From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning

Latent tuberculosis infection(LTBI)has become a major source of active tuberculosis(ATB).Although the tuberculin skin test and interferon-gamma release assay can be used to diagnose LTBI,these methods can only differentiate infected individuals from healthy ones but cannot discriminate between LTBI and ATB.Thus,the diagnosis of LTBI faces many challenges,such as the lack of effective biomarkers from Mycobacterium tuberculosis(MTB)for distinguishing LTBI,the low diagnostic efficacy of biomarkers derived from the human host,and the absence of a gold standard to differentiate between LTBI and ATB.Sputum culture,as the gold standard for diagnosing tuberculosis,is time-consuming and cannot distinguish between ATB and LTBI.In this article,we review the pathogenesis of MTB and the immune mechanisms of the host in LTBI,including the innate and adaptive immune responses,multiple immune evasion mechanisms of MTB,and epigenetic regulation.Based on this knowledge,we summarize the current status and challenges in diagnosing LTBI and present the application of machine learning(ML)in LTBI diagnosis,as well as the advantages and limitations of ML in this context.Finally,we discuss the future development directions of ML applied to LTBI diagnosis.

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

Primary extrapulmonary tuberculosis diagnosis warrants extraprecautious pulmonary tuberculosis exclusion workup

This editorial article takes an opportunity to apprehend the diagnostic challenges of primary gastrointestinal tuberculosis(an uncommon extrapulmonary tuberculosis condition)utilizing the recently published case report of a young male with prolonged gastrointestinal symptoms and weight loss who received intermittent anti-tubercular treatment and underwent operative interventions to relieve gastric outlet obstruction.The diagnosis chiefly relied on high-end examinations,like computed tomography scans and histopathological evaluation of postoperatively resected bowel tissue,which wasn't preceded by an all-inclusive stepwise primary pulmonary tuberculosis exclusion approach that usually begins with a detailed tuberculosis-pertinent history acquisition.Given the geographic locations where the patient had been(and/or treated),pivotal consideration of tuberculosis-associated endemicities in those regions,like human immunodeficiency virus(HIV)infection,might have improved the case description.The obtainment of HIV-relevant histories,like intravenous drug use and sexual practice,are good places to start.The sputum bacteriology also seems imperative to rule out atypical Mycobacterium species infection because of its clinico-radiohistopathological resemblance with pulmonary Mycobacterium tuberculosis.Altogether,this editorial aims to underscore that primary extrapulmonary tuberculosis diagnosis should comprise an elaborative,comprehensive,systematic,and stepwise primary pulmonary Mycobacterium tuberculosis exclusion workup.

Differential diagnosis of Crohn’s disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning

BACKGROUND Crohn’s disease(CD)is often misdiagnosed as intestinal tuberculosis(ITB).However,the treatment and prognosis of these two diseases are dramatically different.Therefore,it is important to develop a method to identify CD and ITB with high accuracy,specificity,and speed.AIM To develop a method to identify CD and ITB with high accuracy,specificity,and speed.METHODS A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB.Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis.RESULTS The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm^(-1) and 1234 cm^(-1) bands,and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy,specificity,and sensitivity of 91.84%,92.59%,and 90.90%,respectively,for the differential diagnosis of CD and ITB.CONCLUSION Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level,and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.

Diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients:A mini review for clinicians

Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.

Prevalence of Latent Tuberculosis Infection [LTBI] in Prison Officers: A Systematic Review and Meta-Analysis

This study aimed to perform a systematic review and meta-analysis to determine the LTBI prevalence in prison officers worldwide. A systematic search was performed in PubMed, WoS, Embase, and BVS, including all articles related to LTBI prevalence and risk factors. After critical evaluation and qualitative synthesis of the identified articles, a meta-analysis was used. Five studies carried out between 2012 and 2022 were included, with a total sample size of 1718 prison officers. The overall LTBI prevalence was 50% [95% confidence interval [CI]: 48% - 52%;n = 816], with high heterogeneity between studies. Smoking [OR = 1.76;CI 95% = 1.26 - 2.46] and males [OR = 2.08;CI 95% = 1.31 - 3.31] were positively related to a higher LTBI prevalence among prison officers. Thus, preventive measures and the rapid and accurate diagnosis of new cases should be emphasized to ensure tuberculosis control, especially among risk groups such as prison officers.

Comparison between Quanti-FERON-TB Gold In-Tube test and tuberculin skin test for diagnosis of latent tuberculosis in children: A cross-section study

Objective: To compare Quanti-FERON-TB Gold In-Tube (QFT-GIT) test and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in children. Methods: In this cross-sectional study, 64 participants who were between 3 months and 14 years old and had close contact with smear-positive pulmonary tuberculosis were included. Both QFT-GIT test and TST were done and the results were analyzed by SPSS software and Kappa test. Results: The distribution of gender and age according to QFT-GIT and TST results were matched (P>0.05). Overall agreement between QFT-GIT and TST for diagnosis of latent tuberculosis infection in children was 75%. In addition, the contingency coefficient was 0.257, and the Kappa measure of agreement was 0.246 (P=0.034). Conclusions: Compared to TST, QFT-GIT shows no apparent advantage for diagnosis of latent tuberculosis infection in children.

Recent Progress in Diagnosis Methods for Latent Tuberculosis Infection and Its Clinical Applications

Most people with latent Mycobacterium tuberculosis infection can partly develop active tuberculosis (TB). Therefore, diagnosis of this condition bears significance in early TB prevention. To date, the main methods for diagnosis of latent TB infection (LTBI) include tuberculin skin test and interferon γ release test. These two methods feature their own advantages and disadvantages. Although new diagnostic markers continually emerge, no uniform diagnostic criteria are available for TB detection. This study summarizes several methods for diagnosis of LTBI and new related markers and their application value in clinical practice.

Profile of Extra-Pulmonary Tuberculosis in Internal Medicine

Introduction: Tuberculosis is an infectious disease that mainly affects the lung. Extrapulmonary localizations are a reason for hospitalization in our health facilities. The objective of this study was to describe the epidemiological, clinical, paraclinical and evolutionary aspects of extra pulmonary tuberculosis (EPT) at the Abass Ndao Hospital Center. Patients and Methods: This was a descriptive cross-sectional study conducted over a period of 11 years (January 1, 2010 to December 30, 2021). All patients with extrapulmonary tuberculosis hospitalized in the department of internal medicine during the recruitment period were included. Results: Fifty-two (52) patients were collected. The year 2019 recorded the most cases 23.08% (n = 20). The mean age of the patients was 40.56 ± 18.24 years. The age group 20 - 34 years 42.31% (n = 22) was the most represented. Females were in the majority 61.54% (n = 32) with a sex ratio (M/F) was 0.63. Housewives were in the majority 40.38% (n = 21). 60.87% of the cases (n = 14) came from a health facility. 38.46% of the cases had been infected. 21.74% (n = 9) were smokers. The reasons for consultation were dominated by fever (67.44%), AEG (62.79%) and cough (41.86%). Eighteen patients (40.91%) had fever. The mean time to consultation was 77.37 ± 90.3 days with extremes of 3 and 365 days. The median was 45 days. More than half of the patients 61.90% (n = 26) had anemia. Positive retroviral serology was noted in 21.43% of cases. All patients had a CRP greater than 6. More than half of the patients 51.92% (n = 27) had multifocal tuberculosis. The peritoneum 44.23% (n = 23) was the main organ affected. The average hospital stay was 9.8 ± 4.9 days with extremes of 1 and 19 days. All patients had received the protocol in force at the national level. Death was noted in 4 patients (9.52%). Conclusion: EPT is characterized in our context by a notorious diagnostic difficulty due to the multiplicity of clinical presentations, the complexity of explorations, and the problems of differential diagnosis notably with other granulomatosis, systemic lupus and cancers. This difficulty is reflected in the low rate of diagnosis with a paraclinical argument of certainty and in the long diagnostic delays.

Unveiling the Threat: Case Reports of Extra-Pulmonary Tuberculosis among Sanctuary Chimpanzees

Primate sanctuaries across Africa play a pivotal role in the rescue and rehabilitation of confiscated and rescued wild primates, many of whom have had extensive contact with humans prior to their arrival and throughout the rehabilitation process, heightening the risk of disease transmission. While tuberculosis is not naturally occurring in free-living chimpanzees, it has been extensively observed in captive primates that have been in close proximity to humans or other captive primates infected with Mycobacterium tuberculosis. This case report delves into an outbreak of extra-pulmonary tuberculosis among juvenile chimpanzees within a sanctuary, detailing the associated diagnostic challenges and treatment approaches. The five cases had close contact with a caregiver infected with tuberculosis, subsequently transmitting the infection to other in-contact chimpanzees. Prolonged treatment, employing the human protocol of quadri-therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol), followed by bi-therapy (rifampicin and isoniazid), resulted in complete resolution for all five cases. These cases underscore the critical importance of maintaining high levels of biosecurity, implementing effective quarantine measures, and adhering to strict hygiene practices when working with non-human primates.

Gastrointestinal tuberculosis:Diagnostic approaches for this uncommon pathology

A case report entitled“Primary gastroduodenal tuberculosis presenting as gastric outlet obstruction”recently published in the World Journal of Clinical Cases presented a rare cause of gastric outlet obstruction and highlighted the atypical manner in which gastrointestinal tuberculosis(TB)can present.The literature with regards to this rare pathology is limited to case reports and case series with the largest being published using data from between 2003 and 2013.However,since then the diagnostic tools available have significantly changed with more modern and increasingly accurate tests now available.This editorial reviews the current state of the art with regards to diagnosis in gastrointestinal TB.

Clinical Evaluation of Two Interferon-Gamma Release Assays for Diagnostic Tests of Tuberculosis Infection in a Tertiary Hospital: Clinical Evaluation of Two IGRAs for TB Infection

Background: The aim of this study was to evaluate the usefulness of two interferon-gamma release assays (IGRAs) (QuantiFERON-TB Plus (QFT-plus) and T-SPOT.TB assay) for patients suspected of having tuberculosis (TB) infection as supportive methods for diagnosing TB. Patients and Methods: The subjects consisted of 45 patients who required clinical differentiation of TB disease from June 2019 to August 2023. The final clinical diagnoses were: 14 patients with active TB disease, 4 with latent TB infection (LTBI), 17 with old (cured) TB disease, and 10 with pulmonary nontuberculous mycobacterial (NTM) disease. We used the two IGRAs for these patients and evaluated the data according to the manufacturer’s guidelines for interpretation or FDA-approved cutoffs. Results: Among the total of 14 patients with active TB disease (mean age: 64 years old, male: 9, and female: 5), a positive response was noted in 10 patients (71%) on QFT-plus and 9 (64%) on T-SPOT.TB. Four patients with a negative response on QFT-plus and T-SPOT.TB were elderly or cancer patients with lymphocytopenia or hypoalbuminemia. All four patients with LTBI showed a positive response (100%) on both QFT-plus and T-SPOT.TB. Among the seventeen patients with old (cured) TB disease, a positive response was noted in 8 patients (47%) on QFT-plus and 9 (53%) on T-SPOT.TB. All patients with pulmonary NTM disease showed a negative response on both QFT-plus and T-SPOT.TB. Conclusions: A false-negative response on QFT-plus as well as T-SPOT.TB was recognized in elderly patients and patients with an immunosuppressed condition, and half of patients with old (cured) TB showed no negative conversion after the completion of treatment through this study. Although it was recently reported that the positive response rate on QFT-plus of patients with active TB disease was high, we consider it necessary to be careful in diagnosing TB infection using IGRAs for patients with severe underlying diseases in a tertiary hospital based on the results.

Tuberculosis in kidney transplant candidates and recipients

Tuberculosis(TB)is the leading cause of infectious mortality and morbidity in the world,second only to coronavirus disease 2019.Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population.Active TB is difficult to diagnose in this population due to close mimics.All transplant candidates should be screened for latent TB infection and given TB prophylaxis.Patients who develop active TB pre-or post-trans-plantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.

Comprehensive review on the diagnostic strategies for esophageal tuberculosis:the role of endoscopic ultrasonography

Esophageal tuberculosis(ET)is a relatively rare clinical condition,characterized by often atypical clinical features.The lack of specificity in diagnostic methods,such as esophagogastroduodenoscopy and various imaging techniques,frequently leads to misdiagnosis and inappropriate treatments.Compared to esophagogastroduodenoscopy,endoscopic ultrasonography(EUS)offers a more comprehensive examination of esophageal tuberculosis lesions,including the extent of wall layer involvement and the internal structure characteristics of the lesions.Furthermore,when necessary,endoscopic ultrasonography-guided fine-needle aspiration can be employed to acquire deeper pathological tissue,significantly aiding diagnosis.When combined with the patient’s clinical presentation,endoscopic findings,and pathological features,EUS plays a crucial role in the definitive diagnosis of ET and in the differential diagnosis process.This article meticulously reviews both national and international literature to summarize the relevant features of ET,with a focus on its appearance under EUS,and to highlight the clinical value of EUS in enhancing the diagnosis of ET and in distinguishing it from other conditions.The aim is to offer guidance for the accurate diagnosis of ET.

Investigation of the Clinical Diagnostic Significance of the T-Cell Test for Tuberculosis combined with Erythrocyte Sedimentation Test in Pulmonary Tuberculosis

Objective:To investigate the clinical diagnostic significance of peripheral blood T-cell test(T-spot test)for tuberculosis(TB)infection combined with erythrocyte sedimentation rate(ESR)in pulmonary TB.Methods:41 patients with a clinical diagnosis of TB during hospitalization from January 2020 to April 2023 in our hospital were selected as the experimental group,and 45 patients without TB(bronchopneumonia patients)were selected as the control group.The diagnostic specificity,sensitivity,and accuracy of the T-spot TB test,ESR test,and the combined test of the two were calculated respectively.Results:The sensitivity,specificity,and accuracy of the T-spot TB test combined with ESR for the diagnosis of TB in the experimental group were significantly higher than the individual results of the T-spot TB test and ESR test alone(P<0.05).Conclusion:The T-spot TB test combined with the ESR test for TB diagnosis has greater clinical value than carrying out the tests individually.

Latent tuberculosis infection in health-care workers in the government sector in Brunei Darussalam:A cross-sectional study

Objective:Health-care workers(HCWs)are known to be at high risk for occupational biological hazards,and this includes exposure to mycobacterium tuberculosis(TB)which can result in either active or latent TB infection(LTBI).This study aims to provide an overview of the incidence of LTBI among HCWs in Brunei Darussalam,to examine associated risk factors,and to evaluate LTBI treatment compliance.Materials and Methods:This is a retrospective cross-sectional study which was conducted using data from January 2018 to December 2021,on notified cases of LTBI in HCWs which identified 115 cases.Demographic data,underlying medical conditions,and compliance to treatment were assessed through reviews of their electronic health records.Results:The incidence of LBTI was 14.6/year/1000 HCWs.The incidence rate reached a high of 24.6/1000 in 2020,and majority of cases were in the older age groups.There was good treatment acceptance and compliance(82.6%),and this was observed to be significantly higher in females than males(P=0.02).Conclusion:This study showed an average incidence of LTBI of 14.6/1000 HCWs over 4 years and high LTBI treatment acceptance(82.6%)and compliance.Emphasis on infection prevention and control measures in health-care settings and actions to increase awareness of LTBI are crucial interventions toward reducing the burden of LTBI.

Chronic Spontaneous Urticaria on Omalizumab Therapy and Latent Tuberculosis Infection: A New Case Report

Background: Chronic Spontaneous urticarial (CSU) is a common dermatological problem characterized by recurrent pruritic or burning wheals last less than 24 hours and treated by many modalities of therapy including systemic antihistamines and in refractory cases with Omalizumab anti-IgE antibody biological injection. Latent tuberculosis infection (LTBI) is diagnosed based on a positive tuberculin skin test or QuantiFERON-TB test without evidence of active tuberculosis. Aim: To document a new case report of a patient with a history of CSU and latent tuberculosis on Omalizumab therapy during Isoniazid (INH) prophylaxis. Case Report: A-53-year-old woman with a history of CSU and newly identified LTBI who have been treated with INH monotherapy before starting Omalizumab injection followed up over 24 weeks course of therapy for any sign of tuberculosis reinfection. Conclusion: Omalizumab injection was used effectively for the treatment of CSU in a patient with latent tuberculosis infection with minimal risk of tuberculosis reactivation.

Effect of Individualized Nursing Intervention on Patients with Tuberculosis Latent Infection and Active Tuberculosis

Objective:This paper aims to explore the effect of individualized nursing intervention on patients with active tuberculosis(ATB)and latent tuberculosis infection(LTBI).Methods:The nursing study started in January 2020 and ended in January 2023.A total of 60 patients with ATB and LTBI were included,and they were divided into two groups according to the intervention schemes selected for control testing,each with 30 cases.The intervention program selected for group A was routine care,and for group B was individualized nursing.The proportion of adverse reactions,changes in the level of lung items,self-management outcomes and satisfaction were evaluated and compared.Results:After evaluating the proportion of adverse reactions,the total proportion of ATB and LTBI in group B was lower than that in group A(P<0.05).Based on the evaluation and testing of the expiratory flow(EF),expiratory volume(EV),and vital capacity(VC)after the intervention,these levels in group B showed higher outcomes than those in group A(P<0.05).The scores in terms of living habits,sleep,diet,and compliance in group B were higher than those in group A(P<0.05).The total proportion of the satisfaction of ATB and LTBI patients in group B was higher than that in group A(P<0.05).Conclusion:After the intervention of individualized nursing measures in patients with ATB and LTBI,it was found that it can not only play a positive role in the prevention and control of adverse reactions,but also improve their lung function,and promote their self-management,with good satisfaction level,thus it has high research and clinical application values.

Routine diagnosis of intestinal tuberculosis and Crohn's disease in Southern India

AIM:To investigate whether routinely measured clinical variables could aid in differentiating intestinal tuberculosis(ITB)from Crohn’s disease(CD).METHODS:ITB and CD patients were prospectively included at four South Indian medical centres from October 2009 to July 2012.Routine investigations included case history,physical examination,blood biochemistry,ileocolonoscopy and histopathological examination of biopsies.Patients were followed-up after 2 and 6 mo of treatment.The diagnosis of ITB or CD was re-evaluated after 2 mo of antituberculous chemotherapy or immune suppressive therapy respectively,based on improvement in signs,symptoms and laboratory variables.This study was considered to be an exploratory analysis.Clinical,endoscopic and histopathological features recorded at the time of inclusion were subject to univariate analyses.Disease variables with sufficient number of recordings and P<0.05 were entered into logistic regression models,adjusted for known confounders.Finally,we calculated the odds ratios with respective confidence intervals for variables associated with either ITB or CD.RESULTS:This study included 38 ITB and 37 CD patients.Overall,ITB patients had the lowest body mass index(19.6 vs 22.7,P=0.01)and more commonly reported weight loss(73%vs 38%,P<0.01),watery diarrhoea(64%vs 33%,P=0.01)and rural domicile(58%vs 35%,P<0.05).Endoscopy typically showed mucosal nodularity(17/31 vs 2/37,P<0.01)and histopathology more frequently showed granulomas(10/30vs 2/35,P<0.01).The CD patients more frequently reported malaise(87%vs 64%,P=0.03),nausea(84%vs 56%,P=0.01),pain in the right lower abdominal quadrant on examination(90%vs 54%,P<0.01)and urban domicile(65%vs 42%,P<0.05).In CD,endoscopy typically showed involvement of multiple intestinal segments(27/37 vs 9/31,P<0.01).Using logistic regression analysis we found weight loss and nodularity of the mucosa were independently associated with ITB,with adjusted odds ratios of 8.6(95%CI:2.1-35.6)and 18.9(95%CI:3.5-102.8)respectively.Right lower abdominal quadrant pain on examination and involvement of≥3 intestinal segments were independently associated with CD with adjusted odds ratios of 10.1(95%CI:2.0-51.3)and 5.9(95%CI:1.7-20.6),respectively.CONCLUSION:Weight loss and mucosal nodularity were associated with ITB.Abdominal pain and excessive intestinal involvement were associated with CD.ITB and CD were equally common.