Tuberculin Skin Test Conversion Research Articles

High conversion of tuberculin skin tests during the first year of antiretroviral treatment among South African adults in primary care.

Anergy reduces the sensitivity of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis infection in people living with HIV. Antiretroviral treatment (ART) can reverse TST anergy, but data is scarce. To estimate TST conversion rates and factors associated with TST conversion, TST was placed at ART initiation, and 6 and 12 months thereafter (if TST negative at prior assessment). Of 328 ART-eligible participants, 70% (231/328) had a valid TST result of whom 78% (180/231) were TST negative. At 6-month follow-up, 22% (24/109, 95% confidence interval [CI] 15%, 31%) of participants on ART, without incident tuberculosis (TB), and with a valid TST result converted to a positive TST. Of these 109 individuals, those with baseline CD4+ cell count >250 cells/μl were more likely to TST convert compared to those with baseline CD4+ cell count ≤250 cells/μl (odds ratio [OR] 3.54, 95% CI 1.29, 11.47). At 12 months post-ART initiation, an additional 12% (9/78, 95% CI 6, 20) of participants on ART, without incident TB and with a valid TST result experienced TST conversion. After 1 year on ART, TST conversion rate was 38 per 100 person-years (95% CI 26, 52), and lower in individuals with baseline CD4+ cell count ≤250 cells/μl (23/100 person-years, 95% CI 11, 41) compared to those with baseline CD4+ cell count >250 cells/μl (50/100 person-years, 95% CI 32, 73). TST conversion rate in the first year of ART is high, especially among people with CD4+ cell count >250 cells/μl. A TST-based eligibility strategy at ART initiation may underestimate eligibility for preventive therapy for tuberculosis.

Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis.

Two weeks' isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization-commissioned review investigated sputum sterilisation dynamics during TB treatment. For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness-including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments-was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%-24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%-86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%-14%, N = 2), increasing to 88% at 2 months (95% CI 84%-92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%-16%, N = 1) and 59% (95% CI 47%-70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation. This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment. Systematic review registration: PROSPERO 85226.

Erratum to `Tuberculosis risk in the biologic era: tuberculin skin test conversion rates in children with rheumatologic diseases` [Turk J Pediatr 2021; 63: 978-985

This article is corrected. DOI: 10.24953/turkjped.2021.06.005.

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.

Effectiveness and outcomes of air travel-related TB incident follow-up: a systematic review.

The World Health Organization (WHO) recommends following up passengers after possible exposure to a case of infectious tuberculosis (TB) during air travel. This is time-consuming and difficult, and increasingly so with higher numbers each year of flights and passengers to and from countries with high TB endemicity. This paper systematically reviews the literature on contact tracing investigations after a plane exposure to active pulmonary TB. Evidence for in-flight transmission was assessed by reviewing the positive results of contacts without prior risk factors for latent TB.A search of Medline, EMBASE, BIOSIS, Cochrane Library and Database of Systematic Reviews was carried out, with no restrictions on study design, index case characteristics, duration of flight or publication date.In total, 22 papers were included, with 469 index cases and 15 889 contacts. Only 26.4% of all contacts identified completed screening after exposure. The yield of either a single positive tuberculin skin test (TST) or a TST conversion attributable to in-flight transmission was between 0.19% (95% CI 0.13%-0.27%) and 0.74% (95% CI 0.61%-0.88%) of all contacts identified (0.00%, 95% CI 0.00%-0.00% and 0.13%, 95% CI 0.00%-0.61% in random effects meta-analysis). The main limitation of this study was heterogeneity of reporting.The evidence behind the criteria for initiating investigations is weak and it has been widely demonstrated that active screening of contacts is labour-intensive and unlikely to be effective. Based on our findings, formal comprehensive contact tracing may be of limited utility following a plane exposure.

PositiveMycobacterium tuberculosisGastric Lavage Cultures from Asymptomatic Children With Normal Chest Radiography

Mycobacterium tuberculosis culture from gastric lavage from apparently healthy children following tuberculin skin test conversion, despite normal chest radiography (CR), is well known but is a contentious subject. A consensus statement regarding classification of childhood tuberculosis excluded this condition, stating that more data were needed. To assist in this discussion, we reviewed early publications that reported the occurrence of this phenomenon and early anatomical pathology studies that described changes that occur in children following tuberculosis infection. Pathology studies describe frequent cavitation in primary foci in children from whom positive M. tuberculosis cultures might easily arise. These foci were very small in some children who might have normal CR. Positive cultures might also arise from ulcerated mediastinal lymph nodes that are invisible on CR. Young children with recent infection very likely have active primary pulmonary tuberculosis.

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.

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

Tubercular infection in children living with adults receiving Directly Observed Treatment Short Course (DOTS): a follow up study

BackgroundChildren living with sputum smear-positive adult tuberculosis (TB) patients are vulnerable to acquire tubercular infection. Contact tracing is an important strategy to control tubercular infection in the community. This study was done to find out prevalence of tuberculosis and tubercular infection in children living with sputum smear-positive adult patients receiving DOTS at recruitment and to find out incidence of tubercular infection and disease in these children on follow up.MethodChildren (< 15 years) living in contact with adults on DOTS were grouped as < 6 years and 6–14 years. They were further sub grouped as being - uninfected, infected, diseased and on prophylaxis and were followed at 3, 6 and 9 months. Tuberculin skin test (TST) and chest X-ray were done.ResultsAt recruitment 152 children were enrolled and 21.1% (n = 32) had TB. On follow up, 4.3% (n = 5), 5.8% (n = 6) and 11.6% (n = 11) children developed TB after 3, 6 and 9 months respectively.9 children did not come for the last follow up so the overall prevalence of TB disease at 9 months was 37.7% (n = 54). Out of the 128 children with TST reading 23.4% (n = 30) child contacts were found to be infected already at recruitment. The incidence of TST conversion was 20.7% (n = 18), 26.9% (n = 18) and 16.3% (n = 7) respectively. The overall prevalence of tubercular infection in the children, who were in contact with TB patients for 9 months was 74.5% (n = 73).ConclusionAbout half the children were either suffering from TB or tubercular infection on recruitment. During 9 months follow up 22 unaffected children developed disease and 43acquired infection.

Novel health system strategies for tuberculin skin test-guided Isoniazid preventive therapy

Abstract Background Global TB elimination demands a scale-up of Isoniazid preventive therapy (IPT) but tuberculin skin test (TST)-guided IPT poses great logistical and human resource challenges. Objectives Performance of TST self-reading by patients and fast-track TST reading by trained low cadre health care workers (task-shifting) was compared to formal TST reading by high cadre staff in a cohort of 278 South African adults living with HIV. Health economic impact of these novel strategies was assessed from a provider and societal perspective and simulations were performed for 5 other countries (USA, Germany, Brazil, India, Russia) to evaluate generalizability. In addition, accuracy of TST at antiretroviral treatment (ART) initiation was assessed by a repeat TST 6 and 12 month later. Results TST self-reading was highly accurate, with 89% sensitivity (95% CI 80, 95) and 100% specificity (95% CI 97,100) for detecting presence/absence of any induration. Agreement in TST reading between low and high cadre health care workers was very high (kappa 0.97). Compared to standard of care, a combined fast-track, task-shifting and self-reading strategy reduced TST reading costs in South Africa from a patient perspective by 81% and from a provider perspective by 92%. In all 5 countries simulated, TST reading cost was reduced by ≥ 78 % from a provider perspective. Repeat testing at 6 and 12 months showed high (31%, 95% CI 23, 40) TST conversion during the first 12 months of ART. Conclusions Empiric IPT for all people living with HIV followed by TST assessment after 6 or 12 months to identify those in need for lifelong IPT could increase the effectiveness of IPT programs. TST self-reading to reduce the number of patients that need to return for TST reading (to only those patients with self-determined presence of any induration) together with fast-tracking and task-shifting of TST reading could increase cost-effectiveness and reduce patient costs associated with IPT programs. Key messages Novel strategies are essential to control TB. Task-shifting, fast-tracking and patient TST self-reading empower patients and HCWs; optimal TST timing can increase cost-effectiveness of IPT programs.

Mycobacterium tuberculosis-specific plasmablast levels are differentially modulated in tuberculosis infection and disease

BackgroundWhile T cell responses to Mycobacterium tuberculosis (Mtb) have been extensively studied, the role of B-cells and antibodies are less well characterised. The aim of this study was to assess levels of Mtb-specific IgG + plasmablasts across the Mtb infection spectrum. MethodsPatients with active TB were analysed at baseline and 6 months of therapy (n = 20).Their exposed household contacts (HHC) included individuals with latent TB infection (LTBI; n = 20); evident at baseline; individuals with a negative Tuberculin Skin Test (TST) at baseline who became; positive at 6 months (converters; n = 11) and those who remained negative (non-converters; n = 10). An e x-vivo B-cell ELISPOT was performed to analyse plasmablast responses. ResultsFrequencies of ESAT-6/CFP-10 (EC)- but not Whole Cell Lysate (WCL)-specific plasmablasts were significantly higher in patients with active TB pre-treatment compared to post-treatment (p = 0.002) and compared to HHC with LTBI (p < 0.0001). Conversely, total IgG + plasmablasts were significantly decreased in TB patients at baseline. No difference was seen in levels of plasmablasts between TST converters and non-converters at baseline. ConclusionsWe show that EC-specific plasmablast levels are differentially modulated during TB infection and disease, with levels highest during active TB. These data provide new insights into TB biomarker development and avenues for novel immune interventions.

Serial testing of health care workers for tuberculosis infection: A prospective cohort study.

Health Care Workers (HCW) may have an occupational risk of latent tuberculosis infection (LTBI) and TB disease. The objective of this study was to evaluate the performance of the 2-step strategy: tuberculin skin test (TST) followed by confirmation with Interferon (IFN)-γ- release assays (IGRAs) in HCW. A secondary objective was to determine the factors related to conversions and reversions. HCW at risk of occupational exposure who attended the Occupational Department of the Hospital Germans Trias i Pujol were included during the study period (2013–2016). All professionals testing negative for LTBI were included in a cohort study. These workers were followed up with the administration of a TST and an IGRA quantification at least one year after inclusion in the study. Workers with positive TST, regardless of the results of the IGRA tests, were followed-up with an IGRA. 255 workers were enrolled in the study and 108 workers from the same cohort were followed up. During the follow-up period, seven workers presented TST test conversion. One of these conversions was also confirmed by an IGRA test. There were 2 conversions of cases only testing positive with the IGRA. There have been only 2 reversions of cases testing negative with the IGRA. In this study, not all TST conversions were confirmed when using the IGRA test, which highlights the importance of the 2-step strategy. We have detected a low number of conversions and reversions. Our conclusions should be confirmed in studies with a longer follow-up time.

Tuberculin skin test conversion in patients under treatment with anti-tumor necrotizing factor alpha agents

BackgroundDespite successful clinical outcomes of biologic medications in patients with chronic rheumatic diseases, some considerable adverse effects such as infections remain a major concern. Possibility of tuberculosis (TB) reactivation over treatment with anti-tumor necrotizing factor (TNF) alpha agents has necessitated a screening test before initiation of treatment. However, screening over the course of treatment is not recommended in those patients with negative baseline screening tests. This study aimed to evaluate the efficacy of tuberculin skin test (TST) before treatment in patients with chronic rheumatologic diseases who were indicated to receive anti-TNF-alpha therapy and the necessity of repeating this test over the course of treatment.MethodsIn this prospective study, patients with chronic rheumatologic diseases receiving anti-TNF-alpha agents were studied in a two-year period. TST was performed before treatment and those with positive results were excluded from the study. Thereafter, treatment with anti-TNF-alpha agents was initiated with the indicated dose. TST was repeated before administration of biologic treatment until TST became positive or 16 weeks after the initiation of treatment with anti-TNF-alpha.ResultsA total of 51 cases were studied, of whom one patient (1.9%) was excluded due to positive TST before treatment. All participants received infliximab and the TST test became positive in one patient (2%) 2 weeks after receiving the first dose. Also, the results of further tests at weeks 6, 10, and 14 were all negative for the remaining patients.ConclusionDue to the possibility of TST conversion after administration of anti-TNF-alpha therapy, it is important to consider TB monitoring in patients under treatment with these agents using available methods such as TST.

Identification of Mycobacterium tuberculosis Peptides in Serum Extracellular Vesicles from Persons with Latent Tuberculosis Infection.

Identification of biomarkers for latent Mycobacterium tuberculosis infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for preventive therapy, predict disease risk, and potentially predict preventive therapy efficacy. Our group developed multiple reaction monitoring mass spectrometry (MRM-MS) assays that detected M. tuberculosis peptides in serum extracellular vesicles from TB patients. We subsequently optimized this MRM-MS assay to selectively identify 40 M. tuberculosis peptides from 19 proteins that most commonly copurify with serum vesicles of patients with TB. Here, we used this technology to evaluate if M. tuberculosis peptides can also be detected in individuals with latent TB infection (LTBI). Serum extracellular vesicles from 74 individuals presumed to have latent M. tuberculosis infection (LTBI) based on close contact with a household member with TB or a recent tuberculin skin test (TST) conversion were included in this study. Twenty-nine samples from individuals with no evidence of TB infection by TST and no known exposure to TB were used as controls to establish a threshold to account for nonspecific/background signal. We identified at least one of the 40 M. tuberculosis peptides in 70 (95%) individuals with LTBI. A single peptide from the glutamine synthetase (GlnA1) enzyme was identified in 61/74 (82%) individuals with LTBI, suggesting peptides from M. tuberculosis proteins involved in nitrogen metabolism might be candidates for pathogen-specific biomarkers for detection of LTBI. The detection of M. tuberculosis peptides in serum extracellular vesicles from persons with LTBI represents a potential advance in the diagnosis of LTBI.

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.

The diagnosis of latent tuberculosis infection (LTBI): currently available tests, future developments, and perspectives to eliminate tuberculosis (TB).

Introduction:Despite great efforts, tuberculosis (TB) is still a major public health threat worldwide. For decades, TB control programs have focused almost exclusively on infectious TB active cases. However, it is evident that this strategy alone cannot achieve TB elimination. To achieve this objective a comprehensive strategy directed toward integrated latent tuberculosis infection (LTBI) management is needed. Recently it has been recognized that LTBI is not a stable condition but rather a spectrum of infections (e.g., intermittent, transient or progressive) which may lead to incipient, then subclinical, and finally active TB disease.Aim:Provide an overview of current available LTBI diagnostic test including updates, future developments and perspectives.Results:There is currently no test for the direct identification of live MT infection in humans. The diagnosis of LTBI is indirect and relies on the detection of an immune response against MT antigens, assuming that the immune response has developed after a contact with the biological agent. Tuberculin skin test (TST) and interferon gamma release assays (IGRAs) are the main diagnostic tools for LTBI, however, both present strengths and limitations. The most ancient diagnostic test (TST) can be associated with several technical errors, has limited positive predictive value, is being influenced by BCG vaccination and several conditions can reduce the skin reactivity. Notwithstanding these limitations, prompt identification of TST conversion, should orientate indications for preventive therapy of LTBI. IGRAs have superior specificity, are not affected by M. bovis, BCG vaccination and other environmental mycobacteria. However, they present some logistical and organisational constraints and are more expensive. Currently, the WHO guidelines recommend that either a TST or an IGRA can be used to detect LTBI in high-income and upper middle-income countries with estimated TB incidences less than 100 per 100,000 population. Two skin tests (C-TB and Diaskintest), using only two specific M. tuberculosis antigens (ESAT-6 and CFP-10) instead of the tuberculin solution, have recently been developed but, to date, none of these tests is available on the European market.Conclusion:Early identification and treatment of individuals with LTBI is an important priority for TB control in specific groups at risk within the population: this is of crucial meaning in recently infected cases both at the community level and in some occupational settings. Currently there is no gold standard test for LTBI: an improved understanding of the available tests is needed to develop better tools for diagnosing LTBI and predicting progression to clinical active disease.

Immunological aspects of tuberculosis pathogenesis

The morphological aspects of TB pathogenesis are well described in the publications. Much is also known about the main stages of development and formation of specific adaptive immunity. However, from our point of view, not enough attention is being paid to the involvement of the immune system in the pathogenesis of clinically relevant TB abnormalities, as well as various forms of the disease. Nevertheless, there is no doubt that the variety of clinical manifestations of any disease associated with the penetration of a foreign agent into the body, and Mycobacterium tuberculosis (MTB) in particular, is due to the collective interaction of the infectious agent and the individual response of the macroorganism to this infectious agent. The mosaic of such interactions usually imposes its own adjustments on the development of different forms of the process, its speed and direction, as well as the outcomes. Certainly, the response of a macroorganism to MTB is an integral part of pathogenesis and consists of many general components including the responses associated with the mechanisms of natural and acquired immunity. Intensity of these reactions depends on the characteristics of an agent (MTB) and a macroorganism. For the development of TB disease, massiveness of TB infection, dose and duration of MTB exposure to the human body, as well as virulence of MTB and the level of body's protection during the exposure play a very important role. TB pathogenesis is somewhat different in primary MTB infection and re - infection. With primary infection, 88-90% of individuals do not have clinical manifestations, and only the tuberculin skin test conversion signals the onset of infection. In some cases, without any use of anti-TB drugs limited abnormalities may result in spontaneous cure with the minimal residual changes in the lungs, intrathoracic lymph nodes and tissues of other organs, often in the form of calcifications and limited areas of fibrosis in more advanced cases. Only 10-12% of newly infected individuals develop TB with severe clinical manifestations requiring TB therapy. The absence of clinical manifestations of primary TB infection can be explained by a high level of natural resistance of the human body to tuberculosis, and sometimes can be an effect of acquired protection due to BCG vaccination. This review attempts to discuss the role of immune mechanisms in the pathogenesis both at the beginning of disease development, and in the process of its various manifestations. Issues of genetically determined resistance or susceptibility to TB are not being covered in detail in this manuscript.

Conversion Rate of Tuberculin Skin Test among Medical Students in Songklanagarind Hospital

OBJECTIVE: Airborne and Tuberculosis (TB) control measures have been implemented in Songklanagarind hospital. The infection control unit of the hospital has provided a voluntary two-step tuberculin skin test (TST) for pre-clinical medical students and serial TST for clinical medical students. This study aimed to determine the incidence of negative outcome and booster phenomenon from two-step TST as well as the TST conversion rate from serial TST among medical students in the hospital. MATERIALS AND METHODS: Percentages of negative cases and boosting phenomenon were calculated from the two-step TST records. Conversion rates of each year were calculated from serial TST data. Then the TST conversion rates were predicted based on the Jointpoint model. RESULTS: Two-step TSTs performed from 2001 to 2016 showed 40 to 100% of negative cases and zero to 14% of boosting phenomenon among 2,271 medical students. Serial TSTs from 2002 to 2016 among 665 medical students showed 60 conversion cases. Conversion rates varied from zero to 13.6%. The decline of conversion rates after the year 2006 is demonstrated in 1-Joinpoint model with statistical significance (p = 0.0129). The model corresponded with the timeline data of airborne infection control measures which were mostly implemented after 2006. CONCLUSIONS: A decline in TST conversion rate was shown after 2006. This coincided with airborne infection control measures at the institute. Keywords: tuberculin skin test, conversion rate, medical student, Songklanagarind hospital Address Correspondence to author: Sarinpant Pongpant, MD. Occupational health unit, Department of family medicine and preventive medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, 90110, Thailand. email: jibpongpant@gmail.com Received: May 25, 2018 Revision received: May 31, 2018 Accepted after revision: July 3, 2018 BKK Med J 2018;14(2): 17-21. DOI: 10.31524/bkkmedj.2018.09.004

Should isoniazid prophylaxis be prescribed to the patients under tumor necrosis factor-alpha antagonists independent of tuberculin skin test?

Introduction The aim of this study was to present the follow-up results of 110 patients who were given anti-tumor necrosis factor alpha (TNF-α) therapy for rheumatic and dermatologic diseases in a country with a high rates of active and latent tuberculosis bacillus infection. Material and Methods Between February 2008 and January 2015, 110 cases in the age range of 23–77 who are using anti-TNF-α were included in the study retro-prospectively. Results 52.7% of them (n = 58) were male. The most common diagnoses were rheumatoid arthritis (42.7%) and ankylosing spondylitis (38.2%). Most frequently given treatment were infliximab 37.3% and etanercept 30.9%, respectively. The 65 patients whose first tuberculin skin test (TST) value “5 mm and above” was started daily 300 mg INH prophylaxis for 9 months but 3 patients had not been started because of refusing treatment. In only one case chemoprophylaxis has had to be interrupted because of high liver function test due to the INH prophylaxis. TST conversion was observed in 14 patients. Further follow-up, it was observed that 4 patients had TST's positivity. Isoniazide (INH) prophylaxis was started these 18 patients (42.9%). Although INH prophylaxis has been given in two patients, they developed active tuberculosis in follow-up. Conclusion Considering the INH resistance in our country, all patients especially the ones with residual lesion and history of previous exposure, should be followed up closely during the anti-TNF-α treatment.

Is there a fundamental flaw in Canada's post-arrival immigrant surveillance system for tuberculosis?

BackgroundNew immigrants to Canada with a history of tuberculosis or evidence of old healed tuberculosis on chest radiograph are referred to public health authorities for medical surveillance. This ostensible public health protection measure identifies a subgroup of patients (referrals) who are at very low risk (compared to non-referrals) of transmission.MethodsTo assess whether earlier diagnosis or a different phenotypic expression of disease explains this difference, we systematically reconstructed the immigration and transmission histories from a well-defined cohort of recently-arrived referral and non-referral pulmonary tuberculosis cases in Canada. Incident case chest radiographs in all cases and sequential past radiographs in referrals were re-read by three experts. Change in disease severity from pre-immigration radiograph to incident radiograph was the primary, and transmission of tuberculosis, the secondary, outcome.ResultsThere were 174 cohort cases; 61 (35.1%) referrals and 113 (64.9%) non-referrals. Compared to non-referrals, referrals were less likely to be symptomatic (26% vs. 80%), smear-positive (15% vs. 50%), or to have cavitation (0% vs. 35%) or extensive disease (15% vs. 59%) on chest radiograph. After adjustment for referral status, time between films, country-of-birth, age and co-morbidities, referrals were less likely to have substantial changes on chest radiograph; OR 0.058 (95% CI 0.018–0.199). All secondary cases and 82% of tuberculin skin test conversions occurred in contacts of non-referrals.ConclusionsPhenotypically different disease, and not earlier diagnosis, explains the difference in transmission risk between referrals and non-referrals. Screening, and treating high-risk non-referrals for latent tuberculosis is necessary to eliminate tuberculosis in Canada.