Validity of using tuberculin skin test erythema measurement for contact investigation during a tuberculosis outbreak in schoolchildren previously vaccinated with BCG

BACKGROUND: Few studies have examined the validity of administering tuberculosis control measures based on tuberculin skin test (TST) erythema measurement. The present study aimed to clarify the relationship between the erythema and the induration seen following TST and to evaluate the validity of diagnosing tuberculosis infection based on the erythema following TST in school-aged contacts who had been vaccinated with bacillus Calmette-Guérin (BCG) in infancy. METHODS: A 56-month longitudinal study from January 1999 through September 2003 followed 566 junior high school students in Kochi City who were contacts of an infectious tuberculosis case. To evaluate the diagnostic accuracy of the erythema and induration following TST of the contacts, false-positive and false-negative TST results were noted. RESULTS: The natural logarithm of the erythematous response size was linearly related to the induration size. When the size of the erythematous response was used to determine the presence of tuberculosis infection, the proportion of infected children increased with increasing exposure to the index case. When the TST results in the contact investigation were interpreted together with the change in the size of the erythematous response from that observed at the regular school-entry checkup, false positive test results were avoidable among the students who had a large erythematous response after the contact investigation TST, but whose response was only slightly larger than their erythematous response following the school-entry TST. Among the students whose TST results were negative, 1.9% developed tuberculosis. CONCLUSION: Both erythema and induration measurement were equally effective for identifying tuberculosis infection in schoolchildren vaccinated with BCG.     

In-hospital contact investigation among health care workers after exposure to pulmonary tuberculosis in an intermediate tuberculosis prevalence area: A prospective study

We carried out in-hospital contact investigations of patients with pulmonary tuberculosis and analyzed the prevalence of latent tuberculosis infection (LTBI) among health care workers (HCWs) after TB exposure. A prospective study was conducted of 872 HCWs who were exposed to 55 index cases diagnosed with active pulmonary TB. HCWs after TB exposure were evaluated both TST and chest X-ray at the time of enrollment and 12 weeks after exposure; 625 HCWs (71.6%) underwent both initial assessments; 41 HCWs (6.6%) had a positive TST result. After 12 weeks, 71.1% of HCWs with initial negative TST (n = 415) underwent a second assessment. Ten HCWs had TST conversion. One HCW (0.2%) developed active pulmonary TB. In multivariable analysis, age over 30 years was associated with TST conversion (p = .02). Point prevalence of latent TB was 6.6%, and incidence of LTBI was estimated as 2.4 per 100 HCWs. Strict infection control measures should be emphasized in intermediate TB-burden, BCG-vaccinated countries, especially in HCWs with high risk for TB exposure.     

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.     

Comparing the performance of QuantiFERON-TB Gold and Mantoux test in detecting latent tuberculosis infection among Iranian health care workers

Objectives  

The risk of transmission of Mycobacterium tuberculosis from patients with tuberculosis to health care workers (HCWs) has been well documented but little is known about the prevalence of latent tuberculosis infection (LTBI) in Iranian HCWs. The aim of this study was to determine the prevalence of LTBI among HCWs by using IFNgamma-release assay and compare the results with those of tuberculin skin test (TST).     

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.     

The effect of Bacille Calmette-Guérin vaccine on tuberculin reactivity in indigenous children from communities with high prevalence of tuberculosis

The Bacille Calmette-Guérin (BCG) vaccine is the most widely used vaccine in the world, however it may cause problems for the appropriate interpretation of the tuberculin skin test (TST). We assessed the diagnostic value of latent infection in vaccinated and unvaccinated indigenous children from communities that have a very high prevalence of adult tuberculosis (TB). A total of 997 children under 15 years old and classified in age groups (0-1.9, 2-5, 6-9 and 10-15 years old) were randomly selected and given TSTs using the Mantoux technique. TST induration values of vaccinated children (n=724) were compared with those of children unvaccinated (n=273). BCG vaccination was not an important cause of false-positive TST, except in communities with a low prevalence of active TB. In conclusion, the results suggested that a history of BCG vaccination on TST+ response after 10 years of vaccination was statistically insignificant but whether at earlier age TST+ reflects most probably the degree of exposure to TB cases than BCG vaccination should be clarified in the future.     

Results of five-year systematic screening for latent tuberculosis infection in healthcare workers in Portugal

Introduction  

The risk of tuberculosis (TB) in healthcare workers (HCWs) is related to its incidence in the general population, and increased by the specific risk as a professional group. The prevalence of latent tuberculosis infection (LTBI) in HCWs in Portugal using the tuberculin skin test (TST) and the interferon-γ release assays (IGRA) was analyzed over a five-year period.     

北京市昌平区某高校大学新生结核潜伏感染调查

目的 调查大学新生结核潜伏感染情况,以便采取预防性措施。 方法 2010年10月随机纳入北京市昌平区某高校入学新生TST≥10 mm的健康受试者420例,应用ELISPOT检测经抗原刺激后分泌IFN-γ的效应T淋巴细胞(即斑点形成细胞,SFCs)数量,并对ELISPOT阳性者进行为期3年的结核感染发病情况监测。 结果 ELISPOT检测LTBI总的阳性率为41.2%,在BCG接种(阳性率41.5%)和未接种(阳性率40.0%)中差异无统计学意义(χ²=0.064, P=0.447),在TST直径10~14、15~19和≥20 mm组间(37.6%、45.4%和64.3%)差异有统计学意义(χ²=8.408, P=0.015),173例未治疗的 ELISPOT+/TST+者经3年的ATB监测,发病率为0。 结论 北京市昌平区某高校大学新生LTBI比率高,但仅以ELISPOT和TST双阳性者为预防性治疗指标,尚不足够。     

Tuberculosis screening programme using the QuantiFERON-TB Gold test and chest computed tomography for healthcare workers accidentally exposed to patients with tuberculosis

Healthcare workers (HCWs) have an increased incidence of tuberculosis (TB). Periodic and as-needed screenings of HCWs exposed to patients with TB are important. We integrated chest computed tomography (CT) and the QuantiFERON-TB Gold (QFT-G) test into our TB screening programme for HCWs. First, contacts were tested using the QFT-G test. Those positive for the QFT-G test were investigated by CT and classified as having active, latent (LTBI), or old TB. Between April 2005 and April 2010, 11 patients who had not been diagnosed with active TB on admission were found to have the disease. A total of 512 close or high risk contacts were identified, and underwent screening. Out of those, 34 (6.64%) were QFT-G positive, whereas 478 (93.36%) were negative. Of the 34 QFT-G-positive HCWs, four had CT findings compatible with active TB and received multidrug treatment; 24 showed no findings of active TB and received isoniazid for six months. All completed their regimens without any adverse effects. The TB screening programme integrating CT and the QFT-G test was safe and feasible. The efficacy of the programme needs to be confirmed by large scale clinical trials.     

To TST or not to TST: Is tuberculin skin testing necessary before BCG immunisation in children?

Bacille Calmette-Guérin (BCG) vaccine is one of the most commonly administered vaccines worldwide. In countries with high tuberculosis (TB) prevalence, it is generally given shortly after birth. In a number of low TB prevalence countries, BCG is used as a travel vaccine, typically given to children outside the neonatal period prior to visiting regions where TB is common. In this setting, it is recommended that latent TB infection (LTBI) resulting from prior exposure to Mycobacterium tuberculosis is excluded by a tuberculin skin test (TST) before BCG immunisation. This is to avoid the risk of an accelerated local reaction that is more common in individuals who have LTBI. In addition, BCG immunisation in individuals with LTBI is unnecessary, as it does not provide protection against progression to active TB disease. We review and discuss current international guidelines and recommendations on the need to screen children for LTBI prior to BCG immunisation. Guidelines vary significantly regarding age-related cut-offs and additional selection criteria. This variation primarily reflects the lack of evidence on which to base recommendations. We suggest an alternative strategy using a risk assessment questionnaire to identify children who should have a TST before BCG immunisation. This targeted approach will reduce the number of children unnecessarily screened, whilst allowing the identification of those with LTBI, who need further evaluation and treatment.     

Risk of tuberculous infection among healthcare workers in a tertiary-care hospital in Ankara, Turkey.

OBJECTIVE: To determine risk factors for tuberculin skin test (TST) positivity among healthcare workers (HCWs). DESIGN: Two-step TST was performed in 2002. SETTING: Tertiary-care hospital in Ankara, Turkey. PARTICIPANTS: A sample of 491 hospital HCWs were included. Information related to demographics, profession, work duration, department, and individual and family history of tuberculosis (TB) was obtained by a structured questionnaire. RESULTS: Four hundred eight (83%) had two-step TST positivity. On multivariate analysis, male physicians (relative risk [RR], 1.5; 95% confidence interval [CI95], 1.23-1.69; P = .001), nurses (RR, 1.5; CI95, 1.29-1.66; P = .005), radiology technicians (RR, 1.7; CI95, 1.35-1.73; P = .002), laboratory technicians (RR, 1.6; CI95, 1.3-1.74; P = .007), and male housekeepers (RR, 1.6; (HCWs). CI95, 1.38-1.7; P < .001) had a higher risk than did female physicians. Among laboratory technicians, radiology technicians had the highest TST positivity (85%). HCWs working for less than 1 year (RR, 0.8; CI95, 0.72-0.98; P = .027) had a lower risk of infection. The HCWs having bacille Calmette-Guerin vaccination (RR, 1.12; CI95, 1.08-1.45) had higher TST positivity. CONCLUSION: Male physicians, nurses, and laboratory technicians had increased risk of Mycobacterium tuberculosis infection in this setting, but community exposure likely accounted for most infections.     

Factors associated with tuberculosis infection,and with anti-mycobacterial immune responses,among five year olds BCG-immunised at birth in Entebbe,Uganda

BackgroundBCG is used widely as the sole licensed vaccine against tuberculosis, but it has variable efficacy and the reasons for this are still unclear. No reliable biomarkers to predict future protection against, or acquisition of, TB infection following immunisation have been identified. Lessons from BCG could be valuable in the development of effective tuberculosis vaccines.ObjectivesWithin the Entebbe Mother and Baby Study birth cohort in Uganda, infants received BCG at birth. We investigated factors associated with latent tuberculosis infection (LTBI) and with cytokine response to mycobacterial antigen at age five years. We also investigated whether cytokine responses at one year were associated with LTBI at five years of age.MethodsBlood samples from age one and five years were stimulated using crude culture filtrates of Mycobacterium tuberculosis in a six-day whole blood assay. IFN-γ, IL-5, IL-13 and IL-10 production was measured. LTBI at five years was determined using T-SPOT.TB^® assay. Associations with LTBI at five years were assessed using multivariable logistic regression. Multiple linear regression with bootstrapping was used to determine factors associated with cytokine responses at age five years.ResultsLTBI prevalence was 9% at age five years. Only urban residence and history of TB contact/disease were positively associated with LTBI. BCG vaccine strain, LTBI, HIV infection, asymptomatic malaria, growth z-scores, childhood anthelminthic treatment and maternal BCG scar were associated with cytokine responses at age five. Cytokine responses at one year were not associated with acquisition of LTBI by five years of age.ConclusionAlthough multiple factors influenced anti-myocbacterial immune responses at age five, factors likely to be associated with exposure to infectious cases (history of household contact, and urban residence) dominated the risk of LTBI.     

Improving hand sensibility in vibration induced neuropathy: A case-series

Introduction

Results of systematic screening of healthcare workers (HCWs) for tuberculosis (TB) with the tuberculin skin test (TST) and interferon-γ release assays (IGRA) in a Portuguese hospital from 2007 to 2010 are reported.

Methods

All HCWs are offered screening for TB. Screening is repeated depending on risk assessment. TST and QuantiFERON Gold In-Tube (QFT) are used simultaneously. X-ray is performed when TST is > 10 mm, IGRA is positive or typical symptoms exist.

Results

The cohort comprises 2,889 HCWs. TST and IGRA were positive in 29.5%, TST-positive but IGRA-negative results were apparent in 43.4%. Active TB was diagnosed in twelve HCWs - eight cases were detected during screening and four cases were predicted by IGRA as well as by TST. However, the progression rate in IGRA-positive was higher than in TST-positive HCWs (0.4% vs. 0.2%, p-value 0.06).

Conclusions

The TB burden in this cohort was high (129.8 per 100,000 HCWs). However, the progression to active TB after a positive TST or positive IGRA was considerably lower than that reported in literature for close contacts in low-incidence countries. This may indicate that old LTBI prevails in these HCWs.     

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.     

Nosocomial transmission of Mycobacterium tuberculosis from an extrapulmonary site.

OBJECTIVE: To assess the extent of nosocomial transmission and risk factors associated with tuberculin skin test (TST) conversions among healthcare workers (HCWs) exposed to a patient with genitourinary Mycobacterium tuberculosis. DESIGN: Retrospective cohort study of exposed HCWs. SETTING: A 275-bed community hospital in Middle Tennessee. PARTICIPANTS: A total of 128 exposed HCWs and the index patient, who required drainage of a prostatic abscess and bilateral orchiectomy and expired after a 27-day hospitalization. Disseminated tuberculosis was diagnosed at autopsy. METHODS: Contact tracing was performed on exposed HCWs. Logistic regression was used to identify independent risk factors associated with TST conversion. RESULTS: A total of 128 HCWs were exposed to the index patient. There was no evidence of active pulmonary tuberculosis throughout the patient's hospitalization; TST conversions occurred only among HCWs who were exposed to the patient during or after his surgical procedures. A total of 12 (13%) of 95 exposed HCWs who were previously nonreactive had newly positive TST: 6 of 28 nurses, 3 of 3 autopsy personnel, 2 of 17 respiratory therapists, and 1 of 12 surgical staff. By logistic regression, irrigation or packing of the surgical site was the only independent risk factor associated with TST conversion among nurses (odds ratio, 9; 95% confidence interval, 1.2-67; P=.03). CONCLUSION: Manipulation of infected tissues of the genitourinary tract can result in nosocomial transmission of tuberculosis.     

A survey of latent tuberculosis infection among laboratory healthcare workers in New York City.

OBJECTIVE: To determine the prevalence of positive tuberculin skin tests (TSTs), incidence of TST conversion, risk factors for positive TSTs, and history of active TB among HCWs in microbiology laboratories in New York City. DESIGN: Two-year survey from May 1999 to June 2001. SETTING: Nineteen microbiology laboratories. RESULTS: During the first year, interviews were conducted with 345 laboratory HCWs (mean, 18 HCWs per site; range, 2 to 51) to assess the prevalence of positive TSTs, but 3 (1%) could not recall their result and were excluded from further analyses. The mean age of the remaining 342 HCWs was 48 years; 68% (n = 233) were female, 54% (n = 183) received bacille Calmette-Guerin (BCG) vaccination, and 71% (n = 244) were foreign born. The prevalence of a positive TST was 57% (n = 196), but only 20% (n = 39) of the HCWs received isoniazid. The incidence of TST conversion in the second year of the study was 1% (1 of 108). Multivariate analysis identified age (odds ratio [OR] per year, 1.05; 95% confidence interval [CI95], 1.02-1.08), foreign birth (OR, 3.80; CI95, 1.98-7.28), BCG immunization (OR, 4.89; CI95, 2.72-8.80), and employment in a mycobacteriology laboratory (OR, 2.14; CI95, 1.25-3.68) as risk factors for a positive TST. Only one HCW had been treated for active TB. CONCLUSIONS: The prevalence of positive TSTs was high among laboratory HCWs, but the TST conversion rate was low. Higher rates of treatment for latent TB infection are desirable.     

Diagnosis of latent tuberculosis infection in candidates for kidney transplantation (comparison of two tests)

It is assumed that about 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis. The rate of tuberculosis in solid organ transplant recipients has been estimated to be 50-fold higher than in the general population. Candidates for solid organ transplantation are routinely screened for latent tuberculosis infection (LTBI). In this study we aimed to compare Tuberculin Skin Test (TST) with QuantiFERON-TB Gold In-Tube (QFT) for the detection of LTBI in candidate for kidney transplantation. Between October 2009 and November 2010, 64 candidates for kidney transplant who referred to the transplant clinic in Imam Khomeini Hospital, were enrolled in the study. Patients were screened for LTBI with both QFT and TST. Concordance between two test results and variables associated with test discordance were assessed. The mean age of patients was 38.5 years (range 16-65); female/male ratio was 26/38. Positive results were found in 21.9% and 21.9%, by TST and QFT, respectively. Four patients (6.3%) had indeterminate QFT. Overall agreement between QFT and TST was 75% (k=0.28 and P=0.028). BCG vaccination and past positive TST were not associated with positive QFT result (P=0.13 and P=0.09 respectively). Overall agreement between test results was fair. Comparison among test results showed that TST andQFT can be used interchangeably for latent TB screening in kidney transplant candidates. The decision to select QFT or TST will depend on the purpose of testing and resource availability.     

Is tuberculin skin testing useful to diagnose latent tuberculosis in BCG-vaccinated children?

BACKGROUND: The tuberculin skin test (TST) is the most commonly used tool to detect infection with Mycobacterium tuberculosis. We sought to determine whether tuberculin skin testing is useful to detect latent infection by M. tuberculosis in a population that was vaccinated with the Bacille Calmette Guérin (BCG) vaccine. METHODS: We performed a cross-sectional study during October 2000-February 2001, enrolling first and sixth graders from a random, stratified sample of public elementary schools in Orizaba, Veracruz, Mexico. We assessed the relationship between sociodemographic and epidemiological information, BCG scars, and TST reactivity. RESULTS: There were 858 children enrolled in the study with a completed questionnaire and TST result. The prevalence of a positive TST result (> or =10 mm) was 12.4%. Controlling for BCG scar, age, and other characteristics, close contact with pulmonary tuberculosis patients (odds ratio 6.56, 95% confidence interval 2.05-21.07, P = 0.001) was independently associated with TST reactivity. CONCLUSIONS: TST results helped identify children in a BCG-vaccinated population who had recent exposure to persons with pulmonary tuberculosis, were probably infected with M. tuberculosis, and could benefit from treatment for their latent tuberculosis infection.     

Tuberculosis in healthcare workers caring for a congenitally infected infant.

OBJECTIVE: To assess the extent of nosocomial transmission of tuberculosis among infants, family members, and healthcare workers (HCWs) who were exposed to a 29-week-old premature infant with congenital tuberculosis, diagnosed at 102 days of age. DESIGN: A prospective exposure investigation using tuberculin skin test (IST conversion was conducted. Contacts underwent two skin tests 10 to 12 weeks apart. Clinical examination and chest radiographs were performed to rule out disease. Isoniazid prophylaxis was administered to exposed infants at higher risk. SETTING: A neonatal intensive care unit in an urban hospital in Brussels, Belgium. PARTICIPANTS: Ninety-seven infants, 139 HCWs, and 180 visitors. RESULTS: Newly positive TST results occurred in HCWs who had been in close contact with the infant. Six (19%) of 32 primary care nurses and physicians had TST conversions and received treatment. Among the 97 exposed infants, 85 were screened and 34 were identified as at higher risk of infection. Of these, 27 received preventive isoniazid. None of the infants and none of the 93 other infants' family members evaluated were infected. CONCLUSIONS: Congenital tuberculosis in an infant poses a risk for nosocomial transmission to HCWs. Delayed diagnosis of this rare disease and close proximity are the most important factors related to transmission.