Tuberculosis Exposure Research Articles

Lung Function Impairment In Patients Treated For Pulmonary Tuberculosis and Associated Factors in Puducherry, South India.

Context:After completion of treatment, a proportion of pulmonary tuberculosis (TB) (PTB) patients experience lung function impairment (LFI) which can influence their quality of life.Aim:This study was aimed to determine the prevalence of LFI in patients treated for PTB and the associated factors.Settings and Design:A cross-sectional study was conducted among patients treated for PTB in eight primary health centers in Puducherry.Subjects and Methods:The study was carried out among 118 patients. Those aged 18 and above whose PTB treatment outcomes were declared as cured or completed between 2018 and 2019 were included. Demographic data, respiratory symptoms before TB diagnosis, comorbidities, and chest radiography findings before TB treatment were collected. All participants underwent spirometric tests before and after dilatation with salbutamol nebulization.Statistical Analysis:Multivariable analysis identified smear-negative TB and indoor exposure to biomass for cooking as significant independent risk factors for LFI.Results:Of 118 participants interviewed, 70.3% were male and the median age of the participants was 47.7 years. The prevalence of LFI was 62.7% (95% confidence interval: 53.3–71.4).Conclusion:LFI was frequent in patients treated previously for TB. Creating awareness about the possible LFI among these patients along with the awareness for seeking health care for this condition is the need of the hour.

HIV and TB Workplace Program for Street Vendors: A Situational Analysis.

In South Africa, 15 percent of informal economy workers are street vendors. The organization of occupational health services in the country is fragmented and does not cover informal workers. Conditions of work make informal workers extremely vulnerable to human immunodeficiency virus (HIV) and tuberculosis (TB) exposure. In this study, a qualitative risk assessment was conducted among street vendors, followed by focus group discussions. Interpretation of data was according to major themes extracted from discussions. Workers are exposed to several occupational health hazards identified during the risk assessment. There is a lack of workplace HIV and TB services and overall poor access to healthcare. Street vendors, especially females, are at higher risk of HIV, due to gender inequalities. Comprehensive gender-sensitive training on occupational health and safety, HIV, and TB should be prioritized. To reach Universal Health Coverage and achieve the Sustainable Developmental Goals' targets, the health system should improve services for informal economy workers.

798. Incomplete Contact Investigation and Risk of Developing Tuberculosis Among Healthcare Professionals After Tuberculosis Exposure

BackgroundTuberculosis (TB) contact investigation is recommended for healthcare professionals (HCPs) after TB exposure. However, association between no participation in or incomplete contact investigation and subsequent TB development has not been well-described. This study aims to determine TB incidences and factors associated with TB development among HCPs requiring contact investigations.MethodsWe conducted a prospective cohort study among Thai HCPs with TB exposure from January 2013 to December 2017. Contact investigations, including baseline TB and latent tuberculosis infection (LTBI) screening and follow-up at 3 months after TB exposure, were recommended to all HCPs. The two-step tuberculin skin test (TST) was used for LTBI testing. All HCPs were followed for 2 years for TB development.ResultsOf the 342 HCPs with TB exposure included in the study, 311 (91%) participated in the contact investigations and 252 (74%) completed baseline TB and LTBI screening. Among the 210 HCPs with negative baseline TST, 45 (21%) completed the follow-up tests. The overall incidence of TB was 2.92/100 person-years. HCPs who did not complete follow-up TST had significantly higher TB incidence than those completed baseline and follow-up TST (3.55 vs. 0/100 person-years; P=0.01). No participation in the contact investigation and no chest radiograph performed at baseline were the independent factors associated with TB development among the HCPs [adjusted odds ratio (aOR) 6.69; P< 0.001 and aOR 8.85; P=0.01, respectively]. Contact with an index patient with concomitant TB at extrapulmonary sites (aOR 49.76, 10.03-246.99; P< 0.001) and with negative sputum AFB but positive sputum GeneXpert MTB/RIF (aOR 3.18, 1.35-7.50; P=0.008) were independently associated with no participation in the contact investigation.ConclusionThe findings indicate the risk of TB development among the HCPs who did not undergo or complete contact investigations and underscore the need for interventions to improve contact investigation participation and completeness.Disclosures All Authors: No reported disclosures

Identification of Recent Tuberculosis Exposure Using QuantiFERON-TB Gold Plus, a Multicenter Study.

ABSTRACTWe investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2−TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8+ T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2−TB1 value >0.6 IU·ml−1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2−TB1 result of >0.6 IU·ml−1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2−TB1 difference of >0.6 IU·ml−1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection.IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml−1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml−1. QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.

Monoclonal antibodies from humans with Mycobacterium tuberculosis exposure or latent infection recognize distinct arabinomannan epitopes

The surface polysacharide arabinomannan (AM) and related glycolipid lipoarabinomannan (LAM) play critical roles in tuberculosis pathogenesis. Human antibody responses to AM/LAM are heterogenous and knowledge of reactivity to specific glycan epitopes at the monoclonal level is limited, especially in individuals who can control M. tuberculosis infection. We generated human IgG mAbs to AM/LAM from B cells of two asymptomatic individuals exposed to or latently infected with M. tuberculosis. Here, we show that two of these mAbs have high affinity to AM/LAM, are non-competing, and recognize different glycan epitopes distinct from other anti-AM/LAM mAbs reported. Both mAbs recognize virulent M. tuberculosis and nontuberculous mycobacteria with marked differences, can be used for the detection of urinary LAM, and can detect M. tuberculosis and LAM in infected lungs. These mAbs enhance our understanding of the spectrum of antibodies to AM/LAM epitopes in humans and are valuable for tuberculosis diagnostic and research applications.

POSSIBLE ZOONOTIC TRANSMISSION OF UNKNOWN MICROBIAL PATHOGEN IN A LUNG TRANSPLANT RECIPIENT: A CASE REPORT

TOPIC: Transplantation TYPE: Fellow Case Reports INTRODUCTION: Lung transplant recipients are at an increased risk for microbial infection, which may at times be difficult to isolate or properly identify, even with repeat transbronchial biopsies (1). CASE PRESENTATION: We reviewed the unique, potential route of transmission and infectious disease course of an enigmatic microbial pathogen that was challenging to identify and associated with an abscess of the lung allograft in a 59-year-old bilateral lung re-transplant recipient. Interestingly, the patient reported having multiple pets at home, including dogs, lizards, cows, horses, and chickens residing on her property, which may have been a source of infection. DISCUSSION: This lung re-transplant recipient presented to our advanced lung disease center at 9-years post-transplant with complaints of sudden fever and chills alongside a 2-week history of productive cough with yellow-tinged sputum. Maintenance immunosuppression consisted of tacrolimus, sirolimus, and prednisone. The patient denied unintentional weight loss, night sweats, or known tuberculosis contacts or exposures;COVID-19 testing was negative in the interim. On thoracic imaging (Figure A), a right upper lobe cavitary lesion was identified. Bronchoscopy was negative for microorganismal growth. She was treated empirically with meropenem, isoniazid, and amikacin. The fever resolved, but the patient reported continued malaise over the next several weeks. Repeated bronchoscopies failed to identify any microorganisms. After six weeks of antibiotic therapy, the size of the lung abscess decreased (Figure B), but all cultures and transbronchial biopsies had failed to determine the infectious origin. The only note regarding her history prior to presentation was that she performed mouth-to-mouth resuscitation on her pet dog who unexpectantly collapsed. It is surmised that this event served as the basis for an oral transmission of a microbial pathogen. CONCLUSIONS: Lung abscesses are generally an early complication in the post-lung transplant period, yet our patient seemingly developed an abscess from an unknown microbial infection at 9-years post-transplant, potentially from a zoonotic source. Although infrequently observed, lung transplant recipients (and other immunosuppressed groups) may be at risk for severe harm or prolonged infection due to direct zoonosis. REFERENCE #1: Pahlman LI, Manoharan L, Aspelund AS. Divergent airway microbiomes in lung transplant recipients with or without pulmonary infection. Respir Res. 2021 Apr 23;22(1):118. doi: 10.1186/s12931-021-01724-w. PMID: 33892717. DISCLOSURES: No relevant relationships by Ashwini Arjuna, source=Web Response No relevant relationships by David Bowman, source=Web Response No relevant relationships by Michael Olson, source=Web Response No relevant relationships by Ali Saeed, source=Web Response

A differential DNA methylome signature of pulmonary immune cells from individuals converting to latent tuberculosis infection

Tuberculosis (TB), caused by Mycobacterium tuberculosis, spreads via aerosols and the first encounter with the immune system is with the pulmonary-resident immune cells. The role of epigenetic regulations in the immune cells is emerging and we have previously shown that macrophages capacity to kill M. tuberculosis is reflected in the DNA methylome. The aim of this study was to investigate epigenetic modifications in alveolar macrophages and T cells in a cohort of medical students with an increased risk of TB exposure, longitudinally. DNA methylome analysis revealed that a unique DNA methylation profile was present in healthy subjects who later developed latent TB during the study. The profile was reflected in a different overall DNA methylation distribution as well as a distinct set of differentially methylated genes (DMGs). The DMGs were over-represented in pathways related to metabolic reprogramming of macrophages and T cell migration and IFN-γ production, pathways previously reported important in TB control. In conclusion, we identified a unique DNA methylation signature in individuals, with no peripheral immune response to M. tuberculosis antigen who later developed latent TB. Together the study suggests that the DNA methylation status of pulmonary immune cells can reveal who will develop latent TB infection.

Occupational Risk of Airborne Mycobacterium tuberculosis Exposure: A Situational Analysis in a Three-Tier Public Healthcare System in South Africa.

This study aimed to detect airborne Mycobacterium tuberculosis (MTB) at nine public health facilities in three provinces of South Africa and determine possible risk factors that may contribute to airborne transmission. Personal samples (n = 264) and stationary samples (n = 327) were collected from perceived high-risk areas in district, primary health clinics (PHCs) and TB facilities. Quantitative real-time (RT) polymerase chain reaction (PCR) was used for TB analysis. Walkabout observations and work practices through the infection prevention and control (IPC) questionnaire were documented. Statistical analysis was carried out using Stata version 15.2 software. Airborne MTB was detected in 2.2% of samples (13/572), and 97.8% were negative. District hospitals and Western Cape province had the most TB-positive samples and identified risk areas included medical wards, casualty, and TB wards. MTB-positive samples were not detected in PHCs and during the summer season. All facilities reported training healthcare workers (HCWs) on TB IPC. The risk factors for airborne MTB included province, type of facility, area or section, season, lack of UVGI, and ineffective ventilation. Environmental monitoring, PCR, IPC questionnaire, and walkabout observations can estimate the risk of TB transmission in various settings. These findings can be used to inform management and staff to improve the TB IPC programmes.

Occupational Screening for Latent Tuberculosis Infection

In people at risk of occupational exposure to tuberculosis, targeted testing for latent tuberculosis infection (e.g., testing for high-risk individuals, testing after tuberculosis exposure) appears to be more cost-effective than repeated testing, such as testing once a year or every 3 years (findings based on 2 economic evaluations that assessed the cost-effectiveness of repeated latent tuberculosis infection screening in workers of health care settings).

Congenital and Perinatal Tuberculosis.

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.

ImmunoStart: preparing patients for immunosuppression.

ObjectivesPatients with immune-mediated inflammatory disease (IMID) present an increased risk of infection. Here, we present the concept of a preventive consultation called ImmunoStart and the first results of its implementation in the care pathway of patients with IMID.MethodsRelevant information about vaccination history, tuberculosis exposure and other infectious risks were collected through blood sampling, complete anamnesis, chest X-ray and Mantoux test. During the ImmunoStart consultation, vaccination schedules, specific treatments and risk considerations were discussed.ResultsBetween October 2016 and February 2020, 437 patients were seen at an ImmunoStart consultation, mainly referred by rheumatologists (56%), dermatologists (25%) and gastroenterologists (18%). A total of 421 (96%) patients needed at least one vaccine (a mean of 3.3 vaccines per patient). Live attenuated vaccine was indicated for 45 patients (10%), requiring them to reduce or interrupt their immunosuppressive drug(s). Ninety-two patients (21%) were treated for latent tuberculosis infection.ConclusionThis preventive consultation provides a centralized and systematic setting for the direct management of patients with IMID in need of vaccination, treatment of latent disease and specific advice regarding their immunomodulating treatments.

Distinguishing Features of Adolescents With Undiagnosed Infectious Tuberculosis Attending a Pediatric Emergency Department

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.

Monitoring frequency of interferon gamma release assay for tuberculosis surveillance following infliximab therapy in patients with Crohn's disease.

To characterize the pattern of positive conversion of interferon gamma release assay (IGRA) in patients with Crohn's disease (CD) during infliximab therapy in China, which has a high burden of tuberculosis. Eligible patients with CD who received serial IGRA screening during infliximab therapy from January 2015 to March 2020 were retrospectively included. The positive conversion rate of IGRA and the risk of subsequent tuberculosis of the patients were analyzed. A total of 128 patients with CD were included, and the median time from the initiation of IFX treatment to positive conversion or the last follow-up test of IGRA was 43.6 weeks. At baseline 3.9% of the patients were positive for IGRA and received prophylactic anti-tuberculosis treatment. In the other 123 patients with negative IGRA at baseline, 6.5% had IGRA positive conversion during infliximab treatment, and one (12.5%) who was exposed to Mycobacterium tuberculosis was diagnosed as having active tuberculosis. The conversion rate at 40 weeks, 2 years and 3 years after treatment were 10.0% (6/60), 2.2% (1/46) and 5.9% (1/17), respectively. Age, sex, history of smoking and alcohol consumption, disease severity (Crohn's disease activity index score) and immunosuppressive therapy were not significantly associated with latent tuberculosis test conversion. Positive conversion of IGRA occurs early during treatment with infliximab for CD and the monitoring frequency of IGRA should be appropriately increased at the early stage of treatment. Physicians should pay attention to patient's history of tuberculosis exposure and carry out surveillance in a timely fashion.

Study on Prevalence of Adverse Drug Reactions and Drug-Drug Interactions and Co-Morbid Conditions of Patients Suffering from Tuberculosis

Background: Tuberculosis is the oldest common infectious disease affecting not only lungs but several organs in a human body. Its caused by the bacteria Mycobacterium tuberculosis. Tuberculosis exposure is through lungs. This disease has co-morbid conditions. The basic treatment according to WHO is with Isoniazid, Rifampicin, Pyrazinamide, Ethambutol, but these drugs may lead to adverse drug reactions and drug interactions. Objective: To determine the adverse effects and drug-drug interactions post administration of anti-tubercular drugs and to determine the influence of drugs on their co-morbid conditions of patients suffering from tuberculosis in Aster Prime Hospital. Methods: The patient’s prescriptions of total 110 were collected from the outpatient and in-patient Pulmonology department. These were noted in the data collection form and the comparative study was done by evaluating the number of male and female affected with Tuberculosis, common drug-drug interaction with respective drug, adverse drug reaction followed by the common co-morbid condition occurring with TB and the effect of drugs on co-morbidities Results: The prevalence of tuberculosis in 110 patients was found to be more in females by 12% than males. The co-morbid conditions found with tuberculosis were Hypertension, diabetes, pleural effusion, hepatitis, cavitary disease and respiratory failure. The least common comorbidities were chronic obstructive pulmonary disease (COPD), gastritis, and stroke and chronic kidney disease (CKD) and ulcerative colitis. The total adverse effect found in the 62 patients (56.36%) and the patients with no adverse drug reactions were 48 (43.63%) The percentage of total drug-drug interactions found in the patients were 44% (n=48) and the percentage of patients with no interactions were 56% (n=62). Conclusion: Health care workers play an important role and considered as a vital group for tuberculosis awareness activities to increase competence in TB management and compliance with national guidelines. Interventions address a combination of varying influences on behaviour, focusing on specific gaps identified to improve their impact.

The Magnitude of Interferon Gamma Release Assay Responses in Children With Household Tuberculosis Contact Is Associated With Tuberculosis Exposure and Disease Status.

The clinical utility of the magnitude of interferon gamma (IFNγ) in response to mycobacterial antigens is unknown. We assessed the association between quantitative IFNγ response and degree of Mycobacterium tuberculosis exposure, infection and tuberculosis (TB) disease status in children. We completed cross-sectional analysis of children (≤15 years) exposed to an adult with bacteriologically confirmed TB, 2007-2012 in Cape Town, South Africa. IFNγ values were reported as concentrations and spot forming units for the QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, respectively. Random-effects linear regression was used to investigate the relation between the M. tuberculosis contact score, clinical phenotype (TB diseased, infected, uninfected) and IFNγ▪response as outcome, adjusted for relevant covariates. We analyzed data from 669 children (median age, 63 months; interquartile range, 33-108 months). A 1-unit increase in M. tuberculosis contact score was associated with an increase of IFNγ 0.60 international unit/mL (95% confidence interval [CI], 0.44-0.76 international unit/mL), and IFNγ spot forming unit 2 counts (95% CI, 1-3). IFNγ response was significantly lower among children with M. tuberculosis infection compared with children with TB disease (β = -1.42; 95% CI, -2.80 to -0.03) for the QFT-GIT, but not for the T-SPOT.TB. This association was strongest among children 2-5 years (β = -2.35 years; 95% CI, -4.28 to -0.42 years) and absent if <2 years. The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children. The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children.

Tuberculosis-associated depression: a population-based cohort study of people immigrating to British Columbia, Canada, 1985–2015

To estimate the risk of tuberculosis (TB)-associated depression. A second aim was to estimate the extent to which any increased risk of depression among TB patients may be mediated by the length of hospital length stay (LOS) METHODS: Retrospective cohort study of linked healthcare claims and public health surveillance data. Our primary outcome, time-to-depression, was analyzed using Cox proportional hazards (PH) regressions. Causal mediation analysis was used to estimate the natural direct and indirect effect of TB mediated by hospital LOS. Among 755,836 participants (52.2% female, median age=35 years, median follow-up=8.75 years), 2295 were diagnosed with TB (exposure), and 128,963 were diagnosed with depression (outcome). We observed a covariate-adjusted hazard ratio (aHR) of 1.24 (95% CI, 1.14-1.34) for depression by TB. The total effect of TB on depression was decomposed into a natural direct effect of TB of aHR=1.11 (95% CI, 1.02-1.21) and an indirect effect through hospital LOS of aHR=1.11 (95% CI, 1.10-1.12), indicating that TB's total effect was mediated by 50% (95% CI, 35-82%) through hospital LOS. TB patients had a 24% higher risk of developing depression. TB's effect was mediated substantially by hospital LOS, requiring further study. Depression screening among TB patients is warranted.

The Relationship between COVID-19 Severity and Bacillus Calmette-Guérin (BCG)/ Mycobacterium tuberculosis exposure history in healthcare workers: a multi-center study

ABSTRACT The COVID-19 pandemic has brought countries’ health services into sharp focus. It was drawn to our group’s attention that healthcare workers (HCWs) had a lower mortality rate against higher COVID-19 incidence compared to the general population in Turkey. Since risk of exposure to tuberculosis bacillus among healthcare workers are higher than the population, we aimed to investigate if there is a relationship between BCG and Mycobacterium tuberculosis exposure history with COVID-19 severity in infected HCWs. This study was conducted with 465 infected HCWs from thirty-three hospitals to assess the relationship between COVID-19 severity (according to their hospitalization status and the presence of radiological pneumonia) and BCG and Mycobacterium tuberculosis exposure history. HCWs who required hospital admission had significantly higher rates of chronic diseases, radiological pneumonia, and longer working hours in the clinics. Higher rates of history of contact and care to tuberculosis patients, history of tuberculosis, and BCG vaccine were observed in hospitalized HCWs. HCWs who had radiological pneumonia had a significantly increased ratio of history of care to tuberculosis patients and a higher family history of tuberculosis. The findings from our study suggest that the lower mortality rate despite the more severe disease course seen in infected HCWs might be due to frequent exposure to tuberculosis bacillus and the mortality-reducing effects of the BCG vaccine.

Increased risk of secondary lung cancer in patients with tuberculosis: A nationwide, population-based cohort study.

BackgroundTuberculosis (TB) presents a global threat in the world and the lung is the frequent site of metastatic focus. A previous study demonstrated that TB might increase primary lung cancer risk by two-fold for more than 20 years after the TB diagnosis. However, no large-scale study has evaluated the risk of TB and secondary lung cancer. Thus, we evaluated the risk of secondary lung cancer in patients with or without tuberculosis (TB) using a nationwide population-based dataset.MethodsIn a cohort study of 1,936,512 individuals, we selected 6934 patients among patients with primary cancer and TB infection, based on the International Classification of Disease (ICD-p-CM) codes 010–011 from 2000 to 2015. The control cohort comprised 13,868 randomly selected, propensity-matched patients (by age, gender, and index date) without TB exposure. Using this adjusted date, a possible association between TB and the risk of developing secondary lung cancer was estimated using a Cox proportional hazards regression model.ResultsDuring the follow-up period, secondary lung cancer was diagnosed in 761 (10.97%) patients with TB and 1263 (9.11%) patients without TB. After adjusting for covariates, the risk of secondary lung cancer was 1.67 times greater among primary cancer in the cohort with TB than in the cohort without TB. Stratification revealed that every comorbidity (including diabetes, hypertension, cirrhosis, congestive heart failure, cardiovascular accident, chronic kidney disease, chronic obstructive pulmonary disease) significantly increased the risk of secondary lung cancer when comparing the TB cohort with the non-TB cohort. Moreover, the primary cancer types (including head and neck, colorectal cancer, soft tissue sarcoma, breast, kidney, and thyroid cancer) had a more significant risk of becoming secondary lung cancer.ConclusionA significant association exists between TB and the subsequent risk for metastasis among primary cancers and comorbidities. Therefore, TB patients should be evaluated for the subsequent risk of secondary lung cancer.

Thyroid Tuberculosis Causing Fever of Unknown Origin in a Patient With Multinodular Goiter

Introduction: Tuberculosis (TB) involving the thyroid gland is rare and typically results in hypothyroidism. Here we report a case of thyroid TB that presented with hyperthyroidism. Clinical Case: A 54-year-old woman with a history of hyperthyroidism due to toxic multinodular goiter presented to the emergency department with fever of unknown origin associated with sore throat, non-productive cough, night sweats, diarrhea, and right anterior neck pain that worsened with coughing. Her fevers were intermittent, ranging from 38 to 39 degrees Celsius, and would subside with acetaminophen. She reported that her symptoms had started after getting a thyroid [Tc-99m] pertechnetate scan and 24 hour [I-131] sodium iodide uptake study a month prior. The scan at the time revealed hyperfunctioning thyroid nodules in the lower lobes bilaterally. The 24-hour uptake was 20.2% which is within the normal range of 7 to 30%. TSH on presentation was 0.01 mIU/L (Normal range 0.3-5.50 mIU/L), free T4 was 2.05 ng/dL (Normal range 0.76 -1.7 ng/dL), and free T3 was 5 pg/mL (Normal range 1.9-3.9 pg/mL). Exam revealed a multinodular goiter, which was firm with mild tenderness, and no cervical lymphadenopathy. Infectious workup was unremarkable other than a positive interferon-gamma release assay. As for TB risk factors, the patient immigrated to the United States from Albania about 13 years prior. The patient denied any known TB exposure, neither had she been treated for TB. Radiograph and computed tomography (CT) of the thorax were unremarkable other than re-demonstration of the multinodular goiter. Fluorodeoxyglucose-18 positron emission tomography (FDG-PET), which was performed to identify any focus of active TB, had revealed intense, infiltrative, heterogeneous FDG uptake of the nodular thyroid gland with reactive level 3 and 4 cervical lymph nodes. Also, the scan revealed hyper-metabolic hilar, pre-tracheal, and sub-carinal lymph nodes which could represent latent TB. Further workup for any other foci of active TB including broncho-alveolar lavage, sputum cultures, lumbar puncture, and bone marrow biopsy were unremarkable. Thyroid ultrasound revealed 2 right sided and 3 left sided thyroid nodules, mostly solid and hypoechoic. Fine needle aspiration of nodules revealed benign follicular nodules bilaterally, however the left aspirate contained loose aggregates of histiocytes consistent with non-necrotizing granulomas. Acid-fast bacilli stain of the aspirate was negative. The patient was started on therapy for active TB with isoniazid, rifampin, pyrazinamide, and ethambutol. Six weeks after treatment her fevers had resolved. Conclusion: Thyroid TB should be considered when the severity of symptoms cannot be explained by the degree of hyperthyroidism alone in patients with increased risk of TB. Additionally, TB in the thyroid can be challenging to identify in a patient with known underlying thyroid disease.

Timing of Mycobacterium tuberculosis exposure explains variation in BCG effectiveness: a systematic review and meta-analysis

RationaleThe heterogeneity in efficacy observed in studies of BCG vaccination is not fully explained by currently accepted hypotheses, such as latitudinal gradient in non-tuberculous mycobacteria exposure.MethodsWe updated previous systematic reviews...