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.

Tuberculosis infection in children visiting friends and relatives in countries with high incidence of tuberculosis: A study protocol.

INTRODUCTION: Tuberculosis (TB) is a global infectious disease. In low-incidence countries, paediatric TB affects mostly immigrant children and children of immigrants. We hypothesize that these children are at risk of exposure to Mycobacterium tuberculosis when they travel to the country of origin of their parents to visit friends and relatives (VFR). In this study, we aim to estimate the incidence rate and risk factors associated to latent tuberculosis infection (LTBI) and TB in VFR children. METHODS AND ANALYSIS: A prospective study will be carried out in collaboration with 21 primary health care centres (PCC) and 5 hospitals in Catalonia, Spain. The study participants are children under 15 years of age, either immigrant themselves or born to immigrant parents, who travel to countries with high incidence of TB (≥ 40 cases/100,000 inhabitants). A sample size of 492 children was calculated. Participants will be recruited before traveling, either during a visit to a travel clinic or to their PCC, where a questionnaire including sociodemographic, epidemiological and clinical data will be completed, and a tuberculin skin test (TST) will be performed and read after 48 to 72 hours; patients with a positive TST at baseline will be excluded. A visit will be scheduled eight to twelve-weeks after their return to perform a TST and a QuantiFERON-TB Gold Plus test. The incidence rate of LTBI will be estimated per individual/month and person/year per country visited, and also by age-group. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Ethics Committee of the Hospital Universitari Mútua Terrassa (code 02/16) and the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P16/094). Articles will be published in indexed scientific journals. TRIAL REGISTRATION: Clinical-Trials.gov: NCT04236765.

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.

Tuberculosis Screening, Testing, and Treatment of US Health Care Personnel: ACOEM and NTCA Joint Task Force on Implementation of the 2019 MMWR Recommendations.

: On May 17, 2019, the US Centers for Disease Control and Prevention and National Tuberculosis Controllers Association issued new Recommendations for Tuberculosis Screening, Testing, and Treatment of Health Care Personnel, United States, 2019, updating the health care personnel-related sections of the Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005. This companion document offers the collective effort and experience of occupational health, infectious disease, and public health experts from major academic and public health institutions across the United States and expands on each section of the 2019 recommendations to provide clarifications, explanations, and considerations that go beyond the 2019 recommendations to answer questions that may arise and to offer strategies for implementation.

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.

HIV prevalence and TB in migrant miners communities of origin in Gaza Province, Mozambique: The need for increasing awareness and knowledge.

BACKGROUND: As part of ongoing efforts to generate evidence needed on HIV and tuberculosis (TB) to inform policies and programs aimed to improve the health outcomes of migrants and communities affected by migration and mining, a preliminary investigation was conducted through a biological and behavioral (BBS) approach related to HIV and TB in two communities of origin of migrant mineworkers in Gaza Province. The main objective was to determine the prevalence of HIV and the rates of asymptomatic infection by TB, and the social and behavioral risk factors associated. METHODS: A cross-sectional survey was conducted from May to June 2017 using a simple random sampling methodology. Eligible participants were individuals who were living in the community at the time the survey was conducted, which included adult mine workers and members of their families aged 18 and above. A socio-behavioral questionnaire was administered, blood specimens were collected for HIV testing (Determine/Unigold) and sputum for TB (GeneXpert MTB/RIF) was collected. The statistical analysis was performed using the R studio software to produce means, proportion and odds ratio at 95% confidence intervals. RESULTS: A total of 1012 participants were enrolled, 75.2% were females, with a median age of 34. The overall prevalence of HIV found in the two communities was 24.2% (CI: 21.6-27.0) and was higher in the rural community (31.6%; 95% CI: 27.0-35.3). The prevalence of active TB was found to be 0.3% (n = 3) while 7.5% of the participants self-reported to have been previously diagnosed with TB at some point in their life. Only 2.8% of participants had knowledge of the basic principles of TB transmission. Condom use at last sexual intercourse with a regular partner was low among both sexes (17.3% male and 12.6% female). A considerable proportion of participants had not been aware of their HIV positive serostatus(31.1% female and 25.0% male). About 1/3 of the participants had had a history of STIs. CONCLUSION: The results of this survey confirm a high prevalence of HIV in communities of origin of migrant miners in Gaza province. Findings also demonstrated low levels of awareness/ knowledge and prevention of TB and HIV. It is important to strengthen strategies that encourage regular HIV testing and TB screening. Appropriate communication interventions on methods of transmission and prevention of HIV and TB in these communities must be intensified, as well as ensuring ongoing linkage to TB and HIV social and healthcare services.

HIV prevalence and TB in migrant miners communities of origin in Gaza Province, Mozambique: the need for increasing awareness and knowledge

As part of ongoing efforts to generate evidence needed on HIV and tuberculosis (TB) to inform policies and programs aimed to improve the health outcomes of migrants and communities affected by migration and mining, a preliminary investigation was conducted through a biological and behavioral (BBS) approach related to HIV and TB in two communities of origin of migrant mineworkers in Gaza Province. The main objective was to determine the prevalence of HIV and the rates of asymptomatic infection by TB, and the social and behavioral risk factors associated. Methods A cross-sectional survey was conducted from May to June 2017 using a simple random sampling methodology. Eligible participants were individuals who were living in the community at the time the survey was conducted, which included adult mine workers and members of their families aged 18 and above. A socio-behavioral questionnaire was administered, blood specimens were collected for HIV testing (Determine/Unigold) and sputum for TB (GeneXpert MTB/RIF) was collected. The statistical analysis was performed using the R studio software to produce means, proportion and odds ratio at 95% confidence intervals. Results A total of 1012 participants were enrolled, 75.2% were females, with a median age of 34. The overall prevalence of HIV found in the two communities was 24.2% (CI: 21.6­27.0) and was higher in the rural community (31.6%; 95% CI: 27.0­35.3). The prevalence of active TB was found to be 0.3% (n = 3) while 7.5% of the participants self-reported to have been previously diagnosed with TB at some point in their life. Only 2.8% of participants had knowledge of the basic principles of TB transmission. Condom use at last sexual intercourse with a regular partner was low among both sexes (17.3% male and 12.6% female). A considerable proportion of participants had not been aware of their HIV positive serostatus(31.1% female and 25.0% male). About 1/3 of the participants had had a history of STIs. Conclusion The results of this survey confirm a high prevalence of HIV in communities of origin of migrant miners in Gaza province. Findings also demonstrated low levels of awareness/ knowledge and prevention of TB and HIV. It is important to strengthen strategies that encourage regular HIV testing and TB screening. Appropriate communication interventions on methods of transmission and prevention of HIV and TB in these communities must be intensified, as well as ensuring ongoing linkage to TB and HIV social and healthcare services.

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.

Cross-validation of existing signatures and derivation of a novel 29-gene transcriptomic signature predictive of progression to TB in a Brazilian cohort of household contacts of pulmonary TB.

The goal of this study was to identify individuals at risk of progression and reactivation among household contacts (HHC) of pulmonary TB cases in Vitoria, Brazil. We first evaluated the predictive performance of six published signatures on the transcriptional dataset obtained from peripheral blood mononuclear cell samples from HHC that either progressed to TB disease or not (non-progressors) during a five-year follow-up. The area under the curve (AUC) values for the six signatures ranged from 0.670 to 0.461, and the PPVs did not reach the WHO published target product profiles (TPPs). We therefore used as training cohort the earliest time-point samples from the African cohort of adolescents (GSE79362) and applied an ensemble feature selection pipeline to derive a novel 29-gene signature (PREDICT29). PREDICT29 was tested on 16 progressors and 21 non-progressors. PREDICT29 performed better in segregating progressors from non-progressors in the Brazil cohort with the area under the curve (AUC) value of 0.911 and PPV of 20%. This proof of concept study demonstrates that PREDICT29 can predict risk of progression/reactivation to clinical TB disease in recently exposed individuals at least 5 years prior to disease development. Upon validation in larger and geographically diverse cohorts, PREDICT29 can be used to risk-stratify recently infected for targeted therapy.

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.

Addressing the threat from within: Investigation of respiratory symptoms in a health care worker with untreated latent tuberculosis infection.

Tuberculosis (TB) in the health care worker demands orchestrated efforts from health care institutions to promptly identify cases and address community risk. We describe a pediatric intensive care unit nurse with latent TB infection who developed hemoptysis and a lung infiltrate concerning for active TB. Her evaluation and contact investigation were facilitated by our institution's command center. Although TB was ultimately ruled out, this case tested our team-based care in response to a suspected high-consequence pathogen.

Directriz nacional para tratamento da tuberculose latente / National Guideline for the Treatment of Latent Tuberculosis

A Tuberculose Latente (TBL) é definida como um estado de resposta imunológica persistente à estimulação pelo antígeno do Mycobacterium tuberculosis sem evidência de manifestação clínica da doença activa. A probabilidade de progressão da infecção para doença activa depende de vários factores dentre os quais a idade, profissão e a condição clínica da pessoa, sendo o mais importante o estado imunológico.

Age-specific prevalence of TB infection among household contacts of pulmonary TB: Is it time for TB preventive therapy?

BACKGROUND: Household contacts (HHCs) of TB patients are at high risk of developing evidence of latent TB infection (LTBI) and active disease from the index patient. We estimated the age-specific prevalence of LTBI and the force of infection (FI), as a measure of recent transmission, among HHCs of active TB patients. METHODS: A cross-sectional analysis of HHCs of pulmonary TB patients enrolled in a prospective study, 'CTRIUMPh', was conducted at two sites in India. LTBI was defined as either a positive tuberculin skin test (induration ≥5 mm) or QuantiFERON-Gold in tube test (value ≥0.35 IU/ml) and was stratified by age. FI, which is a measure of recent transmission of infection and calculated using changes in age-specific prevalence rates at specific ages, was calculated. Factors associated with LTBI were determined by logistic regression models. RESULTS: Of 1020 HHCs of 441 adult pulmonary TB cases, there were 566 (55%) females and 289 (28%) children aged ≤15 y. While screening for the study 3% of HHC were diagnosed with active TB. LTBI prevalence among HHCs of pulmonary TB was 47% at <6 y, 53% between 6-14 y and 78% between 15-45 y. FI increased significantly with age, from 0.4 to 1.15 in the HHCs cohort (p=0.05). CONCLUSION: This study observed an increased prevalence of LTBI and FI among older children and young adults recently exposed to infectious TB in the household. In addition to awareness of coughing etiquette and general hygiene, expanding access to TB preventive therapy to all HHCs, including older children, may be beneficial to achieve TB elimination by 2035.

Effectiveness of interventions for reducing TB incidence in countries with low TB incidence: a systematic review of reviews.

AIMS: What is the evidence base for the effectiveness of interventions to reduce tuberculosis (TB) incidence in countries which have low TB incidence? METHODS: We conducted a systematic review of interventions for TB control and prevention relevant to low TB incidence settings (<10 cases per 100 000 population). Our analysis was stratified according to "direct" or "indirect" effects on TB incidence. Review quality was assessed using AMSTAR2 criteria. We summarised the strength of review level evidence for interventions as "sufficient", "tentative", "insufficient" or "no" using a framework based on the consistency of evidence within and between reviews. RESULTS: We found sufficient review level evidence for direct effects on TB incidence/case prevention of vaccination and treatment of latent TB infection. We also found sufficient evidence of beneficial indirect effects attributable to drug susceptibility testing and adverse indirect effects (measured as sub-optimal treatment outcomes) in relation to use of standardised first-line drug regimens for isoniazid-resistant TB and intermittent dosing regimens. We found insufficient review level evidence for direct or indirect effects of interventions in other areas, including screening, adherence, multidrug-resistant TB, and healthcare-associated infection. DISCUSSION: Our review has shown a need for stronger evidence to support expert opinion and country experience when formulating TB control policy.

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.

Temporal trends in the prevalence of Mycobacterium tuberculosis infection in South African adolescents.

South Africa. 1) To measure changes in the adolescent prevalence of latent tuberculous infection (LTBI) between 2005 and 2015, and 2) to evaluate medium-term impact of TB control measures on LTBI prevalence. We compared baseline data from a cohort study (2005-2007) and a vaccine trial (2014-2015) which enrolled adolescents from the same eight South African high schools. LTBI was defined based on QuantiFERON®-TB Gold In-Tube test positivity. We analysed data from 4880 adolescents between 2005 and 2007, and 1968 adolescents between 2014 and 2015, when the average LTBI prevalence was respectively 43.8% (95%CI 28.4-59.1) vs. 48.5% (95%CI 41.1-55.8). Age-specific LTBI prevalence increased between the ages 12 and 18 years by 13% only in lower socio-economic quintile schools, where the average LTBI prevalence was unchanged between the two periods (54% vs. 53%). In the highest socio-economic quintile schools, LTBI prevalence did not increase with age; however, the average LTBI prevalence increased from 20% to 38% between the two periods. Adolescent LTBI prevalence remained high and constant over a decade, suggesting that Mycobacterium tuberculosis transmission to children was not impacted in the medium term by effective TB control efforts. Trends in adolescent LTBI prevalence should be interpreted in the context of the sociodemographic factors that affect the risk of transmission before and during adolescence. .

Tuberculosis incidence among infected contacts detected through contact tracing of smear-positive patients.

BACKGROUND: The contacts of people with pulmonary tuberculosis (PTB) have a high risk of becoming infected and developing tuberculosis (TB). Our aim was to determine the incidence of TB and its risk factors in a cohort of contacts with latent TB infection (LTBI) detected through contact tracing of smear-positive PTB cases. METHODS AND FINDINGS: We performed a population-based retrospective cohort study including contacts that had LTBI, and were contacts of people with PTB who started treatment between 2008 and 2014. We followed up contacts until they developed TB or until the end date for follow-up (31st December 2016). We used Kaplan-Meier curves to compute incidence at 2 and 5 years, and Cox regression to compute hazard ratios (HR) and their 95% confidence intervals (CI). We analyzed 3097 close contacts of 565 PTB cases. After exclusion of 81 co-prevalent TB cases, 953 contacts had LTBI, of which 14 developed TB. Their risk of developing TB after two and five years was 0.7% (CI: 0.3-1.6) and 1.8% (CI: 1.1-3.1) respectively. Contacts who had not been referred for LTBI treatment had a 1.0% (CI: 0.2-4.0) risk at 5 years. Risk of developing TB at 5 years was 1.2% (CI: 0.5-3.0) among people who completed treatment, and 11.1% (CI: 5.1-23.3) for those who did not. Risk factors for TB were not completing LTBI treatment (HR 9.4, CI: 2.9-30.8) and being female (HR 3.5, CI: 1.1-11-3). CONCLUSIONS: LTBI treatment plays a fundamental role in decreasing the risk of developing TB. It is necessary to achieve a maximum contact tracing coverage and the highest possible compliance with LTBI treatment.

Achieving TB elimination in India: The role of latent TB management.

The elimination of Tuberculosis (TB) in settings with a high dual burden of active and latent TB is one of the most important public health challenges of the 21st century. India has the highest TB burden in the world and nearly 40% of the population being infected with TB. There also exist large often overlapping socially and medically vulnerable populations like the PLHIV, pediatric TB contacts, children with protein-energy malnutrition, homeless people, workers in silica industry and adults with low BMI. A significantly higher risk of progression into active tubercular disease exists in those with compromised immune or nutritional status. It is uncertain if global TB elimination targets can be achieved in the absence of aggressive LTBI treatment strategies for interrupting the chain of transmission of the disease. India hence needs to accelerate and prioritize capacity building in latent TB research. A research agenda is outlined for generating evidence towards the evolution of critical evidence-based policy for LTBI management under Indian health settings.