Reactivation Of Latent Tuberculosis Research Articles

Human-immunodeficiency virus infection associated with the impaired Th1 and pro-inflammatory cytokine response in latent tuberculosis-infected individuals: A comparative cross-sectional study.

Tuberculosis (TB) and HIV co-infections are extensively overlapping, especially in developing countries. HIV infection is known as a major risk factor for the reactivation of latent TB into active TB. Although not fully understood and needs further study, HIV infection might enhance the reactivation of latent TB by breaching immune control mechanisms. We investigated the influence of HIV infection on the cytokine response of LTB-infected individuals. Heparinized venous blood was collected from 40 ART-naïve HIV-infected and 30 HIV-negative healthy controls for LTB screening, plasma collection, and PBMC isolation and stimulation. The level of cytokines in plasma and their production by PBMCs stimulated with purified protein derivative (PPD), staphylococcus enterotoxin B (SEB), or unstimulated PBMCs were analyzed using a cytometric bead array (CBA) assay. PPD-induced IL-2 by PBMCs was higher in LTB-infected groups compared with HIV-negative LTB-negative groups (p = 0.0015). When LTB-infected groups were co-infected with HIV (HIV+LTB+), the IL-2 (p < 0.0001) and IFN-gamma (p = 0.0144) production by PPD-stimulated PBMCs was reduced. The level of IL-2 (p = 0.0070), IL-6 (p = 0.0054), and TNF-alpha (p = 0.0045) in plasma were lower in HIV+LTB+ individuals compared with HIV-negative LTB-positive (HIV-LTB+) groups. Our findings suggested that HIV co-infection in LTB-positive individuals is associated with the diminished production of PPD-induced Th1 (IFN-gamma and IL-2) cytokines by PBMCs and in the plasma level of IL-2 and proinflammatory cytokines (IL-6 and TNF-alpha).

Analyzing the seasonality of tuberculosis case notifications in the UK, 2000-2018.

Globally, there is seasonal variation in tuberculosis (TB) incidence, yet the biological and behavioural or social factors driving TB seasonality differ across countries. Understanding season-specific risk factors that may be specific to the UK could help shape future decision-making for TB control. We conducted a time-series analysis using data from 152,424 UK TB notifications between 2000 and 2018. Notifications were aggregated by year, month, and socio-demographic covariates, and negative binomial regression models fitted to the aggregate data. For each covariate, we calculated the size of the seasonal effect as the incidence risk ratio (IRR) for the peak versus the trough months within the year and the timing of the peak, whilst accounting for the overall trend. There was strong evidence for seasonality (p < 0.0001) with an IRR of 1.27 (95% CI 1.23-1.30). The peak was estimated to occur at the beginning of May. Significant differences in seasonal amplitude were identified across age groups, ethnicity, site of disease, latitude and, for those born abroad, time since entry to the UK. The smaller amplitude in older adults, and greater amplitude among South Asians and people who recently entered the UK may indicate the role of latent TB reactivation and vitamin D deficiency in driving seasonality.

A Case Report on Peritoneal Tuberculosis in an Immunocompromised Patient

Background: Peritoneal tuberculosis (PTB) is one of the most challenging forms of extra pulmonary tuberculosis. Abdominal TB cases make up above 3% of all extra pulmonary TB as per the Index TB Guidelines. PTB is commonly due to reactivation of latent tuberculosis in the peritoneum. Numerous cases were still misdiagnosed due to nonspecific presentation. The golden standard for diagnosis is laparoscopic biopsy. Presenting signs and symptoms of PTB are unspecific such as ascites, abdominal pain and distension, fever, weight loss, diarrhea/constipation. Peritoneal tuberculosis is a significant cause of ascites in developing countries. The causative agent of peritoneal tuberculosis is Mycobacterium tuberculosis. Case Presentation: In this case study, a 52 year old male had complaints of progressive abdominal distension and fever for 2 weeks. Patient underwent diagnostic paracentesis, upper and lower GI endoscopy, biopsy and gene xpert to confirm peritoneal tuberculosis. Patient with peritoneal TB have gradually progressive abdominal swelling due to ascites and abdominal pain. Conclusion: Peritoneal tuberculosis should be considered in differential diagnosis. Differential diagnosis, especially in the developing countries or under developed countries. This case highlights the easy diagnosis of the condition other than the other case reports.

Immunoinformatics and structural aided approach to develop multi-epitope based subunit vaccine against Mycobacterium tuberculosis

Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis (Mtb), which is one of the prominent reasons for the death of millions worldwide. The bacterium has a substantially higher mortality rate than other bacterial diseases, and the rapid rise of drug-resistant strains only makes the situation more concerning. Currently, the only licensed vaccine BCG (Bacillus Calmette–Guérin) is ineffective in preventing adult pulmonary tuberculosis prophylaxis and latent tuberculosis re-activation. Therefore, there is a pressing need to find novel and safe vaccines that provide robust immune defense and have various applications. Vaccines that combine epitopes from multiple candidate proteins have been shown to boost immunity against Mtb infection. This study applies an immunoinformatic strategy to generate an adequate multi-epitope immunization against Mtb employing five antigenic proteins. Potential B-cell, cytotoxic T lymphocyte, and helper T lymphocyte epitopes were speculated from the intended proteins and coupled with 50 s ribosomal L7/L12 adjuvant, and the vaccine was constructed. The vaccine’s physicochemical profile demonstrates antigenic, soluble, and non-allergic. In the meantime, docking, molecular dynamics simulations, and essential dynamics analysis revealed that the multi-epitope vaccine structure interacted strongly with Toll-like receptors (TLR2 and TLR3). MM-PBSA analysis was performed to ascertain the system’s intermolecular binding free energies accurately. The immune simulation was applied to the vaccine to forecast its immunogenic profile. Finally, in silico cloning was used to validate the vaccine’s efficacy. The immunoinformatics analysis suggests the multi-epitope vaccine could induce specific immune responses, making it a potential candidate against Mtb. However, validation through the in-vivo study of the developed vaccine is essential to assess its efficacy and immunogenicity profile, which will assure active protection against Mtb.

BI44 Latent tuberculosis reactivation in a patient with chronic plaque psoriasis treated with ustekinumab with a review of the literature

Abstract Ustekinumab, a monoclonal antibody against interleukin (IL)-12 and IL-23, is used for the treatment of psoriasis and psoriatic arthritis. The IL-12 pathway also plays an important role in regulating immunity to Mycobacterium tuberculosis. A multicentre, double-blind, randomized clinical trial study of 121 Korean patients with moderate-to-severe psoriasis revealed at least 75% improvement in Psoriasis Area and Severity Index (PASI) score after 12 weeks of ustekinumab treatment. Ten cases of latent tuberculosis infection (LTBI) were reported. Lupea-Chilom et al. [Lupea-Chilom DS, Solovan CS, Farcas SS et al. Latent tuberculosis in psoriasis patients on biologic therapies: real-world data from a care center in Romania. Medicina (Kaunas) 2023; 59: 1015] conducted a retrospective observational study on a total of 97 patients with severe psoriasis who were on different biologics. That study showed that two of seven patients on monotherapy ustekinumab developed LTBI. In this abstract, we present the case of a 49-year-old White woman with resistant moderate-to-severe chronic psoriasis without psoriatic arthritis who developed LTBI while on ustekinumab. She was diagnosed with psoriasis in 2012 with involvement of the scalp, flexural, vulval and gluteal regions as well as the nails. She was started on ustekinumab in October 2013 following a satisfactory prebiologics screen (including a negative QuantiFERON test). Her PASI score was zero at week 12. In 2017, she developed a malar rash and positive antinuclear antibody test, which was not tested prior to starting biologics. As lupus is a potential adverse effect of this medication, the ustekinumab was stopped in April 2017. Further rheumatological investigations ruled out lupus and ustekinumab was restarted in November 2017. As part of the screening process prior to restarting treatment, she had a repeat QuantiFERON test, which was positive. The respiratory team reviewed the patient and issued a 3-month course of rifampicin and isoniazid to treat LTBI. Following a few months of monitoring, it was deemed safe to restart ustekinumab in December 2018 and her PASI improved. In February 2020, due to the COVID pandemic, this medication had to be stopped. She was started on acitretin as an alternative in 2021 with a resulting worsening of her condition. In December 2021, the patient was restarted on ustekinumab. In this abstract, we illustrate that ustekinumab has the potential to reactivate latent tuberculosis, a phenomenon that is infrequently reported and attributed to its impact on the IL-12 pathway. To address this concern, we recommend conducting repeated annual screening during treatment in addition to a comprehensive baseline evaluation, including a chest X-ray and QuantiFERON test. Additionally, it is advisable to consider initiating isoniazid chemoprophylaxis concurrently with ustekinumab treatment as a precautionary measure.

Paradoxical tuberculous reaction to anti-tnfα discontinuation: a complex case of miliary tuberculosis and macrophagic activation syndrome with hepatic manifestations

Tuberculosis reactivation during anti-TNF-alpha therapy paradoxically worsened following reconstitution of pathogen-specific immune responses after cessation of TNFα antagonist treatment and initiation of anti-bacillary therapy. We report the case of a 46-year-old woman who was prescribed a tumor necrosis factor blocker (anti-TNF) for a relapse of Behçet's disease. The patient developed pulmonary miliary tuberculosis following the reactivation of latent tuberculosis, despite a normal pre-therapeutic work-up. Discontinuation of anti-TNF and initiation of anti-bacillary drugs triggered a paradoxical tubercular reaction (PTR). The diagnosis of paradoxical reaction to anti-tuberculosis drugs was evoked by the clinical and biological deterioration and the appearance of miliary cerebral tuberculosis and cerebral venous thrombosis after a period of clinical improvement. Although this phenomenon has been documented, it represents a major challenge for clinicians. The peculiarity of this case lies in its association with a macrophagic activation syndrome (MAS) with hepatic involvement, retained on clinical-biological and histological criteria. The overlap between MAS and PTR makes it difficult to diagnose these two entities with certainty. The patient responded favorably to moderate-dose systemic corticosteroid therapy with progressive degression, and the reintroduction of anti-tuberculosis drugs.This work aims to highlight the importance of close monitoring of TB patients on anti-TNFα therapy for early diagnosis and management of complications to improve the prognosis of these complex patients.

Late Tuberculosis Reactivation After Severe Covid-19.

Although there is no specific therapy for COVID-19, it is recommended that patients with severe SARS-CoV-2 infection are treated with corticosteroids and anti-IL-6 receptor monoclonal antibodies. Both COVID-19 itself and the treatment modalities mentioned above have suppressive effects on the immune system which may lead to an increased susceptibility to other infections. In patients with latent tuberculosis (TB) reactivation of TB infection after recovery from severe COVID-19 has been described. Most of these cases have occurred in parts of the world where tuberculosis is endemic. The patient is a female in her 70s who was born and raised in Southeast Asia and has lived in the Netherlands for more than 30 years. She was treated for a severe COVID-19 requiring mechanical ventilation for several weeks and pharmaceutical treatment with corticosteroids and anti-IL-6 receptor monoclonal antibodies (Sarilumab). She recovered well. Two years later she was readmitted with symptoms of a serious pulmonary infection and meningitis. Her condition deteriorated in a short time. An active TB infection was diagnosed. Despite adequate antibiotic treatment and supportive therapy her condition worsened and four days after admission to the ICU she deceased. Reactivation of latent TB after recovery from a severe COVID-19 has been described several times and may occur several months after the SARS-CoV-2 infection. In this case the reactivation presented two years after COVID-19. This case illustrates that long-term follow-up of patients with latent TB that recover from a severe COVID-19 may be indicated. Reactivation of latent tuberculosis infection in patients treated for a severe COVID-19 may occur even two years after recovery from SARS-CoV-2 infection.Most cases of reactivation of tuberculosis after COVID-19 are described in regions where tuberculosis is endemic. However, it may also occur in countries with a relatively low prevalence of tuberculosis infection. The exact incidence of tuberculosis reactivation after COVID-19 is unknown and probably underestimated.A long-term follow-up of patients after severe COVID-19 treated with corticosteroids and/or anti-IL-6 receptor monoclonal antibodies with a history of tuberculosis or patients migrated from countries where tuberculosis is endemic seems to be important.

Challenges in Diagnosing and Managing Pulmonary Conditions: A Case Series Highlighting Pulmonary Tuberculosis and Lung Cancer

This study delves into the intricate challenges encountered in diagnosing and managing pulmonary conditions, focusing on tuberculosis (TB) and lung cancer, especially in individuals with a history of cancer treatment and tobacco use. Through a detailed analysis of clinical cases, we explore the complexities associated with TB reactivation post-cancer therapy and the hurdles in timely diagnosing lung cancer in tobacco users. Three cases are presented: A 60-year-old male with a history of pulmonary TB, bidi smoking, and a diagnosis of adenocarcinoma after presenting with persistent cough and imaging findings suggestive of lung cancer. A 57-year-old male, post-cancer treatment, presenting with cough, diagnosed with TB after immunosuppression, highlighting diagnostic challenges in this population. A 63-year-old female with a prolonged cough and blood streaks in sputum, not responding to anti-TB treatment, ultimately diagnosed with lung cancer due to tobacco use. These cases underscore the need for vigilant monitoring and early intervention in post-cancer individuals vulnerable to latent TB reactivation, comprehensive diagnostic approaches for immunocompromised patients, and heightened awareness of the association between tobacco use and lung cancer. The study emphasizes the importance of thorough assessments, timely interventions, and collaborative efforts among healthcare providers to optimize outcomes in patients with overlapping health concerns. In conclusion, this study sheds light on the complexities of managing patients with a history of cancer, TB, and tobacco use, advocating for a holistic approach in diagnosis and management to improve patient outcomes and quality of life. Further research and clinical guidelines are warranted to refine treatment strategies and enhance the care of individuals facing these dual health challenges. Keywords: Lung Cancer, Pulmonary Tuberculosis, Lung Cancer and Pulmonary.

Characteristics, management, and outcome of tuberculosis after liver transplant: A case series and literature review

BackgroundLiver transplant recipients are at risk of tuberculosis, which is particularly difficult-to diagnose and to treat in this population. MethodsRetrospective study of all cases of tuberculosis diagnosed from 2007 to 2022 in the French network of liver transplant sites. ResultsTwenty-three liver transplant recipients were diagnosed with tuberculosis (six females, median age 59 years [interquartile range, 54–62]), with a median time lapse of 10 months [5–40.5] after transplant, and 38 days [26–60] after symptoms onset. Primary modes of pathogenesis were latent tuberculosis reactivation (n = 15) and transplant-related transmission (n = 3). Even though most patients with pre-transplant data had risk factors for tuberculosis (11/20), IFN-gamma release assay was performed in only three. Most cases involved extra-pulmonary tuberculosis (20/23, 87 %). With median follow-up of 63 months [24–108], five patients died (22 %), including four tuberculosis-related deaths. ConclusionsExtrapulmonary tuberculosis is a severe disease in liver transplant recipients. Systematic pre-transplant screening of latent tuberculosis may prevent most of them.

Lack of Reactivation of Latent Tuberculosis despite PD-1 Immunotherapy and Chemotherapy: A Case Report and Systematic Review

Background: Programmed Death 1 (PD-1) has a controversial role in the treatment of Tuberculosis (TB). Several clinical cases of TB development have been reported by administration of anti–PD-1 antibodies for patients with advanced unresectable cancers. Case presentation: In this article, we report an interesting case about a male patient with history of cured pulmonary tuberculosis and a 4-month history of repeated hemoptysis. Imaging showed one mass in the lower lobe of left lung and the other in the left upper lobe. The diagnosis of Non-Small-Ccell Lung Cancer (NSCLC) was determined by biopsy specimens in the lower lobe nodule and cured pulmonary tuberculosis determined by past medical history. He was given neoadjuvant treatment with an anti–PD-1 inhibitor and chemotherapy. He underwent surgery. Pathological examination revealed Mtb in left upper lobe nodule but previous imaging showed without reactivation and slight reduction in tubercular infection inflammation. The left lower lobe nodule was poorly differentiated carcinoma. Conclusions: Overall, the role of immune checkpoint inhibitors in patients with cancers and latent tuberculosis infection is inconclusive. Although we cannot establish whether patients with stage IIIA NSCLC and concurrent latent pulmonary tuberculosis after surgical evaluation can receive a PD-1 and chemotherapy as neoadjuvant therapy without the activation of pulmonary tuberculosis, our case endorses the need of further evaluation.

Infection of Fetal Membranes with Mycobacterium tuberculosis and Tissue Processing to Isolate RNA for Expression Analysis.

This chapter outlines the methodology employed to infectthe chorionic and amniotic membranes with Mycobacterium tuberculosis during pregnancy. Particularly, congenital tuberculosis, a rare and serious condition associated with cases in neonates and reactivation of latent tuberculosis in pregnant mothers, is interesting to study. Understanding the mechanisms of infection and the response of fetal membranes is crucial for developing effective treatments in these cases, which will promote better neonatal and maternal health in situations of tuberculosis during pregnancy. Establishing a standardized infection model in the chorioamniotic membranes is imperative, followed by a treatment protocol for isolating both cellular and mycobacterial RNA. This will enable the expression analysis during the maternal-fetal interface interaction with M. tuberculosis. The proposed methodology might be invaluable for qRT-PCR, microarrays, and sequencing research.

Rituximab Use and the Increased Risk of Reactivation of Latent Tuberculosis?

Rituximab Use and the Increased Risk of Reactivation of Latent Tuberculosis?

The Risk of Latent Tuberculosis Reactivation in COVID-19 Therapy

The high mortality rate among COVID-19 patients in the acute respiratory distress syndrome (ARDS) phase led to the administration of immunosuppressive drugs. Corticosteroids could block inflammation caused by cytokine storm, and prevent pneumonia, edema, fibrosis, and ARDS. Even though it was believed to have beneficial effects, corticosteroids can suppress T CD4+ and CD8+ cell-mediated immunity reaction through decreased IFNγ production thus leading to reactivation of latent Tuberculosis (LTBI). Therefore, the usage of corticosteroids in the ARDS phase of COVID-19 patients should be carefully given; pre-screening of LTBI may be done to avoid Tuberculosis reactivation.

The Use of Viral Vectors for Gene Therapy and Vaccination in Tuberculosis.

Tuberculosis (TB), an infection caused by Mycobacterium tuberculosis (Mtb), is one of the primary causes of death globally. The treatment of TB is long and based on several drugs, producing problems in compliance and toxicity, increasing Mtb resistance to first-line antibiotics that result in multidrug-resistant TB and extensively drug-resistant TB. Thus, the need for new anti-TB treatments has increased. Here, we review some model strategies to study gene therapy based on the administration of a recombinant adenovirus that encodes diverse cytokines, such as IFNγ, IL12, GM/CSF, OPN, TNFα, and antimicrobial peptides to enhance the protective immune response against Mtb. These models include a model of progressive pulmonary TB, a model of chronic infection similar to latent TB, and a murine model of pulmonary Mtb transmission to close contacts. We also review new vaccines that deliver Mtb antigens via particle- or virus-based vectors and trigger protective immune responses. The results obtained in this type of research suggest that this is an alternative therapy that has the potential to treat active TB as an adjuvant to conventional antibiotics and a promising preventive treatment for latent TB reactivation and Mtb transmission. Moreover, Ad vector vaccines are adequate for preventing infectious diseases, including TB.

A case of laryngeal tuberculosis mimicking supraglottic carcinoma in a pregnant patient and literature review

Tuberculosis (TB) is the most common granulomatous disease, but laryngeal involvement is rare. The risk of developing this clinical form is higher in immunocompromised patients due to primary infection or reactivation of latent TB. Laryngeal TB can be misdiagnosed as laryngeal cancer since they have similar macroscopic lesions, and both cause dysphonia. We present a case of laryngeal TB in a 37-week pregnant patient who complained of dysphonia, odynophagia, and dysphagia. A mass with supraglottic carcinoma findings was discovered during a laryngoscopic examination. The reason for presenting this case is to emphasize the necessity for a high degree of suspicion for laryngeal TB involvement in patients with upper respiratory tract lesions in regions with high TB prevalence, to achieve early diagnosis and treatment.

Addressing mechanism bias in model-based impact forecasts of new tuberculosis vaccines

In tuberculosis (TB) vaccine development, multiple factors hinder the design and interpretation of the clinical trials used to estimate vaccine efficacy. The complex transmission chain of TB includes multiple routes to disease, making it hard to link the vaccine efficacy observed in a trial to specific protective mechanisms. Here, we present a Bayesian framework to evaluate the compatibility of different vaccine descriptions with clinical trial outcomes, unlocking impact forecasting from vaccines whose specific mechanisms of action are unknown. Applying our method to the analysis of the M72/AS01E vaccine trial -conducted on IGRA+ individuals- as a case study, we found that most plausible models for this vaccine needed to include protection against, at least, two over the three possible routes to active TB classically considered in the literature: namely, primary TB, latent TB reactivation and TB upon re-infection. Gathering new data regarding the impact of TB vaccines in various epidemiological settings would be instrumental to improve our model estimates of the underlying mechanisms.

Disseminated tuberculosis in elderly-latent activation mimics metastasis: a case study

Tuberculosis (TB) is an infectious disease caused by mycobacterium species, that affects the lungs and involvement of the musculoskeletal system is not uncommon. Two or more systemic non-contiguous spread is termed as disseminated TB, and its additional involvement of lungs constitute the diagnosis of miliary TB (MTB). Immuno-suppressive conditions including malnutrition and immune-senescence in elderly can predispose to reactivation of latent TB and wide spread dissemination of the bacilli. Screening for dormant TB infection remains an impractical task and its diagnostic confirmation remains a challenge. With raising elderly population, there is a need for a high index of suspicion in the diagnosis of disseminated TB and its management, as delayed approach has increased mortality. Atypical presentation of disseminated TB with concomitant vertebral collapse and extensive lymphadenopathy needs exclusion of metastatic disease although the old nemesis of TB remains a differential diagnosis. We present one such case in a 71 years old lady to highlight the atypical presentation of disseminated TB. The disease presentation had spino-dermal pattern with lympho-reticular involvement including asymptomatic lesions bilaterally in the adrenal glands lesions.

P42 Are chest X-rays still necessary for prebiologic tuberculosis screening? A retrospective audit

Abstract Biologics are commonly used in autoimmune dermatological conditions as an option if other treatments are unsuccessful or contraindicated. However, one major side-effect of biologics is immunosuppression, which may lead to the reactivation of latent tuberculosis (TB) in patients. The British Association of Dermatology has implemented guidelines that require doctors to screen for TB before prescribing biologics to patients. The 2020 guidelines advise screening questions, performance of a chest X-ray (CXR) and an interferon-γ release assay (IGRA). Current studies show that CXR has a sensitivity of 15% when diagnosing latent TB. While there is no gold standard for diagnosing latent TB, the IGRA is a commonly used test and is shown to be four times more effective than the tuberculin skin test. This study questions the diagnostic value of CXR in the screening of TB in asymptomatic patients, and whether it should be removed from the guidelines for such patients. A retrospective audit of dermatological patients in our trust was done over a 24-month period (January 2020–January 2022). Patients selected for the audit were those diagnosed with psoriasis or hidradenitis suppurativa and started on biologics during this 24-month period. Patients were assessed on the following: patient history, CXR results, IGRA results and screening outcomes. The data were quantitatively analysed to uncover the necessity of performing a CXR on patients starting biologics. Between January 2020 and January 2022, 77 patients were scheduled for prebiologic TB screening; CXRs were performed in 74 patients (96%), while 72 (94%) of patients had IGRA tests. During this period, three patients (4%) were diagnosed with latent TB based on positive IGRA results and normal CXR findings. They were subsequently treated for latent TB infection prior to biologic therapy. None of the patients with negative IGRA results had positive CXR findings for TB. This finding suggests that CXR is unnecessary at the initial stage of prebiologic TB screening for asymptomatic patients. IGRA can detect both latent and active TB, while CXR is recommended for the diagnosis of active TB. Mandating CXR comes at a cost to the National Health Service and subjects patients to unnecessary radiation exposure. We propose that CXR be done only for patients who are either symptomatic for TB or have a positive IGRA result.

Biapenem, a Carbapenem Antibiotic, Elicits Mycobacteria Specific Immune Responses and Reduces the Recurrence of Tuberculosis.

Tuberculosis (TB) still tops the list of global health burdens even after COVID-19. However, it will sooner transcend the current pandemic due to the prevailing risk of reactivation of latent TB in immunocompromised individuals. The indiscriminate misuse and overuse of antibiotics have resulted in the emergence of deadly drug-resistant variants of Mycobacterium tuberculosis (M.tb). This study aims to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM) in generating long-lasting immunity against TB. BPM treatment significantly boosted the activation status of the innate immune arm-macrophages by augmenting p38 signaling. Macrophages further primed and activated the adaptive immune cells CD4+ and CD8+ T-cells in the lung and spleen of the infected mice model. Furthermore, BPM treatment significantly amplified the polarization of T lymphocytes toward inflammatory subsets, such as Th1 and Th17. The treatment also helped generate a long-lived central memory T-cell subset. The generation of central memory T lymphocyte subset upon BPM treatment in the murine model led to a significant curtailing in the recurrence of TB due to reactivation and reinfection. These results suggest the potentiality of BPM as a potent adjunct immunomodulator to improve host defense against M.tb by enriching long-term protective memory cells. IMPORTANCE Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) tops the list of infectious killers around the globe. The emergence of drug-resistant variants of M.tb has been a major hindrance toward realizing the "END TB" goal. Drug resistance has amplified the global burden toward the quest for novel drug molecules targeting M.tb. Host-directed therapy (HDT) offers a lucrative alternative to tackle emerging drug resistance and disease relapse by strengthening the host's immunity. Through our present study, we have tried to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM). BPM treatment significantly augmented long-lasting immunity against TB by boosting the innate and adaptive immune arms. The generation of long-lived central memory T lymphocyte subset significantly improved the disease outcome and provided sterilizing immunity in the murine model of TB. The present investigation's encouraging results have helped us depict BPM as a potent adjunct immunomodulator for treating TB.

Miliary Tuberculosis in a Patient With Ulcerative Colitis Treated With Tofacitinib

ABSTRACT Immunosuppression with tumor necrosis factor-alpha inhibitors and tofacitinib is a risk factor for reactivation of latent tuberculosis (TB) and the development of active TB. We report a case of miliary TB in a patient on treatment with tofacitinib for active ulcerative colitis. By week 4 of therapy, a clinical response was achieved. Subsequently, although being on treatment, the patient started having fever with night sweats and myalgias. The investigative workup revealed pulmonary miliary TB. Tofacitinib was withdrawn, and antitubercular therapy was initiated. The patient responded, both clinically and radiologically, to the antitubercular therapy. This case report highlights the importance of screening for latent TB in patients receiving tofacitinib.