The Profile and Treatment Outcomes of the Older (Aged 60 Years and Above) Tuberculosis Patients in Tamilnadu,South India

Background

With changing demographic patterns in the context of a high tuberculosis (TB) burden country, like India, there is very little information on the clinical and demographic factors associated with poor treatment outcome in the sub-group of older TB patients. The study aimed to assess the proportion of older TB patients (60 years of age and more), to compare the type of TB and treatment outcomes between older TB patients and other TB patients (less than 60 years of age) and to describe the demographic and clinical characteristics of older TB patients and assess any associations with TB treatment outcomes.

Methods

A retrospective cohort study involving a review of records from April to June 2011 in the 12 selected districts of Tamilnadu, India. Demographic, clinical and WHO defined disease classifications and treatment outcomes of all TB patients aged 60 years and above were extracted from TB registers maintained routinely by Revised National TB Control Program (RNTCP).

Results

Older TB patients accounted for 14% of all TB patients, of whom 47% were new sputum positive. They had 38% higher risk of unfavourable treatment outcomes as compared to all other TB patients (Relative risk (RR)-1.4, 95% CI 1.2–1.6). Among older TB patients, the risk for unfavourable treatment outcomes was higher for those aged 70 years and more (RR 1.5, 95% CI 1.2–1.9), males (RR 1.5, 95% CI 1.0–2.1), re-treatment patients (RR 2.5, 95% CI 1.9–3.2) and those who received community-based Direct Observed Treatment (RR 1.4, 95% CI 1.1–1.9).

Conclusion

Treatment outcomes were poor in older TB patients warranting special attention to this group – including routine assessment and recording of co-morbidities, a dedicated recording, reporting and monitoring of outcomes for this age-group and collaboration with National programme of non-communicable diseases for comprehensive management of co-morbidities.     

Association between RAD51, XRCC2 and XRCC3 gene polymorphisms and risk of ovarian cancer: a case control and an in silico study

Molecular Biology Reports - Homologous recombination (HR) is one of the important mechanisms in repairing double-strand breaks to maintain genomic integrity and DNA stability from the cytotoxic...     

Catching the adaptor—WDFY1, a new player in the TLR–TRIF pathway

The innate immune system detects microbes and abnormal self through pattern recognition receptors (PRRs), which detect molecules that are either specific for microbes (such as lipopolysaccharide), present in much higher concentrations during infection (such as double‐stranded RNA), or present in aberrant locations (such as cytosolic DNA) 1 . The Toll‐like receptors (TLRs) are the best‐described set of PRRs. TLRs are membrane‐bound receptors localized on the plasma membrane and in endosomes, the ligand‐binding regions of which face the extracellular environment and the endosomal lumen, respectively 1 . In this issue of EMBO Reports, Hu and colleagues report that WD‐repeat and FYVE‐domain‐containing protein 1 (WDFY1) recruits the signaling adaptor TRIF to TLR3 and TLR4, thereby potentiating signaling from these PRRs (Fig  1 ); 2 .     

A High-Throughput Cidality Screen for Mycobacterium Tuberculosis

Exposure to Mycobacterium tuberculosis (Mtb) aerosols is a major threat to tuberculosis (TB) researchers, even in bio-safety level-3 (BSL-3) facilities. Automation and high-throughput screens (HTS) in BSL3 facilities are essential for minimizing manual aerosol-generating interventions and facilitating TB research. In the present study, we report the development and validation of a high-throughput, 24-well ‘spot-assay’ for selecting bactericidal compounds against Mtb. The bactericidal screen concept was first validated in the fast-growing surrogate Mycobacterium smegmatis (Msm) and subsequently confirmed in Mtb using the following reference anti-tubercular drugs: rifampicin, isoniazid, ofloxacin and ethambutol (RIOE, acting on different targets). The potential use of the spot-assay to select bactericidal compounds from a large library was confirmed by screening on Mtb, with parallel plating by the conventional gold standard method (correlation, r² = 0.808). An automated spot-assay further enabled an MBC90 determination on resistant and sensitive Mtb clinical isolates. The implementation of the spot-assay in kinetic screens to enumerate residual Mtb after either genetic silencing (anti-sense RNA, AS-RNA) or chemical inhibition corroborated its ability to detect cidality. This relatively simple, economical and quantitative HTS considerably minimized the bio-hazard risk and enabled the selection of novel vulnerable Mtb targets and mycobactericidal compounds. Thus, spot-assays have great potential to impact the TB drug discovery process.     

DGKι regulates presynaptic release during mGluR-dependent LTD

Diacylglycerol (DAG) is an important lipid second messenger. DAG signalling is terminated by conversion of DAG to phosphatidic acid (PA) by diacylglycerol kinases (DGKs). The neuronal synapse is a major site of DAG production and action; however, how DGKs are targeted to subcellular sites of DAG generation is largely unknown. We report here that postsynaptic density (PSD)-95 family proteins interact with and promote synaptic localization of DGKι. In addition, we establish that DGKι acts presynaptically, a function that contrasts with the known postsynaptic function of DGKζ, a close relative of DGKι. Deficiency of DGKι in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGKι-/- synapses show a reduction in metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) at neonatal (～2 weeks) stages that involve suppression of a decrease in presynaptic release probability. Inhibition of protein kinase C normalizes presynaptic release probability and mGluR-LTD at DGKι-/- synapses. These results suggest that DGKι requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD.     

Identification of cross-contaminated animal cells by PCR and isoenzyme analysis

Animal cell lines have become very popular substrates for the production of vaccines and biopharmaceuticals. Characterization of candidate production cell lines is central to ensure product safety and maintenance of consistency in the manufacture of biologicals. Nested PCR and isoenzyme analysis have been used widely to prove the identity and purity of various cell lines and primary cells individually and also after deliberate cross-contamination. The nested PCR based on the Cytochrome b (Cyt b) gene of mitochondrial DNA (Mt DNA) was found to be more sensitive than isoenzyme analysis in detecting low levels of contaminants (as low as 1%). Interestingly, competition between different co-cultured cell lines has shown in one case that cross-contamination need not always results in a mixed cell population. The nested PCR technique for the Cyt b gene described in this study appears to be a potential replacement for isoenzyme analysis and here we demonstrate the PCR method used is sensitive and reliable for cell line authentication in a simple, rapid and reliable format to help assure the authenticity of cell substrates for the production of safe vaccines and biopharmaceuticals.