Previous BCG Vaccination Research Articles

Safety of BCG vaccination and revaccination in healthcare workers

ABSTRACT BCG vaccination and revaccination are increasingly being considered for the protection of adolescents and adults against tuberculosis and, more broadly, for the off-target protective immunological effects against other infectious and noninfectious diseases. Within an international randomized controlled trial of BCG vaccination in healthcare workers (the BRACE trial), we evaluated the incidence of local and serious adverse events, as well as the impact of previous BCG vaccination on local injection site reactions (BCG revaccination). Prospectively collected data from 99% (5351/5393) of participants in Australia, Brazil, Spain, The Netherlands and the UK was available for analysis. Most BCG recipients experienced the expected self-limiting local injection site reactions (pain, tenderness, erythema, swelling). BCG injection site itch was an additional common initial local symptom reported in 49% of BCG recipients. Compared to BCG vaccination in BCG-naïve individuals, BCG revaccination was associated with increased frequency of mild injection site reactions, as well as earlier onset and shorter duration of erythema and swelling, which were generally self-limiting. Injection site abscess and regional lymphadenopathy were the most common adverse events and had a benign course. Self-resolution occurred within a month in 80% of abscess cases and 100% of lymphadenopathy cases. At a time when BCG is being increasingly considered for its off-target effects, our findings indicate that BCG vaccination and revaccination have an acceptable safety profile in adults.

Previous BCG vaccination is associated with less severe clinical progression of COVID-19

BackgroundBCG vaccination, originally used to prevent tuberculosis, is known to “train” the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19MethodsA case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of “severe” above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis.ResultsBCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74–93%) in subjects aged 60 or less and 35% (95% CI − 44–71%) in older subjects.ConclusionsThis protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

Characteristics and factors associated with COVID-19-related deaths in Africans

Background: COVID-19 is a disease of public health importance that is highly transmissible and associated with significant morbidity and mortality. There has been concern that the pandemic will result in mass deaths in Africa as a result of the weak health system and insecurity on the continent. However, the evidence available did not support the assumption. Aims &amp; Objectives: This communication presents a systematic review on factors associated with low COVID-19 related mortality in Africa. Materials and Methods: We searched the Google scholar, MEDLINE, Embase, Publius Ovidius Naso and Cochrane databases for all studies on COVID-19 related deaths in Africa published in English language from December 2019 to January, 2021. The references of relevant articles were also searched for additional publications. Data from the studies were independently extracted and assessed by the three authors using a standardised form. There was consensus among the authors on the selected studies used in this review. Results: Twenty-one studies were identified and independently assessed based on the objectives of the study by the authors. All the studies presented at least a factor that could possibly be associated with low death rate from COVID-19 in Africa. Conclusion: Younger population age, cross and herd immunities, previous BCG vaccination, relative hot climatic advantage, community practice and dominance of blood group O were main factors suggested to be associated with low mortality rate from the pandemic in Africa.

In-vivo expressed Mycobacterium tuberculosis antigens recognised in three mouse strains after infection and BCG vaccination

Novel tuberculosis (TB)-vaccines preferably should (i) boost host immune responses induced by previous BCG vaccination and (ii) be directed against Mycobacterium tuberculosis (Mtb) proteins expressed throughout the Mtb infection-cycle. Human Mtb antigen-discovery screens identified antigens encoded by Mtb-genes highly expressed during in vivo murine infection (IVE-TB antigens). To translate these findings towards animal models, we determined which IVE-TB-antigens are recognised by T-cells following Mtb challenge or BCG vaccination in three different mouse strains. Eleven Mtb-antigens were recognised across TB-resistant and susceptible mice. Confirming previous human data, several Mtb-antigens induced cytokines other than IFN-γ. Pulmonary cells from susceptible C3HeB/FeJ mice produced less TNF-α, agreeing with the TB-susceptibility phenotype. In addition, responses to several antigens were induced by BCG in C3HeB/FeJ mice, offering potential for boosting. Thus, recognition of promising Mtb-antigens identified in humans validates across multiple mouse TB-infection models with widely differing TB-susceptibilities. This offers translational tools to evaluate IVE-TB-antigens as diagnostic and vaccine antigens.

A Survey Among Italian Physicians During COVID-19 Outbreak. Could Bacillus Calmette-Guérin Vaccine Be Effective Against SARS-CoV2?

Background: Epidemiological studies show that BCG-vaccinated population seems to be more likely protected from COVID-19 infection, but WHO gave a stark warning on use of BCG vaccine without confirmed COVID-19 trials. The aim of the study is to evaluate whether TB vaccination, performed several years earlier, could confer protection against COVID-19. Methods: After the Ethical Committee authorization, professional orders were used to contact physicians with an online survey. Specialty, COVID-19 infection and previous BCG vaccination were recorded. Statistical data analysis was performed. Results: 1906 physicians answered the questionnaire, (M = 1068; F = 838; mean age 50.7 ± 13.3 years; range 24–87), more than half (1062; 55.7%) experienced BCG vaccination. Professional activity was recorded, and only 49 subjects (2.6%) of them were infected by SARS-CoV2. Among the group of infected people, asymptomatic form occurred in 12 subjects (24.5%); a pauci-symptomatic form in 24 subjects (49.0%); and a severe form (pneumonia and/or respiratory distress) in 13 (26.5%). Considering only the clinically relevant form of COVID-19, period prevalence was 2.2% (23/1062) in the vaccinated group and 1.7% (14/844) in the unvaccinated group (OR: 1.31, 95% C.I.: 0.68–2.63, p = 0.427). Conclusion: Our experience does not confirm the possible protective role of BCG vaccination, performed years earlier, against COVID-19. Although recent epidemiological studies point out in BCG-vaccinated population a lower prevalence of SARS-CoV2 infection, in our cohort of physicians no significant difference was found in terms of prevalence of COVID-19 infection. Our data underline the necessity to follow the WHO warning about the indiscriminate use of BCG vaccine, until clear evidence of protection by BCG vaccination against COVID-19 is fully demonstrated.

An Ebola virus vaccine that leverages helper T cells induced by prior BCG immunization

Abstract Protective antibody responses against the Ebola virus (EBOV) are dependent on the quality of CD4+ helper T (Th) cells. We propose that BCG specific Th cells may provide a source of Th cells that can be recruited to drive antibody responses against EBOV, given that the majority of individuals residing in EBOV endemic regions have been previously vaccinated with BCG. To take advantage of pre-existing BCG Th cells, a vaccine was developed that consists of the EBOV GP fused to the mycobacteria Th cell epitope (P25) of Ag85B (P25-EBOV GP). Presentation of the P25 epitope by B cells recruited cognate interactions with P25 Th cells to promote antibody responses against the EBOV GP. Experiments in mice showed BCG priming induced a broad range of Th cells including Th1, Th2, and Tfh subsets. These P25 Th subsets provided a significant dose sparing effect on the P25-EBOV GP vaccine in the induction of EBOV GP antibodies and resulted in increased titers of high affinity neutralizing IgG1 antibodies. The induction of IgG2c antibodies only occurred in BCG primed mice, where BCG vaccination is known to be a strong inducer of Th1 responses that drive class-switching to IgG2c. Microscopy of sections from secondary lymphoid organs of BCG primed mice showed that the majority of P25 Th cells remained in extrafollicular regions outside germinal centers and were most responsible for the induction of the IgG2c class-switched antibodies that were weakly neutralizing but capable of mediating antibody-dependent cellular toxicity (ADCC). BCG priming followed by vaccination with P25-EBOV GP protected mice against lethal EBOV infection, thus suggesting a potentially useful strategy for vaccination against EBOV in populations with high prevalence of previous BCG vaccination.

An updated systematic review on the applied TST and IGRA Test for diagnosing LTBI in patients treated with TNF-α inhibitor drugs

Present systematic review was designed to compare the efficacy of interferon-γ release assays (IGRAs) and tuberculin skin test (TST) for diagnosing latent tuberculosis infection (LTBI) in patients subjected to the anti-TNF-α therapy. The MEDLINE (Ovid), PubMed, Embase, Scopus, Cochrane library, and Web of Science ISI databases were searched for selecting studies to compare the efficiency of IGRAs [QuantiFERONTB Gold (QFT-GT), QuantiFERON-TB Gold In-Tube (QFT-GIT)and T-SPOT.TB] and TST in patients under the anti-TNF-α therapy. After evaluating all studies, we systemically reviewed the results of 37 studies with a total sample size of 8584 patients. The agreement between IGRASs and TST was poor to moderate, however, the anti-TNF-α therapy mostly decreased the percentage of this agreement. BCG vaccination could cause false results of TST assay. The developed active TB in patients with IGRAs positive results during follow-up showed lower than TST positive patients. In conclusion, in the treated patients with anti-TNF-α with previous BCG vaccination, IGRAs might be the better assay to diagnosis LTBI by reducing the false results rate in comparison with the TST. However, more investigations should be done to compare the advantage of IGRAs with conventional test in the treated patients with TNF-α antagonists.

Tuberculin sensitivity among inmates of children’s home

Background: Tuberculin sensitivity and its relationship to nutritional status in inmates of children's home.Methods: Tuberculin sensitivity was checked in 180 apparently healthy orphan children and its relationship with nutritional status, previous vaccination status was studied. setting: children's home run by NGOs participants: all inmates of children's home aged 2-15 years who meet inclusion and exclusion criteria.Results: Out of 180 apparently healthy children 27 (15%) were tuberculin positive. 109 (60.5%) were undernourished children out of which 15 (55.56%) were tuberculin positive. Out of 71 normal nourished children, 12 (44.4%) were tuberculin positive. BCG scar was present in 120 (66.6%) children out of which 19 were tuberculin positive and BCG scar was absent in 60% children out of which 8 were tuberculin positive. 8 children had history of contact with TB and 6 of them were tuberculin positive.Conclusions: Tuberculin sensitivity testing using 5 TU PPD-RT23 is a simple feasible method to screen inmates of children home at the time of entry and it is not influenced by nutritional status or previous BCG vaccination. Early diagnosis and treatment of TB will go a long way in reducing the burden of TB in our country.

Relation between BCG vaccine scar and an interferon-gamma release assay in immigrant children with "positive" tuberculin skin test (≥10mm).

BackgroundImmigrants from countries with high incidence of tuberculosis (TB) are usually offered screening when they arrive to low incidence countries. The tuberculin skin test (TST) is often used. The interferon gamma release assays (IGRAs) are more specific and not affected by BCG vaccination. The aims of this study were 1. To see if there if there is a correlation between a positive IGRA (QFT) and presence of a BCG scar in children with TST ≥10 mm, 2. To compare the TST diameter with QFT result, 3. To see if chest X-ray can be omitted in QFT negative children despite TST ≥10 mm.Methods762 healthy children/adolescents (median age 14 years) arriving to Gothenburg and surroundings with TST ≥10 mm were tested with QFT.ResultsA total of 163/492 (33 %) children with BCG scar had positive QFT, whereas 205/270 (76 %) without BCG scar had positive QFT (p < 0.0001). The median TST was 12 mm in QFT negative and 18 mm in QFT positive children (p < 0.0001) but with considerable overlap. Median TST was the same (12 mm) in QFT negative children with and without BCG scar. Among the QFT positive children 25/368 had chest X-ray changes compared to 2/393 among the QFT negative children (p < 0.0007).ConclusionsPrevious BCG vaccination had an effect on the TST diameter so an IGRA is recommended to diagnose latent TB. Using only TST for screening of latent TB would lead to overdiagnosis. The TST diameter was larger in QFT positive than in QFT negative children but could not predict QFT in the individual patient. Chest X ray contributes little to the diagnosis of TB in QFT negative children but can not be omitted because of late seroconversion of QFT in some patients.Trial registrationNot applicable.

Prevalence and predictors of latent tuberculosis infection among Italian State Policemen engaged in assistance to migrants: a national cross-sectional study.

ObjectivesBetter knowledge about tuberculosis (TB) and latent TB infection (LTBI) epidemiology is a crucial step for the development of effective strategies towards the control and elimination of this deadliest and persistent health threat. No study has investigated LTBI epidemiology in policemen who act as an interface with cross-border migrants.MethodsA survey to measure the LTBI prevalence and assess the demographic, professional and clinical features potentially associated with tuberculin skin test (TST) positivity was performed in Italian State Police (ISP) employees engaged, even occasionally, in relief activities, hospitality, photographical identification, escorting and accompanying of migrants, regardless of contact with active TB cases. Variables potentially associated with TST positivity were evaluated with univariate and multivariate analysis.ResultsFrom September to December 2014, 4225 ISP workers underwent TST screening and completed the questionnaire for data collection, according to study procedures. The TST was positive in 9.9% of individuals: no active TB cases were registered among the entire study population. Age, previous BCG vaccination and work category resulted independently associated with TST positivity.ConclusionsThis is the first study providing updated data about LTBI epidemiology among ISP employees engaged in assistance to migrants and furnish preliminary evidence of possible associations between TST positivity and different conditions that need to be deeply investigated with prospective studies.

Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality? A meta-analysis testing the hypotheses of sex-differential non-specific effects of DTP vaccine.

BackgroundTen years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG, DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review by WHO found no convincing evidence that DTP increases mortality in females.MethodsWe used previous DTP reviews as well as the recent WHO review for assessing the hypotheses. As pre-specified we excluded studies with survival or frailty bias; if children had received BCG and DTP simultaneously; and if the children had received neonatal vitamin A.ResultsIn seven studies of BCG-vaccinated children, DTP vaccination was associated with a 2.54 (95% CI 1.68–3.86) increase in mortality in girls (with no increase in boys [ratio 0.96, 0.55–1.68]). In 10 studies of BCG-vaccinated children, the female-to-male mortality ratio was 2.45 (1.48–4.06) times higher after DTP than before DTP. In 15 studies of children who had received DTP after previous BCG vaccination, mortality was 1.53 (1.21–1.93) times higher in girls than boys. The findings were similar in studies conducted before and after formulation of the hypotheses.ConclusionsThe two hypotheses were confirmed in the studies that fulfilled pre-specified criteria.

Impact of BCG Vaccination Status on Sputum Conversion Rate in New Sputum Positive cases of Pulmonary Tuberculosis

Objectives: Sputum conversion rates (SCR) at the end of intensive phase of treatment of pulmonary tuberculosis varies and knowledge of factors involved is, inadequate. It has been reported that presence of a BCG scar was associated with greater rate of sputum conversion at the end of intensive phase (IP) of treatment. Hence, this study was undertaken with aim of studying the relationship between BCG vaccination status and sputum conversion rate in pulmonary tuberculosis (PTB) patients. Materials And Methods: This was a hospital based observational study done at Assam Medical College and Hospital, Dibrugarh from July 2012 to June 2013. All new sputum smear positive (SSP-PTB) patients were put on antitubercular therapy under DOTS and followed up with repeat sputum microscopy at the end of intensive phase. A comparative study on the outcome was done between BCG scar positive and negative cases and statistical analysis done. Results: All the 102 new SSP-PTB cases successfully completed intensive phase treatment under DOTS. Out of these 19 patients had to be put on extended IP of 1 month. BCG scar was present in 64.17% cases and absent in 35.29%. Overall, 81.37% of new sputum positive (NSP) cases converted at the end of second month IP on DOTS. In BCG scar present group, sputum conversion rate (SCR) was 90.90% whereas in scar absent group it was 63.89%, showing a significant ‘p’ value of 0.0013.In the extended IP group 94.48% cases with scar converted, while 22.22% without BCG scar remained non-converted with a significant ‘p’ value of 0.0009. Conclusion: New SSP-PTB patients with evidence of previous BCG vaccination, show a significantly better sputum conversion rate at the end of intensive phase of DOTS.

A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents

We compared T cell recognition of 59 prevalently recognized Mycobacterium tuberculosis (MTB) antigens in individuals latently infected with MTB (LTBI), and uninfected individuals with previous BCG vaccination, from nine locations and populations with different HLA distribution, MTB exposure rates, and standards of TB care. This comparison revealed similar response magnitudes in diverse LTBI and BCG-vaccinated cohorts and significant correlation between responses in LTBIs from the USA and other locations. Many antigens were uniformly recognized, suggesting suitability for inclusion in vaccines targeting diverse populations. Several antigens were similarly immunodominant in LTBI and BCG cohorts, suggesting applicability for vaccines aimed at boosting BCG responses. The panel of MTB antigens will be valuable for characterizing MTB-specific CD4 T cell responses irrespective of ethnicity, infecting MTB strains and BCG vaccination status. Our results illustrate how a comparative analysis can provide insight into the relative immunogenicity of existing and novel vaccine candidates in LTBIs.

Transmissibility of tuberculosis among school contacts: An outbreak investigation in a boarding middle school, China

Tuberculosis (TB) outbreak occurred in a boarding middle school of China. We explored its probable sources and quantified the transmissibility and pathogenicity of TB. Clinical evaluation, tuberculin skin testing and chest radiography were conducted to identify TB cases. Mycobacterium tuberculosis isolates underwent genotyping analysis to identify the outbreak source. A chain-binomial transmission model was used to evaluate transmissibility and pathogenicity of TB. A total of 46 active cases were ascertained among 258 students and 15 teachers/staff, an attack rate of 16.8%. Genetic analyses revealed two groups of M. tuberculosis cocirculating during the outbreak and possible importation from local communities. Secondary attack rates among students were 4.1% (2.9%, 5.3%) within grade and 7.9% (4.9%, 11%) within class. An active TB case was estimated to infect 8.4 (7.2, 9.6) susceptible people on average. The smear-positive cases were 28 (8, 101) times as infective as smear-negative cases. Previous BCG vaccination could reduce the probability of developing symptoms after infection by 70% (1.4%, 91%). The integration of clinical evaluation, genetic sequencing, and statistical modeling greatly enhanced our understanding of TB transmission dynamics. Timely diagnosis of smear-positive cases, especially in the early phase of the outbreak, is the key to preventing further spread among close contacts.

Utilidad del Quantiferon-TB Gold in Tube® en el cribado de la infección latente tuberculosa en personal sanitario

IntroductionHealthcare workers (HW) are considered a risk group for exposure to tuberculosis. Screening for latent tuberculosis infection (LTBI) is mandatory in all HW. The Tuberculin test (TT) has been used up until now for LTBI screening, but gives a high number of false positives, especially in patients vaccinated with BCG. Diagnostic methods based on detection of specific gamma interferon (IGRA) have recently appeared on the market in order to improve these drawbacks, but pose other dilemmas. The aim of this study is to determine the agreement between the two types of test and to carry out a cost-benefit study of the possible diagnostic strategies. Material and methodsAll newly hired HW by the Hospital Universitari Mútua Terrassa between January 2010 and October 2011 we were included in the study, as well as those who had their occupational review. Workers who been in contact with patients admitted with tuberculosis before the initial isolation were also tested. In all cases a parallel TT and serum QuantiFeron-TB Gold-in-Tube® (QF-G-IT) assays were performed. TB disease was ruled out in all professional by chest X-ray. The TT was considered positive when it was equal to or more than 10mm and if the QF-G-IT was 0.35IU/mL. A cost-effectiveness analysis was designed with three possible strategies to detect LTBI in order to find the one with the best cost-benefit. ResultsA total of 226 HW were studied, with a mean age 30.65±16, of whom 44 (19.4%) had previous BCG vaccination history, and 8 (3.5%) unknown. The TT was positive in 33 (14.6%) cases and the QF-G-IT in 17 (7.5%). The values of the TT and QF-G-IT were both positive in 15 cases. In 18 (8%) The TT was positive in 18 (8%) of cases with a negative QF-G-IT value. The agreement between the two tests was 91%, with a Kappa of 0.55. In vaccinated cases, the correlation was 70.5%, with a Kappa of 0.33, while in unvaccinated it was 98.9% with a Kappa of 0.65. The cheapest screening strategies for LTBI diagnosis were those based on TT, but followed closely by the strategy based on TT with reconfirmation of positives with QF-G-IT. ConclusionsQF-G-IT seems to be a very sensitive technique to detect LTBI and allows false positives due to TT to be detected, particularly in BCG vaccinated HW. In this group QF-G-IT could be the ideal test to detect truly infected staff, and avoid unnecessary chemoprophylaxis. The most cost-benefit strategy was those based in TT with reconfirmation or rejection of positive cases by QF-G-IT.

Screening of latent tuberculosis infection by interferon-γ release assays in rheumatic patients: a systemic review and meta-analysis.

The aim of this study is to assess the diagnostic value of interferon-γ release assays (IGRAs) for latent tuberculosis infection (LTBI) in patients with rheumatic disease before receiving biologic agents. MEDLINE and EMBASE databases were used for searching studies concerning the evaluation on the performance of IGRAs [QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB] in rheumatic patients before biological therapy. After assessing the quality of all studies included in the review, we summarized the results in subgroups using forest plots and calculated pooled estimates if applicable. The search identified 11 studies with a total sample size of 1940 individuals. Compared with the tuberculin skin test (TST), the pooled agreements in QFT-G/GIT and T-SPOT.TB were 72 % (95 % confidence interval (CI) 65, 78 %) and 75 % (95 % CI 67, 83 %), respectively. BCG vaccination was positively correlated with positive rates of TST (pooled odds ratio (OR) 1.64, 95 % CI 1.06, 2.53). Compared with TST, IGRAs were better associated with the presentence of one or more tuberculosis (TB) risk factors. Neither steroid nor disease-modifying anti-rheumatic drugs (DMARDs) significantly affect positive IGRA results. In contrast, TST positivity was significantly impacted by the use of steroid (pooled OR 0.45, 95 % CI 0.30, 0.69), but less significantly by the use of DMARDs (pooled OR 0.78, 95 % CI 0.50, 1.21). In conclusion, in rheumatic patients with previous BCG vaccination or currently on steroid therapy, IGRAs would be the better choice to identify LTBI by decreasing the false-positivity and false-negativity rate compared with conventional TST.

Tuberculin Positivity in Kawasaki Disease: An Unusual Occurrence

To the Editor:A 3-y-old girl presented with high grade fever, irritability, red eyes, lips and tongue and a pruritic rash. She had conjunctival injection, red, cracked lips, ‘strawberry tongue’, edematous hands and feet, and an erythematous, popular rash on the trunk, face and extremities, sparing the palms and soles with classical periungual desquamation. Mobile, non-tender, cervical lymph nodes were palpable. There was erythema and induration at the site where tuberculin had been administered 4 wk ago (Fig. 1). The BCG scar site was normal. Rest of the examination was unremarkable. She had anemia, leukocytosis, thrombocytosis and high erythrocyte sedimentation rate (57 mm) and C reactive protein (92.95 mg/L). Urine showed 7–8 leucocytes per high power field; culture was sterile. Echocardiogram did not reveal any coronary artery abnormalities. Due to the presence of typical features, a diagnosis of Kawasaki disease (KD) was made. Intravenous immunoglobulin was given followed by aspirin. Tomisaku Kawasaki, first reported reactivation of the BCG vaccination site in children with KD. Erythema at the BCG site is reported in upto 50 % of children with KD [1]. However, it has been an uncommon finding in reports from India. The first child with KD and erythema at both BCG and tuberculin administration sites was reported by Kadowaki et al. [2]. Beretto et al. reported tuberculin skin test to be a highly sensitive and specific diagnostic test for KD [3]. They observed that children with acute KD had swelling at the site of previous BCG vaccination or an erythematous reaction at BCG inoculation sites if given during acute KD. They compared tuberculin skin tests in typical KD patients and patients with other febrile illnesses and found that all KD patients had a positive tuberculin skin test. However, a similar study by Kollmann et al. did not support these findings [4]. Skin lesions at the site of BCG or tuberculin administration have been ascribed to molecular mimicry between a mycobacterial heat shock protein (HSP-65) and human homologue HSP 63. Mice inoculated with BCG followed by a crude extract ofMycobacterium intracellulare (cMI) developed coronary arteritis, whereas control animals inoculated with only cMI or BCG did not, suggesting that the immune response to the mycobacteria probably induced autoimmune damage to the vascular wall [5]. In countries with universal BCG vaccination, skin changes at the site of BCG or tuberculin inoculation can be a valuable aid in diagnosis of KD.

Performance of QuantiFERON-TB Gold In-Tube test and Tuberculin Skin Test for diagnosis of latent tuberculosis infection in BCG vaccinated health care workers

BackgroundTuberculin skin test (TST) has been used for years as an aid in diagnosing latent tuberculosis infection (LTBI) but it suffers from a number of well-documented performance and logistic problems. Quantiferon-TB Gold In Tube test (QFT-GIT) has been reported to have better sensitivity and specifity than TST. In this study, it was aimed to compare the performance of a commercial IFN-γ release assay (QFT-GIT) with TST in the diagnosis of HCWs at risk for latent TB infection in BCG vaccinated population.Material/MethodsHundred healthy volunteer health care workers were enrolled. All were subjected to TST and QFT-GIT. Results were compared among Health Care Workers (HCWs) groups in terms of profession, workplace, working duration.ResultsTST is affected by previous BCG vaccinations and number of cases with QFT-GIT positivity is increased in accordance with the TST induration diameter range. QFT-GIT result was negative in 17 of 32 TST positive (≥15 mm) cases and positive in 4 of 61 cases whose TST diameters are between 6–14 mm, that is attritutable to previous BCG vaccination(s). It was negative in all cases with TST diameters between 0–5 mm.HCWs with positive QFT-GIT results were significantly older than the ones with negative results. Furthermore duration of work was significantly longer in QFT-GIT positive than in negative HCWs.ConclusionsThere was a moderate concordance between QFT-GIT and TST, when TST result was defined as positive with a ≥15 mm diameter of induration. We suggest that QFT-GIT can be used as an alternative to TST for detection of LTBI, especially in groups with high risk of LTBI and in population with routine BCG vaccination program.

Skin test screening for tuberculosis among healthcare students: a retrospective cohort study.

Aim of the study was to document the baseline prevalence of healthcare students positive to tuberculosis skin tests screening. Between 2008-2010, students admitted to healthcare courses (medicine, nursing, physiotherapy...) at Sapienza university in Rome were requested to carry out personal tuberculosis skin test screening in their local district or town healthcare centers according to the italian guidelines. At the time interferongamma release assays (IGRA) testing was not adopted for large screening. Demographic characteristics, tuberculosis screening results, healthcare course, tuberculosis vaccination status were recorded. A cohort of 2,500 university healthcare students were screened by several Italian Hygiene Offices using tuberculin skin test and Tine test. Overall 131 (5.2%) healthcare students resulted positive to some tuberculosis skin test screening. Tuberculin skin test was carried out on 2,029 students (81.2%) and conversion was observed in 107 (5.3%), whereas Tine test was carried out on 498 students (19.9%) and positive result was observed in 24 (4.8%). The Tine test use and non optimal (<72h) recording of the forearm induration in tuberculin skin tests was related mostly to some healthcare centers in Lazio and Campania regions. Previous BCG vaccination was reported by 27 healthcare students (1.1%), and only two of them showed tuberculin skin test conversion, whereas the large majority 105 (98.1%) of Mantoux positives had not been vaccinated. In univariate analysis positive tuberculin skin test was associated to growing students age (29.2 ± 10.3 vs. 23.1 ± 6.0; p<0.01). Positive tuberculin skin test was recorded in 25 (20.3%) foreign and 82 (4.3%) italian students showing a higher risk for International students (RR 4.72; 95%CI 3.14 - 7.11; p<0.01). There was no significant correlation between the different Italian regions, the various healthcare courses or gender. The study evaluated the baseline positive skin test rate for tuberculosis among healthcare students in their first university year, showing a higher risk for the international group and revealed some problematic screening practices which need to be improved in the future screening programs.

AB0363 Rate of tuberculin skin test or interferon gamma release assay conversion during anti-tumor necrosis factor therapy in rheumatic patients

BackgroundDespite negative baseline testing for tuberculosis (TB) with traditional (tuberculin skin test/TST, chest X-ray/CXR) or newer (interferon-gamma release assays/IGRAs) screening methods, a small number of patients receiving anti-tumor necrosis factor...