Surveillance of Employees of Swiss Federal Asylum Centres for Latent Tuberculosis Infection.

BACKGROUND: Asylum seekers in Switzerland have to register in federal asylum centres (FACs) before formal permission to enter the country. Some of them may have active tuberculosis (TB), exposing fellow refugees and employees. OBJECTIVES: The aim of this study was to assess the risk of TB infection among employees of Swiss FACs. METHODS: Between 2010 and 2018, a free interferon-gamma release assay (IGRA) was offered to all employees of 8 FACs, at employment and at yearly intervals. We defined latent TB infection as IGRA conversion from negative to positive. IGRA-positive employees were referred to a medical centre for further clinical follow-up. RESULTS: 1,427 tests were performed among 737 employees (54.6% male). 403 (55%) persons were tested only once; 330 (44.5%) were tested several times; for 4 (0.5%) persons, the number of IGRA tests is unknown. Twenty employees (2.7%) had a positive IGRA at baseline, 2 (0.6%) converted from negative to positive during follow-up, resulting in an incidence of 22/10,000 person-years. We observed no case of active TB among employees. CONCLUSIONS: The prevalence of latent TB among employees to Swiss FACs and the risk of acquiring TB infection through work-related exposure are low. Yearly IGRA controls in the absence of documented TB exposure seem unnecessary.

Explaining age disparities in tuberculosis burden in Taiwan: a modelling study.

BACKGROUND: Tuberculosis (TB) burden shows wide disparities across ages in Taiwan. In 2016, the age-specific notification rate in those older than 65 years old was about 100 times as much as in those younger than 15 years old (185.0 vs 1.6 per 100,000 population). Similar patterns are observed in other intermediate TB burden settings. However, driving mechanisms for such age disparities are not clear and may have importance for TB control efforts. METHODS: We hypothesised three mechanisms for the age disparity in TB burden: (i) older age groups bear a higher risk of TB progression due to immune senescence, (ii) elderly cases acquired TB infection during a past period of high transmission, which has since rapidly declined and thus contributes to little recent infections, and (iii) assortative mixing by age allows elders to maintain a higher risk of TB infection, while limiting spillover transmission to younger age groups. We developed a series of dynamic compartmental models to incorporate these mechanisms, individually and in combination. The models were calibrated to the TB notification rates in Taiwan over 1997-2016 and evaluated by goodness-of-fit to the age disparities and the temporal trend in the TB burden, as well as the deviance information criterion (DIC). According to the model performance, we compared contributions of the hypothesised mechanisms. RESULTS: The 'full' model including all the three hypothesised mechanisms best captured the age disparities and temporal trend of the TB notification rates. However, dropping individual mechanisms from the full model in turn, we found that excluding the mechanism of assortative mixing yielded the least change in goodness-of-fit. In terms of their influence on the TB dynamics, the major contribution of the 'immune senescence' and 'assortative mixing' mechanisms was to create disparate burden among age groups, while the 'declining transmission' mechanism served to capture the temporal trend of notification rates. CONCLUSIONS: In settings such as Taiwan, the current TB burden in the elderly may be impacted more by prevention of active disease following latent infection, than by case-finding for blocking transmission. Further studies on these mechanisms are needed to disentangle their impacts on the TB epidemic and develop corresponding control strategies.

Identification of subclinical tuberculosis in household contacts using exposure scores and contact investigations.

BACKGROUND: The goal of tuberculosis elimination put forward in the End TB Strategy prioritizes diagnosis and treatment of incipient and subclinical TB, recently defined by key stakeholders as "asymptomatic, early pre-clinical disease during which pathology evolves". Regarded as indicative of a high risk of TB progression, considerable efforts have been made to identify these cases through exploration of biomarkers. The present study aimed to evaluate simple scoring systems for TB exposure as screening tools for subclinical TB, the only identifiable of the incipient and subclinical disease states, in a contact investigation (CI) setting of low HIV-prevalence. METHODS: Nested within a large prospective study in household contacts (HHCs) of smear positive pulmonary TB cases in South-India conducted 2010-2012, we assessed 1) the association between the Tuberculosis Contact Score (TCS) and the Infectivity Score, with established tools for Mycobacterium tuberculosis (Mtb) infection, corrected for established TB risk factors, and 2) the capability of the TB exposure scores to identify subclinical TB defined by Mtb-culture positivity in sputum or gastric aspirate (subjects < 5 years) specimen. RESULTS: Of 525 HHCs, 29 were Mtb-culture positive and 96.6% of these asymptomatic. The TCS and the Infectivity Score associated with positive Tuberculin Skin Test and QuantiFeron TB-Gold In-tube assay (QFT) results in multivariate analyses (TCS: ORTST 1.16, 95% CI: 1.01, 1.33; ORQFT 1.33 95% CI: 1.16, 1.51. Infectivity Score: ORTST 1.39, 95% CI: 1.10, 1.76; ORQFT 1.41 95% CI: 1.16, 1.71). The Infectivity Score showed a moderate capability to identify subclinical TB (AUC of 0.61, 95% CI: 0.52, 0.70). CONCLUSIONS: Although our results did not identify an easily applicable screening tool for subclinical TB, the present study indicates that focusing on TB-related symptoms in CI settings may be of limited value for early identification of HHCs with high risk for TB progression.

A blood RNA transcript signature for TB exposure in household contacts.

BACKGROUND: Current tools for diagnosing latent TB infection (LTBI) detect immunological memory of past exposure but are unable to determine whether exposure is recent. We sought to identify a whole-blood transcriptome signature of recent TB exposure. METHODS: We studied household contacts of TB patients; healthy volunteers without recent history of TB exposure; and patients with active TB. We performed whole-blood RNA sequencing (in all), an interferon gamma release assay (IGRA; in contacts and healthy controls) and PET/MRI lung scans (in contacts only). We evaluated differentially-expressed genes in household contacts (log2 fold change ≥1 versus healthy controls; false-discovery rate < 0.05); compared these to differentially-expressed genes seen in the active TB group; and assessed the association of a composite gene expression score to independent exposure/treatment/immunological variables. RESULTS: There were 186 differentially-expressed genes in household contacts (n = 26, age 22-66, 46% male) compared with healthy controls (n = 5, age 29-38, 100% male). Of these genes, 141 (76%) were also differentially expressed in active TB (n = 14, age 27-69, 71% male). The exposure signature included genes from inflammatory response, type I interferon signalling and neutrophil-mediated immunity pathways; and genes such as BATF2 and SCARF1 known to be associated with incipient TB. The composite gene-expression score was higher in IGRA-positive contacts (P = 0.04) but not related to time from exposure, isoniazid prophylaxis, or abnormalities on PET/MRI (all P > 0.19). CONCLUSIONS: Transcriptomics can detect TB exposure and, with further development, may be an approach of value for epidemiological research and targeting public health interventions.

Factors associated with household contacts' tuberculosis testing and evaluation.

PURPOSE: No research has been done in New York City that shows the demographic characteristics of household contacts testing, evaluation, and treatment of LTBI. The objective of the study was to identify demographic factors associated with household contacts' TB testing, evaluation, and LTBI treatment. DESIGN AND METHODS: A retrospective analysis of the New York City (NYC) TB registry data that examined the factors (gender, age, country of birth, race/ethnicity, and borough of residence) associated with TB testing, evaluation, and LTBI treatment. The study sample included all household contacts of TB cases identified from 2010 to 2014 (N = 3,008). The data set was chosen when nurses were the primary case managers at chest centers in the department of health. Descriptive and inferential analysis was used to identify factors associated with testing, evaluation, and LTBI treatment. RESULTS: The demographic characteristics of household contacts associated with testing, evaluation, and LTBI treatment were consistent with those of TB cases in NYC from 2010 to 2014. Those not tested, not fully evaluated, and refusing LTBI treatment were most often aged 18-44 years and were non-US born. Males were significantly more likely than females not to be fully evaluated. Among racial/ethnic groups, Asian and Hispanic persons were at higher risk of not being fully evaluated, and residents of Queens had the highest risk among the five boroughs. In multivariate analyses, age was a significant predictor of behavior, such that the older the person the less likely to get TB testing or to accept LTBI treatment. Non-US country of birth was associated with lower likelihood of being fully evaluated but more likely to accept LTBI treatment when fully evaluated, while Asian or Hispanic race/ethnicity was associated with higher likelihood of both behaviors. CONCLUSIONS: Findings on age from this study will enable public health agencies and public health nurses to plan for effective strategies that will increase the number of household contacts who accept TB testing and evaluation, as well as the numbers who will accept and complete LTBI treatment.

Predicting progression to active tuberculosis: A rate-limiting step on the path to elimination.

In a Perspective, Ajit Lalvani and colleagues discuss new approaches to predicting progression to active tuberculosis.

Evaluating strategies for control of tuberculosis in prisons and prevention of spillover into communities: An observational and modeling study from Brazil.

BACKGROUND: It has been hypothesized that prisons serve as amplifiers of general tuberculosis (TB) epidemics, but there is a paucity of data on this phenomenon and the potential population-level effects of prison-focused interventions. This study (1) quantifies the TB risk for prisoners as they traverse incarceration and release, (2) mathematically models the impact of prison-based interventions on TB burden in the general population, and (3) generalizes this model to a wide range of epidemiological contexts. METHODS AND FINDINGS: We obtained individual-level incarceration data for all inmates (n = 42,925) and all reported TB cases (n = 5,643) in the Brazilian state of Mato Grosso do Sul from 2007 through 2013. We matched individuals between prisoner and TB databases and estimated the incidence of TB from the time of incarceration and the time of prison release using Cox proportional hazards models. We identified 130 new TB cases diagnosed during incarceration and 170 among individuals released from prison. During imprisonment, TB rates increased from 111 cases per 100,000 person-years at entry to a maximum of 1,303 per 100,000 person-years at 5.2 years. At release, TB incidence was 229 per 100,000 person-years, which declined to 42 per 100,000 person-years (the average TB incidence in Brazil) after 7 years. We used these data to populate a compartmental model of TB transmission and incarceration to evaluate the effects of various prison-based interventions on the incidence of TB among prisoners and the general population. Annual mass TB screening within Brazilian prisons would reduce TB incidence in prisons by 47.4% (95% Bayesian credible interval [BCI], 44.4%-52.5%) and in the general population by 19.4% (95% BCI 17.9%-24.2%). A generalized model demonstrates that prison-based interventions would have maximum effectiveness in reducing community incidence in populations with a high concentration of TB in prisons and greater degrees of mixing between ex-prisoners and community members. Study limitations include our focus on a single Brazilian state and our retrospective use of administrative databases. CONCLUSIONS: Our findings suggest that the prison environment, more so than the prison population itself, drives TB incidence, and targeted interventions within prisons could have a substantial effect on the broader TB epidemic.

Social network analysis and whole genome sequencing in a cohort study to investigate TB transmission in an educational setting.

BACKGROUND: TB outbreaks in educational institutions can result in significant transmission and pose a considerable threat to TB control. Investigation using traditional microbiological and epidemiological tools can lead to imprecise screening strategies due to difficulties characterising complex transmission networks. Application of whole genome sequencing (WGS) and social network analysis can provide additional information that may facilitate rapid directed public health action. We report the utility of these methods in combination with traditional approaches for the first time to investigate a TB outbreak in an educational setting. METHODS: Latent tuberculosis infection (LTBI) cases were screenees with a positive T-SPOT®.TB test. Active TB cases were defined through laboratory confirmation of M. tuberculosis on culture or through clinical or radiological findings consistent with infection. Epidemiological data were collected from institutional records and screenees. Samples were cultured and analysed using traditional M. tuberculosis typing and WGS. We undertook multivariable multinomial regression and social network analysis to identify exposures associated with case status and risk communities. RESULTS: We identified 189 LTBI cases (13.7% positivity rate) and nine active TB cases from 1377 persons screened. The LTBI positivity rate was 39.1% (99/253) among persons who shared a course with an infectious case (odds ratio 7.3, 95% confidence interval [CI] 5.2 to 10.3). The community structure analysis divided the students into five communities based on connectivity, as opposed to the 11 shared courses. Social network analysis identified that the community including the suspected index case was at significantly elevated risk of active disease (odds ratio 7.5, 95% CI 1.3 to 44.0) and contained eight persons who were lost to follow-up. Five sputum samples underwent WGS, four had zero single nucleotide polymorphism (SNP) differences and one had a single SNP difference. CONCLUSION: This study demonstrates the public health impact an undiagnosed case of active TB disease can have in an educational setting within a low incidence area. Social network analysis and whole genome sequencing provided greater insight to evolution of the transmission network and identification of communities of risk. These tools provide further information over traditional epidemiological and microbiological approaches to direct public health action in this setting.

Using Reports of Latent Tuberculosis Infection Among Young Children to Identify Tuberculosis Transmission in New York City, 2006-2012.

The presence of latent tuberculosis infection (LTBI) in young children indicates recent tuberculosis (TB) transmission. We reviewed surveillance reports of children with LTBI to assess whether more follow-up is needed to prevent TB in this high-risk population. Data on all children under 5 years of age who were reported by health-care providers or laboratories to the New York City Department of Health during 2006-2012 were abstracted from the TB surveillance and case management system, and those with LTBI were identified. Potential source cases, defined as any infectious TB case diagnosed in the 2 years before a child was reported and whose residence was within 0.5 miles (0.8 km) of the child's residence, were identified. Neighborhood risk factors for TB transmission were examined. Among 3,511 reports of children under age 5 years, 1,722 (49%) had LTBI. The children were aged 2.9 years, on average, and most (64%) had been born in the United States. A potential source case was identified for 92% of the children; 27 children lived in the same building as a TB patient. Children with potential source cases were more likely to reside in neighborhoods with high TB incidence, poverty, and population density. The high proportion of children born in the United States and the young average age of the cases imply that undetected TB transmission occurred. Monitoring reports could be used to identify places where transmission occurred, and additional investigation is needed to prevent TB disease.

Transmission of Mycobacterium Tuberculosis in Households and the Community: A Systematic Review and Meta-Analysis.

The individual- and population-level impact of household tuberculosis exposure on transmission is unclear but may have implications for the effectiveness and implementation of control interventions. We systematically searched for and included studies in which latent tuberculosis infection was assessed in 2 groups: children exposed and unexposed to a household member with tuberculosis. We also extracted data on the smear and culture status of index cases, the age and bacillus Calmette-Guérin vaccination status of contacts, and study design characteristics. Of 6,176 citations identified from our search strategy, 26 studies (13,999 children with household exposure to tuberculosis and 174,097 children without) from 1929-2015 met inclusion criteria. Exposed children were 3.79 (95% confidence interval (CI): 3.01, 4.78) times more likely to be infected than were their community counterparts. Metaregression demonstrated higher infection among children aged 0-4 years of age compared with children aged 10-14 years (ratio of odds ratios = 2.24, 95% CI: 1.43, 3.51) and among smear-positive versus smear-negative index cases (ratio of odds ratios = 5.45, 95% CI: 3.43, 8.64). At the population level, we estimated that a small proportion (<20%) of transmission was attributable to household exposure. Our results suggest that targeting tuberculosis prevention efforts to household contacts is highly effective. However, a large proportion of transmission at the population level may occur outside the household.

A highly transmissible tuberculosis outbreak: the importance of bars.

The transmission of tuberculosis (TB) in bars is difficult to study. The objective was to describe a large TB outbreak in a company's bar and other leisure settings. A descriptive study of a TB outbreak was carried out. Contacts were studied in the index case's workplace bar (five circles of contacts) and other recreational areas (social network of three bars in the index case's neighbourhood). Chest X-rays were recommended to contacts with positive tuberculin skin tests (TST) (⩾5 mm). The risk of latent tuberculosis infection (LTBI) was determined using an adjusted odds ratio. The dose-response relationship was determined using the chi-square test for linear trend. We studied 316 contacts at the index case's workplace and detected five new cases of TB. The prevalence of LTBI was 57·9% (183/316) and was higher in the first circle, 96·0% (24/25), and lower in the fifth, 46·5% (20/43) (P < 0·0001). Among 58 contacts in the three neighbourhood bars, two TB cases were detected and the LTBI prevalence was 51·7% (30/58). Two children of one secondary TB company patient became ill. Bars may be transmission locations for TB and, as they are popular venues for social events, should be considered as potential areas of exposure.

Infectiousness of HIV-Seropositive Patients with Tuberculosis in a High-Burden African Setting.

RATIONALE: Policy recommendations on contact investigation of HIV-seropositive patients with tuberculosis have changed several times. Current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of HIV-seropositive and -seronegative index cases have been performed in sub-Saharan Africa. OBJECTIVES: We assessed the infectiousness of HIV-seropositive and -seronegative patients with tuberculosis to their household contacts and examined potential modifiers of this relationship. METHODS: Adults suffering from their first episode of pulmonary tuberculosis were identified in Kampala, Uganda. Field workers visited index households and enrolled consenting household contacts. Latent tuberculosis infection was measured through tuberculin skin testing, and relative risks were calculated using modified Poisson regression models. Standard assessments of interaction between latent tuberculosis infection, the HIV serostatus of index cases, and other variables were performed. MEASUREMENTS AND MAIN RESULTS: Latent tuberculosis infection was found in 577 of 878 (65.7%) and 717 of 974 (73.6%) household contacts of HIV-seropositive and -seronegative tuberculosis cases (relative risk, 0.89; 95% confidence interval, 0.82-0.97). On further stratification, cavitary lung disease (P < 0.0001 for interaction) and smear status (P = 0.02 for interaction) of tuberculosis cases modified the infectiousness of HIV-seropositive indexes. Cough duration of index cases did not display interaction (P = 0.499 for interaction). CONCLUSIONS: This study suggests that HIV-seropositive tuberculosis cases may be less infectious than HIV-seronegative patients only when they are smear-negative or lack cavitary lung disease. These results may explain heterogeneity between prior studies and provide evidence suggesting that tuberculosis contact investigation should include HIV-seropositive index cases in high disease burden settings.

Position statement on interferon-γ release assays for the detection of latent tuberculosis infection.

Interferon-y release assays (IGRAs), such as the Quantiferon (QIFN) TB-Gold Plus assay (Qiagen, Hilden, Germany) and the T-SPOT.TB test (Oxford Immunotec Limited, Abingdon, United Kingdom), are marketed as a substitute for the tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI). The relative merits of IGRAs and TST have been hotly debated over the last decade. The specificity of IGRAs has been optimised by using Mycobacterium tuberculosis-specific antigens. However, IGRAs are functional in vitro T-cell-based assays that may lack reproducibility due to specimen collection, transport, processing and kit manufacturing issues. Longitudinal studies comparing the ability of IGRAs and TST to predict the future development of active tuberculosis disease (TB) are the ultimate arbiters on the respective utility of these assays. Three meta-analyses addressing this comparison have now been published and clinical experience with IGRAs is accumulating. The systematic reviews show that IGRAs and TST have similar (but poor) ability to identify patients with LTBI at risk of developing active TB disease. The improved specificity of IGRAs however may reduce the number of patients requiring preventative therapy. Based on these meta-analyses, The National Tuberculosis Advisory Committee (NTAC) now recommends either TST or an IGRA for the investigation of LTBI in most circumstances. Both tests may be used in patients where the risk of progression to active TB disease is high and the disease sequelae potentially severe (eg. LTBI testing in immunocompromised patients or those commencing anti-tumour necrosis factor-a (TNF) therapy). Neither test should be used in the investigation of active TB disease (though TST and/or IGRA may be used as supplementary tests in paediatric cases). The choice of test for serial testing in healthcare workers (HCWs) remains controversial. A preference remains for TST in this circumstance because IGRAs have been bedevilled by higher rates of reversions and conversions when used for serial testing. These recommendations supersede all previous NTAC IGRA statements.

Tuberculosis screening in an aged care residential facility in a low-incidence setting.

Tuberculosis (TB) remains a disease of high morbidity in Australia, with implications for both public health and the individual. Cost analyses is relevant for programmatic evaluation of TB. There is minimal published TB cost data in the Australian setting. Patients with drug sensitive active pulmonary TB (DS-PTB) and latent TB (LTBI) were enrolled in a single tertiary referral centre to evaluate healthcare provider costs. The median cost of treating drug susceptible pulmonary TB in this case series was 11,538 AUD. Approximately 50% of total costs is derived from inpatient hospitalisation bed days. In comparison, the average cost of managing latent TB was 582 AUD per completed course. We find the median provider cost of our DS-PTB treatment group comparable to costs from other regions globally with similar economic profiles. A program designed to detect and treat LTBI to prevent subsequent disease may be cost effective in appropriately selected patients and warrants further study.

The epidemiology of tuberculosis in the Australia Capital Territory, 2006-2015.

AIM: To review the epidemiology of tuberculosis (TB) in the Australian Capital Territory (ACT) over a 10 year period. Methods: A retrospective analysis of the ACT TB notification data from 1 January 2006 to 31 December 2015 was conducted. RESULTS: Over the 10 year study period there were 171 TB notifications in the ACT, with an increasing trend in the number of notifications over time. The median age of cases was 36 years (range 14 to 91 years) and 53.8% of cases were male. Most TB cases (84.2%) were born overseas. Among Australian-born cases the most common risk factor for acquiring TB was close/household contact with a known case of TB (30.8%). The most common risk factor in the overseas-born population was past travel or residence in a high-risk country (86.9%). Of all the TB cases notified, 82.4% successfully completed treatment. CONCLUSION: There was an increasing trend in the number of TB notifications in the ACT over the study period. The highest rate of TB notifications remained in the overseas-born population; with other studies suggesting this is commonly due to reactivation of latent tuberculosis infection (LTBI). As Australia starts working towards TB elimination, options for the screening and management of LTBI, especially in high risk populations, need to be explored.

Tuberculosis notifications in Australia, 2014.

In 2014, the National Notifiable Diseases Surveillance System received 1,339 tuberculosis (TB) notifications, representing a rate of 5.7 per 100,000 population. Australia has achieved and maintained good tuberculosis (TB) control since the mid-1980s, sustaining a low annual TB incidence rate of approximately 5 to 6 cases per 100,000 population. The number of multi-drug resistant TB (MDR-TB) cases diagnosed in Australia is low by international standards, with approximately 1-2% of notifications per year being classified as MDR-TB. Australia's overseas-born population continued to represent the majority (86%) of TB notifications and Australia's Aboriginal and Torres Strait Islander population continue to record TB rates around 6 times higher than the Australian born non Indigenous population. Whilst Australia has achieved excellent and sustained control of TB in Australia, sustained effort is still required to reduce rates further and contribute to the achievement of the World Health Organization's goal to end the global TB epidemic by 2035.

First evaluation of QuantiFERON-TB Gold Plus performance in contact screening.

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-γ release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells in contacts of TB patients.Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's κ of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-γ production between the two antigen tubes (TB2-TB1) was used as an estimate of CD8+ stimulation provided by the TB2. TB2-TB1 values >0.6 IU·mL-1 were significantly associated with proximity to the index case and European origin.QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon-γ response in the new antigen tube used an indirect estimate of specific CD8+ response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection.

Risk Assessment of Tuberculosis in Contacts by IFN-γ Release Assays. A Tuberculosis Network European Trials Group Study.

RATIONALE: Latent infection with Mycobacterium tuberculosis is defined by a positive IFN-γ release assay (IGRA) result in the absence of active tuberculosis. Only few, mostly monocentric studies have evaluated the role of IGRAs to predict the development of tuberculosis in recent contacts in low-incidence countries of tuberculosis. OBJECTIVES: To analyze IGRA results and the effect of preventive chemotherapy on tuberculosis progression rates among recent contacts. METHODS: Results from contact investigations at 26 centers in 10 European countries including testing for latent infection with M. tuberculosis by the QuantiFERON-TB Gold In-Tube (QFT) test or the T-SPOT.TB (TSPOT) were prospectively collected and analyzed. MEASUREMENTS AND MAIN RESULTS: Among 5,020 contacts of 1,023 index cases, 25 prevalent secondary cases were identified at screening. Twenty-four incident cases occurred among 4,513 contacts during 12,326 years of cumulative follow-up. In those with a positive IGRA result, tuberculosis incidence was 0.2 (QFT) and 0 (TSPOT) per 100 patient-years when contacts received preventive chemotherapy versus 1.2 (QFT) and 0.8 (TSPOT) per 100 patient-years in those not treated (38 and 37 patients needed to be treated to prevent one case, respectively). Positive and negative predictive values were 1.9% (95% confidence interval [CI], 1.1-3.0) and 99.9% (95% CI, 99.7-100) for the QFT and 0.7% (95% CI, 0.1-2.6) and 99.7% (95% CI, 99.1-99.9) for the TSPOT. CONCLUSIONS: Tuberculosis rarely developed among contacts, and preventive chemotherapy effectively reduced the tuberculosis risk among IGRA-positive contacts. Although the negative predictive value of IGRAs is high, the risk for the development of tuberculosis is poorly predicted by these assays.

Vitamin D status and incidence of tuberculosis infection conversion in contacts of pulmonary tuberculosis patients: a prospective cohort study.

The objective of this study was to estimate the relationship between serum vitamin D (VitD) status and tuberculosis (TB) infection conversion (TBIC), measured by the tuberculin skin test (TST) and an interferon-gamma release assay, the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in the contacts of pulmonary TB patients in Castellon (Spain) in a prospective cohort study from 2010 to 2012. Initially, the participants were negative to latent TB infection after a screening that included TST and QFT-GIT tests, and other examinations. A baseline determination of 25-hydroxyvitamin D [25(OH)D] was obtained by chemiluminescence immunoassay. After 8-10 weeks, participants were screened for a second time to determine TB infection conversion (TBIC). Poisson regression models were used in the statistical analysis. Of the 247 participants in the cohort, 198 (80·2%) were screened twice and 18 (9·1%) were TBIC cases. The means of VitD concentration in the TBIC cases and the non-cases were 20·7±11·9 and 27·2±11·4 ng/ml (P = 0·028), respectively. Adjusted for high exposure and TB sputum acid-fast bacilli (AFB)-positive index case, higher serum VitD concentration was associated with low incidence of TBIC (P trend = 0·005), and an increase of 1 ng/ml VitD concentration decreased the incidence of TBIC by 6% (relative risk 0·94, 95% confidence interval 0·90-0·99, P = 0·015). The results suggest that sufficient VitD level could be a protective factor of TBIC.

TRANSMISSION AND RISK FACTORS FOR LATENT TUBERCULOSIS INFECTIONS AMONG INDEX CASE-MATCHED HOUSEHOLD CONTACTS.

An understanding of the risk factors associated with acquiring and transmitting Mycobacterium tuberculosis (MTB) is required for controlling tuberculosis (TB). We aimed to determine the risk factors and transmission factors for latent tuberculosis infection (LTBI) in northeastern Thailand. Household contact persons (n = 70) and matched index patients with pulmonary TB (n = 42) who presented to Srinagarind Hospital, Khon Kaen, Thailand were interviewed from September 1, 2012 to March 31, 2014. LTBI was determined by positive results on both a tuberculin skin test and the QuantiFERON-TB Gold In-Tube test. Multivariate analysis of host and environmental risk factors was performed. Among contact persons, being aged 20 years (adjusted OR=14.0; 95% CI: 1.2-159.5), having a family relationship with a TB subject such as being a spouse or parent (adjusted OR=24.9; 95% CI: 2.4-263.9) and exposure to a TB subject for 5 hours/day (adjusted OR=9.2; 95% CI: 1.4-58.1) were risk factors for LTBI. Having a high bacillary load (adjusted OR=2; 95% CI: 1.26-3.17) or a moderate bacillary load (adjusted OR=1.39; 95% CI: 1.04-1.84) among TB subjects correlated with increased transmissibility compared to having a low bacillary load. The type of dwelling and density of household members were not found to be risk factors for LTBI in our study. We conclude being aged 20 years and having a relationship with a TB patient as a spouse or parent were risk factors for acquiring LTBI, and having a higher bacillary load was a risk factor for transmitting TB. Keywords: latent tuberculosis infection, transmission factor, risk factor, Mycobacterium tuberculosis, interferon-gamma release assay, Thailand