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.

Extensive transmission of Mycobacterium tuberculosis among congregated, HIV-infected prison inmates in South Carolina, United States.

BACKGROUND: In August 1999, a prison inmate infected with the human immunodeficiency virus (HIV) was diagnosed with pulmonary tuberculosis (TB). This source patient lived in a prison dormitory housing over 300 HIV-infected men, and was symptomatic for at least 2 months prior to diagnosis. We report a large outbreak of TB in HIV-infected prison inmates with subsequent transmission of Mycobacterium tuberculosis outside the prison. METHODS: Exposed inmates were screened by symptom review, chest radiograph and tuberculin skin test (TST) in September and December 1999. We recorded CD4 cell counts, viral loads and receipt of highly active antiretroviral therapy (HAART). RESULTS: The source patient lived on the right side of a two-sided dormitory exclusively housing HIV-infected men. Of 114 men tested from the right side, 75 (66%) had documented TST conversions. Of 96 converters overall, 82 (85%) had TSTs measuring > or = 15 mm. Within 6 months of diagnosis of TB in the source patient, 30 additional inmates and a healthcare worker who cared for the source patient developed TB disease. Two other inmates developed TB disease in spring of 2001. CONCLUSIONS: We describe extensive transmission of M. tuberculosis in a group of HIV-infected prison inmates with high TST conversion rates and subsequent transmission in the community. In settings where HIV-infected persons are congregated, the consequences of TB outbreaks are magnified.

Drug-drug interactions in inmates treated for human immunodeficiency virus and Mycobacterium tuberculosis infection or disease: an institutional tuberculosis outbreak.

The use of rifamycins is limited by drug interactions in human immunodeficiency virus (HIV)-infected persons who are receiving highly active antiretroviral therapy (HAART). During a tuberculosis (TB) outbreak at a prison housing HIV-infected inmates, rifabutin was used to treat 238 men (13 case patients and 225 contacts). Steady-state peak plasma rifabutin concentrations were obtained after rifabutin dosages were adjusted for men receiving single-interacting HAART (with either 1 protease inhibitor [PI] or efavirenz), multi-interacting HAART (with either 2 PIs or > or =1 PI with efavirenz), and for noninteracting HAART (>1 nucleoside reverse-transcriptase inhibitor or no HAART) without rifabutin dose adjustments. Low rifabutin concentrations occurred in 9% of those receiving noninteracting HAART, compared with 19% of those receiving single-interacting and 29% of those receiving multi-interacting HAART (chi2, 3.76; P=.05). Of 225 contacts treated with rifabutin-pyrazinamide, 158 (70%) completed treatment while incarcerated. Rifabutin-pyrazinamide therapy was difficult to implement, because of the need for dosage adjustments and expert clinical management.

An investigation of suspected exogenous reinfection in tuberculosis patients in Kampala, Uganda.

Exogenous reinfection with Mycobacterium tuberculosis is an important phenomenon that occurs with unknown frequency in both immunocompromised and immunocompetent persons. As previous investigations suggest that exogenous reinfection can occur in both of these populations, we reviewed data for 40 cases of suspected TB relapse in an attempt to determine the frequency of this phenomenon in patients treated at the TB Research Unit in Kampala, Uganda. Our findings suggest that while this entity can occur in immunocompetent persons, immunocompromised persons are probably at higher risk for exogenous reinfection with M. tuberculosis.

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.

Use and efficacy of tuberculosis infection control practices at hospitals with previous outbreaks of multidrug-resistant tuberculosis.

OBJECTIVE: To evaluate the implementation and efficacy of selected Centers for Disease Control and Prevention guidelines for preventing spread of Mycobacterium tuberculosis. DESIGN: Analysis of prospective observational data. SETTING: Two medical centers where outbreaks of multidrug-resistant tuberculosis (TB) had occurred. PARTICIPANTS: All hospital inpatients who had active TB or who were placed in TB isolation and healthcare workers who were assigned to selected wards on which TB patients were treated. METHODS: During 1995 to 1997, study personnel prospectively recorded information on patients who had TB or were in TB isolation, performed observations of TB isolation rooms, and recorded tuberculin skin-test results of healthcare workers. Genetic typing of M tuberculosis isolates was performed by restriction fragment-length polymorphism analysis. RESULTS: We found that only 8.6% of patients placed in TB isolation proved to have TB; yet, 19% of patients with pulmonary TB were not isolated on the first day of hospital admission. Specimens were ordered for acid-fast bacillus smear and results received promptly, and most TB isolation rooms were under negative pressure. Among persons entering TB isolation rooms, 44.2% to 97.1% used an appropriate (particulate, high-efficiency particulate air or N95) respirator, depending on the hospital and year; others entering the rooms used a surgical mask or nothing. We did not find evidence of transmission of TB among healthcare workers (based on tuberculin skin-test results) or patients (based on epidemiological investigation and genetic typing). CONCLUSIONS: We found problems in implementation of some TB infection control measures, but no evidence of healthcare-associated transmission, possibly in part because of limitations in the number of patients and workers studied. Similar evaluations should be performed at hospitals treating TB patients to find inadequacies and guide improvements in infection control.

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.

Risk factors for positive mantoux tuberculin skin tests in children in San Diego, California: evidence for boosting and possible foodborne transmission.

OBJECTIVES: Source case finding in San Diego, California, rarely detects the source for children with tuberculosis (TB) infection or disease. One third of all pediatric TB isolates in San Diego are Mycobacterium bovis, a strain associated with raw dairy products. This study was conducted to determine risk factors for TB infection in San Diego. DESIGN: Case-control study of children /=10 mm) Mantoux skin test (TST) were matched by age to 1 to 2 children with negative TST from the same clinic. We assessed risk factors for TB infection through parental interview and chart review. RESULTS: A total of 62 cases and 97 controls were enrolled. Eleven cases and 25 controls were excluded from analysis because of previous positive skin tests. Compared with controls, cases were more likely to have received BCG vaccine (73% vs 7%, odds ratio [OR] 44), to be foreign born (35% vs 11%, OR 4.3), and to have eaten raw milk or cheese (21% vs 8%, OR 3.76). The median time between the most recent previous TST and the current test was 12 months for cases and 25 months for controls. Other factors associated with a positive TST included foreign travel, staying in a home while out of the country, and having a relative with a positive TST. There was no association between contact with a known TB case. In a multivariable model, receipt of BCG, contact with a relative with a positive TST, and having a previous TST within the past year were independently associated with TB infection. CONCLUSIONS: We identified several new or reemerging associations with positive TST including cross border travel, staying in a foreign home, and eating raw dairy products. The strong associations with BCG receipt and more recent previous TST may represent falsely positive reactions, booster phenomena, or may be markers for a population that is truly at greater risk for TB infection. Unlike studies conducted in nonborder areas, we found no association between positive TB skin tests and contact with a TB case or a foreign visitor. Efforts to control pediatric TB in San Diego need to address local risk factors including consumption of unpasteurized dairy products and cross-border travel. The interpretation of a positive TST in a young child in San Diego who has received BCG is problematic.

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.

Risk factors for latent tuberculosis infection among children in New York City.

OBJECTIVE: Although identification and appropriate treatment of children with latent tuberculosis (TB) infection (LTBI) is considered critical to the control and elimination of TB in the United States, there are limited data on risk factors for LTBI in pediatric populations. METHODS: To further improve targeted screening for LTBI, we performed a matched case-control study from September 1996 to December 1998. We actively surveyed 24 primary care clinics serving Northern Manhattan and Harlem twice monthly for case participants 1 to 5 years old with LTBI, defined as a child with a Mantoux tuberculin skin test (TST) >/=10 mm and a normal chest radiograph. Two age- and clinic-matched control participants with TSTs equal to 0 mm were enrolled per case. To determine risk factors for LTBI, a bilingual research worker reviewed the medical records of study participants and administered a questionnaire to the parents of participants. RESULTS: We enrolled 96 cases and 192 controls whom did not differ by age, gender, ethnicity, and race; overall, the mean age of participants was 2.9 years, 51% were male, 80% were Hispanic, and 9% black. Logistic regression analysis demonstrated that contact with an adult with active TB, foreign birth, foreign travel, and a relative with a positive TST were predictive of case status. In contrast, a history of a previous negative TST proved protective and BCG immunization was not an independent risk factor for a positive TST, suggesting that boosting was not important in this population. CONCLUSIONS: We identified several risk factors for LTBI in children that can be used to refine targeted surveillance for TB among Hispanic immigrant populations in the United States.

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.

Completeness and timeliness of tuberculosis case reporting. A multistate study.

BACKGROUND: Tuberculosis (TB) control activities are contingent on the timely identification and reporting of cases to public health authorities to ensure complete assessment and appropriate treatment of contacts and identification of secondary cases. We report the results of a multistate evaluation of completeness and timeliness of reporting of TB cases in the United States during 1993 and 1994. METHODS: To determine completeness of TB reporting, laboratory log books, death certificates, hospital discharge, Medicaid databases, and pharmacy databases were reviewed in seven states to identify possible unreported cases. Timeliness of TB reporting was calculated using the number of days between date of TB diagnosis and date of report to the local or state health department. Cases reported >7 days after diagnosis were considered to have delayed reporting. RESULTS: Of 2711 cases identified through review of secondary data sources, 14 (0.5%) were previously unreported to public health. The largest yield of unreported cases was identified through review of laboratory records; 13 of the 14 unreported cases were identified, of which eight were found only through this method. Timeliness of reporting varied between sites from a median of 7 days to a median of 38 days. The number of cases with delayed reporting varied from 5% to 53% between sites. Factors associated with delayed reporting included infectiousness, type of provider, diagnosing provider, and reporting source. CONCLUSIONS: Through a review of several different secondary data sources, few unreported TB cases were detected; however, timeliness of reporting was poor among the reported cases.

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.

Cross-matching TB and AIDS registries: TB patients with HIV co-infection, United States, 1993-1994.

OBJECTIVES: Because of limited reporting of HIV status in case reports to the national tuberculosis (TB) surveillance system, the authors conducted this study to estimate the proportion of US TB cases with HIV co-infection and to describe demographic and clinical characteristics of co-infected patients. METHODS: The 50 states, New York City, and Puerto Rico submitted the results of cross-matches of TB registries and HIV-AIDS registries. The authors determined the number of TB cases reported for 1993-1994 that were listed in HIV-AIDS registries and analyzed data on demographic and clinical characteristics by match status. RESULTS: Of 49,938 TB cases reported for 1993-1994, 6863 (14%) were listed in AIDS or HIV registries. The proportions of TB-AIDS cases among TB cases varied by reporting area, from 0% to 31%. Anti-TB drug resistance was higher among TB-AIDS cases, particularly resistance to isoniazid and rifampin (multidrug resistance) and rifampin alone, In some areas with low proportions of multidrug-resistant TB cases, however, the difference in multidrug resistance between TB-AIDS patients and non-AIDS TB patients was not found. CONCLUSIONS: The proportion of TB cases with HIV co-infection, particularly in some areas, underscores the importance of the HIV-AIDS epidemic for the epidemiology of TB. Efforts to improve HIV testing as well as reporting of HIV status for TB patients should continue to ensure optimum management of coinfected patients, enhance surveillance activities, and promote judicious resource allocation and targeted prevention and control activities.