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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-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.

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Laboratory algorithms using Acid-Fast Bacilli staining and Mycobacterium tuberculosis (Mtb) polymerase chain reaction (PCR) are often used to remove isolation precautions. A retrospective case review of 52 patients with culture-confirmed pulmonary Mtb revealed 4 subjects with negative sputum Acid-Fast Bacilli smears and negative Mtb PCRs. All had significant risk factors for Mtb and had a positive interferon-gamma release assay. A negative PCR test result does not exclude an Mtb diagnosis.

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Diagnosis of M. tuberculosis (Mtb) infection in close contacts is critical for TB control. Smoking is a risk factor for Mtb infection and TB disease but its effect on longitudinal interferon-gamma release assay (IGRA) results remains unknown. We conducted a multi-site prospective study in Brazil between 2015-2019, among close contacts of adults with culture-confirmed pulmonary TB. IGRA was performed at baseline, month 6 if negative at baseline, and month 24-30 after enrollment. IGRA results were categorized as IGRA-positive (maintained from baseline to last visit), IGRA-conversion (from negative to positive at any time), IGRA-reversion (from positive to negative at any time), and IGRA-negative (maintained from baseline to last visit). Associations between IGRA results and smoking status at baseline (current/former vs never) in contacts were evaluated using propensity score-adjusted logistic regression models. Estimated propensity score was used as a covariate in models, which regressed the outcome (IGRA-positive, IGRA-conversion, IGRA-reversion) on smoking status. Of 430 close contacts, 89 (21%) were IGRA-positive, 30 (7%) were converters, 30 (7%) were reverters and 22 were indeterminate. Smoking frequency was 26 (29%) among IGRA-positive contacts, 7 (23%) in converters, and 3 (10%) in reverters. Smoking in contacts was associated with lower odds of IGRA-reversion (adjusted odds ratio = 0.16; 95% confidence interval = [0.03-0.70]). We did not detect associations between smoking and IGRA-positive or IGRA-conversion. Our findings highlight the importance of smoking on longitudinal IGRA results. This has implications for clinical care and clinical trials in which IGRA status is monitored or used as an outcome.

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Sarcoidosis shows high similarity with tuberculosis in clinical manifestations and imaging features. It is rarely reported whether sarcoidosis patients with suspected latent tuberculosis can be treated safely with immunosuppressive therapy. We reported on a 54-year-old man who presented with enlarged lymph nodes persisting for decades, accompanied by renal impairment and refractory hypercalcemia. The patient was diagnosed with sarcoidosis and suspected latent tuberculosis (as suggested by a positive tuberculin test and tuberculosis interferon-gamma release assays) and received prednisone under follow-up. The patient showed significant amelioration in hypercalcemia and shrinkage of lymph nodes, without evidence of developing active tuberculosis. For sarcoidosis patients with suspected latent tuberculosis, immunosuppressive agents can be utilized safely based on close monitoring. Further efforts are required to reveal whether sarcoidosis and tuberculosis can trigger similar immune responses and what the clinical implications are.

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Globally, tuberculosis (TB) was the leading cause of death from a single infectious agent until the coronavirus (COVID-19) pandemic. In 2020, an estimated 10 million people fell ill with TB and a total of 1.5 million people died from the disease. About one-quarter of the global population, almost two billion people, is estimated to be latently infected with Mycobacterium tuberculosis (MTB). Although latent TB infection (LTBI) is asymptomatic and noncontagious, about 5-10% of LTBI patients have a lifetime risk of progression to active TB. The diagnosis and treatment of active cases are extremely vital for TB control programs. However, achieving the End TB goal of 2035 without the ability to identify and treat the pool of latently infected individuals will be a big challenge. To do so, improved technology to provide more accurate diagnostic tools and accessibility are crucial. Therefore, this chapter covers the current WHO-endorsed tests and advances in diagnostic and screening tests for active and latent TB.

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Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

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We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥ 7.5 mg prednisolone) at the time of QFT-Plus test were classified as the "high dose" group and the rest of the patients constituted the "low dose" group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7-38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

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Most patients with active pulmonary tuberculosis (TB) are difficult to be differentiated from pneumonia (PN), especially those with acid-fast bacillus smear-negative (AFB-) and interferon-γ release assay-positive (IGRA+) results. Thus, the aim of the present study was to develop a risk model of low-cost and rapid test for the diagnosis of AFB- IGRA+ TB from PN. A total of 41 laboratory variables of 204 AFB- IGRA+ TB and 156 PN participants were retrospectively analyzed. Candidate variables were identified by t-statistic test and univariate logistic model. The logistic regression analysis was used to construct the multivariate risk model and nomogram with internal and external validation. A total of 13 statistically differential variables were compared between AFB- IGRA+ TB and PN by false discovery rate (FDR) and odds ratio (OR). By integrating five variables, including age, uric acid (UA), albumin (ALB), hemoglobin (Hb) and white blood cell counts (WBC), a multivariate risk model with a concordance index (C-index) of 0.7 (95% CI: 0.61, 0.8) was constructed. The nomogram showed that UA and Hb acted as protective factors with an OR <1, while age, WBC and ALB were risk factors for TB occurrence. Internal and external validation revealed that nomogram prediction was consistent with the actual observations. Collectively, it was revealed that an integration of five biomarkers (age, UA, ALB, Hb and WBC) may be used to quickly predict TB in AFB- IGRA+ clinical samples from PN.

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Background and objective: Patients with latent tuberculosis infection (LTBI) receiving chemotherapy for hematological malignancy (HM) are at high risk of developing active tuberculosis (TB) infection. The aim of this study is to show real-life data and results of the T-SPOT test and preventive isoniazid (INH) therapy in pre-chemotherapy LTBI screening in the HM patient group. Methods: This retrospective study includes 209 HM patients who had T-SPOT test between 2016 and 2021 in Sultan 2. Abdulhamid Han Training and Research Hospital in Istanbul, Turkey. Results: The prevalence of LTBI was 26.8% in 209 patients (n=56). Preventive INH therapy was initiated in 82.1% (n=46) of 56 patients with LTBI. 23.9% (n=11) of the 46 patients who received preventive INH therapy were unable to complete the treatment. Nine patients died due to malignancy; one was lost to follow-up, and only one had to stop INH treatment due to elevated liver enzymes. Elevated liver enzymes occurred in 4 (8.7%) patients using INH, while gastrointestinal symptoms occurred in 3 (6.5%) patients. Active TB infection emerged in none of the T-SPOT positive or indeterminate individuals but in one HIV(+) patient in the T-SPOT negative group. The active TB infection incidence rate was 217 cases/100.000hab/year (95% CI, 29-748). Conclusions: INH treatment was generally well tolerated, and very few serious drug-related side effects were observed. Although LTBI cannot be demonstrated in patients with HIV(+) HM who are scheduled for chemotherapy, these patients should be closely monitored for the development of active TB infection.

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Tuberculous uveitis (TBU) comprises a broad clinical spectrum of ocular manifestations, making its diagnosis challenging. Ophthalmologists usually require evidence from investigations to confirm or support a clinical diagnosis of TBU. Since direct isolation of the causative organism from ocular specimens has limitations owing to the small volume of the ocular specimens, resultant test positivities are low in yield. Immunodiagnostic tests, including the tuberculin skin test and interferon-gamma release assays (IGRAs), can help support a clinical diagnosis of TBU. Unlike the tuberculin skin test, IGRAs are in vitro tests that require a single visit and are not affected by prior Bacillus Calmette-Guerin vaccination. Currently, available IGRAs consist of different techniques and interpretation methods. Moreover, newer generations have been developed to improve the sensitivity and ability to detect active tuberculosis. This narrative review collates salient practice points as a reference for general ophthalmologists, such as evidence for the utilization of IGRAs in patients with suspected TBU, and summarizes basic knowledge and details of clinical applications of these tests in a clinical setting.

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BackgroundIt is crucial to assess the levels of protection generated by natural infection or SARS-CoV-2 vaccines, mainly in individuals professionally exposed and in vulnerable groups. Measuring T-cell responses may complement antibody tests currently in use as correlates of protection. Our aim was to assess the feasibility of a validated assay of T-cell responses.MethodsTwenty health-care-workers (HCW) were included. Antibody test to SARS-CoV-2 N and S-proteins in parallel with a commercially available whole-blood-interferon-gamma-release-assay (IGRA) to S-peptides and two detection methods, CLIA and ELISA were determined.ResultsIGRA test detected T-cell responses in naturally exposed and vaccinated HCW already after first vaccination dose. The correlation by the two detection methods was very high (R>0.8) and sensitivity and specificity ranged between 100 and 86% and 100-73% respectively. Even though there was a very high concordance between specific antibody levels and the IGRA assay in the ability to detect immune response to SARS-CoV-2, there was a relatively low quantitative correlation. In the small group primed by natural infection, one vaccine dose was sufficient to reach immune response plateau. IGRA was positive in one, with Ig(S) antibody negative vaccinated immunosuppressed HCW illustrating another advantage of the IGRA-test.ConclusionWhole-blood-IGRA-tests amenable to automation and constitutes a promising additional tool for measuring the state of the immune response to SARS-CoV-2; they are applicable to large number of samples and may become a valuable correlate of protection to COVID-19, particularly for vulnerable groups at risk of being re-exposed to infection, as are health-care-workers. (AU)

IntroducciónEs fundamental evaluar los niveles de protección inmune en infectados o tras la vacunación frente a SARS-CoV-2. La cuantificación de la respuesta inmune celular T puede complementar la determinación de anticuerpos. Evaluamos la viabilidad de un ensayo comercial validado de respuesta celular T específica frente a SARS-CoV-2.MétodosSe incluyeron veinte trabajadores sanitarios (TS). Medimos anticuerpos contra las proteínas N y S de SARS-CoV-2 y realizamos el ensayo de liberación de interferón-gamma (IFNγ) en sangre completa (IGRA) frente a péptidos de la proteína S. IFNγ se determinó mediante dos métodos de detección: CLIA y ELISA.ResultadosIGRA detectó respuesta celular T en TS tanto infectados como vacunados. La correlación de los dos métodos de detección de IFNγ fue muy alta (R>0,8) y la sensibilidad y la especificidad variaron entre 100 y 86% y 100-73% respectivamente. Hubo una concordancia muy alta entre los niveles de anticuerpos específicos y el ensayo IGRA aunque la correlación cuantitativa fue relativamente baja. En el grupo de infectados, una dosis de vacuna fue suficiente para alcanzar el «plateau» de respuesta inmune. IGRA fue claramente positivo en un profesional vacunado inmunosuprimido que presentaba anticuerpos contra la proteína S negativos.ConclusionesIGRA frente a péptidos de la proteína-S es susceptible de automatización y constituye una herramienta prometedora para medir la respuesta inmune celular frente a SARS-CoV-2; es aplicable a un gran número de muestras y puede servir para valorar la protección, particularmente en los grupos vulnerables en riesgo de volver a exponerse a la infección, como los TS. (AU)

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Background: It is crucial to assess the levels of protection generated by natural infection or SARS-CoV-2 vaccines, mainly in individuals professionally exposed and in vulnerable groups. Measuring T-cell responses may complement antibody tests currently in use as correlates of protection. Our aim was to assess the feasibility of a validated assay of T-cell responses. Methods: Twenty health-care-workers (HCW) were included. Antibody test to SARS-CoV-2 N and S-proteins in parallel with a commercially available whole-blood-interferon-gamma-release-assay (IGRA) to S-peptides and two detection methods, CLIA and ELISA were determined. Results: IGRA test detected T-cell responses in naturally exposed and vaccinated HCW already after first vaccination dose. The correlation by the two detection methods was very high (R > 0.8) and sensitivity and specificity ranged between 100 and 86% and 100-73% respectively. Even though there was a very high concordance between specific antibody levels and the IGRA assay in the ability to detect immune response to SARS-CoV-2, there was a relatively low quantitative correlation. In the small group primed by natural infection, one vaccine dose was sufficient to reach immune response plateau. IGRA was positive in one, with Ig(S) antibody negative vaccinated immunosuppressed HCW illustrating another advantage of the IGRA-test. Conclusion: Whole-blood-IGRA-tests amenable to automation and constitutes a promising additional tool for measuring the state of the immune response to SARS-CoV-2; they are applicable to large number of samples and may become a valuable correlate of protection to COVID-19, particularly for vulnerable groups at risk of being re-exposed to infection, as are health-care-workers.

Introducción: Es fundamental evaluar los niveles de protección inmune en infectados o tras la vacunación frente a SARS-CoV-2. La cuantificación de la respuesta inmune celular T puede complementar la determinación de anticuerpos. Evaluamos la viabilidad de un ensayo comercial validado de respuesta celular T específica frente a SARS-CoV-2. Métodos: Se incluyeron veinte trabajadores sanitarios (TS). Medimos anticuerpos contra las proteínas N y S de SARS-CoV-2 y realizamos el ensayo de liberación de interferón-gamma (IFNγ) en sangre completa (IGRA) frente a péptidos de la proteína S. IFNγ se determinó mediante dos métodos de detección: CLIA y ELISA. Resultados: IGRA detectó respuesta celular T en TS tanto infectados como vacunados. La correlación de los dos métodos de detección de IFNγ fue muy alta (R >0,8) y la sensibilidad y la especificidad variaron entre 100 y 86% y 100-73% respectivamente. Hubo una concordancia muy alta entre los niveles de anticuerpos específicos y el ensayo IGRA aunque la correlación cuantitativa fue relativamente baja. En el grupo de infectados, una dosis de vacuna fue suficiente para alcanzar el «plateau¼ de respuesta inmune. IGRA fue claramente positivo en un profesional vacunado inmunosuprimido que presentaba anticuerpos contra la proteína S negativos. Conclusiones: IGRA frente a péptidos de la proteína-S es susceptible de automatización y constituye una herramienta prometedora para medir la respuesta inmune celular frente a SARS-CoV-2; es aplicable a un gran número de muestras y puede servir para valorar la protección, particularmente en los grupos vulnerables en riesgo de volver a exponerse a la infección, como los TS.

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BACKGROUND: Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex (MTBC) and is endemic in West Africa, where it causes up to half of all cases of pulmonary tuberculosis. Here, we report the first isolation of Mycobacterium africanum from the pericardial effusion culture of a patient with tuberculous pericarditis. CASE PRESENTATION: A 31-year-old man, native from Senegal, came to the emergency room with massive pericardial effusion and cardiac tamponade requiring pericardiocentesis. M. africanum subtype II was identified in the pericardial fluid. The patient completed 10 months of standard treatment, with a favorable outcome. CONCLUSIONS: We report the first case of tuberculous pericarditis caused by Mycobacterium africanum, which provide evidence that this microorganism can cause pericardial disease and must be considered in patients from endemic areas presenting with pericardial effusion.

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(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-×¥-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.

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INTRODUCTION: The diagnosis of smear-negative pulmonary tuberculosis (SNPTB) is challenging. Interferon gamma-release assays (IGRAs) may be helpful in early diagnosis among these patients resulting in prompt treatment and favorable outcomes. METHODS: We performed a comprehensive search from each databases' inception to April 5, 2021. The studies that provided sufficient data regarding the sensitivity and specificity of IGRAs included QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB, or QuantiFERON-TB Gold Plus for diagnosis of SNPTB were included. RESULTS: Of 1,312 studies screened, 16 studies were included; 11 QFT-GIT, 2 T-SPOT.TB, and 3 QFT-GIT and T-SPOT.TB. For diagnosis of SNPTB, QFT-GIT had sensitivity of 0.77 (95% CI 0.71-0.82), specificity of 0.70 (95% CI 0.58-0.80), diagnostic odds ratio (DOR) of 8.03 (95% CI 4.51-14.31), positive likelihood ratio (LR) of 2.61 (95% CI 1.80-3.80), negative LR of 0.33 (95% CI 0.25-0.42), and area under receiver operating characteristic (AUROC) of 0.81 (95% CI 0.77-0.84). T-SPOT.TB had sensitivity of 0.74 (95% CI 0.71-0.78), specificity of 0.71 (95% CI 0.49-0.86), DOR of 6.96 (95% CI 2.31-20.98), positive LR of 2.53 (95% CI 1.26-5.07), negative LR of 0.36 (95% CI 0.24-0.55), and AUROC of 0.77 (95% CI 0.73-0.80). The specificity seemed lower in the subgroup analyses of studies from high tuberculosis burden counties compared to the studies from low tuberculosis burden. CONCLUSION: IGRAs do have insufficient diagnostic performance for SNPTB. However, the tests are still helpful to exclude tuberculosis among patients with low pre-test probability. Registry: PROSPERO: CRD42021274653.

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INTRODUCTION: Diabetes mellitus (DM) is a known risk factor for tuberculosis (TB), leading to an approximate three-fold higher risk of developing active TB. However, epidemiological studies on the prevalence of latent TB infection (LTBI) in DM patients are lacking. In this study, we investigated the presence of LTBI and determined risk factors for LTBI in DM patients. METHODOLOGY: We conducted a cross-sectional study at Taipei Medical University-Shuang Ho Hospital in northern Taiwan. The study population comprised DM patients (aged 20-70 years) attending a metabolism outpatient clinic between February 2011 and February 2013, excluding patients who were suspected or confirmed to have active TB. Venous blood samples were drawn from patients to detect LTBI using the QuantiFERON-TB Gold In-Tube (QFT-GIT) method. RESULTS: We enrolled 1120 patients with DM. The QFT-GIT showed positive results for 241 people (21.5%) and negative results for 879 people (78.5%). The mean age at QFT-GIT positivity was 58.2 years, which was significantly dissimilar to the mean age at QFT-GIT negativity, which was 55.0 years (p < 0.001). Multivariate logistic regression indicated that the trend of QFT-GIT positivity increased after the age of 50 years. Effective glycemic control did not differ significantly between QFT-GIT-positive and -negative patients. Moreover, men were predominant were predominant in both QFT-GIT-positive and -negative patients. CONCLUSIONS: More than one-fifth of DM patients have LTBI. Among the DM patients, those older than 50 years may have a higher risk of LTBI. Moreover, effective glycemic control did not differ significantly in patients with LTBI.

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Elderly patients constitute a significant proportion of patients with psoriasis. Nonetheless, treatment for older patients is more challenging than that for younger ones. Biologic agents are preferable to other systemic drugs for elderly patients with moderate-to-severe psoriasis owing to their high efficacy and favorable tolerability. However, there are limited data on tuberculosis infection risk in elderly patients with psoriasis receiving biologic therapy. This study aimed to evaluate the risk of active tuberculosis and latent tuberculosis infection, assess the serial interferon-gamma release assay results, and evaluate treatment compliance and adverse effects of latent tuberculosis infection treatment in elderly patients with psoriasis on biologic therapy. In this single-center retrospective study, medical charts of elderly patients (age ≥ 65 years) with psoriasis who were treated with a biologic agent (guselkumab, adalimumab, secukinumab, or ustekinumab) between January 2015 and December 2020 were reviewed. We analyzed the results of chest X-rays and those of whole-blood interferon-gamma release assays performed for latent tuberculosis infection screening at baseline (IGRA0) and subsequently at follow-up after initiating biologic therapy (IGRA1). In total, 90 patients underwent IGRA0; 46 (51.11%) of them had latent tuberculosis infection before starting biologic therapy. Overall, four and two patients experienced seroconversion and active tuberculosis during biologic therapy, respectively. The interferon-gamma release assay reversion rate was 29.1%, and the interferon-gamma level significantly decreased in all patients after latent tuberculosis infection treatment (p = 0.004). Latent tuberculosis infection treatment was well tolerated in elderly patients (completion rate, 100%). The risk of latent tuberculosis infection in elderly patients with psoriasis on biologic therapy was comparable to that previously reported for all age groups. However, the active tuberculosis rate was relatively higher.

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In December 2019, a case of atypical pneumonia was reported in Wuhan, China. It was named COVID-19 and caused by SARS-CoV-2. In a few months, scientific groups around the world developed vaccines to reduce the disease's severity. The objective was to evaluate the humoral and cellular immune response post immunization with three different vaccination schedules administered in Chile until January 2022. Sixty volunteers were recruited with a three-dose schedule, who had no history of infection nor close contact with a positive patient. IgG against the spike antigenic domain was detected, and the neutralization capacity against two groups of variants, Original/Alpha and Beta/Gamma, was also measured. Finally, the cellular response with interferon release was measured through IGRA. Results showed that there were significant differences in the neutralizing antibodies for the original and alpha variant when comparing three Comirnaty doses with Coronavac and Vaxzevria. A high number of reactive subjects against the different SARS-CoV-2 variants, alpha, gamma, and delta, were observed, with no significant differences between any of the three schemes, confirming the existence of a cellular immune response against SARS-CoV-2. In conclusion, the three vaccine schemes generated a cellular immune response in these volunteers.

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Interferon-gamma release assays (IGRAs) are widely used in the diagnosis of Mycobacterium tuberculosis (M. tuberculosis) infection by detecting interferon-γ released by previously sensitized T-cells in-vitro. Currently, there are two assays based on either enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot (ELISPOT) technology, with several generations of products available. The diagnostic value of IGRAs in the immunocompromised population is significantly different from that in the immunocompetent population because their results are strongly affected by the host immune function. Both physiological and pathological factors can lead to an immunocompromised situation. We summarized the diagnostic value and clinical recommendations of IGRAs for different immunocompromised populations, including peoplewith physiological factors (pregnant and puerperal women, children, and older people), as well as people with pathological factors (solid organ transplantation recipients, combination with human immunodeficiency virus infection, diabetes mellitus, end-stage renal disease, end-stage liver disease, and chronic immune-mediated inflammatory diseases). Though the performance of IGRAs is not perfect and often requires a combination with other diagnostic strategies, it still has some value in the immunocompromised population. Hopefully, the newly developed IGRAs could better target this population.