Reactivation Of Tuberculosis Research Articles

Prevalence of elevated liver transaminases and their relationship with alcohol use in people living with HIV on anti-retroviral therapy in Uganda.

Isoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude "regular and heavy alcohol drinkers" from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use. The Immune Suppression Syndrome Clinic of Mbarara, Uganda. We defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI). Among 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8-21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (p<0.01). In multivariable analyses, those currently using alcohol had higher odds of elevated transaminases compared to those abstaining (aOR 1.65, 95% CI 1.15-2.37) as did males compared to females (aOR 2.68, 95% CI 1.90-3.78). Pre-IPT elevated transaminases among PLWH receiving ART were common, similar to prior estimates, but severe elevations were rare. Current drinking and male sex were independently associated with elevated transaminases. Further research is needed to determine the implications of such transaminase elevations and alcohol use on providing IPT.

Efficacy of standard treatment protocol in recently diagnosed Lupus Nephritis at our tertiary care teaching hospital

Introduction: Lupus Nephritis occurred in approximately 50% of Systemic Lupus Erythematosuspatients at some point during their illness and is associated with a poor prognosis. Material andMethod: A prospective observational study of 50 newly diagnosed LN cases was conducted toinvestigate the response of standard treatment protocol (Cyclophosphamide -NIH protocol andMycophenolate Mofetil-MMF). Results: Of the 50 newly diagnosed cases of LN, 94 % (n=47) werefemales, and 6 % (n=3) were males, with class IV LN accounting for the majority of patients 69.39% (n=34). At six months, 36.7 % (n=11) of patients in the cyclophosphamide (CYP) group had acomplete response. Only 27.3 % of patients in the MMF group had a complete response; however,this difference was not statistically significant. At the end of one year, only 56.7 % of the CYP groupand 81.8 % of the MMF group had a complete response; however, this difference was notstatistically significant (p=0.282). Although the initial response with CYP was better and later in theMMF group, these differences were not significant statistically. Tuberculosis or its reactivation wasthe most common complication during treatment, either with MMF or CYP. One patient died due tolatent tuberculosis reactivation, another as a result of severe disease activity at presentation(proteinuria was 20 gm/24 hours in that patient), and the third as a result of pneumonia withsepticemia. Conclusion: Treatment with either CYP or MMF is equally effective, but underlyinginfection, particularly tuberculosis, should be ruled out before initiating therapy.

Severe Pulmonary Parenchymal Involvement Due to Reactivation of Latent Tuberculosis in a Patient With Small Cell Lung Cancer

Severe Pulmonary Parenchymal Involvement Due to Reactivation of Latent Tuberculosis in a Patient With Small Cell Lung Cancer

P448 Safety of anti-TNF introduction following tuberculosis treatment in Inflammatory Bowel Disease patients in an endemic area

Abstract Background Patients with inflammatory bowel diseases (IBD) have a greater risk of developing opportunistic infections, especially if they are under immunosuppressants and biological agents. Anti-tumor necrosis factor alpha (anti-TNF) has considerably increased the risk of tuberculosis (TB) in IBD patients. Brazil is considered an endemic area for TB and the safety of anti-TNF agents in IBD patients previous diagnosed with TB infection remains to be elucidated. The aim of this study was to evaluate the safety of anti-TNFs in patients with previous TB infection at a tertiary center in São Paulo, Brazil. Methods We retrospectively reviewed IBD patients with active TB followed in our center between January 2010 and December 2020. Data regarding disease phenotype, TB clinical presentation, IBD treatment at TB diagnosis and following TB treatment were collected from electronic medical records. TB diagnosis was based on symptoms, identification of the bacillus in body secretions, sample cultures, radiologic, endoscopic and histopathologic exams. Results Among 1040 IBD patients, we identified 37 patients with active TB (mean age at TB diagnosis 41.2 [25–69]; 59.4% male). Overall, 33 patients (89.2%) were under immunosuppressive medications. Of them, 27 (72.9%) were under anti-TNF drugs, 8 (29.6%) in monotherapy and 19 (70.3%) in combination with thiopurines or methotrexate. Pulmonary TB was the most common clinical presentation (40.5%) followed by disseminated TB (37.8%). Only 4 patients (10.8%) were not under immunosuppressant drugs and all of them were smokers. Sixteen (43.2%) patients received anti-TNF therapy after TB treatment, 4 of them had not been previously exposed to biologics. Median interval from TB diagnosis and anti-TNF initiation was 8 months (interquartile range [IQR] 4–24) and patients have been followed for a median of 34 months (IQR 7–108). Only one patient developed “de novo” tuberculosis, ten years after the first infection and after 48 months of treatment with infliximab and azathioprine. Conclusion Our findings suggest that treatment with anti-TNF following antituberculosis treatment is probably safe, even in endemic areas. TB occurred infrequently and after long-term follow-up, suggesting “de novo” infection rather than TB reactivation. This data emphasize the importance of periodic TB screening in IBD patients living in endemic areas.

Reactivation of latent tuberculosis with TNF inhibitors: critical role of the beta 2 chain of the IL-12 receptor.

Tumor necrosis factor (TNF) inhibitors have improved a lot the treatment of numerous diseases, with the well-known example of rheumatoid arthritis (RA). In the early 2000s, postmarketing data quickly revealed an alarming number of severe tuberculosis (TB) under such treatment. These findings were consistent with previous results in mice where TNF is essential for lymph node formation and granuloma organization. The effects of TNF inhibition on RA synovium structure are very similar to those on granuloma, with changes in cellular interactions, cytokine, and chemokine production. In addition to the role of TNF in granuloma, the interleukin (IL)-12/interferon (IFN)-γ pathway is required for an efficient host defense against TB. Primary and secondary immunodeficiencies affecting this pathway lead to severe bacillus Calmette-Guérin (BCG) reaction or full TB. Any chronic inflammation as in RA induces a systemic Th1 defect that predisposes to TB through specific downregulation of the IL-12Rß2 chain. When TNF inhibitors are initiated, this transiently increases this risk of TB, through effects on cellular interactions in a latent TB granuloma. At a later stage, when a better control disease activity is obtained, the risk of TB is reduced but not abrogated. Given the clear benefit from TNF inhibition, latent TB infection screening at baseline is essential for an optimal safety.

POS1437 LATENT TUBERCULOSIS INFECTION IN RHEUMATIC DISEASES: A REAL-LIFE STUDY OF THREE APULIAN CENTRES. DATA FROM BIOPURE REGISTRY

Background:Latent tuberculous infection (LTBI) is very common in the world and screening for it is essential before starting treatment with biotechnological drugsObjectives:The aims of our study were to assess the prevalence in Apulia of LTBI among patients affected with rheumatic disease and to record the cases of tuberculosis (TB) infection among patients treated with biologic agents.Methods:We analysed data of patients included in BIOPURE registry from 2008 to 2018, who underwent Quantiferon (QTF) test as routinely screening for biologic treatment. Demographic and clinical data were recorded at the time of the first QTF assessment and this time point was considered the “baseline” of the study. Data regarding further QTF tests performed during follow-up was also acquired by electronic charts. Prophylaxis administration and bDMARD treatments were recorded for patients with positive QTF test. All tuberculosis infections were recorded during the entire time of follow-up.Results:Three thousand thirty-five patients (female 67.2%, mean age 52 ± 18.3 years) were included in these study, 2692 patients (88.7%) had inflammatory arthritis (28.2% rheumatoid arthritis, 33% psoriatic arthritis and 27.4% spondyloarthritis), 129 (4.2%) patients had connective tissue disease, whereas 214 (7.1%) patients were affected by others rheumatic diseases. The prevalence of LTBI was 10.7% (326 patients) at baseline. Comparisons between positive and negative patients for QTF are reported in Table 1. We acquired data of LTBI prophylaxis of 284 patients; 235 out 265 patients treated with isoniazid completed the treatment, whereas 19 out 19 patients treated with rifampicin completed the prophylaxis regimen. The main cause of isoniazid withdrawal was hypertransaminasemia, but 8 patients then completed prophylaxis with rifampicin. During the entire follow-up (42.6±30.5 months), we recorded 5 (0.02%) cases of primary TB infection in patients on anti-TNFα agents treatment, which had baseline screening negative for LTBI. Data and outcome of these patients are reported in Table 2. The mean time of follow-up of patients on bDMARDs treatment with positive QTF at baseline was 52.7±35.2 months. bDMARD treatment regimens are reported in Table 3. No case of TB reactivation was found among patients with positive baseline QTF. Moreover, of 1563 (51.5%) patients who repeated QTF during follow-up, 62 (4%) of them showed a change in the test result. We observed a change to a positive state in 36 patients with previous negative QTF test, whereas 26 patients with previous positive QTF showed a shift to a negative test during follow-up.Conclusion:Our study shows a prevalence of LTBI of 10.7% in Apulian patients affected with rheumatic disease. bDMARDs therapy appears to be safe in patients with positive QTF test treated according to current recommendations1. However, cases of primary TB infections, especially in patients receiving anti-TNFα drugs, have been observed.

Latent and active tuberculosis infection in allogeneic hematopoietic stem cell transplant recipients: a prospective cohort study.

Tuberculosis (TB) is a major infectious complication in hematopoietic stem cell transplant (HSCT) recipients in countries with high TB prevalence. Identifying and treating latent tuberculosis infection (LTBI) helps to prevent TB reactivation after transplantation. Few studies have compared the tuberculin skin test (TST) with interferon Gamma release assays (IGRA) to diagnose LTBI in HSCT candidates. We compared TST and QuantiFeron TB gold in tube (QTF-GIT) and prospectively evaluated the incidence of active tuberculosis in 126 HSCT candidates and 58 HSCT recipients with chronic GVHD followed at the outpatient clinic. TB was diagnosed by culture in Mycobacteria media and by commercial real-time PCR kit. Considering the positivity of any test, the prevalence of LTBI was 8.7% in HSCT candidates (11 out of 126) and 12.5% in HSCT recipients with chronic GVHD (6 out of 48). QTF-GIT indeterminate results were detected in 2.4% of the HSCT candidates. Fair to good agreement (K > 0.50) between tests was observed in both cohorts. Cumulative incidence of TB was 3% in the GVHD cohort. TB was diagnosed in 2 chronic GVHD recipients, both cases confirmed by positive culture and PCR. None of the 11 patients with LTBI diagnosed pre-HSCT who received INH prophylaxis developed TB.

Coronavirus Activates an Altruistic Stem Cell–Mediated Defense Mechanism that Reactivates Dormant Tuberculosis: Implications in Coronavirus Disease 2019 Pandemic

We postulate that similar to bacteria, adult stem cells may also exhibit an altruistic defense mechanism to protect their niche against external threat. Herein, we report mesenchymal stem cell (MSC)–based altruistic defense against a mouse model of coronavirus, murine hepatitis virus-1 (MHV-1) infection of lung. MHV-1 infection led to reprogramming of CD271+ MSCs in the lung to an enhanced stemness phenotype that exhibits altruistic behavior, as per previous work in human embryonic stem cells. The reprogrammed MSCs exhibited transient expansion for 2 weeks, followed by apoptosis and expression of stemness genes. The conditioned media of the reprogrammed MSCs exhibited direct antiviral activity in an in vitro model of MHV-1–induced toxicity to type II alveolar epithelial cells by increasing their survival/proliferation and decreasing viral load. Thus, the reprogrammed MSCs can be identified as altruistic stem cells (ASCs), which exert a unique altruistic defense against MHV-1. In a mouse model of MSC-mediated Mycobacterium tuberculosis (MTB) dormancy, MHV-1 infection in the lung exhibited 20-fold lower viral loads than the MTB-free control mice on the third week of viral infection, and exhibited six-fold increase of ASCs, thereby enhancing the altruistic defense. Notably, these ASCs exhibited intracellular replication of MTB, and their extracellular release. Animals showed tuberculosis reactivation, suggesting that dormant MTB may exploit ASCs for disease reactivation.

Use of thiopurines in inflammatory bowel disease: an update.

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.

Corticosteroids for COVID-19 Therapy: Potential Implications on Tuberculosis.

On 11 March 2020, the World Health Organization announced the Corona Virus Disease-2019 (COVID-19) as a global pandemic, which originated in China. At the host level, COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), affects the respiratory system, with the clinical symptoms ranging from mild to severe or critical illness that often requires hospitalization and oxygen support. There is no specific therapy for COVID-19, as is the case for any common viral disease except drugs to reduce the viral load and alleviate the inflammatory symptoms. Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), also primarily affects the lungs and has clinical signs similar to pulmonary SARS-CoV-2 infection. Active TB is a leading killer among infectious diseases and adds to the burden of the COVID-19 pandemic worldwide. In immunocompetent individuals, primary Mtb infection can also lead to a non-progressive, asymptomatic latency. However, latent Mtb infection (LTBI) can reactivate symptomatic TB disease upon host immune-suppressing conditions. Importantly, the diagnosis and treatment of TB are hampered and admixed with COVID-19 control measures. The US-Center for Disease Control (US-CDC) recommends using antiviral drugs, Remdesivir or corticosteroid (CST), such as dexamethasone either alone or in-combination with specific recommendations for COVID-19 patients requiring hospitalization or oxygen support. However, CSTs can cause immunosuppression, besides their anti-inflammatory properties. The altered host immunity during COVID-19, combined with CST therapy, poses a significant risk for new secondary infections and/or reactivation of existing quiescent infections, such as LTBI. This review highlights CST therapy recommendations for COVID-19, various types and mechanisms of action of CSTs, the deadly combination of two respiratory infectious diseases COVID-19 and TB. It also discusses the importance of screening for LTBI to prevent TB reactivation during corticosteroid therapy for COVID-19.

Tuberculosis in Biologic-naïve Patients With Rheumatoid Arthritis: Risk Factors and Tuberculosis Characteristics.

To investigate risk factors and characteristics of active tuberculosis (TB) in biologic-naïve patients with rheumatoid arthritis (RA). We conducted a population-based case-control study using the Swedish Rheumatology Quality Register, the National Patient Register, and the Tuberculosis Register to identify RA patients with active TB and matched RA controls without TB between 2001-2014. Clinical data were obtained from medical records. TB risk was estimated as adjusted OR (aOR) with 95% CI using univariate and multivariable logistic regression analyses. After validation of diagnoses, the study included 31 RA patients with TB and 122 matched RA controls. All except 3 cases had reactivation of latent TB. Pulmonary TB was most prevalent (84%). Ever use of methotrexate was not associated with increased TB risk (aOR 0.8, 95% CI 0.3-2.0), whereas ever treatment with leflunomide (aOR 6.0, 95% CI 1.5-24.7), azathioprine (aOR 3.8, 95% CI 1.1-13.8), and prednisolone (PSL; aOR 2.4, 95% CI 1.0-6.0) was. There were no significant differences between maximum dose of PSL, treatment duration with PSL before TB, or cumulative dose of PSL the year before TB diagnosis between cases and controls. Obstructive pulmonary disease was associated with an increased TB risk (aOR 3.9, 95% CI 1.5-10.7). Several RA-associated factors may contribute to increased TB risk in biologic-naïve patients with RA, making the risk of TB activation difficult to predict in the individual patient. To further decrease TB in patients with RA, the results suggest that screening for latent TB should also be considered in biologic-naïve patients.

Surgical treatment of children with a combination of congenital lung malformations and tuberculosis

Congenital malformations of the bronchopulmonary system in combination with tuberculosis are extremely rare in practice, but they usually require surgical treatment. This combination often causes diagnostic difficulties.Characteristics of children and research methods. We have analyzed the experience of surgical treatment of a combination of various congenital lung defects and tuberculosis in 20 children. 9 (45%) children had lung sequestration, 4 (20%) children had lung hypoplasia, 5 (25%) children had congenital bronchiectasis, 1 (5%) child had arteriovenous malformation, and 1 (5%) child had a congenital lung cyst. There were 3 segmental resections, 15 lobeand bilobectomies, and 3 pneumonectomies. All surgeries were performed using minimally invasive approaches (VATS).Results. 11 (55%) patients had diagnostic difficulties of concomitant pathology. Only in 5 (25%) cases they found mycobacteria in sputum before surgery. Postoperative study of material from tuberculous lesions helped to establish multidrug resistance of mycobacterium tuberculosis and to change the chemotherapy regimen in 3 (15%) patients. There were no postoperative complications or deaths. All surgeries were effective. Long-term results were studied in 16 (80%) of 20 patients over a period from 1 to 10 years. No cases of reactivation of tuberculosis or disability.Conclusion. Resection surgery for combination of tuberculosis and congenital lung defects allowed to clarify the diagnosis and to achieve a direct effect in all patients by clarifying the drug resistance of mycobacterium tuberculosis and to optimize postoperative chemotherapy.

COVID-19 and Tuberculosis Coinfection: A Report of Two Cases

COVID-19 and its sequelae are primarily known to affect the respiratory system. However, it can have varied manifestations affecting other systems as well. COVID-19 can lead to reactivation of tuberculosis which can have unusual extrapulmonary presentations as well. Coinfection of COVID-19 and tuberculosis is a risk factor for poor outcome. Here, we describe a series of two cases of COVID-19 with tuberculosis. In the first case, a patient who had apparently recovered from COVID-19 presented only a week later with polyserositis, and ultimately was diagnosed to be a case of disseminated tuberculosis. In the second case, the patient presented with COVID-19 and TB together. Clinicians must be aware and vigilant for this coinfection and complication in COVID-19 recovered patients even if they were of mild/ asymptomatic category.

Improved Awareness of Tuberculosis Infection in Advanced Stage Chronic Renal Disease Could Reduce Cases of Active TB: Lessons from Four Challenging Cases

Patients with chronic kidney disease (CKD) have an increased risk of developing tuberculosis (TB) compared to those with normal renal function. The reasons for this are well described, but include impaired cellular immunity, a high incidence of co-morbid conditions as well as the concomitant use of immunosuppressive medications. Ethnicity as well as socio-economic factors also prevail. Expert guidelines recommend TB chemoprophylaxis in renal transplant recipients deemed at high risk – invariably those from ethnic minorities or recent arrivals from areas with high endemic rates of TB. However, in most renal centres within the UK including our own, high risk patients with advanced CKD (stages 4 and 5) are not routinely screened for latent TB infection (LTBI) prior to transplantation, thus contributing to missed opportunities for preventing TB disease. We report four challenging cases of patients diagnosed with TB disease on a background of advanced CKD, who all presented within an 18-month period whilst under the care of a large tertiary renal centre. Two of the cases were patients with well-functioning renal transplants and two were on renal replacement therapy. We describe our experience and share practical considerations on how to manage TB in CKD including the role of therapeutic drug monitoring in peritoneal dialysis. These cases highlight the need for a better awareness of the possibility of TB reactivation and underscore the arguments in favour of screening programmes for LTBI in patients with advanced CKD.

A150 INFLIXIMAB INDUCED EOSINOPHILIC PNEUMONITIS IN AN ADOLESCENT

Abstract Background Infliximab is used to induce and maintain remission of inflammatory bowel disease (IBD). Pulmonary abnormalities in IBD are rare, but comprise airway, parenchymal and interstitial lung complications. Pulmonary adverse effects reported after Infliximab include tuberculosis reactivation, invasive aspergillosis, interstitial pneumonitis, pulmonary oedema and alveolar hemorrhage. Aims Four cases previously reported associate Infliximab to eosinophilic pneumonitis. However, this is the first in pediatrics. Methods Case report of an adolescent female with IBD and a rare adverse reaction to Infliximab Results Our patient was diagnosed with ulcerative pancolitis, Mayo 2, initially treated with 5-ASA. Five months into therapy she was switched to azathioprine and Infliximab (10mg/kg every 8 weeks) due to worsening disease. She attained and maintained clinical and biochemical remission for the next 1.5 years. Azathioprine was stopped at the patient’s request. One month later, she presented with cough and nasal congestion but was afebrile. Peripheral eosinophilia was noted. Salbutamol and steroid inhalers were started, without improvement. She was admitted to hospital due to progressive cough, shortness of breath, and wheezing. Physical examination was otherwise unremarkable. Pulmonary function test showed FVC of 69%, FEV1 of 45% with bronchodilator effect of 12% and a FEV1/FVC of 59. Her blood work showed eosinophilia (4.42 x109/L) and an elevated IgE (4596 ug/L). Serum-specific IgE for Aspergillus was positive; but skin testing was negative. An X-ray showed marked bilateral interstitial thickening in the mid and lower zones. Chest CT showed extensive bronchiectasis with bronchial mucous plugging. A bronchoscopy with bronchoalveolar lavage (BAL) reported marked eosinophilia, negative for mycobacterium, bacterial and fungal growth. Other infectious and autoimmune etiologies were ruled out. She responded successfully to high-dose prednisone (50 mg/day). At discharge, symptoms had improved, and her pulmonary function tests were normal (FEV1 of 95% predicted and FEV1/FVC 84). Upon steroid taper, she relapsed in pulmonary symptoms, eosinophilia, as well as a flare of her IBD. Reinduction with steroids resolved her symptoms and eosinophilia. Due to her loss of response to Infliximab and pulmonary, she was switched to Vedolizumab with good response. After stopping Infliximab her lung function improved significantly (FVC of 96% predicted and FEV1 of 98% predicted) and has remained so. Peripheral eosinophilia dropped to 0.2 x109/L. Her IBD is currently in remission without any respiratory symptoms. Conclusions Eosinophilic pneumonitis can be a complication of Infliximab. Our patient had a delayed presentation of respiratory symptoms, 16 months after a satisfactory response to Infliximab. Although responsive to steroids, she ultimately needed to be switched to another immunosuppressive agent. Funding Agencies None

Joint Statement (DZK, DGRh, DDG) on the Tuberculosis Risk with Treatment Using Novel Non-TNF-Alpha Biologicals.

While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed. We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019. Of interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria. 677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63 %, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68 %) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33 %, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment. The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future.

Deletion of pknG Abates Reactivation of Latent Mycobacterium tuberculosis in Mice.

Eradication of tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), has been a challenge due to its uncanny ability to survive in a dormant state inside host granulomas for decades. Mtb rewires its metabolic and redox regulatory networks to survive in the hostile hypoxic and nutrient-limiting environment, facilitating the formation of drug-tolerant persisters. Previously, we showed that protein kinase G (PknG), a virulence factor required for lysosomal escape, aids in metabolic adaptation, thereby promoting the survival of nonreplicating mycobacteria. Here, we sought to investigate the therapeutic potential of PknG against latent mycobacterium. We show that inhibition of PknG by AX20017 reduces mycobacterial survival in in vitro latency models such as hypoxia, persisters, and nutrient starvation. Targeting PknG enhances the bactericidal activity of the frontline anti-TB drugs in peritoneal macrophages. Deletion of pknG resulted in 5- to 15-fold-reduced survival of Mtb in chronically infected mice treated with anti-TB drugs. Importantly, in the Cornell mouse model of latent TB, the deletion of pknG drastically attenuated Mtb's ability to resuscitate after antibiotic treatment compared with wild-type and complemented strains. This is the first study to investigate the sterilizing activity of pknG deletion and inhibition for adjunct therapy against latent TB in a preclinical model. Collectively, these results suggest that PknG may be a promising drug target for adjunct therapy to shorten the treatment duration and reduce disease relapse.

Impact of latent tuberculosis infection on health and wellbeing: a systematic review and meta-analysis.

The impact of latent tuberculosis infection (LTBI) on health and wellbeing is not well understood. This review aims to evaluate the health and wellbeing of individuals with LTBI. A systematic literature search was performed to assess studies reporting patient-reported outcomes in LTBI management including health-related quality of life (HRQoL), health utilities, disease burden and experience of individuals with LTBI. A pooled analysis was performed to estimate the effect of LTBI on HRQoL.A total of 4464 studies were screened, of which 13 eligible articles describing nine unique studies were included for review. The HRQoL of individuals with LTBI and without tuberculosis (TB) infection were comparable, and better than patients with active TB disease. However, individuals with LTBI reported poorer mental health compared with individuals without TB infection (mean difference -4.16, 95% CI -7.45- -0.87; p=0.01). Qualitative studies suggest the presence of fear, anxiety and stigma in individuals with LTBI.This review highlights potential psychosocial challenges in individuals with LTBI despite the absence of clinical symptoms. While their quality of life was marginally affected, this could be evidence to support LTBI management in preventing TB re-activation and the severe consequences of active TB disease that affect all domains of HRQoL.

Various Forms of Tuberculosis in Patients with Inflammatory Bowel Diseases Treated with Biological Agents.

Although there are undeniable advantages of treatment of the inflammatory bowel diseases, Crohn's disease, and ulcerative colitis, with biological agents, the increased susceptibility to tuberculosis should not be ignored. Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis complex which includes M. tuberculosis, M. bovis, and M. africanum. Primary tuberculosis is uncommon in the setting of inflammatory bowel disease: reactivation of latent tuberculosis is of greater concern. Consequently, latent infection should be excluded in patients who qualify for immunosuppressive treatments. Apart from the review of the literature, this article also presents three cases of different patterns of tuberculosis that occurred during treatment with infliximab, adalimumab, or vedolizumab. The first case reports a case of tuberculosis presenting as right middle lobe pneumonia. The second case featured miliary tuberculosis of the lungs with involvement of the mediastinal lymph nodes, liver, and spleen. The third patient developed a tuberculoma of the right parietal lobe and tuberculous meningitis. It is important to reiterate that every patient qualifying for a biologic agent should undergo testing to accurately identify latent tuberculosis, as well as precise monitoring for the possible development of one of the various forms or patterns of tuberculosis during treatment.

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Pulmonary tuberculosis surgery is characterized by a number of aspects associated with adhesions in the pleural cavity, fibrosis of the lung root, destruction of the parenchyma, which contribute to the development of intra- and postoperative complications such as residual pleural cavity and reactivation of tuberculosis in operated lung due to compensatory tissue distortion. Aim: to improve video-assisted lung resection (VATS) in tuberculosis patients with the presence of pleural cavity obliteration. Materials and methods. The developed method of VATS for tuberculosis patients with pleural cavity obliteration is based on separate intubation of right and left main bronchi for mechanical ventilation of one lung, placement of thoracic port, performing revision of pleural cavity using video-assisted thoracoscopy, performing mini-thoracotomy and resection of lung with separate treatment of anatomical structures in required volume by means of disposable stapler or regular open thoracotomy instruments, pleural cavity draining and layered wound closure. Computed tomography of chest is performed during the operation in order to assess the extent and severity of pleural adhesions and to locate safe position of thoracic ports. Hydraulic needle preparation of parietal pleura is performed in severe adhesions area. Hemorrhage is treated using hemostatic plate Surgicel Fibrillar made of restored cellulose. Phrenicotripsy, pleural cavity drainage and, finally, artificial pneumoperitoneum are performed. The proposed method of video-assisted lung resection was used in 41 patients, 25 patients underwent video-assisted resection according to the prototype method. Results. The proposed method reduced duration of the surgical intervention by 52.7 minutes; the frequency of intraoperative complications by 14.4%; the incidence of postoperative complications by 14.2; the duration of patient�s stay at the hospital by 5.8 days and increased of overall treatment efficiency by 14.5%. The proposed method of VATS for patients with pulmonary tuberculosis and pleural cavity obliteration is safe, effective, simple to implement and can be performed at thoracic surgery departments of various pulmonary hospitals of city and regional level. Key words: pulmo