RESUMEN

BACKGROUND: Researchers increasingly use social contact data to inform models for infectious disease spread with the aim of guiding effective policies about disease prevention and control. In this article, we undertake a systematic review of the study design, statistical analyses, and outcomes of the many social contact surveys that have been published. METHODS: We systematically searched PubMed and Web of Science for articles regarding social contact surveys. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines as closely as possible. RESULTS: In total, we identified 64 social contact surveys, with more than 80% of the surveys conducted in high-income countries. Study settings included general population (58%), schools or universities (37%), and health care/conference/research institutes (5%). The largest number of studies did not focus on a specific age group (38%), whereas others focused on adults (32%) or children (19%). Retrospective (45%) and prospective (41%) designs were used most often with 6% using both for comparison purposes. The definition of a contact varied among surveys, e.g., a nonphysical contact may require conversation, close proximity, or both. We identified age, time schedule (e.g., weekday/weekend), and household size as relevant determinants of contact patterns across a large number of studies. CONCLUSIONS: We found that the overall features of the contact patterns were remarkably robust across several countries, and irrespective of the study details. By considering the most common approach in each aspect of design (e.g., sampling schemes, data collection, definition of contact), we could identify recommendations for future contact data surveys that may be used to facilitate comparison between studies.

Asunto(s)

RESUMEN

The potential role of Eulemur fulvus (brown lemur) in the epidemiology of Rift Valley fever (RVF) in Mayotte, during an interepidemic period, was explored. In February and March 2016, 72 animals were blood sampled and tested for RVF. No evidence of RVF genome or antibodies was found in the samples. The role of other wild mammals on the island should, however, be further investigated.

Asunto(s)

RESUMEN

BACKGROUND: Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. METHODS: The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. RESULTS: Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. CONCLUSIONS: Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example, incidence of pneumonia, distribution of serotypes causing pneumonia) were influential parameters in the models we compared. Understanding the differences and similarities of such CE tools through regular comparisons could render decision-making processes in different countries more efficient, as well as providing guiding information for further clinical and epidemiological research. A tool comparison exercise using standardized data sets can help model developers to be more transparent about their model structure and assumptions and provide analysts and decision makers with a more in-depth view behind the disease dynamics. Adherence to the WHO guide of economic evaluations of immunization programs may also facilitate this process. Please see related article: http://www.biomedcentral.com/1741-7007/9/55.

Asunto(s)

RESUMEN

The 2003 outbreak of severe acute respiratory syndrome (SARS) showed that infectious disease outbreaks can have notable macroeconomic impacts. The current H1N1 and potential H5N1 flu pandemics could have a much greater impact. Using a multi-sector single country computable general equilibrium model of the United Kingdom, France, Belgium and The Netherlands, together with disease scenarios of varying severity, we examine the potential economic cost of a modern pandemic. Policies of school closure, vaccination and antivirals, together with prophylactic absence from work are evaluated and their cost impacts are estimated. Results suggest GDP losses from the disease of approximately 0.5-2% but school closure and prophylactic absenteeism more than triples these effects. Increasing school closures from 4 weeks at the peak to entire pandemic closure almost doubles the economic cost, but antivirals and vaccinations seem worthwhile. Careful planning is therefore important to ensure expensive policies to mitigate the pandemic are effective in minimising illness and deaths.

Asunto(s)

RESUMEN

BACKGROUND: Mathematical modelling of infectious disease is increasingly used to help guide public health policy. As directly transmitted infections, such as influenza and tuberculosis, require contact between individuals, knowledge about contact patterns is a necessary pre-requisite of accurate model predictions. Of particular interest is the potential impact of school closure as a means of controlling pandemic influenza (and potentially other pathogens). METHODS: This paper uses a population-based prospective survey of mixing patterns in eight European countries to study the relative change in the basic reproduction number (R0--the average number of secondary cases from a typical primary case in a fully susceptible population) on weekdays versus weekends and during regular versus holiday periods. The relative change in R0 during holiday periods and weekends gives an indication of the impact collective school closures (and prophylactic absenteeism) may have during a pandemic. RESULTS: Social contact patterns differ substantially when comparing weekdays to the weekend and regular to holiday periods mainly due to the reduction in work and/or school contacts. For most countries the basic reproduction number decreases from the week to weekends and regular to holiday periods by about 21% and 17%, respectively. However for other countries no significant decrease was observed. CONCLUSION: We use a large-scale social contact survey in eight different European countries to gain insights in the relative change in the basic reproduction number on weekdays versus weekends and during regular versus holiday periods. The resulting estimates indicate that school closure can have a substantial impact on the spread of a newly emerging infectious disease that is transmitted via close (non sexual) contacts.

Asunto(s)

RESUMEN

Understanding the function of histone modifications across inducible genes in mammalian cells requires quantitative, comparative analysis of their fate during gene activation and identification of enzymes responsible. We produced high-resolution comparative maps of the distribution and dynamics of H3K4me3, H3K36me3, H3K79me2 and H3K9ac across c-fos and c-jun upon gene induction in murine fibroblasts. In unstimulated cells, continuous turnover of H3K9 acetylation occurs on all K4-trimethylated histone H3 tails; distribution of both modifications coincides across promoter and 5' part of the coding region. In contrast, K36- and K79-methylated H3 tails, which are not dynamically acetylated, are restricted to the coding regions of these genes. Upon stimulation, transcription-dependent increases in H3K4 and H3K36 trimethylation are seen across coding regions, peaking at 5' and 3' ends, respectively. Addressing molecular mechanisms involved, we find that Huntingtin-interacting protein HYPB/Setd2 is responsible for virtually all global and transcription-dependent H3K36 trimethylation, but not H3K36-mono- or dimethylation, in these cells. These studies reveal four distinct layers of histone modification across inducible mammalian genes and show that HYPB/Setd2 is responsible for H3K36 trimethylation throughout the mouse nucleus.

Asunto(s)

Asunto(s)

RESUMEN

Phosphorylation of histone H3 is implicated in transcriptional activation and chromosome condensation, but its immediate molecular function has remained obscure. By affinity chromatography of nuclear extracts against modified H3 tail peptides, we identified 14-3-3 isoforms as proteins that bind these tails in a strictly phosphorylation-dependent manner. Acetylation of lysines 9 and 14 does not impede 14-3-3 binding to serine 10-phosphorylated H3 tails. In vivo, 14-3-3 is inducibly recruited to c-fos and c-jun nucleosomes upon gene activation, concomitant with H3 phosphoacetylation. We have determined the structures of 14-3-3zeta complexed with serine 10-phosphorylated or phosphoacetylated H3 peptides. These reveal a distinct mode of 14-3-3/phosphopeptide binding and provide a structural understanding for the lack of effect of acetylation at lysines 9 and 14 on this interaction. 14-3-3 isoforms thus represent a class of proteins that mediate the effect of histone phosphorylation at inducible genes.

Asunto(s)

RESUMEN

Mitogen-activated protein kinase (MAPK) pathways regulate eukaryotic gene expression in response to extracellular stimuli. MAPKs and their downstream kinases phosphorylate transcription factors, co-regulators and chromatin proteins to initiate transcriptional changes. However, the spatial context in which the MAPKs operate in transcription complexes is poorly understood. Recent findings in budding yeast show that MAPKs can form integral components of transcription complexes and have novel structural functions in addition to phosphorylating local substrates. Hog1p MAPK is stably recruited to target promoters by specific transcription factors in response to osmotic stress, and acts as both a structural adaptor and enzymatic activator driving the assembly and activation of the transcription complex. We review the evidence that suggests a similar bifunctional role for MAPKs in mammalian transcription complexes.

Asunto(s)