Timely diagnosis of paucibacillary tuberculosis (TB) which includes smear-negative pulmonary TB (PTB) and extra-pulmonary TB (EPTB) remains a challenge. This study was performed to assess the ...diagnostic utility of stool as a specimen of choice for detection of mycobacterial DNA in paucibacillary TB patients in a TB-endemic setting. Stool samples were collected from 246 subjects including 129 TB patients (62 PTB and 67 EPTB) recruited at TB hospital in Delhi, India. Diagnostic efficacy of stool IS6110 PCR (n = 228) was measured, using microbiologically/clinically confirmed TB as the reference standard. The clinical sensitivity of stool PCR was 97.22% (95% confidence interval (CI), 85.47-99.93) for detection of Mycobacterium tuberculosis in stool samples of smear-positive PTB patients and 76.92% (CI, 56.35-91.03) in samples from smear-negative PTB patients. Overall sensitivity of PCR for EPTB was 68.66% (CI, 56.16-79.44), with the highest sensitivity for stool samples from patients with lymph node TB (73.5%), followed by abdominal TB (66.7%) and pleural effusion (56.3%). Stool PCR presented a specificity of 95.12%. The receiver operating characteristic curve also indicated the diagnostic utility of stool PCR in TB detection (AUC: 0.882). The performance characteristic of the molecular assay suggests that stool DNA testing has clinical value in detection of TB.
Prolonged treatment of tuberculosis (TB) often leads to poor compliance, default and relapse, converting primary TB patients into category II TB (Cat IITB) cases, many of whom may convert to ...multi-drug resistant TB (MDR-TB). We have evaluated the immunotherapeutic potential of Mycobacterium indicus pranii (MIP) as an adjunct to Anti-Tubercular Treatment (ATT) in Cat II pulmonary TB (PTB) patients in a prospective, randomized, double blind, placebo controlled, multicentric clinical trial. 890 sputum smear positive Cat II PTB patients were randomized to receive either six intra-dermal injections (2 + 4) of heat-killed MIP at a dose of 5 × 10
bacilli or placebo once in 2 weeks for 2 months. Sputum smear and culture examinations were performed at different time points. MIP was safe with no adverse effects. While sputum smear conversion did not show any statistically significant difference, significantly higher number of patients (67.1%) in the MIP group achieved sputum culture conversion at fourth week compared to the placebo (57%) group (p = 0.0002), suggesting a role of MIP in clearance of the bacilli. Since live bacteria are the major contributors for sustained incidence of TB, the potential of MIP in clearance of the bacilli has far reaching implications in controlling the spread of the disease.
Tuberculosis (TB) continues to be a global public health problem. Physicians fail to clearly interpret cycle threshold (Ct) values as a measure of mycobacterial burden due to the paucity of ...literature correlating Ct values with the clinical scoring. This study aims to correlate the clinical scoring parameters (Bandim TB score and Karnofsky Performance score (KPS)) with Ct values obtained by Cartridge-Based Nucleic Acid Amplification Test (CBNAAT).
The study spanned from November 2019 to October 2021, during which a total of 40 cases were recruited. These cases were identified as pulmonary TB patients based on Ziehl-Neelsen staining for acid-fast bacilli and/or the GeneXpert MTB/RIF assay. Bandim TB scores and KPSs were recorded using standardized questionnaires.
There was a strong negative correlation between Bandim TB score and Ct value (mean), and this correlation was statistically significant (rho = -0.82, p < 0.001). There was a moderate positive correlation between KPS and Ct value (mean), and this correlation was statistically significant (rho = 0.57, p < 0.001).
No literature has compared Bandim TB score and KPS with the Ct values obtained by CBNAAT for pulmonary TB. Thus, the knowledge on the proper utilization of CBNAAT cycle threshold values and its correlation with clinical scoring parameters will help clinicians in the early identification and prompt initiation of appropriate treatment.
Cyclin kinase inhibitor p21 is one of the most potent inhibitors of aortic smooth muscle cell proliferation, a key mediator of atherosclerosis. This study tests if p2l deficiency will result in ...severe atherosclerosis in a mouse model. p21-/- and strain matched wild type mice were fed with high fat diet for 21 weeks. Analysis for biochemical parameters (cholesterol, triglycerides) in serum and mRNA expression of CD36, HO-1, TGF-beta, IFN-gamma, TNF-alpha, PPAR-gamma and NADPH oxidase components (p22phox, NOX-1 and Rac-1) was performed in aortic tissues by Real Time PCR. p21-/- mice gained significantly (p < 0.01) more weight than wild type mice, triglycerides (p < 0.05) and cholesterol levels (p < 0.01) were more pronounced in the sera of p21-/- compared to wild type mice fed with high fat diet. High fat diet resulted in significantly decreased TGF-beta (p < 0.02), HO-l (p < 0.02) and increased CD36 (p < 0.03) mRNA expression in aortic tissues of p21-/- mice compared to animal fed with regular diet. IFN-gamma mRNA expression (235 +/- 11 folds) increased significantly in high fat diet fed p21-/- mice and a multifold modulation of PPAR-gamma(136 +/- 7), p22phox, NOX-1 and Rac-1 (15-35-folds) mRNA in aortic tissues from p21-/- mice compared to the wild type mice. Severity of atherosclerotic lesions was significantly higher in p21-/- compared to wild type mice. The results demonstrate that the deficiency of p21 leads to altered expression of pro-atherogenic genes, and severe atherosclerosis in mice fed with high fat diet. This opens the possibility of p21 protein as a therapeutic tool to control progression of atherosclerosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Tuberculosis (TB) patients with human immunodeficiency virus (HIV) co-infection have worse TB treatment outcomes compared to patients with TB alone. The distribution of unfavourable treatment ...outcomes differs by socio-demographic and clinical characteristics, allowing for early identification of patients at risk.
To develop a statistical model that can provide individual probabilities of unfavourable outcomes based on demographic and clinical characteristics of TB-HIV co-infected patients.
We used data from all TB patients with known HIV-positive test results (aged ≥15 years) registered for first-line anti-TB treatment (ATT) in 2015 under the Revised National TB Control Programme (RNTCP) in Delhi, India. We included variables on demographics and pre-treatment clinical characteristics routinely recorded and reported to RNTCP and the National AIDS Control Organization. Binomial logistic regression was used to develop a statistical model to estimate probabilities of unfavourable TB treatment outcomes (i.e., death, loss to follow-up, treatment failure, transfer out of program, and a switch to drug-resistant regimen).
Of 55,260 TB patients registered for ATT in 2015 in Delhi, 928 (2%) had known HIV-positive test results. Of these, 816 (88%) had drug-sensitive TB and were ≥15 years. Among 816 TB-HIV patients included, 157 (19%) had unfavourable TB treatment outcomes. We developed a model for predicting unfavourable outcomes using age, sex, disease classification (pulmonary versus extra-pulmonary), TB treatment category (new or previously treated case), sputum smear grade, known HIV status at TB diagnosis, antiretroviral treatment at TB diagnosis, and CD4 cell count at ATT initiation. The chi-square p-value for model calibration assessed using the Hosmer-Lemeshow test was 0.15. The model discrimination, measured as the area under the receiver operator characteristic (ROC) curve, was 0.78.
The model had good internal validity, but should be validated with an independent cohort of TB-HIV co-infected patients to assess its performance before clinical or programmatic use.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The contribution of chronic tobacco exposure in determining post-myocardial infarction (MI) left ventricular (LV) remodeling and possible therapeutic strategies has not been investigated ...systematically. In this small animal investigation, we demonstrate that chronic tobacco smoke exposure leading up to acute MI in rats is associated with greater histological extent of myocardial necrosis and consequent worse LV function. These findings are associated with increased transcriptomic expression of pro-inflammatory cytokines, tissue repair molecules and markers of oxidative stress in the myocardium. The results demonstrate that an N-acetyl cysteine (NAC) treatment significantly reduced tobacco-exposed induced infarct size and percent fractional shortening. A significantly increased LV end-systolic diameter was observed in tobacco-exposed sham compared to tobacco-naïve sham (4.92±0.41 vs 3.45±0.33; P<0.05), and tobacco-exposed MI compared to tobacco-naïve MI (8.24±0.3 vs 6.1±0.49; P<0.01) rats. Decreased intracardiac mRNA expression of the markers of inflammation, tissue repair and oxidative stress and circulating levels of pro-inflammatory cytokines accompanied these positive effects of NAC. The treatment of tobacco-exposed MI rats with NAC resulted in significantly increased levels of intracardiac mRNA expression of antioxidants, including superoxide dismutase, thioredoxin and nuclear factor-E2-related factor 2, as well as circulating levels of glutathione (7±0.12 vs 10±0.18; P⩽0.001), where the levels were almost identical to the tobacco-naïve sham rats. These findings identify a novel post-infarction therapy for amelioration of the adverse effects of tobacco exposure on the infracted myocardium and advocate the use of dietary supplement antioxidants for habitual smokers to prevent and reverse cardiovascular adverse effects in the absence of successful achievement of cessation of smoking.
Background: Suboptimal adherence to anti-tuberculosis medication in patients is associated with adverse treatment outcomes including treatment failure, relapse, and emergence of drug resistance. ...Objectives: We conducted the present study with the objectives of evaluating the effectiveness of a mHealth package on the medication adherence of patients with tuberculosis (TB) on antitubercular (directly observed treatment short-course DOTS) treatment. Methods: We conducted Quasi-experimental study at six DOTS centers of Delhi among 220 newly diagnosed TB patients. We included adult TB patients (18 years and above) who were on DOTS therapy ≥30 days, had access to a mobile phone and were able to read messages and receive calls. We excluded patients with impaired hearing, blindness and those on non-DOTS therapy or having multidrug-resistant/extensively drug-resistant TB. Participants in the intervention group received amHealth package for 90 days. The medication adherence of the study participants was measured using Morisky, Green, and Levine Adherence Scale. Results: A total of 130 men and 90 women were recruited for the study. Occupational interference and forgetfulness were the most common reasons for medication nonadherence in the patients. In the intervention group, the medication adherence to antitubercular medication (daily DOTS regimen) was 85.5% at baseline which increased to 96.4% at endline (postintervention) (P = 0.004). No significant change was observed in the control group (P = 0.328). The increase in adherence was observed across the following subgroups: age, gender, education, and Socioeconomic status. Conclusions: The mHealth intervention in TB patients was effective in improving the adherence to DOTS therapy.
Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. ...Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care.
A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities.
The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up.
The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diagnosis of TB in pediatric population poses several challenges. A novel initiative was implemented in several major cities of India aimed at providing upfront access to free-of-cost Xpert MTB/RIF ...to presumptive pediatric TB cases. This paper aims to describe the experience of implementing this large initiative and assess feasibility of the intervention in high TB burden settings.
Data were drawn from the pediatric TB project implemented in 10 major cities of India between April 2014 and March 2018. In each city, providers, both public and private, were engaged and linked with a high throughput Xpert MTB/RIF lab (established in that city) through rapid specimen transportation and electronic reporting system. Rates and proportions were estimated to describe the characteristics of this cohort.
Of the total 94,415 presumptive pediatric TB cases tested in the project, 6,270 were diagnosed positive for MTB (6.6%) on Xpert MTB/RIF (vs 2% on smear microscopy). Among MTB positives, 545 cases were rifampicin resistant (8.7%). The median duration between collection of specimens and reporting of results was 0 days (same day) and >89% cases were initiated on treatment. Approximately 50% of the specimens tested were non-sputum. The number of providers/facilities engaged under the project increased >10-fold (from 124 in Q2'14 to 1416 in Q1'18).
This project, which was one of the largest initiatives globally among pediatric population, demonstrated the feasibility of sustaining rapid and upfront access to free-of-cost Xpert MTB/RIF testing. The project underscores the efficiency of this rapid diagnostic assay in tackling several challenges in pediatric TB diagnosis, identifies opportunities for further interventions as well as brings to light scope for effective engagement with healthcare providers. The findings have facilitated a policy decision by National TB Programme mandating the use of Xpert MTB/RIF as a primary diagnostic tool for TB diagnosis in children, which is being scaled-up.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The National TB Elimination Programme (NTEP) has quite successfully involved private sector for referral of presumptive drug resistant TB (DR-TB) patients for molecular testing and referral for DR-TB ...management. There was a challenge as all the referred patients were not reaching to the facilities. A "DOST" intervention model was implemented to strengthen the patient care pathway. We conducted this study to describe the patient care cascade, the clinico-demographic characteristics of patients linked to the treatment and to estimate the mean turn-around time for drug resistant TB care services.
It is a cross-sectional study conducted at New Delhi during the period July 2019-December 2020 under programmatic settings.
A total of 9,331 patients were subjected to CB-NAAT test and 382 (4%) were found to be resistant for rifampicin and 231 (76%) were initiated on treatment in the public sector under NTEP.
The DOST intervention model developed to link the DR-TB patients from private sector to the public sector DR-TB centers is found to be efficient and effective.
PDF
