PubMed HealthSearch

Biomedical subjects

T R Frieden

Publications and source records attributed to T R Frieden.

At least 19 recordsLinked to original sources

A continuing outbreak of multidrug-resistant tuberculosis, with transmission in a hospital nursery.

We investigated an increase in cases of multidrug-resistant tuberculosis (MDRTB) at a large urban facility where a prior nosocomial outbreak of MDRTB had occurred. Nosocomial transmission appeared to account for this outbreak as well, including a cluster of cases in a newborn nursery. Seven of 24 patients (29%) described in this investigation may have been exposed in the hospital nursery during an approximately 2-week period. We believe this to be the first documented outbreak of MDRTB in a hospital nursery. The transmission in the nursery demonstrates that the possibility of exposure to unrecognized active tuberculosis in nursery and hospital personnel is always present. Infection and active disease in the infants developed after a relatively short period of exposure. These findings underscore the need for adherence to published infection control guidelines in health care settings.

Antitubercular Agents

Mycobacterium tuberculosis infection in a green-winged macaw (Ara chloroptera): report with public health implications.

Mycobacterium tuberculosis was isolated from the eyelid, skin, tongue, and lungs of a green-winged macaw (Ara chloroptera). Two persons living in the same household were culture positive for pulmonary tuberculosis 3 to 4 years before tuberculosis was diagnosed in the bird. Although humans have not been shown to acquire tuberculosis from birds, an infected bird may be a sentinel for human infection.

Animals

A continuing survey of drug-resistant tuberculosis, New York City, April 1994.

BACKGROUND: A 1991 survey showed high levels of drug resistance among tuberculosis patients in New York, NY. As a result, the tuberculosis control program was strengthened, including expanded use of directly observed therapy and improved infection control. METHODS: We collected isolates from every patient in New York City with a positive culture for Mycobacterium tuberculosis during April 1994; results were compared with those in the April 1991 survey. RESULTS: From 1991 to 1994, the number of patients decreased from 466 to 332 patients. The percentage with isolates resistant to 1 or more antituberculosis drugs decreased from 33% to 24% (P < .01); with isolates resistant to at least isoniazid decreased from 26% to 18% (P < .05); and with isolates resistant to both isoniazid and rifampin decreased from 19% to 13% (P < .05). The number of patients with isolates resistant to both isoniazid and rifampin decreased by more than 50%. Among never previously treated patients, the percentage with resistance to 1 or more drugs decreased from 22% in 1991 to 13% in 1994 (P < .05). The number of patients with consistently positive culture results for more than 4 months decreased from 130 to 44. A history of antituberculosis treatment was the strongest predictor of drug resistance (odds ratio = 3.1; P < .001). Human immunodeficiency virus infection was associated with drug resistance among patients who never had been treated for tuberculosis. CONCLUSIONS: Drug-resistant tuberculosis declined significantly in New York City from 1991 to 1994. Measures to control and prevent tuberculosis were associated with a 29% decrease in the proportion of drug resistance and a 52% decrease in the number of patients with multidrug-resistant tuberculosis.

AIDS-Related Opportunistic Infections

Nonadherence in tuberculosis treatment: predictors and consequences in New York City.

BACKGROUND: Poor adherence to antituberculosis treatment is the most important obstacle to tuberculosis control. PURPOSE: To identify and analyze predictors and consequences of nonadherence to antituberculosis treatment. PATIENTS AND METHODS: Retrospective study of a citywide cohort of 184 patients with tuberculosis in New York City, newly diagnosed by culture in April 1991-before the strengthening of its control program-and followed up through 1994. Follow-up information was collected through the New York City tuberculosis registry. Nonadherence was defined as treatment default for at least 2 months. RESULTS: Eighty-eight of the 184 (48%) patients were nonadherent. Greater nonadherence was noted among blacks (unadjusted relative risk [RR] 3.0, 95% confidence interval [CI] 1.1 to 8.6, compared with whites), injection drug users (RR 1.5, 95% CI 1.1 to 2.0), homeless (RR 1.4, 95% CI 1.0 to 1.8), alcoholics (RR 1.4, 95% CI 1.0 to 1.9), and HIV-infected patients (RR 1.4, 95% CI 1.1 to 1.9); also, census-derived estimates of household income were lower among nonadherent patients (P = 0.018). In multivariate analysis, only injection drug use and homelessness predicted nonadherence, yet 46 (39%) of 117 patients who were neither homeless nor drug users were nonadherent. Nonadherent patients took longer to convert to negative culture (254 versus 64 days, P < 0.001), were more likely to acquire drug resistance (RR 5.6, 95% CI 0.7 to 44.2), required longer treatment regimens (560 versus 324 days, P < 0.0001), and were less likely to complete treatment (RR 0.5, 95% CI 0.4 to 0.7). There was no association between treatment adherence and all-cause mortality. CONCLUSIONS: In the absence of public health intervention, half the patients defaulted treatment for 2 months or longer. Although common among the homeless and injection drug users, the problem occurred frequently and unpredictably in other patients. Nonadherence may contribute to the spread of tuberculosis and the emergence of drug resistance, and may increase the cost of treatment. These data lend support to directly observed therapy in tuberculosis.

AIDS-Related Opportunistic Infections

Directly observed therapy in New York City. History, implementation, results, and challenges.

The history of the New York City Department of Health Bureau of Tuberculosis Control Program, and the events leading to the adoption of wide-scale directly observed therapy (DOT) in 1992 are described. The organization and role of Department of Health and non-Department of Health directly observed programs are discussed. Details are provided regarding the Department of Health's program: the use of standard treatment and program protocols, the use of incentives and enablers, a profile of the successful DOT worker, the detention program, and other issues. Program data and outcomes from 1992 through 1995 are presented, along with some of the challenges and questions for the future.

Communicable Disease Control

Rifampin-monoresistant tuberculosis in New York City, 1993-1994.

All New York City patients whose cultures yielded Mycobacterium tuberculosis with isolated resistance to rifampin in 1993 and 1994 were included in this study. Of the 96 patients, 48 (50%) had primary resistance, 32 (33%) had acquired resistance, and 16 (17%) had unclassified resistance; 66% had histories of illicit drug use, and 79% were infected with human immunodeficiency virus (HIV). The median time to emergence of resistance was 40 weeks among the 32 patients with acquired resistance. Each of the HIV-infected patients with acquired resistance (cases, n = 29) was matched to two HIV-infected patients who had disease due to fully susceptible M. tuberculosis (controls, n = 58). In multivariate analysis, factors associated with the emergence of rifampin resistance were as follows: a sputum smear positive for acid-fast bacilli, advanced immunosuppression, and nonadherence to therapy.

Acquired Immunodeficiency Syndrome

Universal radiographic screening for tuberculosis among inmates upon admission to jail.

OBJECTIVES: This study evaluated the efficacy of radiographic screening for tuberculosis in correctional facilities. METHODS: Inmates at an admission facility in New York, NY, were screened for tuberculosis by registry cross-match, symptom interviews, tuberculin testing, and chest radiography. RESULTS: Thirty-two cases of tuberculosis were detected among 4172 inmate admissions (767 cases per 100,000). Twenty-five inmates (78%) were previously diagnosed but incompletely treated; all were identified by registry cross-match. Seven inmates (22%) were newly diagnosed, of whom four (57%) were asymptomatic, had negative skin tests, and were detected only by their abnormal radiographs. CONCLUSIONS: Screening strategies that limit radiographic testing to inmates with either positive skin tests or symptoms may result in missed opportunities for diagnosing active tuberculosis.

Adolescent

The relationship between delayed or incomplete treatment and all-cause mortality in patients with tuberculosis.

OBJECTIVE: To analyze the factors associated with survival in patients with pulmonary and extrapulmonary tuberculosis in New York City. DESIGN: Observational study of a citywide cohort of tuberculosis cases. SETTING: New York City, April 1991, before the strengthening of its control program. PATIENTS: All 229 newly diagnosed cases of tuberculosis documented by culture in April 1991. Most patients (74%) were male, and the median age was 37 years (range, 1-89 years). In all, 89% belonged to minority groups. Human immunodeficiency virus (HIV) infection was present in 50% and multidrug resistance in 7% of the cases. Twenty-one patients (9%) were not treated. MAIN OUTCOME MEASURES: Follow-up information was collected through the New York City tuberculosis registry; death from any cause was verified through the National Death Index. RESULTS: Cumulative all-cause mortality by October 1994 was 44%; the median survival for those who died was 6.3 months (range, 0 days to 3 years). The most important baseline predictors of mortality, adjusted for baseline clinical and demographic factors, were acquired immunodeficiency syndrome (AIDS) (91% vs 11% in HIV-seronegative patients; Cox relative risk [RR], 7.8; 95% confidence interval [CI], 2.1-29.1), multidrug resistance (87% vs 39% in pansensitive cases; adjusted RR, 5.8; 95% CI, 2.3-14.5), and lack of treatment (81% vs 40%; adjusted RR, 3.1; 95% CI, 1.0-9.7). Also, 11 of 13 HIV-infected patients who started treatment after a 1-month delay died. Among 173 patients surviving the recommended treatment period, those who completed therapy (66%) had a lower subsequent mortality (20% vs 37%; RR, 0.5; 95% CI, 0.3-0.9). CONCLUSIONS: Mortality from tuberculosis was high, even among patients without multidrug resistance who were not known to be infected with HIV. Most HIV-seropositive patients with delayed therapy died. Multidrug resistance predicted higher mortality, and treatment completion was associated with improved subsequent patient survival.

Adolescent

A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes.

OBJECTIVE: To investigate a multi-institutional outbreak of highly resistant tuberculosis and evaluate patient outcome. DESIGN: Epidemiologic investigation of every tuberculosis case reported in New York City. SETTING: Patients cared for at all public and nonpublic institutions from January 1, 1990, to August 1, 1993 (43 months). PATIENTS: We reviewed medical and public health records and conducted clinical, epidemiologic, drug susceptibility, and restriction fragment length polymorphism (RFLP) analyses. A case was defined as tuberculosis in a patient with an isolate resistant to isoniazid, rifampin, ethambutol hydrochloride, and streptomycin (and rifabutin, if sensitivity testing included it), and, if RFLP testing was done, a pattern identical to or closely related to strain W. MAIN OUTCOME MEASURES: Patient survival and the conversion of sputum cultures from positive to negative. RESULTS: Of the 357 patients who met the case definition, 267 had identical or nearly identical RFLP patterns; isolates from the other 90 patients were not available for RFLP testing. Among these 267 patients, 86% were human immunodeficiency virus (HIV)-infected, 7% were HIV-negative, and 7% had unknown HIV status. All-cause mortality was 83%. Epidemiologic linkages were identified for 70% of patients, of whom 96% likely had nosocomially acquired disease at 11 hospitals. Survival was prolonged among patients who received medications to which their isolate was susceptible, especially capreomycin sulfate, and among patients with a CD4+ T-lymphocyte count greater than 0.200 x 10(9)/L (200/microL). Treatment with isoniazid and a fluoroquinolone antibiotic was also independently associated with longer survival. CONCLUSIONS: This outbreak accounted for nearly one fourth of the cases of multidrug-resistant tuberculosis in the United States during a 43-month period. Most patients had nosocomially acquired disease, were infected with HIV, and unless promptly and appropriately treated, died rapidly. With appropriate directly observed treatment, especially combinations including an injectable medication, even severely immunocompromised patients had culture conversion and prolonged, tuberculosis-free survival.

Adolescent

Tuberculosis, AIDS, and death among substance abusers on welfare in New York City.

BACKGROUND: In New York City, the incidence of tuberculosis has more than doubled during the past decade. We examined the incidence of tuberculosis and the acquired immunodeficiency syndrome (AIDS) and the rate of death from all causes in a very-high-risk group--indigent subjects who abuse drugs, alcohol, or both. METHODS: In 1984 we began to study prospectively a cohort of welfare applicants and recipients 18 to 64 years of age who abused drugs or alcohol. The incidence rates of tuberculosis, AIDS, and death for this group were ascertained through vital records and New York City's tuberculosis and AIDS registries. RESULTS: The cohort was followed for eight years. Of the 858 subjects, tuberculosis developed in 47 (5.5 percent), 84 (9.8 percent) were given a diagnosis of AIDS, and 183 (21.3 percent) died. The rates of incidence per 100,000 person-years were 744 for tuberculosis, 1323 for AIDS, and 2842 for death. In this group of welfare clients, the rate of newly diagnosed tuberculosis was 14.8 times that of the age-matched general population of New York City; the rate of AIDS was 10.0 times as high; and the death rate was 5.2 times as high. There was no significant difference in the rate of new cases of tuberculosis between subjects with positive skin tests and those with negative skin tests at examination in 1984. CONCLUSIONS: Among indigent alcohol and drug abusers in New York City, the rates of tuberculosis, AIDS, and death are extremely high. In this population, a single positive or negative skin test does not predict the development of tuberculosis, probably because both anergy and new infections are common. If programs to control tuberculosis and AIDS are to be effective in groups of indigent substance abusers, health services must be integrated into the welfare delivery system.

Acquired Immunodeficiency Syndrome

The molecular epidemiology of tuberculosis in New York City: the importance of nosocomial transmission and laboratory error.

SETTING: During the 1980s, New York City experienced a rapid increase of tuberculosis cases, more than 40% of which were human immunodeficiency virus (HIV)-associated. OBJECTIVE: To better define the molecular epidemiology of tuberculosis in New York City. DESIGN: We collected an isolate from every patient in New York City with a positive culture for Mycobacterium tuberculosis, including both incident and prevalent cases, in April 1991. Restriction fragment length polymorphism (RFLP) analysis using IS6110 was performed and the clinical, demographic, epidemiologic, and drug susceptibility patterns of patients were correlated with RFLP results. RESULTS: Of 441 patients, 12 (3%) had laboratory, clinical, and RFLP evidence of falsely positive cultures. The remaining 429 patients had 252 distinct RFLP patterns. Patients with clustered 1-3 band isolates did not share demographic or drug susceptibility patterns. Eliminating these patients from the analysis, 344 patients remained, of whom 126 (37%) belonged to one of 31 clusters ranging in size from 2-17 patients (median cluster size = 3). Clustering was more common among patients with multidrug-resistant isolates (53%), African Americans (44%), and the homeless (49%), but was not associated with HIV infection or acquired immune deficiency syndrome (AIDS), Multidrug-resistance, being African American, and homelessness remained independently associated with clustering in multivariate analysis. Of 79 patients in clusters of > or = 4 patients, 25 (32%) had identifiable epidemiologic linkages; 17 (74%) of these patients, and 6% of all cases, were documented to have been nosocomially associated. CONCLUSION: A small but non-negligible proportion (3%) of New York City patients had falsely positive cultures for M. tuberculosis as a result of laboratory error. More than one third of all patients and most patients with multidrug-resistance in April 1991 had clustered RFLP patterns, suggesting recent transmission of M. tuberculosis. Homelessness, multidrug-resistance, and being African American independently increased the risk of clustering. Most of the identified epidemiologic linkages and 6% of all cases resulted from transmission in hospitals.

AIDS-Related Opportunistic Infections

Tuberculosis in New York City--turning the tide.

BACKGROUND: From 1978 through 1992, the number of patients with tuberculosis in New York City nearly tripled, and the proportion of such patients who had drug-resistant isolates of Mycobacterium tuberculosis more than doubled. METHODS: We reviewed, confirmed, and analyzed data obtained during the surveillance of patients with tuberculosis. RESULTS: From 1992 through 1994, there was a 21 percent decrease in reported cases of tuberculosis in New York City. An evaluation of the surveillance system revealed very few unreported cases. The number of cases decreased by more than 20 percent among blacks and Hispanics, persons with documented human immunodeficiency virus infection, homeless persons, and patients with multidrug-resistant tuberculosis; in all these groups, tuberculosis is likely to result from recent transmission. In contrast, the number of cases of tuberculosis increased among elderly and foreign-born persons, in whom the disease is likely to result from the reactivation of an infection acquired many years earlier. Enrollment in a program of directly observed therapy, in which health workers watch patients take their medications, increased from fewer than 100 patients to nearly 1300, with more than 32,000 patient-months of observation from 1992 through 1994. CONCLUSIONS: Epidemiologic patterns strongly suggest that the decrease in cases resulted from an interruption in the ongoing spread of M. tuberculosis infection, primarily because of better rates of completion of treatment and expanded use of directly observed therapy. Another contributing factor may have been efforts to reduce the spread of tuberculosis in institutional settings, such as hospitals, shelters, and jails. Expansion of measures to prevent and control tuberculosis and support of international control efforts are needed to ensure continued progress.

Adolescent

Emergence of fluoroquinolone-resistant tuberculosis in New York City.

22 patients infected with fluoroquinolone-resistant Mycobacterium tuberculosis in New York City were identified between January, 1991, and November, 1993. In 16 patients resistance arose as a result of inadequate or inappropriate treatment. 6 patients had primary infection with fluoroquinolone-resistant organisms; 5 acquired the organisms nosocomially. Seven distinct patterns of restriction-fragment length polymorphism were identified in isolates from 21 patients. Fluoroquinolones should be restricted to patients with multidrug-resistant disease or intolerance to other antituberculosis drugs. All patients with multidrug-resistant tuberculosis should be on directly observed therapy.

AIDS-Related Opportunistic Infections