Reactivation Of Latent Tuberculosis Research Articles

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.

JAK inhibitors in dermatology

The four Janus Kinase (JAK) proteins and seven signal transducer and activator of transcription (STAT) factors mediate the intracellular signaling pathway of cytokine receptors, which are described in the pathogenesis of many autoimmune, allergic, and inflammatory dermatoses. The development of targeted small-molecule therapies like JAK inhibitors has enabled a paradigm shift in the treatment of various cutaneous disorders. JAK inhibitors are effective in the treatment of atopic dermatitis, vitiligo, alopecia areata, psoriasis, lupus erythematosus, dermatomyositis, mastocytosis, etc. Various blood parameters include complete blood count, liver, and renal function, the viral marker to be checked and tuberculosis to be ruled out before starting the therapy. There is a risk of acquiring serious infections such as upper respiratory tract infections, urinary tract infections, reactivation of latent tuberculosis, opportunistic infections, hepatitis B virus reactivation, and alteration of various blood parameters; so regular monitoring is required. The use of JAK inhibitors will open a new horizon by reducing the burden of systemic steroids and other non-specific immunosuppressants in the treatment of immune-mediated inflammatory dermatoses.

Design of multi-epitope based vaccine against Mycobacterium tuberculosis: a subtractive proteomics and reverse vaccinology based immunoinformatics approach

Tuberculosis is an airborne transmissible disease caused by Mycobacterium tuberculosis that infects millions of lives worldwide. There is still no single comprehensive therapy or preventative available for the lethal illness. Currently, the available vaccine, BCG is ineffectual in preventing the prophylactic adult pulmonary TB and reactivation of latent tuberculosis. Therefore, this investigation was intended to design a new multi-epitope vaccine that can address the existing problems. The subtractive proteomics approach was implemented to prioritize essential, virulence, druggable, and antigenic proteins as suitable vaccine candidates. Furthermore, a reverse vaccinology-based immunoinformatics technique was employed to identify potential B-cell, helper T lymphocytes (HTL), and cytotoxic T lymphocytes (CTL) epitopes from the target proteins. Immune-stimulating adjuvant, linkers, and PADRE (Pan HLA-DR epitopes) amino acid sequences along with the selected epitopes were used to construct a chimeric multi-epitope vaccine. The molecular docking and normal mode analysis (NMA) were carried out to evaluate the binding mode of the designed vaccine with different immunogenic receptors (MHC-I, MHC-II, and Tlr4). In addition, the MD simulation, followed by essential dynamics study and MMPBSA analysis, was carried out to understand the dynamics and stability of the complexes. In-silico cloning was accomplished using E.coli as an expression system to express the designed vaccine successfully. Finally, the immune simulation study has foreseen that our designed vaccine could induce a significant immune response by elevation of different immunoglobulins in the host. However, there is an imperative need for the experimental validation of the designed vaccine in animal models to confer effectiveness and safety.HIGHLIGHTSMulti-epitope based vaccine was designed against Mycobacterium tuberculosis using subtractive proteomics and Immunoinformatics approach.The vaccine was found to be antigenic, non-allergenic, immunogenic, and stable based on in-silico prediction.Population coverage analysis of the proposed vaccine predicts an effective response in the world population.The molecular docking, MD simulation, and MM-PBSA study confirm the stable interaction of the vaccine with immunogenic receptors.In silico cloning and immune simulation of the vaccine demonstrated its successful expression in E.coli and induction of immune response in the host. Communicated by Ramaswamy H. Sarma

Clinical characteristics, course and outcome of critically ill COVID-19 patients with previous or current TB admitted in ICU of a tertiary care COVID centre of Indian subcontinent.

Clinical characteristics, course and outcome of critically ill COVID-19 patients with previous or current TB admitted in ICU of a tertiary care COVID centre of Indian subcontinent.

1426. Characterization of Patients with Iatrogenic Mycobacterial Infections: A Hospital-Based Survey

Abstract Background Tuberculosis (TB) is a chronic granulomatous inflammation usually involving the lung parenchyma and hilar lymph nodes. Extra-pulmonary involvement is seen in ∼20% of all TB cases. Developing tuberculosis following treatment for another primary medical condition is a rare occurrence. Iatrogenic literally means illness caused by medical examination or treatment. Mycobacteria have been used to treat a few medical conditions and the therapeutic use has been validated extensively in literature. The mycobacteria used for therapeutic purposes are supposed to be either attenuated or non pathogenic strains. Growth and dissemination of this mycobacterium is a rare but serious possibility. Reactivation of latent mycobacterial infection following therapy is also a part of iatrogenic mycobacterial infection. Methods We report a retrospective study investigating adverse events manifesting with development of iatrogenic tuberculosis. The data was obtained from a tertiary care centre over a period of 2 years. Diagnosis of tuberculosis was established based on clinical, radiological(chest X-Ray and High resolution CT scan), sputum smear microscopy and skin/tissue biopsy and Xpert MTB/RIF. Tuberculin skin test(TST) and Interferon gamma release assay (IGRA) were used as additional diagnostic tests. Results The search yielded 26 cases of iatrogenic tuberculosis, with a median age of 56.5 years. Most common cause was reactivation of latent tuberculosis due to use of anti-TNF alpha biologic agents(53.8%). Development of Tuberculosis verrucosa cutis following BCG inoculation for verruca vulgaris was noted in about 19.2% of cases and Tubercular abscess due to Mycobacterium w or BCG inoculation for Covid-19 was noted in 11.5% cases. Bacillus Calmette Guérin(BCG) induced balanitis secondary to therapy for Carcinoma urinary bladder was noted in 7.69%of cases. Bacillus Calmette-Guerin or BCG induced balanitis following use of intravesical immunotherapy for treating early-stage urinary bladder cancer and successful clearance of lesions post therapy Tuberculosis Verrucosa Cutis following Immunotherapy for plantar warts Conclusion All patients were managed successfully with anti tubercular therapy. These observations indicate that tuberculosis infection can develop in previously healthy individuals in endemic zones following biologic therapy of use of mycobacterial agents for other therapeutic indications. Disclosures All Authors: No reported disclosures.

Evaluation of Mycobacterium tuberculosis specific antigen-stimulated CD27−CD38+IFN-γ+CD4+ T cells for discrimination of active tuberculosis

BackgroundActive tuberculosis (ATB) originates from primary Mycobacterium tuberculosis (MTB) infection or reactivation of latent tuberculosis. Besides bacteriological examination, MTB-reactive immunocytes detection can be an alternative testing for discrimination of active tuberculosis. The purpose of this study is to investigate the accuracy of peripheral blood CD27−CD38+IFN-γ+CD4+T cells in ATB diagnosis.MethodsThis prospective diagnostic accuracy study was conducted at Shanghai Pulmonary Hospital between January 2019 and December 2021. Patients with ATB, non-tuberculosis mycobacterium infection (NTM), latent tuberculosis infection (LTBI), other respiratory diseases (OD), and healthy individuals (HC) were enrolled. The accuracy of CD27−CD38+IFN-γ+CD4+/CD4+ and other phenotypic markers for ATB diagnosis was assessed.ResultsA total of 376 patients (237 ATB, 38 LTBI, 8 NTM, 50 OD, and 43 HC) were enrolled. The ratios of CD4+IFN-γ+CD27− and CD4+IFN-γ+CD27−CD38+ profiles in CD4+IFN−γ+ cells and the ratios of CD4+IFN-γ+CD38+, CD4+IFN-γ+CD27−, and CD4+IFN-γ+CD38+CD27− profiles in CD4+ cells in the ATB group were significantly higher than in the other groups. The area under the curve (AUC) of CD27−CD38+IFN-γ+CD4+/CD4+ for the diagnosis of ATB was the highest, with a value of 0.890. With the optimal cutoff value of 1.34 × 10–4, the sensitivity and specificity of CD27−CD38+IFN-γ+CD4+/CD4+ for ATB diagnosis was 0.869 and 0.849, respectively.ConclusionCD27−CD38+IFN-γ+CD4+/CD4+ might be a potential biomarker for active tuberculosis diagnosis.