Comparing Socio- epidemiological, Clinical Features and Treatment Outcome of Adolescent and Adult TB in Bardhman and Malda districts of West Bengal state in India

Data from five tuberculosis treatment units was collected from Malda and Bardhman districts in West Bengal, India for treatment success rate and dropout rates. The objective was to study, compare and contrast the socio- epidemiological and clinical features of TB between adults and adolescents including treatment success and dropout rates under the revised national tuberculosis control program of government of India. The study cohort was of the year 2011; both primary and secondary data was collected using patient TB cards, TB registers and interviews with patient and/ or patient guardians. Of a total of 1,327 patients registered during this period in the five treatment units, data from 729 registered patients was randomly selected for the study. The cohort data was studied for adolescents aged between 10-19 years and adults aged between 20-45 years. Our results show that adolescents had higher education than adults, had similar socio- economic status, and proportionately had more extra pulmonary tuberculosis than adults. Unlike adult women, females comprise a much higher proportion of TB patients in the adolescent cohort, possibly showing that the protective effect that adult women have against tuberculosis is not as strong among adolescent girls. Finally, treatment success rates are much higher in adolescents than adults. In conclusion, the socio-demographics, clinical picture and treatment outcomes for TB among adolescents are different than that of adults

Linking Poor TB Patients to Government Welfare Schemes to Improve Treatment Adherence in West Bengal, India

Among new smear-positive TB patients in 2010, 7% in West Bengal did not complete treatment. Some patients may discontinue treatment because side-effects of the medicine prevented them from working in the context of financial strain. The objective of the study was to ascertain whether linking TB patients to government welfare schemes was associated with completing the full course of treatment and reducing death rate and default rate. In 2009, CARE India worked with the Ministry of Health and the national TB Control Program to link TB patients to already-existing welfare schemes. TB patients received cash, food and/or employment. The study area was in Murshidabad District in the state of West Bengal. The study period was July 2009 to December 2011. The intervention subjects are those TB patients who received aid through welfare schemes while undergoing DOTS treatment. The comparison subjects are those who received the same DOTS treatment, but did not receive any aid. Data was derived from India’s revised national TB Control Program. Data on the receipt of welfare benefit was ascertained directly by asking the patient. Effectiveness of the intervention was determined by comparing treatment success rate, default rate and death rate of both new and retreatment patients in the intervention and comparison groups. Treatment Success Rate among new patients was 92.2% for those who received welfare and 88.5% for non-recipients. Treatment Success Rate among retreatment patients was 83.4% in the intervention group and 72% in the comparison group. Among both new and retreatment patients, there is a statistically significant difference between the Treatment Success Rates of the comparison and intervention groups (p<0.01). Treatment Success Rate increased for both new and retreatment patients when linked to welfare. The effect is seen to be modest for new patients, largely due to the ‘ceiling effect’, but much more in retreatment cases

Autoregulation of yeast ribosomal proteins discovered by efficient search for feedback regulation

Post-transcriptional autoregulation of gene expression is common in bacteria but many fewer examples are known in eukaryotes. We used the yeast collection of genes fused to GFP as a rapid screen for examples of feedback regulation in ribosomal proteins by overexpressing a non-regulatable version of a gene and observing the effects on the expression of the GFP-fused version. We tested 95 ribosomal protein genes and found a wide continuum of effects, with 30% showing at least a 3-fold reduction in expression. Two genes, RPS22B and RPL1B, showed over a 10-fold repression. In both cases the cis-regulatory segment resides in the 5\u27 UTR of the gene as shown by placing that segment of the mRNA upstream of GFP alone and demonstrating it is sufficient to cause repression of GFP when the protein is over-expressed. Further analyses showed that the intron in the 5\u27 UTR of RPS22B is required for regulation, presumably because the protein inhibits splicing that is necessary for translation. The 5\u27 UTR of RPL1B contains a sequence and structure motif that is conserved in the binding sites of Rpl1 orthologs from bacteria to mammals, and mutations within the motif eliminate repression

Optimizing Village-Level Targeting of Active Case Detection to Support Visceral Leishmaniasis Elimination in India.

Background: India has made major progress in improving control of visceral leishmaniasis (VL) in recent years, in part through shortening the time infectious patients remain untreated. Active case detection decreases the time from VL onset to diagnosis and treatment, but requires substantial human resources. Targeting approaches are therefore essential to feasibility. Methods: We analyzed data from the Kala-azar Management Information System (KAMIS), using village-level VL cases over specific time intervals to predict risk in subsequent years. We also graphed the time between cases in villages and examined how these patterns track with village-level risk of additional cases across the range of cumulative village case-loads. Finally, we assessed the trade-off between ACD effort and yield. Results: In 2013, only 9.3% of all villages reported VL cases; this proportion shrank to 3.9% in 2019. Newly affected villages as a percentage of all affected villages decreased from 54.3% in 2014 to 23.5% in 2019, as more surveillance data accumulated and overall VL incidence declined. The risk of additional cases in a village increased with increasing cumulative incidence, reaching approximately 90% in villages with 12 cases and 100% in villages with 45 cases, but the vast majority of villages had small cumulative case numbers. The time-to-next-case decreased with increasing case-load. Using a 3-year window (2016-2018), a threshold of seven VL cases at the village level selects 329 villages and yields 23% of cases reported in 2019, while a threshold of three cases selects 1,241 villages and yields 46% of cases reported in 2019. Using a 6-year window increases both effort and yield. Conclusion: Decisions on targeting must consider the trade-off between number of villages targeted and yield and will depend upon the operational efficiencies of existing programs and the feasibility of specific ACD approaches. The maintenance of a sensitive, comprehensive VL surveillance system will be crucial to preventing future VL resurgence

Development and Evaluation of Active Case Detection Methods to Support Visceral Leishmaniasis Elimination in India.

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case's knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 via ACD (15 (0.8%) via house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with =90 days compared to the referent of <30 days for ACD vs PCD were 0.88, 0.56 and 0.42 respectively. These ACD strategies not only reduce time to diagnosis, and thus risk of transmission, but also ensure that there is a double check on the proportion of cases actually getting captured. Such a process can supplement passive case detection efforts that must go on, possibly perpetually, even after elimination as a public health problem is achieved

Synthesis and thermal reactivity of pyrrolidine- and 2-pyrrolidinone-fused cyclic enediynes

Various bicyclic enediynes containing pyrrolidine and pyrrolidinone moieties were synthesised. Thermal reactivity studies indicated the lowering of the onset temperature for Bergman cyclisation upon fusion of these heterocyclic systems onto the cyclic enediyne