Elucidating the aetiology of human Campylobacter coli infections

Peer reviewedPublisher PD

Geographic determinants of reported human Campylobacter infections in Scotland

<p><b>Background:</b> Campylobacteriosis is the leading cause of bacterial gastroenteritis in most developed countries. People are exposed to infection from contaminated food and environmental sources. However, the translation of these exposures into infection in the human population remains incompletely understood. This relationship is further complicated by differences in the presentation of cases, their investigation, identification, and reporting; thus, the actual differences in risk must be considered alongside the artefactual differences.</p> <p><b>Methods:</b> Data on 33,967 confirmed Campylobacter infections in mainland Scotland between 2000 and 2006 (inclusive) that were spatially referenced to the postcode sector level were analysed. Risk factors including the Carstairs index of social deprivation, the easting and northing of the centroid of the postcode sector, measures of livestock density by species and population density were tested in univariate screening using a non-spatial generalised linear model. The NHS Health Board of the case was included as a random effect in this final model. Subsequently, a spatial generalised linear mixed model (GLMM) was constructed and age-stratified sensitivity analysis was conducted on this model.</p> <p><b>Results:</b> The spatial GLMM included the protective effects of the Carstairs index (relative risk (RR) = 0.965, 95% Confidence intervals (CIs) = 0.959, 0.971) and population density (RR = 0.945, 95% CIs = 0.916, 0.974. Following stratification by age group, population density had a significant protective effect (RR = 0.745, 95% CIs = 0.700, 0.792) for those under 15 but not for those aged 15 and older (RR = 0.982, 95% CIs = 0.951, 1.014). Once these predictors have been taken into account three NHS Health Boards remain at significantly greater risk (Grampian, Highland and Tayside) and two at significantly lower risk (Argyll and Ayrshire and Arran).</p> <p><b>Conclusions:</b> The less deprived and children living in rural areas are at the greatest risk of being reported as a case of Campylobacter infection. However, this analysis cannot differentiate between actual risk and heterogeneities in individual reporting behaviour; nevertheless this paper has demonstrated that it is possible to explain the pattern of reported Campylobacter infections using both social and environmental predictors.</p&gt

Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel

Genetic imputation is a cost-efficient way to improve the power and resolution of genome-wide association (GWA) studies. Current publicly accessible imputation reference panels accurately predict genotypes for common variants with minor allele frequency (MAF) >= 5% and low-frequency variants (0.5Peer reviewe

Construction of a large scale integrated map of macrophage pathogen recognition and effector systems

<p>Abstract</p> <p>Background</p> <p>In an effort to better understand the molecular networks that underpin macrophage activation we have been assembling a map of relevant pathways. Manual curation of the published literature was carried out in order to define the components of these pathways and the interactions between them. This information has been assembled into a large integrated directional network and represented graphically using the modified Edinburgh Pathway Notation (mEPN) scheme.</p> <p>Results</p> <p>The diagram includes detailed views of the toll-like receptor (TLR) pathways, other pathogen recognition systems, NF-kappa-B, apoptosis, interferon signalling, MAP-kinase cascades, MHC antigen presentation and proteasome assembly, as well as selected views of the transcriptional networks they regulate. The integrated pathway includes a total of 496 unique proteins, the complexes formed between them and the processes in which they are involved. This produces a network of 2,170 nodes connected by 2,553 edges.</p> <p>Conclusions</p> <p>The pathway diagram is a navigable visual aid for displaying a consensus view of the pathway information available for these systems. It is also a valuable resource for computational modelling and aid in the interpretation of functional genomics data. We envisage that this work will be of value to those interested in macrophage biology and also contribute to the ongoing Systems Biology community effort to develop a standard notation scheme for the graphical representation of biological pathways.</p

Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries:results of an internet-based global point prevalence survey

Summary: Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux

Genetic analysis for a shared biological basis between migraine and coronary artery disease

Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD).Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci.Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP).Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.</div

Bovine cryptosporidiosis: impact, host-parasite interaction and control strategies

International audienceAbstractGastrointestinal disease caused by the apicomplexan parasite Cryptosporidium parvum is one of the most important diseases of young ruminant livestock, particularly neonatal calves. Infected animals may suffer from profuse watery diarrhoea, dehydration and in severe cases death can occur. At present, effective therapeutic and preventative measures are not available and a better understanding of the host–pathogen interactions is required. Cryptosporidium parvum is also an important zoonotic pathogen causing severe disease in people, with young children being particularly vulnerable. Our knowledge of the immune responses induced by Cryptosporidium parasites in clinically relevant hosts is very limited. This review discusses the impact of bovine cryptosporidiosis and describes how a thorough understanding of the host–pathogen interactions may help to identify novel prevention and control strategies

Campylobacter genotypes from food animals, environmental sources and clinical disease in Scotland 2005/6

A nationwide multi-locus sequence typing (MLST) survey was implemented to analyze patterns of host association among Campylobacter jejuni and Campylobacter coli isolates from clinical disease in Scotland (July 2005-September 2006), food animals (chickens, cattle, sheep, pigs and turkey), non-food animals (wild birds) and the environment. Sequence types (STs) were determined for 5247 clinical isolates and 999 from potential disease sources (augmented with 2420 published STs). Certain STs were over represented among particular sample sets/host groups. These host-associated STs were identified for all sample groups in both Campylobacter species and host associated clonal complexes (groups of related STs) were characterized for C. jejuni. Some genealogical lineages were present in both human disease and food animal samples. This provided evidence for the relative importance of different infection routes/food animal sources in human disease. These results show robust associations of particular genotypes with potential infection sources supporting the contention that contaminated poultry is a major source of human disease