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Background: To decrease tuberculosis case rates and cases due to recent infection (clustered cases) in San Francisco, California, tuberculosis control measures were intensified beginning in 1991 by focusing on prevention of Mycobacterium tuberculosis transmission and on the use of preventive therapy., Objective: To describe trends in rates of tuberculosis cases and clustered cases in San Francisco from 1991 through 1997., Design: Population-based study., Setting: San Francisco, California., Patients: Persons with tuberculosis diagnosed between 1 January 1991 and 31 December 1997., Measurements: DNA fingerprinting was performed. During sequential 1-year intervals, changes in annual case rates per 100,000 persons for all cases, clustered cases (cases with M. tuberculosis isolates having identical fingerprint patterns), and cases in specific subgroups with high rates of clustering (persons born in the United States and HIV-infected persons) were examined., Results: Annual tuberculosis case rates peaked at 51.2 cases per 100,000 persons in 1992 and decreased significantly thereafter to 29.8 cases per 100,000 persons in 1997 (P < 0.001). The rate of clustered cases decreased significantly over time in the entire study sample (from 10.4 cases per 100,000 persons in 1991 to 3.8 cases per 100,000 persons in 1997 [P < 0.001]), in persons born in the United States (P < 0.001), and in HIV-infected persons (P = 0.003)., Conclusions: The rates of tuberculosis cases and clustered tuberculosis cases decreased both overall and among persons in high-risk groups. This occurred in a period during which tuberculosis control measures were intensified.

Setting: San Francisco, California., Objectives: To identify the characteristics of persons in whom tuberculosis was diagnosed after death, and determine whether secondary cases of tuberculosis resulted from them., Design: Retrospective review of all cases of tuberculosis reported in San Francisco from 1986 through 1995, combined with a prospective evaluation of the molecular epidemiology of tuberculosis., Results: Four per cent of the reported 3102 tuberculosis cases were diagnosed after death. The rate of tuberculosis cases diagnosed after death was 1.63 per 100000 population. Age 43 years or older, male sex, white race, and birth in the United States were characteristics independently associated with a diagnosis of tuberculosis after death. During 1993-1995, injecting drug use was also independently associated with a diagnosis of tuberculosis after death (odds ratio 9.24, 95% confidence interval 1.77-39.38). Cases of tuberculosis diagnosed after death do not appear to be significant sources of undetected tuberculosis transmission causing new secondary tuberculosis cases in the community., Conclusions: Health care providers in San Francisco, and probably other urban areas, should maintain a high index of suspicion for tuberculosis in ageing, white, US-born males, and injecting drug users.

To determine the factors contributing to tuberculosis incidence in the U.S.-born and foreign-born populations in San Francisco, California, and to assess the effectiveness of tuberculosis control efforts in these populations, we performed a population-based molecular epidemiologic study using 367 patients with strains of Mycobacterium tuberculosis recently introduced into the city. IS6110-based and PGRS-based restriction fragment length polymorphism (RFLP) analyses were performed on M. tuberculosis isolates. Patients whose isolates had identical RFLP patterns were considered a cluster. Review of public health and medical records, plus patient interviews, were used to determine the likelihood of transmission between clustered patients. None of the 252 foreign-born cases was recently infected (within 2 yr) in the city. Nineteen (17%) of 115 U. S.-born cases occurred after recent infection in the city; only two were infected by a foreign-born patient. Disease from recent infection in the city involved either a source or a secondary case with human immunodeficiency virus (HIV) infection, homelessness, or drug abuse. Failure to identify contacts accounted for the majority of secondary cases. In San Francisco, disease from recent transmission of M. tuberculosis has been virtually eliminated from the foreign-born but not from the U.S.-born population. An intensification of contact tracing and screening activities among HIV-infected, homeless, and drug-abusing persons is needed to further control tuberculosis in the U.S.-born population. Elimination of tuberculosis in both the foreign-born and the U.S. -born populations will require widespread use of preventive therapy.

Contact tracing, the evaluation of persons who have been in contact with patients having tuberculosis, is an important component of tuberculosis control. We used DNA fingerprinting to test the assumption that tuberculosis in contacts to active cases represents transmission from that person. Cases of tuberculosis in San Francisco between 1991 and 1996 with positive cultures who had been previously identified as contacts ("contact cases") to active cases ("index cases") were studied. Of 11,211 contacts evaluated, there were 66 pairs of culture-positive index and contact cases. DNA fingerprints were available for both members of these pairs in 54 instances (82%). The index and contact cases were infected with the same strain of Mycobacterium tuberculosis in 38 instances (70%; 95% CI: 56 to 82%); 16 pairs (30%) were infected with unrelated strains. Unrelated infections were more common among foreign-born (risk ratio [RR] = 5.22, p < 0.001), particularly Asian (RR = 3.89, p = 0.002) contacts. Contact investigation is an imperfect method for detecting transmission of M. tuberculosis, particularly in foreign-born persons. However, because such investigations target a group with a high prevalence of tuberculosis and tuberculous infection, these efforts remain an important activity in the control of tuberculosis.

Between 1990 and 1994, we conducted a prospective study in five methadone maintenance clinics in San Francisco to determine the rate of tuberculosis (TB) in injection drug users, including those who were anergic. Of the 1,745 persons seen in the clinics, 1,109 completed an evaluation that included skin testing with tuberculin and at least two other antigens (mumps, tetanus, and/or Candida), as well as HIV testing. All persons with a positive tuberculin skin test (TST) and anergic individuals who had radiographic evidence of tuberculous infection (i.e., calcified granulomas) were offered isoniazid (INH) preventive therapy. The median follow-up was 22.0 mo. There were 338 (30.5%) human immunodeficiency virus (HIV)-seropositive patients and 771 (69.5%) HIV-seronegative patients; 96 (28.0%) and 336 (44.0%), respectively, had positive TSTs. Of the HIV-seropositive subjects, 108 (31.9%) had no reaction to any of the three antigens, and were therefore classified as anergic. The rate of TB among the HIV-seropositive, TST-positive patients who did not take INH preventive therapy was 5.0 per 100 person-yr, compared with 0.4 per 100 person-yr among the HIV-seronegative, TST-positive patients (p = 0.007). There were no cases of TB among the anergic subjects. These data indicate that INH preventive therapy is not routinely indicated in anergic, HIV-seropostive patients.

Setting: San Francisco, California., Objective: To determine the relative contributions of infection acquired in San Francisco and reactivation of tuberculous infection acquired elsewhere in Mexican-born persons who developed tuberculosis in San Francisco, and to determine the frequency of transmission leading to secondary cases of tuberculosis in other persons., Design: The study population consisted of all Mexican-born tuberculosis patients reported in San Francisco from 1991 through June 1995. All patients had positive cultures for Mycobacterium tuberculosis and DNA fingerprinting of isolates using IS6110 with more than two bands. Patients were classified as infected in San Francisco or infected elsewhere based on pre-defined criteria that included a second DNA fingerprinting technique (polymorphic guanine-cytosine-rich sequence), chart reviews, and selected patient interviews., Results: Of the 43 Mexican-born patients studied, nine (21%) met the definition of infection acquired in San Francisco and 34 (79%) met the definition of reactivation of infection acquired elsewhere. Only one of the 43 cases resulted in two secondary cases in US-born persons., Conclusion: One-fifth of the Mexican-born patients who developed tuberculosis in San Francisco acquired their tuberculous infection in San Francisco; transmission from Mexican-born persons leading to tuberculosis in other persons is uncommon.

DOT is challenging, rewarding, and the best way we have of ensuring patients' adherence to treatment. Although labor intensive, the team approach with well-defined roles for the RN, DCI, and outreach worker is efficient and effective. Although the human touch-a welcoming, tolerant, and caring approach to the patient-is the single key element, the use of incentives and enablers makes DOT more attractive to patients and the program more successful. An organized approach is necessary, yet flexibility must be maintained. Each patient has unique needs. Using other programs to help, such as school-based nurserun clinics or methadone sites, is more convenient for the patient and increases adherence. Helping patients access other services is important. And, finally, recognizing and appreciating the hard work and skills of the DOT staff contribute to maintaining high staff morale and esprit de corps.

Background: The increasing incidence of tuberculosis caused by drug-resistant Mycobacterium tuberculosis is thought in part to reflect inadequate implementation of standard tuberculosis control measures. However, in San Francisco, USA, which has an effective tuberculosis control programme, we have recently observed an increase in cases of acquired drug-resistance., Methods: To explore further this observation, we analysed the secular trend of acquired drug-resistance and conducted a population-based case-control study of all reported tuberculosis cases in the city of San Francisco between 1985 and 1994., Findings: We identified 14 patients with tuberculosis caused by fully susceptible M tuberculosis who subsequently developed drug-resistance. Of these acquired drug-resistance cases, two occurred between 1985 and 1989, whereas 12 occurred between 1990 and 1994 (p = 0.028). In the case-control study, AIDS (odds ratio 20.2, 95% CI 1.12-363.6), non-compliance with therapy (19.7, 1.66-234.4), and gastrointestinal symptoms (11.5, 1.23-107.0) were independently associated with acquired drug-resistance. Between 1990 and 1994, one in 16 tuberculosis patients with AIDS and either gastrointestinal symptoms or non-compliance developed acquired drug- resistance., Interpretation: The substantial increase in acquired drug- resistance in San Francisco seems to be a product of the increasing prevalence of HIV/M tuberculosis coinfection. Our data suggest that the interface of the HIV and tuberculosis epidemics fosters acquired drug-resistance, and that traditional tuberculosis control measures may not be sufficient in communities with high rates of HIV infection.

Background: The epidemiology of tuberculosis in urban populations is changing. Combining conventional epidemiologic techniques with DNA fingerprinting of Mycobacterium tuberculosis can improve the understanding of how tuberculosis is transmitted., Methods: We used restriction-fragment-length polymorphism (RFLP) analysis to study M. tuberculosis isolates from all patients reported to the tuberculosis registry in San Francisco during 1991 and 1992. These results were interpreted along with clinical, demographic, and epidemiologic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical patterns were grouped in clusters. Risk factors for being in a cluster were analyzed., Results: Of 473 patients studied, 191 appeared to have active tuberculosis as a result of recent infection. Tracing of patients' contacts with the use of conventional methods identified links among only 10 percent of these patients. DNA fingerprinting, however, identified 44 clusters, 20 of which consisted of only 2 persons and the largest of which consisted of 30 persons. In patients under 60 years of age, Hispanic ethnicity (odds ratio, 3.3; P = 0.02), black race (odds ratio, 2.3; P = 0.02), birth in the United States (odds ratio, 5.8; P < 0.001), and a diagnosis of the acquired immunodeficiency syndrome (odds ratio, 1.8; P = 0.04) were independently associated with being in a cluster. Further study of patients in clusters confirmed that poorly compliant patients with infectious tuberculosis have a substantial adverse effect on the control of this disease., Conclusions: Despite an efficient tuberculosis-control program, nearly a third of new cases of tuberculosis in San Francisco are the result of recent infection. Few of these instances of transmission are identified by conventional contact tracing.

Background: Tuberculosis typically develops from a reactivation of latent infection. Clinical tuberculosis may also arise from a primary infection, and this is thought to be more likely in persons infected with the human immunodeficiency virus (HIV). However, the relative importance of these two pathogenetic mechanisms in this population is unclear., Methods: Between December 1990 and April 1991, tuberculosis was diagnosed in 12 residents of a housing facility for HIV-infected persons. In the preceding six months, two patients being treated for tuberculosis had been admitted to the facility. We investigated this outbreak using standard procedures plus analysis of the cultured organisms with restriction-fragment-length polymorphisms (RFLPs)., Results: Organisms isolated from all 11 of the culture-positive residents had similar RFLP patterns, whereas the isolates from the 2 patients treated for tuberculosis in the previous six months were different strains. This implicated the first of the 12 patients with tuberculosis as the source of this outbreak. Among the 30 residents exposed to possible infection, active tuberculosis developed in 11 (37 percent), and 4 others (13 percent) had newly positive tuberculin skin tests. Of 28 staff members with possible exposure, at least 6 had positive tuberculin-test reactions, but none had tuberculosis., Conclusions: Newly acquired tuberculous infection in HIV-infected patients can spread readily and progress rapidly to active disease. There should be heightened surveillance for tuberculosis in facilities where HIV-infected persons live, and investigation of contacts must be undertaken promptly and be focused more broadly than is usual.

The outcome of treatment for pulmonary tuberculosis using isoniazid and rifampin for 9 months supplemented by ethambutol for the initial 2 months was evaluated in a cohort of 233 patients. All patients had sputum cultures positive for Mycobacterium tuberculosis sensitive to isoniazid and rifampin. Of the 233 patients, 200 completed the regimen without change. Four patients had adverse reactions necessitating discontinuation and four became pregnant and had ethambutol substituted for rifampin. All eight were treated successfully with altered regimens. Ten patients were lost to follow-up, seven died, and eight were transferred to other jurisdictions. No patients failed to convert their sputum during therapy. At completion of therapy, three patients (1.5%) were found to have positive sputum. Follow-up 6 months after completion of treatment in 174 successfully treated patients revealed four (2.3%) with positive sputum. No further relapses were detected on evaluation 12 months after treatment was completed. All seven patients who failed therapy or relapsed were retreated successfully using the same regimen. These data provide a reference standard against which newer treatment regimens, such as the 6-month regimen currently in use, can be compared. In addition, the value of routine evaluations in detecting relapses at the time treatment is completed and 6 months later was substantiated, but 12-month follow-up was not useful.