Tuberculin Skin Test Reactivity Research Articles

A-285 Performance Evaluation of LIAISON® QuantiFERON®-TB Gold Plus Assay and Its Use in Long-Term Care Facilities

Abstract Background Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis with 7860 cases reported in 2021 in the United State and estimated 13 million people are living with Latent TB infection (LTBI); Early detection of TB infection is crucial to prevent the spread of the disease; there are two types of tests for TB and LTBI: Tuberculin Skin Test (TST) and Interferon-Gamma Release Assay (IGRA). Although TST has good sensitivity but false-negative reactions occur in certain population and the specificity of is decreased among persons with prior Bacillus Calmette-Guérin (BCG) vaccination, especially those vaccinated post-infancy and those with repeat vaccination. Similarly, persons living in areas where nontuberculous mycobacteria are common are at increased risk of having false-positive TST reactions. IGRA is blood-based laboratory test that measures responses to TB-specific peptide antigens in whole blood. Like the tuberculin skin test (TST), it is an indirect test for M. tuberculosis infection, but is more specific than TST and is unaffected by prior BCG vaccination and most environmental mycobacterial infections. Methods The LIAISON® QuantiFERON®-TB Gold Plus assay is an in vitro diagnostic test for the detection of interferon-γ (IFN-γ) in human lithium heparin plasma by chemiluminescence immunoassay (CLIA) using the LIAISON ® XL Analyzer. The clinical specificity and sensitivity were 96.9% and 84.4% respectively. Clinical studies have shown Positive Percent Agreement (PPA) of 97.4% and Negative Percent Agreement (NPA) of 98.6%. We evaluated the precision, reproducibility, and correlated patient results to our reference lab results. 452 samples collected from Long-Term Care facilities resident were run over 9 months. Statistical analyses were done using Analyse-it. Results The percentage agreement for precision, reproducibility, and accuracy were 100%. The correlation with the reference laboratory was 100% agreement. We found 14.8% of samples tested were positive, 83.2% were negative and 2.0% were indeterminate. Conclusion The LIAISON® QuantiFERON®-TB Gold Plus assay offers the benefit of a fully automated with high sensitivity and specificity. The faster turnaround will aid the physician in the diagnosing M. tuberculosis, eliminates the need for two-step testing, and is preferred in patients who received BCG vaccination. In addition, with the growing geriatric population, the availability of this test will give the physician the opportunity to follow the 2016 American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA)/CDC clinical practice guidelines for using IGRAs in older patients.

Differentially expressed transcript isoforms associate with resistance to tuberculin skin test and interferon gamma release assay conversion.

A mechanistic understanding of uncommon immune outcomes such as resistance to infection has led to the development of novel therapies. Using gene level analytic methods, we previously found distinct monocyte transcriptional responses associated with resistance to Mycobacterium tuberculosis (Mtb) infection defined as persistently negative tuberculin skin test (TST) and interferon gamma release assay (IGRA) reactivity among highly exposed contacts (RSTR phenotype). Using transcript isoform analyses, we aimed to identify novel RSTR-associated genes hypothesizing that previous gene-level differential expression analysis obscures isoform-specific differences that contribute to phenotype. Monocytes from 49 RSTR versus 52 subjects with latent Mtb infection (LTBI) were infected with M. tuberculosis (H37Rv) or left unstimulated (media) prior to RNA isolation and sequencing. RSTR-associated gene expression was then identified using differential transcript isoform analysis. We identified 81 differentially expressed transcripts (DETs) in 70 genes (FDR <0.05) comparing RSTR and LTBI phenotypes with the majority (n = 79 DETs) identified under Mtb-stimulated conditions. Seventeen of these genes were previously identified with gene-level bulk RNAseq analyses including genes in the IFNγ response that had increased expression among LTBI subjects, findings consistent with a clinical phenotype based on IGRA reactivity. Among the subset of 23 genes with positive differential expression among Mtb-infected RSTR monocytes, 13 were not previously identified. These novel DET genes included PDE4A and ZEB2, which each had multiple DETs with higher expression among RSTR subjects, and ACSL4 and GAPDH that each had a single transcript isoform associated with RSTR. Transcript isoform-specific analyses identify transcriptional associations, such as those associated with resistance to TST/IGRA conversion, that are obscured when using gene-level approaches. These findings should be validated with additional RSTR cohorts and whether the newly identified candidate resistance genes directly influence the monocyte Mtb response requires functional study.

A retrospective analysis of the tuberculin skin test reactions of a single source population of Mauritian Macaca fascicularis held in quarantine during 2017.

A published range of reactions to the tuberculin skin test (TST) using mammalian (human) old tuberculin (MOT) in a population of Mauritius origin Macaca fascicularis in US laboratory animal medicine does not exist. The objectives of this report are to quantify the reactions among juvenile, adolescent, and male adult cynomolgus macaques and to provide the laboratory animal medicine practitioner with a reference range of reactions to MOT in Mauritian juvenile macaques. Monkeys in a US foreign animal quarantine must be tested negative for mycobacterial infection including Mycobacterium tuberculosis (Mtb) using MOT as required by the CDC Division of Global Migration and Quarantine. The TST relies on visual observation post injection of an individual animal’s reaction or nonreaction. During 2017, 933 Mauritius origin macaques from one supplier were quarantined in nine separate cohorts in our facility. 848 or > 90% of the animals were juveniles between 1.5 to 3 years of age, comprised of 425 males and 423 females. The population also included 46 adolescents (21 males, 25 females) and 39 adult males. A total of 33 TST sets were performed on the nine cohorts, resulting in 3418 individual TSTs being administered. 1595 (46.6%) injections were made in juvenile males and 1529 (44.7%) in juvenile females. A total of 172 reactions to the TST were recorded at the final assessment completed at the 72-hour post injection time point from all animal ages and sexes. 162 reactions (94.2% of all reactions) occurred in juvenile animals, consisting of 96 bruises (59.3% of all juvenile reactions) in males and 58 bruises (35.8% of all juvenile reactions) in females. Bruising was the most common reaction in juvenile animals and in all animals regardless of age or sex. Bruising occurred within all 33 TST sets ranging from a low of 0% to a high of 30% in male juveniles and a low of 0% to a high of 17% in female juveniles. Bruising was the only finding in the adolescents and adult males. Erythema was observed only in juvenile animals, two males and three females. Generalized eyelid edema was observed only in juvenile animals, one male and one female. These animals had concurrent erythema in the affected eyelid. Animals with generalized eyelid edema and erythema are considered suspect for active tuberculosis and warrant further diagnostics. In this report, the most observed reaction among all age groups and sexes was bruising. Erythema and edema were rarely observed. Only juvenile animals were observed with either erythema, edema or both.

Strong tuberculin response after BCG vaccination is associated with low multiple sclerosis risk: a population-based cohort study.

BackgroundMultiple sclerosis (MS) is characterized by inflammatory lesions in the central nervous system involving pro-inflammatory T-cells. Immune dysregulation is well described in prevalent disease, but it is not known whether this precedes disease development. Bacillus Calmette–Guérin (BCG) vaccination ameliorates MS-like disease in mice. In people vaccinated with BCG, the tuberculin skin test (TST) offers a standardized measure of a T-cell-mediated immune response. We therefore hypothesized that the strength of the TST response after BCG vaccination is associated with subsequent MS risk.MethodsUsing data from a Norwegian tuberculosis screening programme (1963–1975), we designed a population-based cohort study and related the size of TST reactions in individuals previously vaccinated with BCG to later MS disease identified through the Norwegian MS registry. We fitted Cox proportional hazard models and flexible parametric survival models to investigate the association between TST reactivity, MS risk and its temporal relationship.ResultsAmong 279 891 participants (52% females), 679 (69% females) later developed MS. Larger TST reactivity was associated with decreased MS risk. The hazard ratio for MS per every 4-mm increase in skin induration size was 0.86 (95% confidence interval 0.76–0.96) and similar between sexes. The strength of the association persisted for >30 years after the TST.ConclusionA strong in vivo vaccine response to BCG is associated with reduced MS risk >30 years later. The immunological mechanisms determining TST reactivity suggest that skewed T-cell-mediated immunity precedes MS onset by many decades.

COVID-19 and Beyond: Exploring Public Health Benefits from Non-Specific Effects of BCG Vaccination.

Bacille Calmette–Guérin (BCG) vaccination, widely used throughout the world to protect against infant tuberculous meningitis and miliary tuberculosis (TB), can provide broad non-specific protection against infectious respiratory diseases in certain groups. Interest in BCG has seen a resurgence within the scientific community as the mechanisms for non-specific protection have begun to be elucidated. The impact of the COVID-19 pandemic on nearly every aspect of society has profoundly illustrated the pressure that respiratory infections can place on a national healthcare system, further renewing interest in BCG vaccination as a public health policy to reduce the burden of those illnesses. However, the United States does not recommend BCG vaccination due to its variable effectiveness against adult TB, the relatively low risk of Mycobacterium tuberculosis infection in most of the United States, and the vaccine’s interference with tuberculin skin test reactivity that complicates TB screening. In this review, we explore the broad immune training effects of BCG vaccination and literature on the effects of BCG vaccination on COVID-19 spread, disease severity, and mortality. We further discuss barriers to scheduled BCG vaccination in the United States and how those barriers could potentially be overcome.

Comparing Tuberculin Anergy Skin Test Reactions and Lymphoblastic Transformation in Medical Student

Background: Tuberculin Skin Test (TST) reaction is an accepted screening test for diagnosing acute and latent Tuberculosis (TB) infection among at-risk populations. It is performed with a standard Protein Purified Derivative (PPD) solution. The skin reaction of PPD is unreliable to distinguish natural infection from the Bacillus Calmette Guerin (BCG) effect. The present survey aimed to determine the prevalence of Tuberculin Anergy (TA) reactions among medical students. Accordingly, we evaluated its sensitivity, specificity, and efficiency by applying the Recall Panel Antigen Test (RPAT) and the Lymphoblastic Transformation Test (LTT). Methods: The participants were sequentially enrolled in this study according to the designed protocol. The current study was conducted on healthy medical students before registering for the hospital training course. All research subjects were healthy, having a cicatrix of Bacillus Calmette Guerin (BCG) vaccination on the arm, and at a young age (20-24 years). Results: In total, 180 medical students met the inclusion criteria of the study. The study subjects’ Mean±SD age was 22±3.07 years (male=89, female=91). Moreover, 75 (42%) subjects presented a TA reaction in the first step of TST screening. Furthermore, 13 (64%) individuals presented a negative result of the RPAT. The sensitivity and specificity of the TST reactions, compared with the LTT were 100% and 94.4 %, respectively. Conclusion: Significant TA reactions were found among medical students with positive cicatrix post-vaccinated. The obtained data suggested that the BCG protection for individuals may be decreased as time expired. Consequently, the medical students will especially be at high risk for TB infection during the clinical training course. The collected data highlighted the patient-safety from the viewpoint of forensic medicine.

Neonatal Bacille Calmette-Guérin vaccination and tuberculin skin test reactions at 2- and 6-months: Effects on mortality up to 1 year of age

BackgroundIn randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies. MethodsObservational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002–04, 2009–2013 and 2014–18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between TSTs > 1 mm (reactors) vs. ≤ 1 mm (non-reactors) and subsequent mortality risk up to age 12 months in Cox-models providing Mortality Rate Ratios (MRRs). We searched PubMed for studies to calculate meta-estimates of the association between TST reactivity by age 2- and 6-months and all-cause mortality. ResultsLarge post-vaccination wheal size was associated with 6-month TST positivity and so was receiving BCG-Denmark or BCG-Japan, compared with BCG-Russia. By age 2 months, 22% (302/1389) of infants were TST reactors with a 2–12-month mortality risk of 1.7% (5/302) vs. 3.3% (36/1087) for non-reactors, the corresponding reactor/non-reactor MRR = 0.49 (0.19–1.26). By age 6 months, 44% (1149/2635) of infants were reactors and the 6–12-month mortality risk was 0.4% (4/1149) vs. 0.6% (9/1486) for non-reactors, the MRR = 0.87 (0.27–2.86). The literature search provided 3 studies. The meta-analysis revealed a uniform pattern of reduced mortality associated with TST reactivity, a TST response by 2 months being associated with an MRR of 0.59 (0.39–0.90); for 6-month TST responses the MRR was 0.65 (0.43–1.00). ConclusionAmong BCG-vaccinated infants, TST reactions were associated with markedly reduced mortality. Improved vaccination technique and using certain BCG strains could lead to a higher TST reaction prevalence, which would enhance BCG’s beneficial non-specific effects.

Mültecilerin kabulünden sonra bir referans çocuk hastanesinde çocukluk çağı tüberkülozu

Aim: We aimed to evaluate epidemiologic, clinical, laboratory, microbiologic features, treatment and outcomes of pediatric tuberculosis (TB) patients also to draw attention to immigrant patients.&#x0D; Material- Methods: We retrospectively conducted the medical records of children below 18 years of age with TB between January 2015 and September 2016. &#x0D; Results: A total of 20 TB patients (35% were Syrian refugees, total 65% female) with a median age of 135.5±52.6 months were evaluated. Fourteen (70%) patients were adolescent. The history of contact with an active TB disease patient was found in seven (35%) patients. Four (20%) patients had no complaint at admission whereas the most common symptom was prolonged cough &gt; 2 weeks. Fifteen (75%) patients had a Bacillus Calmette–Guérin scar on the left shoulder. A total of 16 (80%) patients had a positive tuberculin skin test (TST) result. Microbiological confirmation was provided in four (20%) patients totally. The most common chest X-ray findings on admission were hilar lymphadenopathy. Ten (50%) patients had normal chest X-ray and were diagosed with abnormal thorax tomography findings. All of the patients were treated succesfully except one Syrian patients with miliary TB who died.&#x0D; Conclusion: Microbiological confirmation of childhood TB may be absent and the diagnosis can be confirmed in the light of contact history, positive TST reaction, compatible symtomps and radiological evidence. Particular attention might be paid to Syrian refugees, taking into epidemiological characteristics of TB disease and the density of immigrants in the place we live in.

Prevalence of Bovine Tuberculosis in Sheep at Sadar and Parbatipur Upazila under Dinajpur District in Bangladesh

Tuberculosis is Zoonotic disease and infected animals continue to spread the disease to other animals and humans by excreting the germs in milk, meat, feces, and respiratory droplets, this study used bPPD (Bovine purified protein derivative) to observe TST (Tuberculin skin test) reactivity in the Sheep population in the Sadar and Parbatipur Upazilas of Dinajpur District. The research conducted from January to June of 2018. There is no history for sheep tuberculosis in the study area. Overall, 5 percent (7/140) of 140 sheep were positive, 15% (21/140) were doubtful, and 80% (112/140) were negative based on sex, age, breed, and body condition score, while lactation stage and reproduction status prevalence was 6.4 percent, 14.9 percent, and 78.7% positive, doubtful, and negative, respectively. Our findings suggest the presence of a skin test reaction response when employing the bPPD reagent, but this needs to be validated by pathological and serological techniques. Nevertheless, my preliminary investigation suggests that abattoirs must implement effective control systems and raise public awareness.

An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa.

BackgroundMycobacterium tuberculosis (Mtb) infection is inferred from positive results of T-cell immune conversion assays measuring Mtb-specific interferon gamma production or tuberculin skin test (TST) reactivity. Certain exposed individuals do not display T-cell immune conversion in these assays and do not develop TB. Here we report a hitherto unknown form of this phenotype: HIV-1-positive persistently TB, tuberculin and IGRA negative (HITTIN).MethodsA community-based case-control design was used to systematically screen and identify adults living with HIV (HIV+), aged 35–60 years, who met stringent study criteria, and then longitudinally followed up for repeat IGRA and TST testing. Participants had no history of TB despite living in TB hyper-endemic environments in Cape Town, South Africa with a provincial incidence of 681/100,000. Mtb-specific antibodies were measured using ELISA and Luminex.FindingsWe identified 48/286 (17%) individuals who tested persistently negative for Mtb-specific T-cell immunoreactivity (three negative Quantiferon results and one TST = 0mm) over 206±154 days on average. Of these, 97·2% had documented CD4 counts<200 prior to antiretroviral therapy (ART). They had received ART for 7·0±3·0 years with a latest CD4 count of 505·8±191·4 cells/mm3. All HITTIN sent for further antibody testing (n=38) displayed Mtb-specific antibody titres.InterpretationImmune reconstituted HIV+ persons can be persistently non-immunoreactive to TST and interferon-γ T-cell responses to Mtb, yet develop species-specific antibody responses. Exposure is evidenced by Mtb-specific antibody titres. Our identification of HIV+ individuals displaying a persisting lack of response to TST and IGRA T-cell immune conversion paves the way for future studies to investigate this phenotype in the context of HIV-infection that so far have received only scant attention.

Prevalence of and risk factors associated with latent tuberculosis infection in a Latin American region

Tuberculosis (TB) represents a health problem in Colombia, and its control is focused on the search for contacts and treatment of TB cases underscoring the role of latent tuberculosis infection (LTBI) as a reservoir of Mycobacterium tuberculosis. The burden of LTBI in Colombia is unknown. We aimed to estimate the prevalence of LTBI and identify the associated risk factors. In this cross-sectional study, we recruited participants from four health care centers in Cali, Colombia. The participants were eligible if they were aged between 14 and 70 years, and all participants answered a survey evaluating their medical history and sociodemographic and lifestyle factors. LTBI status was based on tuberculin skin test (TST) positivity using two thresholds: ≥10 mm (TST-10) and ≥15 mm (TST-15). The magnitude of the associations between independent factors and dependent outcomes (LTBI status and TST induration) were evaluated by logistic regression and generalized linear models, respectively. A total of 589 individuals were included with TST positivity rates of 25.3% (TST-10) and 13.2% (TST-15). Logistic regression showed that being between age 40 and 69 years (OR = 7.28, 95% CI [1.62–32.7]), being male (OR = 1.71, 95% CI [1.04–2.84]), being employed (OR = 1.56, 95% CI [1.02–2.38]), and having a low intake of alcohol (OR = 2.40, 95% CI [1.13–5.11]) were risk factors for TST positivity, while living in the north zone (OR = 0.32, 95% CI [0.18–0.55]), living in the suburb zone (OR = 0.28, 95% CI [0.15–0.52]) and having a secondary education (OR = 0.49 95% CI [0.29–0.83]) lowered the risk of TST positivity. The generalized linear model showed that the previous predictors, as well as a low body mass index, had an effect on TST reaction size. The LTBI prevalence found in the population was moderate, reflecting the continuous transmission of M. tuberculosis. Social factors seem to play a decisive role in the risk of LTBI. Employed males, who are over 40 years of age, are overweight, have a lower level of education and have a low intake of alcohol (50–100 mL, once/week) should be a priority group for prophylactic treatment as a strategy for TB control in this city.

Tuberculosis Skin Test Screening in the National Tuberculosis Program of Trinidad and Tobago.

Globally, a quarter of the population is infected with tuberculosis (TB), caused by Mycobacterium tuberculosis. About 5–10% of latent TB infections (LTBI) progress to active disease during the lifetime. Prevention of TB and treating LTBI is a critical component of the World Health Organization’s (WHO) End TB Strategy. This study aims to examine the screening practices for prevention and treatment employed by the National Tuberculosis Program of Trinidad and Tobago in comparison to the WHO’s standard guidelines. A cross-sectional retrospective study was conducted from the TB registers (2018–2019) for persons aged 18 years and above with recorded tuberculin skin test reactions (TST). Bivariate comparisons for categorical variables were made using Chi-square or Fisher’s exact test. Binary logistic regression was used for exploring predictors of TST positivity with adjustment for demographic confounders in multivariable models. Of the total 1972 eligible entries studied, 384 (19.4%) individuals were tested positive with TST. TB contact screening (aOR 2.49; 95% CI 1.65, 3.75) and Bacillus Calmette–Guerin (BCG) vaccination status (aOR 1.66; 95% CI, 1.24 to 2.22) were associated with a positive TST reaction, whereas, preplacement screening failed to show such association when compared to those screened as suspect cases. The findings suggest that TB contact screening and positive BCG vaccination status are associated with TST positivity independent of age and gender.

Performance and correlation of QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test in young children with tuberculosis exposure or tuberculosis disease

Objective: To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children. Methods: A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis. QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test were performed in each patient. Results: Of the 60 children, median age 3.3 years, 17 had tuberculosis and 43 had recent tuberculosis exposure. Overall, 15 (25.0%) children had tuberculin skin test reaction ≥ 10 mm; 8 (13.3%) were positive by QuantiFERON-TB Gold In-Tube test, and 12 (20.0%) by T-SPOT.TB. Nineteen (31.7%) children had at least one positive test. There was a moderate agreement between interferon gamma release assays and tuberculin skin test. Conclusions: The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis, supporting the management strategy without testing in children younger than 5 years.

Tuberculin skin test reaction depends on type of purified protein derivative: implications for cut-off values.

SETTING: Due to purified protein derivative (PPD) RT23 stock-outs in 2014, PPD-Tubersol and PPD-Bulbio have been used for latent tuberculosis infection (LTBI) testing in the Netherlands.OBJECTIVE: To determine whether PPD-RT23, PPD-Tubersol and PPD-Bulbio were associated with differential indurations and confirmation using interferon-gamma release assays (IGRAs).DESIGN: LTBI surveillance data from 2013 to 2016 were extracted. Regression analyses were used to determine whether IGRA confirmation of TST-positive indurations depended on PPD, controlling for sex, age, incidence in country of origin, and bacille Calmette-Guérin (BCG) status.RESULTS: A total of 20 956 individuals were tested with PPD-RT23: 10 382 with PPD-Tubersol and 18 562 with PPD-Bulbio. Overall, 21% with PPD-Bulbio had an induration of ≥5 mm compared to 12% of those tested with PPD-RT23 and PPD-Tubersol. Compared to PPD-RT23, PPD-Bulbio indurations ≥5 mm were significantly less often IGRA-confirmed among contacts (aOR 1.3, 95% CI 1.1-1.6) and BCG-vaccinated immigrants (PPD-RT23, aOR 2.4, 95% CI 1.4-4.1). Increasing the PPD-Bulbio cut-off from ≥5 to ≥10 mm would save respectively 26%, 42%, and 35% of IGRAs among contacts, health care workers (HCWs) and BCG-vaccinated immigrants, with small absolute numbers of positive IGRAs missed (range 0-55 annually).CONCLUSION: PPD-Bulbio shows larger TST indurations than other PPDs, but is less often IGRA-confirmed. Increasing the TST cut-off from 5 to 10 mm prior to testing with an IGRA in HCWs and immigrants is recommended.

Healthcare facility-based strategies to improve tuberculosis testing and linkage to care in non-U.S.-born population in the United States: A systematic review.

ContextAn estimated 21% of non-U.S.-born persons in the United States have a reactive tuberculin skin test (TST) and are at risk of progressing to TB disease. The effectiveness of strategies by healthcare facilities to improve targeted TB infection testing and linkage to care among this population is unclear.Evidence acquisitionFollowing Cochrane guidelines, we searched several sources to identify studies that assessed strategies directed at healthcare providers and/or non-U.S.–born patients in U.S. healthcare facilities.Evidence synthesisSeven studies were eligible. In a randomized controlled trial (RCT), patients with reactive TST who received reminders for follow-up appointments were more likely to attend appointments (risk ratio, RR = 1.05, 95% confidence interval 1.00–1.10), but rates of return in a quasi-RCT study using patient reminders did not significantly differ between study arms (P = 0.520). Patient-provider language concordance in a retrospective cohort study did not increase provider referrals for testing (P = 0.121) or patient testing uptake (P = 0.159). Of three studies evaluating pre and post multifaceted interventions, two increased TB infection testing (from 0% to 77%, p < .001 and RR 2.28, 1.08–4.80) and one increased provider referrals for TST (RR 24.6, 3.5–174). In another pre-post study, electronic reminders to providers increased reading of TSTs (RR 2.84, 1.53–5.25), but only to 25%. All seven studies were at high risk of bias.ConclusionsMultifaceted strategies targeting providers may improve targeted TB infection testing in non-U.S.-born populations visiting U.S. healthcare facilities; uncertainties exist due to low-quality evidence. Additional high-quality studies on this topic are needed.

Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials

BackgroundAdolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations.MethodsAdolescents aged 12–18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive.ResultsOf 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2–35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2–3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3).ConclusionWe conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

The association between tuberculin skin test result and active tuberculosis risk of college students in Beijing, China: a retrospective cohort study

BackgroundAbout 10% latent tuberculosis infections (LTBI) would progress to active tuberculosis (TB), if left prophylactic therapy. Tuberculin skin test (TST) is the most widely used method for LTBI screening in the school of China. However, for college students, the association between TST reaction size and active TB risk was unclear.MethodsWe conducted a retrospective study to assess whether the TST reaction size would predict active TB during the next two years after TST screening for college students. Multivariable Cox regression was performed to identify the size of TST reaction and other factors associated with active TB risk.ResultsA total of 67292 college students in Beijing, China were included in this study; 8021 (11.92%) individuals were TST positive (≥10 mm), and 3879 (5.76%) of them were strong TST positive (≥15 mm). During the two years of follow-up, 26 active TB cases were reported in 134575 person-years with an incidence rate of 19.32 (95% CI: 12.61–28.32) per 100000 person-years. The adjusted hazard ratios (HR) (95% CI) were 1.094 (0.247~4.846), 3.644 (1.188~11.179), 6.832 (2.436~19.163) and 9.768 (2.203~43.315) of cohorts with the TST reaction size intervals 5~9, 10~14, 15~20 and ≥ 20 mm, respectively, compared to cohort with interval 0~4 mm. Besides, the adjusted HR (95% CI) was 3.593 (1.354~9.537) of males compared to females.ConclusionsThis study indicated that the risk of active TB increased in college students when the TST reaction size was ≥10 mm, and males had a higher risk compared to females.

Effect of neonatal bacille Calmette-Guérin on the tuberculin skin test reaction in the first 2 years of life.

Latent tuberculous infection (LTBI) is an important reservoir of disease reactivation that is sufficient to generate new cases for decades. The tuberculin skin test (TST) is an important tool to diagnose LTBI; however, neonatal bacille Calmette-Guérin (BCG) vaccination may impact interpretation of TST data. To analyse the effect of the neonatal BCG vaccine on TST reaction in the first 2 years of life in children with no identified contact with tuberculosis (TB). This was a cross-sectional study in children up to 2 years of age who received neonatal BCG vaccination. In the absence of baseline comorbidities or contact with the bacillus, the children were given the TST. Seventy-nine children participated in the study. A decline in TST reactivity was observed in the first 12-24 months of age in patients who had been vaccinated with neonatal BCG but with no contact with TB. After the age of 10 months, no patient showed a TST reaction of >5 mm. BCG had low impact on the TST in children with no TB contact. This finding suggests the need to reassess the cut-off point to 5 mm of induration to improve TST specificity in LTBI identification.

Prevalence of Latent Tuberculosis Infection (LTBI) among Health Care Workers at Al-Thawrah Modern General Hospital, Sana’a-Yemen 2016

Objective: To determine the prevalence of latent tuberculosis infection among Healthcare Workers (HCWs) in Al- Thawra Modern General Hospital. Methods: We carried out cross sectional study to determine the prevalence of Latent Tuberculosis Infection (LTBI) among HCW. Two-steps Tuberculin Skin Test (TST) was performed among health care workers (HCWs) in Al -Thawra Modern General Hospital (TMGH) Sana'a- Yemen during the year 2016. We included all health care workers in the hospital. Out of 466 total HCWs 426 were fulfilled the inclusion criteria. Questionnaire was distributed to HCWs and information related to demographic data, profession, and duration of work, individual and in the family history of Tuberculosis (TB) was recorded. TST was done by a single investigator using the standard Mantoux test. The reaction was read 48 to 72 hours after injection, and the widest axis of indurations was measured by a standardized palpation method. Those with negative result were advised to come, after1- 2 weeks for second step TST. Results: The total number of health workers in the hospital were 466, Eligible cases who fulfilled the including criteria were 426. The remaining either excluded or not present at the time of study. Of them 232 (54.5%) were males and 194 (45.5 %), were females with a ratio of 1.2:1.269 (70%) were positive for TST. The positive result was highest among radiology assistant and laboratory worker represented 91%, 80% respectively, while 76% of doctors found positive for TST. There was an increase in TST reactivity with an older age, and there is a positive correlation between work duration and TST reaction. Conclusion: Latent tuberculosis infection is prominent among HCW who work in high-risk departments. This suggests that some TBI develops via in-hospital infection

Risk of Tuberculosis Infection among Healthcare Workers in a Tertiary Care Hospital in Bengaluru City.

Introduction:Tuberculosis (TB) is an airborne communicable disease caused by Mycobacterium tuberculosis. Infection is most likely to occur when an individual is exposed to someone with pulmonary TB on a day-to-day basis, such as by living or working in close quarters with someone who has an active disease. This study was undertaken using reliable screening and investigation tools for assessing the incident latent tuberculosis infection (LTBI) among healthcare workers (HCWs).Methodology:This descriptive longitudinal study was conducted among 600 HCWs at a tertiary care hospital in Bengaluru city for a period of 1 year 4 months (March 2016–June 2017). All HCWs were stratified according to their work profile as doctors, nurses, laboratory technicians, nursing aides, pharmacists, laundry workers (only those who come in contact with patients), dietary workers (only those who come in contact with patients), and workers from housekeeping department. Study subjects were enrolled in proportion to their population size. The data were collected by administering TB screening questionnaire and performing tuberculin skin test (TST). All the subjects who had negative TST reaction were followed up after 1 year from March 2017 to June 2017.Results:The study subjects consisted of 600 HCWs with a mean age of 27.8 ± 7.1 years. Initially, 600 study subjects underwent TST, 2 of whom were not contactable between 48 and 72 h of test administration. Of the remaining 598 subjects, 120 (20.1%) had a positive TST reaction. After 1 year, of the 478 subjects who tested negative, 345 study subjects underwent the repeat TST and 67 (19.4%) of the study subjects had a positive TST reaction.Conclusion:The prevalence of LTBI was 20.1% and it was significantly associated with age, place of residence, education, work commute time, and mode of transport. The incidence of LTBI was 19.4% and it was significantly associated with gender, place of residence, education, work commute time, and marital status.