Evaluation of the quality of informed consent in a vaccine field trial in a developing country setting

<p>Abstract</p> <p>Background</p> <p>Informed consent is an ethical and legal requirement for research involving human participants. However, few studies have evaluated the process, particularly in Africa.</p> <p>Participants in a case control study designed to identify correlates of immune protection against tuberculosis (TB) in South Africa. This study was in turn nested in a large TB vaccine efficacy trial.</p> <p>The aim of the study was to evaluate the quality of consent in the case control study, and to identify factors that may influence the quality of consent.</p> <p>Cross-sectional study conducted over a 4 month period.</p> <p>Methods</p> <p>Consent was obtained from parents of trial participants. These parents were asked to complete a questionnaire that contained questions about the key elements of informed consent (voluntary participation, confidentiality, the main risks and benefits, etc.). The recall (success in selecting the correct answers) and understanding (correctness of interpretation of statements presented) were measured.</p> <p>Results</p> <p>The majority of the 192 subjects interviewed obtained scores greater than 75% for both the recall and understanding sections. The median score for recall was 66%; interquartile range (IQR) = 55%–77% and for understanding 75% (IQR = 50%–87%). Most (79%) were aware of the risks and 64% knew that they participated voluntarily. Participants who had completed Grade 7 at school and higher were more likely (OR = 4.94; 95% CI = 1.57 – 15.55) to obtain scores greater than 75% for recall than those who did not. Participants who were consented by professional nurses who had worked for more than two years in research were also more likely (OR = 2.62; 95% CI = 1.35–5.07) to obtain such scores for recall than those who were not.</p> <p>Conclusion</p> <p>Notwithstanding the constraints in a developing country, in a population with low levels of literacy and education, the quality of informed consent found in this study could be considered as building blocks for establishing acceptable standards for public health research. Education level of respondents and experience of research staff taking the consent were associated with good quality informed consent.</p

Haemophilus influenzae type b conjugate vaccines : a South African perspective

Introduction of Hib vaccine is known to positively impact on reduction of both morbidity and mortality in children less than 5 years of age. Incorporation of this vaccine into a National EPI, however, does come at a significant cost, which is especially important in non-GAVI funded countries. Compounded reduction in response in certain patient populations and possible indication of booster doses further impacts on cost-benefit analyses. Despite these issues, South Africa has supplied Hib vaccine as part of the National EPI in the form of a combination vaccine, Pentaxim®, which combines Hib with Diphtheria, Tetanus, acellular Pertussis (DTP) and Poliomyelitis since 2009. Prior to this, another combination vaccine was utilized containing Hib and DTP. This has subsequently lead to a significant reduction in invasive Hib disease post-introduction, therefore largely justifying utilization.http://www.elsevier.com/locate/vaccin

Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth

BACKGROUND: Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. However, our understanding of the complexity of immunity to BCG in infants is inadequate, making interpretation of vaccine-induced immune responses difficult. METHODS: To better understand BCG-induced immunity, we performed gene expression profiling in five 10-week old infants routinely vaccinated with BCG at birth. RNA was extracted from 12 hour BCG-stimulated or purified protein derivative of tuberculin (PPD)-stimulated PBMC, isolated from neonatal blood collected 10 weeks after vaccination. RNA was hybridised to the Sentrix(R) HumanRef-8 Expression BeadChip (Illumina) to measure expression of >16,000 genes. RESULTS: We found that ex vivo stimulation of PBMC with PPD and BCG induced largely similar gene expression profiles, except that BCG induced greater macrophage activation. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, including PPAR-gamma, involved in activation of the alternative, anti-inflammatory macrophage response was down-regulated following stimulation with both antigens. In contrast, up-regulation of genes associated with the classic, pro-inflammatory macrophage response was noted. Further analysis revealed a decrease in the expression of cell adhesion molecules (CAMs), including integrin alpha M (ITGAM), which is known to be important for entry of mycobacteria into the macrophage. Interestingly, more leukocyte genes were down-regulated than up-regulated. CONCLUSION: Our results suggest that a combination of suppressed and up-regulated genes may be key in determining development of protective immunity to TB induced by vaccination with BCG

Efficacy of percutaneous versus intradermal BCG in the prevention of tuberculosis in South African infants: randomised trial

Objective To compare the incidence of tuberculosis over two years in infants vaccinated at birth with intradermal BCG or with percutaneous BCG

Patients' views on interactions with practitioners for type 2 diabetes:a longitudinal qualitative study in primary care over 10 years

BACKGROUND: It has been suggested that interactions between patients and practitioners in primary care have the potential to delay progression of complications in type 2 diabetes. However, as primary care faces greater pressures, patient experiences of patient-practitioner interactions might be changing.AIM: To explore the views of patients with type 2 diabetes on factors that are of significance to them in patient-practitioner interactions in primary care after diagnosis, and over the last 10 years of living with the disease.DESIGN AND SETTING: A longitudinal qualitative analysis over 10 years in UK primary care.METHOD: The study was part of a qualitative and quantitative examination of patient experience within the existing ADDITION-Cambridge and ADDITION-Plus trials from 2002 to 2016. The researchers conducted a qualitative descriptive analysis of free-text comments to an open-ended question within the CARE measure questionnaire at 1 and 10 years after diagnosis with diabetes. Data were analysed cross-sectionally at each time point, and at an individual level moving both backwards and forwards between time points to describe emergent topics.RESULTS: At the 1-year follow-up, 311 out of 1106 (28%) participants had commented; 101 out of 380 (27%) participants commented at 10-year follow-up; and 46 participants commented at both times. Comments on preferences for face-to-face contact, more time with practitioners, and relational continuity of care were more common over time.CONCLUSION: This study highlights issues related to the wider context of interactions between patients and practitioners in the healthcare system over the last 10 years since diagnosis. Paradoxically, these same aspects of care that are valued over time from diagnosis are also increasingly unprotected in UK primary care.</p

Are there new models of computation? Reply to Wegner and Eberbach

Wegner and Eberbach[Weg04b] have argued that there are fundamental limitations to Turing Machines as a foundation of computability and that these can be overcome by so-called superTuring models such as interaction machines, the [pi]calculus and the $-calculus. In this paper we contest Weger and Eberbach claims

Marine mammal hotspots across the circumpolar Arctic

Aim: Identify hotspots and areas of high species richness for Arctic marine mammals. Location: Circumpolar Arctic. Methods: A total of 2115 biologging devices were deployed on marine mammals from 13 species in the Arctic from 2005 to 2019. Getis-Ord Gi* hotspots were calculated based on the number of individuals in grid cells for each species and for phyloge-netic groups (nine pinnipeds, three cetaceans, all species) and areas with high spe-cies richness were identified for summer (Jun-Nov), winter (Dec-May) and the entire year. Seasonal habitat differences among species’ hotspots were investigated using Principal Component Analysis. Results: Hotspots and areas with high species richness occurred within the Arctic continental-shelf seas and within the marginal ice zone, particularly in the “Arctic gateways” of the north Atlantic and Pacific oceans. Summer hotspots were generally found further north than winter hotspots, but there were exceptions to this pattern, including bowhead whales in the Greenland-Barents Seas and species with coastal distributions in Svalbard, Norway and East Greenland. Areas with high species rich-ness generally overlapped high-density hotspots. Large regional and seasonal dif-ferences in habitat features of hotspots were found among species but also within species from different regions. Gap analysis (discrepancy between hotspots and IUCN ranges) identified species and regions where more research is required. Main conclusions: This study identified important areas (and habitat types) for Arctic marine mammals using available biotelemetry data. The results herein serve as a benchmark to measure future distributional shifts. Expanded monitoring and teleme-try studies are needed on Arctic species to understand the impacts of climate change and concomitant ecosystem changes (synergistic effects of multiple stressors). While efforts should be made to fill knowledge gaps, including regional gaps and more com-plete sex and age coverage, hotspots identified herein can inform management ef-forts to mitigate the impacts of human activities and ecological changes, including creation of protected areas