Latent Tuberculosis Infection In Patients Research Articles

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.

Features of detection of latent tuberculosis infection in patients with inflammatory intestinal diseases

A quarter of the world’s population has latent tuberculosis infection (LTBI). Systemic immunosuppression is a risk factor for the reactivation of LTBI and the development of active tuberculosis, and such reactivation is associated with a substantial risk of morbidity and mortality. Despite the growing global prevalence of inflammatory bowel diseases (IBD) and the use of immunosuppressive therapies, current recommendations for LTBI testing and treatment in IBD patients lack a systematic approach due to a lack of evidence. Currently, the main challenge in accurately diagnosing inflammatory bowel diseases (IBD) is the high prevalence of conditions that lead to intestinal lesions mimicking IBD.

1869. Knowledge about and Perceptions of Latent Tuberculosis Infection (LTBI) among Physicians and Advanced Practice Providers at Tufts Medical Center

Abstract Background Mycobacterium Tuberculosis (TB) is a leading cause of infectious disease mortality worldwide. Most active TB cases result from reactivation of latent tuberculosis infection (LTBI). A large reservoir of latent TB is a major public health problem worldwide and in the United States. A better understanding of provider perspectives on LTBI could improve a sub-optimal LTBI care cascade. Methods A 13-question survey was fielded to attending physicians, fellows, and advanced practice providers working in the infectious disease, pulmonary/critical care, and general medicine departments at Tufts Medical Center (TMC), an academic tertiary care center in Boston, Massachusetts. Results The response rate of the survey was 33% (62/186). Only 17 (30.9%) providers were able to correctly identify all indications for screening. When asked how they decide who to treat, 26.8% (15/56) of providers selected that they would refer their patient to another specialist. Overall, provider confidence in LTBI management decreased along the care cascade (Figure 1). Infectious disease providers expressed more confidence in management than general medicine and pulmonary/critical care providers. The two most observed issues/barriers to care for patients were language, reported by 39 (76.5%) providers, and lack of knowledge or understanding about TB, reported by 39 (76.5%) providers. The two most selected interventions to improve LTBI care at TMC were use of in-person language interpreters, chosen by 37 (71.2%) providers, and information pamphlets available in patients’ preferred languages, chosen by 36 (69.2%) providers. Providers were asked “On a scale of 1-5, (“1” = not at all, and “5” = perfectly) “How confident are you in your ability to do the following” for the listed management tasks. Conclusion Results suggest that providers believe the largest barriers to patient LTBI treatment completion are due to a lack of patient comprehension about their infection. Improving patient understanding could be accomplished through in-person interpreters, information pamphlets about LTBI in patients’ preferred languages, and forming community partnerships to improve awareness and understanding of the risks of LTBI. Additionally, ensuring that providers feel confident in their ability to manage LTBI, are updated on screening guidelines, and have referral resources when needed, could help close the gaps in the LTBI care cascade. Disclosures All Authors: No reported disclosures

Latent Tuberculosis Infection in Patients with Oncological Pathology Based on Skin Test with Recombinant Tuberculosis Allergen

Введение. Возникновение туберкулёза у лиц из групп высокого онкологического риска и активное выявление заболевания остаётся актуальной проблемой здравоохранения. У больных с онкологическими заболеваниями снижение иммунитета и иммуносупрессивная терапия могут привести к прогрессированию латентной туберкулёзной инфекции. Цель. Выявление наличия латентной туберкулёзной инфекции у больных со злокачественными новообразованиями различной локализации с помощью кожной пробы с аллергеном туберкулёзным рекомбинантным. Методы исследования. По архивным историям болезни изучены данные иммунологического обследования пациентов с помощью пробы с аллергеном туберкулёзным рекомбинантным на наличие латентной туберкулёзной инфекции у 132 больных с верифицированным диагнозом злокачественной опухоли различных локализаций, поступивших в Воронежский областной противотуберкулёзный диспансер в течение 2011-2022 гг. для исключения наличия активного туберкулёза органов дыхания. Среди них было 100 (75,76 %) мужчин и 32 (24,24 %) женщины в возрасте от 44 до 86 лет. Наличие латентной туберкулёзной инфекции у пациентов подтверждалось положительной реакцией на пробу с аллергеном туберкулёзным рекомбинантным. Результаты. Установлено, что пациенты с онкологическими заболеваниями в 37,1 % случаев имеют латентную туберкулёзную инфекцию и, следовательно, повышенный риск прогрессирования туберкулёза. При наличии у больных остаточных неактивных туберкулёзных изменений в различных органах латентная туберкулёзная инфекция наблюдается чаще, чем при их отсутствии — 53,8 % против 30,1 % (p < 0,05). Заключение. При выявлении и подготовке к лечению больных с онкологическими заболеваниями целесообразным является обследование их на латентный туберкулёз с помощью кожной пробы с аллергеном туберкулёзным рекомбинантным с последующим решением вопроса о необходимости профилактической терапии и наблюдения.

Prevalence of LTBI in patients with autoimmune diseases and accuracy of IGRA in predicting TB relapse.

The current study evaluated latent tuberculosis infection (LTBI) positivity in a cohort of Indian subjects and the accuracy of IFN-gamma release assay (IGRA) in predicting tuberculosis (TB) reactivation. This cross-sectional, retrospective chart-based study considered patients diagnosed with autoimmune rheumatic diseases (AIRDs), especially those who received treatment with biologics or targeted synthetic (ts)DMARDs. The patients had undergone LTBI screening and IGRA test. The study excluded patients with inadequate information and those who had undergone test exclusively for diagnostic purpose. Statistical analyses were carried out for descriptive, demographic and clinical variables. Accuracy and error rate in predicting the absence of TB reactivation were calculated for IGRA test. The study selected 943 patients who had undergone IGRA pre-screening prior to the initiation of biologics or tsDMARDs with a mean age of 42.93 ± 14.01 years and male-to-female ratio of 1:2.08. RA was the most common primary diagnosis (43.16%). The proportion of subjects who received single, double and triple or more DMARDs or immune suppressants were 54.35%, 33.33% and 7.69%, respectively. Among the selected subjects, 125 patients were LTBI positive and 816 were negative. All patients, except one who tested positive at baseline, received antitubercular prophylaxis. Accuracy of IGRA in predicting the absence of TB reactivation was 99.6%, with an error rate of 0.46. LTBI screening is beneficial in AIRDs patients prior to the prescription of biologics or tsDMARDs. IGRA is ideal for identifying patients with increased likelihood of developing TB upon receiving biologics or tsDMARDs with reasonable accuracy.

The prevalence of latent tuberculosis infection in patients with chronic kidney disease: A systematic review and meta-analysis

ObjectiveTo estimate the prevalence of latent tuberculosis infection (LTBI) in chronic kidney disease (CKD) patients. MethodsThis study was conducted following the PRISMA guidelines. We identified, 3694 studies from the whole search, and 59 studies were included. Each study's quality was assessed using JBI checklist. We employed STATA version 17 for statistical analysis. We assessed heterogeneity using I2 heterogeneity test. Publication bias was assessed using funnel plot and Egger's test. We estimated the pooled LTBI prevalence in CKD patients along with 95%CI. ResultsThe pooled prevalence of LTBI among CKD patients using data collected from 53 studies having 12,772 patients was 30.2% (95%CI; 25.5, 34.8). The pooled prevalence among pre-dialysis, hemodialysis, peritoneal dialysis, and renal transplanted patients was 17.8% (95%CI; 3.3, 32.4), 34.8% (95%CI; 29.1, 40.5), 25% (95%CI; 11, 38), and 16% (95%CI; 7, 25), respectively. The pooled prevalence of LTBI stratified by the laboratory screening methods was 25.3% (95%CI: 20.3–30.3) using TST, 28.0% (95%CI; 23.9–32.0) using QFT, and 32.6%, (95%CI: 23.7–41.5) using T-SPOT. ConclusionThere is high prevalence of LTBI among CKD patients mainly in patients on dialysis. Thus, early diagnosis and treatment of LTBI in CKD patients should be performed to prevent active TB in CKD patients.PROSPERO registration number: CRD42022372441.

Performance of two interferon-gamma release assays for tuberculosis infection screening in Kawasaki children before immunosuppressive therapy.

We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) and X.DOT-TB for screening latent tuberculosis infection (LTBI) in kawasaki patients, and to identify the risk factors associated with indeterminate IGRA results. We conducted a retrospective study on children with KD, who were screened for mycobacterium tuberculosis (Mtb) infection by either ELISA-based QFT-GIT or ELISPOT-based X.DOT-TB tests, admitted in Department of Cardiology, Beijing Children's Hospital from July 2019 to April 2022. A total of 1327 cases were included. Among them, 932 cases were tested by QFT-GIT and 395 cases by X.DOT-TB. The positive rate of children was 0.1% and 0.2%, and the indeterminate rate was 68.2% and 6.1% for QFT-GIT and X.DOT-TB, respectively. Patients with hypoproteinemia had a higher risk of indeterminate X.DOT-TB result. Female, critical ill, shock or hypoproteinemia presented statistically significant associations with an increased risk of indeterminate QFT-GIT result. High-dose of IVIG inhibited the release of IFN-γ by more than 90%, which might account for the high indeterminate incidence. It is recommended to perform X.DOT-TB rather than QFT-GIT to screen LTBI in patients with high level of the mitogen that can inhibit IFN-γ release. For KD children with positive IGRA results, it has a higher risk of activation TB infection when treated with immunosuppressive therapy in the future. Children with KD aged <5 years old had higher frequency of indeterminate IGRA results.

Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes

BackgroundDiabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain.MethodsWe prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota.ResultsCompared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa.ConclusionsThe study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.

1438. Latent tuberculosis infection (LTBI) in hematopoietic stem cell transplantation (HSCT) recipients: a retrospective Italian cohort study in Tor Vergata University Hospital, Rome.

Abstract Background Patients undergoing haematopoietic stem cell transplantation (HSCT) have severe and prolonged immunodeficiency and the incidence of tuberculosis (TB) disease in those patients is 10 to 40 times higher than the general population Methods This retrospective study performed at Tor Vergata University Hospital in Rome (Italy) included all adult patients who underwent a HSCT in the Hematologic Transplant Unit from January 2015 to December 2019. Data on TB screening, performed through interferon-γ release assay (IGRA), were collected; patients were observed for TB reactivation in a follow up period of at least 3 years Results 323 HSCT recipients were enrolled in this study. Patients’ characteristics are summarized in table 1. 63 patients (19.5%) were not screened for TB, of which 6.3% were born overseas. 260 HSCT recipients (80.5%) were screened: 228 patients (87.7%) had a negative IGRA result, 21 (8.1%) tested positive, and 11 (4.2%) had an indeterminate result. 98.5% were screened before the HSCT. Of the 21 patients with a positive pre-HSCT IGRA test, 14 (66.7%) were males and significantly (p&amp;lt; 0.001) older (median age 60 [IQR] 58-65 years) than those with negative or indeterminate results. Almost all patients (95.2%) were Italian. Patients with a positive IGRA showed a higher monocyte count compared to the other groups (p=0.044), while those with indeterminate IGRA showed a tendence to lower lymphocyte absolute counts, compared to the other groups (p=0.060) (Table 2). All the 21 patients with a pre-HSCT positive IGRA test were radiologically and clinically screened for active TB and, once it was ruled out, treated for latent TB (LTBI) with isoniazid (INH) for 6 months. No events of toxicity or treatment interruption were reported. None of the patients was treated with rifampin. None of the 21 patients with pre-HSCT positive IGRA test developed active TB during the follow up period. Table 1.Characteristics of the study population, overall and divided according to IGRA testingTable 2.Characteristics of the IGRA tested patients, overall and divided by IGRA test results Conclusion To our knowledge, this is the first Italian study on the prevalence of LTBI in patients undergoing HSCT. 8.1% of the 260 patients screened with an IGRA tested positive. The great majority (95.2%) of LTBI patients were Italian and significantly older than IGRA-negative patients. All LTBI HSCT patients received INH treatment and no drug toxicity, nor TB reactivation was observed during the follow-up period Disclosures All Authors: No reported disclosures.

Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases

Rheumatic diseases, a typical kind of autoimmune disease, are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, which often leads to immune dysfunction in patients and increases the risk of activation of latent tuberculosis infection. To regulate the screening, diagnosis, and prophylactic treatment of latent tuberculosis infection in patients with rheumatic diseases, reduce the risk of developing active tuberculosis and improve the prognosis, Peking University Shenzhen Hospital, Shenzhen Third People's Hospital and Peking Union Medical College Hospital jointly organized domestic experts in the field of rheumatology and tuberculosis to establish the expert consensus on the diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases. This consensus focuses on epidemiology, the importance of screening, screening methods, and prophylactic anti-tuberculosis treatment strategies for latent tuberculosis infection combined with rheumatic diseases.

Serial testing of latent tuberculosis infection in patients with diabetes mellitus using interferon-gamma release assay, tuberculin skin test, and creation tuberculin skin test.

Diabetes mellitus (DM) patients with latent tuberculosis infection (LTBI) have an increased risk of developing active tuberculosis (TB) due to impaired immunity. The performance of currently available immune response-based assays for identification of TB infection had been rarely evaluated in patients with type 2 DM (T2DM) in China. A prospective study was conducted to investigate the status of LTBI in patients with confirmed T2DM. At the baseline survey, the prevalence of LTBI was tested using interferon-gamma release assay (IGRA), tuberculin skin test (TST) and creation tuberculin skin test (C-TST) in parallel. After a 3-month interval, the participants were retested by the three assays to estimate their performance in the serial testing. A total of 404 participants with T2DM were included in the study. At baseline, after excluding active TB, the prevalence of LTBI identified by TST (≥ 10 mm), C-TST (≥ 5 mm) and IGRA (≥ 0.35 IU/ml) were 9.65% (39/404), 10.40% (42/404) and 14.85% (60/404), respectively. The concordance of TST and C-TST results with IGRA results was 86.39% (349/404) and 92.08% (372/404) with a Kappa coefficient of 0.37 [95% confidence interval (CI): 0.24- 0.50] and 0.64 (95% CI: 0.53- 0.76), respectively. After a 3-month interval, the continuous results of TST, C-TST and IGRA were observed to be increased with testing conversion for 50, 26 and 27 patients, respectively. For TST and C-TST conversions, the distribution of their quantitative results in serial tests varied significantly when further classified by baseline IGRA dichotomous results. In studied patients with T2DM, C-TST showed higher consistency with IGRA as compared to TST. The present of conversion observed in serial testing suggested that boosting effect of skin testing should be considered for identify of LTBI in patients with T2DM.

Prevalence of Hepatitis B Virus and Latent Tuberculosis Coinfection in the United States.

Underlying chronic hepatitis B virus (HBV) infection increases the risk of drug-induced liver injury (DILI) when receiving tuberculosis therapies. Prevalence of HBV and latent tuberculosis infection (LTBI) coinfection is not well reported and no studies have evaluated testing patterns for and prevalence of HBV-LTBI coinfection in the United States. To evaluate patterns of HBV and LTBI testing and prevalence of HBV-LTBI coinfection in the United States. Retrospective cohort study. Quest Diagnostics clinical laboratory data, 2014-2020. Chronic HBV infection was defined as any combination of 2 positive HBV surface antigen, HBV e antigen, or detectable HBV DNA tests at least 6 months apart. LTBI was defined as a positive QuantiFERON-TB or T-SPOT.TB test without evidence of active tuberculosis infection. Testing patterns for chronic HBV infection and LTBI and prevalence of HBV-LTBI coinfection were evaluated from 2016 through 2020 and stratified by age, sex, and race and ethnicity. Among 89 259 patients with chronic HBV infection, 9508 (10.7%) were tested for LTBI, among whom prevalence of HBV-LTBI coinfection was 19.6%, more than twice the observed prevalence of LTBI in patients with no chronic HBV infection in our cohort. Among 394 817 LTBI patients, 127 414 (32.3%) were tested for HBV, among whom prevalence of HBV-LTBI coinfection was 1.5%, approximately 3 times higher than prevalence of HBV infection in patients with no LTBI. The HBV-LTBI coinfection prevalence was highest among Asian Americans and older individuals. The HBV-LTBI coinfection prevalence was likely underestimated because of suboptimal awareness and testing among at-risk populations. Among US individuals with chronic HBV infection or LTBI, prevalence of HBV-LTBI coinfection is substantial and highlights the need of testing for HBV-LTBI coinfection to mitigate risk of DILI associated with tuberculosis medications in patients with chronic HBV infection.

The Pitfalls of Mining for QuantiFERON Gold in Severely Ill Patients With COVID-19.

ObjectiveTo assess the proportion of indeterminate QuantiFERON-TB Gold Plus (QFT-Plus) results in patients admitted for severe coronavirus disease 2019 (COVID-19) pneumonia and evaluate the factors associated with indeterminate QFT-Plus results.Patients and MethodsData on COVID-19 admissions at Mayo Clinic in Florida were extracted between October 13, 2020, and September 20, 2021, and data from a prepandemic cohort were extracted between October 13, 2018, and September 20, 2019. A secondary analysis of the COVID-19 cohort was performed using gradient boosting modeling to generate variable importance and SHapley Additive exPlanations plots.ResultsOur findings demonstrated more indeterminate QFT-Plus test results in patients hospitalized for severe COVID-19 infection than in patients without COVID-19 (139 of 495, 28.1%). The factors associated with indeterminate QFT-Plus test results included elevated levels of C-reactive protein, ferritin, lactate dehydrogenase and interleukin-6 and included lower levels of leukocyte, lymphocyte, and platelet counts.ConclusionThe patients with severe COVID-19 had a higher likelihood of indeterminate QFT-Plus results, which were associated with elevated levels of inflammatory markers consistent with severe infection. Interferon-gamma release assay screening tests are likely confounded by COVID-19 infection itself, limiting the screening ability for latent tuberculosis infection reactivation. Indeterminate QFT-Plus results may also require follow-up QFT-Plus testing after patient recovery from COVID-19, increasing the cost and complexity of medical decision making and management. Additional risk assessments may be needed in this patient population for screening for latent tuberculosis infection in patients with severe COVID-19.

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU.

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-ץ-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18–20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50–0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66–0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20–22%] vs. 14% [95% CI 13–16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.

Interferon-Inducible Protein-10 as a Marker to Detect Latent Tuberculosis Infection in Patients with Inflammatory Rheumatic Diseases.

It is important to identify cases of latent tuberculosis infection (LTBI) who are at risk for tuberculosis (TB) reactivation. We aimed to evaluate the performance of interferon (IFN)-gamma-inducible protein 10 (IP-10) as a marker to detect LTBI in patients with inflammatory rheumatic diseases (IRD). This study comprised 76 consecutive subjects with IRD. Patients with a history of TB or having active TB were excluded. In all patients, IP-10 level was measured and tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFT-GIT) were performed. Seventy patients with complete test results were analyzed. Twenty-one (30%) QFT-GIT-positive patients were defined as having LTBI. IP-10 yielded 2197 pg/mL cut-off point. At this cut-off point, IP-10 showed 89% specificity with a sensitivity of 91% (AUC: 0.950, 95% CI 0.906–0.994). TST, QFT-GIT, and IP-10 were positive in 77.1%, 30%, and 44.3% of the patients, respectively. Concordance among the results of TST, QFT-GIT, and IP-10 tests was evaluated. Agreement was poor between IP-10 and TST (58.6%, κ = 0.19), whereas it was good between QFT-GIT and IP-10 (84.3%, κ = 0.65). The results of the present study demonstrated that sensitivity and specificity of released IP-10 were as high as those of QFT-GIT in indicating LTBI in IRD patient group.

Review article: latent tuberculosis in patients with inflammatory bowel diseases receiving immunosuppression-risks, screening, diagnosis and management.

SummaryBackgroundOne quarter of the world's population has latent tuberculosis infection (LTBI). Systemic immunosuppression is a risk factor for LTBI reactivation and the development of active tuberculosis. Such reactivation carries a risk of significant morbidity and mortality. Despite the increasing global incidence of inflammatory bowel disease (IBD) and the use of immune‐based therapies, current guidelines on the testing and treatment of LTBI in patients with IBD are haphazard with a paucity of evidence.AimTo review the screening, diagnostic practices and medical management of LTBI in patients with IBD.MethodsPublished literature was reviewed, and recommendations for testing and treatment were synthesised by experts in both infectious diseases and IBD.ResultsScreening for LTBI should be performed proactively and includes assessment of risk factors, an interferon‐gamma releasing assay or tuberculin skin test and chest X‐ray. LTBI treatment in patients with IBD is scenario‐dependent, related to geographical endemicity, travel and other factors. Ideally, LTBI therapy should be used prior to immune suppression but can be applied concurrently where urgent IBD medical treatment is required. Management is best directed by a multidisciplinary team involving gastroenterologists, infectious diseases specialists and pharmacists. Ongoing surveillance is recommended during therapy. Newer LTBI therapies show promise, but medication interactions need to be considered. There are major gaps in evidence, particularly with specific newer therapeutic approaches to IBD.ConclusionsProactive screening for LTBI is essential in patients with IBD undergoing immune‐suppressing therapy and several therapeutic strategies are available. Reporting of real‐world experience is essential to refining current management recommendations.

Frequency of Latent Tuberculosis Infection in Patients with Type 2 Diabetes referred to Shahid Rahimi Hospital in Khorramabad City with Tuberculin Skin Test in 2018-2020

Introduction: Tuberculosis is the leading cause of death from infectious diseases worldwide. Diabetes has been suggested as an important risk factor for tuberculosis. To date, few studies have examined the association between diabetes and tuberculosis. In this study, the prevalence of latent tuberculosis in diabetic patients was investigated.&#x0D; Methods: In this study, 195 patients with type 2 diabetes were studied in a cross-sectional study to diagnose latent tuberculosis infection with a tuberculin skin test. Individuals with symptoms of active tuberculosis were excluded from the study, and individuals with a positive tuberculin test were evaluated for active tuberculosis by chest x-ray. For analyzing the data, SPSS software version 16 was run, a t-test was used to analyze quantitative variables, and for qualitative variables, Chi-square was applied. The significance level of 0.05 was considered for all the results.&#x0D; Results: Out of 195 diabetic patients, 115 patients were referred for tuberculin test results. 43 out of 115 patients (37.39%) had an induration diameter greater than or equal to 5 mm, 29 patients (25.21%) had an induration diameter greater than or equal to 8 mm, and 3 patients (2.61%) had an induration diameter greater than or equal to 10 mm (Positive tuberculin test) (p&gt;0.05).&#x0D; Conclusion: False tuberculin skin test results can hide the true prevalence of latent tuberculosis infection. The sensitivity of the tuberculin test decreases in immunocompromised patients and leads to limitations in assessing the prevalence of latent tuberculosis infection. Although not enough information was available in this study to establish a significant association between diabetes and latent tuberculosis infection, further studies will help to investigate this association.

Possibilities of quantiferon test in detection of latent tb infection

Objective: to determine the capabilities of the quantiferon test in detecting latent tuberculosis infection in patients with comorbid pathology. Materials and methods. A retrospective analysis of the quantiferon test results was carried out in 420 patients with suspected tuberculosis or with a hyperergic Mantoux or Diaskintest reaction using the QuantiFERON-TB Gold Plus test system (Qiagen, Germany). Results. Different levels of tuberculosis infection were established in different age groups of patients with comorbid pathology, with a higher infection rate at a young age – 21.42%. The shift of tuberculosis infection to an older age group (61-70 years) was determined – 16.32%. Latent tuberculosis infection was significantly more often detected in patients with comorbid pathology compared to healthy individuals (59.0% and 32.78%, respectively, χ2=8.45, p=0.004). Conclusion. The data obtained confirms the assumption of a high level of latent tuberculosis infection in patients with comorbid pathology.

High glycosylated hemoglobin level as a risk factor of latent tuberculosis infection in patients with uncomplicated type 2 diabetes mellitus

Background Diabetes mellitus (DM) is known to increase the risk of infection including tuberculosis (TB). Some studies also showed that 2-15% of latent TB infection (LTBI) will progress to active TB. This study aimed to obtain the prevalence of LTBI and to determine the risk factors of LTBI in patients with type 2 diabetes mellitus (T2DM). Methods This was a cross-sectional study on 242 adult T2DM patients. For LTBI screening we performed the interferon gamma release assay (IGRA) (Quantiferon TB Gold Plus test) and for confirmation of active TB (pulmonary TB) we performed GeneXpert MTB/Rif sputum examination and chest X-ray. Glycosylated hemoglobin (HbA1c) levels, smoking history and BCG scar were collected. Multivariate logistic regression was used to analyze the data. Results Positive IGRA results were found in 99 of 242 uncomplicated T2DM patients while LTBI was found in 82 patients (33.8%). There were significant differences between T2DM patients with latent TB and T2DM patients without infection in HbA1c and specific IFN-ã levels (TB1 minus nil and TB2 minus nil), i.e. 8.5% and 7.6%, 2.5 IU/mL and 0.06 IU/mL, and 2.6 IU/mL and 0.08 IU/mL, respectively. Multivariate analysis showed that the risk factors for LTBI in T2DM patients were smoking history, HbA1c &gt;7%, and no BCG scar. Conclusions Because LTBI is prevalent in T2DM, it is important to screen for it in T2DM patients due to the risk of developing severe active TB. Absence of a BCG scar and high HbA1c levels are strong predictors of LTBI in T2DM patients.

1410. Isoniazid Therapy for Latent Tuberculosis Infection in Patients with Cancer Treated with Checkpoint Inhibitors Immunotherapy

BackgroundData on the efficacy and tolerability of latent tuberculosis infection (LTBI) treatment in cancer patients receiving checkpoint inhibitor immunotherapy (CPI) is limited. We sought to assess LTBI therapy and its adverse events and outcomes in patients treated with CPI. MethodsWe performed a retrospective cohort study at MD Anderson Cancer Center of adult patients, between April 2016 and May 2021, who were receiving CPI and were diagnosed with LTBI based on positive T-SPOT TB test. We then compared those patients treated with isoniazid (INH) 5mg/kg daily versus those that did not receive INH therapy. ResultsWe identified 35 patients treated with CPI who had a diagnosis of LTBI. Patients were divided into 2 groups: CPI alone (23 patients, 65.7%) and CPI+INH (12 patients, 34.3%). The majority of patients in both groups had renal cell carcinoma (34.3%) and melanoma (17.1%). Nivolumab as monotherapy was the most commonly used CPI agent in both groups (37.1%), whereas nivolumab and ipilimumab combination was mainly used in the CPI group (34.7%) compared to CPI+INH group (8.3%). In the CPI+INH group, 7 patients (58.3%) developed moderate to severe hepatoxicity that led to discontinuation of INH and CPI therapy versus none in the CPI group (p= 0.001). There was no statistically significant difference in the alanine aminotransferase (ALT) at baseline between both groups (p=0.117), whereas the median ALT level was significantly higher during CPI+INH therapy compared to CPI alone (135 U/L vs 24 U/L respectively, p=0.025. Furthermore, immune-related adverse events were reported in a total of 12 of 35 patients (34.2%). None of the patients in either group developed tuberculosis reactivation during a follow up period of up to 1148 days. ConclusionOur data suggest that latent tuberculosis reactivation is rare in cancer patients on CPI immunotherapy. Hepatotoxicity remains a concern in this patient population with LTBI treated with CPI and INH. With the widespread use of CPI, close laboratory and clinical monitoring is required to avoid life-threatening drug-induced liver injury and interruption of LTBI therapy and immunotherapy. Further clinical studies are warranted to determine the optimal management of LTBI during CPI therapy.Disclosures Pablo C. Okhuysen, MD, FACP, FIDSA, Deinove Pharmaceuticals (Grant/Research Support)Ferring Pharmaceuticals (Consultant)Melinta Therapeutics (Grant/Research Support)Merck & Co. (Grant/Research Support)Napo Pharmaceuticals (Consultant, Scientific Research Study Investigator, Research Grant or Support)Singulex (Consultant)Summit Therapeutics (Grant/Research Support) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)