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Using a matched case control design conducted at MRC Gambia in 2015, we measured vitamin D levels in pairs of asymptomatic children with discordant tuberculin skin test status despite the same sleeping proximity to the same adult TB index case. Median ages of groups (infected; 10.0 years, uninfected 8.8 years) were not significantly different (p = 0.13). Mean vitamin D levels were 2.05 ng/mL (95% CI − 0.288 to 4.38) higher in 24 highly TB-exposed uninfected children compared with 24 matched highly TB-exposed infected children (p = 0.08). The findings warrant further investigation in larger studies to understand the implications and significance. Conclusion: Vitamin D levels were higher in TB-uninfected children compared with TB-infected despite equal high exposure to a TB case. What is Known:• Paediatrics TB represents one of the leading causes of child death globally.• Current literature shows an inconsistent relationship between vitamin D deficiency and increased risk of TB disease however a large Phase 3 trial of vitamin D supplementation in (largely vitamin D deficient) Mongolian children did not find any association with TB infection rates. What is New:• This study adds to the literature in a vitamin D sufficient paediatric population whereby children with equal exposure to a household TB case with no evidence of TB infection have higher levels of vitamin D compared with matched children with TB infection.

This review discusses the recent literature (2006–2020) about the epidemiology, clinical presentation, diagnosis, and management of infants with congenital or perinatal tuberculosis (TB). While the incidence of childhood TB is declining in the United States and worldwide, many case reports describe how clinical suspicion for neonatal TB is raised only if an ill-appearing neonate does not improve with broad-spectrum antibiotics. Furthermore, the delay in initiating appropriate anti-TB therapy often results in the need for significant cardiopulmonary support and/or an increase in mortality. This review summarizes important clinical indications in the maternal and newborn history, the evaluation of an infant with possible TB exposure, and step-by-step recommendations for the treatment and follow-up of infants with TB.

Background: In high TB/HIV settings, the increased risk for TB amongst children exposed to HIV has been established through biomedical tests. Screening HIV exposed children for TB can improve early childhood TB detection and treatment. Objective: This study assessed the utility of a modified World Health Organization (WHO) tool by including HIV variables, to determine TB exposure amongst HIV exposed children presenting to a “Well Child” Clinic (CWC). Methods: Clinical data were obtained from medical records and/or from the caregivers of children presenting to CWC. Data was analyzed to explore factors associated with positive screening for TB, including being exposed to HIV and current HIV status. Results: Five percent (55/1100) screened reported a close TB contact and 21% (n=231) had positive TB symptom screen. History of close TB contact was a risk factor for positive screening for TB symptoms (OR 1.89 CI 1.05-3.4) while being HIV negative was protective (OR 0.3, Cl 0.19-0.62). HIV exposure was associated with increased risk of TB exposure (OR 2.9 CI 1.61-5.19). Conclusion: Integrating HIV variables in the existing WHO screening tool for childhood TB can be useful in early detec- tion and treatment of TB in HIV exposed children in resource limited settings. Keywords: Childhood TB screening; HIV Exposure screening; TB/HIV integration.

SETTING: Adolescents (age: 15–19 years) from the National Family Health Survey-4 (2015–2016), India.OBJECTIVE: To examine the sociodemographic and nutritional characteristics of adolescents with reported TB and those with a reported household TB exposure.METHODS: This was a cross-sectional study using secondary data. We assessed the factors associated with TB (reported in adolescents, or in a household member) using log binomial regression. We used height-for-age and body mass index for age Z-scores for stunting and thinness, respectively.RESULTS: Of the total 277 059 adolescents, 377 (136/100 000, 95%CI 123–151) were reported with TB and this was similar in both sexes. Another 4528 adolescents (1.6%, 95%CI 1.6–1.7) reported household TB exposure. Poverty and urban residence were associated with higher prevalence of TB and household TB exposure. The proportion of stunting was 40.7% (95%CI 33.5–48.0) in adolescents with reported TB and 38.2% (95%CI 36.2–40.2) (P = 0.248) in those with household TB exposure.CONCLUSION: Prevalence of reported adolescent TB was lower than adult TB. Poverty and urban residence were risk factors for both TB and household TB exposure. Chronic undernutrition was highly prevalent among those reported to have TB and in those at risk of TB by virtue of having household TB exposure.

Patients with diabetes mellitus are susceptible to active tuberculosis (TB) and latent TB infection (LTBI) [1–3]. Close contact with patients with infectious TB is associated with an increased risk of having coprevalent TB or developing incident TB [4, 5]. However, information on the burden of incident TB in contacts with underlying diabetes is limited. Considering post-exposure TB in patients with diabetes, metformin has demonstrated anti-TB effects in preclinical studies and association with a low LTBI prevalence in a cross-sectional survey [6, 7]. Despite metformin's wide use and correlation with a lower TB risk in patients with type 2 diabetes (T2D) [8], the impact of metformin use during TB exposure on subsequent TB risk has not been thoroughly investigated. We aimed to obtain the rate of post-exposure incident TB, but not coprevalent TB, in T2D patients and evaluate whether TB risk can be modified by metformin use during the TB-exposure period., This TB contact cohort study showed that the risk of incident TB, not coprevalent TB, was highest in the diabetes group without metformin use during TB exposure, followed by the nondiabetes population, and was lowest in the diabetes group with metformin use https://bit.ly/3fpJyF0

Background: After the breakup of the Soviet Union, the annual incidence of tuberculosis (TB) in children 15–17 years of age increased in the Russian Federation from 16 per 100 000 population in 1992 to 37 per 100 000 in 2009, and new control measures were implemented. Methods: Children were screened annually for TB exposure with a tuberculin skin test (TST) at age 1–8 years. If positive, they were investigated for active TB. If no active TB was found, they were treated with isoniazid for 4–6 months; they then underwent 6-monthly skin tests (which included two recombinant proteins) until negative and annual skin tests thereafter. From the age of 8 years, the yearly follow-up was performed using the skin test that included two recombinant proteins, either until they became negative, developed active TB, or turned 18 years. Results: The annual incidence of TB in Russian children decreased from 19.1 per 100 000 population in 2001 to 8.3 per 100 000 population in 2018. Conclusions: Annual screening for TB exposure with treatment for latent or active TB has reduced the annual incidence of TB in Russian children aged 15–17 years to 1992 levels. Keywords: Latent tuberculosis, Screening of children and adolescents, Recombinant tuberculosis antigen

Childhood tuberculosis (TB) has been underreported and underrepresented in TB statistics across the globe. Contributing factors include health system barriers, diagnostic barriers, and community barriers leading to an underdetected epidemic of childhood tuberculosis. Despite considerable progress in childhood TB management, there is a concerning gap in policy and practice in high-burden countries leading to missed opportunities for active case detection, early diagnosis and treatment of TB exposure, and infection and disease in children regardless of human immunodeficiency virus status. Bridging this gap requires multisectoral coordination and political commitment along with an eye to research and innovation with potential to scale.

Background Childhood tuberculosis (TB) is acquired after exposure to an infectious TB case, often within the household. We prospectively screened children 6-59 months of age, exposed and unexposed to an infectious TB case within the same household, for latent tuberculosis infection (LTBI), in Dar es Salaam, Tanzania. Methods We collected medical data and clinical specimens (to evaluate for helminths, TB and HIV coinfections) and performed physical examinations at enrollment and at 3-month and 6-month follow-up surveys. LTBI was assessed using QuantiFERON-TB Gold (QFT) at enrollment and at 3 months. Results In total, 301 children had complete data records (186 with TB exposure and 115 without known TB exposure). The median age of children was 26 months (range: 6-58); 52% were females, and 4 were HIV positive. Eight children (3%) developed TB during the 6-month follow-up. We found equal proportions of children with LTBI among those with and without exposure: 20% (38/186) versus 20% (23/115) QFT-positive, and 2% (4/186) versus 4% (5/115) indeterminate QFT. QFT conversion rate was 7% (22 children) and reversion 8% (25 children). Of the TB-exposed children, 72% initiated isoniazid preventive therapy, but 61% of parents/caregivers of children with unknown TB exposure and positive QFT refused isoniazid preventive therapy. Conclusions In this high burden TB setting, TB exposure from sources other than the household was equally important as household exposure. Nearly one third of eligible children did not receive isoniazid preventive therapy. Evaluation for LTBI in children remains an important strategy for controlling TB but should not be limited to children with documented TB exposure.

More than 10 days of fever or 13 days of cough differentiated adolescent patients presenting to a pediatric emergency department with infectious tuberculosis (TB) from most patients with pneumonia. Upper lobe involvement was significantly more common in patients with TB. Symptom- and radiograph-based algorithms could minimize TB exposure and aid diagnosis.

In a matched case-control study in Pakistan, we found that quantified tuberculosis (TB) exposure using a 10-point score is associated with prevalent TB disease in pediatric household contacts. A 1 unit increase in TB exposure score increased the odds of TB disease by 44% (conditional odds ratio: 1.44, 95% confidence interval: 1.33-1.56). Collecting well-documented exposure history can help TB diagnosis in resource-limited settings.

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.

Delayed diagnosis of congenital tuberculosis (TB) in the neonatal intensive care unit (NICU) is a serious problem in terms of infection control. Here, we report our preemptive infection control activities implemented after the diagnosis of miliary TB in a mother of preterm twins (index twins, NB1 and NB2) in the NICU. In addition, we reviewed previous case reports of congenital TB exposure in the NICU setting. Immediately after diagnosing miliary TB in the mother, the index twins were isolated before their TB diagnosis and received preemptive anti-TB medication; contact investigations were also conducted. Eventually, NB1 was diagnosed with congenital TB at 29 days of age, and NB2 showed no definite evidence of TB. Through contact investigation, 11 of the 16 exposed infants received isoniazid prophylaxis and no positive tuberculin skin test results were obtained after 3 months. One of the 31 exposed healthcare workers showed new interferon-gamma release assay conversion. Moreover, our case showed a much shorter contagious period compared to that in previous reports (8 versus 17-102 days). This suggests that a high index of suspicion and prompt measures can help prevent congenital TB outbreaks and reduce the burden of infection control activities in the NICU.

Case Presentation A 33-year-old white man presented to the ED with 1-month history of worsening dyspnea. He experienced gradual onset of right-sided scapular pain and shortness of breath on exertion that progressively worsened over the course of 1 month. He had a mild nonproductive cough and intermittent subjective fevers and reported weight loss of approximately 2 kg over 1 month. He had a history of two episodes of acute pancreatitis that was thought to be autoimmune in origin. He was a never smoker; he denied illicit drug use or recent alcohol consumption. He had no known TB exposure, but his mother had a history of sarcoidosis.

Background The understanding of early events following TB exposure is limited by traditional tests that rely on detection of an immune response to infection, which is delayed, or on imaging tests with low sensitivity for early disease. We investigated for evidence of lung abnormalities in heavily exposed TB contacts using PET/MRI. Methods 30 household contacts of 20 index patients underwent clinical assessment, IGRA testing, chest x-ray and PET/MRI scan using 18-F-FDG. MRI images were examined by a radiology/nuclear medicine dual-qualified physician using a standardised report form, while PET/MRI images were examined independently by another radiology/nuclear medicine dual-qualified physician using a similar form. Standardised uptake value (SUV) was quantified for each abnormal lesion. Results IGRA was positive in 40%. PET/MRI scan was abnormal in 30%, predominantly FDG uptake in hilar or mediastinal lymph nodes and lung apices. We did not identify any relationship between PET/MRI findings and degree of exposure or IGRA status. Conclusion PET-based imaging may provide important insights into the natural history following exposure to TB that may not be available from traditional tests of TB immune response or imaging. The clinical significance of the abnormalities is uncertain and merits further investigation in longitudinal studies.

Background: To prevent the spread of infection of tuberculosis (TB), sufficient knowledge and safe practices regarding occupational exposure are crucial for all employees working in TB hospitals. Objectives: To explore and describe the knowledge and practices of employees working in three specialised TB hospitals in Nelson Mandela Bay, Eastern Cape, regarding occupational exposure to TB. Methods: A quantitative, descriptive and contextual study was conducted using convenience sampling to have 181 employees at the three hospitals elected to complete the self-administered questionnaire, which was distributed in December 2016. Three scores on a scale of 0–10 were calculated per participant: knowledge, personal practice and institutional practice. Descriptive and inferential statistics were utilised. Results: Approximately, one-third (34%) of the participants were between the ages of 36 and 45 years. Most of the participants (63%) attended high school and less than one-third (28%) had a tertiary qualification. The majority of participants (62%) had not received any clinical training. Participants displayed high scores (> 6) for knowledge (75%; mean = 6.65), personal practice (68%; mean = 6.12) and institutional practice (51%; mean = 6.15). The correlation between knowledge and personal practice was found to be non-significant (r = 0.033). An analysis of variance revealed that Knowledge is significantly related to age and education level. Conclusion: Employees’ knowledge regarding occupational TB exposure was generally high, but they were not necessarily practicing what they knew. Further research is required regarding appropriate managerial interventions to ensure that employees’ practices improve, which should reduce the risk of occupational TB exposure.

Background: Global fight against tuberculosis (TB) has received increasing attention over the years. However, the disease remains one of the top-most global health problems, especially in Sub-Saharan Africa and Ghana. Aims: This paper examined geographical (regional) and seasonal distribution of TB cases providing relative risk of TB exposure in Ghana and step by step procedure to perform the analysis. Methods and material: We modelled reported TB cases between 2015 and 2018 using wavelet analysis and applied maximum covariance analysis (MCA) to determine regional and seasonal patterns and the risk of TB exposure in Ghana. This study is based on the old administrative regions of Ghana. Results: More TB cases were recorded in the Greater Accra and Ashanti regions and less cases in the rest of the regions. There is significant increase in the number of TB cases from 2015 to 2018. High number of TB cases is observed in the dry season relative to the rainy season. There is high variability in TB prevalence with high prevalence moving towards the Southern part of Ghana. Conclusion: The study highlights that TB cases is clustered in space and time and that even at small spatial scale, differences in prevalence can be substantial. The prevelance of TB exposure is higher in the dry season relative to the rainy season. Hence, enough resources should be timely provided during the dry season as well as intensifying preventive strategies to control the spread of the disease. Keywords: Space-time modelling, Tuberculosis, Tuberculosis prevalence, Wavelet analysis, Wavelet cluster analysis

Background: The U.S. Centers for Disease Control and Prevention (CDC) funds five Regional Tuberculosis Training and Medical Consultation Centers (RTMCCs) that provide training and consultation for tuberculosis (TB) control and management. RTMCC utilization for assistance with diagnosis and management of TB in children has not been described. We analyzed pediatric TB consultations performed across all RTMCCs in terms of question type, provider type, and setting. Methods: The CDC medical consultation database was queried for consultations regarding patients ≤ 18 years provided between 1/1/13–4/22/15 by all RTMCCs (Curry International TB Center, Heartland National TB Center, Mayo Clinic Center for TB, New Jersey Medical School Global TB Institute, Southeastern National TB Center). Each query was categorized into multiple subject areas based on provider type, setting, consultation topic, and patient age. Results: The 5 RTMCCs received 1164 pediatric consultation requests, representing approximately 20% of all consultations performed by the centers during the study period. Providers requesting consults were primarily physicians (46.3%) or nurses (45.0%). The majority of pediatric consult requests were from state and local public health departments (679, 58.3%) followed by hospital providers (199, 17.1%); fewer requests came from clinicians in private practice (84, 7.2%) or academic institutions (40, 3.4%). Consults addressed 14 different topics, most commonly management of children with TB disease (19.1%), latent TB infection (LTBI) (18.2%), diagnosis or laboratory testing (18.7%), and pharmacology (9.2%). Discussion: Pediatric consultations accounted for approximately 20% of all consultations performed by RTMCCs during the study period. RTMCCs were utilized primarily by public health departments regarding management of TB disease, LTBI, and diagnosis or laboratory testing. The relative underutilization of the RTMCCs by clinicians in non-public health settings, who often manage children with TB exposure or infection, warrants further study. As US TB case rates decline and providers become less experienced with childhood TB, medical consultation support may become increasingly important. Keywords: Tuberculosis, Pediatric, Consultation

Objective To describe mandates and policy gaps in tuberculosis (TB) contact investigation and management. Design We conducted a systematic review of national TB policy documents obtained using a systematic internet search and by contacting national TB programs. We included policies published in English, Spanish, and French, and abstracted data using a standardized form. Results We reviewed policy documents for 68 of 216 (31%) countries and territories. All countries recommended performing contact investigations, but 40% did not specify how contacts enter the health system for evaluation or who was responsible for this process. All countries recommended preventive therapy for contacts, but in 14 (21%) countries only young children were eligible. While four preventive therapy regimens exist, 48 (71%) countries recommended only isoniazid monotherapy. In addition, 28 (41%) countries lacked guidance on whether to give preventive therapy to contacts exposed to drug-resistant TB. Policies in 28 (41%) countries lacked recommendations for managing contacts with the human immunodeficiency virus (HIV) after new TB exposure. Conclusion Policies recommending contact investigation and preventive therapy for contacts are widespread, but policy gaps exist in the areas of ensuring accountability and the management of vulnerable populations such as people living with HIV and those exposed to drug-resistant TB.

Diagnosis and interventional treatment of latent tuberculosis (TB) infection (LTBI) are important components in tuberculosis control. But systematic studies regarding the epidemic of LTBI are still rare in China. The objective of this study was to assess the prevalence and risk factors associated with LTBI based on the results of a domestic TB-specific gamma interferon (IFN-γ) release assay (TB-IGRA) in rural Jiangsu, China.Cross-sectional study of subjects registered in eight villages in Jiangsu, China.This study was conducted in 2012 in eight villages. After recruitment, individuals with active TB or a history of TB were excluded. The TB-IGRA was performed for diagnosis of LTBI.2169 of 2185 subjects met the requirement and were analysed in this study. 524 (24.3%) had a positive result, and positive rate gradually increased with age (P for trend0.001). Multivariate analyses showed that increasing age, male gender and a history of TB exposure were risk factors associated with LTBI. Bacillus Calmette-Guérin (BCG) vaccination did not reduce the risk of TB infection in participants (aged ≥20 years).The findings of this study demonstrate that the prevalence of LTBI in China might be overestimated by tuberculin skin test compared with IFN-γ release assay (IGRA). The degree of TB exposure is related to Mycobacterium tubercuium (MTB) infection, and BCG vaccination offers little protection against MTB infection in adults. The early and effective detection and treatment of active TB patients, and screening and intervention for LTBI patients with a high risk of developing active TB could be cost-effective methods for TB control in China.

While tuberculosis (TB) preventive therapy among household contacts is effective at an individual level, its population-level impact on reducing TB incidence has been unclear. In this study, we aimed to assess, among the new tuberculosis patients started on treatment between 1 October, 2018 and 30 June, 2019 in the public health facilities of Udupi district (South India): i) the proportion with a &lsquo, history of household TB exposure&rsquo, and ii) sociodemographic and clinical factors associated with it. We conducted a cross-sectional study involving record review and patient interviews. Of 565 TB patients, 273(48%) were interviewed. Of them, 71(26%, 95% CI: 21%&ndash, 32%) patients had a &lsquo, history of household TB exposure (ever)&rsquo, with about half exposed in the past five years of diagnosis. Considering a new TB case as a proxy for incident TB, and &lsquo, a proxy for household transmission, and assuming 100% effectiveness of preventive therapy, we may infer that a maximum of 26% of the incident cases can be prevented by giving preventive therapy to all household contacts of TB patients. In multivariable analysis, females and tobacco users had a significantly higher prevalence of household TB exposure. If there are resource constraints, these subgroups may be prioritized.

Among new smear-positive pulmonary tuberculosis (TB) patients aged ⩾15 years from marginalised populations in India, one in four had a history of a household member with TB and one in 10 had a TB-related death in the household. This contribution of household transmission to overall TB transmission provides evidence for a potential population-level benefit of TB preventive treatment for all household contacts (without active TB). Females with TB had a significantly higher household TB exposure than males. Targeted TB preventive treatment (if implemented in a phased manner) among female household contacts may be explored after considering other factors.Parmi les nouveaux cas de tuberculose (TB) pulmonaire confirmés par bactériologie de patients (⩾15 ans) de populations marginalisées en Inde, un quart avait eu un membre du foyer atteint de TB et un sur 10, un décès dû à la TB au sein du foyer. La contribution de la transmission domiciliaire à l’ensemble de la transmission de la TB est en faveur d’un bénéfice potentiel pour la population, du traitement préventif de la TB pour tous les membres du foyer (sans TB active). Les patients TB de sexe féminin ont une exposition domiciliaire à la TB significativement plus élevée que les hommes. Un traitement préventif de la TB ciblé (s’il est mis en œuvre par phases) sur les contacts féminins du foyer pourrait être évalué après avoir tenu compte des autres facteurs.

Introduction: Timely detection of Mycobacterium tuberculosis (Mtb) remain critical in the effective management of patients with suspected tuberculosis (TB) disease. While recommendations for determination of latent TB or TB exposure in industrialized countries support the use of interferon-gamma release assays (IGRA), including the QuantiFERON Gold In-Tube (QFT-GIT) and T-SPOT.TB tests, disagreement exists within neuro-ophthalmologic practice on screening protocols for TB which affects ocular function.Areas covered: The authors have reviewed the current literature discussing the manifestation of tuberculosis in neuro-ophthalmic disease. Our literature search expands on current recommendations for TB screening in neuro-ophthalmology, including a comparison of the currently available tests for screening: the TST, QFT-GIT, and T-SPOT.TB tests. We review the literature on regional TB prevalence as it applies to clinical decision making for screening, as well as medical and social factors which may cre...

In developed countries there is a 15-20% prevalence of Extrapulmonary Tuberculosis (EPTB) among all TB patients but in developing countries like the Philippines it is much higher. EPTB is transmitted blood borne to extrapulmonary sites like the lymph nodes of the neck, pleura, meninges, bone, intrabadominal and urogential sites from the lungs where TB bacilli is inhaled, deposited and grown. Main objective is to find out the clinical profile of patients with EPTB enrolled at WVMC DOTS Clinic from January 2016 to December 2017. Chart review of patients with EPTB enrolled at WVMC DOTS Clinic with histopathologic report was done. 21 cases were reviewed. EPTB lesions mostly presented as neck masses 7 followed by inguinal 2, vertebral mass 2, submandibular 1, upper eyelid 1, intraabdominal abscess 1, endometrium 1, psoas abscess 1, parotid gland 1, ileocecal 1, axillary abscess 1, TB meningitis 1 and liver nodule 1. Most presented with weight loss (43%) cough (33%), back pain (28%) & tiredness (28%). Majority were newly diagnosed EPTB in 86% and treated as Cateogry I cases (71%). Subjects were mostly 19-29 yrs old (43%), males (62%), urban dwellers (48%), single (67%), had prior TB exposure (48%), alcohol drinkers (43%)and smokers (52%) and had normal chest xray (67%) In conclusion we should be more vigilant in the diagnosis of EPTB as most patients have normal chest xray findings and lesions could present in a variety of ways. It is recommended that there should be an increase in awareness of this elusive diagnoses.

Background. Childhood tuberculosis (TB) remains a significant health problem worldwide despite the increase on its emphasis in national health programs. Objective. This study aimed to describe how TB in children is identified and managed in a routine TB program in a rural setting in a high-burden country. Methods. This is a prospective, community-based surveillance study in public rural clinics in the Philippines. Observations on case finding and management of TB in children as well as contact tracing in an existing TB program are described. Results. Out of 266 children with presumptive TB, 41 (15.4%) were cases of TB, 15 (5.6%) had latent TB infection (LTBI), 81 (30.5%) had TB exposure, and 129 (48.5%) had no TB. There were 37 (90%) TB cases who were clinically diagnosed. Ninety-three per cent (93%) of children with TB disease were cured or completed treatment. Among 25 children targeted for isoniazid preventive therapy (IPT) for LTBI and TB exposure, only 12 (52%) completed the recommended 6 months of IPT. Only 40 (43%) children aged 0 to 4 years exposed to smear-positive TB cases were screened. Conclusion. Barriers in the diagnosis, low IPT completion and problems in contact tracing may hinder successful implementation of TB programs for children.

Setting: A provincial tertiary hospital in Gauteng province, South Africa, with a high burden of tuberculosis (TB) patients and high risk of TB exposure among health care workers (HCWs). Objective: To determine HCWs' adherence to recommended TB infection prevention and control practices, TB training and access to health services and HCW TB rates. Design: Interviews with 285 HCWs using a structured questionnaire as part of a large, international mixed-methods study. Results: Despite 10 HCWs (including seven support HCWs) acquiring clinical TB during their period of employment, 62.8% of interviewees were unaware of the hospital's TB management protocol. Receipt of training was low (34.5% of all HCWs and

A “stone in the pond” strategy is a practical approach to investigating large-scale nosocomial tuberculosis (TB) exposures. Here, we describe such a risk-stratified approach to contact tracing after a TB exposure that occurred over 5 months in a pediatric inpatient ward in a country with a moderate TB burden.Infect Control Hosp Epidemiol 2017;38:1509–1511

OBJECTIVE: Interferon-γ and IP-10 release assays are diagnostic tests for tuberculosis infection. We have compared the accuracy of IP-10 and QuantiFERON-TB Gold In-tube [QFT-IT] in Tanzanian children suspected of having active tuberculosis (TB). METHODS: Hospitalized Tanzanian children with symptoms of TB were tested with the QFT-IT and IP-10 tests and retrospectively classified into diagnostic groups. Adults with confirmed TB were assessed in parallel. RESULTS: A total of 203 children were included. The median age was 3.0 years (interquartile range: 1.2–7.0), 38% were HIV infected, 36% were aged CONCLUSIONS: Although IP-10 and QFT-IT performed well in Tanzanian adults, the tests exhibited an equally poor performance in diagnosing active TB in children. Test performance was especially compromised in young children. Neither test can be recommended for use in hospitalized children in high-burden settings.

Citrullinated Immunoglobulin Binding Protein (BiP) is a newly described autoimmune target in rheumatoid arthritis (RA), one of many cyclic citrullinated peptides(CCP or ACPA). BiP is over-expressed in RA patients causing T cell expansion and increased interferon levels during incubation for the QuantiFERON-Gold tuberculosis test (QFT-G TB). The QFT-G TB has never been validated where interferon is increased by underlying disease, as for example RA.Of ACPA-positive RA patients (n =â¯126), we found a 13% false-positive TB test rate by QFT-G TB. Despite subsequent biologic therapy for 3 years of all 126 RA patients, none showed evidence of TB without INH. Most of the false-positive RA patients after treatment with biologic therapy reverted to a negative QFT-G test. False TB tests correlated with ACPA level (pÂ

Despite the promising results of QuantiFERON-TB test (QFT) in diagnosis of latent tuberculosis infection (LTBI) ,false negative or indetermined test results are well documented in diffrent study settings. Cigarette smoking is known to reduce the interferon gamma (IFN-γ) response to antigenic challenge.But the influence of smoking on QTF test performance to diagnose LTBI among healthy subjects is unknown. The aim of this study to evaluate the effect of smoking on QFT test performance in healty subjects in intermidate TB prevalence setting. Method: 240 donor candiddates for organ transplantation (110 women, 130 men) with a mean age 42,5± 12,3 involved in this study. Patients recruited prospectively between March 2014 and March 2015. Their demographic features, smoking history, QTF test levels and results were recorded. The risk of LTBI was evaluated via questionnaire consisting the history of occupation, high probability for TB exposure, Isoniazide prophlaxis and radiologic (chest Xray or thorax Ct scan) findings related to sequelae tuberculosis lesion. Smoking was analysed as a risk factor for false negative QFT results. Results: In the study group 128 (% 53) subjects had negative smoking history, 31 (%12,9) were quited and 80(%33) were active smokers. When we analyse the QTB results; sattistically higher quantitative MTB specific response were observed in non smokers (3,09±3,6 ; 1,6±3,1 p= 0,027). False nefative result rate were high among smokers than nonsmokers (29 % 76,3 vs 9 %23,7; p Conclusion: Smoking has a role in QFT false negative results, causing a decrease of QFT sensitivity in helathy population.

Regular monitoring of latent tuberculosis (TB) infection in healthcare workers (HCWs) is recommended, but the view about the effective method and performance of serial monitoring is controversial. The aim of this study was to determine differences in conversion rates according to TB exposure risk using the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT), and to evaluate the reproducibility and within-subject variability of the QFT-GIT in South Korea. Fifty-three HCWs were grouped according to their risk for TB exposure: group 1, high risk (n = 21); group 2, low risk (n = 32). Baseline and follow-up TSTs and QFT-GITs were performed from June 2009 to July 2011. Enzyme-linked immunosorbent assays (ELISAs) were repeated for the second QFT-GIT and a third QFT-GIT was performed after 8 weeks when discordant results of the second TST and QFT-GIT or a conversion or reversion were observed. No difference in the QFT-GIT conversion rate was evident between the two groups (15.4 vs. 6.5 %, p = 0.57), and no TST conversion was observed. The rate of QFT-GIT positivity was higher in the high-risk group (first QFT-GIT: 38.1 vs. 3.1 %, p = 0.002; second QFT-GIT: 33.3 vs. 9.4 %, p = 0.039). The re-test reproducibility of QFT-GIT results was high (100 %), and the within-subject results of repetitive QFT-GITs were variable. Stricter prevention strategies remain necessary in HCWs at high risk of TB exposure, and serial interferon-γ release assays (IGRAs) should be interpreted with caution in HCWs.

OBJECTIVES To retrospectively assess the proportion of contacts tested with QuantiFERON ® -TB Gold (QFT-G) compared to the tuberculin skin test (TST) who were successfully evaluated and treated for latent tuberculosis infection (LTBI), and to assess the correlation of positive test results with measures of TB exposure. METHODS Contacts of culture-confirmed pulmonary TB cases reported to the San Francisco Department of Public Health between 1 March 2005 and 31 December 2007 were included. RESULTS Of 1291 contacts meeting the eligibility criteria, 641 (50%) were tested with QFT-G and 650 (50%) with TST. Contacts tested with QFT-G were more likely to complete evaluation (64% vs. 56%, OR(adj ) = 1.52, 95%CI 1.12-2.06). Infected contacts started (89% vs. 72%, OR(adj) = 5.18, 95%CI 2.10-14.18) and completed (70% vs. 53%, OR(adj) = 3.37, 95%CI 1.78-6.56) LTBI treatment more often in the group tested with QFT-G. Positive QFT-G results, but not positive TST results, correlated with the intensity, proximity and duration of TB exposure in foreign-born subjects. CONCLUSION More contacts were successfully evaluated and treated for LTBI when screened with QFT-G compared to TST. Measures of exposure correlated better with QFT-G-positive results and, therefore, appropriately identified high-risk contacts for TB prevention.

The endpoint definition for infant tuberculosis (TB) vaccine trials should match the TB disease phenotype expected in the control arm of the study population. Our aim was to analyse selected combinations of the clinical, radiological, and microbiological features of pulmonary TB among children investigated under vaccine trial conditions, in order to estimate case frequency for a range of expected TB phenotypes. Two thousand one hundred and eighty five South African children were investigated over a nine-year period (2001-2009). Evidence of TB exposure and classical symptoms were several times more common than chest radiography (CXR) compatible with TB, or positive Mycobacterium tuberculosis culture. Discordance between clinical, radiological, and microbiological features was common in individual children. Up to one third of children with compatible CXR, and up to half the children who were M. tuberculosis culture positive, were asymptomatic. The culture positive rate fell over time, although rates of TB exposure and compatible chest radiography increased. Consequently, the annual incidence of diagnostic combinations that included M. tuberculosis culture fell to0.2%. However, in this study population (children2 years of age), annual incidence of the TB disease phenotype that included the triad of TB exposure, symptoms, and compatible CXR, approached 1% (n=848 per 100,000). These findings allow modelling of expected TB case frequency in multi-centre infant TB vaccine trials, based upon benchmarking of diagnostic data against the key indicator variables that constitute the building blocks of a trial endpoint.

Background Tuberculosis (TB) causes substantial health burden to the Korean military. This study aims to assess the impact of infectious TB cases on close and casual contacts in the Korean Army settings based on contact investigation data. Methods Six Army units with infectious TB cases from September 2012 to May 2013 were enrolled in the study. We analyzed the clinical data from close and casual contacts screened using the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube to identify latent tuberculosis infection (LTBI) cases. For the control group, 286 military conscripts with no reported TB exposure were tested by TST only. Results Of the 667 contacts of index cases, LTBI cases identified were as follows: 21.8% of close contacts of smear-positive cases (71/326), 8.5% of casual contacts of smear-positive cases (26/305), and 2.8% of close contacts of smear-negative cases (1/36). In the control group, 16.8% showed positivity in TST. In a multivariate analysis, having stayed in the same room or next room with TB patients was identified as a risk factor of LTBI. Conclusion Using the data from TB contact investigations in the Korean Army units, we found an overall LTBI rate of 14.7% among the contacts screened. This study demonstrates that contacts living in the same building, especially the same room or next room, with TB patients are at a high risk of acquiring LTBI, serving as additional evidence for defining close and casual contacts of a TB patient with regard to Army barrack settings.

Aim Tuberculosis (TB) continues to challenge global health systems, especially in South Africa. Nurses are especially vulnerable to TB exposure, because of their prolonged front-line contact with infected patients-especially in primary health care (PHC) clinics. Their infection control practices, influenced by key factors such as knowledge and attitudes towards TB prevention, become an important consideration. The aim of the study was to (1) describe the TB prevention knowledge, attitudes, and practices of PHC nurses in a South African district and (2) explore moderating factors on TB prevention practices. Methods A cross-sectional survey was undertaken at all 41 PHC facilities in Mangaung Metropolitan district, Free State province, South Africa, using self-administered questionnaires. Captured data were analysed to yield descriptive and multivariate statistics. Results Results suggest several instances of inadequate TB prevention knowledge, attitudes, and practices. Good TB practice was predicted by TB attitudes and knowledge, and the relationship between TB prevention knowledge and practices was not moderated by training, attitudes, or nurse category. Conclusion Results echo previous indications that nurses often do not exhibit the desired knowledge, attitudes, and practices required to adequately protect themselves and others against TB and suggest further exploration towards understanding the influences on TB prevention practice among nurses.

The advent of interferon-γ release assays (IGRAs) has provided a new insight into the diagnosis and immunology of TB. IGRAs are being widely accepted and marketed in low-TB-burden countries. However, globally, the impact of TB is concentrated in 22 high-burden countries, where high percentages of the population are infected with TB, HIV coinfection rates are high, continuous community TB exposure occurs, laboratory infrastructure is weak and latent TB infection is not treated. What role do these new assays play in these settings? Can they really have an important benefit in these countries, among people who most need an innovation in TB diagnostics? Here, we examine the most current literature in order to answer specific diagnostic questions that are relevant to these settings.

BACKGROUND: On April 1, 2004, BCG (bacille Calmette-Guérin), a tuberculosis (TB) control vaccine, was discontinued in all but four high-risk communities in Alberta. To confirm the safety of vaccine withdrawal, and for future planning, the annual risk of infection (ARI) was determined in preschool First Nations children. METHODS: First Nations children born into reserve communities in Alberta between April 1, 1998 and March 31, 2004, and still living on reserve in 2004–2005, were identified. Health centre TB histories were validated by cross-referencing the birth cohort with the provincial TB Registry. Children that were not BCG vaccinated and not known to be tuberculin skin test (TST) positive underwent a TST. Birth cohort children were grouped as follows: (i) BCG vaccinated; (ii) BCG non-vaccinated, no TST; (iii) BCG non-vaccinated, TST; (iv) BCG vaccination status unknown. The ARI was calculated and the age and community characteristics of the groups were compared. RESULTS: There were 8,447 children in the 6-year birth cohort, 4,699 (55.6%) vaccinated, 2,696 (31.9%) non-vaccinated, and 1,052 (12.5%) whose vaccination status was unknown. Of the non-vaccinated children, 1,921 (71.3%) were tested and only 2 were TST positive. No other TST positive, BCG non-vaccinated children were identified in the TB Registry cross-match. The prevalence of infection in 2004–2005 was 0.1% and the ARI was 0.03%. The community risk of TB exposure was comparable in tuberculin-tested and non-tested BCG non-vaccinated children. CONCLUSION: In low BCG-uptake First Nations communities in Alberta, the ARI is low and it is safe to withdraw BCG.

Diagnosis of latent tuberculosis infection (LTBI) should be targeted toward individuals and groups with high risk of progression to active tuberculosis (TB). Low-risk populations should not be screened. Interferon-gamma release assays (IGRAs) perform as well or better than the tuberculin skin test in most targeted populations. IGRAs are preferred for bacille Calmette-Guerin (BCG)-vaccinated populations. A positive IGRA in a person at low risk for TB exposure should be confirmed with a repeat test or another method before recommending LTBI treatment. The choice of which IGRA to use is generally based on the costs and feasibility of performing the test.

Isoniazid preventive therapy (IPT) prevents tuberculosis (TB) in immunocompetent childrenlt;5 years of age after exposure to an infectious TB source case. Routine IPT has been advocated in all HIV-infected children without TB, but has been controversial. Antiretroviral therapy markedly reduces the risk for TB in HIV-infected children, especially when started early in infancy. In HIV-infected children, as in HIV- uninfected children, we recommend post-exposure IPT after each TB exposure episode; but in HIV-infected children, this should be given irrespective of age or antiretroviral therapy. However, evidence for routine IPT without known exposure to TB in HIV-infected children is not convincing and is therefore not recommended.

Background Although North American hospitals are switching from tuberculin testing (TST) to interferon-gamma release assays (IGRAs), data are limited on the association between occupational exposure and serial QuantiFERON-TB Gold In-Tube (QFT) results in healthcare workers (HCWs). Methods In a cohort of Canadian HCWs, TST and QFT were performed at study enrolment (TST1 and QFT1) and 1 year later (TST2 and QFT2). Conversion and reversion rates were estimated, and correlation with TB exposure was assessed. Results Among 258 HCWs, median age was 36.8 years, 188/258 (73%) were female and 183/258 (71%) were Canadian-born. In 245 subjects with a negative QFT1 we found a QFT conversion rate of 5.3% (13/245, 95% CI 2.9–8.9%). Using more stringent definitions, QFT conversion rates ranged from 2.0 to 5.3%. No TST conversions were found among the 241 HCWs with negative TST1, and no measure of recent TB exposure was associated with QFT conversions. In the 13 HCWs with a positive QFT1, 62% reverted. Conclusion Using the conventional QFT conversion definition, we found a higher than expected rate of conversion. Recent occupational exposures were not associated with QFT conversions, and no TST conversions occurred in this cohort, suggesting the ‘conversions’ may not reflect new TB infection.

Tuberculosis (TB) is the most deadly infectious disease in the world. TB control relies on passive case findings and targeted treatment of latently infected individuals at high risk of disease progression. Tuberculin skin testing (TST) is conventionally used for detection of TB infection. Recently, blood assays measuring the release of IFN-gamma by TB-specific effector memory T cells have been developed to overcome TST limitations. Overall, IFN-gamma release assays are more specific than TST, more sensitive in detecting active TB and correlate better with TB exposure in immune-competent patients, at least in low-burden settings. There are three US FDA-approved assays commercially available: the ELISpot-based assay T-SPOT.TB (Oxford Immunotech, UK) and two ELISA-based formats, QuantiFERON TB Gold (QFT) and QFT-in tube (Cellestis, Australia). Recent international guidelines and consensus statements recommend the use of IFN-gamma release assays at different levels in TB management. However, conclusive evidence-based information targeting populations at high TB risk, including HIV-infected individuals, children and patient candidates for biotherapy with TNF-alpha blockers, are lacking. The aim of this review is to focus our attention on studies addressing the performance of commercial IFN-gamma release assays in clinical management of TB infection in these highly selected settings to provide a more comprehensive picture of the actual scenario and to identify areas to be investigated further.

BACKGROUND National guidelines recommend targeted tuberculin testing and treatment of latent tuberculosis infection (LTBI) among high-risk groups but discourage testing low-risk persons. METHODS We determined the LTBI prevalence (tuberculin skin test [TST] reaction > or = 10 mm) among adults with and without TB exposure risk factors screened in Tennessee from 1/2/2002 to 4/19/2005. We then quantified LTBI risk among groups at high-risk for TB using multivariate analysis. RESULTS Of 53,061 adults tested, the LTBI prevalence was 34% among foreign-born persons, compared with 3.2% among nonforeign-born persons (prevalence odds ratio [POR] 15.7, 95% confidence interval [CI] 14.5-16.8). Among nonforeign-born adults, Asian race (POR 11.7, 95% CI 5.9-23.4), and Hispanic ethnicity (POR 11.7, 95% CI 9.0-15.2) were most strongly associated with LTBI. Only 2.4% of low-risk persons had LTBI. CONCLUSIONS Risk-based screening can effectively distinguish persons who will benefit from LTBI testing and treatment. Targeted testing programs should prioritize foreign-born persons. Testing of low-risk persons is unnecessary.

BACKGROUND: Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings. METHODS AND FINDINGS: The study was carried out in eight hospitals in Lima, Peru; five were hospitals of "old-fashioned" design built pre-1950, and three of "modern" design, built 1970-1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open. CONCLUSIONS: Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion.

This article estimates the risk of tuberculosis (TB) transmission on a typical commercial airliner using a simple one box model (OBM) and a sequential box model (SBM). We used input data derived from an actual TB exposure on an airliner, and we assumed a hypothetical scenario that a highly infectious TB source case (i.e., 108 infectious quanta per hour) travels as a passenger on an 8.7-hour flight. We estimate an average risk of TB transmission on the order of 1 chance in 1,000 for all passengers using the OBM. Applying the more realistic SBM, we show that the risk and incidence decrease sharply in a stepwise fashion in cabins downstream from the cabin containing the source case assuming some potential for airflow from more contaminated to less contaminated cabins. We further characterized spatial variability in the risk within the cabin by modeling a previously reported TB outbreak in an airplane to demonstrate that the TB cases occur most likely within close proximity of the source TB patient.

Objectives Provision of medical surveillance for staff in health facilities with large numbers of TB and HIV positive patients is important. South African legislation also requires medical surveillance to be conducted in all hospitals. Methods Staff in the medical wards of a large public hospital in Johannesburg were invited to participate in the survey covering TB symptoms and attitudes towards regular surveillance. A walk through audit was also conducted in the wards to evaluate TB controls. Results Of the 200 staff available to participate 44% returned questionnaires with doctors and consultants noticeably missing. TB exposure was found in all wards with an average of 10% of patients diagnosed with TB; despite this 30% of staff felt they were not exposed. Further investigations were recomended for 9% of staff who indicated TB symptoms were present, of those followed up 11% were diagnosed with TB. This gives a 2.3% prevalence of TB in the medical wards of the hospital. 85% of staff were in favour of routine medical surveillance and 48% were willing to disclose HIV status if early treatment were provided. Conclusions A symptom questionnaire can help identify those requiring investigation for TB. This is a cost effective means of conducting regular medical surveillance in a medical facility. For a medical surveillance program to be successful there needs a dedicated occupational health staff to run the program to involve doctors in the process and to conduct training on health risks.