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Tuberculous uveitis can be a manifestation of extrapulmonary tuberculosis or an allergic reaction to tuberculosis infection. The clinical signs and symptoms of other uveitis causes are generic, making a false diagnosis simple. We present a brief introduction to theoretical modelling and simulation in systems biology and explore the consequences of TB uveitis if left untreated. Patients were admitted to our hospital with recurrent fever. They had a previous definitive diagnosis of binocular uveitis and a positive interferon gamma release assay (IGRA) test result. At the time, there was no antituberculosis medicine available, and immunosuppressive and glucocorticoid therapy did not work. After the admission, their pleural fluid tested positive for Mycobacterium tuberculosis. No other causes to explain the fever were found. A diagnosis of tuberculosis was made, and their body temperature normalized after antituberculosis treatment and closed chest drainage. Vigilance should be exercised to rule out tuberculous uveitis in cases of unexplained uveitis; this calls for IGRA screening, tuberculin skin testing, and cyst imaging. For patients with latent tuberculosis infections, it is recommended to administer antituberculosis treatment, after excluding other possible causes, and to avoid using glucocorticoids in isolation. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate retrospectively extrapulmonary tuberculosis patients followed and treated in the infectious diseases clinic and outpatient clinic. Methods: The study included patients aged 18 years and older who were followed and treated with a diagnosis of extrapulmonary tuberculosis between January 1, 2013, and December 31, 2019. Data on the patient's demographics, clinical and laboratory findings, microbiological tests, histopathological examination results, radiological findings, treatments, and treatment durations were collected from patient files and the electronic document management system. Results: Of the 81 patients in the study, 49 (60.4%) were female, and 32 (39.6%) were male. The mean age was 49.55±18.85 years. Hypertension and diabetes mellitus were the most common comorbidities. Gastrointestinal system tuberculosis, musculoskeletal system tuberculosis, lymph node tuberculosis, and central nervous system tuberculosis were the most frequently observed clinical forms. Conclusions: Contrary to literature data, gastrointestinal system tuberculosis was found to be the most common form of extrapulmonary tuberculosis. Histopathological examinations were found to be at least as important and valuable as microbiological tests in the diagnosis of extrapulmonary tuberculosis. The rate of extrapulmonary involvement in tuberculosis is increasing worldwide. Tuberculosis should always be considered in differential diagnosis. [ABSTRACT FROM AUTHOR]

Antituberculosis drug‐induced liver injury (ATLI) is a major adverse effect during antituberculosis treatment. Early detection or prediction is essential to prevent ATLI in antituberculosis treatment patients. The purpose of this work is to explore the relationship between alanine aminotransferase (ALT) trajectories within 15 days of initial treatment and the risk of ATLI. Based on a historical cohort of patients hospitalized for antituberculosis treatment and group‐based trajectory modeling analysis, ALT trajectories within 15 days of initial treatment were determined. Conditional logistic regression model was used to estimate the association between different ALT trajectories and the risk of ATLI, and the corresponding odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with covariates. Based on the ALT levels within 15 days of initial treatment, a total of 853 patients were divided into four ALT trajectories. The incidence of ATLI significantly increased with the increase of ALT trajectories (2.33%, 4.38%, 5.90%, and 2.44%, respectively). Compared with trajectory 1, the adjusted OR for ATLI in trajectory 2, trajectory 3, and trajectory 4 were 2.448 (95% CI: 0.302–19.856, P = 0.402), 5.373 (95% CI: 0.636–45.411, P = 0.123), 11.010 (95% CI: 0.720–168.330, P = 0.085), respectively, and there was an increasing trend of ATLI risk (Ptrend = 0.015). Different ALT trajectories within 15 days of initial treatment were associated with different risk of ATLI, and it is necessary to pay attention to the ALT trajectory within 15 days of initial treatment to predict the occurrence of ATLI. [ABSTRACT FROM AUTHOR]

Tuberculosis is a worldwide public health problem, particularly in developing countries. Anti-tuberculosis treatment, which combines several drugs over several months, is potentially hepatotoxic. Hepatotoxicity spectrum of anti-tuberculosis drugs ranges from a simple transient disturbance of the liver tests to fulminant hepatitis, requiring immediate discontinuation of anti-tuberculosis drugs. The anti-tuberculosis drugs responsible are isoniazid, pyrazinamide and rifampicin. The best way to prevent hepatitis is to identify certain risk factors before starting treatment, and to ensure adequate monitoring. Anti-tuberculosis treatment, discontinued in the event of severe hepatotoxicity, may be reinstated once liver tests have returned to normal value. [ABSTRACT FROM AUTHOR]

ABSTRACTThe incidence of isoniazid (INH) resistant Mycobacterium tuberculosis is increasing globally. This study aimed to identify the molecular mechanisms behind the development of INH resistance in M. tuberculosis strains collected from the same patients during the standard course of treatment. Three M. tuberculosis strains were collected from a patient before and during antituberculosis (anti-TB) therapy. The strains were characterized using phenotypic drug susceptibility tests, Mycobacterial Interspersed Repeated Unit-Variable-Number Tandem Repeats (MIRU-VNTR), and whole-genome sequencing (WGS) to identify mutations associated with INH resistance. To validate the role of the novel mutations in INH resistance, the mutated katG genes were electroporated into a KatG-deleted M. tuberculosis strain (GA03). Three-dimensional structures of mutated KatG were modeled to predict their impact on INH binding. The pre-treatment strain was susceptible to INH. However, two INH-resistant strains were isolated from the patient after anti-TB therapy. MIRU-VNTR and WGS revealed that the three strains were clonally identical. A missense mutation (P232L) and a nonsense mutation (Q461Stop) were identified in the katG of the two post-treatment strains, respectively. Transformation experiments showed that katG of the pre-treatment strain restored INH susceptibility in GA03, whereas the mutated katG genes from the post-treatment strains rendered negative catalase activity and INH resistance. The protein model indicated that P232L reduced INH-KatG binding affinity while Q461Stop truncated gene transcription. Our results showed that the two katG mutations, P232L and Q461Stop, accounted for the co-emergence of INH-resistant clones during anti-TB therapy. The inclusion of these mutations in the design of molecular assays could increase the diagnostic performance.IMPORTANCEThe evolution of drug-resistant strains of Mycobacterium tuberculosis within the lung lesions of a patient has a detrimental impact on treatment outcomes. This is particularly concerning for isoniazid (INH), which is the most potent first-line antimycobacterial drug. However, the precise genetic factors responsible for drug resistance in patients have not been fully elucidated, with approximately 15% of INH-resistant strains harboring unknown genetic factors. This raises concerns about the emergence of drug-resistant clones within patients, further contributing to the global epidemic of resistance. In this study, we revealed the presence of two novel katG mutations, which emerged independently due to the stress exerted by antituberculosis (anti-TB) treatment on a parental strain. Importantly, we experimentally demonstrated the functional significance of both mutations in conferring resistance to INH. Overall, this research sheds light on the genetic mechanisms underlying the evolution of INH resistance within patients and provides valuable insights for improving diagnostic performance by targeting specific mutations.

Abstract Introduction Acute kidney injury (AKI) is occasionally detected in patients receiving anti-tuberculosis (TB) treatment. This prospective cohort study is the first to investigate the incidence, risk factors, and renal outcomes of AKI during anti-TB treatment. Methods This study was conducted from January 1, 2016, to May 31, 2018. Patients with a new diagnosis of TB and on standard anti-TB treatment were enrolled, and the patients received regular laboratory monitoring. AKI was defined according to the Kidney Disease: Improving Global Outcome (KDIGO) criteria. Urinalysis, renal ultrasonography, blood erythrocyte morphology, and fractional excretion of sodium were performed at AKI onset. The TB treatment regimen was adjusted by the primary physician if necessary. Risk factors for AKI were identified through Cox regression. Results In total, 106 patients were recruited (mean age 52.6 years, 71.7% men). Eleven (10.3%) patients experienced AKI. Increased serum uric acid and hemoglobin levels were noted at AKI onset. All patients with AKI achieved renal recovery and completed anti-TB treatment containing rifampin. Age [hazard ratio (HR) 1.06 (1.02–1.11)], a higher baseline estimated glomerular filtration rate [eGFR; HR 1.04 (1.02–1.06)], and a blood eosinophil count > 350 (109/L) [HR 10.99 (2.28–53.02)] were associated with a higher risk of AKI during TB treatment. Conclusion Regular pharmacovigilant monitoring revealed an incidence of renal impairment during anti-TB treatment that was higher than expected. AKI was more common in older patients with a higher eGFR and blood eosinophil count. However, the complications had no influence on TB treatment completion, and no permanent renal impairment occurred.

Adrenal tuberculosis (TB) is a rare disease, which is difficult to diagnose because of its atypical symptoms. We reported a 41-year-old female who was admitted to hospital due to a left adrenal tumor, which was found in health examination without any symptoms. Abdominal CT showed a mass in her left adrenal. The results of blood test were normal. A retroperitoneal laparoscopic adrenalectomy was carried out, and adrenal TB was finally pathologically diagnosed. Following this, examinations focusing on TB were conducted which revealed negative results except for T-cell enzyme-linked immunospot. After the operation, the hormone level was normal. However, a wound infection occurred, which was recovered after antituberculosis treatment. In conclusion, even if there is no evidence of TB, we should be alert when diagnosing adrenal masses. Examinations of pathology, radiography, and hormone play important roles in determining the definite diagnosis of adrenal TB. [ABSTRACT FROM AUTHOR]

BackgroundDolutegravir (DTG) has recently been recommended as a preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. However, potential drug interactions between DTG and rifampicin remain a clinical and public health concern.MethodsWe analyzed HIV and Tuberculosis (TB) treatment outcomes of HIV-infected patients concomitantly receiving rifampicin- and DTG-based regimens under programmatic conditions in Botswana. The outcomes of interest were successful TB treatment and viral load suppression. We used multivariable logistic models to determine predictors for each outcome of interest.ResultsA total of 1225 patients were included in the analysis to evaluate predictors of successful TB outcome. Among patients on DTG and non-DTG regimens, 90.9% and 88.3% achieved favorable TB treatment outcomes, respectively. Of those who received DTG-based regimen; 44% received once-daily dosing and 53% twice-daily dosing. We found that DTG was associated with favorable TB treatment outcome (adjusted odds ratio = 1.56; 95% confidence interval = 1.06 to 2.31), after adjusting for age, gender, and CD4 cell counts. High rates of viral load suppression were found across all antiretroviral therapy (ART) regimen categories (>92% for all). We did not find an independent association between DTG and viral suppression after adjustment of other covariates.ConclusionsThe use of DTG-based ART regimens in patients coinfected with TB and HIV lead to favorable TB and HIV treatment outcomes, comparable to those achieved with alternative ART regimens. Our results provide reassurance to TB and HIV programs about the overall programmatic concomitant use of these first-line treatment regimens for the management of HIV and TB coinfected patients.

Introduction: Acute kidney injury (AKI) is occasionally detected in patients receiving anti-tuberculosis (TB) treatment. This prospective cohort study is the first to investigate the incidence, risk factors, and renal outcomes of AKI during anti-TB treatment. Methods: This study was conducted from January 1, 2016, to May 31, 2018. Patients with a new diagnosis of TB and on standard anti-TB treatment were enrolled, and the patients received regular laboratory monitoring. AKI was defined according to the Kidney Disease: Improving Global Outcome (KDIGO) criteria. Urinalysis, renal ultrasonography, blood erythrocyte morphology, and fractional excretion of sodium were performed at AKI onset. The TB treatment regimen was adjusted by the primary physician if necessary. Risk factors for AKI were identified through Cox regression. Results: In total, 106 patients were recruited (mean age 52.6 years, 71.7% men). Eleven (10.3%) patients experienced AKI. Increased serum uric acid and hemoglobin levels were noted at AKI onset. All patients with AKI achieved renal recovery and completed anti-TB treatment containing rifampin. Age [hazard ratio (HR) 1.06 (1.02–1.11)], a higher baseline estimated glomerular filtration rate [eGFR; HR 1.04 (1.02–1.06)], and a blood eosinophil count > 350 (109/L) [HR 10.99 (2.28–53.02)] were associated with a higher risk of AKI during TB treatment. Conclusion: Regular pharmacovigilant monitoring revealed an incidence of renal impairment during anti-TB treatment that was higher than expected. AKI was more common in older patients with a higher eGFR and blood eosinophil count. However, the complications had no influence on TB treatment completion, and no permanent renal impairment occurred. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the effects of 25-hydroxy vitamin D (25[OH]D) on T lymphocyte subsets and sputum smear conversion during antituberculosis (TB) treatment. Methods: A total of 120 newly diagnosed patients with active pulmonary TB were collected and classified into vitamin D sufficiency group, vitamin D insufficiency group, and vitamin D deficiency group according to serum 25(OH)D levels. The clinical data and sputum smear conversion were collected and serum 25(OH)D and T lymphocyte subsets were also measured and compared. Results: Our data showed that 25(OH)D levels reached the lowest point at two months of anti-TB treatment. Significant differences existed in the increase of CD4+ and CD8+ T cells on the basis of vitamin D levels. The vitamin D sufficiency group had a significantly higher increase of CD4+ T cells during six months of anti-TB treatment and CD8+ T cells after four months of anti-TB treatment than the other groups. Vitamin D had no effect on the time-to-sputum smear conversion (vitamin D sufficiency group: adjusted hazard ratio: 1.27, 95% confidence interval [CI]: 0.78–2.06); vitamin D insufficiency group: adjusted hazard ratio: 1.05, 95% CI: 0.63–1.75)]. Conclusion: Through null effects on sputum smear conversion, vitamin D may have a beneficial effect on the increase of CD4+ and CD8+ T cells during anti-TB treatment.

Background: Dysglycemia (i.e., prediabetes or diabetes) in patients with tuberculosis (PWTB) is associated with increased odds of mortality and treatment failure. Whether such association holds true when dysglycemia is transient or persistent is unknown. In this study, we tested the association between persistent dysglycemia (PD) during anti-tuberculosis (TB) treatment and unfavorable treatment outcomes in PWTB from Lima, Peru. Methods: PWTB enrolled between February and November 2017 were followed for 24-months. Dysglycemia was measured through fasting glucose and HbA1c at baseline during the 2nd- and 6th-month of TB treatment. PD was defined as dysglycemia detected in 2 different visits. The association between PD and unfavorable TB treatment outcome was evaluated using logistic regression. Results: Among 125 PWTB, PD prevalence was 29.6%. PD was associated with more lung lesion types, higher bacillary loads, low hemoglobin (Hb), and high body mass index (BMI). Unfavorable TB treatment outcome was associated with older age, higher BMI, more lung lesion types, and PD. After adjusting for age, Hb levels, smoking, and smear grade, PD was independently associated with unfavorable treatment outcomes (adjusted odds ratio (aOR): 6.1; 95% CI: 1.9–19.6). Conclusion: PD is significantly associated with higher odds of unfavorable TB treatment outcomes. Dysglycemia control during anti-TB treatment gives the opportunity to introduce appropriate interventions to TB management.

Objectives: The objective was to estimate the proportion of adverse drug reactions (ADRs) to daily regimen antituberculosis treatment (ATT) among the ADRs received in the ADR monitoring center (AMC) of the institution and to describe its pattern. Materials and Methods: This was a descriptive study conducted in the Department of Pharmacology of a Government Medical College in Central Kerala and the period under study was October 2017-June 2020. The data on ADR were entered into a structured pro forma and data were analyzed using SPSS for Windows Version 16.0 (SPSS Inc., Chicago, USA). Results: Of the 643 ADRs, 98 (15.24%) were suspected to be due to the daily regimen of ATT. The most common organ system affected was hepatobiliary 46 (46.9%) namely hepatitis in 35 and asymptomatic elevated liver enzymes in 11 followed by eye with 26 reports of decreased vision. In 96 (97.95%), the suspected ADR had probable causality and in 2 (2.04%) it was possible. Seventy-seven (78.6%) ADR reports were serious as well as moderate-level 4b in severity and 57 (58.16%) were probably preventable. The mean days of onset of ADR after starting the ATT regimen were 56.40 ± 58.29 days (range 1-180). Decrease in vision with a mean duration of 125.23 ± 55.46 days had the longest latency in onset among all the ADRs. Conclusions: Of all the ADRs reported to AMC 15.24% were due to the daily regimen of ATT. Hepatitis was the most common ADR encountered followed by decrease in vision. The majority of the ADRs were probable in causality, serious, moderate-level 4b in severity, and probably preventable. [ABSTRACT FROM AUTHOR]

Background: Oxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of M. tuberculosis (Mtb) among persons on anti-TB treatment (ATT) are unknown. Quantification of urinary eicosanoid metabolites can provide insights into the circulating lipid mediators involved in Mtb immune responses. Methods: We conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had subgroups with or without dysglycemia at baseline. Participants were enrolled from RePORTBrazil (Salvador site) and RePORT-South Africa (Durban site) and stratified according to TB status and baseline glycated hemoglobin levels: a) TB-dysglycemia (n=69); b) TBnormoglycemia (n=64); c) non-TB/dysglycemia (n=31); d) non-TB/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11α-hydroxy-9,15- dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE1 (metabolite of PGE2, TN-E), 9α-hydroxy11,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (metabolite of PGD2, PGD-M), 11-dehydro-thromboxane B2 (11dTxB2), 2,3-dinor-6-keto-PGF1α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE4). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy. Results: PGE-M and LTE4 values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p<0.001). In addition, there was a significant decrease in PGI-M and LTE4 levels from baseline to month 6 in the TBdysglycemia and TB-normoglycemia groups. Finally, TB-dysglycemia was independently associated with increased concentrations of PGD-M, PGI-M, and LTE4 at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status. Conclusion: The urinary eicosanoid metabolite profile was associated with TBdysglycemia before and during ATT. These observations can help identify the mechanisms involved in the pathogenesis of TB-dysglycemia, and potential biomarkers of TB treatment outcomes, including among persons with dysglycemia. [ABSTRACT FROM AUTHOR]

Background/Aim: Cancer and tuberculosis are common in the world, and the intersection of these two diseases affects oncology practice inevitably. Fortunately, the co-occurrence of cancer and tuberculosis is rare and there are no guidelines for the management of therapy in these patients. The information on these patients is obtained from small-scaled studies. This study aimed to question the efficacy and safety of tuberculosis treatment in cancer patients receiving chemotherapy. Methods: Twenty-two patients who were treated with chemotherapy due to cancer and followed up and treated for concurrent tuberculosis in Diyarbakır Gazi Yaşargil Training and Research Hospital Medical Oncology Clinic between February 2009 and March 2021 were included in this retrospective case-control study. The clinical laboratory and treatment data of these patients were reviewed retrospectively. Then, the clinical, laboratory and treatment data of twenty-two cancer patients of the same age, who had the same stage cancer and received the same chemotherapy treatment but did not have tuberculosis disease were compared with the patients with tuberculosis. Thus, the efficacy, safety, and effect of tuberculosis treatment on cancer treatment were investigated. Results: Twenty-two patients were diagnosed with tuberculosis and cancer. Six (27.3%) patients were receiving single agent chemotherapy, 16 (72%) were receiving combination chemotherapy, and 5 (22.5%) were receiving a combination of chemotherapy and targeted therapy. While 10 (45.5%) patients were diagnosed with non-pulmonary tuberculosis, 12 (54.5%) patients were diagnosed with pulmonary tuberculosis. Among all patients, the rate of completion of antituberculosis treatment was 77.2%, and the success rate with initial antituberculosis agents was 72.7%. Except for elevated liver enzymes, nausea- vomiting and grade-3 neutropenia (P<0.001, P<0.001, P=0.012 respectively), there was no significant difference in toxicity between the patients with and without tuberculosis. The mortality rate in the first 6 months of anti-tuberculosis treatment was 18.2% in patients who received tuberculosis and cancer treatment, compared to 9.1% in cancer patients who did not receive tuberculosis treatment. There was no significant difference in the mortality rate in both groups at the end of 12-year follow-up period (P=0.658). Conclusion: Our results show that the combined use of chemotherapy and antituberculosis treatment in patients with cancer and tuberculosis is effective and safe. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to assess and enhance the application value of ureteral stents in the adjunctive treatment of renal tuberculosis, thus providing a robust evidence-based framework for guiding clinical management strategies., Methods: A total of 360 patients diagnosed with renal tuberculosis between January 2019 and December 2023 were meticulously selected for this study. Utilizing a random number table, the patients were stratified into a control group and a study group, with 180 patients in each cohort. The control group received standard antituberculosis treatment, while the study group underwent adjunctive treatment with ureteral stents. A comparative analysis was conducted to evaluate the differential clinical efficacy, renal excision rate, renal function, degree of renal pelvis separation, and renal parenchymal thickness between the two groups., Results: The study group showed significantly better clinical cure rates and effectiveness compared to the control group. While the 12-month renal excision rate was similar between groups, the 18-month rate was significantly lower in the study group. The study group also had lower posttreatment BUN and serum creatinine levels, reduced renal pelvis separation, and greater renal parenchymal thickness. At 3 and 9 months, complications were significantly fewer in the study group (p < 0.001, p < 0.05), with no severe complications reported. Additionally, the study group had higher overall SF-36 scores (p < 0.001), indicating better quality of life. The treatment success rate (87.2% vs. 70.6%, p < 0.001), renal function preservation (76.7% vs. 60.6%, p = 0.001), and lower recurrence rate (16.1% vs. 26.1%, p = 0.028) further highlighted the benefits of ureteral stenting., Conclusion: The adjunctive use of ureteral stents in the treatment of renal tuberculosis presents a significantly enhanced application value. It not only improves clinical efficacy but also diminishes the need for renal excision, effectively preserves renal function, reduces the degree of renal pelvis separation, and maintains optimal renal parenchymal thickness. Thus, advocating for the widespread implementation of ureteral stents as an adjunctive therapeutic modality for managing renal tuberculosis is strongly recommended., (© 2024 S. Karger AG, Basel.)

Sacroiliac joint (SIJ) tuberculosis (TB) is an infrequent clinical entity, especially in developed countries. The symptoms are usually non-specific, and therefore it may mimic a variety of degenerative and non-degenerative diseases, hampering the diagnosis. An interesting case of SIJ infection with psoas abscess in a 77-year-old male is presented in the current article. The patient presented to the Infectious Diseases Clinic complaining of prolonged fever and difficulty walking. The fever was intermittent, it appeared usually at night, and it reached up to 39 degrees Celsius and was accompanied by chills. Magnetic resonance imaging (MRI) indicated SIJ osteomyelitis accompanied by two iliopsoas abscesses above the joint. Computed tomography (CT)-guided aspiration of the abscess was performed twice, but the microbiological culture did not grow any pathogens; Gene-X-Pert performed on the drained pus was negative. An open biopsy with drainage of the abscess cavities and bone biopsy was performed and set the diagnosis, and the anti-TB treatment was initiated. Shortly after the surgical procedure, the patient developed confusion and relapse of high-grade fever, and tubercular meningoencephalitis was diagnosed following an MRI of the brain, which revealed compatible lesions. The patient was intubated and transferred to the intensive care unit (ICU). A quadruple anti-TB regimen was administered. However, the patient's condition deteriorated as he developed necrosis in the cortex and basal ganglia and the outcome was fatal. This article aims to raise awareness regarding this rare clinical entity, whose diagnostic and therapeutic management is particularly demanding., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Symeonidou et al.)

Background: Organizing pneumonia secondary to pulmonary tuberculosis is rare. Moreover, the temporal boundary between pulmonary tuberculosis and secondary organizing pneumonia has not been defined. We report a case of secondary organizing pneumonia associated with pulmonary tuberculosis occurring after nine months of antituberculosis treatment., Case Summary: A 54 years old man, previously diagnosed with pulmonary tuberculosis and tuberculous pleurisy, underwent nine months of antituberculosis treatment. Follow-up lung computed tomography revealed multiple new subpleural ground-glass opacities in both lungs, and a lung biopsy confirmed organizing pneumonia. Treatment continued with anti-tuberculosis agents and hormone therapy, and subsequent dynamic pulmonary computed tomography exams demonstrated improvement in lesion absorption. No disease recurrence was observed after corticosteroid therapy discontinuation., Conclusion: When treating patients with active pulmonary tuberculosis, if an increase in lesions is observed during anti-tuberculosis treatment, it is necessary to consider the possibility of tuberculosis-related secondary organizing pneumonia, timely lung biopsy is essential for early intervention., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: 99DOTS (Directly Observed Treatment, Short course) is a low-cost, mobile phone-based technology that enables real-time remote monitoring of daily intake of treatment, first introduced by the Revised National Tuberculosis Programme under the national programme in 2015 in high-burden antiretroviral therapy (ART) centers. This project was launched for the first time in 2016 in Rajkot district, Gujarat, India, and hence this was an effort to evaluate 99DOTS. Objectives: The objective of this study was to evaluate treatment adherence rate and treatment outcome of 99DOTS-information communication technology (ICT)-based approach for tuberculosis (TB) management. Materials and Methods: Data from 99DOTS were obtained from February 2016 to September 2017 after obtaining approval from the Institutional Ethical Committee and permission from the head of the department of district TB center (DTC), Rajkot. Data were evaluated for sociodemographic pattern, adherence rate, and treatment outcome. Results: A total of total 347 registered patients, 197 (56.77%) patients diagnosed by private practitioners and 150 (43.22%) patients having HIV-TB from ART center were initiated TB treatment under 99DOTS project from nine different talukas of Rajkot district. Mean age of the registered TB patients was 36 ± 13.55 years with predominance of “new cases” (n = 275, 79.25%) and “male” gender (n = 257, 74.06%). The overall treatment adherence rate of 99DOTS was 96.03%, while adherence by “call” was 92.25% and adherence by “manual” was 32.12%. Cure rate was higher in patients with TB only (n = 113, 78.47%) as compared to patients with HIV-TB co-infection (n = 46, 67.64%). Defaulter rate (n = 19, 13.19%) was also higher in patients with TB only, while death rate (n = 14, 20.58%) was higher in patients of TB with HIV co-infection. Conclusion: 99DOTS is an effective approach for improving TB medication adherence, thereby increasing the compliance to TB treatment. It will be helpful for easy access of treatment to patients from remote areas, improve notification of patients from private practitioners, and enable differentiated care.

We investigated the delays in the diagnosis of tuberculosis and/or HIV, their treatment initiation, and factors associated with each delay. All drug-susceptible tuberculosis cases diagnosed in 2014 and 2015 in Colombia, with a confirmed diagnosis of HIV were included. A total of 1909 patients were registered with tuberculosis/HIV co-infection. Seventy-nine percent of patients were men, 50% had sputum smear-negative tuberculosis, culture was done in 50% of cases, 68.5% had <200 CD4 cell count at diagnosis, and 35% had concurrent tuberculosis/HIV diagnosis. Delays in the tuberculosis diagnosis were identified in 54.8% of the patients, and delays in tuberculosis and HIV treatment initiation in 41.8% and 27.4%, respectively. The risk factors associated with delay in tuberculosis diagnosis were age between 15–34 and ≥45 years, and those patients who received tuberculin skin test. The risk factor associated with antiretroviral therapy initiation delay was previously-treated tuberculosis patients after failure. It is necessary to implement strategies for early detection and treatment initiation of HIV and to use rapid test for tuberculosis diagnosis in this population. [ABSTRACT FROM AUTHOR]

Tuberculosis is a common health care problem worldwide, though the incidence has come down in recent years due to various health care programs targeting tuberculosis and improved living conditions. Cervical lymph nodes are among the common sites for extrapulmonary tuberculosis. They usually present with painless enlargement of cervical lymph nodes with or without constitutional symptoms. Tuberculosis rarely coexists with malignancy in the geographical area where the prevalence of tuberculosis is high. The disease needs to be treated with antituberculosis treatment as per standard guidelines and the primary treatment of malignancy. We report a case of an adult male presented with a lesion on the pinna, which was diagnosed as squamous cell carcinoma of the pinna on biopsy; he was later found to have coexistent tuberculosis after undergoing surgery for carcinoma. [ABSTRACT FROM AUTHOR]

Chunlan Zheng,1,* Xiufen Hu,2,* Li Zhao,1 Minhui Hu,1 Feng Gao3 1Department of Internal Medicine – Section 5, Wuhan Pulmonary Hospital (Wuhan Tuberculosis Control Institute), 2Department of Paediatrics, Tongji Hospital, 3Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Rifapentine is a rifamycin derivate approved by the US Food and Drug Administration in 1998 for the treatment of active, drug-susceptible tuberculosis (TB). In 2014, rifapentine was approved for the treatment of latent TB infection in patients at high risk of progression to active disease and is currently under evaluation by the European Medicines Agency. Expanding indications of rifapentine largely affect diabetes patients, since about one-third of them harbor latent TB. Clinical consequences of rifapentine use in this population and potentially harmful interactions with hypoglycemic agents are widely underexplored and generally considered similar to the ones of rifampicin. Indeed, rifapentine too may decrease blood levels of many oral antidiabetics and compete with them for protein-binding sites and/or transporters. However, the two drugs differ in protein-binding degree, the magnitude of cytochrome P450 induction and auto-induction, the degree of renal elimination, and so on. Rifapentine seems to be more suitable for use in diabetes patients with renal impairment, owing to the fact that it does not cause renal toxicity, and it is eliminated via kidneys in smaller proportions than rifampicin. On the other hand, there are no data related to rifapentine use in patients >65 years, and hypoalbuminemia associated with diabetic kidney disease may affect a free fraction of rifapentine to a greater extent than that of rifampicin. Until more pharmacokinetic information and information on the safety of rifapentine use in diabetic patients and drug–drug interactions are available, diabetes in TB patients treated with rifapentine should be managed with insulin analogs, and glucose and rifapentine plasma levels should be closely monitored. Keywords: rifamycin, antituberculosis treatment, glucose intolerance, hyperglycemia, safety

Background: 99DOTS (Directly Observed Treatment, Short course) is a low‑cost, mobile phone‑based technology that enables real‑time remote monitoring of daily intake of treatment, first introduced by the Revised National Tuberculosis Programme under the national programme in 2015 in high‑burden antiretroviral therapy (ART) centers. This project was launched for the first time in 2016 in Rajkot district, Gujarat, India, and hence this was an effort to evaluate 99DOTS. Objectives: The objective of this study was to evaluate treatment adherence rate and treatment outcome of 99DOTS‑information communication technology (ICT)‑based approach for tuberculosis (TB) management. Materials and Methods: Data from 99DOTS were obtained from February 2016 to September 2017 after obtaining approval from the Institutional Ethical Committee and permission from the head of the department of district TB center (DTC), Rajkot. Data were evaluated for sociodemographic pattern, adherence rate, and treatment outcome. Results: A total of total 347 registered patients, 197 (56.77%) patients diagnosed by private practitioners and 150 (43.22%) patients having HIV‑TB from ART center were initiated TB treatment under 99DOTS project from nine different talukas of Rajkot district. Mean age of the registered TB patients was 36 ± 13.55 years with predominance of “new cases” (n = 275, 79.25%) and “male” gender (n = 257, 74.06%). The overall treatment adherence rate of 99DOTS was 96.03%, while adherence by “call” was 92.25% and adherence by “manual” was 32.12%. Cure rate was higher in patients with TB only (n = 113, 78.47%) as compared to patients with HIV‑TB co‑infection (n = 46, 67.64%). Defaulter rate (n = 19, 13.19%) was also higher in patients with TB only, while death rate (n = 14, 20.58%) was higher in patients of TB with HIV co‑infection. Conclusion: 99DOTS is an effective approach for improving TB medication adherence, thereby increasing the compliance to TB treatment. It will be helpful for easy access of treatment to patients from remote areas, improve notification of patients from private practitioners, and enable differentiated care. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) is one of the most important public health problems worldwide. Detecting patients with active pulmonary TB (PT) is an important component of TB control programs. However, at times in patients even with a compatible clinical picture, sputum smears do not reveal acid-fast bacilli (AFB) and smear-negative PT remains a common problem. This study compares the results of induced sputum (IS) and bronchial washings (BWs) in detecting sputum negative PT. Materials and Methods: A prospective study conducted from June 2014 to June 2015, comprising 120 patients fulfilling study criteria. Patients with respiratory symptoms and chest roentgenogram suspicious of PT with no previous history of antiTB treatment (ATT) and two spontaneous sputum smear samples negative for AFB were included in the study. Patients with active hemoptysis and sputum positive were excluded from the study. Sputum induction was done using 5–10 ml of 3% hypertonic saline through ultrasonic nebulizer taking safety precautions. All the patients underwent fiberoptic bronchoscopy after 6 h fasting on the same day. About 20 ml of normal saline instilled into the suspected pathology area and washings were taken with gentle suction. The sample processing and fluorescent staining for AFB were done in a designated microscopy laboratory. Results: Of 120 smear-negative PT patients, IS smear examination detected AFB in 76 patients (63.3%) and AFB detected from BWs in 94 patients (78.5%). Smear positivity higher in cavitary and infiltrative lesions compared to consolidation and infrahilar pattern disease. Conclusions: Even though both IS and BWs procedures were valuable for the diagnosis of smear-negative TB, sputum induction with hypertonic saline should be the initial procedure of choice, which can be repeated twice/thrice in a day or 2 consecutive days. If the patient remains IS smear-negative and if the clinical probability of TB is high, starting ATT and closely monitoring patient and reserving bronchoscopy to those patients who do not improve and to exclude alternative diagnosis seems to be a practically useful approach.

Tuberculosis (TB) is a life-threatening disease and a main cause of death worldwide. It mainly affects the lungs, and it is attributed to the infection with Mycobacterium tuberculosis (MTB). Current treatments consist of the oral administration of combinations of antibiotics including rifabutin, in high doses and for long periods of time. These therapeutic regimens are associated with many side effects and high rates of drug resistance. To overcome these problems, this study aims at developing a nanosystem for the improved delivery of antibiotics, with potential application in pulmonary delivery. Chitosan-based nanomaterials are widely used in biomedical applications, due to their biodegradability and biocompatibility, as well as their potential antimicrobial effects and lack of toxicity. In addition, this polymer is particularly attractive for mucosal delivery due to its bioadhesive properties. Therefore, the structure of the proposed nanocarrier consists of a chitosan shell and a lipid core with a combination of different oils and surfactants to allow optimal association of the hydrophobic drug rifabutin. These nanocapsules were characterized in terms of size, polydispersity index, surface charge, morphology, encapsulation efficiency and biological stability. The release kinetics of the drug-loaded nanostructures was evaluated in simulated lung media. Moreover, in vitro studies in different cell models (A549 and Raw 264.7 cells) demonstrated the safety of the nanocapsules as well as their efficient internalization. An antimicrobial susceptibility test was performed to evaluate the efficacy of the rifabutin-loaded nanocapsules against Mycobacterium phlei. This study indicated complete inhibition for antibiotic concentrations within the expected susceptibility range of Mycobacterium (≤ 0.25–16 mg/L). [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate serum cytokines and natural antimicrobial peptide profiles in pulmonary tuberculosis, and compare them with levels in controls without tuberculosis, to explore the associations between these biomarkers and response to antituberculosis treatment. Serum levels of 10 biomarkers were measured using a Luminex bead array platform. Tuberculosis biosignatures were identified from the discovery cohort (n = 148) and were validated in the independent cohort (n = 148). Association between biosignatures and clinical outcome was investigated with negative conversion in follow-up sputum culture after 2 months of treatment. Serum concentrations of eotaxin, MIP-1α, sIL-2Rα, and lipocalin 2 were significantly different between pulmonary tuberculosis patients and controls ( P < 0.05). Serum concentrations of eotaxin and sIL-2Rα were higher in pulmonary tuberculosis patients than in controls, while those of MIP-1α and lipocalin 2 were lower ( P < 0.05). Eotaxin concentrations were significantly higher in good responders to treatment ( P < 0.05), indicating this immunomolecule may serve as a positive predictor for therapy response in pulmonary tuberculosis. The magnitude serum eotaxin, MIP-1α, sIL-2Rα, and lipocalin 2 are important indicators for pulmonary tuberculosis. These biomarkers alone or combinatorial detections have potential applicability in monitoring tuberculosis patients during antituberculosis treatment. Significance Cytokines and endogenous antimicrobial peptides represent an important part of immune system and the identification of a pattern of differentially expressed those biomarkers (a “biosignature”) could help to differentiate tuberculosis infection from the non-infected state which might eventually assist case identification and accelerate access to treatment. In this direction, cytokine analysis including multiple serum biomarkers to evaluate biosignatures of pulmonary tuberculosis would provide basic knowledge to aid understanding of the pathophysiology of tuberculosis infection and for the development of future diagnostic methods, treatments, and monitoring for pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) is one of the most important public health problems worldwide. Detecting patients with active pulmonary TB (PT) is an important component of TB control programs. However, at times in patients even with a compatible clinical picture, sputum smears do not reveal acid-fast bacilli (AFB) and smear-negative PT remains a common problem. This study compares the results of induced sputum (IS) and bronchial washings (BWs) in detecting sputum negative PT. Materials and Methods: A prospective study conducted from June 2014 to June 2015, comprising 120 patients fulfilling study criteria. Patients with respiratory symptoms and chest roentgenogram suspicious of PT with no previous history of antiTB treatment (ATT) and two spontaneous sputum smear samples negative for AFB were included in the study. Patients with active hemoptysis and sputum positive were excluded from the study. Sputum induction was done using 5-10 ml of 3% hypertonic saline through ultrasonic nebulizer taking safety precautions. All the patients underwent fiberoptic bronchoscopy after 6 h fasting on the same day. About 20 ml of normal saline instilled into the suspected pathology area and washings were taken with gentle suction. The sample processing and fluorescent staining for AFB were done in a designated microscopy laboratory. Results: Of 120 smear-negative PT patients, IS smear examination detected AFB in 76 patients (63.3%) and AFB detected from BWs in 94 patients (78.5%). Smear positivity higher in cavitary and infiltrative lesions compared to consolidation and infrahilar pattern disease. Conclusions: Even though both IS and BWs procedures were valuable for the diagnosis of smear-negative TB, sputum induction with hypertonic saline should be the initial procedure of choice, which can be repeated twice/thrice in a day or 2 consecutive days. If the patient remains IS smear-negative and if the clinical probability of TB is high, starting ATT and closely monitoring patient and reserving bronchoscopy to those patients who do not improve and to exclude alternative diagnosis seems to be a practically useful approach. [ABSTRACT FROM AUTHOR]

Tuberculosis of the central nervous system is an ominous consequence of disseminated tuberculosis which usually manifests as meningitis, an abscess or rarely as a tuberculoma. Though infrequent, intracranial tuberculomas especially within the sella, are notorious for simulating as pituitary tumors, by jeopardising pituitary hormonal function and exerting compressive effects on adjacent intracranial structures. However, a prompt evaluation can help tackle this diagnostic challenge with timely institution of anti-tuberculosis treatment, (ATT). Although in rare instances surgery may be a favourable option especially for managing extensive intrasellar masses, ATT usually facilitates resolution of such lesions. Long term hormonal replacement therapy may be required for established endocrine dysfunction.

Solitary splenic tuberculosis (TB) is rare, with less than ten cases ever being reported. The diagnosis is established by the pathological analysis of a biopsy from a surgical operation or from a fine-needle aspiration sample. Manifestations of splenic TB include low-grade fever, weight loss, abdominal pain, and diarrhea. This case, however, has no obvious symptoms, and multiple splenic tubercles were discovered during a routine physical examination. Splenic abscesses from TB were diagnosed after the operation. Postoperative spread of TB lead to cerebral tuberculous abscesses and pulmonary TB. Resolution was achieved with anti-TB therapy. [ABSTRACT FROM AUTHOR]

What is known and objective Evidence demonstrates that the delicate balance between pro- and anti-inflammatory cytokines determines the further progress to severe injury or recovery. Therefore, understanding which cytokines are associated with the development of drug-induced hepatotoxicity ( DIH) might guide the prevention and therapeutic direction. Some polymorphisms of cytokine genes have been reported to be associated with DIH involving interleukin-4 ( IL-4), interleukin-10 ( IL-10) and tumour necrosis factor-α ( TNF-α); however, these studies are still scanty with inconsistent results. In addition, most of these associations have not been investigated in antituberculosis drug-induced hepatotoxicity ( ATDH) patients with the exception of TNF-α polymorphisms. Therefore, we aimed to investigate the association between IL-4 and IL-10 gene polymorphisms with the risk of ATDH in a Chinese population. Methods The study was designed as a nested case-control study within a prospective cohort. Each case was matched with four controls by sex, age at baseline (±5 years), treatment history, disease severity, drug dosage and place of sample collection. Genetic polymorphisms of IL-4 and IL-10 were determined by TaqMan single nucleotide polymorphism ( SNP) genotyping assay. Odds ratio ( OR) with 95% confidence intervals ( CIs) was estimated by conditional logistic regression model. Results and discussion A total of 89 incident ATDH cases and 356 controls undergoing antituberculosis treatment were included. Six SNPs were selected for genotyping, which were rs2243289, rs2243250 and rs2070874 for IL-4, and rs1800896, rs1800871 and rs1800872 for IL-10. No significant difference was observed in genotypes frequencies of the six selected SNPs between case and control group, and the distributions of IL-4 and IL-10 haplotypes were similar in ATDH patients and controls. What is new and conclusion This study is the first attempt to evaluate the associations of genetic polymorphisms of IL-4 and IL-10 genes with ATDH using a nested case-control study design. We provide preliminary evidence that there is no statistically significant association between IL-4 and IL-10 genotypes/haplotypes and the risk of ATDH in Chinese population. [ABSTRACT FROM AUTHOR]

Objectives Tuberculosis ( TB) is an infectious disease with a global distribution. The mainstay of treatment is a combination of antituberculous ( AT) drugs. The standard combination uses four first-line AT drugs; however, in certain groups of patients, the combination must be modified or reduced in dosage. This is especially true of patients with comorbidities, in the elderly and in pregnant women. The aim of this review is to provide up-to-date information regarding AT treatment in a variety of special patient populations. Data Source The recommendations presented here are based on the clinical experience of the author, as well as data presented in textbooks, World Health Organization national and international guidelines, various respiratory societies and original articles quoted in medical databases. The time frame for this review was from 1995 to 2013. The data search was carried out only in English and the index words were as follows: tuberculosis - treatment - liver disease - kidney disease - HIV infection - skin toxicity - elderly - pregnancy. Results Based on our experience and the described sources above, we present AT treatment recommendations for specific patient populations. Conclusions TB can be difficult to diagnose and treat. This can be especially true in patients with comorbidities, adverse reactions to AT drugs, the elderly and pregnant women. Despite the difficulties, an early diagnosis followed immediately by AT treatment should be the norm for these patients. When choosing a suitable AT regimen, we must consider the potential side effects of the drugs, which could exacerbate an underlying comorbidity, harm an expectant mother or fetus, or adversely affect the elderly. [ABSTRACT FROM AUTHOR]

Tuberculosis is a challenge in organ transplantation due to the interaction between Anti- Tuberculosis Treatment (ATT) and immunosuppressive drugs, such as Tacrolimus (TAC). This study aimed to assess this interaction and discuss the guidelines used in this specific case., Methods: A retrospective, observational, single-center analysis was performed at the Department of Clinical Pharmacology (National Centre of Pharmacovigilance, Tunisia). We analyzed the database of patients who received TAC from 2009 until 2018. We included samples provided from renal transplant patients infected by Mycobacterium tuberculosis after transplantation. Trough blood levels (C0) were determined using an immunoassay analyzer. The Therapeutic Range (TR) of TAC was considered between 5 and 10 ng/mL. Pharmacokinetic parameters were compared between the period of co-administration of TAC/ATT (period A) and the period during which patients received only TAC (period B)., Results: Seven renal transplant patients treated by TAC were included. 41 samples were analyzed (16; period A, 25; period B). Only 6 % of C0 values were found within TR during period A, while this rate was 44% during period B. During period A, 88% of TAC C0 was under the lower limit of TR, indicating a high risk of transplant rejection. The mean C0 and C0/D were significantly lower during period A (3.11±1.53 ng/mL vs 7.11 ± 3.37 ng/mL; p = 0.001 and 33.06 ± 24.89 vs 83.14 ± 44.46; p = 0.0006, respectively), without difference in doses between periods., Conclusion: Considering the results of this study, clinicians are suggested to monitor TAC closely in this particular circumstance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

What is known and objective Research on genetic factors associated with antitubercular drug-induced liver injuries ( ATLI) has been reported. However, most of the research has focused on genetic polymorphisms of genes encoding metabolic enzymes, including NAT2, GST and CYP450. It is probable that the immune system also contributes to the onset of drug adverse effects. A few small studies have explored the possible association of HLA genes with drug-induced liver injuries ( DILI), but more supportive evidence from larger studies or prospective cohort designs is needed. We aim to explore the possible association of HLA- DQB1 gene polymorphisms with ATLI in a case-control study. Methods A case-control study design was used. ATLI was recorded in a prospectively followed-up cohort of patients receiving antituberculosis treatment. Identified cases were matched with control tuberculosis patients within the same cohort but with no adverse effects in 1 : 1 ratio. We used the sequence-based typing method to determine the HLA- DQB1 genotypes. Odds ratios ( OR) and 95% confidence intervals ( CI) were calculated using conditional logistic regression. Results and discussion Eighty-nine cases were included in this case-control study. HLA- DQB1 typing was successful for 177 subjects. No association between frequency of HLA- DQB1 genotypes and ATLI was statistically significant in univariate analyses. Multivariate analysis using the conditional logistic regression model revealed that the individuals with two DQB1*05 alleles were at higher risk of ATLI than control subjects. The OR was 5·28 adjusted for use of liver protective drugs and weight (10/88 VS 2/88, 95% CI: 1·134-24·615, P = 0·034). Analysis according to the liver injury type showed that both mixed liver injury patients and cholestatic/mixed liver injury patients had higher proportions of DQB1*05 : 02 alleles ( P values were 0·028 and 0·005, respectively). What is new and conclusion This study suggests that ATLI was more likely in subjects of HLA- DQB1*05/*05 genotype. Further studies are needed to verify this association. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication of antiretroviral therapy (ART) in countries with high rates of endemic TB, but data from South-East Asia are incomplete. Identification of prevalence, risk factors and treatment outcomes of TB-IRIS in Malaysia was sought. Methods: A 3-year retrospective study was conducted among TB-HIV co-infected patients treated at the University of Malaya Medical Centre. Simple and adjusted logistic regressions were used to identify the predictors for TB-IRIS while Cox regression was used to assess the influence of TB-IRIS on long-term CD4 T-cell recovery. Results: One hundred and fifty-three TB-HIV patients were enrolled, of whom 106 had received both anti-TB treatment (ATT) and ART. The median (IQR) baseline CD4 T-cell count was 52 cells µL-1 (13-130 cells µL-1). Nine of 96 patients (9.4%) developed paradoxical TB-IRIS and eight developed unmasking TB-IRIS, at a median (IQR) time of 27 (12-64) and 19 (14-65) days, respectively. In adjusted logistic regression analysis, only disseminated TB was predictive of TB-IRIS [OR: 10.7 (95% CI: 1.2-94.3), P = 0.032]. Mortality rates were similar for TB-IRIS (n = 1, 5.9%) and non- TB-IRIS (n = 5, 5.7%) patients and CD4 T-cell recovery post-ART was not different between the two groups (P = 0.363). Conclusion: Disseminated TB was a strong independent predictor of TB-IRIS in Malaysian HIV-TB patients after commencing ART. This finding underscores the role of a high pathogen load in the pathogenesis of TB-IRIS; so interventions that reduce pathogen load before ART may benefit HIV patients with disseminated TB. [ABSTRACT FROM AUTHOR]

What is Known and Objective: The pathogenic mechanism of antituberculosis drug-induced hepatotoxicity (ATDH) is thought to involve drug-metabolizing enzymes including N-acetyl transferase2 (NAT2), cytochrome P4502E1 (CYP2E1) and glutathione S-transferase (GST) M1, T1. The associations between genetic polymorphisms of those genes and ATDH have been reported but with inconsistent results. Moreover, most studies were hospital-based retrospective studies and not prospective. We aimed to investigate possible associations of CYP2E1, GSTM1 and GSTT1 genetic polymorphisms with ATDH using a more robust case-control study nested in a population-based prospective antituberculosis treatment cohort. Methods: A total of 4304 patients with smear-positive tuberculosis (TB) who received standard short-course chemotherapy were monitored for 6-9 months. Incidence density sampling method was adopted to select controls and 4 : 1 matched with each ATDH cases by age (±5 years), sex, treatment history, disease severity and drug dosage. The CYP2E1, GSTM1 and GSTT1 polymorphisms were genotyped using PCR-RFLP and multiplex PCR methods. Conditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI), as well as corresponding P-values. Results and Discussion: A total of 89 ATDH cases and 356 controls were included in this study. There was no statistically significant association between CYP2E1 RsaI c1/ c1 genotype or DraI C/C genotype and ATDH (OR = 0·99, 95% CI:0·62-1·59; OR = 1·13, 95% CI: 0·40-3·20, respectively) compared with CYP2E1 RsaI c1/c2 or c2/c2 genotypes or DraI D/D genotype, or between GSTM1/ GSTT1 null genotypes and ATDH (OR = 1·22, 95% CI: 0·76-1·96; OR = 0·96, 95% CI: 0·60-1·52, respectively) compared with non-null genotypes. What is new and Conclusion: This is the first study of the involvement of CYP2E1, GSTM1 and GSTT1 genetic polymorphisms in ATDH using a nested case-control population-based prospective cohort design. We could not confirm positive associations of genetic polymorphisms of CYP2E1 RsaI, CYP2E1 DraI, GSTM1 null and GSTT1 null with ATDH reported by various groups, in our Chinese TB population. [ABSTRACT FROM AUTHOR]

Antituberculosis drugs, isoniazid and rifampicin, in combination, are known to develop drug-induced hepatotoxicity (DIH). A higher risk of DIH during antituberculosis treatment (ATT) has been reported in the Indian subcontinent compared to its Western counterparts. The role of genetic factors in a higher incidence of ATT hepatotoxicity in the Indian population is still unclear. The present study was aimed at investigating the role of the N-acetyltransferase2 (NAT2) and cytochrome P4502E1 (CYP2E1) gene polymorphisms in ATT hepatotoxicity. The study population included 218 pulmonary tuberculosis patients who were started on ATT and followed up for the occurrence of ATT-induced hepatitis. The genetic polymorphisms of the NAT2 and CYP2E1 genes were studied by polymerase chain reaction-restriction fragment length polymorphism. The occurrence of DIH was 18.8% (41/218). There was a higher prevalence of NAT2 slow-acetylator genotypes in DIH (70.73%) compared to non-DIH (44.63%; P < 0.05). The frequency of the NAT2*5/*7 and NAT2*6/*7 genotypes was significantly higher in DIH than non-DIH (19.51% vs 6.78%, and 19.51% vs 5.08%). No association of the CYP2E1 RsaI polymorphism could be demonstrated with DIH. However, the DraI C/D genotype of the CYP2E1 gene was mostly prevalent in DIH (85.37%), compared to non-DIH (64.41%) ( P < 0.05). Slow-acetylator status and the CYP2E1 C/D or C/C genotype together showed a higher frequency in DIH (65.85%) compared to non-DIH (28.81%) ( P < 0.0001). The study demonstrates for the first time a possible association between the DraI polymorphism of the CYP2E1 gene and the risk of ATT hepatotoxicity. The genotyping of the NAT2 and CYP2E1 genes could possibly identify the groups at highest risk of developing ATT-induced hepatitis prior to medication. [ABSTRACT FROM AUTHOR]

Despite the important role of pyrazinamide in tuberculosis treatment, little is known about the mechanism of pyrazinamide-induced hepatotoxicity. We inhibited xanthine oxidase in HepG2 cells by using a nontoxic concentration of allopurinol, a well-known xanthine-oxidase inhibitor. This increased in vitro pyrazinamide toxicity in HepG2 cells, which suggests that the hydroxy metabolites of pyrazinamide are probably not fully responsible for pyrazinamide-induced toxicity, and that pyrazinoic acid and pyrazinamide are involved in pyrazinamide toxicity. [ABSTRACT FROM AUTHOR]

A 42-year-old Indian man received 450 mg rifampicin (RIF) and 150 mg isoniazid (INH) daily after being diagnosed of a latent tuberculosis infection. Baseline serum aminotransferase and total bilirubin levels were within normal limits. On day 31 of treatment, the patient experienced epigastric discomfort and general malaise and one week later he developed nausea and episodic vomiting. The patient missed his first scheduled clinic appointment and he continued taking RIF-INH despite his symptoms. He visited the tuberculosis clinic on day 47 of treatment where he was found to be jaundiced and his liver enzymes were elevated. RIF-INH was stopped and the patient was admitted to our hospital as a case of RIF-INH induced hepatitis. On the 7th day of hospitalization, the patient developed consciousness disturbance with flapping tremor and high ammonia level. The patient was diagnosed with fulminant hepatic failure and transferred immediately to the medical intensive care unit, where he died 4 days later. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The impact of the TB-info® software was assessed on the care of patients treated with antituberculosis regimen (ATT). Methods: Cohort study of patients with tuberculosis who received an ATT in 2004 in two hospitals and five medical centres in Paris. Follow-up was implemented with the TB-Info® software. Data were compared to those of the 1999–2003 cohort. Results: Two hundred and nine ATT were initiated in 2004, with a mean duration of 7.2 months. Demographic and clinical data reflected this population precariousness: 79% were foreign-born, 25% lived in institutions and half of them had no or unusual health insurance. Compared to the previous cohort, viral co-infections were tested in more than 80% cases and showed association with HIV, HBV or HCV in 11, 10 and 5% of the patients, respectively. Twenty-one patients were lost for follow-up (11%) and 76% of the smear-positive pulmonary tuberculosis therapies were declared successful but only 34% were declared cured with the WHO criteria. Conclusion: Analysis of the data obtained with TB-info® software showed an improvement of tuberculosis patients care with more co-infection tested and less lost for follow-up. These results confirm the usefulness of this software for patients care and assessment of physicians practice in France. [Copyright &y& Elsevier]

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CD11c is involved in Mycobacterium tuberculosis phagocytosis by human macrophages. CD11c has not been evaluated during antituberculosis (anti-TB) treatment. CD11c expression was evaluated on monocytes from peripheral blood leukocytes of pulmonary TB (PTB) patients and healthy controls by flow cytometry, whereas CD11c/Arg47Trp polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism. PTB patients had increased levels of CD11c on blood monocytes as compared to healthy controls. CD11c levels decreased in response to anti-TB treatment. CD11c/Arg47Trp polymorphism is not associated with PTB. [Copyright &y& Elsevier]

Abstract: Introduction: Tuberculous dactylitis (TD) is a rare disorder. It is the source of a diagnostic hardship as it is difficult to distinguish from other lesions. We report an unusual case with multiple affected sites both in hands and the right big toe. Case report: A 42-year-old female initially presented with two painful tumefactions affecting the left third finger and the right middle finger. These tumefactions had been present for two months. Conventional radiography and computed tomography of the hand revealed soft tissue swelling with bone expansion and cortical destruction in the proximal, middle and distal phalanx of the third finger, the proximal phalanx of the middle finger in the left hand, the proximal and middle phalanx of the middle finger of the right hand. Bone scintigraphy showed additionally infraradiologic localisation in the proximal phalanx of the first right toe. Pathology examination of a biopsy specimen revealed granulomatous osteitis with caseous necrosis. Antituberculosis treatment led to initial clinical remission followed by a recurrence and lesion spreading due to bacteria resistance. The second line treatment with Rifampicine, Ciprofloxacine, Ethambutol and Clarithromycine induced favorable outcome. Conclusion: Tuberculosis dactylitis is well tolerated for a long time leading to a late diagnosis which may favour its spreading. Antituberculosis treatment is effective but the functional outcome depends on early diagnosis. [Copyright &y& Elsevier]

Abstract: Background: Intramedullary spinal tuberculoma is a rare form of central nervous system tuberculosis. This article describes the successful management of intramedullary spinal tuberculoma in 3 patients who received treatment between 2000 and 2003. Case Description: The character of 3 cases was analyzed retrospectively, including clinical manifestation and magnetic resonance imaging findings. All masses were excised totally under microscope. Histopathologic examination revealed tuberculoma. Postoperatively, all patients received a 6 to 9 month course of ATT. The outcome was favorable. Conclusions: The intramedullary spinal tuberculoma must be considered in the differential diagnosis of the spinal cord compression in patients with a history of tuberculosis. When confronted with a progressing neurologic deficit and poor response to ATT, surgical intervention should be considered. The optimal treatment is a combination of microsurgical resection and ATT. [Copyright &y& Elsevier]