Most cases of severe Staphylococcus aureus disease cannot be explained by the action of a single virulence determinant, and it is likely that a number of factors act in combination during the infective process. This study examined the relationship between disease in humans and a large number of putative virulence determinants, both individually and in combination. S. aureus isolates (n ‫؍‬ 334) from healthy blood donors and from patients with invasive disease were compared for variation in the presence of 33 putative virulence determinants. After adjusting for the effect of clonality, seven determinants (fnbA, cna, sdrE, sej, eta, hlg, and ica) were significantly more common in invasive isolates. All seven factors contributed independently to virulence. No single factor predominated as the major predictor of virulence, their effects appearing to be cumulative. No combinations of the seven genes were either more or less likely to cause disease than others with the same number of virulence-associated genes. There was evidence of considerable horizontal transfer of genes on a background of clonality. Our findings also suggested that allelic variants of a polymorphic locus can make different contributions to the disease process, further study of which is likely to expand our understanding of staphylococcal disease pathogenesis.

Invasive Staphylococcus aureus infection frequently involves bacterial seeding from the bloodstream to other body tissues, a process necessarily involving interactions between circulating bacteria and vascular endothelial cells. Staphylococcus aureus fibronectin‐binding protein is central to the invasion of endothelium, fibronectin forming a bridge between bacterial fibronectin‐binding proteins and host cell receptors. To dissect further the mechanisms of invasion of endothelial cells by S. aureus, a series of truncated FnBPA proteins that lacked one or more of the A, B, C or D regions were expressed on the surface of S. aureus and tested in fibronectin adhesion, endothelial cell adhesion and invasion assays. We found that this protein has multiple, substituting, fibronectin‐binding regions, each capable of conferring both adherence to fibronectin and endothelial cells, and endothelial cell invasion. By expressing S. aureus FnBPA on the surface of the non‐invasive Gram‐positive organism Lactococcus lactis, we have found that no other bacterial factor is required for invasion. Furthermore, we have demonstrated that, as with other cell types, invasion of endothelial cells is mediated by integrin α5β1. These findings may be of relevance to the development of preventive measures against systemic infection, and bacterial spread in the bacteraemic patient.

BackgroundPeople who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed.Methods and FindingsWe searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade.ConclusionKey data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID.

Nasal carriage of Staphylococcus aureus is a major risk factor for invasive S. aureus disease. The aim of this study was to define factors associated with carriage. We conducted a prospective, longitudinal communitybased study of infants and their mothers for a period of 6 months following delivery. The epidemiology of carriage was examined for 100 infant-mother pairs. Infant carriage varied significantly with age, falling from 40 to 50% during the first 8 weeks to 21% by 6 months. Determinants of infant S. aureus carriage included maternal carriage, breastfeeding, and number of siblings. Bacterial typing of S. aureus was performed by pulsed-field gel electrophoresis and multilocus sequence typing. The majority of individuals carried a single strain of S. aureus over time, and the mother was the usual source for colonizing isolates in infants. The effect of other components of the normal nasal flora on the development of S. aureus carriage was examined in 157 consecutive infants. Negative associations (putative bacterial interference) between S. aureus and other species occurred early in infancy but were not sustained. An increasing antistaphylococcal effect observed over time was not attributable to bacterial interference. S. aureus carriage in infants is likely to be determined by a combination of host, environmental, and bacterial factors, but bacterial interference does not appear to be an ultimate determinant of carrier status.Staphylococcus aureus is a major cause of community-acquired and nosocomial sepsis (7, 23). The rising prevalence of antibiotic-resistant strains, such as methicillin-resistant S. aureus and S. aureus with reduced susceptibility to glycopeptides (15,17,22), increases the need to prevent disease through the identification and modification of risk factors. Three sets of observations indicate that nasal carriage of S. aureus is an important risk factor for sepsis with this organism: carriers have higher rates of infection than noncarriers (16,29,30,31); the strain causing infection is usually the carriage strain in a given individual (16,18,28,31); and eradication of carriage reduces nosocomial infection (2,10,20,31). Temporary eradication of S. aureus in those at high risk of sepsis is desirable but relies on the unlikely premise of sustained susceptibility to antibiotics such as mupirocin. There is a need to develop alternative methods of S. aureus eradication, the success of which may depend on a detailed understanding of the determinants of carriage. The relative importance of host, bacterial, and environmental factors in determining S. aureus carriage is currently unknown. The aim of this study was to explore these factors during a prospective, longitudinal community-based study of carriage in mothers and their infants for a period of 6 months after delivery. MATERIALS AND METHODSStudy design. The study was conducted in two parts. Epidemiological factors influencing infant carriage were examined for a group of 100 consecutively recruited infants and their mothers who were derived fr...

Coagulase-negative staphylococci (CoNS) are a major cause of sepsis in the neonatal intensive care unit (NICU). We evaluated the hypothesis that the ica operon and biofilm production are associated with CoNS disease in this setting. CoNS associated with bacteremia or blood culture contamination and from the skin of infants with CoNS bacteremia or healthy controls were obtained during a prospective case-control study on a busy NICU. A total of 180 strains were identified, of which 122 (68%) were Staphylococcus epidermidis and the remainder were S. capitis (n ‫؍‬ 29), S. haemolyticus (n ‫؍‬ 11), S. hominis (n ‫؍‬ 9), S. warneri (n ‫؍‬ 8), and S. auricularis (n ‫؍‬ 1). The presence of the genes icaA, icaB, icaC, and icaD was determined by PCR, and biofilm production was examined using qualitative (Congo red agar [CRA]) and quantitative (microtiter plate) techniques. There were no significant differences in the presence of the ica operon or CRA positivity among the four groups of strains. However, quantitative biofilm production was significantly greater in strains isolated from either the blood or the skin of neonates with S. epidermidis bacteremia. We conclude that the quantity of biofilm produced may be associated with the ability to cause CoNS infection. This conclusion suggests that the regulation of biofilm expression may play a central role in the disease process.Coagulase-negative staphylococci (CoNS) are the major cause of late-onset sepsis in preterm infants (27,39,42,44). Approximately one in six very-low-birth-weight (Ͻ1,500-g) neonates develops an episode of CoNS bacteremia (21, 44), an event that is associated with a significant increase in morbidity and mortality (44), duration of hospital stay (18,21,44), and overall cost of treatment (44). There is thus a need to reduce the risk of sepsis in this setting, a goal which depends in part on defining the pathogenesis of infection.The role of biofilm formation as a determinant of CoNS infection has been the subject of ongoing study since the observation that some isolates of Staphylococcus epidermidis produced mucoid growth in vitro that adhered to the walls of culture tubes (2). A series of studies subsequently reported that this material, termed slime, was more commonly produced by isolates associated with sepsis, including intravenous-catheter-related bacteremia and other prosthetic device infections (5,6,10,14,28,31). The relevance to the neonatal intensive care unit (NICU) setting of slime production by CoNS isolates has been studied in relation to both carriage flora and isolates causing infection. The proportion of slime-producing CoNS in carriage flora increased on repeated sampling of neonates during the first 4 weeks of age in one unit (9) but did not vary in two other units over either 2 weeks (35) or a mean of 8 weeks (24). Endemic clones of CoNS that were associated with disease and that were slime producers were demonstrated to persist over a period of 10 years in one unit (26); however, carriage flora was not examined, and an association be...

Objectives We examined HIV prevalence and risk factors among injection drug users (IDUs) in Athens, Greece, during an HIV outbreak. Methods We used respondent-driven sampling (RDS) to recruit 1404 IDUs to the Aristotle intervention in August to October 2012. We interviewed participants and tested for HIV. We performed bivariate and multivariate analyses. Results Estimated HIV prevalence was 19.8% (RDS-weighted prevalence = 14.8%). Odds of infection were 2.3 times as high in homeless as in housed IDUs and 2.1 times as high among IDUs who injected at least once per day as among less frequent injectors (both, P < .001). Six percent of men and 23.5% of women reported transactional sex in the past 12 months, and condom use was low. Intercourse with non-IDUs was common (53.2% of men, 25.6% of women). Among IDUs who had been injecting for 2 years or less the estimated incidence rate was 23.4 new HIV cases per 100 person-years at risk. Conclusions Efforts to reduce HIV transmission should address homelessness as well as scaling up prevention services, such as needle and syringe distribution and other risk reduction interventions.

Objective:To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO).Methods:A study was eligible if it enrolled AIS patients older than 18 years, with an LVO treated with either successful or unsuccessful EVT, and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed using a generalized linear mixed-effects model.Results:A total of 5874 patients (mean age: 69±14 years, 50% women, median NIHSS on admission: 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common OR=0.82, 95%CI:0.80-0.85; adjusted common OR=0.88, 95%CI:0.84-0.93) and modified Ranking Scale score≤2 (unadjusted OR=0.82, 95%CI:0.79-0.85; adjusted OR=0.87, 95%CI:0.82-0.93), and a higher odds of all-cause mortality (unadjusted OR=1.18, 95%CI:1.13-1.24; adjusted OR=1.15, 95%CI:1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurological deterioration (unadjusted OR=1.14, 95%CI:1.07-1.21; adjusted OR=1.14, 95%CI:1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR=1.20, 95%CI:1.09-1.29; adjusted OR=1.20, 95%CI:1.03-1.38) after EVT.Conclusion:Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurological deterioration, three-month mortality, and worse three-month functional outcomes.

Though imperfect, condoms reduce HIV transmission by more than 70% when used consistently by HIV serodiscordant heterosexual couples. Social, cultural and biological differences need to be studied further to inform projection modelers and policy makers.