Control of MRSA infection and colonisation in an intensive care unit by GeneOhm MRSA assay and culture methods

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major nosocomial pathogens. Due to the diffusion of MRSA strains in both hospital and community settings, prevention and control strategies are receiving increased attention. Approximately 25% to 30% of the population is colonised with S. aureus and 0.2% to 7% with MRSA. The BD GeneOhm MRSA real-time PCR assay offers quicker identification of MRSA-colonised patients than do culture methods. Ninety-five patients admitted to the Intensive Care Unit of IRCCS Policlinico San Matteo of Pavia (Italy) for a period > 24 h were screened for MRSA colonisation with both the culture method and the GeneOhm assay. Of the 246 nasal swabs collected from 95 patients, 36 samples were found to be positive by both methods (true-positive). 30% of colonised patients had developed the MRSA infection. Our results show that the GeneOhm MRSA assay is a valuable diagnostic tool for detecting MRSA quickly in nasal swabs. This study confirms that colonisation represents a high risk factor for MRSA infection, and that good MRSA surveillance in an Intensive Care Unit is therefore an excellent way to prevent MRSA infectio

Comparing Pandemic to Seasonal Influenza Mortality: Moderate Impact Overall but High Mortality in Young Children

Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. Methods and Findings: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influen

Estimation of acute and chronic Q fever incidence in children during a three-year outbreak in the Netherlands and a comparison with international literature

Background:  In the Dutch 2007-2009 Q fever outbreak Coxiella burnetii was transmitted aerogenically from dairy goat farms to those living in the surrounding areas. Relatively few children were reported. The true number of pediatric infections is unknown. In this study, we estimate the expected number of acute and chronic childhood infections. Methods:  As Coxiella was transmitted aerogenic to those living near infected dairy goat farms, we could use adult seroprevalence data to estimate infection risk for inhabitants, children and adults alike. Using Statistics Netherlands data we estimated the number of children at (high) risk for developing chronic Q fever. Literature was reviewed for childhood (0-15 years) Q fever reports and disease rates. We compared this with Dutch reported and our estimated data for 2007-2009. Results:  In The Netherlands epidemic, 44 children were reported (1.2 % of total notifications). The childhood incidence was 0.15 compared to 2.6 per 10,000 inhabitants for adults. No complications were reported. Based on the expected similarity in childhood and adult exposure we assume that 9.8 % of children in the high-risk area had Q fever infection, resulting in 1562 acute infections during the Q fever epidemic interval. Based on the prevalence of congenital heart disease, at least 13 children are at high risk for developing chronic Q fever. In medical literature, 42 case reports described 140 childhood Q fever cases with a serious outcome (four deaths). In chronic Q fever, cardiac infections were predominant. Four outbreaks were reported involving children, describing 11 childhood cases. 36 National and/or regional studies reported seroprevalences varying between 0 and 70 %. Conclusion:  In the 3-year Dutch epidemic, few childhood cases were reported, with pulmonary symptoms leading, and none with a serious presentation. With an estimated 13 high-risk children for chronic infection in the high exposure area, and probably forty in the whole country, we may expect several chronic Q fever complications in the coming years in paediatric practice

Vitamin d status predicts 30 day mortality in hospitalised cats

Vitamin D insufficiency, defined as low serum concentrations of the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated with the development of numerous infectious, inflammatory, and neoplastic disorders in humans. In addition, vitamin D insufficiency has been found to be predictive of mortality for many disorders. However, interpretation of human studies is difficult since vitamin D status is influenced by many factors, including diet, season, latitude, and exposure to UV radiation. In contrast, domesticated cats do not produce vitamin D cutaneously, and most cats are fed a commercial diet containing a relatively standard amount of vitamin D. Consequently, domesticated cats are an attractive model system in which to examine the relationship between serum 25(OH)D and health outcomes. The hypothesis of this study was that vitamin D status would predict short term, all-cause mortality in domesticated cats. Serum concentrations of 25(OH)D, together with a wide range of other clinical, hematological, and biochemical parameters, were measured in 99 consecutively hospitalised cats. Cats which died within 30 days of initial assessment had significantly lower serum 25(OH)D concentrations than cats which survived. In a linear regression model including 12 clinical variables, serum 25(OH)D concentration in the lower tertile was significantly predictive of mortality. The odds ratio of mortality within 30 days was 8.27 (95% confidence interval 2.54-31.52) for cats with a serum 25(OH)D concentration in the lower tertile. In conclusion, this study demonstrates that low serum 25(OH)D concentration status is an independent predictor of short term mortality in cats

Calcium-dependent phospholipid scrambling by TMEM16F.

血小板において止血の引き金となるリン脂質の暴露に関与する因子の同定－ヒトの遺伝病（スコット症候群）の原因遺伝子の同定. 京都大学プレスリリース. 2010-11-25.In all animal cells, phospholipids are asymmetrically distributed between the outer and inner leaflets of the plasma membrane. This asymmetrical phospholipid distribution is disrupted in various biological systems. For example, when blood platelets are activated, they expose phosphatidylserine (PtdSer) to trigger the clotting system. The PtdSer exposure is believed to be mediated by Ca(2+)-dependent phospholipid scramblases that transport phospholipids bidirectionally, but its molecular mechanism is still unknown. Here we show that TMEM16F (transmembrane protein 16F) is an essential component for the Ca(2+)-dependent exposure of PtdSer on the cell surface. When a mouse B-cell line, Ba/F3, was treated with a Ca(2+) ionophore under low-Ca(2+) conditions, it reversibly exposed PtdSer. Using this property, we established a Ba/F3 subline that strongly exposed PtdSer by repetitive fluorescence-activated cell sorting. A complementary DNA library was constructed from the subline, and a cDNA that caused Ba/F3 to expose PtdSer spontaneously was identified by expression cloning. The cDNA encoded a constitutively active mutant of TMEM16F, a protein with eight transmembrane segments. Wild-type TMEM16F was localized on the plasma membrane and conferred Ca(2+)-dependent scrambling of phospholipids. A patient with Scott syndrome, which results from a defect in phospholipid scrambling activity, was found to carry a mutation at a splice-acceptor site of the gene encoding TMEM16F, causing the premature termination of the protein

Getting to the Outer Leaflet: Physiology of Phosphatidylserine Exposure at the Plasma Membrane

Phosphatidylserine (PS) is a major component of membrane bilayers whose change in distribution between inner and outer leaflets is an important physiological signal. Normally, members of the type IV P-type ATPases spend metabolic energy to create an asymmetric distribution of phospholipids between the two leaflets, with PS confined to the cytoplasmic membrane leaflet. On occasion, membrane enzymes, known as scramblases, are activated to facilitate transbilayer migration of lipids, including PS. Recently, two proteins required for such randomization have been identified: TMEM16F, a scramblase regulated by elevated intracellular Ca2+, and XKR8, a caspase-sensitive protein required for PS exposure in apoptotic cells. Once exposed at the cell surface, PS regulates biochemical reactions involved in blood coagulation, and bone mineralization, and also regulates a variety of cell-cell interactions. Exposed on the surface of apoptotic cells, PS controls their recognition and engulfment by other cells. This process is exploited by parasites to invade their host, and in specialized form is used to maintain photoreceptors in the eye and modify synaptic connections in the brain. This review discusses what is known about the mechanism of PS exposure at the surface of the plasma membrane of cells, how actors in the extracellular milieu sense surface exposed PS, and how this recognition is translated to downstream consequences of PS exposure