Investigation of Laboratory cross-contamination of Mycobacterium tuberculosis cultures.

Many clinicians and laboratory personnel are unaware that a culture positive for Mycobacterium tuberculosis may represent contamination. Laboratory cross-contamination with the M. tuberculosis laboratory control strain (H37Ra) occurs infrequently and therefore demands heightened awareness and recognition. We report 3 occurrences of laboratory cross-contamination from the same laboratory. These occurrences illustrate the importance of interpreting laboratory results in conjunction with the patient's clinical presentation. Failure to recognize laboratory cross-contamination with M. tuberculosis leads to both erroneous administration of unnecessary medications and expenditure of resources required to conduct contact investigations.

A preventable outbreak of tuberculosis investigated through an intricate social network.

In 1998, a city in Indiana reported 4-fold increase in the number of cases of tuberculosis (TB). An investigation to assess the increase in cases and to identify possible epidemiologic links among persons with TB identified 41 cases of active TB. Epidemiologic links and/or matching DNA fingerprints were identified for 31 patients (76%). The majority of these patients were members of a single social network within the community. Links for most of these patients were identified after multiple interviews with patients and their contacts. TB control activities in the county were limited prior to the identification of the outbreak. At least 24 cases may have been preventable. This outbreak may have been prevented with prompt case identification and effective contact tracing and screening during the years before the outbreak. The use of social networks should be considered in the investigation of outbreaks that involve difficult-to-reach populations. TB control measures should be maintained in areas with historically low TB incidence.

Simultaneous infection with multiple strains of Mycobacterium tuberculosis.

Drug-susceptible and drug-resistant isolates of Mycobacterium tuberculosis were recovered from 2 patients, 1 with isoniazid-resistant tuberculosis (patient 1) and another with multidrug-resistant tuberculosis (patient 2). An investigation included patient interviews, record reviews, and genotyping of isolates. Both patients worked in a medical-waste processing plant. Transmission from waste was responsible for at least the multidrug-resistant infection. We found no evidence that specimens were switched or that cross-contamination of cultures occurred. For patient 1, susceptible and isoniazid-resistant isolates, collected 15 days apart, had 21 and 19 restriction fragments containing IS6110, 18 of which were common to both. For patient 2, a single isolate contained both drug-susceptible and multidrug-resistant colonies, demonstrating 10 and 11 different restriction fragments, respectively. These observations indicate that simultaneous infections with multiple strains of M. tuberculosis occur in immunocompetent hosts and may be responsible for conflicting drug-susceptibility results, though the circumstances of infections in these cases may have been unusual.

Tuberculosis cases reported among migrant farm workers in the United States, 1993-97.

Migrant farm workers (MFWs) are considered a high-risk group for tuberculosis. MFW tuberculosis cases reported to the Centers for Disease Control and Prevention represented 1 percent of all reported tuberculosis cases from 1993 to 1997. Most of these cases (70 percent) were reported from Florida, Texas, and California. MFW tuberculosis cases were more likely to be male, foreign-born, or Hispanic and to have a history of alcohol abuse and homelessness than were non-MFWs. Most (79 percent) foreign-born MFWs were from Mexico. HIV status was poorly reported, with results available for only 28 percent of MFW and 33 percent of non-MFW cases. Of the MFWs tested, 28 percent were HIV infected, whereas 34 percent of non-MFWs were HIV infected. Twenty percent of MFWs move or are lost to follow-up before completing therapy; these cases pose a management challenge for the nation's tuberculosis control efforts.

Outbreak of multidrug-resistant tuberculosis at a methadone treatment program.

SETTING: An out-patient methadone treatment program MTP). OBJECTIVE: To investigate transmission of multidrug-resistant tuberculosis (MDR-TB) in the MTP. DESIGN: Cases were defined as MTP clients or staff who developed TB between 1 January 1994 and 1 January 1996, with at least one positive culture for Mycobacterium tuberculosis resistant to isoniazid and rifampin. Contacts were identified, located and evaluated. RESULTS: Thirteen cases of MDR-TB occurred among 462 clients and staff. One fifth (6/30) of the members of a counseling group for human immunodeficiency virus (HIV) infected clients developed MDR-TB. Individuals known to be HIV positive were at greater risk for TB than those who were HIV negative (RR 5.2, 95%CI 1.2-22.7). Of 449 clients and staff identified as contacts, 393 (87.5%) were located and screened. Among those with a negative baseline tuberculin skin test, 18.5% (56/303) were skin test converters. Attendance at the MTP during a period when the index case was infectious was associated with an increased risk of conversion (RR 2.5, 95%CI 1.1-6.0). CONCLUSION: Extensive transmission of MDR-TB occurred at an out-patient MTP serving numerous clients with HIV infection. This outbreak underscores the importance of developing effective strategies to prevent TB transmission in this setting.

Transmission of Mycobacterium tuberculosis from medical waste.

CONTEXT: Washington State has a relatively low incidence rate of tuberculosis (TB) infection. However, from May to September 1997, 3 cases of pulmonary TB were reported among medical waste treatment workers at 1 facility in Washington. There is no previous documentation of Mycobacterium tuberculosis transmission as a result of processing medical waste. OBJECTIVE: To identify the source(s) of these 3 TB infections. DESIGN, SETTING, AND PARTICIPANTS: Interviews of the 3 infected patient-workers and their contacts, review of patient-worker medical records and the state TB registry, and collection of all multidrug-resistant TB (MDR-TB) isolates identified after January 1, 1995, from the facility's catchment area; DNA fingerprinting of all isolates; polymerase chain reaction and automated DNA sequencing to determine genetic mutations associated with drug resistance; and occupational safety and environmental evaluations of the facility. MAIN OUTCOME MEASURES: Previous exposures of patient-workers to TB; verification of patient-worker tuberculin skin test histories; identification of other cases of TB in the community and at the facility; drug susceptibility of patient-worker isolates; and potential for worker exposure to live M tuberculosis cultures. RESULTS: All 3 patient-workers were younger than 55 years, were born in the United States, and reported no known exposures to TB. We did not identify other TB cases. The 3 patient-workers' isolates had different DNA fingerprints. One of 10 MDR-TB catchment-area isolates matched an MDR-TB patient-worker isolate by DNA fingerprint pattern. DNA sequencing demonstrated the same rare mutation in these isolates. There was no evidence of personal contact between these 2 individuals. The laboratory that initially processed the matching isolate sent contaminated waste to the treatment facility. The facility accepted contaminated medical waste where it was shredded, blown, compacted, and finally deactivated. Equipment failures, insufficient employee training, and respiratory protective equipment inadequacies were identified at the facility. CONCLUSION: Processing contaminated medical waste resulted in transmission of M tuberculosis to at least 1 medical waste treatment facility worker. JAMA. 2000;284:1683-1688.

Using DNA fingerprinting to detect transmission of Mycobacterium tuberculosis among AIDS patients in two health-care facilities in Puerto Rico.

BACKGROUND: Fourteen cases of tuberculosis (TB) in Puerto Rico, diagnosed from April 1993 to April 1995, had the same DNA fingerprint, documenting disease caused by the same strain of Mycobacterium tuberculosis. The 14 cases were retrospectively investigated for epidemiologic links. METHODS: Records were reviewed and staffs of the TB program, hospital/clinic, and AIDS residential facilities were interviewed. RESULTS: Half of the AIDS cases were epidemiologically related, providing evidence of TB transmission in an emergency department, an AIDS inpatient ward, and an AIDS residential facility. DNA fingerprinting allowed detection of M tuberculosis transmission, but contact investigators could have documented it sooner. Factors contributing to transmission included delayed diagnosis, prolonged infectiousness, inadequate discharge planning and infection control procedures, and poor communication between health-care facilities. CONCLUSIONS: The numbers of AIDS residential facilities are increasing and must understand proper monitoring of TB patients and infection control measures that prevent transmissions.

Analysis of Mycobacterium tuberculosis transmission patterns in a homeless shelter outbreak.

SETTING: From July 1997 through May 1998, ten tuberculosis (TB) cases were reported among men in a Syracuse New York homeless shelter for men. OBJECTIVE AND DESIGN: Investigation to determine extent of, and prevent further, transmission of Mycobacterium tuberculosis. RESULTS: Epidemiologic and laboratory evidence suggests that eight of the ten cases were related. Seven cases had isolates with matching six-band IS6110 DNA fingerprints; the isolate from another case had a closely related fingerprint pattern and this case was considered to be caused by a variant of the same strain. Isolates from eight cases had identical spoligotypes. The source case had extensive cavitary disease and stayed at the shelter nightly, while symptomatic, for almost 8 months before diagnosis. A contact investigation was conducted among 257 shelter users and staff, 70% of whom had a positive tuberculin skin test, including 21 with documented skin test conversions. CONCLUSIONS: An outbreak of related TB cases in a high-risk setting was confirmed through the use of IS6110 DNA fingerprinting in conjunction with spoligotyping and epidemiologic evidence. Because of the high rate of infection in the homeless population, routine screening for TB and preventive therapy for eligible persons should be considered in shelters.

Extensive transmission of Mycobacterium tuberculosis from a child.

BACKGROUND AND METHODS: Young children rarely transmit tuberculosis. In July 1998, infectious tuberculosis was identified in a nine-year-old boy in North Dakota who was screened because extrapulmonary tuberculosis had been diagnosed in his female guardian. The child, who had come from the Republic of the Marshall Islands in 1996, had bilateral cavitary tuberculosis. Because he was the only known possible source for his female guardian's tuberculosis, an investigation of the child's contacts was undertaken. We identified family, school, day-care, and other social contacts and notified these people of their exposure. We asked the contacts to complete a questionnaire and performed tuberculin skin tests. RESULTS: Of the 276 contacts of the child whom we tested, 56 (20 percent) had a positive tuberculin skin test (induration of at least 10 mm), including 3 of the child's 4 household members, 16 of his 24 classroom contacts, 10 of 32 school-bus riders, and 9 of 61 day-care contacts. A total of 118 persons received preventive therapy, including 56 young children who were prescribed preventive therapy until skin tests performed at least 12 weeks after exposure were negative. The one additional case identified was in the twin brother of the nine-year-old patient. The twin was not considered infectious on the basis of a sputum smear that was negative on microscopical examination. CONCLUSIONS: This investigation showed that a young child can transmit Mycobacterium tuberculosis to a large number of contacts. Children with tuberculosis, especially cavitary or laryngeal tuberculosis, should be considered potentially infectious, and screening of their contacts for infection with M. tuberculosis or active tuberculosis may be required.

Transmission of tuberculosis in a jail.

BACKGROUND: Outbreaks of tuberculosis are uncommonly recognized in jails. In 1996, an increase in active tuberculosis cases was noted among inmates of a large urban jail. OBJECTIVES: To determine the source and extent of a tuberculosis outbreak in an urban jail and to recommend control measures. DESIGN: Retrospective cohort study. SETTING: Urban jail. PATIENTS: Inmates and guards with tuberculosis. INTERVENTION: Outbreak evaluation and control. MEASUREMENTS: Medical records of inmates and guards with tuberculosis were reviewed, and inmates were interviewed. DNA fingerprinting was performed on Mycobacterium tuberculosis isolates. RESULTS: From 1 January 1995 through 31 December 1997, active tuberculosis was diagnosed in 38 inmates and 5 guards from the jail. Nineteen (79%) of the 24 culture-positive inmates had isolates with DNA fingerprints matching those of other inmates. Isolates from both culture-positive guards matched the predominant inmate strain; only 6 (14%) of 43 isolates from infected persons in the community had this pattern. The median length of incarceration of all inmates in the jail was 1 day; the median length of continuous incarceration before diagnosis of tuberculosis in inmates was 138 days. Inmates with tuberculosis had been incarcerated a median of 15 times. Forty-three percent of persons in this city with tuberculosis diagnosed from January 1995 through July 1997 had been incarcerated in the jail at some time before diagnosis. CONCLUSIONS: Traditional and molecular epidemiologic investigations suggest that tuberculosis was transmitted among inmates and guards in an urban jail. Aggressive measures to screen for active tuberculosis upon incarceration are important for preventing spread of disease in jails and to the surrounding community.

Spread of strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, across the United States.

Strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, was responsible for large nosocomial outbreaks in New York in the early 1990s. To describe the spread of strain W outside New York, we reviewed data from epidemiologic investigations, national tuberculosis surveillance, regional DNA fingerprint laboratories, and the Centers for Disease Control and Prevention Mycobacteriology Laboratory to identify potential cases of tuberculosis due to strain W. From January 1992 through February 1997, 23 cases were diagnosed in nine states and Puerto Rico; 8 were exposed to strain W in New York before their diagnosis; 4 of the 23 transmitted disease to 10 others. Eighty-six contacts of the 23 cases are presumed to be infected with strain W; 11 completed alternative preventive therapy. Strain W tuberculosis cases will occur throughout the United States as persons infected in New York move elsewhere. To help track and contain this strain, health departments should notify the Centers for Disease Control and Prevention of cases of tuberculosis resistant to isoniazid, rifampin, streptomycin, and kanamycin.

Immigration and tuberculosis among children on the United States-Mexico border, County of San Diego, California.

OBJECTIVE: To identify factors contributing to a 400% increase in tuberculosis among children in San Diego County, California, from 1985 to 1993. DESIGN: Review of medical records of reported cases in 1989, 1991, and 1993 and their source case. RESULTS: Of 192 children with tuberculosis, the largest increase was observed in children younger than 5 years old, of whom 77.4% were born in the United States, 67.8% had a foreign-born parent, 73.1% came from a non-English-speaking household, and 46.2% were known to visit Mexico. Of 28 source cases, 82.1% were born outside the United States, primarily in Mexico (67.9%). Resistance to at least one first-line antituberculous drug was identified in 27.5% of isolates from children and in 33.3% of isolates from source cases. CONCLUSIONS: The increase in tuberculosis and high level of drug-resistance among children born in the United States may be attributed to transmission outside of the United States or within the United States from household contacts born in countries in which tuberculosis is highly endemic.

Tuberculosis screening in private physicians' offices, Pennsylvania, 1996.

OBJECTIVE: To assess tuberculin skin testing practices of physicians after community-wide screening of 1400 children exposed to a pediatrician with active tuberculosis (TB). DESIGN: A self-administered questionnaire. SETTING: Medium-sized city in eastern Pennsylvania. PARTICIPANTS: Pediatricians and family practitioners seeing pediatric patients. MAIN OUTCOME MEASURES: Percentages of physicians who followed published recommendations for placement and reading of TB skin tests published by the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC). RESULTS: Questionnaires were completed by 60/80 (75%) physicians. The 60 physicians had practiced a mean of 17 years (range 3-38 years), and only one did not do TB skin testing for pediatric patients. The 59 physicians doing TB skin testing reported routinely tuberculin testing more than 900 children per month. Only 8/59 (14%) physicians followed published guidelines for placement and reading of tuberculin tests. Those physicians screened 158 (17%) of the pediatric patients undergoing TB skin testing in a typical month. CONCLUSION: In this community where a highly publicized TB case prompted massive pediatric screening, most physicians seeing children in private practice do not follow standard TB skin testing guidelines. Increased understanding of how private-practice physicians learn about and decide to use recommended standards are needed if tuberculin tests are to be correctly performed and TB appropriately diagnosed.

Tuberculin skin testing among economically disadvantaged youth in a federally funded job training program.

Low income, medically underserved communities are at increased risk for tuberculosis. Limited population-based national data are available about tuberculous infection in young people from such backgrounds. To determine the prevalence of a positive tuberculin skin test among economically disadvantaged youth in a federally funded job training program during 1995 and 1996, the authors evaluated data from medical records of 22,565 randomly selected students from over 100 job training centers throughout the United States. An estimated 5.6% of students had a documented positive skin test or history of active tuberculosis. Rates were highest among those who were racial/ethnic minorities, foreign born, and (among foreign-born students) older in age (p < 0.001). Weighted rates (adjusting for sampling) were 1.3% for white, 2.2% for Native American, 4.0% for black, 9.6% for Hispanic, and 40.7% for Asian/Pacific Islander students; rates were 2.4% for US-born and 32.7% for foreign-born students. Differences by geographic region of residence were not significant after adjusting for other demographic factors. Tuberculin screening of socioeconomically disadvantaged youth such as evaluated in this study provides important sentinel surveillance data concerning groups at risk for tuberculous infection and allows recommended public health interventions to be offered.

A train passenger with pulmonary tuberculosis: evidence of limited transmission during travel.

In January 1996, smear- and culture-positive tuberculosis (TB) was diagnosed for a 22-year-old black man after he had traveled on two U.S. passenger trains (29.1 hours) and a bus (5.5 hours) over 2 days. To determine if transmission had occurred, passengers and crew were notified of the potential exposure and instructed to undergo a tuberculin skin test (TST). Of the 240 persons who completed screening, 4 (2%) had a documented TST conversion (increase in induration of > or = 10 mm between successive TSTs), 11 (5%) had a single positive TST (> or = 10 mm), and 225 (94%) had a negative TST (< 10 mm). For two persons who underwent conversion, no other risk factors for a conversion were identified other than exposure to the ill passenger during train and/or bus travel. These findings support limited transmission of Mycobacterium tuberculosis from a potentially highly infectious passenger to other persons during extended train and bus travel.

Tuberculin skin test screening practices among US colleges and universities.

CONTEXT: Concern about transmission of Mycobacterium tuberculosis on college campuses has prompted some schools to institute tuberculin skin test screening of students, but this screening has never been evaluated. OBJECTIVE: To describe tuberculin skin test screening practices and results of screening in colleges and universities in the United States. DESIGN AND SETTING: Self-administered mail and telephone questionnaire in November and December 1995 to a stratified random sample of US 2-year and 4-year colleges and universities. MAIN OUTCOME MEASURES: Type of tuberculin screening required; types of schools requiring screening; number and rate of students with positive skin test results and/or diagnosed as having tuberculosis. RESULTS: Of the 3148 US colleges and universities, 624 (78%) of 796 schools surveyed responded. Overall, 378 schools (61%) required tuberculin screening; it was required for all new students (US residents and international students) in 161 (26%) of 624 schools, all new international students but not new US residents in 53 (8%), and students in specific academic programs in 294 (47%). Required screening was more likely in 4-year vs 2-year schools, schools that belonged to the American College Health Association vs nonmember schools, schools with immunization requirements vs schools without, and schools with a student health clinic vs those without (P<.001 for all). Public and private schools were equally likely to require screening (64% vs 62%; P=.21). In the 378 schools with screening requirements, tine or multiple puncture tests were accepted in 95 (25%); test results were recorded in millimeters of induration in 95 (25%); and 100 (27%) reported collecting results in a centralized registry or database. Of the 168 (27%) of 624 schools accepting only Mantoux skin tests and reporting results for school years 1992-1993 through 1995-1996, 3.1% of the 348 368 students screened had positive skin test results (median percentage positive, 0.8%). International students had a significantly higher case rate for active tuberculosis than US residents (35.2 vs 1.1 per 100000 students screened). CONCLUSIONS: Widespread tuberculin screening of students yielded a low prevalence of skin test reactors and few tuberculosis cases. To optimize the use of limited public health resources, tuberculin screening should target students at high risk for infection.

Evaluation of transmission of Mycobacterium tuberculosis in a pediatric setting.

OBJECTIVE: To determine the extent of transmission of Mycobacterium tuberculosis to pediatric patients exposed to a pediatrician with smear- and culture-positive pulmonary tuberculosis (TB). METHODS: Clinic billing and hospital admission records were used to identify patients seen during the pediatrician's infectious period. Patients were notified of the potential exposure and were offered screening. RESULTS: A total of 1416 pediatric patients were identified as exposed. Of the 606 who completed screening, 12 (2%) had a skin test result > or = 10 mm, 2 (0.3 had a result 5 to 9 mm, and 592 (98%) had a negative test result (0 to 4 mm). No active TB cases were identified. Of the 14 children with a skin test result > or = 5 mm, 7 were U.S.-born and had no other risk for a positive skin test. The remaining seven had either been exposed to another person with infections TB or were from countries with a high prevalence of TB. CONCLUSION: We found evidence of limited transmission of Mycobacterium tuberculosis in the outpatient pediatric setting. Despite extensive resources dedication, only 43% of exposed children completed screening. In similar situations decision should balance the responsibility to protect children exposed to Mycobacterium tuberculosis with other public health priorities and available resources.

Pseudo-outbreak of tuberculosis in an acute-care general hospital: epidemiology and clinical implications.

A 10-fold increase in patients with Mycobacterium tuberculosis-positive specimens in one hospital laboratory prompted an investigation. Clinical and epidemiological data, along with M tuberculosis DNA fingerprinting results, indicated that laboratory contamination led to nine false-positive M tuberculosis cultures. Pseudo-infection should be considered in patients with unusual tuberculosis presentations, negative acid-fast bacilli smears, and only one positive culture with a low colony count.

Risk factors for rifampin mono-resistant tuberculosis.

Use of rifampin is required for short-course treatment regimens for tuberculosis. Tuberculosis caused by isolates of M. tuberculosis with resistance to rifampin and susceptibility to isoniazid is unusual, but it has been recognized through surveillance. Patients with tuberculosis (cases) with rifampin mono-resistance were compared with HIV-matched controls with tuberculosis caused by a drug-susceptible isolate. A total of 77 cases of rifampin mono-resistant tuberculosis were identified in this multicenter study. Three were determined to be laboratory contaminants, and 10 cases had an epidemiologic link to a case with rifampin mono-resistant tuberculosis, suggesting primary acquisition of rifampin-resistant isolates. Of the remaining 64 cases and 126 controls, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, or history of incarceration. Cases were more likely to have a history of prior tuberculosis than were controls. Of the 38 cases and 74 controls with HIV infection, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, history of incarceration, or prior tuberculosis. Cases were more likely to have histories of diarrhea, rifabutin use, or antifungal therapy. Laboratory analysis of available isolates showed that there was no evidence of spread of a single clone of M. tuberculosis. Further studies are needed to identify the causes of the development of rifampin resistance in HIV-infected persons with tuberculosis and to develop strategies to prevent its emergence.