-five (5%) reported having known someone with active tuberculosis and 4,607 (64%) reported having had a previous tuberculin skin test.

Outcomes and Their Associations with Participant Variables and Site of Enrollment

Progression of the 7,246 participants through each step of the tuberculin skin testing and preventive therapy is summarized in Figure 1.

Return for tuberculin test reading. Overall 4,701 (65%) of the participants returned for tuberculin test reading. In univariate analysis, variables significantly associated with adherence with tuberculin test reading were having completed high school (OR = 1.19, CI = 1.06–1.33, p = 0.003), current homelessness (OR = 1.13, CI = 1.01–1.26, p = 0.03), no current alcohol or drug abuse (OR = 1.12, CI = 1.01–1.23, p = 0.03), self-report of previous tuberculin testing (OR = 1.42, CI = 1.25–1.60, p < 0.0001), and age category other than 16 to 24 yr (OR = 1.26, CI = 1.09–1.46, p = 0.002). Compared with participants enrolled at Grady Memorial Hospital, those enrolled at the jail were more likely to have their skin test read (OR = 1.77, CI = 1.57–2.00, p < 0.0001), as were those enrolled through the homeless clinics (OR = 1.32, CI = 1.19–1.46, p < 0.0001). Those enrolled through the STARR team were less likely to be adherent with skin test reading (OR = 0.48, CI = 0.37– 0.63, p < 0.0001).

In multivariate analysis using logistic regression, factors associated with returning for skin test reading were self-report of knowing someone with active tuberculosis, having completed high school, no current alcohol or drug abuse, non- African-American race, and self-report of previous tuberculin testing (Table 1).


Participants with Test Read (n = 4,701)Participants with Test Not Read (n = 2,545)Adjusted Odds RatioConfidence Intervalp Value
Variablen% n %
Completed high school1,31828622241.251.01–1.29  0.03
Knew someone with active tuberculosis385 8196 81.401.15–1.700.0007
No current alcohol or drug abuse* 2,658561,370541.311.16–1.48< 0.0001
Self-report of previous tuberculin testing3,089661,518601.311.17–1.46< 0.0001
African American race3,813812,181860.790.68–0.91  0.002
Age categories, yr
  0–15316 7130 52.111.63–2.75< 0.0001
 25–442,871611,512591.311.12–1.53< 0.0001
 45–6486018472181.451.20–1.75< 0.0001
 ⩾ 65115 269 31.741.22–2.48  0.002
Enrolled at:
 Grady Memorial Hospital1,06623814321.00
 Jail1,38029483193.372.77–4.09< 0.0001
 Homeless clinic2,00242916361.971.66–2.34< 0.0001
 STARR team120 2131 50.400.30–0.55< 0.0001
Current homelessness* 1,38029685271.090.97–1.24NS
Foreign-born200 4103 40.900.70–1.16NS
Male gender2,961631,566610.980.88–1.09NS

Definition of abbreviation: NS = not significant.

* See text for definition.

Positive tuberculin test. Eight hundred nine (17%) of the 4,701 participants who had their tuberculin test read had a positive test. Factors associated with having a positive tuberculin skin test included foreign birth (OR = 6.03, CI = 4.50– 8.08, p < 0.0001), male gender (OR = 1.65, CI = 1.40–1.95, p < 0.0001), minority race/ethnicity (OR = 3.53, CI = 2.53– 4.93, p < 0.0001), age categories older than 16 to 24 yr (χ2 test for trend 165.2, p < 0.001), not having completed high school (OR = 1.63, CI = 1.35–1.96, p < 0.001), knowing someone with active tuberculosis (OR = 1.41, CI = 1.08–1.82, p = 0.008), current alcohol or drug abuse (OR = 1.31, CI = 1.12–1.52, p < 0.001), and enrollment with the STARR team compared with enrollment at Grady Memorial Hospital (OR = 1.90, CI = 1.18–3.04, p < 0.001). Significantly lower rates of positive tests were found among those enrolled through the jail (OR = 0.72, CI = 0.59–0.88, p < 0.001) or homeless clinics (OR = 0.45, CI = 0.37–0.55, p < 0.001) compared with those enrolled at Grady Memorial Hospital.

In multivariate analysis, the factors most strongly associated with having a positive tuberculin skin test were foreign birth and older age (Table 2). Other factors associated with a positive tuberculin test were not having completed high school, self-report of no previous tuberculin testing, current homelessness, African-American race, and male gender. Participants enrolled through the jail or the homeless clinics were less likely, and those enrolled through the STARR team were more likely, to have a positive test than those enrolled through Grady Memorial Hospital.


Participants with Positive Tuberculin Test (n = 809)Participants with Negative Tuberculin Test (n = 3,892)Adjusted Odds RatioConfidence Intervalp Value
Variable n % n %
Current homelessness* 245301,13529 1.271.04–1.54  0.02
Foreign-born 9211108 312.298.67–17.42< 0.0001
Did not complete high school587732,53665 1.611.31–1.98< 0.001
Self-report of no previous  tuberculin testing1571970118 1.281.07–1.54  0.006
African American race681843,13280 1.901.47–2.46< 0.0001
Male gender584722,37761 1.731.43–2.09< 0.0001
Age category, yr
  0–15  7 1310 8 0.720.10–0.50  0.003
 16–24 55 747612 1.00
 25–44466582,40562 2.011.46–2.75< 0.0001
 45–642332962716 4.493.17–6.35< 0.0001
 ⩾ 65 47 668 2 7.644.54–12.86< 0.0001
Enrolled at:
 Grady Memorial Hospital2783490823 1.00
 Jail245301,13529 0.700.56–0.89  0.004
 Homeless clinic238291,76445 0.470.37–0.59< 0.0001
 STARR team 29 488 2 1.691.01–2.83  0.04
Current alcohol or drug abuse* 396491,64742 1.190.97–1.45NS
Knew someone with active tuberculosis 8510300 8 1.150.86–1.53NS

* See text for definition.

Completion of therapy. Of the 809 persons with a positive skin test, 409 (50.5%) had an indication for preventive therapy according to current ATS/CDC guidelines (9). Of these 409, 310 (76%) started preventive therapy and 84 (20%) completed the prescribed course of 6 or 12 mo. The 84 persons who completed preventive therapy were 1.1% of the 7,426 who participated in the program by undergoing placement of a tuberculin skin test.

Of the 99 patients who did not start preventive therapy, 94 failed to have a chest radiograph taken. Individuals referred from the homeless clinics or from the STARR team were significantly more likely to fail to have their chest radiograph done compared with participants screened at the Grady Memorial Hospital outpatient areas (47/116 [40%] versus 13/114 [11%], OR = 5.29, CI = 2.54–11.17, p < 0.0001). Those referred by the jail for X-ray were transported to the hospital radiology department by jail deputies the day after the tuberculin tests were read. The proportion of those from the jail who did not get a chest radiograph, 20 (14%) of 143, did not differ significantly from that of the Grady outpatient participants (p = 0.54).

In univariate analysis, factors associated with completion of therapy included foreign birth (OR = 2.11, CI = 1.12–3.94, p = 0.01), age categories 45 to 64 yr (OR = 4.27, CI = 1.74– 10.49, p = 0.002) and ⩾ 65 yr (OR = 10.11, CI = 3.45–29.66, p < 0.001), and history of having known someone with active tuberculosis (OR = 2.21, CI = 1.04– 4.65, p = 0.02). Lower rates of completion of therapy were associated with jail as the enrollment site (OR = 0.19, CI = 0.10– 0.37, p < 0.001). In multivariate analysis, foreign birth and age category ⩾ 65 yr were associated with higher rates of completion of therapy, and jail as the enrollment site with a lower rate (Table 3).


Completed Preventive Therapy (n = 84)Did Not Complete Preventive Therapy (n = 325)Adjusted Odds RatioConfidence Intervalp Value
Variable n % n %
Foreign-born4452 21 64.061.78–9.29  0.0009
Age category, yr
  0–24 7 8 49151.00
 45–642530 41132.860.95–8.60NS
 ⩾ 651315  9 35.961.45–24.54  0.013
Enrolled at:
 Grady Memorial Hospital4857122371.00
 Jail1113132410.260.11–0.62  0.002
 Homeless clinic2327 87270.660.31–1.41NS
 STARR team 1 1  6 20.590.05–6.53NS
Knew someone with  active tuberculosis1417 27 81.890.82– 4.38NS
No current alcohol or drug abuse 6173150460.660.34–1.28NS
Male gender5363235721.030.57–1.85NS
Completed high school1619 64201.480.71–3.05NS
African American race6881271831.240.55–2.77NS
Self-reported previous  tuberculin testing4958210650.830.47–1.50NS
Current homelessness 1821 95291.120.52–2.43NS

*Indications according to ATS/CDC guidelines (9).

See text for definition.

HIV testing. All persons with a positive tuberculin test and risk factors for HIV infection were offered HIV counseling and testing. Thirteen persons reported being HIV-positive before testing and 22 reported a recent negative HIV test result. Of 809 persons with a positive tuberculin test, 470 were offered HIV testing; 354 (75%) agreed to testing. Of these 354, five (1.4%) had a positive HIV serology; the other 349 had a negative serology.

We carried out a tuberculin screening and isoniazid preventive therapy program among a high-risk inner-city population in Atlanta, a city with high rates of tuberculosis in the early 1990s. The goal of our project, which was coordinated by a coalition of groups working with persons with risk factors for tuberculosis infection and disease, was to identify individuals with tuberculosis infection and have them complete a course of preventive therapy. We conducted tuberculin screening at sites previously identified by patients with active tuberculosis as places they had been within a few years before developing tuberculosis disease, where they could have received tuberculin skin testing and preventive therapy (10). The identified sites were a jail, homeless clinics, neighborhoods frequented by drug users, and the public hospital outpatient clinic waiting areas. In addition to attempting to improve physical access to tuberculosis prevention services, we reduced financial barriers to services by providing screening, including chest radiography and follow-up treatment, free of charge.

Comparing the outcomes of our tuberculin screening and isoniazid preventive therapy project with those of the project conducted in Washington, DC 30 yr earlier, we found that little had changed (2). Khoury and coworkers intended to perform tuberculin skin testing on all 9,000 persons in a particular census tract by going to each home, but could locate only 55% for testing and reading. We performed tuberculin skin testing on approximately 7,000 people at four different sites, and 65% had their skin test read. Twenty-one percent of those screened by Khoury and coworkers had a reaction of ⩾ 10 mm induration, compared with 17% of those we screened. In the Washington, DC project, 28% of those referred for chest radiograph because of a positive tuberculin test failed to have their chest radiograph taken and to continue follow-up; in Atlanta 24% were lost to follow-up at this point. Although Khoury and coworkers do not report the proportion of patients who completed preventive therapy, they report that only 18% of the patients who were prescribed preventive therapy were fully adherent with their daily isoniazid during periods when adherence was closely monitored. In the Atlanta project 20% of the patients completed preventive therapy. Thus 30 yr later we were unable to demonstrate improved efficacy of a community-based isoniazid preventive therapy program. Clearly new approaches are necessary for a tuberculosis elimination program in the United States to be successful (6).

Shorter preventive therapy regimens may be the key to altering outcomes of community-based tuberculin screening and preventive therapy programs. Recently 2- and 3-mo regimens with rifampin plus pyrazinamide or isoniazid have been demonstrated to be effective in preventing tuberculosis in HIV- infected tuberculin-positive persons (14, 15). Such rifampin-based regimens are likely to be as or more effective in patients without HIV infection. The shorter duration of treatment facilitates use of directly observed therapy, which increases adherence (16, 17), as does shorter treatment duration itself (14). Patients may feel more self-efficacious when contemplating only 2 mo rather than 6 or 12 mo of treatment, and therefore more likely to complete therapy (18). Amending current ATS/ CDC preventive therapy guidelines based on these recently reported data must be a priority, as should expanding clinical and programmatic trials of shorter regimens to determine efficacy, safety, and tolerability in broad populations.

Older patients (age categories 45 to 64 and ⩾ 65 yr) were more adherent with treatment in our project than were younger adults. We treated only those older than 35 yr who fulfilled ATS/CDC criteria for preventive therapy regardless of age (9), although during this time period more than half of the reported tuberculosis cases in Atlanta were in persons older than 35 yr (Beverly DeVoe, Georgia TB Control, personal communication). If a regimen had been recommended for use in patients between 36 and 64 yr, we could have increased the number of tuberculin-positive patients with “indications” for preventive therapy by 355 or 87%. As tuberculosis transmission in the community decreases, an even larger proportion of cases will occur in older persons with reactivation of latent infection. Thus, trials of short-course preventive therapy regimens must evaluate safety and tolerability in older age groups.

One difference in outcome between our screening program and the one in Washington, DC in 1965 was that we found no cases of active tuberculosis among the tuberculin reactors who underwent chest radiograph, whereas Khoury and coworkers found 10 among 1,009 persons who had chest radiograph (2). The reasons for this difference are unclear, but probably do not reflect better access to health care among impoverished inner-city residents 30 yr later. A recent tuberculin screening program among social service clients of community-based organizations in New York City detected 11 tuberculosis cases among 591 tuberculin reactors undergoing chest radiograph (19). In our project cases may have been missed among tuberculin reactors who failed to follow through with chest radiograph.

The purpose of community-based tuberculin screening is to identify and give effective preventive therapy to persons infected with M. tuberculosis. Community-based programs are especially important for certain high-risk populations, such as the urban poor and homeless, for whom traditional contact investigations may not reliably identify infected persons (20). As tuberculosis case rates continue to decline in the United States, preventive therapy will become an increasingly important aspect of tuberculosis control and elimination programs. New guidelines for preventive therapy based on recent short-course therapy trials need to be formulated and implemented and further research on tuberculosis preventive therapy needs to be a national priority.

The authors wish to thank Philip C. Hopewell, M.D., and Andrew R. Moss, Ph.D., for their advice regarding this project, Beverly DeVoe for logistic support, Cecilia Hunter for administrative support, and Ann Gilchrist for maintaining the database.

Supported in part by grants from the Robert Wood Johnson Foundation, the National Institutes of Health Award K07-HL03078, and the Georgia Department of Human Resources.

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Correspondence and requests for reprints should be addressed to Naomi N. Bock, M.D., Division of Infectious Diseases, Emory University School of Medicine, 69 Butler Street, Atlanta, GA 30303.


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