Dual skin testing for latent tuberculosis infection: a decision analysis

BACKGROUND: Recent data indicate that 10- to 14-mm Mycobacterium tuberculosis purified protein derivative (PPD) reactions are often due to prior infections with nontuberculous mycobacteria. Therefore, use of a 10-mm cutpoint to define latent tuberculosis infection (LTBI) results in false-positive diagnoses and unnecessary treatment for LTBI. A second skin test, Mycobacterium avium sensitin (MAS), has been shown to accurately identify false-positive PPD results. OBJECTIVE: To compare the costs and accuracy of a single skin-test strategy (SST) with PPD alone with a dual skin-test strategy (DST) where 10- to 14-mm PPD results are also tested with MAS. METHODS: A decision analytic model was developed to evaluate the two strategies. The model accounted for the costs of skin testing, the costs of LTBI treatment, the costs of undetected LTBI, and the sensitivity and specificity of each strategy. RESULTS: We estimated that DST saved US dollars 3 per subject tested compared to SST. Savings were due to a reduction in false-positive PPD results and consequent reduction in unnecessary treatment for LTBI of >60%. The DST strategy was associated with a minimal increase in undetected LTBI (6% vs 7%). Results were stable for a broad range of parameter values. CONCLUSIONS: DST is a promising approach to improving the specificity of LTBI testing when a 10-mm PPD cutpoint is used and would reduce costs and unnecessary drug treatment.     

Evaluation of the two-step tuberculin skin test in health care workers at an inner-city medical center.

The increased rate of tuberculosis (TB) infection and transmission from patients to health care workers (HCWs) has brought awareness of the need for better surveillance programs. The two-step purified protein derivative (PPD) skin test decreases the misinterpretation of a "boosted reaction" as a recent infection with Mycobacterium tuberculosis in HCWs. We reviewed the medical records of 4082 HCWs at an inner-city medical center who had PPD skin-testing performed as a component of the TB medical surveillance program during the years 1994 and 1995. Of those HCWs tested, 3896 (95.4%) returned for the PPD skin-test evaluation. Of those 3896 HCWs, 3659 (93.9%) had a negative baseline PPD skin test, and 237 (6.1%) had a positive skin test. Of those HCWs with a negative baseline skin test, 252 (6.9%) were eligible for the second PPD skin test. Of the 241 who returned for their second PPD skin-test reading, six (2.5%) had positive results. All six cases were foreign-born physician residents with a previous history of Bacille bilié de Calmette-Guérin (BCG) vaccination. We conclude that the two-step PPD skin test method is not indicted for HCWs at this urban medical facility.     

Evaluation of a western blot test as a potential screening tool for occupational exposure to Mycobacterium tuberculosis in health care workers

Health care workers (HCWs) have a higher than average risk for contracting Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB). No markers of MTB-exposure are available, and TB risk assessment is performed by tuberculin screening, identifying individuals with acquired MTB infection. This study evaluated a western blot (WB) anti-M. bovis A60 complex antibody as a MTB-exposure marker. WB reactivity was evaluated on 127 exposed and 28 non-exposed HCWs from four divisions of the Policlinico Hospital of Modena, and 140 non-exposed bacille Calmette-Guérin-vaccinated controls. Excess of occupational TB risk according to the Occupational Safety and Health Administration (OSHA) was calculated in each division. WB-positivity (%) was: (1) significantly higher in exposed HCWs compared with non-exposed (72% vs 25%, P < 0.00001), (2) highly related (r = 0.99) to OSHA risk excess in all divisions, (3) higher than non-exposed in HCWs with short (< 5 years) MTB-exposure (purified protein derivative [PPD], P > 0.18; WB, P < 0.04). PPD-positivity (%) was higher than controls only in HCWs with longer (> 5 years) MTB-exposure. The study suggests that the WB antibody might represent a more sensitive biological marker of MTB contact among exposed HCWs, related to the level of TB risk and detectable earlier than the PPD skin test, thus providing new tools for TB risk assessment in health care facilities.     

Tuberculin skin testing among healthcare workers in the University of Malaya Medical Centre, Kuala Lumpur, Malaysia.

OBJECTIVES: To determine the occupational risk of Mycobacterium tuberculosis infection among healthcare workers (HCWs) and to examine the utility of tuberculin skin testing in a developing country with a high prevalence of bacille Calmette-Guerin vaccination. DESIGN: Tuberculin skin test (TST) survey. SETTING: A tertiary-care referral center and a teaching hospital in Kuala Lumpur, Malaysia. PARTICIPANTS: HCWs from medical, surgical, and orthopedic wards. INTERVENTION: Tuberculin purified protein derivative RT-23 (State Serum Institute, Copenhagen, Denmark) was used for the TST (Mantoux method). RESULTS: One hundred thirty-seven (52.1%) and 69 (26.2%) of the HCWs tested had indurations of 10 mm or greater and 15 mm or greater, respectively. Medical ward HCWs were at significantly higher risk of a positive TST reaction than were surgical or orthopedic ward HCWs (odds ratio, 2.18; 95% confidence interval, 1.33 to 3.57; P = .002 for TST positivity at 10 mm or greater) (odds ratio, 2.61; 95% confidence interval, 1.44 to 4.70; P = .002 for TST positivity at 15 mm or greater). A previous TST was a significant risk factor for a positive TST reaction at either 10 mm or greater or 15 mm or greater, but a duration of employment of more than 1 year and being a nurse were only significantly associated with a positive TST reaction at a cut-off point of 15 mm or greater. CONCLUSIONS: HCWs at the University of Malaya Medical Centre had an increased risk for M. tuberculosis infection that was significantly associated with the level of occupational tuberculosis exposure. A TST cut-off point of 15 mm or greater may correlate better with M. tuberculosis infection than a cut-off point of 10 mm or greater in settings with a high prevalence of bacille Calmette-Guerin vaccination.     

Tuberculin skin test conversion among medical students at a teaching hospital in Rio de Janeiro, Brazil.

OBJECTIVE: To describe the cumulative incidence of and risk factors for tuberculosis (TB) infection among medical students. DESIGN: In 1999, a cohort study of medical students with negative results (induration < 10 mm) on tuberculin skin test (TST) was performed. Students who had undergone two-step testing in 1998 were retested. SETTINGS: University and teaching hospital and referral center for TB and acquired immunodeficiency syndrome, and the Health Sciences Building of the Medical School of the Federal University of Rio de Janeiro, Brazil. PARTICIPANTS: A sample of 618 consecutive medical students with negative TST results who had been tested 12 months before were approached. Information about sociodemographic characteristics, bacille Calmette-Guérin vaccination history, and potential exposures to TB was obtained using a standardized questionnaire. Four hundred fourteen (67%) students completed the study. Students were at two different levels of their training programs (juniors = no contact with patients; seniors = intensive contact with patients). RESULTS: Of 414 participants, 16 (3.9%; 95% confidence interval, 1.06% to 12.1%) had converted to a positive reaction after 1 year. In a multivariate logistic regression analysis, higher level of clinical training was confirmed to be an independent factor associated with TST conversion (odds ratio, 4.77; 95% confidence interval, 1.01 to 22.46; P= .048). CONCLUSION: Senior medical students are at increased risk of Mycobacterium tuberculosis infection in this setting. Therefore, a program of routine tuberculin skin testing and specific TB infection control guidelines are needed for this population.     

Prevalence of tuberculin skin test positivity and conversions among healthcare workers in New York City during 1994 to 2001.

OBJECTIVE: To determine the prevalence of and risk factors for tuberculin skin test positivity and conversion among New York City Department of Health and Mental Hygiene employees. DESIGN: Point-prevalence survey and prospective cohort analysis. Sentinel surveillance was conducted from March 1, 1994, to December 31, 2001. PARTICIPANTS: HCWs in high-risk and low-risk settings for occupational TB exposure. RESULTS: Baseline tuberculin positivity was 36.2% (600 of 1,658), 15.5% (143 of 922) among HCWs born in the United States, and 48.5% (182 of 375) among HCWs not born in the United States. There were 36 tuberculin conversions during 2,754 observation-years (rate, 1.3 per 100 person-years). For HCWs born in the United States, the risk for tuberculin conversion was greater in high-risk occupational settings compared with low-risk settings (OR, 5.7; CI95, 1.7-19.2; P < .01). HCWs not born in the United States and those employed at the Office of the Chief Medical Examiner (OCME) were at high risk for baseline tuberculin positivity (OR, 3.2; CI95, 1.7-5.8; P < .001); OCME HCWs (OR, 4.7; CI95, 2.3-9.4; P < .001), those of Asian ethnicity (OR, 4.3; CI95, 1.4-13.5; P < .01), and older HCWs (OR, 1.0; CI95, 1.0-1.1; P < .05) were at a higher risk for conversion. CONCLUSIONS: Although the prevalence of tuberculin positivity decreased after the peak of the recent TB epidemic in New York City, the conversion rate among HCWs in high-risk occupational settings for TB exposure was still greater than that among HCWs in low-risk settings. Continued surveillance of occupational TB infection is needed, especially among high-risk HCWs.     

Evaluation of Exposure to Tuberculosis Among Employees at a Medical Center

Tuberculosis (TB), a disease caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis), is spread from person to person through the air. TB usually infects the lungs, but it can also infect other body parts such as the brain, kidneys, or spine. People who are infected by the bacteria but who do not exhibit symptoms have latent TB infection. It is estimated that one-third of the world's population has latent TB infection, and approximately 5%–10% of those infected will develop TB disease within their lifetimes.^(–)

In July 2011, the National Institute for Occupational Safety and Health (NIOSH) received a health hazard evaluation request from management representatives at a medical center in Arizona concerning exposure of employees to M. tuberculosis. They asked for our assistance in evaluating the infection control and occupational health practices related to TB.

At the time of our visit, the medical center included an inpatient hospital with 73 beds and adjacent outpatient facility, and the center had approximately 1000 employees. One nurse, the infection control practitioner, was responsible for all infection control and occupational health activities at the medical center. The medical center's TB policy required annual tuberculin skin testing (TST) of all employees with face-to-face patient contact, which included the majority of employees.     

结核病专科医院医务人员结核感染风险研究

目的 探讨结核病专科医院医务人员职业暴露危险因素,以采取有效地预防控制措施降低结核感染风险.方法 采用整群抽样的方法,进行问卷调查,采集基本信息,对受试人群进行结核菌素试验(PPD)和T细胞斑点试验(T-SPOT.TB)检测.结果 共有符合条件的497人纳入本研究,98.59％认为自己在工作中有机会接触结核病患者,81.89％工作时佩戴口罩,82.70％接种过卡介苗;受试者中,PPD试验阳性率为66.60％,T-SPOT.TB试验阳性率较低,为10.87％,两种试验结果在医院内不同职业人群间差异无统计学意义,PPD试验阳性率与工作年限有相关性(x2=11.1936,P=0.0107),而T-SPOT.TB试验结果与工作年限无明显相关.结论 加强全体医务人员,特别是行政管理人员和新上岗医务人员的个人防护和健康教育有重要意义.     

Clinical inquiries. How should we manage a patient with a positive PPD and prior BCG vaccination?

Prior bacille Calmette-Guerin (BCG) vaccination increases the likelihood of a positive tuberculosis (TB) 5TU purified protein derivative (PPD) skin test. The PPD response following BCG vaccine varies with age at vaccination, number of years since the BCG vaccination, number of times vaccinated, and number of PPDs performed. An induration of greater than 14 mm is unlikely to be due to prior BCG vaccination (strength of recommendation [SOR]: A, based on meta-analysis of validation cohort studies). The variable reaction after BCG vaccination, along with the desire to detect all cases of TB, has led to recommendations that all patients with a positive PPD test be treated as true positives. These patients should undergo chest radiography and appropriate treatment, regardless of history of BCG vaccine (SOR: B, extrapolation from level 1 study). A recently developed alternative is the interferon-gamma assay (QuantiFERON-TB Gold test), which may be used in place of, or in addition to, the PPD skin test for patients who are known to have received a BCG vaccine (SOR: B, extrapolation from a validation cohort study).     

1486名结防机构医务人员结核病感染现状调查

目的了解河南省结核病防治机构不同岗位医务人员结核病感染现状。方法于2005年1月从该省18个地市和109个县中随机抽取40个县,对抽取的58个结核病防治机构的所有在职医务人员作为调查对象;进行PPD皮试检查。结果 1 486名医务人员接受了PPD皮试检查,阳性率为66.1%,其中住院医生(75.9%)、门诊医生(75.3%)、住院护理(74.6%)、放射人员(72.3%)、督导医生(71.8%)。经x2检验,PPD皮试阳性率与强阳性率医务人员均明显高于非医务人员。结论该省结防工作人员结核病感染率较高,应加强医务人员的感染控制工作。     

Evaluation of results from occupational tuberculin skin tests--Mississippi, 2006

In October 2006, the National Institute for Occupational Safety and Health (NIOSH) received a request for a health hazard evaluation from a fire department in Mississippi. In June 2006, the fire department had administered two-step tuberculin skin tests (TSTs) and determined that nine firefighters tested positive for tuberculosis (TB) infection. Local investigation had identified no source of TB infection. The NIOSH evaluation was conducted to 1) determine whether TB transmission was occurring among department firefighters, 2) assess the accuracy of positive TST results, and 3) make recommendations regarding administration of future fire department TB-testing programs. This report describes the results of that evaluation, which indicated that all nine firefighters had false-positive TST findings, likely caused by errors in interpretation of the test results. These results highlight the importance of conducting TB testing only when indicated by TB risk assessment and following CDC guidelines to avoid errors in TST administration and interpretation that might result in unnecessary medical evaluation and follow-up.     

Mycobacterium tuberculosis transmission in a newborn nursery and maternity ward--New York City, 2003

Evaluating young children recently exposed to airborne Mycobacterium tuberculosis is a public health priority. If infected, children aged <2 years are at high risk for severe tuberculosis (TB) disease (e.g., TB meningitis). In December 2003, infectious pulmonary TB disease was diagnosed in a foreign-born nurse working in the newborn nursery and maternity ward of a New York City hospital (hospital A); the nurse had declined treatment for latent TB infection (LTBI) after testing positive 11 years earlier. An investigation including medical evaluation of contacts in the nursery and maternity ward was conducted by the Bureau of TB Control (BTBC) at the New York City Department of Health and Mental Hygiene, hospital A, and CDC. This report summarizes the results of that investigation, which determined that approximately 1,500 patients had been exposed to the nurse but the majority could not be located for evaluation. Among those who were tested, four infants had positive tuberculin skin test (TST) results, likely attributable to recent transmission of M. tuberculosis. The findings emphasize the difficulty of conducting contact investigations in certain settings and the importance of effective LTBI testing and treatment programs for health-care workers (HCWs) to prevent TB disease and subsequent health-care--associated transmission.     

Factors associated with tuberculin reactivity in two general hospitals in Mexico.

OBJECTIVE: To identify risk factors associated with tuberculin reactivity in healthcare workers (HCWs). DESIGN: Cross-sectional survey of tuberculin reactivity (2 TU of purified protein derivative (PPD) RT23, using the Mantoux two-step test). SETTING: Two general hospitals located in a region with a high prevalence of tuberculosis and high bacille Calmette-Guerin (BCG) coverage. PARTICIPANTS: Volunteer sample of HCWs. RESULTS: 605 HCWs were recruited: 71.2% female; mean age, 36.4 (standard deviation [SD], 8.2) years; 48.9% nurses, 10.4% physicians, 26.8% administrative personnel; mean time of employment, 10.9 (SD, 6.7) years. PPD reactivity (> or =10 mm) was found in 390 (64.5%). Multivariate analysis revealed an association of tuberculin reactivity with occupational exposure in the hospital: participation in autopsies (odds ratio [OR], 9.3; 95% confidence interval [CI95], 2.1-40.5; P=.003.), more than 1 year of employment (OR, 2.4; CI95, 1.1-5.0; P=.02), work in the emergency or radiology departments (OR, 2.0; CI95, 1.03-3.81; P=.04), being physicians or nurses (OR, 1.5; CI95, 1.04-2.11; P=.03), age (OR, 1.04; CI95, 1.02-1.07 per year of age; P<.001), and BCG scar (OR, 2.1; CI95, 1.2-3.4; P=.005). CONCLUSIONS: Although the studied population has a high baseline prevalence of tuberculosis infection and high coverage of BCG vaccination, nosocomial risk factors associated with PPD reactivity were identified as professional risks; strict early preventive measures must be implemented accordingly.     

Tuberculosis in healthcare workers at a general hospital in Mexico.

OBJECTIVE: To determine the incidence rate of tuberculosis (TB) disease among healthcare workers (HCWs) at a general hospital. DESIGN: Retrospective analysis of TB cases among HCWs over the course of 5 years. SETTING: A 140-bed general hospital in Tijuana, Mexico. PARTICIPANTS: All hospital employees who developed TB during the 5-year period. RESULTS: From 1 January 1999 through 31 December 2003, 18 TB cases were diagnosed among the hospital personnel. During that period, the mean (+/- standard deviation) annual work force of the hospital was 819+/-21.7 employees. The TB incidence rate was 439.56 cases per 100,000 employees; this rate was 10.98 times higher than the rate for the general population of the city. The TB incidence rate for physicians was 860.21 cases per 100,000 employees, that for nurses was 365.85 cases per 100,000 employees, and that for physicians in training was 1,846.15 cases per 100,000 employees. Physicians in training had a higher risk of acquiring TB than did either physicians (relative risk, 2.14 [95% confidence interval, 1.34-35.66) or nurses (relative risk, 5.04 [95% confidence interval, 3.16-83.33). Three of the HCWs with TB disease were infected with a drug-resistant strain of Mycobacterium tuberculosis, and one of the infecting strains was multidrug resistant. Asymptomatic TB infection among HCWs was not addressed during this study. CONCLUSIONS: The TB incidence rate among the HCWs at the hospital is extremely high, compared with that in the general population. The implementation of infection control measures is an urgent priority, to reduce this occupational hazard.     

传染病医院医务人员结核感染状况

目的了解传染病医院医务人员结核(TB)感染现况,探讨其感染TB的危险性及影响因素。方法对某传染病医院的全体医务工作者进行问卷调查和TB菌素纯蛋白衍化物（PPD）试验检测。结果该传染病医院全体职工TB感染发病率为48.18%。不同科室医务工作者的TB感染情况差异无统计学意义（P＞0.05）,不同工作年限、不同年龄、不同职称的医务工作者TB感染情况差异均有统计学意义（均P＜0.05）。文化程度、职称、目前居住情况、在结核感染门诊或病区的工作时间是TB感染的危险因素,其OR(95%CI)分别为1.70（1.03～2.80）、1.95（1.10～3.45）、1.84（1.03～3.28）、2.38（1.40～4.04）;个人防护是TB感染的保护因素［OR及OR95%CI为0.92（0.85～0.99）］。结论传染病医院的医务工作者是TB感染的高危人群,应加强自我防护意识,及早采取防护措施。     

Screening for tuberculosis among 2381 household contacts of sputum-smear-positive cases in The Gambia

Contact investigation is a key component of tuberculosis (TB) control in developed, but not developing, countries. We aimed to measure the prevalence of TB among household contacts of sputum-smear-positive TB cases in The Gambia and to assess the sensitivity of an enzyme-linked immunospot (ELISPOT) assay in this regard. Household contacts of adult smear-positive TB patients were assessed by questionnaire, purified protein derivative (PPD) skin test, ELISPOT assay, physical examination, chest X-ray and sputum/gastric aspirate. Thirty-three TB cases were identified from 2174 of 2381 contacts of 317 adult smear-positive pulmonary TB patients, giving a prevalence of 1518/100000. The cases identified tended to have milder disease than those passively detected. The sensitivity of ESAT-6/CFP-10 ELISPOT test as a screening test for TB disease was estimated as 71%. Fifty-six per cent of contacts with a PPD skin test result >or=10mm induration had detectable responses to ESAT-6/CFP-10 by ELISPOT; 11% with a negative PPD skin test (<10mm) had a positive ESAT-6/CFP-10 response. Active screening for TB among contacts of TB patients may have a role in TB control in The Gambia. These individuals are a high-risk group, and the disease identified is less advanced than that found through passive case detection. An ELISPOT assay was relatively insensitive as a screening test for TB.     

A tuberculosis screening and chemoprophylaxis project in children from a high risk population in Edmonton, Alberta.

Current recommendations for tuberculosis control are to screen high risk populations and provide chemoprophylaxis for those infected. In Edmonton, Alberta, one strategy has been to identify and provide TB skin tests to newly arrived immigrant school age children from TB endemic areas. The difficulty has been in identifying these children in the school population. This article describes a process tried in 1993-94 to find a better approach and to determine the outcome of a concentrated effort at screening and follow-up of this population. Using this method, 1,146 students were TB skin tested using 5tu PPD: 15% showed significant reactions (10 mm), 89% were offered chemoprophylaxis, and 68% of those offered (84% of those accepting) completed 9 months of chemoprophylaxis. The success of this process was dependent on the dedicated follow-up provided by the specialty public health clinic devoted to the prevention and treatment of tuberculosis.     

Tuberculosis and HIV co-infection in healthcare workers in England and Wales, 1999-2005

This study used linked national tuberculosis (TB) and HIV surveillance data to investigate recent trends and factors associated with HIV co-infection (TB-HIV) in healthcare workers (HCWs) with TB in England and Wales. Methods applied were the χ2 trend test and logistic regression. Overall 14% (231/1627) of HCWs with TB were co-infected with HIV, increasing from 8% in 1999 to 14% in 2005 (P<0·001). Most (78%) HCWs were non-UK born and 74% of these developed TB ?2 years post-entry. Being born in Sub-Saharan Africa was an independent predictor for TB-HIV, especially for female HCWs (odds ratio 66·5, 95% confidence interval 16·3-271·1), who also had a lower median CD4 count than other co-infected women (106/mm3, interquartile range 40-200, P<0·01). Voluntary HIV testing of new HCWs should be encouraged as an opportunity for early diagnosis. Post-entry, a high index of clinical suspicion for TB in those most at risk remains important.     

Environmental risk factors for infection with Mycobacterium avium complex

Infection with Mycobacterium avium complex is acquired from the environment, but risk factors for M. avium complex infection and disease are poorly understood. To identify risk factors for infection, the authors performed a 1998-2000 cross-sectional study in western Palm Beach County, Florida, using a population-based random household survey. M. avium complex infection was identified by use of the M. avium sensitin skin test. Of 447 participants, 147 (32.9%) had a positive test reaction, 186 (41.6%) had a negative test reaction, and, for 114 (25.5%), test results were indeterminate. Among the 333 participants with positive or negative M. avium sensitin skin tests, age-adjusted independent predictors of M. avium complex infection in a multivariate model included Black race (odds ratio = 3.8, 95% confidence interval: 2.2, 6.6), birth outside the United States (odds ratio = 2.1, 95% confidence interval: 1.1, 3.9), and more than 6 years' cumulative occupational exposure to soil (odds ratio = 2.7, 95% confidence interval: 1.3, 6.0). Exposure to water, food, or pets was not associated with infection. Results indicate that soil is a reservoir for M. avium complex associated with human infection and that persons whose occupations involve prolonged soil exposure are at increased risk of M. avium complex infection.     

Latent tuberculosis in nursing professionals of a Brazilian hospital

Tuberculosis (TB) is considered an occupational disease among health-care workers (HCWs). Direct contact with TB patients leads to an increased risk to become latently infected by Mycobacterium tuberculosis. The objective of this study is to estimate the prevalence of latent M. tuberculosis minfection among nursing professionals of a hospital in Rio Grande do Sul, Brazil, assessed by tuberculin skin test (TST). From November 2009 to May 2010, latent M. tuberculosis infection was assessed by TST in 55 nursing professionals. Epidemiological information was collected using a standardized questionnaire. A positive TST result (> or = 10 mm) was observed in 47.3% of the HCWs tested. There was no significant difference in TST positivity when duration of employment or professional category (technician or nurse) was evaluated. The results of this work reinforce the need for control measures to prevent latent M. tuberculosis infection among nursing professionals at the hospital where the study was conducted.