How participatory is parental consent in low literacy rural settings in low income countries? Lessons learned from a community based study of infants in South India

<p>Abstract</p> <p>Background</p> <p>A requisite for ethical human subjects research is that participation should be informed and voluntary. Participation during the informed consent process by way of asking questions is an indicator of the extent to which consent is informed.</p> <p>Aims</p> <p>The aims of this study were to assess the extent to which parents providing consent for children's participation in an observational tuberculosis (TB) research study in India actively participated during the informed consent discussion, and to identify correlates of that participation.</p> <p>Methods</p> <p>In an observational cohort study of tuberculosis in infants in South India, field supervisors who were responsible for obtaining informed consent noted down questions asked during the informed consent discussions for 4,382 infants who were enrolled in the study. These questions were post-coded by topic. Bivariate and multivariate analysis was conducted to examine factors associated with asking at least one question during the informed consent process.</p> <p>Results</p> <p>In total, 590 out of 4,382 (13.4%) parents/guardians asked any question during the informed consent process. We found that the likelihood of parents asking questions during the informed consent process was significantly associated with education level of either parent both parents being present, and location.</p> <p>Conclusions</p> <p>The findings have implications for planning the informed consent process in a largely rural setting with low levels of literacy. Greater effort needs to be directed towards developing simple participatory communication materials for the informed consent process. Furthermore, including both parents in a discussion about a child's participation in a research study may increase the extent to which consent is truly informed. Finally, continuing efforts need to be made to improve the communication skills of research workers with regard to explaining research processes and putting potential research participants at ease.</p

The Tuberculin Skin Test versus QuantiFERON TB Gold® in Predicting Tuberculosis Disease in an Adolescent Cohort Study in South Africa

Setting: This study was conducted in a high tuberculosis (TB) burden area in Worcester, South Africa, with a notified all TB incidence rate of 1,400/100,000. Main Objective: To compare the predictive value of a baseline tuberculin skin test (TST) with that of the QuantiFERON TB Gold (In-tube) assay (QFT) for subsequent microbiologically confirmed TB disease among adolescents. Methods: Adolescents aged 12-18 years were recruited from high schools in the study area. At baseline, blood was drawn for QFT and a TST administered. Participants were followed up for up to 3.8 years for incident TB disease (median 2.4 years). Results: After exclusions, 5244 (82.4%) of 6,363 adolescents enrolled, were analysed. The TB incidence rate was 0.60 cases per 100 person years (pyrs) (95% CI 0.43-0.82) for baseline TST positive (>= 5 mm) participants and 0.64 cases per 100 pyrs (95% CI 0.45-0.87) for baseline QFT positive participants. TB incidence rates were 0.22 per 100 pyrs (0.11-0.39) and 0.22 per 100 pyrs (0.12-0.38) among those with a negative baseline TST and QFT respectively. Sensitivity for incident TB disease was 76.9% for TST and 75.0% for QFT (p = 0.81). Positive predictive value was 1.4% for TST and 1.5% for QFT. Conclusion: Positive TST and QFT tests were moderately sensitive predictors of progression to microbiologically confirmed TB disease. There was no significant difference in the predictive ability of these tests for TB disease amongst adolescents in this high burden setting. Therefore, these findings do not support use of QFT in preference to TST to predict the risk of TB disease in this study populatio

Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis

Data Availability: The full datasets can be obtained from the Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) as GSE94438 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94438) and GSE89403 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89403). These details are also provided in the Methods. Additional data on PET-CT scores accompany the revised document as S1 Table (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0278295#pone.0278295.s001).The authors acknowledge the Centre for High Performance Computing (CHPC), South Africa, for providing computational resources to this research project.Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M.tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13–18 months, 742 at 7–12 months and 5,131 detected 1–6 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1–6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology.SM, EM, GT and GW were supported by the South African Tuberculosis Bioinformatics Initiative (SATBBI), a Strategic Health Innovation Partnership grant from the South African Medical Research Council (https://www.samrc.ac.za/) and South African Department of Science and Innovation (https://www.dst.gov.za/); no grant number. STM received funding from the EDCTP2 program (Grant Number CDF1576) supported by the European Union (http://www.edctp.org/projects-2/#). GW received funding from the South African National Research Foundation (SARChI TB Biomarkers #86535) and the South African Medical Research Council (https://www.samrc.ac.za/). SHEK, TJS and GW received funding from the Bill and Melinda Gates Foundation (Grant Numbers OPP37772 & OPP1055806), (https://www.gatesfoundation.org/) GW received funding from the Bill and Melinda Gates Foundation (Grant Number OPP51919) (https://www.gatesfoundation.org/) through the Catalysis Foundation for Health (https://catalysisfoundation.org/) AGL is supported by the NRF-CSUR (Grant Number CSUR60502163639) and by the Centre for Tuberculosis Research from the South African Medical Research Council (https://www.samrc.ac.za/). JAS is supported by a Clinician Scientist Fellowship (Grant Number MR/R007942/1) jointly funded by the UK Medical Research Council (MRC; https://www.ukri.org/about-us/mrc/) and the UK Department for International Development [DFID; replaced by Foreign, Commonwealth & Development Office (FCDO); https://www.gov.uk/government/organisations/foreign-commonwealth-development-office] under the MRC/DFID Concordat agreement

RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response

Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying individuals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood samples collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies

Morphological shifts in the House Sparrows Passer domesticus of Helgoland: insular syndrome or founder effects?

Islands are natural laboratories for the study of evolution and help us to explain the patterns of diversification at large spatial scales. The colonisation of an island by a bird species inevitably involves divergence from the mainland mother population due to non-selective and selective evolution. On the island of Helgoland, House Sparrows Passer domesticus established a resident island population in 1958 which now numbers over 100 breeding pairs.We compared measurements of ringing data between Helgoland and two nearby mainland populations (length of 8th primary, bodymass) and found a significantly higher body mass and lower P8 length/ body mass ratio on the island. Further, we found that P8 length and bodymass significantly increased between the years 1989 and 2008 in Helgoland, indicating that the population changed in size towards larger individuals. This morphological shiftmight best be explained by the “insular syndrome” theory, which predicts increasing size of island birds as a result of reduced predation risk, reduced dispersal and increased intraspecific competition due to high population densities. On the other hand, founder effects could have added to the shift in the P8/ body mass ratio, assuming that the founder individuals yet showed this feature and the population had not much exchange with themainland since the colonisation in 1958. Future molecular analyses of the population structure may help to revealmore details on the isolation, colonisation process and geographical origin of the Helgoland House Sparrow population

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