Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

Background: Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years.Methods: Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV) seropositivity was assessed by ELISA in adolescents.Results: HIV-negative Malawian adolescents were shown to have a lower percentage of naive T cells (CD45RO-CD62L(hi)CD11a(lo)), a higher proportion of memory T cells and a higher percentage of CD28(-) memory (CD28(-)CD45RO(+)) T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA(-)CCR7(+)) T cells and a higher percentage of stable memory (CD45RA(+)CCR7(-)) T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59), compared to 21/58 (36%) of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naive T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of naive and memory T cell populations were observed in cord blood samples from the two sites.Conclusion: It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections

Feasibility Study of the World Health Organization Health Care Facility-Based Antimicrobial Stewardship Toolkit for Low- and Middle-Income Countries

Antimicrobial stewardship (AMS) has emerged as a systematic approach to optimize antimicrobial use and reduce antimicrobial resistance. To support the implementation of AMS programs, the World Health Organization developed a draft toolkit for health care facility AMS programs in low- and middle-income countries. A feasibility study was conducted in Bhutan, the Federated States of Micronesia, Malawi, and Nepal to obtain local input on toolkit content and implementation of AMS programs. This descriptive qualitative study included semi-structured interviews with national- and facility-level stakeholders. Respondents identified AMS as a priority and perceived the draft toolkit as a much-needed document to further AMS program implementation. Facilitators for implementing AMS included strong national and facility leadership and clinical staff engagement. Barriers included lack of human and financial resources, inadequate regulations for prescription antibiotic sales, and insufficient AMS training. Action items for AMS implementation included improved laboratory surveillance, establishment of a stepwise approach for implementation, and mechanisms for reporting and feedback. Recommendations to improve the AMS toolkit\u27s content included additional guidance on defining the responsibilities of the committees and how to prioritize AMS programming based on local context. The AMS toolkit was perceived to be an important asset as countries and health care facilities move forward to implement AMS programs

From regional pulse vaccination to global disease eradication: insights from a mathematical model of Poliomyelitis

Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, $R_e$, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase $R_e$ and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of $R_e$ when pulse vaccination is present.Comment: Added section 6.1, made other revisions, changed titl

Feedback on video recorded consultations in medical teaching: why students loathe and love it – a focus-group based qualitative study

BACKGROUND: Feedback on videotaped consultations is a useful way to enhance consultation skills among medical students. The method is becoming increasingly common, but is still not widely implemented in medical education. One obstacle might be that many students seem to consider this educational approach a stressful experience and are reluctant to participate. In order to improve the process and make it more acceptable to the participants, we wanted to identify possible problems experienced by students when making and receiving feedback on their video taped consultations. METHODS: Nineteen of 75 students at the University of Bergen, Norway, participating in a consultation course in their final term of medical school underwent focus group interviews immediately following a video-based feedback session. The material was audio-taped, transcribed, and analysed by phenomenological qualitative analysis. RESULTS: The study uncovered that some students experienced emotional distress before the start of the course. They were apprehensive and lacking in confidence, expressing fear about exposing lack of skills and competence in front of each other. The video evaluation session and feedback process were evaluated positively however, and they found that their worries had been exaggerated. The video evaluation process also seemed to help strengthen the students' self esteem and self-confidence, and they welcomed this. CONCLUSION: Our study provides insight regarding the vulnerability of students receiving feedback from videotaped consultations and their need for reassurance and support in the process, and demonstrates the importance of carefully considering the design and execution of such educational programs

Endemicity response timelines for Plasmodium falciparum elimination

Background: The scaling up of malaria control and renewed calls for malaria eradication have raised interest in defining timelines for changes in malaria endemicity. Methods: The epidemiological theory for the decline in the Plasmodium falciparum parasite rate (PfPR, the prevalence of infection) following intervention was critically reviewed and where necessary extended to consider superinfection, heterogenous biting, and aging infections. Timelines for malaria control and elimination under different levels of intervention were then established using a wide range of candidate mathematical models. Analysis focused on the timelines from baseline to 1% and from 1% through the final stages of elimination. Results: The Ross-Macdonald model, which ignores superinfection, was used for planning during the Global Malaria Eradication Programme (GMEP). In models that consider superinfection, PfPR takes two to three years longer to reach 1% starting from a hyperendemic baseline, consistent with one of the few large-scale malaria control trials conducted in an African population with hyperendemic malaria. The time to elimination depends fundamentally upon the extent to which malaria transmission is interrupted and the size of the human population modelled. When the PfPR drops below 1%, almost all models predict similar and proportional declines in PfPR in consecutive years from 1% through to elimination and that the waiting time to reduce PfPR from 10% to 1% and from 1% to 0.1% are approximately equal, but the decay rate can increase over time if infections senesce. Conclusion: The theory described herein provides simple "rules of thumb" and likely time horizons for the impact of interventions for control and elimination. Starting from a hyperendemic baseline, the GMEP planning timelines, which were based on the Ross-Macdonald model with completely interrupted transmission, were inappropriate for setting endemicity timelines and they represent the most optimistic scenario for places with lower endemicity. Basic timelines from PfPR of 1% through elimination depend on population size and low-level transmission. These models provide a theoretical basis that can be further tailored to specific control and elimination scenarios

The duration of protection of school-aged BCG vaccination in England: a population-based case–control study

BACKGROUND: Evidence of protection from childhood Bacillus Calmette-Guerin (BCG) against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation. METHODS: We conducted a population-based case–control study of protection by BCG given to children aged 12–13 years against tuberculosis occurring 10–29 years later. We recruited UK-born White subjects with tuberculosis and randomly sampled White community controls. Hazard ratios and 95% confidence intervals (CIs) were estimated using case–cohort Cox regression, adjusting for potential confounding factors, including socio-economic status, smoking, drug use, prison and homelessness. Vaccine effectiveness (VE = 1 – hazard ratio) was assessed at successive intervals more than 10 years following vaccination. RESULTS: We obtained 677 cases and 1170 controls after a 65% response rate in both groups. Confounding by deprivation, education and lifestyle factors was slight 10–20 years after vaccination, and more evident after 20 years. VE 10–15 years after vaccination was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15–20 years. Subsequently, BCG protection appeared to wane; 20–25 years VE = 25% (CI –14%, 51%) and 25–29 years VE = 1% (CI –84%, 47%). Based on multiple imputation of missing data (in 17% subjects), VE estimated in the same intervals after vaccination were similar [56% (CI 33, 72%), 57% (CI 36, 71%), 25% (–10, 48%), 21% (–39, 55%)]. CONCLUSIONS: School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years, which is longer than previously thought. This has implications for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines

Nature and frequency of respiratory involvement in chronic progressive external ophthalmoplegia

Chronic progressive external ophthalmoplegia (CPEO) is a relatively common mitochondrial disorder. Weakness of the extra-ocular, limb girdle and laryngeal muscles are established clinical features. Respiratory muscle involvement however has never been studied systematically, even though respiratory complications are one of the main causes of death. We therefore determined the prevalence and nature of respiratory muscle involvement in 23 patients with genetically confirmed CPEO. The main finding was decreased respiratory muscle strength, both expiratory (76.8% of predicted, p = 0.002) and inspiratory (79.5% of predicted, p = 0.004). Although the inspiratory vital capacity (92.5% of predicted, p = 0.021) and the forced expiratory volume in 1 s (89.3% of predicted, p = 0.002) were below predicted values, both were still within the normal range in the majority of patients. Expiratory weakness was associated with a decreased vital capacity (ρ = 0.502, p = 0.015) and decreased peak expiratory flow (ρ = 0.422, p = 0.045). Moreover, expiratory muscle strength was lower in patients with limb girdle weakness (62.6 ± 26.1% of predicted vs. 98.9 ± 22.5% in patients with normal limb girdle strength, p = 0.003), but was not associated with other clinical features, subjective respiratory complaints, disease severity or disease duration. Since respiratory involvement in CPEO is associated with severe morbidity and mortality, the present data justify periodic assessment of respiratory functions in all CPEO patients

Social and ethical checkpoints for bottom-up synthetic biology, or protocells

An alternative to creating novel organisms through the traditional “top-down” approach to synthetic biology involves creating them from the “bottom up” by assembling them from non-living components; the products of this approach are called “protocells.” In this paper we describe how bottom-up and top-down synthetic biology differ, review the current state of protocell research and development, and examine the unique ethical, social, and regulatory issues raised by bottom-up synthetic biology. Protocells have not yet been developed, but many expect this to happen within the next five to ten years. Accordingly, we identify six key checkpoints in protocell development at which particular attention should be given to specific ethical, social and regulatory issues concerning bottom-up synthetic biology, and make ten recommendations for responsible protocell science that are tied to the achievement of these checkpoints

Genetic, household and spatial clustering of leprosy on an island in Indonesia: a population-based study

BACKGROUND: It is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but only few studies have tempted to quantify this. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often share the same environment. The first aim of this study was to test which correlation structure (genetic, household or spatial) gives the best explanation for the distribution of leprosy patients and seropositive persons and second to quantify the role of genetic factors in the occurrence of leprosy and seropositivity. METHODS: The three correlation structures were proposed for population data (n = 560), collected on a geographically isolated island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and persons harbouring Mycobacterium leprae-specific antibodies. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M. leprae antibodies were measured using ELISA. RESULTS: For leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the spatial model, but the genetic model was also significant. Heritability was 57% for leprosy per se and 31% for seropositivity. CONCLUSION: Genetic factors seem to play an important role in the clustering of patients with a more advanced form of leprosy, and they could explain more than half of the total phenotypic variance

Co-located wind and wave energy farms: Uniformly distributed arrays

publisher: Elsevier articletitle: Co-located wind and wave energy farms: Uniformly distributed arrays journaltitle: Energy articlelink: http://dx.doi.org/10.1016/j.energy.2016.07.069 content_type: article copyright: © 2016 Elsevier Ltd. All rights reserved