Project description:INTRODUCTION:There is lack of information on the proportion of new smear-positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome. OBJECTIVE:To estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined. METHODOLOGY:Adult (aged ? 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared "treatment success" at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence. RESULTS:Of the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2-21.6] and TB recurrence rate per 100 person-years was 12.7 [95% CI: 0.4-25]. TB recurrence per 100 person-years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence. CONCLUSION:A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings.

Project description:BackgroundThe National Tuberculosis Elimination Programme (NTEP) of India is aiming to eliminate TB by 2025. The programme has increased its services and resources to strengthen the accurate and early detection of TB. It is important to estimate the cost of TB diagnosis in India considering the advancement and implementation of new diagnostic tools under the NTEP. The objective of this study was to estimate the unit costs of providing TB diagnostic services at different levels of public health facilities with different algorithms implemented under the NTEP in Chennai, Tamil Nadu, South India.MethodsThis costing study was conducted from the perspective of the health system. This study used only secondary data and information that were available in the public domain. Data were collected with the approval of health authorities. The patient's diagnostic path from the point of registration until the final diagnosis was considered in the costing exercise. The unit costs of different diagnostic tools used in the NTEP implemented by Chennai Corporation were calculated.ResultsWe estimated the unit cost of the eight laboratory tests (Ziehl-Neelsen [ZN], fluorescence microscopy [FM], x-ray, digital x-ray, gene Xpert MTB/RIF (cartridge-based nucleic acid amplification test [NAAT] that identifies rifampicin resistant Mycobacterium Tuberculosis) Mycobacterium Tuberculosis/Rifampicin [MTB/RIF], mycobacteria growth indicator tube [MGIT], line probe assay [LPA] and Lowenstein Jensen [LJ] culture) for diagnosis of drug-sensitive and drug-resistant TB. The unit costs included fixed and variable costs for smear examination by ZN microscopy (₹ [Indian Rupee] 326 [US${\$}$4.72], FM (₹104 [US${\$}$1.5]), x-ray (₹218 [US${\$}$3.15]), digital X-ray (₹281 [US${\$}$4.07]), gene Xpert MTB/RIF (₹1137 [US${\$}$16.47]), MGIT (₹7038 [US${\$}$102]), LPA (₹6448 [US${\$}$93.44]) and LJ culture (₹4850 [US${\$}$70.28]). Out of 10 diagnostic algorithms used for TB diagnosis, algorithms using only smear microscopy had the lowest cost, followed by smear microscopy with x-ray for drug-sensitive TB (₹104 [US${\$}$1.5] to ₹544 [US${\$}$7.88]). Diagnostic algorithms for drug-resistant TB involving LPA and gene Xpert MTB/RIF were the most expensive.ConclusionsUnderstanding the various costs contributing to TB diagnosis in India provides crucial evidence for policymakers, programme managers and researchers to optimise programme spending and efficiently use resources.

Project description:BACKGROUND:Early initiation of breastfeeding (EIBF) reduces the risk of neonatal mortality. Previous studies from India have documented some factors associated with EIBF. However, those studies used data with limited sample size that potentially affect the application of the evidence. Additionally, the effectiveness of national breastfeeding programmes requires up-to-date analysis of new and robust EIBF data. The present study aimed to investigate the prevalence and determinants of EIBF in India and determine to what extent these factors differ by a mother's residence in the rural or urban area. METHODS:This study used information from a total weighted sample of 94,401 mothers from the 2015-2016 India National Family Health Survey. Multivariate logistic regression was used to investigate the association between the study factors and EIBF in India and rural-urban populations, after adjusting for confounders and sampling weight. RESULTS:Our analysis indicated that 41.5% (95% confidence interval (CI): 40.9-42.5, P < 0.001) of Indian mothers initiated breastfeeding within 1-h post-birth, with similar but significant different proportions estimated for those who resided in rural (41.0, 95% CI: 40.3-41.6, P < 0.001) and urban (42.9, 95% CI: 41.7-44.2, P < 0.001) areas. Mothers who had frequent health service contacts and those with higher educational attainment reported higher EIBF practice. Multivariate analyses revealed that higher educational achievement, frequent antenatal care visits and birthing in a health facility were associated with EIBF in India and rural populations (only health facility birthing for urban mothers). Similarly, residing in the North-Eastern, Southern, Eastern and Western regions were also associated with EIBF. Birthing through caesarean, receiving delivery assistance from non-health professionals and residing in rural areas of the Central region were associated with delayed EIBF in all populations. CONCLUSION:We estimated that more than half of Indian mothers delayed breastfeeding initiation, with different rural-urban prevalence. Key modifiable factors (higher maternal education and frequent health service contacts) were associated with EIBF in India, with notable difference in rural-urban populations. Our study suggests that targeted and well-coordinated infant feeding policies and interventions will improve EIBF for all Indian mothers.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013.

Project description:India launched a national community-based active TB case finding (ACF) campaign in 2017 as part of the strategic plan of the National Tuberculosis Elimination Programme (NTEP). This review evaluated the outcomes for the components of the ACF campaign against the NTEP's minimum indicators and elicited the challenges faced in implementation. We supplemented data from completed pretested data proformas returned by ACF programme managers from nine states and two union territories (for 2017-2019) and five implementing partner agencies (2013-2020), with summary national data on the state-wise ACF outcomes for 2018-2020 published in annual reports by the NTEP. The data revealed variations in the strategies used to map and screen vulnerable populations and the diagnostic algorithms used across the states and union territories. National data were unavailable to assess whether the NTEP indicators for the minimum proportions identified with presumptive TB among those screened (5%), those with presumptive TB undergoing diagnostic tests (>95%), the minimum sputum smear positivity rate (2% to 3%), those with negative sputum smears tested with chest X-rays or CBNAAT (>95%) and those diagnosed through ACF initiated on anti-TB treatment (>95%) were fulfilled. Only 30% (10/33) of the states in 2018, 23% (7/31) in 2019 and 21% (7/34) in 2020 met the NTEP expectation that 5% of those tested through ACF would be diagnosed with TB (all forms). The number needed to screen to diagnose one person with TB (NNS) was not included among the NTEP's programme indicators. This rough indicator of the efficiency of ACF varied considerably across the states and union territories. The median NNS in 2018 was 2080 (interquartile range or IQR 517-4068). In 2019, the NNS was 2468 (IQR 1050-7924), and in 2020, the NNS was 906 (IQR 108-6550). The data consistently revealed that the states that tested a greater proportion of those screened during ACF and used chest X-rays or CBNAAT (or both) to diagnose TB had a higher diagnostic yield with a lower NNS. Many implementation challenges, related to health systems, healthcare provision and difficulties experienced by patients, were elicited. We suggest a series of strategic interventions addressing the implementation challenges and the six gaps identified in ACF outcomes and the expected indicators that could potentially improve the efficacy and effectiveness of community-based ACF in India.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 Î¼m and smaller than 0.5 Î¼m (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013. The PM filter samples used in the present study were PM10 and PM0.5 from the urban site - total of 4 samples from 2 sampling months; and PM0.5 from the rural site - total of 2 samples from 2 sampling months (PM10 samples from the rural site were not tested due to their very low concentration in organic compounds, and insignificant biological activity, previously measured). Sampling occurred during the cold periods of the year 2012/2013. The organic fraction of PM samples was extracted by sonication using a mixture of dichloromethane:methanol. Then, the extracts were filtered, evaporated and re-dissolved in Dimethyl sulfoxide (DMSO). Zebrafish fertilized eggs were exposed to PM organic extracts (0.2% DMSO) from the urban and rural sites from 24 to 120h post-fertilization. Total RNA was isolated from whole embryos (pools of 20 individuals), using Trizol reagent protocol (Invitrogen Life Technologies, Carlsberg, CA). The microarray study was performed using the Agilent Two-colour D. rerio Oligo Microarray v3 platform, following the Agilent Microarray â?? Based Gene Expression Analysis protocol. Three biological replicates were performed for each PM sample and controls. Biological replicates, a technical replicate and a self-to-self, were simultaneously amplified and labelled using Cyanine 3 (Cy3) and Cyanine 5 (Cy5) dye. After cRNA purification (RNeasy Kit, Quiagen GmbH, Hilden, Germany), the cRNA concentration and labelling were quantified in the NanoDrop spectrophotometer, obtaining incorporation rates in the range of 15-20pmol of cyanide dye/Âµl cRNA and yield values > 0.825ug, as recommended. cRNA was fragmented and hybridized in 4x44K arrays, for 17h at 65oC. After the hybridization the array slides were washed, and immediately scanned using Microarray Scanner Agilent G2505C system. Data was extracted using Agilent Feature Extraction Software v10.5.1.1, and the quality of microarray data was evaluated using the Quality Control report provided by Agilent Software. Based on the microarray data analysis, 22 primers were selected and designed using Primer Express 2.0 software (Applied Biosystems, Foster City, CA). Genes were quantified by real-time PCR to validate the microarray data, and a subset of 13 genes were further selected by their robust behaviour in the validation assays, allowing to differentiate the toxic potential of PM from urban and rural sources.

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A model-based investigation into urban-rural disparities in tuberculosis treatment outcomes under the Revised National Tuberculosis Control Programme in India.

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A model-based investigation into urban-rural disparities in tuberculosis treatment outcomes under the Revised National Tuberculosis Control Programme in India.

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