Previous Tuberculosis Infection Research Articles

Clinical and socio-economic characteristics of a cohort of MDR/XDR TB patients in Bucharest, Romania

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) patients are likely to suffer from TB-related morbidity, social and economic consequences during and beyond anti-TB treatment. The aim of this study is to describe clinical and socio-economic outcomes of TB patients in Bucharest, Romania. Methods We have established a prospective cohort of patients with MDR/XDR TB followed for more than 2 years from TB diagnosis. We have collected TB-related, laboratory and clinical data, including chest X-ray, lung function measured by spirometry, St. George's Respiratory Questionnaire (SGRQ), and socio-economic information. Results From 50 enrolled participants, 31 remained in the study till month 6. 71% were male with mean age 46.7 (SD 15.4). 41.9% had a previous TB infection and median BMI of 20.3 kg/m2. Baseline CXR showed that on average 47.3% of the lung was affected, with 32.7% at month 6. The majority (71%) of participants had lung impairment at baseline, which remained stable till month 6. The total SGRQ score improved between baseline and month 6 (30 vs 22.8), but remained significantly worse compared to healthy individuals. 52% of participants stated that TB affected their social or private life as well as their household financially at treatment start. Conclusions From the start of anti-TB treatment patients are suffering from lung impairment and experiencing socio-economic impact of TB. This cohort demonstrates a slow and slight longitudinal improvement of these outcomes and brings awareness to the need of employing social and rehabilitation programs to target TB impact. Key messages • MDR/XDR TB patients suffer from a significant morbidity and socio-economic burden in Romania. • Targeted measures are needed to address this burden during and after TB treatment.

Non-Mycobacteria Tuberculosis in Africa: A Literature Review.

Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa. A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review. In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection. In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.

1234 Enlarging Pericardial Cyst Compressing the Right Ventricle

Abstract 52-year-old Indian builder initially presented to his General Practitioner with exertional breathlessness but no angina. His medical history included previous tuberculosis infection, Type 2 Diabetes Mellitus and hypothyroidism. He was referred to the cardiologist to exclude coronary artery disease. Stress testing found T-wave inversion in the inferior electrocardiogram leads and transthoracic echocardiogram showed reduced right ventricular (RV) function with basal wall hypokinesia. Cardiac Magnetic Resonance Imaging (MRI) revealed a 5cm x 2.5cm pericardial cyst (Figure 1a). As imaging suggested minimal RV compression and no venous obstruction, the patient was investigated for other causes of breathlessness. Repeat computed tomography (CT) two years later demonstrated enlargement of the cyst (6cm x 3.6cm) with contrast reflux into the inferior vena cava (IVC) (Figure 1b). Due to worsening breathlessness, surgical excision was offered. Surgery was attempted through a lower hemi-sternotomy. However, due to limited access to the cyst and thickened pericardium, median sternotomy was performed. The cyst measured 10cm x 7cm and was heavily adherent to the RV wall, right atrium and IVC preventing complete excision. The cyst was therefore unroofed, releasing cheese-like material suspicious of a tuberculous cyst (Figure 2). Adhesiolysis was undertaken to remove remaining cyst wall. Prior to closure, inflamed pericardial tissue was excised. Histopathology revealed a chronically inflamed pseudocyst with necrotising and non-necrotising granulomatous inflammation. Ziehl-Neelsen, Grocott, Gram and periodic acid-Schiff-diastase stains were negative. Intraoperative and histological findings and history of tuberculosis suggested a diagnosis of tuberculous pericardial cyst. The patient recovered uneventfully with significant symptomatic improvement at 2-month follow-up.

Increased Lung Cancer Risk and Associated Risk Factors in Tuberculosis Survivors: A Korean Population-Based Study.

Few studies have comprehensively evaluated the risk of lung cancer in tuberculosis survivors with consideration of smoking status and chronic obstructive pulmonary disease (COPD). Furthermore, little is known about lung cancer risk factors in tuberculosis survivors. This population-based cohort study enrolled tuberculosis survivors (n = 75 467) between 2010 and 2017 and 1:1 age- and sex-matched controls. Subjects were followed up for 1 year from the date of tuberculosis diagnosis to the date of the incident lung cancer, death, or December 2018, whichever came first. The risk of lung cancer was evaluated according to smoking and COPD status. We also evaluated the risk factors for lung cancer and developed an individualized lung cancer prediction model for tuberculosis survivors. During a median follow-up duration of 4.8 years, the incident lung cancer risk was 1.72-fold higher in tuberculosis survivors than in the controls. Among tuberculosis survivors, those who were current smokers with ≥20 pack-years showed the highest risk of lung cancer (adjusted hazard ratio, 6.78) compared with never-smoker, non-tuberculosis-infected controls. tuberculosis survivors with COPD had a higher risk (2.43) than non-COPD, non-tuberculosis-infected controls. Risk factors for lung cancer in tuberculosis survivors were pulmonary tuberculosis, age >60 years, smoking, and the presence of COPD or asthma. The individualized lung cancer risk model showed good discrimination (concordance statistic = 0.827). Previous tuberculosis infection is an independent risk factor regardless of smoking status or amount and COPD. Closer monitoring of tuberculosis survivors, especially heavy smokers or those with COPD, is needed for early lung cancer diagnosis.

Previous tuberculosis infection associated with increased frequency of asthma and respiratory symptoms in a Nordic-Baltic multicentre population study.

Tuberculosis (TB) infection induces profound local and systemic, immunological and inflammatory changes that could influence the development of other respiratory diseases; however, the association between TB and asthma is only partly understood. Our objective was to study the association of TB with asthma and respiratory symptoms in a Nordic-Baltic population-based study. We included data from the Respiratory Health in Northern Europe (RHINE) study, in which information on general characteristics, TB infection, asthma and asthma-like symptoms were collected using standardised postal questionnaires. Asthma was defined based on asthma medication usage and/or asthma attacks 12 months prior to the study, and/or by a report of ≥three out of five respiratory symptoms in the last 12 months. Allergic/nonallergic asthma were defined as asthma with/without nasal allergy. The associations of TB with asthma outcomes were analysed using logistic regressions with adjustments for age, sex, smoking, body mass index and parental education. We included 8379 study participants aged 50-75 years, 61 of whom reported having had TB. In adjusted analyses, participants with a history of TB had higher odds of asthma (OR 1.99, 95% CI 1.13-3.47). The associations were consistent for nonallergic asthma (OR 2.17, 95% CI 1.16-4.07), but not for allergic asthma (OR 1.20, 95% CI 0.53-2.71). We found that in a large Northern European population-based cohort, persons with a history of TB infection more frequently had asthma and asthma symptoms. We speculate that this may reflect long-term effects of TB, including direct damage to the airways and lungs, as well as inflammatory responses.

Abstract 3012: Increased lung cancer risk and associated risk factors in tuberculosis survivors: a Korean population-based study

Abstract Background: Although studies have suggested an association between previous tuberculosis (TB) infection and increased lung cancer risk, there are limited data comprehensively evaluating the effects of smoking and chronic obstructive pulmonary disease (COPD) on the association. Methods: This population-based cohort study enrolled TB survivors (n=75,467) ≥20 years of age between 2010-2017 and 1:1 age- and sex-matched controls (n=75,467). Subjects were followed for one year after the date of TB diagnosis to the date of the incidental lung cancer, death, or December 2018. Results: During a median follow-up duration of 4.8 (interquartile range, 2.9-6.6) years, the incident lung cancer risk was 1.71-fold (95% confidence interval [CI], 1.49-1.97) higher in TB survivors than in the controls. Compared to never-smoker, non-TB infected controls, TB survivors who were current smokers with ≥20 pack-years showed the highest risk of lung cancer (adjusted hazard ratio [aHR], 6.78; 95% CI, 5.26-8.74). In terms of COPD, the risk of lung cancer was higher in TB survivors with COPD compared to non-COPD, non-TB-infected controls (aHR, 2.43; 95% CI, 2.03-2.91). However, smoking as well as COPD did not have significant interaction on the association between TB and lung cancer development (p for interaction>0.05 for both). Risk factors related to incident lung cancer among TB survivors were pulmonary TB, age >60 years, smoking, and the presence of COPD or asthma. Conclusions: Previous TB infection is an independent risk factor for lung cancer without significant interaction with smoking status or amount and COPD. Citation Format: Dong Won Park, Seong Mi Moon, Hayoung Choi, Sang Hyuk Kim, Hyung Koo Kang, Jin Hyung Jung, Kyungdo Han, Dong Wook Shin, Hyun Lee. Increased lung cancer risk and associated risk factors in tuberculosis survivors: a Korean population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3012.

Transverse myelitis after Johnson & Johnson COVID-19 vaccine: illustrative case

Transverse myelitis is a rare neurological occurrence with varied presentation. Imaging is necessary to properly diagnose this condition; however, identifying the cause of this condition may often be difficult. An otherwise healthy patient presented to the clinic with peculiar neurological symptoms without an obvious underlying cause. Imaging evidenced no significant structural defects but did lead to discovery of cord enhancement compatible with a diagnosis of transverse myelitis. Corticosteroid treatment was initiated rapidly to address this pathology, and the patient recovered without deficits. To identify the underlying cause, patient medical history was reviewed thoroughly and compared with existing literature. Previous tuberculosis infection could be a less likely cause of the neurological symptoms. However, recent vaccination with the Johnson & Johnson coronavirus disease 2019 (COVID-19) vaccine could be a more likely cause of the transverse myelitis, which has been rarely reported. Transverse myelitis after COVID-19 infection has been an escalating phenomenon. However, transverse myelitis after COVID-19 vaccination is a rare occurrence that is also on the rise. Given the increased rates of vaccination, transverse myelitis should not be overlooked as a potential pathology, due to the severity of neurological impairment if this condition is not treated rapidly.

The Prevalence of Mycobacterium tuberculosis Infection Among Cancer Patients Receiving Chemotherapy in a Tertiary Care Center.

To estimate the prevalence of tuberculosis (TB) infection among patients receiving cancer chemotherapy and to identify risk factors for latent TB reactivation. A cross-sectional study was conducted at a tertiary care center in Jeddah, Saudi Arabia. Patients were surveyed for TB risk factors, their records were reviewed for previous TB infection or disease, and blood samples were collected for interferon-gamma release assays (IGRAs). A total of 203 patients were included. One hundred and twenty-five were females (62%). Median age was 52 years, and mean age was significantly higher in positive IGRA patients compared to negative IGRA (57.32 vs. 47.27; p = 0.009). Twenty-five patients (12.3%) had evidence of TB infection, 16 (68%) among them had a latent TB infection, while the rest received treatment for an active TB disease. The rate of active disease among cancer patients was 8 (3.9%). Additionally, 92% (23) of those with positive IGRA had solid cancers (p = 0.007), and all active TB cases occurred in this group of solid cancers. TB prevalence was higher in chemotherapy patients compared to the general Saudi population. Patients with solid tumors and older age had a greater risk of developing the infection, signifying the importance of preventing TB and malignancy coexistence by initiating screening policies in cancer patients.

Fatal Pneumonia Caused by Omicron Subvariant BA.2 of Severe Acute Respiratory Syndrome Coronavirus 2 with the Pulmonary Tuberculosis

The coronavirus disease 2019 (COVID-19) pandemic resulted from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Variants of SARSCoV-2 have caused distinct COVID-19 surges worldwide. The Omicron variant has replaced other variants as a cause of COVID-19 in the Republic of Korea. Fortunately, COVID-19 patients infected with Omicron have a decreased disease severity. Tuberculosis (TB) remains a major public health threat worldwide, and the incidence of TB is still high in the Republic of Korea. We report the case of a deceased illegal migrant who died at home. An autopsy revealed fatal pneumonia with pulmonary TB caused by the Omicron subvariant BA.2 of SARS-CoV-2. We assumed that a superimposed SARS-CoV-2 infection caused this fatal pneumonia with a previous TB infection. After a comprehensive postmortem (PM) examination, including gross dissection, microscopic studies, PM computed tomography, and PM laboratory tests, the cause of death was determined to be pneumonia, and the death manner was natural. We present this case with a comprehensive PM examination from the perspective of forensic pathology and the public healthcare system.

Interstitial lung disease in patients with connective tissue disease: Subtypes, clinical features and comorbidities in the Western Cape, South Africa.

Background Interstitial lung disease (ILD) is highly prevalent in patients with connective tissue disease (CTD) and is poorly characterised in South Africa. Objectives To describe the clinical, serological and radiological features of CTD-ILD and their associations in patients attending a tertiary referral hospital. Methods A cross-sectional study collating clinical, serological and radiological features of CTD-ILD in patients attending rheumatology and respiratory outpatient clinics in a tertiary referral hospital. ResultsOf 124 CTD-ILD patients, 37 (29.8%) had rheumatoid arthritis (RA), 32 (25.8%) systemic sclerosis (SSc) and 55 (44.4%) other autoimmune connective tissue diseases (OCTD). Most patients were female (86.3%), of mixed racial ancestry (75.0%), and the median age was 55 years. Nonspecific interstitial pneumonia (NSIP) was the most common ILD pattern (63.7%), followed by usual interstitial pneumonia (UIP) (26.6%). Overall, 60.5% were current or past smokers, 33.1% had previous pulmonary tuberculosis infection, and 75.6% had gastro-oesophageal reflux disease. Patients with RA were older, had similar frequencies of NSIP and UIP, and had significantly better pulmonary function tests than the SSc and OCTD groups. Within three years of CTD diagnosis, two-thirds of the SSc and OCTD patients and almost half of the RA patients had developed ILD. Clinical features, chest X-rays and pulmonary function tests correlated poorly with high-resolution computerised tomography (HRCT). No case of acute pneumonitis was documented in CTD-ILD patients treated with methotrexate (MTX). Conclusion We suggest routine HRCT in all newly diagnosed CTD patients, particularly those with SSc and OCTD, where more than two-thirds of the patients had developed ILD within three years of their CTD. The use of MTX was not associated with the development of acute pneumonitis in patients with ILD. Key points Clinical features, chest X-rays and pulmonary function tests correlated poorly with high-resolution computerised tomography (HRCT).Smoking, environmental toxins, gastro-oesophogeal reflux and previous pulmonary tuberculosis infection were significant comorbidities in CTD-ILD patients.Early screening of ILD with HRCT is recommended, particularly in SSc.Use of MTX before and after ILD diagnosis was not associated with acute pneumonitis.

Correlation between tuberculosis-specific interferon-γ release assay and intrathoracic calcification: A cross-sectional study.

BackgroundAlthough persistent tuberculosis (TB) infection is known to cause calcification in the lungs, the relationship between intrathoracic calcification and the results of the interferon-γ release assay (IGRA) has not been fully elucidated. This study aimed to assess the association between intrathoracic calcification and IGRA results.MethodsWe retrospectively included consecutive patients who concurrently underwent chest X-ray, chest computed tomography (CT), and an IGRA. Patients with a current diagnosis of active TB or treatment history of active TB or latent tuberculosis infection (LTBI) were excluded. The association between calcification according to the chest X-ray or CT and IGRA results were analyzed using binomial logistic regression.ResultsThis study included 574 patients, and 38 (7%) patients had a positive IGRA result. Patients with a positive result were significantly older and had a higher proportion of comorbidities, and history of tuberculosis exposure compared to those with a negative result. Calcification of the lung field and mediastinal lymph nodes according to chest CT was more frequently observed in patients with a positive IGRA result, whereas no significant difference was observed concerning the proportion of lung field calcification on chest X-ray between patients with positive and negative IGRA results. In multivariate analysis, calcification of mediastinal lymph nodes alone (adjusted odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.76–8.26) and the combination of lung field and mediastinal lymph node calcification (adjusted OR = 4.12, 95% CI = 1.51–11.76) on chest CT was independently associated with positive IGRA results.ConclusionsThe finding of mediastinal lymph node calcification, with or without lung field calcification, on chest CT was associated with positive IGRA results independent of TB exposure history. Previous TB infection including eliminated TB infection and LTBI can be suspected when calcified lymph nodes in are observed the mediastinum on chest CT.

Hyponatremia Incidence and its Association with Mortality in Patients with Pulmonary Tuberculosis Observational Study

Introduction: Pulmonary tuberculosis has been of great interest for us given the high number of cases in our community at the Mexican-American border, however, this abundance of patients allows us to observe whether there is an association between the previously described development of hyponatremia and mortality in these patients. Objective: To determine the association between mortality and hyponatremia in patients with pulmonary tuberculosis. Material and Methods: We analyzed the electronic health record of patients with a pulmonary tuberculosis diagnosis from a 4-year period in the General Hospital of Mexicali, in México. Inclusion criteria were patients over the age of 18, a pulmonary tuberculosis diagnosis, and complete laboratory tests. The collected data was then analyzed through descriptive statistics. Results: 116 patients with pulmonary tuberculosis were included, of which 91 (78.4%) were male. A history of past Infection with the Human immunodeficiency virus and previous tuberculosis infection were shown to correlate with higher mortality and requirement of intensive care. The logistic regression analysis showed that hyponatremia had no association with mortality or the need for intensive care. Complications such as Acute respiratory distress syndrome and Acute kidney injury were related to higher mortality and need for critical care. Conclusions: The incidence of hyponatremia was higher than previously described, but there was no statistical association between hyponatremia and mortality in comparison to patients with normal sodium. Among this study’s weaknesses, most patients were hospitalized at the time of diagnosis, implying they could already have had a complication, thus increasing the incidence.

Previous pulmonary tuberculosis enhances the risk of lung cancer: systematic reviews and meta-analysis

Purpose The possible association between history of pulmonary tuberculosis (TB) and lung cancer (LC) has attracted researchers’ attention for several decades. This systematic review and meta-analysis aim to assess the association between previous pulmonary TB infection and LC risk. Methods A Systematic and comprehensive search was performed in the following databases: PubMed, Embase, clinical key, Web of Science and Google Scholar, in articles and abstracts published from 1987 to 2021. Thirty-two articles (involving 50,290 cases and 846,666 controls) met the inconclusive criteria. The Comprehensive Meta-Analysis version 2.2 software was used for this meta-analysis. Results The result of this meta-analysis demonstrates that pre-existing active pulmonary TB increases the risk of LC (RR = 2.170, 95% confidence interval [CI] 1.833–2.569, p < .001, I 2 = 91.234%). The results showed that the risk of the history of active pulmonary TB infection in adenocarcinoma was 2.605 (95% CI 1.706–3.979, p < .001, I 2 = 55.583%), in small-cell carcinoma was 2.118 (95% CI 1.544–2.905, p < .001, I 2 = 0.0%), in squamous-cell carcinoma, was 3.570 (95% CI 2.661 − 4.791, p < .001, I 2 = 42.695%) and 2.746 (95% CI 2.300–3.279, p < .001, I 2 = 41.686%) for other histological types of LCs. According to these results, a history of active pulmonary TB increases the risk of LC. Conclusions This study emphasizes the importance of LC screening in pulmonary TB patients even after the infection is treated. With the increased chances of LC in a patient who had a history of active pulmonary TB, there could be a need for a further follow-up period after pulmonary TB recovery.

Presumed tuberculosis-related scleritis

AimsTo evaluate the clinical characteristics and therapeutic outcome of patients with recurrent scleritis of unknown demonstrable aetiology and positive QuantiFERON-TB Gold In-Tube test (QFT).MethodsRetrospective chart review of the demographic, clinical,...

Descriptive analysis of a tuberculosis outbreak from a northern Saskatchewan First Nations community-December 2018 to May 2019.

The tuberculosis (TB) incidence rate for northern Saskatchewan First Nations on-reserve is 1.5 higher than the national average. In December 2018 a member of one of these communities was diagnosed with 4+ smear-positive TB, spurring an outbreak investigation. To describe the public health response to TB outbreak investigation and highlight the risk factors associated with TB transmission in northern Saskatchewan; and to highlight the relevance of social network contact investigation tool in outbreak management. Descriptive analysis included active TB cases and latent TB infection (LTBI) cases linked by contact investigation to the index case. Data were collected from active TB case files. Statistical analyses were performed and social network analysis conducted using household locations as points of contact between cases. A total of eight active TB cases and 41 LTBI cases were identified as part of the outbreak between December 2018 and May 2019. Half of the cases (4/8) were 25 to 34 years old, and five were smear negative. One-third of the people with LTBI were 15 to 24 years old, and about a half tested positive to the new tuberculin skin test (TST). The commonly reported risk factors for TB and LTBI cases were alcohol use, cigarette use, marijuana use, previous TB infection and homelessness. Social network analysis indicated a relationship between increased node centrality and becoming an active case. Real-time social network contact investigation used in active-case finding was very successful in identifying cases, and enhanced nursing support, mobile clinics and mobile X-ray worked well as a means of confirming cases and offering treatment. TB outbreaks in northern Saskatchewan First Nations on-reserve communities are facilitated by population-specific factors. Efforts to implement context-specific interventions are paramount in managing TB outbreaks and preventing future transmission.

Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers.

ObjectivesLung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women.Materials and MethodsDuring September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.ResultsA total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2.ConclusionsNovel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.

The latent tuberculosis cascade-of-care among people living with HIV: A systematic review and meta-analysis.

Tuberculosis preventive therapy (TPT) reduces TB-related morbidity and mortality in people living with HIV (PLHIV). Cascade-of-care analyses help identify gaps and barriers in care and develop targeted solutions. A previous latent tuberculosis infection (LTBI) cascade-of-care analysis showed only 18% of persons in at-risk populations complete TPT, but a similar analysis for TPT among PLHIV has not been completed. We conducted a meta-analysis to provide this evidence. We first screened potential articles from a LTBI cascade-of-care systematic review published in 2016. From this study, we included cohorts that reported a minimum of 25 PLHIV. To identify new cohorts, we used a similar search strategy restricted to PLHIV. The search was conducted in Medline, Embase, Health Star, and LILACS, from January 2014 to February 2021. Two authors independently screened titles and full text and assessed risk of bias using the Newcastle-Ottawa Scale for cohorts and Cochrane Risk of Bias for cluster randomized trials. We meta-analyzed the proportion of PLHIV completing each step of the LTBI cascade-of-care and estimated the cumulative proportion retained. These results were stratified based on cascades-of-care that used or did not use LTBI testing to determine eligibility for TPT. We also performed a narrative synthesis of enablers and barriers of the cascade-of-care identified at different steps of the cascade. A total of 71 cohorts were included, and 70 were meta-analyzed, comprising 94,011 PLHIV. Among the PLHIV included, 35.3% (33,139/94,011) were from the Americas and 29.2% (27,460/94,011) from Africa. Overall, 49.9% (46,903/94,011) from low- and middle-income countries, median age was 38.0 [interquartile range (IQR) 34.0;43.6], and 65.9% (46,328/70,297) were men, 43.6% (29,629/67,947) were treated with antiretroviral therapy (ART), and the median CD4 count was 390 cell/mm3 (IQR 312;458). Among the cohorts that did not use LTBI tests, the cumulative proportion of PLHIV starting and completing TPT were 40.9% (95% CI: 39.3% to 42.7%) and 33.2% (95% CI: 31.6% to 34.9%). Among cohorts that used LTBI tests, the cumulative proportions of PLHIV starting and completing TPT were 60.4% (95% CI: 58.1% to 62.6%) and 41.9% (95% CI:39.6% to 44.2%), respectively. Completion of TPT was not significantly different in high- compared to low- and middle-income countries. Regardless of LTBI test use, substantial losses in the cascade-of-care occurred before treatment initiation. The integration of HIV and TB care was considered an enabler of the cascade-of-care in multiple cohorts. Key limitations of this systematic review are the observational nature of the included studies, potential selection bias in the population selection, only 14 cohorts reported all steps of the cascade-of-care, and barriers/facilitators were not systematically reported in all cohorts. Although substantial losses were seen in multiple stages of the cascade-of-care, the cumulative proportion of PLHIV completing TPT was higher than previously reported among other at-risk populations. The use of LTBI testing in PLHIV in low- and middle-income countries was associated with higher proportion of the cohorts initiating TPT and with similar rates of completion of TPT.

Analysis of the clinical characteristics and species distribution of non-tuberculous mycobacteria in a general hospital

Objective: To summarize the clinical characteristics and species distribution of nontuberculous mycobacteria(NTM). Methods: We conducted a retrospectively chart review of 453 adult patients with 532 positive cultures with NTM diagnosed and treated in Peking Union Medical College Hospital from January 2014 to December 2018. The information including clinical findings, imaging and etiological data were obtained from clinical examination system. Among these 453 patients, 75 cases met the diagnostic criteria for NTM, with detailed clinical data, culture results and radiological images. Of these patients, 38 were males and 37 were females, with an average age of (50.8±16.2) years. Clinical manifestations, imaging features, NTM species and treatment were analyzed. Results: Among 75 NTM patients, 43 cases (57.3%, 43/75) were infected with Mycobacterium avium Complex (MAC)/intracellular, 18 cases (24.0%, 18/75) with Mycobacterium turtle/abscess, and 7 cases (9.3%, 7/75) with Mycobacterium kansasii. Comorbidities existed in 64.0% patients (48/75). The top two common comorbidities were previous tuberculosis (25.3%, 19/75) infection and clinical bronchiectasis (18.7%, 14/75). After the respiratory disease (82.7%, 62/75), we identified bloodstream as the most frequent manifestation of NTM infection (25.3%, 19/75). MAC was often associated with infection in respiratory system and bloodstream, while rapidly growing mycobacteria (RGM) was more commonly detected in lymph nodes and skin and soft tissues. Cough/expectoration (77.4%, 48/62) was the most common clinical symptom of NTM disease, followed by fever and dyspnea. The frequent imaging findings were nodules (41.9%, 26/62), bronchiectasis (37.1%, 23/62), and fibrous cavities (24.2%, 15/62). In disseminated NTM disease, 94.7% (18/19) patients had underlying diseases and 89.5% (17/19) patients had long-term immunosuppression. Conclusion: The most common NTM species was Mycobacterium avium/intracellular in our series. The predominant infected organ was the respiratory system. Previous tuberculosis history likely increased the risk of infection.

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.

Tuberculosis infection in HIV vs. non-HIV patients.

Tuberculosis (TB) is the most common opportunistic infection and cause of mortality among people living with HIV, and it is possible that it may also influence the evolution of the HIV infection. We assessed the differences between HIV-positive and -negative people infected with TB. The present study is a cross-sectional retrospective study by electronic record revision. We included patients admitted to a tertiary hospital with a diagnosis of TB between 2011 and 2016, comparing those with HIV coinfection with non-HIV patients, according to demographic and clinical characteristics. This study included 591 patients, of whom 32% were HIV-coinfected. HIV-TB patients were younger, with a predominance of male gender. Considering TB risk factors, there was a higher prevalence of homelessness and intravenous drug use in the HIV group. In the non-HIV group, direct contact with other patients with TB and immunosuppression were more prevalent. Relative to TB characteristics, the HIV-coinfected group presents with a higher prevalence of disseminated disease and a higher occurrence of previous TB infection. Cancer was the most frequent cause of immunosuppression in the HIV group and the number testing positive for TB via microbiological culture was lower. Assessment of microbiological resistance and in-hospital mortality showed similar numbers in both groups. There are few papers comparing clinical course of TB between HIV-infected and non-infected patients. Our study differs from others in the literature as we focused on a country with middling incidence of TB and further characterized the differences between HIV-infected and non-infected patients which can contribute to the management of these patients.