Baseline Tuberculin Skin Test Research Articles

Prevalence and incidence of tuberculosis infection among healthcare workers in chest diseases hospitals, Bangladesh: Putting infection control into context.

Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh.

Risk of tuberculosis in children with rheumatologic diseases treated with biological agents: A cross-sectional cohort study.

This study aimed to evaluate the risk of tuberculosis (TB) disease in children receiving biological agents for rheumatologic diseases, focusing on appropriate screening tests in a high-priority country for TB control. One hundred nine children (56 females, 53 males; range, 3.4 to 16.2 years) who received any biological agent for rheumatologic diseases for more than two years between May 2012 and October 2021 were included in this retrospective study. Patients were screened for TB infection using tuberculin skin test (TST) or interferon-gamma release assay (IGRA). Following the initial evaluation, patients were clinically examined for TB every three months by a comprehensive medical history and physical examination, and every 12 months using TST or IGRA. At the initiation of the biological agent, the patients' mean age was 12.4±4.5 years. The average follow-up duration was 3.6±1.3 years (range, 2.6 to 10.2 years) for patients treated with biological agents. Each patient had a documented Bacillus Calmette-Guérin vaccination. Before the initiating of therapy, TST was performed alone in 45 (41.3%) patients and in combination with IGRA in 64 (58.7%) patients. In the 64 patients who underwent both TST and IGRA, IGRA revealed nine (14.1%) positive results. Six (66.7%) of these nine patients, however, had negative baseline TST. Four (7.3%) of the 55 individuals whose initial IGRA results were negative also had positive TST results. Overall, no TB disease was observed after a follow-up period. This study reveals that biological agents were not associated with an increased risk of TB disease in closely monitored children. Additionally, the concomitant use of TST and IGRA for screening of TB is reasonable in patients receiving biological agents.

Contribution of remote M.tuberculosis infection to tuberculosis disease: A 30-year population study.

The importance of remote infection with M.tuberculosis as a cause of tuberculosis disease (TB) is unclear, with limited evidence of impact on TB rates beyond 10 years. Our objective was to assess rates of tuberculosis over 30 years by M.tuberculosis infection status at baseline in Karonga District, Northern Malawi. Population-based surveys of tuberculin skin testing (TST) from the 1980s were linked with follow-up and TB surveillance in Karonga district. We compared rates of microbiologically-confirmed TB by baseline TST induration <5mm (no evidence of M.tuberculosis infection) and those with baseline TST >17mm (evidence of M.tuberculosis infection), using hazard ratios by time since baseline and attributable risk percent. The attributable risk percent was calculated to estimate the proportion of TB in those infected that can be attributed to that prior infection. We analysed whole genome sequences of M.tuberculosis strains to identify recent transmission. Over 412,959 person-years, 208 incident TB episodes were recorded. Compared to the small induration group, rates of TB were much higher in the first two years in the large induration group, and remained higher to 20 years: age, sex and area-adjusted hazard ratios (HR) 2-9 years post-TST 4.27 (95%CI 2.56-7.11); 10-19 years after TST 2.15 (1.10-4.21); ≥20 years post-TST 1.88 (0.76-4.65). The attributable risk percent of remote infection was 76.6% (60.9-85.9) 2-9 years post-TST, and 53.5% (9.1-76.2) 10-19 years post-TST. Individuals with large TST indurations had higher rates of unique-strain TB (HR adjusted for age, sex and area = HR 6.56 (95% CI 1.96-22.99)), suggesting disease following remote infection, but not of linked-strain TB (recent transmission). M.tuberculosis infection can increase the risk of TB far beyond 10 years, accounting for a substantial proportion of TB occurring among those remotely infected.

Incomplete contact investigation and risk of developing TB among healthcare professionals.

BACKGROUND: Data on the impact of incomplete contact investigation on TB incidence among healthcare professionals (HCPs) after TB exposure are limited.METHODS: This was a prospective cohort study with 2-year follow-up among Thai HCPs exposed to TB to determine TB incidences and factors associated with TB development.RESULTS: Of the 398 HCPs with TB exposure, 367 (92%) participated in the study; 342 HCPs were included in the final analysis; 311 participated in contact investigations; 303 underwent chest X-ray; 252 completed baseline TB and latent TB infection screening using tuberculin skin test (TST); 210 had negative baseline TST; and 45 completed follow-up tests at 3 months. Altogether, 20 HCPs developed TB (2.92/100 person-years). TB incidences in HCPs not participating in or not completing the investigation at any step were higher than in those who completed the evaluation (11.29 and 2.90, respectively, vs. 0/100 person-years; P < 0.05). No participation in contact investigation and no baseline chest X-ray were independent factors associated with TB development (adjusted odds ratio [aOR] 6.7; P < 0.001 and aOR 8.9; P = 0.01, respectively).CONCLUSION: Study findings indicate increased risks of TB development among HCPs not undergoing or not completing contact investigations and underscore the need for interventions to improve contact investigation participation and completeness.

798. Incomplete Contact Investigation and Risk of Developing Tuberculosis Among Healthcare Professionals After Tuberculosis Exposure

BackgroundTuberculosis (TB) contact investigation is recommended for healthcare professionals (HCPs) after TB exposure. However, association between no participation in or incomplete contact investigation and subsequent TB development has not been well-described. This study aims to determine TB incidences and factors associated with TB development among HCPs requiring contact investigations.MethodsWe conducted a prospective cohort study among Thai HCPs with TB exposure from January 2013 to December 2017. Contact investigations, including baseline TB and latent tuberculosis infection (LTBI) screening and follow-up at 3 months after TB exposure, were recommended to all HCPs. The two-step tuberculin skin test (TST) was used for LTBI testing. All HCPs were followed for 2 years for TB development.ResultsOf the 342 HCPs with TB exposure included in the study, 311 (91%) participated in the contact investigations and 252 (74%) completed baseline TB and LTBI screening. Among the 210 HCPs with negative baseline TST, 45 (21%) completed the follow-up tests. The overall incidence of TB was 2.92/100 person-years. HCPs who did not complete follow-up TST had significantly higher TB incidence than those completed baseline and follow-up TST (3.55 vs. 0/100 person-years; P=0.01). No participation in the contact investigation and no chest radiograph performed at baseline were the independent factors associated with TB development among the HCPs [adjusted odds ratio (aOR) 6.69; P< 0.001 and aOR 8.85; P=0.01, respectively]. Contact with an index patient with concomitant TB at extrapulmonary sites (aOR 49.76, 10.03-246.99; P< 0.001) and with negative sputum AFB but positive sputum GeneXpert MTB/RIF (aOR 3.18, 1.35-7.50; P=0.008) were independently associated with no participation in the contact investigation.ConclusionThe findings indicate the risk of TB development among the HCPs who did not undergo or complete contact investigations and underscore the need for interventions to improve contact investigation participation and completeness.Disclosures All Authors: No reported disclosures

Brief Report: Yield of Repeat Tuberculin Skin Testing for People Living With HIV in Brazil.

In Brazil, annual tuberculin skin tests (TSTs) are recommended for people living with HIV (PLWH) with CD4 >350, with tuberculosis preventive therapy provided on test conversion. We aimed to determine the yield of repeat TSTs for PLWH. Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT) to prevent tuberculosis (TB). We analyzed data from newly registered PLWH with negative baseline TST results. We calculated the number of TST conversions after 1 and/or 2 years among patients eligible for follow-up TSTs, the proportion of converters initiating IPT, and incidence of TB/death. Among 1770 PLWH with a negative baseline TST, 679 (38%) were female and median age was 36 years (IQR 29-43). Eighty-six (5%) developed TB or died within 1 year. Among 1684 eligible for a follow-up 1-year TST, 582 (35%) were tested and 53 (9%) were positive. Forty-nine converters (92%) started IPT. Of 529 patients with a negative 1-year TST, 7 (1%) developed TB or died over the following year. Of 522 patients eligible for a 2-year TST, 158 (30%) were tested and 13 (8%) were positive. Ten converters (77%) started IPT. Of 1102 patients who did not receive a 1-year TST, 33 (3%) developed TB or died. Of the 1069 patients eligible for a 2-year TST, 259 (24%) were tested and 34 (13%) were positive. Thirty converters (88%) started IPT. In this cohort of PLWH in Brazil, TST conversion was high among those retested, but only 48% received a follow-up TST within 2 years.

Utility of the Interferon-Gamma Release Assay for Latent Tuberculosis Infection Screening among Indian Health-Care Workers.

Background:The utility of interferon-gamma release assays (IGRAs) for latent tuberculosis infection (LTBI) screening among health-care workers (HCWs) in low- and middle-income countries (LMICs) remains unclear.Methods:This was a prospective cohort study among HCW trainees undergoing annual LTBI screening via tuberculin skin test (TST) and QuantiFERON® TB Gold Test-in-tube (QFT-GIT) in Pune, India. TST induration ≥ 10 mm and QFT-GIT ≥ 0.35 IU/ml were considered positive. Test concordance was evaluated at entry among the entire cohort and at 1 year among baseline TST-negative participants with follow-up testing. Overall test agreement was evaluated at both timepoints using the kappa statistic: fair (k < 0.40), good (0.41 ≥ k ≤0.60), or strong (k > 0.60).Results:Of 200 participants, prevalent LTBI was detected in 42 (21%) via TST and 45 (23%) via QFT-GIT; QFT-GIT was positive in 27/42 (64%) TST-positive and 18/158 (11%) TST-negative trainees. Annual TST conversion was 28% (40/142) and included 11 trainees with baseline TST-/IGRA+; QFT-GIT was positive in 17/40 (43%) TST-positive and 5/102 (5%) TST-negative trainees. Overall test concordance was 84% (k = 0.52; 95% confidence interval [CI]: 0.38–0.66) and 80% (k = 0.44; 95% CI: 0.29–0.59) at baseline and 12 months, respectively.Conclusions:We observed good overall agreement between TST and QFT-GIT, and QFT-GIT detected additional LTBI cases among TST-negative trainees with possible early detection of LTBI conversion. Overall, our results support the use of IGRA for annual LTBI screening among HCWs in a high burden LMIC setting.

Tuberculosis Exposure and Conversion Rates Can Guide Deimplementation of Annual Tuberculosis Screening

Background: The CDC recently updated recommendations on tuberculosis (TB) screening in healthcare facilities, suggesting the discontinuation of annual TB screening. However, hospitals may opt to continue based on their local TB epidemiology. We assessed TB infection control parameters in our facility to guide the implementation of the new CDC recommendations. Methods:We retrieved data for patients with an International Classification of Disease, Tenth Revision (ICD-10) code for TB treated at the University of Iowa Hospitals and Clinics during 2016–2019. We supplemented our search with microbiology data: culture or PCR for Mycobacterium tuberculosis. Based on manual chart review, we adjudicated each patient as active TB, latent TB, previously treated TB, unclear history, or no TB. We further labeled active TB cases based on their risk of transmission (pulmonary or extrapulmonary cases that underwent an aerosol generating procedure). We then calculated the number of exposure events associated with those patients and tuberculin skin test (TST) conversion rates among the exposed. Results: During 2016–2019, we identified 197 patients based on ICD-10 codes. In total, 10 additional patients were detected by microbiology data review. Of these 207 patients, 48 (23.2%) had active TB: lung, n = 24 (50%); lymph node, n = 9 (19%); bone or spine, n = 5 (10%); eye, n = 3 (6%); disseminated, n = 2 (4%); pleura, n = 2 (4%); skin abscess, n = 2 (4%); and meningitis, n = 1 (2%). Of the 24 pulmonary patients, 6 (25%) had either a positive smear or a cavity on imaging. In total, 159 patients were excluded: no TB, n = 22 (14%); latent TB, n = 27 (17%); old or treated TB, n = 93 (58%); and unclear history, n = 9 (6%). Of the 48 cases with active TB, 31 (65%) were deemed potentially infectious. Also, 10 cases (32%) led to the exposure of 204 healthcare workers (HCWs). Baseline and postexposure TST were available for 179 HCWs (88%); 72 (35%) followed up in the employee health clinic within the 8–12 weeks after exposure. Of 161 HCWs with a negative TST at baseline, no conversions occurred. Of 18 HCWs with positive TST at baseline, no HCW developed symptoms during the observation period. Conclusions: Nearly one-third of infectious TB cases led to HCW exposures in a low-incidence setting. However, no TST conversions or active TB infections were seen. Exposure and conversion rates are useful indicators of TB infection control in healthcare facilities and may help guide implementation of the new CDC TB control recommendations.Funding: NoneDisclosures: None

Impact of Baseline Tuberculin Skin Test and Isoniazid Chemoprophylaxis on Subsequent Quantiferon-TB Gold In-Tube Performance in Young Children Assessed After Tuberculosis Contact in Catalonia.

We investigated the impact of baseline tuberculin skin tests (TSTs) and preventive isoniazid chemoprophylaxis on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) assays performed after a 10- to 12-week window period in 114 children <5 years of age. Previous TSTs and chemoprophylaxis had no impact on the magnitude of subsequent antigen-induced responses in QFT-GIT. Furthermore, previous TSTs did not induce conversion from a negative to a positive QFT-GIT result.

Incidence of latent tuberculosis infection among health science students during clinical training.

BACKGROUND:The prevalence of latent tuberculosis infection (LTBI) has been found to be high among students undergoing clinical training. The aim of this study is to determine the incidence of LTBI among undergraduate health science students after their clinical training and to compare the risk between different college specialties.METHODS:This is a retrospective cohort study of students who completed their clinical training from 2010 to 2017. The risk of LTBI was defined based on the conversion of tuberculin skin test (TST) results from negative at the start of training to positive after the completion of training.RESULTS:A total of 2000 students were evaluated, of whom 1997 were included in this analysis. Six percent tested positive in the first TST of the initial screening. Ten percent of students with a normal baseline TST converted to positive on the follow-up TST. Clinical training in the college of medicine increased the risk of LTBI by 76% (odds ratio: 1.76; 95% confidence interval: 1.04– 2.96; P = 0.03) compared to clinical training in other medical colleges.CONCLUSIONS:The risk of acquiring LTBI during clinical training in health science colleges is 10%. Students in the college of medicine are at significantly higher risk of LTBI than students of other health science specialties.

Resistance and Susceptibility to Mycobacterium tuberculosis Infection and Disease in Tuberculosis Households in Kampala, Uganda.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major public health problem. Household contact studies identify children and adults along the spectrum from Mtb exposure to disease. In the Kawempe Community Health Study (conducted in Kampala, Uganda), 872 culture-confirmed pulmonary TB cases and their 2,585 contacts were enrolled during 2002-2012 and followed for up to 2 years each. Risk factors identified by time-to-event analysis for secondary TB differed among children, women, and men. Younger age (P = 0.0061), human immunodeficiency virus (HIV) (P = 0.0002), thinness (P = 0.01), absent bacille Calmette-Guérin vaccination (P = 0.002), and epidemiologic risk score (P < 0.0001) were risks for children. For women, risks were HIV (P < 0.0001), thinness (World Health Organization criteria; P < 0.0001), and epidemiologic risk score (P = 0.003). For men, HIV (P = 0.0007) and low body mass index (P = 0.008) resulted in faster progression to TB. Tuberculin skin testing (TST) identified contacts with Mtb infection and those with persistently negative TST. Risks for faster time to Mtb infection were identified, and included age (P = 0.0007), baseline TST induration (P < 0.0001), and epidemiologic risk score (P < 0.0001) only in children. Those with persistently negative TST comprised 10% of contacts but had no unique epidemiologic characteristics among adults. The burden of Mtb infection and disease is high in TB households, and risk factors for progression from exposure to infection and disease differ among children, women, and men.

Follow-up of 1887 patients receiving tumor necrosis-alpha antagonists: Tuberculin skin test conversion and tuberculosis risk.

To evaluate the characteristics of patients who developed tuberculosis while receiving tumor necrosis factor-alpha (TNF-α) antagonists and the related factors with tuberculosis. Patient's demographics, tuberculin skin test (TST), isoniazid prophylaxis and type of TNF-α antagonist were recorded. TST conversion (≥5mm increase) was evaluated for patients who had baseline and 1-year TST. Files of 1887 patients who were receiving TNF-α antagonists between August 2005 and June 2015 were evaluated. TST significantly increased at the end of 1year (n=748 baseline:7.36±7.2mm vs. 1year:9.52±7.5mm, P<0.001). One-third of patients (31.2%) who had negative TST at baseline had positive TST at 1year. Tuberculosis developed in 22 patients (1.16%). The annual incidence of tuberculosis was 423/100000 patient-year. TNF-α antagonist indications were ankylosing spondylitis (n=8), inflammatory bovel diseases (n=7) and rheumatoid arthritis (n=4). Ten (45.5%) patients received infliximab, six (27.3%) patients received etanercept and six (27.3%) patients received adalimumab. Nineteen (86.4%) patients were under isoniazid prophylaxis. Twelve patients had extrapulmonary tuberculosis (54.5%; four lymph node, three pleura, two periton, one pericarditis, one intestinal, one joint). Atypical mycobacterium was detected in one patient. Adalimumab treatment (9.5× increase), male sex (15.6× increase) and previous tuberculosis disease history (11.5× increase) were risk factors for active tuberculosis. Conversion of TST was not found related with tuberculosis. Despite the high proportion of isoniazid prophylaxis, the incidence of tuberculosis in our patients receiving TNF-α antagonist was higher than the literature. Adalimumab treatment, male sex and previous tuberculosis disease history were found as risk factors for tuberculosis.

Impact of mass-screening on tuberculosis incidence in a prospective cohort of Brazilian prisoners.

BackgroundGlobally, prison inmates are a high-risk population for tuberculosis (TB), but the specific drivers of disease and impact of mass screening interventions are poorly understood.MethodsWe performed a prospective cohort study to characterize the incidence and risk factors for tuberculosis infection and disease in 12 Brazilian prisons, and to investigate the effect of mass screening on subsequent disease risk. After recruiting a stratified random sample of inmates, we administered a questionnaire to ascertain symptoms and potential risk factors for tuberculosis; performed tuberculin skin testing (TST); collected sera for HIV testing; and obtained two sputum samples for smear microscopy and culture, from participants reporting a cough of any duration. We repeated the questionnaire and all tests for inmates who remained incarcerated after 1 year. TST conversion was defined as TST ≥10 mm and an induration increase of at least 6 mm in an individual with a baseline TST <10 mm. Cox proportional hazard models were performed to identify risk factors associated with active TB. To evaluate the impact of screening on subsequent risk of disease, we compared TB notifications over one year among individuals randomized to screening for active TB with those not randomized to screening.ResultsAmong 3,771 inmates recruited, 3,380 (89.6 %) were enrolled in the study, and 1,422 remained incarcerated after one year. Among 1,350 inmates (94.9 %) with paired TSTs at baseline and one-year follow-up, 25.7 % (272/1060) converted to positive. Among those incarcerated for the year, 10 (0.7 %) had TB at baseline and 25 (1.8 %) were diagnosed with TB over the subsequent year. Cases identified through active screening were less likely to be smear­positive than passively detected cases (10.0 % vs 50.9 %; p < 0.01), suggesting early case detection. However, there was no reduction in subsequent disease among individuals actively screened versus those not screened (1.3 % vs 1.7 %; p = 0.88). Drug use during the year (AHR 3.22; 95 % CI 1.05–9.89) and knows somebody with TB were (AHR 2.86; 95 % CI 1.01–8.10) associated with active TB during one year of follow upConclusionsMass screening in twelve Brazilian prisons did not reduce risk of subsequent disease in twelve Brazilian prisons, likely due to an extremely high force of infection. New approaches are needed to control TB in this high-transmission setting.

Poor agreement between diagnostic tests for latent tuberculosis infection among HIV-infected persons in Hong Kong.

The tuberculin skin test (TST), T-Spot.TB (T-Spot) and QuantiFERON-TB Gold-In Tube (QFT) were compared in diagnosing latent tuberculosis infection (LTBI) among human immunodeficiency virus (HIV)-infected persons. Human immunodeficiency virus-infected persons without previous history of tuberculosis or LTBI were simultaneously tested by TST, T-Spot and QFT annually and followed up for tuberculosis. Among 110 HIV-infected subjects with 85% previous TST screening coverage, 75% on anti-retroviral therapy, well-preserved median CD4 count (414/μL) and low median viral load (<75/μL), baseline TST, T-Spot and QFT were positive in 5.5%, 5.6% and 4.9%, respectively, with almost complete discordance of positive results. Among 91 (83%), 66 (60%) and 26 (24%) subjects successfully undergoing the first, second and third annual retesting, TST, T-Spot and QFT were, respectively, positive in 11/123 (8.9%), 13/173 (7.5%) and 21/182 (11.5%) on retesting, with similar discordance of positive results. There was no significant association with the concurrent CD4 count or viral load. Conversion occurred in 11/123 (8.9%), 8/160 (5.0%) and 18/168 (10.7%) of TST, T-Spot and QFT, respectively, and none was associated with changes in CD4 count or viral load. More than half of the positive T-SPOT and QFT results reverted to negative on follow-up. None of these tests picked up the single case of culture-confirmed tuberculosis observed after 798 person-years of follow-up. Major discordance in positive results, high reversion rates and low tuberculosis incidence among test-positive subjects cast serious doubt on the utility of the currently available LTBI tests in the annual screening of HIV-infected persons in an intermediate tuberculosis burden area.

Discordance between Tuberculin Skin Test and Interferon Gamma Release Assay is Associated with Previous Latent Tuberculosis Infection Treatment

Background: The performance of Interferon gamma release assays (IGRA) in drug users and the impact of previous latent tuberculosis infection (LTBI) treatment on discordance of IGRA and tuberculin skin test (TST) are unclear. Objective: To determine the prevalence and incidence of LTBI using TST and Quantiferon Gold In-Tube test (QFT-G-IT) in a cohort of persons with hepatitis C virus (HCV) and drug use history. Design: Eligible participants had baseline TST and QFT-G-IT assay and were retested with QFT-G-IT after 12 months to assess prevalence and incidence of LTBI. Results: Of 193 HCV-infected persons enrolled, 162 (84%) were HIV infected; 132 (81%) were on anti-retroviral therapy and 131 (81%) had a CD4 count >200. 190 (98%) had a history of drug use; only 19 (10%) were active intravenous drug users. 55 (28.5%) had LTBI based on TST results and 13 (7%) were diagnosed with LTBI based on QFT-G-IT. 46/193 persons (23.8%) had positive TST with negative QFT-G-IT test. History of LTBI treatment was a strong predictor of this discordance (OR=41.5; 95%CI 16.2-106.7; p<0.0001). No QFT-G-IT conversions were detected among the 101 initially QFT-G-IT negative patients retested at one year (95% CI: 0-3.6%). Conclusions: Intravenous drug users who are not actively using drugs have a low prevalence and incidence of LTBI by IGRA. Previous LTBI treatment is associated with a positive TST and a concurrent negative QFT-G-IT.

Safety of the two-step tuberculin skin test in Indian health care workers

BackgroundHealth care workers (HCW) in low and middle income countries are at high risk of nosocomial tuberculosis infection. Periodic screening of health workers for both TB disease and infection can play a critical role in TB infection control. Occupational health programs that implement serial tuberculin skin testing (TST) are advised to use a two-step baseline TST. This helps to ensure that boosting of waned immune response is not mistaken as new TB infection (i.e. conversion). However, there are no data on safety of the two-step TST in the Indian context where HCWs are repeatedly exposed. Materials and methodsNursing students were recruited from 2007 to 2009 at the Christian Medical College and Hospital, Vellore, India. Consenting nursing students were screened with a baseline two-step TST at the time of recruitment. From 2007 to 2008 adverse events were recorded when reported during the TST reading (Cohort A). Nurses recruited in the final study year (2009) answered an investigator administered questionnaire assessing all likely side-effects Cohort B). This information was extracted from the case report forms and analysed. ResultsBetween 2007 and 09, 800 trainees consented to participate in the annual TB screening study and 779 did not have a past history of TB or recall a positive TST and were selected to administer TST. Of these, 755 returned for reading the result and had complete data and were included for the final analysis – 623 subjects in (cohort A) and 132 in (cohort B). These were included for the final analysis. In cohort A only 1.3% reported adverse events. In cohort B, as per the investigator administered questionnaire; 25% reported minor side effects. Itching and local pain were the most common side effects encountered. There were no major adverse events reported. In particular, the adverse events were similar in the second step of the test and not more severe. ConclusionScreening of HCWs with two-step TST for LTBI is simple and safe, and hence suitable for wide scale implementation in high-burden settings such as India.

Disseminated Tuberculosis in 2 Children With Inflammatory Bowel Disease Receiving Infliximab

Patients with inflammatory bowel disease are predisposed to opportunistic infections. We report 2 cases of disseminated tuberculosis in adolescents receiving a TNF antagonist, infliximab. Both had negative baseline tuberculin skin tests. Multimodal testing using tuberculin skin tests and interferon gamma release assays at the time of inflammatory bowel disease diagnosis and annually may increase the sensitivity of LTBI testing in these high risk children.

Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults

RationaleGlobal tuberculosis (TB) control may require mass vaccination with a new TB vaccine, such as a recombinant bacille Calmette Guerin (BCG) or attenuated Mycobacterium tuberculosis (MTB). The safety profile of live mycobacterial vaccines in latently infected adults with prior infant BCG vaccination is unknown. ObjectivesEvaluate safety and reactogenicity of BCG revaccination, with or without isoniazid (INH) pretreatment, in adults with latent MTB infection (LTBI). MethodsEighty-two healthy, HIV uninfected, South African adults, with a BCG scar and tuberculin skin test (TST) diameter ≥15mm, were randomized to receive 6 months of INH, starting either before, or 6 months after, intradermal revaccination with BCG Vaccine SSI (Statens Serum Institut, Copenhagen). Safety and reactogenicity data are reported through 3 months post BCG revaccination. ResultsBaseline characteristics were similar between treatment arms. Mean baseline TST diameter was 20±4mm. Seventy-two subjects received BCG revaccination. Injection site erythema (68%) and induration (86%) peaked 1 week after revaccination. Ulceration (76%) peaked at 2 weeks, and resolved by 3 months in all but 3 subjects. Diameter of ulceration was >10mm in only 8%, but a residual scar was common (85%). No regional lymphadenitis or serious morbidity related to BCG was seen. Reactogenicity was not affected by INH pretreatment. ConclusionBCG revaccination of MTB infected adults is safe, well tolerated, and reactogenicity is similar to that of primary BCG vaccination. Clinical trials of live recombinant BCG or attenuated MTB vaccines may be considered in latently infected adults, with or without INH pretreatment (ClinicalTrials.gov identifier: NCT01119521).

Compliance with Postexposure Screening and Treatment of Latent Tuberculosis Infection among Healthcare Workers in a Tertiary Care Hospital in Saudi Arabia

Controlling tuberculosis (TB) infection among occupationally exposed healthcare workers (HCWs) may be challenging. We retrospectively reviewed clinical records of HCWs who were exposed to patients diagnosed with infectious TB at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between 2008 and 2010. The collected data included baseline tuberculin skin test (TST) status, potential predictors of TST positivity, postexposure diagnosis of latent TB infection (LTBI), and postexposure compliance with LTBI therapy. Thirteen patients were diagnosed with infectious pulmonary TB during the study period. A total of 298 HCWs met our definition for exposure. Exposed HCWs tended to be female (62.9%), non-Saudi (83.9%), nurses (68.6%), or respiratory therapists (24.0%) working in critical care locations (72.8%). Baseline (preemployment) TST documentation existed for 41.3% (123/298). Among those with documented baseline TSTs, 51.2% (63/123) were positive, representing 21.1% (63/298) of all HCWs. Only 48.9% (115/235) of exposed HCWs who had negative or unknown preexposure TST status had their TST tested after exposure. Approximately 46.1% (53/115) of them were diagnosed with postexposure LTBI, and 92.5% (49/53) of them were prescribed LTBI therapy. Among those, 93.9% (46/49) started LTBI therapy; however, 82.6% (38/46) failed to complete the recommended course. We found low rates of baseline TST documentation and postexposure screening among exposed HCWs. Compliance with initiating postexposure isoniazid prophylaxis among HCWs was fair, but only a small fraction of those who started prophylaxis completed the recommended course of therapy. These findings suggest substantial opportunities to implement administrative measures to enhance LTBI management among HCWs.

TB Incidence in an Adolescent Cohort in South Africa

BackgroundTuberculosis (TB) is a major public health problem globally. Little is known about TB incidence in adolescents who are a proposed target group for new TB vaccines. We conducted a study to determine the TB incidence rates and risk factors for TB disease in a cohort of school-going adolescents in a high TB burden area in South Africa.MethodsWe recruited adolescents aged 12 to 18 years from high schools in Worcester, South Africa. Demographic and clinical information was collected, a tuberculin skin test (TST) performed and blood drawn for a QuantiFERON TB Gold assay at baseline. Screening for TB cases occurred at follow up visits and by surveillance of registers at public sector TB clinics over a period of up to 3.8 years after enrolment.ResultsA total of 6,363 adolescents were enrolled (58% of the school population targeted). During follow up, 67 cases of bacteriologically confirmed TB were detected giving an overall incidence rate of 0.45 per 100 person years (95% confidence interval 0.29–0.72). Black or mixed race, maternal education of primary school or less or unknown, a positive baseline QuantiFERON assay and a positive baseline TST were significant predictors of TB disease on adjusted analysis.ConclusionThe adolescent TB incidence found in a high burden setting will help TB vaccine developers plan clinical trials in this population. Latent TB infection and low socio-economic status were predictors of TB disease.