Linking healthcare associated norovirus outbreaks: a molecular epidemiologic method for investigating transmission.

BACKGROUND: Noroviruses are highly infectious pathogens that cause gastroenteritis in the community and in semi-closed institutions such as hospitals. During outbreaks, multiple units within a hospital are often affected, and a major question for control programs is: are the affected units part of the same outbreak or are they unrelated transmission events? In practice, investigators often assume a transmission link based on epidemiological observations, rather than a systematic approach to tracing transmission.Here, we present a combined molecular and statistical method for assessing:1) whether observed clusters provide evidence of local transmission and2) the probability that anecdotally|linked outbreaks truly shared a transmission event. METHODS: 76 healthcare associated outbreaks were observed in an active and prospective surveillance scheme of 15 hospitals in the county of Avon, England from April 2002 to March 2003. Viral RNA from 64 out of 76 specimens from distinct outbreaks was amplified by reverse transcription-PCR and was sequenced in the polymerase (ORF 1) and capsid (ORF 2) regions. The genetic diversity, at the nucleotide level, was analysed in relation to the epidemiological patterns. RESULTS: Two out of four genetic and epidemiological clusters of outbreaks were unlikely to have occurred by chance alone, thus suggesting local transmission. There was anecdotal epidemiological evidence of a transmission link among 5 outbreaks pairs. By combining this epidemiological observation with viral sequence data, the evidence of a link remained convincing in 3 of these pairs. These results are sensitive to prior beliefs of the strength of epidemiological evidence especially when the outbreak strains are common in the background population. CONCLUSION: The evidence suggests that transmission between hospitals units does occur. Using the proposed criteria, certain hypothesized transmission links between outbreaks were supported while others were refuted. The combined molecular/epidemiologic approach presented here could be applied to other viral populations and potentially to other pathogens for a more thorough view of transmission

Compensation for Commuting in Imperfect Urban Markets

We develop an urban equilibrium job search model with employed and unemployed individuals where residential mobility of the unemployed is restricted. We assume a standard mono-centric model (firms are located in one location), but allow for imperfect labour markets. In contrast to models with perfect labour markets, the model predicts that the employed are only partially compensated for commuting costs in the form of wages. As a result, rent gradients are less steep than predicted by standard urban theories that assume perfectly competitive labour markets. © 2007 the author(s). Journal compilation © 2007 RSAI

Loop-mediated isothermal amplification (LAMP) for the rapid detection of Mycoplasma genitalium

Mycoplasma genitalium is a sexually transmissible, pathogenic bacterium and a significant cause of nongonococcal urethritis in both men and women. Due to the difficulty of the culture of M. genitalium from clinical samples, the laboratory diagnosis of M. genitalium infection is almost exclusively carried out using nucleic acid amplification tests. Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification technology, utilising a set of 4 primers specific to 6 distinct regions of the target DNA sequence, in order to amplify target DNA in a highly specific and rapid manner. A LAMP assay was designed to the pdhD gene of M. genitalium, and the limit of detection of the assay was determined as 10. fg of M. genitalium genomic DNA, equating to ~16 copies of the M. genitalium genome, which was equally sensitive as a gold standard 16S rRNA polymerase chain reaction assay. © 2015 Elsevier Inc

Development and internal validation of a clinical rule to improve antibiotic use in children presenting to primary care with acute respiratory tract infection and cough: a prognostic cohort study

BACKGROUND: Antimicrobial resistance is a serious threat to public health, with most antibiotics prescribed in primary care. General practitioners (GPs) report defensive antibiotic prescribing to mitigate perceived risk of future hospital admission in children with respiratory tract infections. We developed a clinical rule aimed to reduce clinical uncertainty by stratifying risk of future hospital admission. METHODS: 8394 children aged between 3 months and 16 years presenting with acute cough (for ≤28 days) and respiratory tract infection were recruited to a prognostic cohort study from 247 general practitioner practices in England. Exposure variables included demographic characteristics, parent-reported symptoms, and physical examination signs. The outcome was hospital admission for respiratory tract infection within 30 days, collected using a structured, blinded review of medical records. FINDINGS: 8394 (100%) children were included in the analysis, with 78 (0·9%, 95% CI 0·7%-1·2%) admitted to hospital: 15 (19%) were admitted on the day of recruitment (day 1), 33 (42%) on days 2-7; and 30 (39%) on days 8-30. Seven characteristics were independently associated (p<0·01) with hospital admission: age <2 years, current asthma, illness duration of 3 days or less, parent-reported moderate or severe vomiting in the previous 24 h, parent-reported severe fever in the previous 24 h or a body temperature of 37·8°C or more at presentation, clinician-reported intercostal or subcostal recession, and clinician-reported wheeze on auscultation. The area under the receiver operating characteristic (AUROC) curve for the coefficient-based clinical rule was 0·82 (95% CI 0·77-0·87, bootstrap validated 0·81). Assigning one point per characteristic, a points-based clinical rule consisting of short illness, temperature, age, recession, wheeze, asthma, and vomiting (mnemonic STARWAVe; AUROC 0·81, 0·76-0·85) distinguished three hospital admission risk strata: very low (0·3%, 0·2-0·4%) with 1 point or less, normal (1·5%, 1·0-1·9%) with 2 or 3 points, and high (11·8%, 7·3-16·2%) with 4 points or more. INTERPRETATION: Clinical characteristics can distinguish children at very low, normal, and high risk of future hospital admission for respiratory tract infection and could be used to reduce antibiotic prescriptions in primary care for children at very low risk. FUNDING: National Institute for Health Research (NIHR)

Whole genome protein microarrays for serum profiling of immunodominant antigens of Bacillus anthracis

&lt;p&gt;A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis &quot;infectome.&quot; These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.&lt;/p&gt;</p

Epidemiology and Cost of Nosocomial Gastroenteritis, Avon, England, 2002–2003

Implementing control measures rapidly may be effective in controlling gastroenteritis outbreaks

Epidemiology of pleural empyema in English hospitals and the impact of influenza

Pleural empyema represents a significant healthcare burden due to extended hospital admissions and potential requirement for surgical intervention. This study aimed to assess changes in incidence and management of pleural empyema in England over the past 10 years and the potential impact of influenza on rates. Hospital Episode Statistics data were used to identify patients admitted to English hospitals with pleural empyema between 2008 and 2018. Linear regression was used to analyse the relationship between empyema rates and influenza incidence recorded by Public Health England. The relationship between influenza and empyema was further explored using serological data from a prospective cohort study of patients presenting with pleural empyema. Between April 2008 and March 2018 there were 55 530 patients admitted with pleural empyema. There was male predominance (67% versus 33%), which increased with age. Cases have increased significantly from 4447 in 2008 to 7268 in 2017. Peaks of incidence correlated moderately with rates of laboratoryconfirmed influenza in children and young adults (r=0.30). For nine of the 10 years studied, the highest annual point incidence of influenza coincided with the highest admission rate for empyema (with a 2-week lag). In a cohort study of patients presenting to a single UK hospital with pleural empyema/ infection, 24% (17 out of 72) had serological evidence of recent influenza infection, compared to 7% in seasonally matched controls with simple parapneumonic or cardiogenic effusions (p<0.001). Rates of empyema admissions in England have increased steadily with a seasonal variation that is temporally related to influenza incidence. Patient-level serological data from a prospective study support the hypothesis that influenza may play a pathogenic role in empyema development

Density Distribution of Pharyngeal Carriage of Meningococcus in Healthy Young Adults: New Approaches to Studying the Epidemiology of Colonization and Vaccine Indirect Effects.

BACKGROUND: Improved understanding of Neisseria meningitidis (Nm) carriage biology and better methods for detection and quantification would facilitate studies of potential impact of new vaccines on colonization and transmission in adolescents. METHODS: We performed plate cultures on 107 oropharyngeal swabs stored frozen in skim milk tryptone glucose glycerol (STGG) broth and previously positive for Nm. We compared quantitative polymerase chain reaction (qPCR) detection of Nm in 601 STGG-swabs with culture. Using qPCR (n = 87), a log-phase broth culture standard curve and semiquantitative plate cultures (n = 68), we measured density of carriage. We compared qPCR genogrouping of DNA extracts from STGG-swabs and from plate culture lawns (n = 110) with purified isolates (n = 80). RESULTS: Swab storage resulted in only 10% loss of culture sensitivity. Direct sodC qPCR Nm detection yielded more positives (87/601, 14.5%) than culture (80/601, 13.3%). Most samples (57/110) positive by culture were also positive by qPCR and vice versa, but discrepancies (single positives) were frequent among low-density samples. sodC qPCR was positive in 79/80 isolates but in only 65 by ctrA qPCR. Density both by culture and qPCR varied across 4 orders of magnitude with the majority being low (1000). Genogrouping qPCRs yielded more positive results when performed on DNA extracts from lawn cultures. CONCLUSIONS: We provide the first description of the distribution of Nm carriage density. This could be important for understanding transmission dynamics and population-level effectiveness of adolescent vaccine programs. Storage of swabs frozen in STGG for batched laboratory analysis facilitates carriage studies and direct sodC qPCR for Nm combined with qPCR genogrouping of lawn culture extracts provides accurate, detailed description of colonization

Insights into Pasteurellaceae carriage dynamics in the nasal passages of healthy beef calves

We investigated three bovine respiratory pathobionts in healthy cattle using qPCR optimised and validated to quantify Histophilus somni, Mannheimia haemolytica and Pasteurella multocida over a wide dynamic range. A longitudinal study was conducted to investigate the carriage and density of these bacteria in the nasal passages of healthy beef calves (n=60) housed over winter in an experimental farm setting. The three pathobiont species exhibited remarkably different carriage rates and density profiles. At housing, high carriage rates were observed for P. multocida (95%), and H. somni (75%), while fewer calves were positive for M. haemolytica (13%). Carriage rates for all three bacterial species declined over the 75-day study, but not all individuals became colonised despite sharing of environment and airspace. Colonisation patterns ranged from continuous to intermittent and were different among pathobiont species. Interval-censored exponential survival models estimated the median duration of H. somni and P. multocida carriage at 14.8 (CI95%: 10.6–20.9) and 55.5 (CI95%: 43.3–71.3) days respectively, and found higher density P. multocida carriage was associated with slower clearance (p = 0.036). This work offers insights into the dynamics of pathobiont carriage and provides a potential platform for further data collection and modelling studies