Changing patterns of household transmission of tuberculosis in an eastern state of India: The impact of COVID19 pandemic.

BACKGROUND: The COVID-19 Pandemic has affected many components of the Tuberculosis (TB) control program. Due to lockdown and restrictions, people, including TB patients, might have spent more time in the household. There might be an increased TB transmission among the household contacts (HHC). The current study was conducted to measure the household transmission of TB and also find out the relationship with several clinico-social factors. METHODS: Contact tracing data of West Bengal, India, was extracted from Nikshay portal of Central TB Division, Government of India. The anonymized data was divided into two parts, firstly before the lockdown initiation in India and secondly during the lockdown. A modified Poisson regression model was developed to determine the statistical association between clinico-social variables and the pandemic with household-level secondary TB cases. RESULTS: There was a 30% reduction in daily TB case notification, but the proportion of HHC screened was 4% higher during the pandemic than the pre-pandemic period. The secondary attack rate of household TB disease transmission was 34% lower during the pandemic period. Index TB patients aged under ten years, microbiologically positive, Drug-Resistant TB, having three or more HHCs, treatment delay more than seven days, notified from the private sector, and diagnosis during the pre-pandemic period was found to be independently associated with a higher risk of having a secondary TB case at household. CONCLUSION: The risk of household TB transmission was significantly lower during the pandemic period compared to the pre-pandemic period, which may be due to better infection prevention and control practices.

Active Case Finding for Tuberculosis through TOUCH Agents in Selected High TB Burden Wards of Kolkata, India: A Mixed Methods Study on Outcomes and Implementation Challenges.

Active case finding (ACF) for tuberculosis (TB) was implemented in 60 selected high TB burden wards of Kolkata, India. Community volunteers called TOUCH (Targeted Outreach for Upliftment of Community Health) agents (TAs) identified and referred presumptive TB patients (PTBPs) to health facilities for TB diagnosis and treatment. We aimed to describe the "care cascade" of PTBPs that were identified during July to December 2018 and to explore the reasons for attrition as perceived by TAs and PTBPs. An explanatory mixed-methods study with a quantitative phase of cohort study using routinely collected data followed by descriptive qualitative study with in-depth interviews was conducted. Of the 3,86242 individuals that were enumerated, 1132 (0.3%) PTBPs were identified. Only 713 (63.0%) PTBPs visited a referred facility for TB diagnosis. TB was diagnosed in 177 (24.8%). The number needed to screen for one TB patient was 2183 individuals. The potential reasons for low yield were stigma and apprehension about TB, distrust about TA, wage losses for attending health facilities, and substance abuse among PTBPs. The yield of ACF was suboptimal with low PTBP identification rate and a high attrition rate. Interviewing each individual for symptoms of TB and supporting PTBPs for diagnosis through sputum collection and transport can be adopted to improve the yield.

Expression and regulation of the Msx1 natural antisense transcript during development.

Bidirectional transcription, leading to the expression of an antisense (AS) RNA partially complementary to the protein coding sense (S) RNA, is an emerging subject in mammals and has been associated with various processes such as RNA interference, imprinting and transcription inhibition. Homeobox genes do not escape this bidirectional transcription, raising the possibility that such AS transcription occurs during embryonic development and may be involved in the complexity of regulation of homeobox gene expression. According to the importance of the Msx1 homeobox gene function in craniofacial development, especially in tooth development, the expression and regulation of its recently identified AS transcripts were investigated in vivo in mouse from E9.5 embryo to newborn, and compared with the S transcript and the encoded protein expression pattern and regulation. The spatial and temporal expression patterns of S, AS transcripts and protein are consistent with a role of AS RNA in the regulation of Msx1 expression in timely controlled developmental sites. Epithelial-mesenchymal interactions were shown to control the spatial organization of S and also AS RNA expression during early patterning of incisors and molars in the odontogenic mesenchyme. To conclude, this study clearly identifies the Msx1 AS RNA involvement during tooth development and evidences a new degree of complexity in craniofacial developmental biology: the implication of endogenous AS RNAs.

Intergenic enhancers with distinct activities regulate Dlx gene expression in the mesenchyme of the branchial arches.

The vertebrate Dlx genes, generally organized as tail-to-tail bigene clusters, are expressed in the branchial arch epithelium and mesenchyme with nested proximodistal expression implicating a code that underlies the fates of jaws. Little is known of the regulatory architecture that is responsible for Dlx gene expression in developing arches. We have identified two distinct cis-acting regulatory sequences, I12a and I56i, in the intergenic regions of the Dlx1/2 and Dlx5/6 clusters that act as enhancers in the arch mesenchyme. LacZ transgene expression containing I12a is restricted to a subset of Dlx-expressing ectomesenchyme in the first arch. The I56i enhancer is active in a broader domain in the first arch mesenchyme. Expression of transgenes containing either the I12a or the I56i enhancers is dependent on the presence of epithelium between the onset of their expression at E9-10 until independence at E11. Both enhancers positively respond to FGF8 and FGF9; however, the responses of the reporter transgenes were limited to their normal domain of expression. BMP4 had a negative effect on expression of both transgenes and counteracted the effects of FGF8. Furthermore, bosentan, a pharmacological inhibitor of Endothelin-1 signaling caused a loss of I56i-lacZ expression in the most distal aspects of the expression domain, corresponding to the area of Dlx-6 expression previously shown to be under the control of Endothelin-1. Thus, the combinatorial branchial arch expression of Dlx genes is achieved through interactions between signaling pathways and intrinsic cellular factors. I56i drives the entire expression of Dlx5/6 in the first arch and contains necessary sequences for regulation by at least three separate pathways, whereas I12a only replicates a small domain of endogenous expression, regulated in part by BMP-4 and FGF-8.