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Results of an accelerated pertussis vaccination schedule for infants introduced in 1990 in England and Wales were examined. Earlier scheduling and sustained high vaccine coverage resulted in fewer reported cases of pertussis among infants, reinforcing the World Health Organization drive for on-time completion of the infant vaccination schedule. As determined by using the screening method, the first dose of vaccine was 61.7% effective in infants <6 months of age, and effectiveness increased with subsequent doses. Three doses of a good whole-cell pertussis vaccine were 83.7% effective in children 10-16 years of age; a preschool booster vaccination further reduced pertussis incidence in children <10 years of age. As in other industrialized countries, surveillance data during 1998-2009 showed that pertussis in England and Wales mainly persists in young infants (i.e., <3 months of age), teenagers, and adults. Future vaccine program changes may be beneficial, but additional detail is required to inform such decisions. [ABSTRACT FROM AUTHOR]

Study Objectives: Disproportionately negative pandemic outcomes, lack of race-based data collection and poor engagement of Black communities in policy decision making have been widely documented for Black Canadians. We examine this to understand how formal public engagement processes might be more inclusive of Black peoples to inform more responsive policies., Methodology: The study employed an asset-based lens to examine how Black communities have engaged in health policy and advocacy in Ontario. In-depth interviews were conducted with eight participants who self-identify as Black, recruited using purposive and intensity sampling to (1) identify information-rich cases, including people who have been at the forefront of high-impact work in this space and (2) participants whose mission and mandates represented diverse approaches and sub-populations., Results: Our findings suggest that while Black community advocates face systemic and contextual barriers, they also embody deep and multifaceted knowledge, training and experience, which inform the rich ways that they approach advocacy., Discussion: Despite its Ontario focus, this study adds breadth and depth to the existing literature on health policy and historically marginalized populations, offering broader lessons for policy makers across jurisdictions. Our findings encourage policy makers to better recognize, make space for and cultivate fertile advocacy foundations, cultural knowledge and community-driven systems already present in Black communities., (Copyright © 2024 Longwoods Publishing.)

Only approximately 356 North Atlantic right whales ( Eubalaena glacialis ) remain. With extremely low levels of genetic diversity, limited options for mates, and variation in reproductive success across females, there is concern regarding the potential for genetic limitations of population growth from inbreeding depression. In this study, we quantified reproductive success of female North Atlantic right whales with a modified de-lifing approach using reproductive history information collected over decades of field observations. We used double-digest restriction site-associated sequencing to sequence approximately 2% of the genome of 105 female North Atlantic right whales and combined genomic inbreeding estimates with individual fecundity values to assess evidence of inbreeding depression. Inbreeding depression could not explain the variance in reproductive success of females, however we present evidence that inbreeding depression may be affecting the viability of inbred fetuses-potentially lowering the reproductive success of the species as a whole. Combined, these results allay some concerns that genetic factors are impacting species survival as genetic diversity is being retained through selection against inbred fetuses. While still far fewer calves are being born each year than expected, the small role of genetics underlying variance in female fecundity suggests that variance may be explained by external factors that can potentially be mitigated through protection measures designed to reduce serious injury and mortality from human activities., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

The present study synthesised and characterised zinc oxide nanoparticles (ZnO NPs) using spinach tree, Cnidoscolus aconitifolius and investigated its potential use as nanofertilizer. The synthesised nanoparticles showed UV-Vis absorption peak at 378 nm which is a feature of ZnO NPs. FT-IR analysis further revealed the presence of O-H stretching, C = C bending, O-H bending and C-N stretching functional groups of the stabilising action of the plant extract on the surface of the nanoparticles. SEM images displayed the shape of NPs to be spherical whereas TEM images showed their distribution sizes to be 100 nm. Synthesised ZnO NPs were used as a nano fertilizer on Sorghum bicolour plant. An increase in the shoot leaf length with an average length of 16.13 ± 0.19 cm as compared to the control group of 15.13 ± 0.07 cm was observed. The rate of photosynthesis also showed a significant increase with total chlorophyll content of 0.2806 ± 0.006 mg/mL as compared with control of 0.2476 ± 0.002 mg/mL. The activity of antioxidative enzymes was measured with an increase in the specific activity of SOD in the plant when ZnO NPs were used over NPK whereas, the specific activities of CAT were similar in all cases.

Background: Point-of-care (POC) hemoglobin A1c (HbA1c) testing has advantages over laboratory testing, but some questions have remained regarding the accuracy and precision of these methods. The accuracy and the precision of the POC Afinion™ HbA1c Dx test were investigated., Methods: Samples spanning the assay range were collected from prospectively enrolled subjects at three clinical sites. The accuracy of the POC test using fingerstick and venous whole blood samples was estimated via correlation and bias with respect to values obtained by an NGSP secondary reference laboratory (SRL). The precision of the POC test using fingerstick samples was estimated from duplicate results by calculating the coefficient of variation (CV) and standard deviation (SD), and separated into its components using analysis of variance (ANOVA). The precision of the POC test using venous blood was evaluated from samples run in four replicates on each of three test cartridge lots, twice per day for 10 consecutive days. The SD and CV by study site and overall were calculated., Results: Across the assay range, POC test results from fingerstick and venous whole blood samples were highly correlated with results from the NGSP SRL ( r = .99). The mean bias was -0.021% HbA1c (-0.346% relative) using fingerstick samples and -0.005% HbA1c (-0.093% relative) using venous samples. Imprecision ranged from 0.62% to 1.93% CV for fingerstick samples and 1.11% to 1.69% CV for venous samples., Conclusions: The results indicate that the POC test evaluated here is accurate and precise using both fingerstick and venous whole blood.

Background: Point-of-care (POC) HbA1c tests hold the promise of reducing the rates of undiagnosed diabetes, provided they exhibit acceptable analytical performance. The precision and total error of the POC (Afinion™ HbA1c Dx) test were investigated using whole blood samples obtained by fingerstick and venipuncture., Methods: Fingerstick samples spanning the assay range were collected from 61 subjects at three representative POC sites. At each site, six fingerstick samples were obtained from each subject and tested on the POC test across two (Afinion AS100) instruments. Repeatability, between-operator, and between-instrument components of variance were calculated using analysis of variance (ANOVA). Four venous samples (low, threshold, medium, and high HbA1c) were measured in duplicate across three instruments using three reagent lots, twice per day over 20-days. Repeatability, between-run, between-day, between-lot, and between-instrument components of variance were calculated. These fingerstick and venous blood results, combined with estimates of imprecision and bias from a prior investigation, allowed for the calculation of the total coefficient of variation (CV) and total error of the POC test using fingerstick and venous whole blood samples., Results: The total imprecision ranged from 1.30% to 2.03% CV using fingerstick samples and from 1.31% to 1.64% CV using venous samples. The total error ranged from 2.87% to 4.75% using fingerstick samples and from 2.93% to 3.80% using venous samples., Conclusions: The POC test evaluated here is precise across its measuring range using both fingerstick and venous whole blood. The calculated total error of the test is well under the accepted quality requirement of ≤6%.

Animal movement plays a fundamental role in the ecology of migratory species, and understanding migration patterns is required for effective management. To evaluate intrinsic and environmental factors associated with probabilities of endangered North Atlantic right whales Eubalaena glacialis migrating to a wintering ground off the southeastern United States (SEUS), we applied a multistate temporary emigration capture-recapture model to 22 years of photo-identification data. Migration probabilities for juveniles were generally higher yet more variable than those for adults, and non-calving adult females were the least likely group to migrate. The highest migration probabilities for juveniles and adult males coincided with years of relatively high calving rates, following years of higher prey availability in a fall feeding ground. Right whale migration to the SEUS can be classified as condition-dependent partial migration, which includes skipped breeding partial migration for reproductive females, and is likely influenced by tradeoffs among ecological factors such as reproductive costs and foraging opportunities that vary across individuals and time. The high variability in migration reported in this study provides insight into the ecological drivers of migration but presents challenges to right whale monitoring and conservation strategies.

Background: Serial measurement of natriuretic peptides may guide management in heart failure (HF) patients. In previous trials, natriuretic peptides were infrequently monitored, which may undervalue the benefit of this approach., Methods and Results: HOME was an adaptive three-arm randomized clinical study to test whether home monitoring of BNP could reduce HF-related death, hospitalization due to acute decompensated HF (ADHF), and ADHF treated with intravenous diuretics in the emergency department or outpatient setting. Enrolment was terminated early because of slow enrolment, low event rates, and the belief that an algorithm for assessing BNP trends was needed. Justification for pooling data from all study arms was made and analysis as a single observational study was performed. The analysis resulted in 107 patients who were monitored for a median of 172 days with BNP measures on a median of 74% of days. BNP values were highly variable within a patient. Dispersion between serial BNPs was calculated to be 39.3%, 57.7%, and 73.6% for 1, 60, and 120 days between measures, respectively. A moving average filter (fBNP) was calculated to reduce day-to-day fluctuations and track changes from week to week. There were 27 primary events in 17 362 patient days of monitoring; the hazard ratio for time-varying fBNP was 2.22 (95% confidence interval 1.48-3.34) per unit natural log (corresponding to a 2.72-fold change in fBNP level)., Conclusion: The HOME HF study demonstrates the feasibility of home BNP measurement and shows the potential value of fBNP as an index of emerging clinical deterioration. Assessment of the clinical value of this is required., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Abnormal modifications in tau such as hyperphosphorylation, oxidation, and glycation interfere with its interaction with microtubules leading to its dissociation and self-aggregation into neurofibrillary tangles, a hallmark of Alzheimer's disease (AD). Previously we reported that an aqueous extract of cinnamon has the ability to inhibit tau aggregation in vitro and can even induce dissociation of tangles isolated from AD brain. In the present study, we carried out investigations with cinnamaldehyde (CA) and epicatechin (EC), two components of active cinnamon extract. We found that CA and the oxidized form of EC (ECox) inhibited tau aggregation in vitro and the activity was due to their interaction with the two cysteine residues in tau. Mass spectrometry of a synthetic peptide, SKCGS, representing the actual tau sequence, identified the thiol as reacting with CA and ECox. Use of a cysteine double mutant of tau showed the necessity of cysteine for aggregation inhibition by CA. The interaction of CA with tau cysteines was reversible and the presence of CA did not impair the biological function of tau in tubulin assembly in vitro. Further, these compounds protected tau from oxidation caused by the reactive oxygen species, H2O2, and prevented subsequent formation of high molecular weight species that are considered to stimulate tangle formation. Finally, we observed that EC can sequester highly reactive and toxic byproducts of oxidation such as acrolein. Our results suggest that small molecules that form a reversible interaction with cysteines have the potential to protect tau from abnormal modifications.

Introduction: Invasive pneumococcal disease due to serotype 19A has become a major concern, particularly in the USA and Asia. We describe the characteristics of pneumococcal serotype 19A related empyema and changes in its incidence in the UK., Methods: Data from paediatric empyema patients between September 2006 and March 2011 were collected from 17 respiratory centres in the UK. Pneumococcal serotypes were identified as part of the Health Protection Agency enhanced paediatric empyema surveillance programme., Results: Four serotypes accounted for over 80% of 136 cases (Serotype 1 : 43%, 3 : 21%, 7 : 11% and 19A:10%). The incidence of empyema due to serotype 19A quadrupled from 0.48 (0.16-1.13) cases per million children in 2006/2007 to 2.02 (1.25-3.09) in 2010/2011. Severity of disease was significantly increased in children with 19A infection when compared to other serotypes., Conclusions: The incidence of empyema due to pneumococcal serotype 19A infection has increased significantly and is associated with substantial morbidity.

In 2003 the existing 23-valent pneumococcal vaccine (PPV23) programme for high risk groups was extended to include all ≥ 65 year olds in England and Wales, starting with ≥ 80 year olds and moving to 75-79 and 65-74 year olds by 2005. We conducted an ecological study to assess the impact of the extended PPV23 programme on serotype-specific incidence of invasive pneumococcal disease (IPD) and a case-control study to assess vaccine effectiveness (VE) using the national IPD surveillance dataset. Between 1998 and 2006 IPD incidence caused by PPV23 serotypes in the targeted age-groups was unchanged. IPD caused by the serotypes covered by the 7-valent conjugate vaccine (PCV7) introduced for children in 2006 declined in ≥ 65 year olds after 2006 but was offset by an increase in non-PCV7 serotypes. This increase was similar for the additional 16 serotypes covered by PPV23 and the non-PPV23 serotypes. For the VE study, vaccine history was obtained for controls (n=1270) with non-PPV23 IPD diagnosed between November 2003 and December 2010 and a subset of cases (n=1272) matched for age and time period. VE declined from 48% (95% confidence interval; 32-60%) within two years of vaccination to 15% (-3% to 30%) after five years. Although differences in VE by age and having risk conditions were not statistically significant the highest estimates were in the youngest age group (65-74 years) and in those without risk conditions with a VE estimate of 65% (23-84%) within 2 years of vaccination for non-risk 65-74 year olds. VE differed by serotype (p=0.005), from -23% (-85% to 19%) for serotype 3 to 63% (29-81%) for 12F. In conclusion PPV23 was effective, particularly in healthy under 75 year olds, but protection waned after 5 years. There was no discernible impact of PPV23 on IPD incidence or PCV7-induced serotype replacement, consistent with the modest overall effectiveness, the 45% increased coverage over the former risk-based programme and lack of herd immunity from the PPV23 programme. Based on the VE estimates PPV23 was still considered a cost-effective intervention for the low risk elderly., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Polychlorinated biphenyls (PCBs), persistent chemicals widely used for industrial purposes, have been banned in most parts of the world for decades. Owing to their bioaccumulative nature, PCBs are still found in high concentrations in marine mammals, particularly those that occupy upper trophic positions. While PCB-related health effects have been well-documented in some mammals, studies among dolphins and whales are limited. We conducted health evaluations of bottlenose dolphins (Tursiops truncatus) near a site on the Georgia, United States coast heavily contaminated by Aroclor 1268, an uncommon PCB mixture primarily comprised of octa- through deca-chlorobiphenyl congeners. A high proportion (26%) of sampled dolphins suffered anaemia, a finding previously reported from primate laboratory studies using high doses of a more common PCB mixture, Aroclor 1254. In addition, the dolphins showed reduced thyroid hormone levels and total thyroxine, free thyroxine and triiodothyronine negatively correlated with PCB concentration measured in blubber (p = 0.039, < 0.001, 0.009, respectively). Similarly, T-lymphocyte proliferation and indices of innate immunity decreased with blubber PCB concentration, suggesting an increased susceptibility to infectious disease. Other persistent contaminants such as DDT which could potentially confound results were similar in the Georgia dolphins when compared with previously sampled reference sites, and therefore probably did not contribute to the observed correlations. Our results clearly demonstrate that dolphins are vulnerable to PCB-related toxic effects, at least partially mediated through the endocrine system. The severity of the effects suggests that the PCB mixture to which the Georgia dolphins were exposed has substantial toxic potential and further studies are warranted to elucidate mechanisms and potential impacts on other top-level predators, including humans, who regularly consume fish from the same marine waters.

Efficacy of the new serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease (IPD) was based on a putative correlate of protection. In England and Wales, PCV13 replaced PCV7 in the 2, 4, and 13 month schedule in April 2010. Using non-vaccine type IPD cases as controls, we estimated vaccine effectiveness (VE) for the new serotypes. Among 166 IPD cases in PCV13 eligible children reported by July 2011 with known serotype and vaccination status, VE for 2 doses under a year was 78% (95% confidence interval -18% to 96%) and 77% (38-91%) for one dose over a year. VE for 7F and 19A was 76% (21-93%) and 70% (10-90%) respectively for ≥one dose. VE for serotypes 1 and 3 was 62% and 66% respectively although confidence intervals spanned zero. IPD due to PCV13-only serotypes halved in children under 2 years in the study period., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Interventional cardiology for paediatric and congenital cardiac disease is a relatively young and rapidly evolving field. As the profession begins to establish multi-institutional databases, a universal system of nomenclature is necessary for the field of interventional cardiology for paediatric and congenital cardiac disease. The purpose of this paper is to present the results of the efforts of The International Society for Nomenclature of Paediatric and Congenital Heart Disease to establish a system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease, focusing both on procedural nomenclature and on the nomenclature of complications associated with interventional cardiology. This system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease is a component of The International Paediatric and Congenital Cardiac Code. This manuscript is the first part of a two-part series. Part 1 will cover the procedural nomenclature associated with interventional cardiology as treatment for paediatric and congenital cardiac disease. This procedural nomenclature of The International Paediatric and Congenital Cardiac Code will be used in the IMPACT Registry™ (IMproving Pediatric and Adult Congenital Treatment) of the National Cardiovascular Data Registry® of The American College of Cardiology. Part 2 will cover the nomenclature of complications associated with interventional cardiology as treatment for paediatric and congenital cardiac disease.

Interventional cardiology for paediatric and congenital cardiac disease is a relatively young and rapidly evolving field. As the profession begins to establish multi-institutional databases, a universal system of nomenclature is necessary for the field of interventional cardiology for paediatric and congenital cardiac disease. The purpose of this paper is to present the results of the efforts of The International Society for Nomenclature of Paediatric and Congenital Heart Disease to establish a system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease, focusing both on procedural nomenclature and the nomenclature of complications associated with interventional cardiology. This system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease is a component of The International Paediatric and Congenital Cardiac Code. This manuscript is the second part of the two-part series. Part 1 covered the procedural nomenclature associated with interventional cardiology as treatment for paediatric and congenital cardiac disease. Part 2 will cover the nomenclature of complications associated with interventional cardiology as treatment for paediatric and congenital cardiac disease.

Bottlenose dolphins (Tursiops truncatus) are apex predators in coastal southeastern U.S. waters; as such they are indicators of persistent organic pollutants (POPs) in coastal ecosystems. POP concentrations measured in a dolphin's blubber are influenced by a number of factors, including the animal's sex and ranging pattern in relation to POP point sources. This study examined POP concentrations measured in bottlenose dolphin blubber samples (n=102) from the Georgia, USA coast in relation to individual ranging patterns and specifically, distance of sightings from a polychlorinated biphenyl (PCB) point source near Brunswick, Georgia. Dolphin ranging patterns were determined based upon 5years of photo-identification data from two field sites approximately 40km apart: (1) the Brunswick field site, which included the Turtle/Brunswick River Estuary (TBRE), and (2) the Sapelo field site, which included the Sapelo Island National Estuarine Research Reserve (SINERR). Dolphins were categorized into one of three ranging patterns from photo-identification data. Individuals with sighting histories exclusively within one of the defined field sites were considered to have either Brunswick or Sapelo ranging patterns. Individuals sighted in both field sites were classified as having a Mixed ranging pattern. Brunswick males had the highest concentrations of PCBs reported for any marine mammal. The pattern of PCB congeners was consistent with Aroclor 1268, a highly chlorinated PCB mixture associated with a Superfund site in Brunswick. PCB levels in Sapelo males were lower than in Brunswick males, but comparable to the highest levels measured in other dolphin populations along the southeastern U.S. Female dolphins had higher Aroclor 1268 proportions than males, suggesting that the highly chlorinated congeners associated with Aroclor 1268 may not be offloaded through parturition and lactation, as easily as less halogenated POPs. Individuals sighted farther from the Superfund point source had lower Aroclor 1268 proportions., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In support of the surveillance of pneumococcal infections in the era of conjugate vaccines, a sensitive and specific multiplex immunoassay using xMAP beads has been developed for direct detection of pneumococcal serotype-specific polysaccharides in clinical samples, particularly urine. The assay was tested on panels of spiked urine specimens, clinical urine specimens and bacterial isolates. Each of the 14 serotypes in the multiplex assay can be detected to 0.1&emsp14;ng purified polysaccharide ml(-1), or less. Testing of a panel of urine specimens from patients with culture-confirmed pneumococcal or non-pneumococcal disease indicated that the multiplex assay is both sensitive and specific. The correct pneumococcal serotype was identified directly from urine in 46/58 (79.3 %) patients who had a contemporaneous blood culture isolate of a multiplex assay serotype. Furthermore, the specificity of the assay on this panel of samples was 99.3 % (145/146). This multiplex assay could be useful, in conjunction with the pneumococcal screening test Binax NOW, in urine for diagnosis of pneumococcal disease and the identification of the aetiological serotype, and potentially be of benefit in culture-negative patients.

Background: The 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2, 3 and 13 month schedule, and has led to large decreases in invasive pneumococcal disease (IPD) caused by the vaccine serotypes in both vaccinated and unvaccinated cohorts. We estimated the effectiveness of PCV-7 against IPD., Methods and Findings: We used enhanced surveillance data, collated at the Health Protection Agency, on vaccine type (n = 153) and non vaccine type (n = 919) IPD cases eligible for PCV-7. The indirect cohort method, a case-control type design which uses non vaccine type cases as controls, was used to estimate effectiveness of various numbers of doses as well as for each vaccine serotype. Possible bias with this design, caused by differential serotype replacement in vaccinated and unvaccinated individuals, was estimated after deriving formulae to quantify the bias. The results showed good effectiveness, increasing from 56% (95% confidence interval (CI): -7-82) for a single dose given under one year of age to 93% (95% CI: 70-98) for two doses under one year of age plus a booster dose in the second year of life. Serotype specific estimates indicated higher effectiveness against serotypes 4, 14 and 18C and lower effectiveness against 6B. Under the assumption of complete serotype replacement by non vaccine serotypes in carriage, we estimated that effectiveness estimates may be overestimated by about 2 to 5%., Conclusions: This study shows high effectiveness of PCV-7 under the reduced schedule used in the UK. This finding agrees with the large reductions seen in vaccine type IPD in recent years in England and Wales. The formulae derived to assess the bias of the indirect cohort method for PCV-7 can also be used when using the design for other vaccines that affect carriage such as the recently introduced 13 valent pneumococcal conjugate vaccine.

Four Streptococcus pneumoniae isolates expressing both 6A and 6B capsular serotypes were detected by a multiplex immunoassay. The sequence of WciP, a GT2-family glycosyltransferase, indicates that point mutation has compromised linkage specificity, allowing two alternative oligosaccharides to be synthesized. This finding highlights that mutation as well as recombination can mediate serotype change.

Reports of the development of antimicrobial resistance by Bordetella pertussis to macrolides in the United States and Taiwan, together with a recent increase in pertussis notifications and laboratory-confirmed cases in England and Wales in 2008, prompted the examination of historical and recent clinical isolates from patients for evidence of such resistance in our collection. Isolates submitted to our laboratory as part of the enhanced surveillance scheme for pertussis, from 2001 to 2009, were tested against three agents, erythromycin, clarithromycin and azithromycin, by the Etest (bioMérieux) method. All isolates (n = 583) were fully susceptible to all three agents tested (minimum inhibitory concentrations [MICs] 256 microg/ml. Although no evidence of resistance was found in the strains tested from the United Kingdom, screening for antimicrobial resistance of B. pertussis may be warranted in cases that are unresponsive to macrolide treatment and to provide early warning of such emergence in the future.

Development of multiple antibiotic resistance in Streptococcus pneumoniae typically involves either mutation or transformation at several well-separated chromosomal loci. We postulated that this series of genetic events would be more likely to occur in organisms with deficient DNA repair mechanisms. Investigation of 27 antibiotic-resistant or -susceptible clinical isolates of S. pneumoniae revealed a broad range of mutation frequencies, but no isolate was as mutable as a mismatch repair (MMR)-deficient laboratory isolate. No correlation was observed between antibiotic resistance and higher mutation frequency. Examination of a further 180 clinical isolates using a newly developed rapid screen method also failed to identify any isolates with a mutation frequency as high as the MMR-deficient control strain. We argue that there is currently no clear evidence of a distinct population of mutators among clinical pneumococci., ((c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

The surveillance of serotypes causing invasive pneumococcal disease (IPD) provides further insight into the pathogenesis of pneumococcal disease and is important in order to track vaccine impact. Although the Quellung reaction has been accepted as the standard method for serotyping, prior antibiotic use causes a gap in studies based on bacterial culture. A total of 31 cerebrospinal fluid (CSF) samples found to be positive for Streptococcus pneumoniae by polymerase chain reaction (PCR) targeting the ply gene during an active surveillance were tested in a Bio-Plex multiplex antigen detection assay capable of detecting 14 serotypes/groups (1, 3, 4, 5, 6A, 6B, 7F/A, 8, 9V, 14, 18, 19A, 19F, and 23F). Twenty-seven CSF samples could be serotyped. The most common serotypes were serotypes 5 (n = 7), 19F (n = 5), 1 (n = 3), and 23F (n = 3). Theoretical coverage rates by the heptavalent (PCV7), 10-valent (PCV10), and 13-valent (PCV13) pneumococcal conjugate vaccines for bacterial meningitis were 48.1, 85.2, and 92.3%, respectively, for all age groups and 71.4, 85.7, and 100.0%, respectively, for those under 2 years of age. We propose that antigen detection assay used in conjunction with a PCR assay can be effectively applied in CSF samples to detect the pneumococcal serotypes, especially when the patient may have already been treated and, therefore, the cultures would be negative.

As part of an enhanced surveillance programme for pertussis in England and Wales, a real-time PCR service for the detection of Bordetella pertussis was introduced for infants aged

Streptococcus pneumoniae strains causing invasive pneumococcal disease (IPD) in the elderly population of England and Wales during the winter of 2003/2004 (1 November 2003 to 30 April 2004) were characterized by serotyping and genotyping in order to determine their population structure in the elderly. Serotyping and multilocus sequence typing (MLST) were carried out on 542 invasive isolates referred to the Respiratory and Systemic Infection Laboratory. Pneumococci were distributed among 32 serotypes and 144 MLST sequence types. A high genetic diversity was observed within the major serotypes. Genetic relatedness varied with regard to serotype. Isolates within serotypes 3, 7F and 8 were the most genetically related whereas serotypes 6A and 19F comprised isolates originating from unrelated ancestors. There was indirect evidence that some pneumococci were derived from clones that had undergone capsular switching in the past. Interestingly one case of IPD was caused by a pneumococcus originating from a clone that had undergone capsular switching from serotype 18C, a serotype included in 7-valent pneumococcal conjugate vaccine (PCV) to serotype 1 (serotype not included in PCV) suggesting that virulent clones with the potential ability to evade PCV existed in the pneumococcal population prior to the routine introduction of this vaccine. Isolates from 28 cases of apparent 23-valent pneumococcal polysaccharide vaccine (PPV) failure were included but there was no evidence of the emergence of particular clones associated with vaccine failures. Longitudinal studies based on serotypic and genetic characterization of pneumococci are fundamental to understanding the impact of both PPV and PCV on the genetic structure of pneumococcal populations.

The diagnosis of severe Streptococcus pneumoniae infection relies heavily on insensitive culture techniques. To improve the usefulness of PCR assays, we developed a dual-PCR protocol (targeted at pneumolysin and autolysin) for EDTA blood samples. This was compared to the Binax NOW S. pneumoniae urine antigen test in patients with bacteremic pneumococcal infections. Patients with nonbacteremic community-acquired pneumonia also were tested by these methods to determine what proportion could be confirmed as pneumococcal infections. A direct comparison was made in a group of patients who each had both tests performed. The Binax NOW S. pneumoniae urine antigen test was positive in 51 of 58 bacteremic pneumococcal cases (sensitivity, 88%; 95% confidence interval [CI], 77 to 95%), whereas the dual PCR was positive in 31 cases (sensitivity, 53.5%; 95% CI, 40 to 67%; P < 0.0001), and all of these had detectable urinary antigens. Both tests gave positive results in 2 of 51 control patients (referred to as other-organism septicemia), giving a specificity of 96% (95% CI, 86.5 to 99.5%). In 77 patients with nonbacteremic community-acquired pneumonia, urinary antigen was detected significantly more often (in 21 patients [27%]) than a positive result by the dual-PCR protocol (6 [8%]) (P = 0.002). The development of a dual-PCR protocol enhanced the sensitivity compared to that of the individual assays, but it is still significantly less sensitive than the Binax NOW urine antigen test, as well as being more time-consuming and expensive. Urinary antigen detection is the nonculture diagnostic method of choice for patients with possible severe pneumococcal infection.

An aqueous extract of Ceylon cinnamon (C. zeylanicum) is found to inhibit tau aggregation and filament formation, hallmarks of Alzheimer's disease (AD). The extract can also promote complete disassembly of recombinant tau filaments and cause substantial alteration of the morphology of paired-helical filaments isolated from AD brain. Cinnamon extract (CE) was not deleterious to the normal cellular function of tau, namely the assembly of free tubulin into microtubules. An A-linked proanthocyanidin trimer molecule was purified from the extract and shown to contain a significant proportion of the inhibitory activity. Treatment with polyvinylpyrolidone effectively depleted all proanthocyanidins from the extract solution and removed the majority, but not all, of the inhibitory activity. The remainder inhibitory activity could be attributed to cinnamaldehyde. This work shows that compounds endogenous to cinnamon may be beneficial to AD themselves or may guide the discovery of other potential therapeutics if their mechanisms of action can be discerned.

Objectives: Pneumococcal disease is prevalent and is a cause of significant morbidity and mortality in the UK and Ireland. We describe the antimicrobial susceptibility and serotype distributions of Streptococcus pneumoniae causing bacteraemia and community-acquired pneumonia in these countries from 1999/2000 to 2006/7, predominantly prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the standard vaccination schedule in September 2006., Methods: The BSAC Respiratory and Bacteraemia Resistance Surveillance Programmes collected S. pneumoniae from sentinel laboratories distributed across the UK and Ireland. A central laboratory for each programme re-identified the isolates, determined their serotypes and measured MICs by the BSAC agar dilution method., Results: The prevalence of antimicrobial non-susceptibility, although significant, was generally below the global average. There was no convincing evidence of increasing non-susceptibility over time in either study. The results showed clear differences in the serotype distribution between respiratory and blood isolates, but suggested that PCV7 would provide adequate coverage of invasive isolates in the UK and Ireland. A significant and rapid increase of the non-vaccine serotype 1 among blood isolates from 2001 to 2006 was worrying, given the spread of hypervirulent serotype 1 clones elsewhere in the world., Conclusions: Continued surveillance of both antimicrobial non-susceptibility and serotype distribution changes following the introduction of PCV7 into the routine immunization schedule in the UK and Ireland is imperative. The data presented here, largely obtained prior to the introduction of PCV7 in the UK, provide a valuable baseline against which to monitor changes in antimicrobial non-susceptibility and serotype distribution and hence to identify the expansion of any significant clones.

Objectives: To describe the current patterns and trends in antimicrobial susceptibility in enterococci and streptococci (excepting pneumococci) from bacteraemia in the UK and Ireland from 2001 to 2006., Methods: In each year 2001-06, blood culture isolates were collected by 25 laboratories distributed across the UK and Ireland. In total, there were 1408 isolates of enterococci, 1332 of beta-haemolytic streptococci and 1012 of alpha- and non-haemolytic streptococci. A single central laboratory re-identified the isolates and measured MICs by the BSAC agar dilution method., Results: The prevalence of reduced susceptibility in streptococci and enterococci did not change significantly for most antibiotics, but trends were noted to increased ampicillin, imipenem and vancomycin resistance in Enterococcus faecium. The prevalence of reduced susceptibility to macrolides and tetracycline in streptococci, to tetracycline and gentamicin (high level) in enterococci and to beta-lactams and glycopeptides in E. faecium were all high, with some differences in the prevalence among species or groups., Conclusions: Reduced susceptibility to some antimicrobial agents among streptococci and enterococci remains common and continued surveillance is warranted.

Introduction of pneumococcal conjugate and polysaccharide vaccines into the United Kingdom's routine immunization programmes is expected to change the epidemiology of invasive pneumococcal disease (IPD). We have documented the epidemiology of IPD in an English region (South West) with high-quality surveillance data before these programmes were established. We analysed data on isolates of Streptococcus pneumoniae from blood and CSF between 1996 and 2005 from microbiology laboratories in the South West that were reported and/or referred for serotyping to the Health Protection Agency Centre for Infections. The mean annual incidence of IPD increased from 11.2/100 000 in 1996 to 13.6/100 000 in 2005 (P<0.04). After adjusting for annual blood-culture sampling rates in hospitals serving the same catchment populations, an increase in annual incidence of IPD was no longer observed (P=1.0). Variation in overall incidence between laboratories could also be explained by variation in blood culture rates. The proportion of disease caused by serotypes 6B, 9V and 14 decreased significantly (P=0.001, P=0.007, and P=0.027 respectively) whereas that caused by serotype 4, 7F and 1 increased (P=0.001, P=0.003, and P<0.001 respectively) between 2000 and 2005. The level of penicillin non-susceptibility and resistance to erythromycin remained stable (2% and 12% respectively). This study provides an important baseline to assess the impact of changing vaccination programmes on the epidemiology of IPD, thus informing future use of pneumococcal vaccines.

During 2003, a cluster of initially unexplained pneumonia cases (two fatal) occurred in patients aged <50 years in a British city. Routine culture tests were inconclusive, however, pneumococcal infection was suspected and the putative outbreak was investigated using non-culture methods. Clinical samples from ten patients were tested by pneumococcal polymerase chain reaction (PCR) and multi-locus sequence typing (MLST), or Binax NOW pneumococcal urine antigen test and serotype-specific enzyme-linked immunosorbent assay (ELISA). Lung samples from the deceased patients were PCR positive and yielded different MLST types. Two patients in one family group were serotype 1 pneumococcal antigen positive. Two further patients were serotype 1 antigen positive, and one serotype 4 positive. Two antigen-positive cases were also serum PCR positive. Non-culture methods confirmed the disease aetiology in six cases. Serotype and MLST results showed no single outbreak, but a family cluster of cases in a high background of pneumococcal pneumonia, providing important epidemiological data that would not otherwise have been available.

Objectives: To assess the incidence of pneumococcal meningitis, associated deaths and serotypes of causative pneumococci in England prior to the inclusion of the 7-valent conjugated pneumococcal vaccine in the routine childhood immunisation programme in 2006., Methods: Cases were identified using hospital episode statistics (HES) and voluntary reports or submission of isolates to the Health Protection Agency. Mortality data and population estimates were from the Office for National Statistics., Results: Based on HES, the annual incidence of pneumococcal meningitis was about 1 case per 100,000 population between 1998 and 2005 (an average of approximately 480 cases per year) with case fatality rates increasing from 5% in <15 year olds to 30% in >64 year olds. Enhanced surveillance comprising a combination of voluntary reporting of cases and referral of isolates gave case ascertainment rates of 50-70% compared to those derived from HES, and similar case fatality rates. The age distribution of pneumococcal meningitis was similar with both datasets, infection being reported mostly commonly in children aged less than 5 years, with the highest incidence in children aged 2-11 months. Based on the serotype distribution of isolates obtained in 2005, the serotype coverage afforded by the 7-valent conjugate vaccine is 72% for patients aged less than 2 years., Conclusions: These data provide baseline information on the incidence of pneumococcal meningitis and associated mortality, together with the serotypes of infecting strains of pneumococci, which will be critical for evaluation of the public health impact of the 7-valent conjugated pneumococcal vaccine in England.

Pneumolysin is an important virulence factor of the human pathogen Streptococcus pneumoniae. Sequence analysis of the ply gene from 121 clinical isolates of S. pneumoniae uncovered a number of alleles. Twenty-two strains were chosen for further analysis, and 14 protein alleles were discovered. Five of these had been reported previously, and the remaining 9 were novel. Cell lysates were used to determine the specific hemolytic activities of the pneumolysin proteins. Six strains showed no hemolytic activity, and the remaining 16 were hemolytic, to varying degrees. We report that the nonhemolytic allele reported previously in serotype 1, sequence type (ST) 306 isolates is also present in a number of pneumococcal isolates of serotype 8 that belong to the ST53 lineage. Serotype 1 and 8 pneumococci are known to be associated with outbreaks of invasive disease. The nonhemolytic pneumolysin allele is therefore associated with the dominant clones of outbreak-associated serotypes of S. pneumoniae.

Objectives: Primary care is thought to bear half the cost of treating infections in the UK. We describe the seasonal variation in NHS Direct respiratory calls (a new source of primary care data) and estimate the contribution of specific respiratory pathogens to this variation., Methods: Linear regression models were used to estimate the weekly contribution of specific respiratory pathogens to the volume of NHS Direct respiratory calls (England and Wales, 2002-2004, all ages and 0-4 years)., Results: Annual peaks in NHS Direct cough and difficulty breathing calls occurred in late December, with peaks in 'cold/flu' and fever calls occurring between November and April. The main explanatory variables were influenza (estimated to account for 72.5 calls per 100,000/year; 22% of 'cold/flu' calls; 15% of cough; and 13% of fever) and Streptococcus pneumoniae (55.5 per 100,000; 33% of 'cold/flu' calls; 20% of cough; and 15% of fever (0-4 years))., Conclusions: It is estimated that respiratory viruses, notably influenza and RSV, are responsible for at least 50% of the seasonal variation in NHS Direct respiratory calls. These results provide estimates of the burden of specific respiratory diseases reported to NHS Direct, and will help interpret syndromic surveillance data used to provide early warning of rises in community morbidity.