On an SEIR Epidemic Model with Vaccination of Newborns and Periodic Impulsive Vaccination with Eventual On-Line Adapted Vaccination Strategies to the Varying Levels of the Susceptible Subpopulation

This paper investigates a susceptible-exposed-infectious-recovered (SEIR) epidemic model with demography under two vaccination effort strategies. Firstly, the model is investigated under vaccination of newborns, which is fact in a direct action on the recruitment level of the model. Secondly, it is investigated under a periodic impulsive vaccination on the susceptible in the sense that the vaccination impulses are concentrated in practice in very short time intervals around a set of impulsive time instants subject to constant inter-vaccination periods. Both strategies can be adapted, if desired, to the time-varying levels of susceptible in the sense that the control efforts be increased as those susceptible levels increase. The model is discussed in terms of suitable properties like the positivity of the solutions, the existence and allocation of equilibrium points, and stability concerns related to the values of the basic reproduction number. It is proven that the basic reproduction number lies below unity, so that the disease-free equilibrium point is asymptotically stable for larger values of the disease transmission rates under vaccination controls compared to the case of absence of vaccination. It is also proven that the endemic equilibrium point is not reachable if the disease-free one is stable and that the disease-free equilibrium point is unstable if the reproduction number exceeds unity while the endemic equilibrium point is stable. Several numerical results are investigated for both vaccination rules with the option of adapting through ime the corresponding efforts to the levels of susceptibility. Such simulation examples are performed under parameterizations related to the current SARS-COVID 19 pandemic.This research was supported by the Spanish Institute of Health Carlos III through Grant COV 20/01213 and by the Spanish Government and European Commission through Grant RTI2018-094336-B-I00 (MCIU/AEI/FEDER, UE)

Haematological abnormalities in new onset rheumatoid arthritis and risk of common infections:a population-based study

Objectives To describe the prevalence of haematological abnormalities in individuals with rheumatoid arthritis (RA) at the point of diagnosis in primary care, and the associations between haematological abnormalities, vaccinations and subsequent risk of common infections. Methods We studied 6,591 individuals with newly diagnosed RA between 2004 and 2016 inclusive using the UK Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. The prevalence of haematological abnormalities at diagnosis (anaemia, neutropenia and lymphopenia) was established. Cox proportional hazards models were used to evaluate i) the association between each haematological abnormality and time to common infections; ii) the influence of vaccination status (influenza and pneumococcal vaccine) on time to common infections in individuals with RA, compared with a matched cohort of individuals without RA. Results Anaemia was common at RA diagnosis (16.1% of individuals), neutropenia (0.6%) and lymphopenia (1.4%) less so. Lymphopenia and anaemia were associated with increased infection risk (respective hazard ratios (HR) 1.18 (95%CI 1.08-1.29); HR 1.37 (95%CI 1.08-1.73)). There was no evidence of an association between neutropenia and infection risk (HR 0.94 (95%CI 0.60-1.47). Pneumonia was much more common in individuals with early RA compared with controls. Influenza vaccination was associated with reduced risk of influenza-like illness only for individuals with RA (HR 0.58 (95% CI 0.37-0.90). Conclusion At diagnosis, anaemia and lymphopenia, but not neutropenia, increase the risk of common infections in individuals with RA. Our data support the effectiveness of the influenza vaccination in individuals with RA.</p

Level of Physical Activity, Sedentary Behavior, and Sleep in the Child and Adolescent Population in the Autonomous Community of the Basque Country (6-17 Years Old): Protocol for the Mugikertu Study.

[EN] BACKGROUND: Physical inactivity and sedentary behavior are increasingly common problems in the general population, which can lead to overweight, obesity, diabetes, cardiovascular disease, and decreased motor and cognitive capacity among children and adolescents. Establishing healthy habits in childhood on the basis of the World Health Organization's 2020 Physical Activity Guidelines is essential for proper physical, motor, and cognitive development. OBJECTIVE: The primary aim of this study is to describe the level of physical activity (PA), sedentary behavior, and sleep of the child and adolescent population from 6 to 17 years of age in the Basque Autonomous Community (BAC). Our secondary aim is to establish a starting point for future research and intervention protocols to improve the existing reality. METHODS: This cross-sectional study aims to recruit 1111 children and adolescents, aged 6 to 17 years from the BAC in a representative random sample. Participants will wear the ActiGraph WGT3X-BT triaxial accelerometer for 7 consecutive days in their nondominant wrist, and fill out a habit diary log of PA, mobility, and sleep routine. PA intensities, sedentary behavior, and sleep parameters (total bedtime, total sleep time, and sleep efficiency) will be calculated from raw accelerometer data using SPSS (IBM Corp). Participants will be randomly selected. RESULTS: The results of this study intend to demonstrate significant differences in PA levels in different age and gender groups since the volume of school PA in the BAC decreases as the age of the schoolchildren increases. The total study sample includes 1111 participants. In April 2021, up to 50% of the sample size was reached, which is expected to increase to 100% by April 2022. This sample will allow us to analyze, discuss, compare, and assess the reality of the school population, in a sensitive period of adherence to behavior patterns, using data from the geographical and administrative area of the BAC. This study will provide a realistic insight into PA levels among children and adolescents in the BAC. It will also offer scientific contributions on the positive relationship between PA levels and sleep quality in this population. CONCLUSIONS: This study might highlight the need for the promotion of cross-sectional policies so that children and adolescents may increase their levels of PA, thus improving both the school environment and positive healthy behavior.This study has been performed with the support of the Basque government and all the centers. In addition, we express our gratitude to all the children, adolescents, and their families who have and will participate in the study

Epidemic and Nonepidemic Multidrug-Resistant Enterococcus faecium

The epidemiology of vancomycin-resistant Enterococcus faecium (VREF) in Europe is characterized by a large community reservoir. In contrast, nosocomial outbreaks and infections (without a community reservoir) characterize VREF in the United States. Previous studies demonstrated host-specific genogroups and a distinct genetic lineage of VREF associated with hospital outbreaks, characterized by the variant esp-gene and a specific allele-type of the purK housekeeping gene (purK1). We investigated the genetic relatedness of vanA VREF (n=108) and vancomycin-susceptible E. faecium (VSEF) (n=92) from different epidemiologic sources by genotyping, susceptibility testing for ampicillin, sequencing of purK1, and testing for presence of esp. Clusters of VSEF fit well into previously described VREF genogroups, and strong associations were found between VSEF and VREF isolates with resistance to ampicillin, presence of esp, and purK1. Genotypes characterized by presence of esp, purK1, and ampicillin resistance were most frequent among outbreak-associated isolates and almost absent among community surveillance isolates. Vancomycin-resistance was not specifically linked to genogroups. VREF and VSEF from different epidemiologic sources are genetically related; evidence exists for nosocomial selection of a subtype of E. faecium, which has acquired vancomycin-resistance through horizontal transfer

Dynamics of ampicillin-resistant Enterococcus faecium clones colonizing hospitalized patients: data from a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Little is known about the dynamics of colonizing <it>Enterococcus faecium </it>clones during hospitalization, invasive infection and after discharge.</p> <p>Methods</p> <p>In a prospective observational study we compared intestinal <it>E. faecium </it>colonization in three patient cohorts: 1) Patients from the Hematology Unit at the University Hospital Basel (UHBS), Switzerland, were investigated by weekly rectal swabs (RS) during hospitalization (group 1a, n = 33) and monthly after discharge (group 1b, n = 21). 2) Patients from the Intensive Care Unit (ICU) at the University Medical Center Utrecht, the Netherlands (group 2, n = 25) were swabbed weekly. 3) Patients with invasive <it>E. faecium </it>infection at UHBS were swabbed at the time of infection (group 3, n = 22). From each RS five colonies with typical <it>E</it>. <it>faecium </it>morphology were picked. Species identification was confirmed by PCR and ampicillin-resistant <it>E. faecium </it>(ARE) isolates were typed using Multiple Locus Variable Number Tandem Repeat Analysis (MLVA). The Simpson's Index of Diversity (SID) was calculated.</p> <p>Results</p> <p>Out of 558 ARE isolates from 354 RS, MT159 was the most prevalent clone (54%, 100%, 52% and 83% of ARE in groups 1a, 1b, 2 and 3, respectively). Among hematological inpatients 13 (40%) had ARE. During hospitalization, the SID of MLVA-typed ARE decreased from 0.745 [95%CI 0.657-0.833] in week 1 to 0.513 [95%CI 0.388-0.637] in week 3. After discharge the only detected ARE was MT159 in 3 patients. In the ICU (group 2) almost all patients (84%) were colonized with ARE. The SID increased significantly from 0.373 [95%CI 0.175-0.572] at week 1 to a maximum of 0.808 [95%CI 0.768-0.849] at week 3 due to acquisition of multiple ARE clones. All 16 patients with invasive ARE were colonized with the same MLVA clone (<it>p </it>< 0.001).</p> <p>Conclusions</p> <p>In hospitalized high-risk patients MT159 is the most frequent colonizer and cause of invasive <it>E. faecium </it>infections. During hospitalization, ASE are quickly replaced by ARE. Diversity of ARE increases on units with possible cross-transmission such as ICUs. After hospitalization ARE are lost with the exception of MT159. In invasive infections, the invasive clone is the predominant gut colonizer.</p

Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death

Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisΔRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective