Multivariate Markovian modeling of tuberculosis: forecast for the United States.

We have developed a computer-implemented, multivariate Markov chain model to project tuberculosis (TB) incidence in the United States from 1980 to 2010 in disaggregated demographic groups. Uncertainty in model parameters and in the projections is represented by fuzzy numbers. Projections are made under the assumption that current TB control measures will remain unchanged for the projection period. The projections of the model demonstrate an intermediate increase in national TB incidence (similar to that which actually occurred) followed by continuing decline. The rate of decline depends strongly on geographic, racial, and ethnic characteristics. The model predicts that the rate of decline in the number of cases among Hispanics will be slower than among white non-Hispanics and black non-Hispanics a prediction supported by the most recent data.

Completion of tuberculosis therapy for patients reported in the United States in 1993.

SETTING: The highest priority for tuberculosis (TB) control is to ensure patients complete therapy. However, standardized, detailed evaluation of national performance on completion of therapy in the United States has been lacking. Since 1982, the Centers for Disease Control and Prevention (CDC) has had a program objective that at least 90% of TB cases complete therapy. Since 1986, the standard of practice for patients with drug-susceptible TB has been 6 months of therapy. OBJECTIVE: To determine completion of therapy rates and duration of therapy for US TB patients reported in 1993. DESIGN: Expanded TB surveillance data on all US TB patients reported to the CDC in 1993 with initial therapy of two or more drugs were analyzed with respect to completion and duration of therapy. RESULTS: A disposition (reason therapy stopped) was obtained on 98.7% of 23 489 treated patients. Overall, 91.2% of evaluable patients completed therapy. The overall completion rate at 12 months of therapy was 66.8%, and 90% completion was reached at 23 months. For patients with initially drug-susceptible TB, completion was 7.1% at 6 months, 66.5% at 12 months, and reached 90% at 22 months. CONCLUSION: While completion rates ultimately exceeded 90% nationwide, there was considerable delay in reaching this objective, especially in patients with drug-susceptible TB. It is critical that health departments and health care providers identify and remedy any deficiencies responsible for prolonged therapy.

Emerging and reemerging infectious diseases: a multidisciplinary perspective.

Predictions that infectious diseases would be eliminated as a major threat to human health have been shattered by emerging and reemerging infections, among them acquired immunodeficiency syndrome (AIDS), hemorrhagic fevers, marked increases in infections caused by antimicrobial-resistant bacteria, and the resurgence of tuberculosis and malaria. Understanding the dynamics of emerging and reemerging infections is critical to efforts to reduce the morbidity and mortality of such infections, to establish policy related to preparedness for infectious threats, and for decisions on where to use limited resources in the fight against infections. In order to offer a multidisciplinary perspective, 23 infectious disease specialists, epidemiologists, geneticists, microbiologists, and population biologists participated in an open forum at Emory University on emerging and reemerging infectious diseases. As summarized below, the group addressed questions about the definition, the identification, the factors responsible for, and multidisciplinary approaches to emerging and reemerging infections.

The association between occupation and tuberculosis. A population-based survey.

There has been increasing interest in the potential association between occupation and the risk of tuberculosis. Therefore, we analyzed occupational information collected on all patients with clinically active tuberculosis in 29 states from 1984 to 1985. Census data were used to estimate the number of persons in each of the occupations. Information on employment and occupation was ascertained for 9,534 (99%) of the working age (16 through 64 yr) tuberculosis patients. The overall case rate of tuberculosis in this age group in the study areas was 8.4 per 100,000 persons, which was slightly lower than the national rate of 9.3 per 100,000 persons. As a group, health care workers had rates of tuberculosis similar to the general population (standardized morbidity ratio [SMR]: 1.0; 95% CI: 0.9 to 1.1). However, elevated rates were observed for inhalation therapists (SMR: 2.9; 95% CI: 1.2 to 6.0), and lower-paid health care workers (SMR: 1.3; 95% CI: 1.1 to 1.5). Elevated rates were also noted for funeral directors (SMR: 3.9; 95% CI: 2.2 to 6.1) and farm workers (SMR: 3.7; 95% CI: 3.4 to 4.1). These data suggest that even in communities with relatively low rates of tuberculosis certain occupations may be associated with an elevated risk.

Transmission of Mycobacterium tuberculosis from tuberculosis patients with HIV infection or AIDS.

Contacts exposed to tuberculosis patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection were compared with contacts of HIV-negative patients for evidence of Mycobacterium tuberculosis transmission, based on a review of records of tuberculin skin tests administered during routine health department follow-up investigations in Miami/Dade County, Florida, from 1985 through 1989. After an adjusted analysis designed to balance background prevalence, tuberculin positivity was 42.0% in 2,158 contacts of HIV-negative patients compared with 28.6% and 31.3% in 363 contacts of HIV-infected patients and 732 contacts of AIDS patients, respectively. Similar results were observed in a subset of 5- to 14-year-old contacts of United States-born black or white tuberculosis patients chosen to minimize the possibility of false-negative tuberculin tests in contacts due to undiagnosed HIV infection. Analysis of contacts as sets showed a more than expected number of sets with none or all contacts infected, but this did not differ by HIV/AIDS group. In this study, tuberculosis patients with AIDS or HIV infection were less infectious to their contacts and, in this community, exposed fewer contacts than HIV-negative tuberculosis patients.

Predictors of survival in HIV-infected tuberculosis patients.

OBJECTIVE: To ascertain predictors of survival in HIV-infected tuberculosis (TB) patients. DESIGN: Retrospective cohort study. SETTING: New York City public hospital. PATIENTS: Fifty-four consecutive HIV-seropositive patients with newly diagnosed TB and no other AIDS-defining illnesses. MAIN OUTCOME MEASURES: CD4+ T-lymphocyte counts, completion of anti-TB therapy, repeat hospitalizations with TB, and survival. RESULTS: Forty-five (84%) of the 54 patients died a median of 15 months after TB diagnosis (range, 1-80 months), five (9%) were alive after a median of 81 months (range, 75-84 months), and four (7%) were lost to follow-up after a median of 42 months (range, 30-66 months). In univariate analyses, disseminated TB, intrathoracic adenopathy, oral candidiasis and CD4 count depletion were each associated with decreased survival. In a multivariate analysis, CD4 count depletion was the only independent predictor of decreased survival. Repeat hospitalization with TB occurred in 10 out of 15 patients who did not complete anti-TB therapy compared with one out of 21 patients who completed anti-TB therapy (P < 0.001). CONCLUSION: The clinical presentation of TB and CD4 count at TB diagnosis are each predictive of survival in HIV-seropositive TB patients. The CD4 count is the only independent predictor of survival.

Epidemiology of tuberculosis in the United States, 1985 through 1992.

OBJECTIVE: To examine the distribution and sources of increased tuberculosis (TB) morbidity in the United States from 1985 through 1992. DESIGN: Review of TB surveillance data. PARTICIPANTS: All incident TB cases in the United States reported to the Centers for Disease Control and Prevention from 1980 through 1992. MAIN OUTCOME MEASURES: Changes in reported number of TB cases from 1985 through 1992 were analyzed by sex, race/ethnicity, age, county of birth (1986 through 1992), site of disease, geographic location, and socioeconomic status (through 1991). From 1985 through 1992, reported number of cases was compared with expected number of cases, extrapolated from 1980 through 1984 trends, to estimate excess cases by sex, race/ethnicity, and age. RESULTS: Increases in number of cases from 1985 through 1992 were concentrated among racial/ethnic minorities, persons 25 to 44 years of age, males, and the foreign-born. Excess cases occurred in both sexes, all racial/ethnic groups, and all age groups. Foreign-born cases accounted for 60% of the total increase in the number of US cases from 1986 through 1992 and had the greatest impact among Asians, Hispanics, females, and persons other than those 25 to 44 years of age. Human immunodeficiency virus infection had the greatest impact on TB morbidity among whites, blacks, males, and persons 25 to 44 years of age. From 1985 through 1992, the number of cases among children 4 years old or younger increased 36%, suggesting that transmission of TB increased during this period. CONCLUSIONS: Multiple factors contributed to the recent increases in the number of TB cases. The effectiveness of TB screening in immigrants needs further evaluation. Intensified efforts to determine the human immunodeficiency virus status of persons with TB are needed. Screening of subpopulations at increased risk for tuberculous infection or TB should be expanded.

Boosting of tuberculin sensitivity among Southeast Asian refugees.

Following an initial negative Mantoux tuberculin skin test, a second test, given as soon as 1 wk later, has been shown to elicit markedly larger reactions (boosting) in 20 to 40% of refugees tested in the United States. We conducted a study to determine the explanation for this phenomenon. Using the Mantoux method of intradermal skin testing, 2,469 refugees from Southeast Asia were initially tested with tuberculin followed by sequential retesting 7 and/or 90 d later. They were also tested initially with nontuberculous mycobacterial antigens. A high proportion (35.5%) of Southeast Asian refugees had reactions (> or = 10 mm induration) to an initial tuberculin test, and 30.9% of the nonreactors exhibited boosting on a subsequent tuberculin test. Boosting, unlike reactivity to the initial tuberculin test, was not associated with exposure to a person with tuberculosis. However, boosting was associated with reactivity to nontuberculous mycobacterial antigens and a history of bacille Calmette-Guérin (BCG) vaccination. Boosting in this population is therefore attributable to environmental exposure to nontuberculous mycobacteria that are endemic in Southeast Asia or to BCG vaccination, rather than to remote infection with Mycobacterium tuberculosis. Sequential tuberculin screening and preventive therapy of persons with boosted reactions is not recommended as a tuberculosis prevention strategy in this population.

Nationwide survey of drug-resistant tuberculosis in the United States.

OBJECTIVE: To determine antituberculosis drug resistance patterns, geographic distribution, demographic characteristics, and risk factors of reported tuberculosis (TB) patients in the United States. DESIGN: Survey of reported TB cases in the United States. For culture-positive cases reported to the Centers for Disease Control and Prevention, we asked health departments to provide drug susceptibility test results from initial Mycobacterium tuberculosis isolates. STUDY POPULATION: Culture-positive TB cases in the United States reported during the first quarter of 1991. MAIN OUTCOME MEASURES: Individual TB case reports submitted to the Centers for Disease Control and Prevention and drug susceptibility test results. RESULTS: Resistance to one or more antituberculosis drugs was found in 14.2% of cases. Resistance to isoniazid and/or rifampin was found in 9.5% of cases whose isolates were tested against one or both drugs; such cases were found in 107 counties in 33 states. Resistance to both isoniazid and rifampin (multidrug-resistant [MDR] TB) was found in 3.5% of cases whose isolates were tested against both drugs; such cases were found in 35 counties in 13 states. New York City accounted for 61.4% of the nation's MDR TB cases. The 3-month population-based incidence rate of MDR TB in New York City was 52.4 times (95% confidence interval [CI], 35.5 to 78.3) that of the rest of the nation (9.559 vs 0.182 cases per million population). Compared with the rate in non-Hispanic whites in the rest of the nation (0.032 cases per million), the relative risk of MDR TB in New York City non-Hispanic whites was 39.0 (95% CI, 8.1 to 164.5), 299.3 (95% CI, 112.5 to 927.1) in Hispanics, 420.9 (95% CI, 121.0 to 1515.8) in Asian/Pacific Islanders, and 701.0 (95% CI, 296.4 to 2018.1) in non-Hispanic blacks. CONCLUSIONS: With nearly 10% of TB patients resistant to isoniazid and/or rifampin, greater use of four-drug regimens and directly observed therapy is indicated. Aggressive intervention to prevent the further spread of MDR TB is needed to find every TB patient and to provide optimal patient management to ensure completion of chemotherapy.

Results of a 29-state survey of tuberculosis in nursing homes and correctional facilities.

A survey of the 15,379 cases of tuberculosis reported to the Centers for Disease Control and Prevention by 29 State health departments in 1984 and 1985 revealed that 7.7 percent of the victims older than age 64 were living in a nursing home at the time of diagnosis and 1.8 percent between the ages of 15 and 64 were living in a correctional institution at the time of diagnosis. Incidence rates of tuberculosis for residents of nursing homes and for inmates of Federal and State prisons and local jails were estimated using denominators derived from institutional population counts provided by the National Center for Health Statistics and by the Department of Justice, Bureau of Justice Statistics, and Bureau of Prisons. The aggregate tuberculosis incidence rate for nursing home residents in the 29 States was 1.8 times higher than the rate seen in elderly persons who were living in the community (95 percent confidence interval on the relative risk 1.64, 2.02). The aggregate tuberculosis incidence rate for inmates in correctional facilities was 3.9 times higher than the rate for persons of a similar age who were not incarcerated (95 percent confidence interval on the relative risk 3.35, 4.49). Strengths and limitations of the design and implications of the first survey of tuberculosis incidence, in a large number of States, among residents of nursing homes and correctional facilities are discussed.

The emergence of drug-resistant tuberculosis in New York City.

BACKGROUND: In the past decade the incidence of tuberculosis has increased nationwide and more than doubled in New York City, where there have been recent nosocomial outbreaks of multidrug-resistant tuberculosis. METHODS: We collected information on every patient in New York City with a positive culture for Mycobacterium tuberculosis during April 1991. Drug-susceptibility testing was performed at the Centers for Disease Control and Prevention. RESULTS: Of the 518 patients with positive cultures, 466 (90 percent) had isolates available for testing. Overall, 33 percent of these patients had isolates resistant to one or more antituberculosis drugs, 26 percent had isolates resistant to at least isoniazid, and 19 percent had isolates resistant to both isoniazid and rifampin. Of the 239 patients who had received antituberculosis therapy, 44 percent had isolates resistant to one or more drugs and 30 percent had isolates resistant to both isoniazid and rifampin. Among the patients who had never been treated, the proportion with resistance to one or more drugs increased from 10 percent in 1982 through 1984 to 23 percent in 1991 (P = 0.003). Patients who had never been treated and who were infected with the human immunodeficiency virus (HIV) or reported injection-drug use were more likely to have resistant isolates. Among patients with the acquired immunodeficiency syndrome, those with resistant isolates were more likely to die during follow-up through January 1992 (80 percent vs. 47 percent, P = 0.02). A history of antituberculosis therapy was the strongest predictor of the presence of resistant organisms (odds ratio, 2.7; P < 0.001). CONCLUSIONS: There has been a marked increase in drug-resistant tuberculosis in New York City. Previously treated patients, those infected with HIV, and injection-drug users are at increased risk for drug resistance. Measures to control and prevent drug-resistant tuberculosis are urgently needed.

Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients.

OBJECTIVE: To describe transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis infection among patients and health care workers (HCWs) in a ward and clinic for human immunodeficiency virus (HIV)-infected patients in a hospital, four studies were conducted. METHODS: Case patients and control patients were persons who had been treated in the HIV ward or clinic, whose clinical course was consistent with tuberculosis and who had at least one positive culture for M tuberculosis between January 1, 1988, and January 31, 1990, resistant to at least isoniazid and rifampin (case patients), or whose isolates were susceptible to all drugs tested (control patients). In the first study, case patients and control patients were compared to identify risk factors for MDR tuberculosis. In the second study, inpatient and outpatient days of MDR tuberculosis case patients were compared to determine whether acid-fast bacillus (AFB) smear-positivity or aerosolized pentamidine use was associated with higher numbers of subsequent MDR tuberculosis cases among exposed patients. In the third study, restriction fragment length polymorphism analysis was performed on available MDR and sensitive M tuberculosis isolates. In the fourth study, skin test conversion rates among HCWs in the HIV ward and clinic were compared with those of HCWs in another ward, and the strength of the associations between skin test conversions among HCWs on the HIV ward and the number of person-days that AFB smear-positive case patients and control patients were on this ward was estimated. RESULTS: Case patients were more likely than control patients to have been exposed on the HIV ward or clinic to an AFB smear-positive case patient (P less than .001). Inpatient and outpatient days of MDR tuberculosis case patients were associated with more subsequent cases of MDR tuberculosis if exposing case patients were smear-positive or if they received aerosolized pentamidine (P less than or equal to .01). Of 13 MDR isolates, all had one of two restriction fragment length polymorphism patterns; 10 sensitive isolates had restriction fragment length polymorphism patterns that were different from each other. The HCW skin test conversion rate was higher on the HIV ward and clinic than on the comparison ward (P less than .01). The risk of occupational acquisition of infection increased in direct proportion to the number of person-days that AFB smear-positive case patients were on the HIV ward (r = .75; P = .005), but did not increase in proportion to the number of person-days that AFB smear-positive control patients were there (r = -.36; P = NS). After isolation measures for AFB smear-positive tuberculosis patients were improved, MDR tuberculosis cases decreased to seven of 214 tuberculosis patients. CONCLUSIONS: Nosocomial transmission of MDR M tuberculosis infection to patients and HCWs occurred on the HIV ward and clinic. Infectiousness of MDR tuberculosis case patients was associated with AFB sputum-smear positivity. Case patients with MDR tuberculosis created a greater risk of skin test conversion for HCWs on the HIV ward than drug-susceptible control patients.

Usefulness of skin testing with mycobacterial antigens in children with cervical lymphadenopathy.

One hundred twenty-three children with chronic cervical lymphadenopathy were skin-tested with purified protein derivative (PPD)-B (Mycobacterium intracellulare), PPD-Y (Mycobacterium kansasii), PPD-G (Mycobacterium scrofulaceum) (nontuberculous mycobacterial antigens (NTMags)) and PPD-T (Mycobacterium tuberculosis). Children with culture-confirmed mycobacterial disease had significantly larger reactions to NTMags and were 6 times more likely to have PPD-B responses of greater than or equal to 10 mm than those with negative microscopy/culture results. Children with acid-fast bacilli present in clinical specimens but with negative culture results were 3 times more likely to have greater than or equal to 10 mm induration to PPD-B than those with negative microscopy/culture results. In all groups except those with culture-confirmed M. tuberculosis, responses to PPD-T were significantly smaller than those to the NTMags. We conclude that NTMags, particularly PPD-B, may be useful in diagnosing childhood mycobacterial cervical adenopathy; however, their usefulness in distinguishing disease caused by M. tuberculosis from that resulting from other mycobacteria is unknown.

Nosocomial transmission of tuberculosis in a hospital unit for HIV-infected patients.

OBJECTIVE: To assess nosocomial transmission of tuberculosis (TB). DESIGN: A historical cohort study of hospitalized patients with the human immunodeficiency virus (HIV) and a purified protein derivative (PPD) tuberculin skin test survey of health care workers (HCWs). SETTING: A large public teaching hospital in San Juan, Puerto Rico. PATIENTS: For the cohort study, a case patient was defined as any patient in the HIV unit at the hospital who developed culture-positive TB from 31 days or more after admission through December 31, 1989. For the PPD survey, of 1420 HCWs from the hospital, 908 agreed to participate and had sufficient data for analysis. MAIN OUTCOME MEASURES: For the cohort study, to compare the risk of developing active TB among patients who were exposed to hospital roommates with infectious TB and the risk among nonexposed patients. For the HCW PPD survey, to determine the prevalence of and risk factors for tuberculous infection. RESULTS: Eight of 48 (9.7/10,000 person-days) exposed case patients vs four of 192 (0.8/10,000 person-days) nonexposed case patients developed active TB (relative risk [RR] = 11; 95% confidence interval [CI], 2.3, 50.3). Positive PPDs (greater than or equal to 10 mm of induration) in HCWs were associated with older age (P = .0001) and with history of community TB exposure (P = .0002). In a multivariable logistic model that adjusted for these variables, HIV unit nurses (nine of 19) and nurses in the internal medicine ward (45 of 90) had a higher proportion of positive PPDs than the reference group (clerical personnel on other floors: 35 of 188, P = .0005). CONCLUSIONS: These data suggest that patient-to-patient transmission of TB in HIV units can occur and that HCWs are at risk of acquiring TB infection.

Evaluation of the clinical usefulness of mycobacterial skin test antigens in adults with pulmonary mycobacterioses.

A double-blind, multicenter study was conducted to evaluate the usefulness of mycobacterial skin test antigens for the specific diagnosis of adult pulmonary mycobacterial disease. The skin test antigens used were PPD-T (M. bovis) and PPD-B (M. intracellulare), made bioequivalent to 5 TU PPD-S through bioassay in human subjects. Of the 192 adults (18 yr of age or older), those with disease caused by M. tuberculosis (MTB) had significantly larger reactions to PPD-T than did those with disease caused by nontuberculous mycobacteria (NTM) or those with negative culture results (NEG)(13.41 mm versus 4.87 and 4.96 mm, respectively, p less than 0.001). The mean induration to PPD-B in NTM was not different from that in MTB or NEG. Defining a "positive" to be greater than or equal to 10 mm induration and a size difference of greater than or equal to 3 mm between PPD-T and PPD-B, the sensitivity, specificity, and positive predictive value (PPV) for PPD-T in diagnosing MTB versus NTM was 29, 90, and 75%. Corresponding values for PPD-B and NTM disease were 70, 61, and 64%. Dual testing was less useful in distinguishing disease caused by any of the mycobacteria from NEG. Although the sensitivity of PPD-B, made bioequivalent to PPD-S, was high, the specificity and PPV were low. We conclude that this preparation of PPD-B is no more useful in distinguishing adult pulmonary disease caused by NTM than is PPD-T alone.

Tuberculosis morbidity in the United States: final data, 1990.

The number of tuberculosis cases reported to CDC has been increasing since 1988, after a long historic decline. In 1990, 25,701 cases were reported, an increase of 9.4% over the 1989 figure and the largest annual increase since 1953. From 1985 to 1990, reported cases increased by 15.8%. Disproportionately greater increases in reported cases occurred among Hispanics, non-Hispanic blacks, and Asians/Pacific Islanders. In contrast, decreases were observed among non-Hispanic whites and American Indians/Alaskan Natives. By age, the largest increase in reported cases occurred in the 25- to 44-year age group; this increase may be largely attributable to rising numbers of tuberculosis cases among persons with human immunodeficiency virus infection or acquired immunodeficiency syndrome. Notable increases also occurred among children. The proportion of cases among foreign-born persons has risen steadily, from 21.6% in 1986 to 24.4% in 1990.