Individual variation in susceptibility or exposure to SARS-CoV-2 lowers the herd immunity threshold

Individual variation in susceptibility and exposure is subject to selection by natural infection, accelerating the acquisition of immunity, and reducing herd immunity thresholds and epidemic final sizes. This is a manifestation of a wider population phenomenon known as “frailty variation”. Despite theoretical understanding, public health policies continue to be guided by mathematical models that leave out considerable variation and as a result inflate projected disease burdens and overestimate the impact of interventions. Here we focus on trajectories of the coronavirus disease (COVID-19) pandemic in England and Scotland until November 2021. We fit models to series of daily deaths and infer relevant epidemiological parameters, including coefficients of variation and effects of non-pharmaceutical interventions which we find in agreement with independent empirical estimates based on contact surveys. Our estimates are robust to whether the analysed data series encompass one or two pandemic waves and enable projections compatible with subsequent dynamics. We conclude that vaccination programmes may have contributed modestly to the acquisition of herd immunity in populations with high levels of pre-existing naturally acquired immunity, while being crucial to protect vulnerable individuals from severe outcomes as the virus becomes endemic

Diabetes hinders community-acquired pneumonia outcomes in hospitalized patients

This deposit is composed by the main article, and it hasn't any supplementary materials associated.This study aimed to estimate the prevalence of diabetes mellitus (DM) in hospitalized patients with community-acquired pneumonia (CAP) and its impact on hospital length of stay and in-hospital mortality.Pfizer Grant; Ernesto Roma Foundation grant: (FER2014/01)

The Portuguese Large Wildfire Spread database (PT-FireSprd)

Wildfire behaviour depends on complex interactions between fuels, topography, and weather over a wide range of scales, being important for fire research and management applications. To allow for significant progress towards better fire management, the operational and research communities require detailed open data on observed wildfire behaviour. Here, we present the Portuguese Large Wildfire Spread database (PT-FireSprd) that includes the reconstruction of the spread of 80 large wildfires that occurred in Portugal between 2015 and 2021. It includes a detailed set of fire behaviour descriptors, such as rate of spread (ROS), fire growth rate (FGR), and fire radiative energy (FRE). The wildfires were reconstructed by converging evidence from complementary data sources, such as satellite imagery and products, airborne and ground data collected by fire personnel, and official fire data and information in external reports.We then implemented a digraph-based algorithm to estimate the fire behaviour descriptors and combined it with the Meteosat Second Generation (MSG) Spinning Enhanced Visible and Infrared Imager (SEVIRI) fire radiative power estimates. A total of 1197 ROS and FGR estimates were calculated along with 609 FRE estimates. The extreme fires of 2017 were responsible for the maximum observed values of ROS (8900mh1) and FGR (4400 ha h1). Combining both descriptors, we describe the fire behaviour distribution using six percentile intervals that can be easily communicated to both research and management communities. Analysis of the database showed that burned extent is mostly determined by FGR rather than by ROS. Finally, we explored a practical example to show how the PT-FireSprd database can be used to study the dynamics of individual wildfires and to build robust case studies for training and capacity building. The PT-FireSprd is the first open-access fire progression and behaviour database in Mediterranean Europe, dramatically expanding the extant information. Updating the PT-FireSprd database will require a continuous joint effort by researchers and fire personnel. PT-FireSprd data are publicly available through https://doi.org/10.5281/zenodo.7495506 (Benali et al., 2022) and have large potential to improve current knowledge on wildfire behaviour and to support better decision making.info:eu-repo/semantics/publishedVersio

The Portuguese Large Wildfire Spread database (PT-FireSprd)

Wildfire behaviour depends on complex interactions between fuels, topography, and weather over a wide range of scales, being important for fire research and management applications. To allow for significant progress towards better fire management, the operational and research communities require detailed open data on observed wildfire behaviour. Here, we present the Portuguese Large Wildfire Spread database (PT-FireSprd) that includes the reconstruction of the spread of 80 large wildfires that occurred in Portugal between 2015 and 2021. It includes a detailed set of fire behaviour descriptors, such as rate of spread (ROS), fire growth rate (FGR), and fire radiative energy (FRE). The wildfires were reconstructed by converging evidence from complementary data sources, such as satellite imagery and products, airborne and ground data collected by fire personnel, and official fire data and information in external reports. We then implemented a digraph-based algorithm to estimate the fire behaviour descriptors and combined it with the Meteosat Second Generation (MSG) Spinning Enhanced Visible and Infrared Imager (SEVIRI) fire radiative power estimates. A total of 1197 ROS and FGR estimates were calculated along with 609 FRE estimates. The extreme fires of 2017 were responsible for the maximum observed values of ROS (8900 m h−1) and FGR (4400 ha h−1). Combining both descriptors, we describe the fire behaviour distribution using six percentile intervals that can be easily communicated to both research and management communities. Analysis of the database showed that burned extent is mostly determined by FGR rather than by ROS. Finally, we explored a practical example to show how the PT-FireSprd database can be used to study the dynamics of individual wildfires and to build robust case studies for training and capacity building. The PT-FireSprd is the first open-access fire progression and behaviour database in Mediterranean Europe, dramatically expanding the extant information. Updating the PT-FireSprd database will require a continuous joint effort by researchers and fire personnel. PT-FireSprd data are publicly available through https://doi.org/10.5281/zenodo.7495506 (Benali et al., 2022) and have large potential to improve current knowledge on wildfire behaviour and to support better decision making.</p

Malaria Liver Stage Susceptibility Locus Identified on Mouse Chromosome 17 by Congenic Mapping

Host genetic variants are known to confer resistance to Plasmodium blood stage infection and to control malaria severity both in humans and mice. This work describes the genetic mapping of a locus for resistance to liver stage parasite in the mouse. First, we show that decreased susceptibility to the liver stage of Plasmodium berghei in the BALB/c mouse strain is attributable to intra-hepatic factors and impacts on the initial phase of blood stage infection. We used QTL mapping techniques to identify a locus controlling this susceptibility phenotype (LOD score 4.2) on mouse chromosome 17 (belr1 locus). Furthermore, analysis of congenic mouse strains delimited the belr1 locus boundaries distally to the H2 region. Quantification of parasites in the liver of infected congenic mice strongly suggested that the belr1 locus represents a genetic factor controlling the expansion of P. berghei in the hepatic tissue. The mapping of belr1 locus raises the hypothesis that host gene variation is able to control the progression of Plasmodium liver stage infection and opens the possibility that the human genomic region orthologue to belr1 may contain genes that confer resistance to the human malaria liver stage

Alcoholism and Strongyloides stercoralis: Daily Ethanol Ingestion Has a Positive Correlation with the Frequency of Strongyloides Larvae in the Stools

It has been reported that Strongyloides stercoralis infection is more prevalent in chronic alcoholic patients than in non alcoholics living in the same country. In a retrospective study on the prevalence of S. stercoralis infection in a large sample of alcoholic patients, we demonstrate that this prevalence is significantly higher than in non-alcoholic patients admitted at the same hospital. Moreover, the frequency of the parasite was in close relationship with the daily amount of ingested ethanol, even in the absence of liver cirrhosis, reinforcing the idea that chronic alcoholism is associated with increased susceptibility to Strongyloides infection. Beside the bad hygiene profile of alcoholic patients, which explains high risk for acquisition of the parasite, the high prevalence of S. stercoralis in alcoholics may be in relationship with other effects of ethanol on the intestinal motility, steroid metabolism and immune system, which could enhance the chance of autoinfection and the survival and fecundity of females in duodenum. In this way, the number of larvae in the stools is higher in alcoholic patients, increasing the chance of a positive result in a stool examination by sedimentation method

Transforming Growth Factor Beta 2 and Heme Oxygenase 1 Genes Are Risk Factors for the Cerebral Malaria Syndrome in Angolan Children

BACKGROUND: Cerebral malaria (CM) represents a severe outcome of the Plasmodium falciparum infection. Recent genetic studies have correlated human genes with severe malaria susceptibility, but there is little data on genetic variants that increase the risk of developing specific malaria clinical complications. Nevertheless, susceptibility to experimental CM in the mouse has been linked to host genes including Transforming Growth Factor Beta 2 (TGFB2) and Heme oxygenase-1 (HMOX1). Here, we tested whether those genes were governing the risk of progressing to CM in patients with severe malaria syndromes. METHODOLOGY/PRINCIPAL FINDINGS: We report that the clinical outcome of P. falciparum infection in a cohort of Angolan children (n = 430) correlated with nine TGFB2 SNPs that modify the risk of progression to CM as compared to other severe forms of malaria. This genetic effect was explained by two haplotypes harboring the CM-associated SNPs (Pcorrec. = 0.035 and 0.036). In addition, one HMOX1 haplotype composed of five CM-associated SNPs increased the risk of developing the CM syndrome (Pcorrec. = 0.002) and was under-transmitted to children with uncomplicated malaria (P = 0.036). Notably, the HMOX1-associated haplotype conferred increased HMOX1 mRNA expression in peripheral blood cells of CM patients (P = 0.012). CONCLUSIONS/SIGNIFICANCE: These results represent the first report on CM genetic risk factors in Angolan children and suggest the novel hypothesis that genetic variants of the TGFB2 and HMOX1 genes may contribute to confer a specific risk of developing the CM syndrome in patients with severe P. falciparum malaria. This work may provide motivation for future studies aiming to replicate our findings in larger populations and to confirm a role for these genes in determining the clinical course of malaria

Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study

<p>Abstract</p> <p>Background</p> <p>Normal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE) inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events.</p> <p>Methods</p> <p>We investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala), catalase (CAT -21A/T), glutathione peroxidase 1 (GPx-1 Pro198Leu), ACE (I/D) and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135) to hydrogen peroxide (H₂O₂), and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H₂O₂at 250 μM and 1 mM).</p> <p>Results</p> <p>After treatment with H₂O₂at 250 μM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress.</p> <p>Conclusions</p> <p>The GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals.</p

Irf4 is a positional and functional candidate gene for the control of serum IgM levels in the mouse

Natural IgM are involved in numerous immunological functions but the genetic factors that control the homeostasis of its secretion and upholding remain unknown. Prompted by the finding that C57BL/6 mice had significantly lower serum levels of IgM when compared with BALB/c mice, we performed a genome-wide screen and found that the level of serum IgM was controlled by a QTL on chromosome 13 reaching the highest level of association at marker D13Mit266 (LOD score¼3.54). This locus was named IgMSC1 and covered a region encompassing the interferon-regulatory factor 4 gene (Irf4). The number of splenic mature B cells in C57BL/6 did not differ from BALB/c mice but we found that low serum levels of IgM in C57BL/6 mice correlated with lower frequency of IgM-secreting cells in the spleen and in the peritoneal cavity. These results suggested that C57BL/6 mice have lower efficiency in late B-cell maturation, a process that is highly impaired in Irf4 knockout mice. In fact, we also found reduced Irf4 gene expression in B cells of C57BL/6 mice. Thus, we propose Irf4 as a candidate for the IgMSC1 locus, which controls IgM homeostatic levels at the level of B-cell terminal differentiation