Clinical characteristics and risk factors for antituberculosis drug-induced hypersensitivity.

AIMS: The aim of this study was to explore the clinical characteristics and risk factors for hypersensitivity reactions induced by antituberculosis drugs. METHODS: A retrospective analysis was conducted on the medical records of patients with active tuberculosis (TB) treated in the TB ward at West China Hospital, Sichuan University, from November 2010 to April 2020. RESULTS: Out of 7106 patients with active tuberculosis, 205 experienced hypersensitivity reactions to antituberculosis drugs; the incidence of hypersensitivity was 2.9%. The predominant clinical manifestation was a rash, observed in 57.1% (117/205) of these cases. Additionally, 19.0% (39/205) of patients presented with concurrent liver injury. The laboratory parameters white blood cell count, total lymphocyte count, monocyte count, eosinophil count, basophil count, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly elevated in patients with hypersensitivity compared to those without. In 38 patients who tested positive for oral antituberculosis drug provocation, 14 (36.8%) were allergic to more than two antituberculosis drugs. Significant risk factors included being female (odds ratio [OR] = 1.387, 95% confidence intervals [CI]: 1.016-1.894), under 65 years of age (OR = 1.826, 95% CI: 1.145-2.913), existing liver disease (OR = 2.464, 95% CI: 1.822-3.333) and a history of allergic diseases (OR = 6.633, 95% CI: 2.681-16.406) and were significantly correlated with hypersensitivity to antituberculosis drugs. CONCLUSIONS: Hypersensitivity reactions to antituberculosis drugs primarily affect the skin, with significant associations observed with liver injury. Females, individuals younger than 65 years, those with pre-existing liver disease and patients with a history of allergic diseases are at elevated risk for hypersensitivity.

Clinical risk factors for moderate and severe antituberculosis drug-induced liver injury.

Objective: To analyze the clinical and laboratory characteristics and to identify predictors of moderate to severe anti-tuberculosis drug-induced liver injury (ATB-DILI) in patients with tuberculosis. Methods: This prospective study enrolled Tuberculosis (TB) patients treated with first-line anti-tuberculosis drugs at the Affiliated Hospital of Zunyi Medical University between May 2022 and June 2023. The occurrence of ATB-DILI was monitored, and demographic and clinical data were gathered. We analyzed risk factors for the development of moderate to severe ATB-DILI. Results: ATB-DILI was detected in 120 (10.7%) of the patients, with moderate to severe ATB-DILI occurring in 23 (2.0%) of the 1,124 patients treated with anti-tuberculosis treatment. Multivariate cox regression analysis identified malnutrition (HR = 4.564, 95% CI: 1.029-20.251, p = 0.046) and hemoglobin levels <120 g/L (HR = 2.825, 95% CI: 1.268-11.540, p = 0.017) as independent risk factors for moderate to severe ATB-DILI. Conclusion: The incidence of moderate to severe ATB-DILI was found to be 2.0%. Malnutrition and hemoglobin levels below 120 g/L emerged as significant independent risk factors for the occurrence of moderate to severe ATB-DILI in this patient population.

Host factors associated with false negative results in an interferon-γ release assay in adults with active tuberculosis.

Objective: To identify host factors associated with false-negative results of interferon-γ release tests in adults with active tuberculosis. Methods: The clinical data of 943 patients with active tuberculosis diagnosed by acid-fast smear staining, Mycobacterium tuberculosis culture, Mycobacterium tuberculosis PCR and pathological examination at West China Hospital of Sichuan University were retrospectively analysed. According to the results of the interferon γ release test (IGRA), the patients were divided into the IGRA- group and IGRA+ group. Logistic regression was used to analyze the sociodemographic data and clinical characteristics of participants in the IGRA- group and IGRA+ group. Results: Among 943 patients with active tuberculosis, 174 (18.5 %) were IGRA negative (false negative), and 769 (81.5 %) were IGRA positive. Multivariate logistic regression analysis identified the following characteristics independently associated with IGRA negativity: age (OR: 1.02; 95 % CI: 1.01 1.03; p = 0.006), anti-tuberculosis treatment >1 month (OR: 1.68; 95 % CI: 1.12 2.52; p = 0.013), HIV infection (OR: 9.48; 95 % CI: 3.23 27.85; p = 0.000), combined with connective tissue diseases (OR: 2.78; 95 % CI: 1.30 5.94; p = 0.008) and low hemoglobin (OR: 0.99; 95 % CI: 0.98 1.00; p = 0.044) was associated with an increased false-negative probability of IGRA. Conclusion: Age, anti-tuberculosis therapy >1 month, coinfection with HIV, coassociated connective tissue disease and decreased hemoglobin were identified as risk factors for false-negative results of IGRA. Our results suggest a careful interpretation of IGRA in adults with these characteristics.

Arteriovenous thrombosis in a patient with miliary tuberculosis complicated by a left ventricular mass and its treatment.

INTRODUCTION: Tuberculosis (TB) is considered one of the two greater long-term global public health threats than the coronavirus disease 2019 (COVID-19) pandemic. Although venous thromboembolism has a low prevalence of 3.5% among patients with active TB, miliary TB complicated by arteriovenous thrombosis is a rare and potentially life-threatening condition. CASE STUDY: We present here an unusual case of a 32-year-old man with a two-month history of shortness of breath and painful swelling in the right lower extremity. In addition, elevated plasma levels of platelets, white blood cells, neutrophils, and D-dimer were observed upon his admission to the hospital. The patient was diagnosed with miliary TB complicated by arteriovenous thrombosis in the right lower extremity and a left ventricular mass measuring 3.5 × 1.7 cm. He was successfully treated with anti-TB drugs and low molecular weight heparin followed by warfarin, aspirin and clopidogrel. CONCLUSIONS: This case study demonstrates that a patient with miliary TB complicated by arteriovenous thrombosis and a left ventricular mass can be cured with timely diagnosis and appropriate treatment. The implications of this report are to raise awareness about miliary TB and arteriovenous thrombosis, to improve diagnosis and treatment, and to reduce patient mortality through sharing our successful experience with clinicians and healthcare providers in the developing countries of the world.

Drug transdermal delivery by electrophonophoresis can increase the concentration of rifampicin in the pleural effusion of patients with tuberculous pleurisy but has no effect on the concentration of rifampicin in plasma.

BACKGROUND: Electrophonophoresis (EP) has been widely used in various clinical fields. The purpose of this study was to evaluate the dermal permeability of rifampicin (RIF) in patients with tuberculous pleurisy assisted by EP and to verify the clinical application of this percutaneous drug delivery system in the treatment of tuberculous pleurisy, verify the system's influencing factors, and determine whether plasma drug concentration was increased. METHOD: Patients were given oral isoniazid 0.3-0.4 g, rifampicin 0.45-0.60 g, pyrazinamide 1.0-1.5 g and ethambutol 0.75 g according to their body weight once a day. After 5 days of anti-tuberculosis treatment, 3 ml of rifampicin was delivered transdermally with EP. Pleural effusion and peripheral blood samples in patients were collected at and after dosing. The drug concentration in the samples was determined by high-performance liquid chromatography. RESULT: The median plasma concentration (interquartile ranges) of RIF in 32 patients was 8.80 (6.65, 13.14) µg/ml before RIF transdermal injection plus EP and decreased to 8.09 (5.58, 11.82) µg/ml after 30 min of RIF transdermal injection plus EP. The RIF concentration in pleural effusion was higher than that before RIF-transdermal plus EP. In patients who received RIF via EP transdermal administration, the concentration of the drug at the local site was statistically higher than the concentration at the local site prior to penetration. However, no such enhancement was observed in plasma after transdermal administration of RIF. CONCLUSION: EP can effectively increase the concentration of rifampicin in the pleural effusion of tuberculous pleurisy and has no effect on the circulating plasma concentration. The increased concentration of the drug in the lesion helps to destroy the bacteria.

Efficacy of BCG Vaccination against COVID-19: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Beneficial off-target effects of the Bacillus Calmette-Guérin (BCG) vaccination might offer general protection from respiratory tract infections. We conducted a systematic review and meta-analysis of published randomized controlled trials (RCTs) to ascertain BCG vaccination effectiveness against COVID-19. We looked up English RCTs from 1 January 2019 to 15 November 2022 in Embase, the Cochrane Library, and the Web of Science in this systematic review and meta-analysis. Nine RCTs, including 7963 participants, were included. The infection rate of COVID-19 was not decreased in people who were vaccinated with BCG (OR, 0.96; 95% CI, 0.82-1.13; I2 = 4%), and the BCG vaccination group did not have decreased COVID-19 related-hospitalization (OR, 0.66; 95% CI, 0.37-1.18; I2 = 42%), admission to the ICU (OR, 0.25; 95% CI, 0.05-1.18; I2 = 0%), and mortality (OR, 0.64; 95% CI, 0.17-2.44; I2 = 0%) compared with the control group. There is not sufficient evidence to support the use of BCG vaccination in the prevention of COVID-19 infection and severe COVID-19 and avoid overstating the role of BCG vaccination leading to its misuse.

Associations between nutritional and immune status and clinicopathologic factors in patients with tuberculosis: A comprehensive analysis.

Objective: This study was designed to assess and analyze nutritional status (NS) and immune status in patients with tuberculosis. Methods: A retrospective analysis was conducted on 93 TB patients hospitalized in the tuberculosis ward of the West China Hospital of Sichuan University. Subgroup comparisons were made according to age (<65 years and ≥65 years), nutritional risk score 2002 (NRS 2002 <3 and ≥3), tuberculosis location [pulmonary tuberculosis and extrapulmonary tuberculosis (including pulmonary tuberculosis complicated with extrapulmonary tuberculosis)], and prognostic nutrition index (PNI) (<45 vs ≥45). Results: Significantly increased weight loss was associated with extrapulmonary tuberculosis (P =0.0010). Serum albumin (P =0.0214), total lymphocyte count (P = 0.0009) and PNI (P = 0.0033) were significantly decreased in older patients. Neutrophils/lymphocytes (NLR) (P =0.0002), monocytes/lymphocytes (MLR) (P < 0.0001), and platelets/lymphocytes (PLR) (P =0.0107) were higher. According to NRS 2002, higher nutritional risk was associated with lower body weight and body mass index (BMI) (P < 0.0001), higher weight loss (P = 0.0012), longer duration of hospitalization (P =0.0100), lower serum albumin level and hemoglobin concentration (P <0.01), lower creatinine level, and lower PNI (P < 0.01). 0.0001), lower total lymphocyte count (P = 0.0004), higher neutrophil and monocyte counts (P <0.05), and higher NLR (P = 0.0002), MLR (P = 0.0006), and PLR (P = 0.0156). Lower PNI was associated with lower body weight (P = 0.0001) and BMI (P =0.0074), lower total protein, albumin, and hemoglobin concentrations (P < 0.0001), and lower total lymphocyte count (P < 0.0001) and creatinine levels (P = 0.0336), higher age (P =0.0002) and NRS 2002 score, P < 0.0001), longer hos-pital stay (P = 0.0003), higher neutrophil count (P = 0.0042), and NLR, MLR, and PLR (P <0.0001) were significantly correlated. In multivariate logistic regression analysis, weight loss (OR: 0.209, 95% CI: 0.060-0.722; p =0.013) was significantly associated with higher nutritional risk (NRS 2002≥3). In multiple linear regression analysis, the NRS 2002 score was higher (B=2.018; p =0.023), and extrapulmonary tuberculosis (B=-6.205; p =0.007) was linked with a longer duration of hos-pitalization. Conclusions: Older tuberculosis patients are at nutritional risk, and older patients (≥65 years old) need to pay attention to nutritional monitoring and intervention. Older TB patients and those at risk of malnutrition have increased immune ratio and impaired immune function. Management of TB patients using basic diagnostic tools to assess nutritional and immune status and calculate PNI and immunological indexes (NLR, MLR, PLR) to improve treatment outcomes.

Upward trends in new, rifampicin-resistant and concurrent extrapulmonary tuberculosis cases in northern Guizhou Province of China.

Similar to global trends, the incidence rate of tuberculosis (TB) in China declined from 2000 to 2018. In this study, we aimed to evaluate TB trends in northern Guizhou Province and identify risk factors associated with rifampicin-resistant (RR) and concurrent extrapulmonary TB (EPTB). We analyzed data of TB patients hospitalized in Affiliated Hospital of Zunyi Medical University from 2011 to 2018, and assessed correlations between demographic characteristics of patients and RR-TB as well as concurrent EPTB. Our results showed that numbers of new, retreated, RR-TB and concurrent EPTB cases increased gradually from 2011 to 2018. Retreated patients had the highest odds of RR-TB but a lower likelihood of concurrent EPTB compared to new patients. Patients between 21 and 40 years of age had a higher likelihood of RR-TB compared to those 20 years and younger. Female patients and patients from Bijie city as well as the Miao ethnic minority had higher odds of concurrent EPTB. In summary, our data demonstrate upward trends in new, rifampicin-resistant and concurrent extrapulmonary TB cases in northern Guizhou Province of China, which should not be overlooked especially during and post the COVID-19 pandemic because TB is a greater long-term global health threat than COVID-19.

Clinical Efficacy and Safety of Tanreqing Injection for Pulmonary Infection in Patients with Tuberculosis: A Meta-Analysis.

BACKGROUND: Tanreqing injection (TRQ) is often used in the treatment of pulmonary infection in patients with tuberculosis (TB). But its efficacy and safety are still unclear; to further reveal its efficacy and safety, the authors systematically evaluated all relevant trials. METHODS: The authors searched published trials using the search strategy as (Tanreqing OR "Tanreqing injection") AND ("Tuberculosis" [MeSH] OR Tuberculosis OR TB) in Embase, PubMed, CNKI, VIP, Wanfang Database, CBM and CENTRAL, and ongoing trials in Chinese and U.S. clinical trials and World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) (established to January 2017). The authors evaluated the methodological bias risk of all included trials using the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0), extracted data following the PICO principles, and synthesized the data using meta-analysis. RESULTS: Twenty-six RCTs involving 2404 patients were included. In TRQ alone versus antibiotics, the merged risk ratio (RR) values and their confidence interval (95% CI) of meta-analysis for overall efficacy, lesion absorption, and bacterial clearance were as follows: 1.05 (0.99-1.10), 0.98 (0.89-1.08), and 1.36 (1.09-1.70). All differences were not statistically significant. In TRQ plus antibiotics versus antibiotics, the RR values and their 95% CI of overall efficacy, lesion absorption, and bacterial clearance were as follows: 1.17 (1.10-1.25), 1.24 (1.11-1.38), and 1.61 (1.36-1.90). All differences were statistically significant. Except for the bacterial clearance, sensitivity analyses showed that the overall efficacy had good stability. CONCLUSIONS: TRQ may have the same overall efficacy as antibiotics in pulmonary infection in patients with TB. TRQ plus antibiotics may improve the clinical efficacy. TRQ may have synergistic effect to antibiotics through bacteriostatic activity and eliminating inflammatory mediators. Its antibacterial activity may be better than some antibiotics and does not increase adverse drug reaction. But all these need new evidences for further investigation.