Comparison of active tuberculosis occurrence associated with Janus kinase inhibitors and biological DMARDs in rheumatoid arthritis.

OBJECTIVES: This study aimed to evaluate the risk of tuberculosis associated with the use of Janus kinase (JAK) inhibitors or biological disease-modifying antirheumatic drugs (bDMARDs) in patients diagnosed with rheumatoid arthritis (RA) in South Korea. METHODS: In this nationwide matched-cohort study, we retrospectively identified adult patients with new-onset RA from the National Health Insurance Service database who were prescribed bDMARDs or JAK inhibitors and recently underwent latent tuberculosis infection (LTBI) screening during 2012‒2021, and followed them up until the end of 2022 for the development of active tuberculosis. HRs were estimated using Cox proportional hazards regression in a propensity score-matched cohort. RESULTS: Among 16 760 matched patients with RA (3352 JAK inhibitor users and 13 408 bDMARD users), 18.8% received tuberculosis preventive therapy for LTBI. Overall, JAK inhibitor users had a significantly lower risk of tuberculosis than bDMARD users (HR (95% CI)=0.37 (0.22 to 0.62)). Among the patients treated for LTBI, patients with low treatment adherence had a significantly higher risk than those without LTBI (HR (95% CI)=2.78 (1.74 to 4.44)). Patients without LTBI and using JAK inhibitors had a significantly lower risk of tuberculosis across all ages and sexes compared with bDMARD users. CONCLUSION: Patients with RA using JAK inhibitors have a significantly lower risk of active tuberculosis than bDMARD users in South Korea; however, patients with RA having LTBI are equally at risk regardless of the treatment received (JAK inhibitor vs bDMARD). Therefore, vigilant tuberculosis monitoring, especially in patients with low adherence to tuberculosis preventive therapy, is essential.

Hematological parameters in newly diagnosed TB patients: A systematic review and meta-analysis.

Despite all efforts, tuberculosis (TB) remains one of the 10 leading causes of death worldwide. The hematopoietic system is seriously affected by TB and there is little information about the hematological profile of patients with TB. In this regard, this systematic review and meta-analysis aimed to assess hematological parameters among newly diagnosed TB patients. Relevant papers were found by searching in the PubMed database until April 2023. Fifteen papers involving 3354 patients were included. One-sample meta-analysis revealed the low pooled mean values for Hgb of 11.679 g/dl (95 % CI: 10.982-12.377) and the increased pooled ESR of 63.569 mm/h (95 % CI: 57.834-69.304) among newly diagnosed TB patients. The pooled prevalence of anemia, leukocytosis, thrombocytosis, and lymphopenia was 61.6 % (95 % CI: 45.4-75.6 %), 45.9 % (95 % CI: 39.1-52.9 %), 31.9 % (95%CI: 15-55.3 %) and 23.1 % (95%CI: 5.4-61.5 %) between TB patients, respectively. From a two-sample meta-analysis, the RBC and HgB values for TB patients were significantly lower than that of healthy controls (p < 0.05). Awareness of common blood abnormalities like elevated ESR, leukocytosis, and anemia in newly diagnosed TB patients helps physicians in early diagnosis and better management of disease.

Risk of tuberculosis after endoscopic resection and gastrectomy in gastric cancer: nationwide population-based matched cohort study.

BACKGROUND: This study aimed to investigate the association between gastrectomy and endoscopic resection for gastric cancer and the subsequent tuberculosis incidence. METHODS: We conducted a nationwide matched cohort study using data from the Korea National Health Insurance Service from 2013 to 2019. We created two cohorts: patients who underwent gastrectomy and those who had endoscopic resection. Each patient was matched 1:1 with an unexposed individual based on index year, age, sex, income, and various comorbidities. The primary outcome was the incidence of tuberculosis during the follow-up period. RESULTS: Our study comprised 90,886 gastrectomy patients and 46,759 endoscopic resection patients. The tuberculosis incidence was significantly higher in the gastrectomy group compared to its matched non-gastrectomy group (IRR 1.69, 95% CI 1.43-1.99, p < .001). In contrast, there was no significant difference in tuberculosis incidence between the endoscopic resection group and its matched non-resection group (IRR 0.95, 95% CI 0.75-1.19, p = 0.627). The Kaplan-Meier cumulative incidence also did not differ between the two groups. However, tuberculosis incidence significantly increased in the first year after endoscopic resection. CONCLUSION: Gastrectomy for gastric cancer is associated with a higher incidence of subsequent tuberculosis, while no significant association was observed for endoscopic resection. However, tuberculosis incidence increases significantly during the first year after endoscopic resection.

Pregnancy and neonatal outcomes in infertile patients with positive tuberculin skin test results.

RESEARCH QUESTION: Do infertile women with positive tuberculin skin test (TST) results have a higher risk of adverse pregnancy outcomes after IVF or intracytoplasmic sperm injection and embryo transfer (ICSI-ET) and does preventive anti-tuberculosis treatment applied to infertile women with positive TST results before IVF/ICSI-ET affect pregnancy and neonatal outcomes? DESIGN: This was a retrospective cohort analysis of 6283 infertile women who underwent IVF/ICSI-ET treatment for the first time at the Reproductive Hospital affiliated to Shandong University from November 2016 to September 2022. None of the participants had prior tuberculosis or active tuberculosis. According to their TST results, 5947 patients who had never received preventive anti-tuberculosis treatment were divided into a TST-positive group (1704 cases) and a TST-negative group (4243 cases). A total of 504 patients with TST (+++) results (using the 20 mm sclerosis threshold) were divided into a treated TST (+++) group (336 cases) and an untreated TST (+++) group (168 cases) according to whether they received preventive anti-tuberculosis treatment before IVF/ICSI-ET. The outcome measures were pregnancy outcomes and neonatal outcomes. RESULTS: There were no significant differences in pregnancy or neonatal outcomes between the TST-positive group and the TST-negative group (P > 0.05). In the TST (+++) group, there were no significant differences in pregnancy or neonatal outcomes between the treated TST (+++) group and the untreated TST (+++) group (P > 0.05). CONCLUSIONS: For infertile women undergoing IVF/ICSI-ET without prior tuberculosis or active tuberculosis, positive TST results and preventive anti-tuberculosis treatments prior to IVF/ICSI-ET do not affect pregnancy or neonatal outcomes.

Ambient PM2.5 exposures could increase risk of tuberculosis recurrence.

BACKGROUND: The effect of ambient PM2.5 on the incidence of tuberculosis (TB) has been investigated in epidemiological studies. However, they did not separately study new and relapsed TB infection and focused on relatively short-term effects of PM2.5. In this regard, we examined the associations of long-term PM2.5 exposures with both new and relapsed TB incidences in South Korea, where the disease burden of TB is greatest among high-income countries. METHODS: An area-level ecological study of 250 districts was conducted from 2015 to 2019. Age- and sex-standardized TB incidence ratios for each district and year were used as outcome variables, and their associations with PM2.5 concentrations for one to five-year average were examined. Negative binomial regression models incorporating spatiotemporal autocorrelation were employed using integrated nested Laplace approximations. Stratified analyses were conducted by type of TB (total, new, and relapsed cases). RESULTS: Districts with higher PM2.5 concentrations tended to have significantly higher TB recurrence rate. The relative risks per 10 µg/m3 PM2.5 increase were 1.218 (95% credible interval 1.051-1.411), 1.260 (1.039-1.527) and 1.473 (1.015-2.137) using the two, three and five-year average PM2.5 exposures, respectively. CONCLUSIONS: The results imply that interventions for reducing air pollution might help prevent TB recurrence.

Association of air pollutants and meteorological factors with tuberculosis: a national multicenter ecological study in China.

The impact of weather variability and air pollutants on tuberculosis (TB) has been a research hotspot. Previous studies have mostly been limited to a certain area or with a small sample size of cases, and multi-scale systematic studies are lacking. In this study, 14,816,329 TB cases were collected from 31 provinces in China between 2004 and 2018 to estimate the association between TB risk and meteorological factors and air pollutants using a two-stage time-series analysis. The impact and lagged time of meteorological factors and air pollutants on TB risk varied greatly in different provinces and regions. Overall cumulative exposure-response summary associations across 31 provinces suggested that high monthly mean relative humidity (RH) (66.8-82.4%, percentile56-100 (P56-100)), rainfall (316.5-331.1 mm, P96-100), PM2.5 exposure concentration (93.3-145.0 µg/m3, P58-100), and low monthly mean wind speed (1.6-2.1 m/s, P0-38) increased the risk of TB incidence, with a relative risk (RR) of 1.10 (95% CI: 1.04-1.16), 1.10 (95% CI: 1.03-1.16), 2.08 (95% CI: 1.18-3.65), and 2.06 (95% CI: 1.27-3.33), and attributable risk percent (AR%) of 9%, 9%, 52%, and 51%, respectively. Conversely, high monthly average wind speed (2.3-2.9 m/s, P54-100) and mean temperature (20.2-25.3 °C, P79-96), and low monthly average rainfall (2.4-25.2 mm, P0-7) and concentration of SO2 (8.1-21.2 µg/m3, P0-16) exposure decreased the risk of TB incidence, with an overall cumulative RR of 0.92 (95% CI: 0.87-0.98), 0.74 (95% CI: 0.59-0.94), 0.87 (95% CI: 0.79-0.95), and 0.72 (95% CI: 0.56-0.93), respectively. Our study provided insights into future planning of public health interventions for TB.

Drivers of sex differences in the South African adult tuberculosis incidence and mortality trends, 1990-2019.

Males have higher tuberculosis incidence and mortality rates than females. This study aimed to assess how sex differences in tuberculosis incidence and mortality could be explained by sex differences in HIV, antiretroviral treatment (ART) uptake, smoking, alcohol abuse, undernutrition, diabetes, social contact rates, health-seeking patterns, and treatment discontinuation. We developed an age-sex-stratified dynamic tuberculosis transmission model and calibrated it to South African data. We estimated male-to-female (M:F) tuberculosis incidence and mortality ratios, the effect of the abovementioned factors on the M:F ratios and PAFs for the tuberculosis risk factors. Over the period 1990-2019, the M:F ratios for tuberculosis incidence and mortality rates persisted above 1.0, and the figures reached 1.70 and 1.65, respectively, by the end of 2019. In 2019, HIV contributed greater increases in tuberculosis incidence among females than males (54.5% vs. 45.6%); however, females experienced more reductions due to ART than males (38.3% vs. 17.5%). PAFs for tuberculosis incidence due to alcohol abuse, smoking, and undernutrition, in men were 51.4%, 29.5%, and 16.1%, respectively, higher than females (30.1%, 15.4%, and 10.7%, respectively); the PAF due to diabetes was higher in females than males (22.9% vs. 17.5%). Lower health-seeking rates in males accounted for a 7% higher mortality rate in men. The higher burden of tuberculosis in men highlights the need to improve men's access to routine screening and ensure earlier diagnosis. Sustained efforts in providing ART remain critical in reducing HIV-associated tuberculosis. Additional interventions to reduce alcohol abuse and tobacco smoking are also needed.

Risk factors for the development of tuberculosis among the pediatric population: a systematic review and meta-analysis.

Pediatric tuberculosis is a major cause of mortality and morbidity in children due to high transmission, poor diagnostic tools, and various respiratory diseases mimicking TB. Identifying risk factors will provide evidence for clinicians to strongly relate their diagnosis to the associated pathology. Studies were retrieved from PubMed, Embase, and Google Scholar, systematically reviewed, and meta-analyzed for various risk factors and their association with pediatric TB. Meta-analysis depicted that four out of eleven risk factors were significant-contact with known TB cases (OR 6.42 [3.85,10.71]), exposure to smoke (OR 2.61 [1.24, 5.51]), overcrowding in the houses (OR 2.29 [1.04, 5.03]), and, poor household conditions (OR 2.65 [1.38, 5.09]). Although significant odds ratio estimates were obtained, we observed heterogeneity in the studies included.    Conclusion: The study findings demand the constant screening of risk factors such as contact with known TB cases, exposure to smoke, overcrowding, and, poor household conditions for the development of pediatric TB. What is Known: • Knowledge of the risk factors of a disease is of utmost importance in the planning and institution of its control measures. Well-established risk factors in the occurrence of TB in the pediatric group are HIV positivity, older age and close contact with a known case of TB. What is New: • In addition to what is already known; this review and meta-analysis has identified exposure to indoor smoking, overcrowding and poor household conditions as important risk factors for developing pediatric TB. • Implications of the study: The findings highlight that in addition to routine contact screening for the pediatric group, the children living in poor household conditions and getting exposed to passive indoor smoking demand more attention to prevent the development of pediatric TB.

Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement.

Importance: In the US, tuberculosis remains an important preventable disease, including active tuberculosis, which may be infectious, and latent tuberculosis infection (LTBI), which is asymptomatic and not infectious but can later progress to active disease. The precise prevalence rate of LTBI in the US is difficult to determine; however, estimated prevalence is about 5.0%, or up to 13 million persons. Incidence of tuberculosis varies by geography and living accommodations, suggesting an association with social determinants of health. Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on LTBI screening and treatment in asymptomatic adults seen in primary care, as well as the accuracy of LTBI screening tests. Population: Asymptomatic adults 18 years or older at increased risk for tuberculosis. Evidence Assessment: The USPSTF concludes with moderate certainty that there is a moderate net benefit in preventing active tuberculosis disease by screening for LTBI in persons at increased risk for tuberculosis infection. Recommendation: The USPSTF recommends screening for LTBI in populations at increased risk. (B recommendation).

Incidence and risk factors of tuberculosis in patients following gastrectomy or endoscopic submucosal dissection: a cohort analysis of country-level data.

BACKGROUND: Gastric cancer adversely affects nutrition and immunity, while increasing the risk of tuberculosis (TB). This study investigated the incidence and risk factors for TB in gastric cancer patients who had undergone gastrectomy or endoscopic submucosal dissection (ESD). METHODS: This retrospective cohort study was conducted using Korean national insurance claims data. We defined three study groups (total gastrectomy, subtotal gastrectomy, and ESD) of patients diagnosed with gastric cancer plus a cancer-free control group. The latent TB infection (LTBI) screening status, TB incidence, and potential confounders in each cohort were analyzed, and the risk of TB was analyzed using a Cox proportional hazard model. RESULTS: LTBI tests were performed in less than 1% of all patients, and the TB incidence rates were 473.8, 287.4, 199.4, 111.1 events/100,000 person-years in the total gastrectomy, subtotal gastrectomy, ESD, and control cohorts, respectively. Compared to the control cohort, the total gastrectomy cohort showed the highest hazard ratio (HR) for TB incidence (HR: 2.896, 95% CI: 2.559-2.337), while the ESD cohort showed a significantly increased risk (HR: 1.578, 95% CI: 1.957-1.980). Age, body mass index, and lack of exercise were risk factors in all cohorts. Comorbidities were also considered risk factors, depending on the cohort type. CONCLUSIONS: Patients who underwent gastrectomy or ESD had an increased risk of TB, and this risk was correlated with the scope of gastrectomy. Considering the low rate of LTBI diagnostic tests and increased risk of TB in the study cohorts, more specific and practical guidelines for TB management are required for gastric cancer patients.

The association between air pollutants, meteorological factors and tuberculosis cases in Beijing, China: A seven-year time series study.

BACKGROUND: Tuberculosis (TB) is a severe public health problem globally. Previous studies have revealed insufficient and inconsistent associations between air pollutants, meteorological factors and TB cases. Yet few studies have examined the associations between air pollutants, meteorological factors and TB cases in Beijing. OBJECTIVE: The purpose of this study was to explore the impact of air pollutants and meteorological factors on TB in Beijing, and to provide novel insights into public health managers to formulate control strategies of TB. METHODS: Data on the daily case of TB in Beijing during 2014-2020 were obtained from Chinese tuberculosis information management system. Concurrent data on the daily PM10, PM2.5, SO2, NO2, CO and O3, were obtained from the online publication platform of the Chinese National Environmental Monitoring Center. Daily average temperature, average wind speed, relative humidity, sunshine duration and total precipitation were collected from the China Meteorological Science Data Sharing Service System. A distributed lag non-linear model was fitted to identify the non-linear exposure-response relationship and the lag effects between air pollutions, meteorological factors and TB cases in Beijing. RESULTS: In the single-factor model, the excess risk (ER) of TB was significantly positively associated with every 10 µg/m3 increase in NO2 in lag 1 week (ER: 1.3%; 95% confidence interval [CI]: 0.4%, 2.3%) and every 0.1 m/s increase in average wind speed in lag 5 weeks (ER: 0.3%; 95% CI: 0.1%, 0.5%), and was negatively associated with every 10 µg/m3 increase in O3 in lag 1 week (ER: -1.2%; 95% CI: -1.8%, -0.5%), every 5 °C increase in average temperature (ER: -1.7%; 95% CI: -2.9%, -0.4%) and every 10% increase in average relative humidity (ER: -0.4%; 95% CI: -0.8%, -0.1%) in lag 10 weeks, respectively. In the multi-factor model, the lag effects between TB cases and air pollutants, meteorological factors were similar. The subgroup analysis suggests that the effects of NO2, O3, average wind speed and relative humidity on TB were greater in male or labor age subgroup, while the effect of CO was greater in the elderly. In addition, no significant associations were found between PM2.5, SO2, sunshine duration and TB cases. CONCLUSION: Our findings provide a better understanding of air pollutants and meteorological factors driving tuberculosis occurrence in Beijing, which enhances the capacity of public health manager to target early warning and disease control policy-making.

Surgical Management of Patients With GI Tuberculosis.

BACKGROUND: The Philippines ranks 10th in tuberculosis prevalence worldwide. Aside from pulmonary tuberculosis, GI tuberculosis remains an important cause of morbidity and mortality, particularly in endemic areas. OBJECTIVE: This study aimed to describe the clinicopathologic profile and surgical outcomes of patients with GI tuberculosis. DESIGN: Retrospective descriptive study. SETTING: Department of Surgery at the Philippine General Hospital, Manila, Philippines. PATIENTS: This study included all newly diagnosed cases of GI tuberculosis from January 1, 2009, to December 31, 2019. MAIN OUTCOME MEASURES: Clinical response to surgery. RESULTS: A total of 241 confirmed new cases were managed during an 11-year period. Of these, 208 patients (86.30%) underwent outright surgery, whereas the remaining patients (13.69%) received antituberculous therapy. Fifteen medically managed patients eventually required surgery, bringing the total surgically managed patients to 223. The patients' age ranged from 19 to 72 years, with a 1.9:1 male to female ratio. The most common complaint was abdominal pain. Intestinal obstruction was the most common indication for surgery. A right hemicolectomy was the most often performed procedure, with the ileocecal area as the most frequently involved segment. The most common histopathologic findings were epithelioid granuloma and caseation necrosis. Postoperative length of stay ranged from 0 to 59 days (mean, 7 days). Morbidity rate was 5.38% and mortality rate was 3.14%. Four deaths were operative and resulted from septic shock because of hollow viscus perforation. LIMITATIONS: This study was limited to histopathologic basis for diagnosis. CONCLUSION: The recommended initial therapy for all forms of extrapulmonary tuberculosis is a 6-month regimen of antituberculous therapy unless the organisms are known or suspected to be resistant to first-line drugs. Surgery is reserved for complications of intra-abdominal tuberculosis: obstruction, perforation, or severe bleeding. Timely surgical intervention, coupled with medical management led to the best outcomes for these patients. See Video Abstract at http://links.lww.com/DCR/C56. MANEJO QUIRRGICO DE PACIENTES CON TUBERCULOSIS GASTROINTESTINAL: ANTECEDENTES:Las Filipinas ocupa el décimo lugar en prevalencia de tuberculosis en todo el mundo. Aparte de la tuberculosis pulmonar, la tuberculosis gastrointestinal sigue siendo una causa importante de morbilidad y mortalidad, especialmente en las zonas endémicas.OBJETIVO:Este estudio tuvo como objetivo describir el perfil clinicopatológico y los resultados quirúrgicos de pacientes con tuberculosis gastrointestinal.DISEÑO:Estudio descriptivo retrospectivo.AJUSTE:Departamento de Cirugía del Hospital General de Filipinas, Manila, Filipinas.PACIENTES:Todos los casos de tuberculosis gastrointestinal recién diagnosticados desde el 1 de Enero del 2009 hasta el 31 de Diciembre del 2019.MEDIDAS DE RESULTADO PRINCIPAL:Respuesta clínica a la cirugía.RESULTADOS:Se manejaron un total de 241 casos nuevos confirmados durante un período de 11 años. De estos, 208 (86,30%) pacientes fueron intervenidos directamente quirúrgicamente mientras que el resto recibió tratamiento antituberculoso (13,69%). Quince pacientes manejados médicamente finalmente requirieron cirugía, lo que elevó el total de pacientes manejados quirúrgicamente a 223. Las edades de los pacientes oscilaron entre 19 y 72 años, con una proporción de 1,9: 1 entre hombres y mujeres. La queja más común fue el dolor abdominal. La obstrucción intestinal fue la indicación más frecuente para cirugía. La hemicolectomía derecha fue el procedimiento más realizado, siendo la zona ileocecal el segmento más afectado. Los hallazgos histopatológicos más comunes fueron granuloma epitelioide y necrosis caseosa. La estancia postoperatoria varió de 0 a 59 días (media, 7 días). Las tasas de morbilidad y mortalidad fueron 5,38% y 3,14%, respectivamente. Cuatro fueron muertes operatorias por choque séptico debido a perforación de víscera.LIMITACIONES:Este estudio se limitó a la base histopatológica para el diagnóstico.CONCLUSIÓN:La terapia inicial recomendada para todas las formas de tuberculosis extrapulmonar es un régimen de 6 meses de terapia antituberculosa a menos que se sepa o se sospeche que los organismos son resistentes a los medicamentos de primera línea. La cirugía se reserva para las complicaciones de la tuberculosis intraabdominal, es decir, obstrucción, perforación o hemorragia grave. La intervención quirúrgica oportuna, junto con el manejo médico, condujo a mejores resultados para estos pacientes. Consulte el Resumen del Video en http://links.lww.com/DCR/C56. (Traducción- Dr. Yesenia Rojas-Khalil).

Effect of Early Bacillus Calmette-Guerin Vaccination of Pediatric Severe Combined Immunodeficiency Patients on the Outcome of Hematopoietic Stem Cell Transplantation Using a Reduced-Intensity Conditioning Regimen.

The eminence of Bacillus Calmette-Guerin (BCG) vaccine in newborn vaccination programs has been conspicuous throughout the years, especially in low-income developing countries where tuberculosis is prevalent; however, application of the BCG vaccine is not without constraints, especially in patients afflicted with immunodeficiency diseases, such as severe combined immunodeficiency (SCID). The present study aimed to evaluate whether the administration of BCG vaccine at birth could improve the outcomes of hematopoietic stem cell transplantation (HSCT) in pediatric patients with SCID. In this study, 30 SCID patients who underwent HSCT using a reduced-intensity conditioning regimen (RIC) were followed-up for 2 years post-HSCT. The outcomes of HSCT were evaluated in both non-BCG-vaccinated patients (n = 12) and BCG-vaccinated patients (n = 18). Our results show a higher incidence of acute graft-versus-host disease (aGVHD), but not of chronic GVHD, in the BCG-vaccinated patients, and a similar overall survival (OS) rate in the 2 groups. We speculate that the similar OS rate in the 2 groups, despite the risk of BGC vaccination, was because this group received an RIC conditioning regimen. There was no other difference between the 2 groups. Considering the effect of the BCG vaccine on HSCT outcome, we suggest that the administration of BCG vaccine be deferred until age 3 months so that APT testing without the interference of maternal antibodies can be performed. However, this study could benefit from a larger cohort to further validate our findings, as the possible reason for some factors not being statistically significant was our small sample size.

Incidence and prevalence of tuberculosis in systemic lupus erythematosus patients: A systematic review and meta-analysis.

Background: Systemic lupus erythematosus (SLE) patients are particularly susceptible to infections, such as pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). This meta-analysis aimed to determine the incidence and prevalence of tuberculosis (TB) in SLE patients. Methods: The Web of Science, PubMed, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched for articles of relevant studies published from the dates the databases were established until April 30, 2022. The I2 statistic and Q test were used to evaluate heterogeneity among the analysed studies. Random-effects models were utilised and subgroup analyses were conducted for analysis of the study data. Results: A total of 35 studies with 46,327 SLE patients were eligible for analysis. The incidence and prevalence of TB among the SLE patients were 1.16 per 100 person-years (95% confidence interval (CI): 0.69-1.93) and 3.59% (95% CI: 2.57%-5.02%), respectively. The pooled prevalence of SLE-PTB and SLE-EPTB was 2.46% (95% CI: 1.73%-3.51%) and 1.42% (95% CI: 0.98%-2.06%), respectively. Subgroup analyses showed that the incidence of SLE-TB was higher in Africa and in countries with a high TB burden than in countries with a low TB burden. The prevalence of SLE-TB was elevated in Asia, in patients taking a mean daily dose of glucocorticoids ≥20 mg, in studies with small sample sizes (n <1000) and ended before 2001. Conclusions: The available evidence suggests that both the incidence and prevalence of TB in SLE patients are high. This study provides a more specific understanding of SLE-TB, which can help health policymakers in the development of preventive strategies for reducing the SLE-TB burden.

Prevalence of modifiable risk factors of tuberculosis and their population attributable fraction in Iran: A cross-sectional study.

BACKGROUND: The mycobacterium tuberculosis (Mtb) is necessary for the morbidity of tuberculosis (TB), but it is insufficient. Many risk factors increase the risk of disease among infected people. We aimed to estimate the prevalence of modifiable risk factors of TB and their related population attributable fraction (PAF) in the marginal population of Markazi province in Iran. DESIGN: In this cross-sectional study, the prevalence of the modifiable risk factors of TB was estimated. We designed and validated a questionnaire to determine the risk factors. The measures of association for the modifiable risk factors of TB were obtained via the review of published literature. We calculated the PAF for each modifiable risk factor. RESULTS: Out of the 1275 calculated sample size, 1146 people participated in this study, and the participation rate was 89.9%. The mean age was 39.26. Out of 1146 participants, 76% did not know anything regarding TB. The highest prevalence was related to the lack of physical activity (58.73%), lack of fish consumption (50.79%), lack of red meat consumption (21.20%), and secondhand smoke (19.02%). The highest PAF was related to secondhand smoke; this value based on the crude relative risk (RR) and crude odds ratio (OR) was 24.54% and 23.44%, respectively. Based on crude hazard ratio (HR) and crude OR, the PAF for smoking was 14.81% and 11.19%, respectively. PAF for lack of BCG vaccination based on the crude OR was 14.79%. CONCLUSION: Based on this study's results, poor nutrition, secondhand smoke, smoking, lack of BCG vaccination, and diabetes are the main prevalent modifiable risk factors for TB. The highest PAF for TB was related to secondhand smoke, smoking, lack of BCG vaccination, and diabetes.

Drug-level change and optimal dose adjustment of tacrolimus with the use of rifabutin for treating mycobacterial disease in solid organ transplant recipients.

BACKGROUND: Little is known about the change in drug level and the need for dose adjustment of calcineurin inhibitor when it is used with rifabutin in solid organ transplant (SOT) recipients. We aimed to analyze whether the drug level of tacrolimus significantly reduced after the use of rifabutin and to assess optimal adjustment of tacrolimus dose in SOT recipients. METHODS: Of the SOT recipients in a tertiary referral center in South Korea in 2000-2019, 50 patients who maintained an unchanged dose of tacrolimus after the use of rifabutin for treating mycobacterial disease were enrolled. Their medical records were reviewed retrospectively. RESULTS: The mean age of the patients was 53.9 ± 11.5 years. The most commonly transplanted organ was the liver (66.0%). The most common indication of rifabutin use was for treating active tuberculosis (78.0%). After rifabutin initiation, the trough level of tacrolimus decreased significantly to the subtherapeutic range in 38 (76.0%) patients. The drug levels of these 38 patients dropped from 7.2 to 3.8 ng/ml (p < .001) after rifabutin treatment. In these patients, the median 1.5-fold increase in the tacrolimus dose was required to restore the drug level to the within-therapeutic range. CONCLUSIONS: These findings indicate that careful tacrolimus drug-level monitoring and dose adjustment are necessary for most SOT recipients when rifabutin is administered for the treatment of mycobacterial disease.

Active tuberculosis infection in moroccan patients with rheumatic diseases under biologic therapy: A multicenter national study.

Background: The aim of this study was to evaluate the prevalence of active tuberculosis (TB) infection in Moroccan patients with rheumatic diseases under biologic therapy, and to describe the demographic characteristics of these patients as well as to explore potential risk factors. Methods: This 14-year nationally representative multicenter study enrolled Moroccan patients with rheumatic diseases who had been treated with biologic therapy. Patient medical records were reviewed retrospectively for demographic characteristics, underlying rheumatic diseases, associated comorbidities, and TB-related data. Results: In total, 1407 eligible patients were studied, detailed records were obtained for only 130 patients; 33 cases with active TB were identified at an estimated prevalence rate of 2.3%. The mean age was 42.9 ± 12 years and 75.8% were males. Ankylosing spondylitis accounted for 84.8% of active TB cases, and the majority of the cases (31/33) occurred among antitumor necrosis factor-alpha (TNF-α) users. A total of 8 out of 33 patients were positive at initial latent TB infection (LTBI) screening by tuberculin skin test and/or interferon-gamma release assay. Consumption of unpasteurized dairy products (odds ratio [OR], 34.841; 95% confidence interval [CI], 3.1-389.7; P = 0.04), diabetes (OR, 38.468; 95% CI, 1.6-878.3; P = 0,022), smoking (OR, 3.941; 95% CI, 1-159.9; P = 0.047), and long biologic therapy duration (OR, 1.991; 95% CI, 1.4-16.3; P = 0.001) were identified as risk factors for developing active TB. Conclusion: Moroccan patients with rheumatic diseases under anti-TNF-α agents are at an increased TB risk, especially when risk factors are present. Strict initial screening and regular monitoring of LTBI is recommended for patients living in high TB prevalence areas.

Increased Tuberculosis Incidence Due to Immunotherapy Based on PD-1 and PD-L1 Blockade: A Systematic Review and Meta-Analysis.

Objectives: In this study, we conducted a systematic review to determine tuberculosis (TB) incidence due to immunotherapy with programmed cell death protein-1 (PD-1)/PD ligand (PD-L1) blockade in cancer patients. Methods: We searched PubMed, Cochrance Library, Excerpt Medica Database (Embase), ClinicalTrials.gov, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure Database (CNKI), Wanfang and China Science and Technology Journal Database to identify studies between January 1, 2000 and April 30, 2021, on the reports of TB cases in patients treated with PD-1/PD-L1 blockade. Methodological quality of eligible studies was assessed, and random-effect model meta-analysis was performed to generate the pooled incidence estimate of TB cases in patients undergoing PD-1/PD-L1 therapy. Results: We initially identified 745 records, of which 27 studies ultimately met the inclusion criteria and were included in our meta-analysis. A total of 35 TB cases occurred among patients treated with PD-1/PD-L1 blockade. Nivolumab (51.4%) was the most frequently used PD-1/PD-L1 blockade for cancer treatment. In addition, pulmonary TB was the most common form of tuberculosis seen in 77.1% cases. Clinical outcomes were recorded in 18 patients, of whom 77.8% were cured or achieved remission, and 22.2% were died of TB. Pooled analysis determined that the TB rate in this population was 2,000 cases per 100,000 persons, and the estimated rate for TB associated with PD-1/PD-L1 blockade was 35 times higher than that in the general population. Conclusion: To conclude, our results demonstrate that the clinical use of PD-1/PD-L1 inhibitors significantly increases risk of TB reactivation. An extremely high mortality rate due to TB disease is noted in the patients with PD-1/PD-L1 blockade.

The impact of climate change on the risk factors for tuberculosis: A systematic review.

BACKGROUND: Tuberculosis (TB) continues to pose a major public health risk in many countries. The current incidence of disease exceeds guidelines proposed by the World Health Organisation and United Nations. Whilst the relationship between climate change and TB has surfaced in recent literature, it remains neglected in global agendas. There is a need to acknowledge TB as a climate-sensitive disease to facilitate its eradication. OBJECTIVE: To review epidemiological and prediction model studies that explore how climate change may affect the risk factors for TB, as outlined in the Global Tuberculosis Report 2021: HIV infection, diabetes mellitus, undernutrition, overcrowding, poverty, and indoor air pollution. METHODS: We conducted a systematic literature search of PubMed, Embase, and Scopus databases to identify studies examining the association between climate variables and the risk factors for TB. Each study that satisfied the inclusion criteria was assessed for quality and ethics. Studies then underwent vote-counting and were categorised based on whether an association was found. RESULTS: 53 studies met inclusion criteria and were included in our review. Vote-counting revealed that two out of two studies found a positive association between the examined climate change proxy and HIV, nine out of twelve studies for diabetes, eight out of seventeen studies for undernutrition, four out of five studies for overcrowding, twelve out of fifteen studies for poverty and one out of three studies for indoor air pollution. DISCUSSION: We found evidence supporting a positive association between climate change and each of the discussed risk factors for TB, excluding indoor air pollution. Our findings suggest that climate change is likely to affect the susceptibility of individuals to TB by increasing the prevalence of its underlying risk factors, particularly in developing countries. This is an evolving field of research that requires further attention in the scientific community.

Association between averaged meteorological factors and tuberculosis risk: A systematic review and meta-analysis.

Inconsistencies were discovered in the findings regarding the effects of meteorological factors on tuberculosis (TB). This study conducted a systematic review of published studies on the relationship between TB and meteorological factors and used a meta-analysis to investigate the pooled effects in order to provide evidence for future research and policymakers. The literature search was completed by August 3rd, 2021, using three databases: PubMed, Web of Science and Embase. Relative risks (RRs) in included studies were extracted and all effect estimates were combined together using meta-analysis. Subgroup analyses were carried out based on the resolution of exposure time, regional climate, and national income level. A total of eight studies were included after screening for inclusion and exclusion criteria. Our results show that TB risk was positively correlated with precipitation (RR = 1.32, 95% CI: 1.14, 1.51), while temperature (RR = 1.15, 95% CI: 1.00, 1.32), humidity (RR = 1.05, 95% CI: 0.99, 1.10), air pressure (RR = 0.89, 95% CI: 0.69, 1.14) and sunshine duration (RR = 0.95, 95% CI: 0.80, 1.13) all had no statistically significant correlation. Subgroup analysis shows that quarterly measure resolution, low and middle Human Development Index (HDI) level and subtropical climate increase TB risk not only in precipitation, but also in temperature and humidity. Moreover, less heterogeneity was observed in "high and extremely high" HDI areas and subtropical areas than that in other subgroups (I2 = 0%). Precipitation, a subtropical climate, and a low HDI level are all positive influence factors to tuberculosis. Therefore, residents and public health managers should take precautionary measures ahead of time, especially in extreme weather conditions.