Efficient national surveillance for health-care-associated infections.

BACKGROUND: Detecting novel healthcare-associated infections (HCAI) as early as possible is an important public health priority. However, there is currently no evidence base to guide the design of efficient and reliable surveillance systems. Here we address this issue in the context of a novel pathogen spreading primarily between hospitals through the movement of patients. METHODS: Using a mathematical modelling approach we compare the current surveillance system for a HCAI that spreads primarily between hospitals due to patient movements as it is implemented in Scotland with a gold standard to determine if the current system is maximally efficient or whether it would be beneficial to alter the number and choice of hospitals in which to concentrate surveillance effort. RESULTS: We validated our model by demonstrating that it accurately predicts the risk of meticillin-resistant Staphylococcus aureus bacteraemia cases in Scotland. Using the 29 (out of 182) sentinel hospitals that currently contribute most of the national surveillance effort results in an average detection time of 117 days. A reduction in detection time to 87 days is possible by optimal selection of 29 hospitals. Alternatively, the same detection time (117 days) can be achieved using just 22 optimally selected hospitals. Increasing the number of sentinel hospitals to 38 (teaching and general hospitals) reduces detection time by 43 days; however decreasing the number to seven sentinel hospitals (teaching hospitals) increases detection time substantially to 268 days. CONCLUSIONS: Our results show that the current surveillance system as it is used in Scotland is not optimal in detecting novel pathogens when compared to a gold standard. However, efficiency gains are possible by better choice of sentinel hospitals, or by increasing the number of hospitals involved in surveillance. Similar studies could be used elsewhere to inform the design and implementation of efficient national, hospital-based surveillance systems that achieve rapid detection of novel HCAIs for minimal effort.

Time-Scaled Evolutionary Analysis of the Transmission and Antibiotic Resistance Dynamics of Staphylococcus aureus Clonal Complex 398.

Staphylococcus aureus clonal complex 398 (CC398) is associated with disease in humans and livestock, and its origins and transmission have generated considerable interest. We performed a time-scaled phylogenetic analysis of CC398, including sequenced isolates from the United Kingdom (Scotland), along with publicly available genomes. Using state-of-the-art methods for mapping traits onto phylogenies, we quantified transitions between host species to identify sink and source populations for CC398 and employed a novel approach to investigate the gain and loss of antibiotic resistance in CC398 over time. We identified distinct human- and livestock-associated CC398 clades and observed multiple transmissions of CC398 from livestock to humans and between countries, lending quantitative support to previous reports. Of note, we identified a subclade within the livestock-associated clade comprised of isolates from hospital environments and newborn babies, suggesting that livestock-associated CC398 is capable of onward transmission in hospitals. In addition, our analysis revealed significant differences in the dynamics of resistance to methicillin and tetracycline related to contrasting historical patterns of antibiotic usage between the livestock industry and human medicine. We also identified significant differences in patterns of gain and loss of different tetracycline resistance determinants, which we ascribe to epistatic interactions between the resistance genes and/or differences in the modes of inheritance of the resistance determinants.

Genome-wide single nucleotide polymorphism-based assay for high-resolution epidemiological analysis of the methicillin-resistant Staphylococcus aureus hospital clone EMRSA-15.

The EMRSA-15 clone is a major cause of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK and elsewhere but existing typing methodologies have limited capacity to discriminate closely related strains, and are often poorly reproducible between laboratories. Here, we report the design, development and validation of a genome-wide single nucleotide polymorphism (SNP) typing method and compare it to established methods for typing of EMRSA-15. In order to identify discriminatory SNPs, the genomes of 17 EMRSA-15 strains, selected to represent the breadth of genotypic and phenotypic diversity of EMRSA-15 isolates in Scotland, were determined and phylogenetic reconstruction was carried out. In addition to 17 phylogenetically informative SNPs, five binary markers were included to form the basis of an EMRSA-15 genotyping assay. The SNP-based typing assay was as discriminatory as pulsed-field gel electrophoresis, and significantly more discriminatory than staphylococcal protein A (spa) typing for typing of a representative panel of diverse EMRSA-15 strains, isolates from two EMRSA-15 hospital outbreak investigations, and a panel of bacteraemia isolates obtained in healthcare facilities in the east of Scotland during a 12-month period. The assay is a rapid, and reproducible approach for epidemiological analysis of EMRSA-15 clinical isolates in Scotland. Unlike established methods the DNA sequence-based method is ideally suited for inter-laboratory comparison of identified genotypes, and its flexibility lends itself to supplementation with additional SNPs or markers for the identification of novel S. aureus strains in other regions of the world.

The fluctuation of plasma carotenoid concentrations by phase of the menstrual cycle: a controlled diet study.

This is the first controlled diet study to examine the fluctuation of plasma carotenoids, lipoproteins, and serum hormone concentrations by phase of the menstrual cycle. Nonsmoking, premenopausal women (n = 12) with confirmed ovulatory cycles were given a standard diet with 10 mg total carotenoids/d for two cycles under isoenergetic conditions. Blood was drawn for simultaneous measurement of carotenoids, lipoproteins, and hormones on menses days 1-2, 4-6, 11 through 1 d after the luteinizing hormone surge, and 7-8 d after the surge, representing the menses, early and late follicular, and midluteal phases, respectively. Regression modeling with adjustment for plasma cholesterol concentrations was used to compare mean individual and total plasma carotenoid concentrations by phase of the cycle. Plasma carotenoid concentrations were at their lowest at menses and significantly higher thereafter, except for alpha-carotene. Compared with plasma concentrations at menses, beta-carotene peaked (increased by 9%, P = 0.01) in the late follicular phase. Plasma lutein/zeaxanthin and anhydrolutein concentrations were higher by 8-11% (P < or = 0.006) and by 15-31% (P < or = 0.02), respectively, during the last three phases. Plasma lycopene and phytofluene concentrations peaked (increased by 12%, P = 0.004; and by 21%, P = 0.006, respectively) at the midluteal phase. This cyclic fluctuation may affect the estimation of the plasma carotenoid-disease relation in studies of premenopausal women.

Relation between sodium balance and menstrual cycle symptoms in normal women.

OBJECTIVE: To determine whether sodium balance affects expression of menstrual symptoms. DESIGN: Prospective study of menstrual symptoms during three cycles: a baseline month (usual intake of sodium, 115 mmol/d) followed by 2 months of sodium restriction (intake of sodium, 73.0 mmol/d). Added salt was allowed during the last month. Investigators were aware of the diet sequence. SETTING: Outpatient. Meals were prepared by a metabolic kitchen during the 2 months that the participants received salt-restricted diets. PARTICIPANTS: 13 healthy menstruant women. MEASUREMENTS: Plasma sodium levels, urinary sodium excretion, and plasma renin activity were measured for five time periods during the baseline cycle and the two cycles of salt-restricted diet. Eleven women completed a questionnaire assessing somatic symptoms and sensory cravings at the same time every day during the 3-month study period. RESULTS: Sodium restriction was associated with a mean decrease (+/- one half of the 95% CI) in plasma sodium levels of 0.9 +/- 0.9 mmol/L from a mean of 139.3 mmol/L during the baseline cycle (P = 0.018), a decrease in urinary sodium excretion of 40.3 +/- 18 mmol/d from a mean of 117 mmol/d during the baseline cycle (P = 0.001), and an increase in plasma renin activity of 0.14 +/- 0.08 ng/(L . s) from a mean of 0.28 ng/(L . s) during the baseline cycle (P = 0.008). During the luteal phase of the sodium restriction cycle, significant decreases in plasma sodium levels of 1.23 +/- 0.5 mmol/L (from values of 138.8 mmol/L during the follicular phase) and increases in urinary sodium excretion of 27.2 +/- 10 mmol/d (from values of 65.5 mmol/d during the follicular phase) preceded periods when menstrual symptoms were most severe. Ratings of breast tenderness increased sixfold to eightfold in the late luteal phase (P < 0.001) and those of swelling or bloating increased twofold to threefold during early menses (P < 0.001) compared with nadir symptom ratings during each cycle. Sodium cravings increased in the luteal phase of all cycles but were not accompanied by increased sodium intake when access to added salt was allowed. CONCLUSIONS: Breast tenderness and bloating did not result from sodium retention in the luteal phase of the menstrual cycle. During normal and sodium-restricted diet cycles, women actually had urinary sodium loss, not retention, during the luteal phase; severity of menstrual symptoms was unchanged.

Cyclic changes in lipoprotein and apolipoprotein levels during the menstrual cycle in healthy premenopausal women on a controlled diet.

Lipoprotein, apolipoprotein (apo), and hormone levels were measured in 12 healthy women over three consecutive menstrual cycles, one free-living and two under controlled dietary conditions. Serum hormone levels were measured to identify menstrual cycle phases (menses, early follicular, late follicular, and midluteal). After stabilization for one cycle on the controlled diet, ANOVA modeling of the second controlled-diet cycle revealed that low-density lipoprotein (LDL) cholesterol levels in the midluteal phase were significantly lower (by 7%) than in the early follicular phase. High-density lipoprotein (HDL) cholesterol levels during the late follicular phase were higher (by 6%) than menses levels. Differences in the HDL-cholesterol and apoA-I fluctuations resulted in a higher proportion of HDL-cholesterol to apoA-I during the late follicular phase than that during the menses phase. The ratios of LDL cholesterol/HDL cholesterol and apoB/apoA-I in the early follicular phase were greater by 5.6% and 6.0%, respectively, than those in the midluteal phase. Fluctuations in total cholesterol, triglyceride, apoA-I, and apoB did not reach significance. Thus, the cyclic fluctuations of LDL and HDL cholesterol need to be considered in the screening and medical monitoring of women with borderline lipoprotein levels, as well as in the design and the interpretation of results of studies involving premenopausal women.

Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake.

We examined the validity of using the selenium level in a single biological specimen as a surrogate measure of usual intake. We used data from 77 free-living adults from South Dakota and Wyoming. Subjects provided multiple 1-day duplicate-plate food composites, repeated specimens of blood and toenails, and 24-hour urine collections. We developed a statistical calibration method that incorporated measurement error correction to analyze the data. The Pearson correlation coefficients between selenium intake and a single selenium status measure, after deattenuation to adjust for the effect of within-person variation in intake, were: 0.78 for whole blood, 0.74 for serum, 0.67 for toenails, and 0.86 for urine. We present formulas to estimate the intake of individuals, based on selenium levels in a single specimen of blood, toenails, or urine. In these data, the concentration of selenium in a single specimen of whole blood, serum, or toenails served reasonably well as a measure for ranking subjects according to long-term selenium intake but provided only a rough estimate of intake for each subject.

Human [74Se]selenomethionine metabolism: a kinetic model.

A study was undertaken to investigate the pharmacokinetics of an organically bound form of selenium. Six adults received a single oral 200-micrograms dose of 74Se as L-selenomethionine. A kinetic model was developed to simultaneously account for the appearance and disappearance of the tracer in plasma, urine, and feces. The model included absorption distributed along the gastrointestinal tract, uptake by the liver-pancreas subsystem, enterohepatic recirculation, distribution to two large tissue pools, and transport through four components of the plasma pool. Average turnover time of the plasma components varied from 0.01 to 1.1 d. The turnover time in the liver-pancreas subsystem ranged from 1.6 to 3.1 d. Turnover time ranged from 61 to 86 d in the peripheral tissues with the slowest turnover. The whole-body residence time was approximately five-fold greater than the turnover time of the tissue pool with the slowest turnover, reflecting substantial reutilization of labeled material.

Selenium in diet, blood, and toenails in relation to human health in a seleniferous area.

To determine whether high dietary selenium intake was associated with adverse effects, selenium in diet, blood, and toenails was studied in relation to human health in adults residing in western South Dakota and eastern Wyoming. Over a 2-y period 142 subjects were recruited from households selected at random and from ranches where unusually high selenium intakes were suspected. Subjects completed health questionnaires, underwent physical examinations, provided blood samples for clinical assessment, and provided blood, urine, toenails, and duplicate-plate food collections for selenium analysis. About half of the 142 free-living subjects had selenium intakes greater than 2.54 mumol/d (200 micrograms/d) (range 0.86-9.20 mumol/d, or 68-724 micrograms/d). Physical findings characteristic of selenium toxicity were not present nor were clinically significant changes in laboratory tests or frequency of symptoms related to selenium in the blood, toenails, or diet. We found no evidence of toxicity from selenium in subjects whose intake was as high as 9.20 mumol/d (724 micrograms/d).

Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area.

Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration.

Human selenite metabolism: a kinetic model.

A model is developed to describe the kinetics of sodium selenite metabolism in humans, based on plasma, urine, and fecal samples obtained from six subjects over a 4-wk period after a single oral 200-micrograms dose of the enriched stable isotope tracer 74Se. The model describes absorption, distributed along the gastrointestinal tract, and enterohepatic recirculation. The model includes four kinetically distinct plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. For the six subjects, the ranges of mean residence times for the four plasma components are, respectively, 0.2-1.1 h, 3-8 h, 9-42 h, and 200-285 h; for the hepatopancreatic subsystem 4-41 days; and for the tissue pool 115-285 days. Approximately 84% of the administered dose was absorbed, and after 12 days approximately 65% remained in the body. The model predicts that after 90 days approximately 35% of this Se would be retained, primarily in the tissues. Separating Se metabolism into several distinct kinetic components is a first step in identifying the efficacious, nutritious, and toxic forms of the element.

Selenium status of malnourished hospitalized patients.

We evaluated selenium (Se) status of 44 hospitalized patients with protein-energy malnutrition. The patients were assigned to "normal" or "low" Se groups-1 and 2, respectively-based on whether the plasma Se level exceeded or was below the value of the mean-2SD of healthy Georgians'. Plasma and erythrocyte Se levels correlated significantly (r = .52, P less than .01). Erythrocyte glutathione peroxidase activity was highly correlated with plasma Se (r = .68) in group 2; there was no significant correlation between these parameters in group 1. In group 2 the mean plasma prealbumin level was significantly lower, and the mean corpuscular volume and serum glutamic oxaloacetic transaminase level were significantly higher compared to group 1. Other nutritional parameters did not correlate with Se status. Concomitant deficiencies of other nutrients were common in both patient groups. Se levels may relate to protein status, and abnormal hematologic and hepatic parameters may reflect low Se status and/or protein-energy malnutrition. Low Se status is common in malnourished patients from a low Se area, and Se supplementation should be included in their nutritional-repletion regimens.

Effect of age, sex, and race on selenium status of healthy residents of Augusta, Georgia.

In this study we determined the possible effects of age, sex, and race on selenium (Se) concentration in plasma and erythrocytes and on glutathione peroxidase (GSH-Px) activity in erythrocytes. Two hundred six healthy blacks, whites, males, and females ranging in age from 11 to 60 yr were studied. For the entire population, mean±SDM Se concentrations were 0.104±0.021 µg/mL for plasma and 0.158±0.035 µg/mL for erythrocytes. Mean concentration of Se in plasma was higher in white subjects compared to black subjects (P<0.02). This difference was due exclusively to higher values in young adult white males (age, race, sex interaction). Neither plasma nor erythrocyte Se concentration nor erythrocyte GSH-Px activity were otherwise affected by age. In all groups plasma Se was correlated with erythrocyte Se (P<0.001), but not with glutathione peroxidase. Erythrocyte Se also was correlated inversely with years of smoking (P<0.033) and coffee intake (p<0.01). These results have defined the Se status in this healthy population in Augusta, Georgia as below the reported US mean. The factors underlying the age, race, sex interaction and the health significance of the low Se status in this population should be investigated.

Mineral profile of blood plasma of lactating dairy cows.

Each of 20 Holstein cows was assigned randomly to a salt treatment upon calving. The experimental design was a 2 x 2 factorial having age (young versus mature) and salt treatment (plain versus mineralized) as factors. Salt was fed ad libitum. All animals were maintained on a balanced ration of corn silage fed ad libitum and concentrate fed in the barn in a ratio of .45 kg concentrate per 1.36 kg actual milk production. Concentrations in blood plasma of calcium, magnesium, sodium, potassium, cobalt, bicarbonate, chloride, phosphorus, total serum protein, sulfur, and fluoride were monitored throughout lactation and gestation. Statistical evaluation of weekly means for each treatment group for each element by analysis of variance showed when concentrations were different. Concentrations of calcium and magnesium were higher in younger animals than in mature animals during much of the lactation cycle. Magnesium concentration was higher in cows fed trace-mineralized salt. Concentration of phosphorus was higher in younger animals throughout the lactation cycle. Total serum protein was higher in mature cows throughout lactation, and concentrations of sulfur and fluoride were higher in mature cows through much of the cycle.