Publications by authors named "Norman Fry"

Background: Pneumococcal infections are associated with significant morbidity and mortality, especially at the extremes of age and in those with underlying conditions. Little is known about the risks, presentations or outcomes of invasive pneumococcal disease (IPD) during pregnancy or the postpartum period.

Methods: The UK Health Security Agency conducts enhanced national surveillance of IPD in England.

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Article Synopsis
  • Haemophilus influenzae serotype b (Hib) conjugate vaccines have decreased Hib disease globally, but some European countries are seeing a rise in invasive cases, prompting a study in England to analyze trends over 11 years.
  • The UK Health Security Agency conducted national surveillance, reporting 6881 invasive infections from 2012 to 2023, with 2% being Hib cases, primarily affecting adults (median age 51) and leading to bacteraemic pneumonia in most instances.
  • The study concluded that while invasive Hib disease remains rare in England, it primarily impacts adults with pre-existing conditions, with a low case-fatality rate and no significant increase in overall incidence.
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Inference on pneumococcal transmission has mostly relied on longitudinal studies which are costly and resource intensive. Therefore, we conducted a pilot study to test the ability to infer who infected whom from cross-sectional pneumococcal sequences using phylogenetic inference. Five suspected transmission pairs, for which there was epidemiological evidence of who infected whom, were selected from a household study.

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Pneumococcal carriage studies have suggested that pneumococcal colonization in adults is largely limited to the oral cavity and oropharynx. In this study, we used total abundance-based β-diversity (dissimilarity) and β-diversity components to characterize age-related differences in pneumococcal serotype composition of respiratory samples. quantitative PCR (qPCR) was applied to detect pneumococcal serotypes in nasopharyngeal samples collected from 946 toddlers and 602 adults, saliva samples collected from a subset of 653 toddlers, and saliva and oropharyngeal samples collected from a subset of 318 adults.

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Background: Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic.

Methods: We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020.

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Antibody testing for evidence of a recent infection by estimating anti-pertussis toxin immunoglobulin G (anti-PT-IgG) titres by enzyme-linked immunosorbent assays is often recommended for those with a cough lasting more than 14 days. Interpreting results varies, with studies recommending different anti-PT-IgG titre thresholds for assigning positivity. In England, early work looking at antibody titre distributions for samples submitted from April 2010 to July 2012 found an optimal threshold of greater than 70 IU ml for good sensitivity, specificity and positive predictive value.

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Background: In July, 2022, an increase in diphtheria cases caused by toxigenic Corynebacterium diphtheriae (C diphtheriae) was reported among asylum seekers arriving by small boats to England. Rising case numbers presented challenges for case and contact management in initial reception centres, prompting changes to national guidance and implementation of population-based control measures. This study aimed to describe the outbreak of toxigenic C diphtheriae among asylum seekers arriving by small boats to England during 2022 by use of national surveillance data.

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Article Synopsis
  • The IRIS Consortium investigated the impact of the COVID-19 pandemic on invasive diseases caused by specific bacteria over a four-year period, comparing data from before and during the pandemic.
  • Laboratories from 30 countries provided surveillance data, revealing a significant decrease in cases of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the pandemic, while Streptococcus agalactiae cases remained unchanged.
  • An estimated 36,289 cases of invasive bacterial disease were prevented due to COVID-19 containment measures during the first two years of the pandemic.
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Combination of PCR and Elek testing to identify toxigenic corynebacteria has revealed organisms described as non-toxigenic toxin-gene bearing (NTTB) or (i.e. PCR positive; Elek negative).

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Article Synopsis
  • Invasive Haemophilus influenzae serotype a (Hia) disease is predominantly found among Indigenous populations in North America, with increased cases identified in England since the 2016-17 epidemiological year, prompting enhanced national surveillance.* -
  • The study involved gathering data from general practitioners and clinicians about confirmed Hia cases from 2008-09 to 2021-22, focusing on demographics, clinical details, and genomic analysis to understand the disease better.* -
  • A total of 52 invasive Hia cases were reported in England during the study period, with a notable rise in cases after 2015-16, peaking at 19 cases in 2021-22, which represented a
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Diphtheria is a potentially life-threatening infection and remains endemic in many low- and middle-income countries (LMICs). A reliable, low-cost method for serosurveys in LMICs is warranted to estimate the accurate population immunity to control diphtheria. The correlation between the ELISA results against diphtheria toxoid and the gold standard diphtheria toxin neutralization test (TNT) values is poor when ELISA values are <0.

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Rationale: epidemiology is changing in response to vaccination and some data suggest that empyema incidence is increasing. However, differences exist between the UK and US studies. We describe trends in the clinical phenotype of adult pneumococcal pleural infection, including simple parapneumonic effusions (SPE) in the pneumococcal conjugate vaccination (PCV) era.

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Background: Despite strong historical records on the accuracy of saliva testing, oral fluids are considered poorly suited for pneumococcal carriage detection. We evaluated an approach for carriage surveillance and vaccine studies that increases the sensitivity and specificity of pneumococcus and pneumococcal serotype detection in saliva samples.

Methods: Quantitative PCR (qPCR)-based methods were applied to detect pneumococcus and pneumococcal serotypes in 971 saliva samples collected from 653 toddlers and 318 adults.

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In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6 months later in 191 of the 213 study infants was 57 % (109/191) and 60 % (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2 + 1 and six in the 1 + 1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21-33 months of age were found in 20 % (7/35) of the 2 + 1 and 15 % (6/41) of the 1 + 1 group.

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Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact.

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Current serological diagnosis of pertussis is usually performed by ELISA, which is typically performed in larger diagnostic or reference laboratories, requires trained staff, and due to sample batching may have longer turnaround times. A rapid point-of-care (POC) assay for pertussis serology would aid in both the diagnosis and surveillance of the disease. A quantitative lateral flow (LF)-based immunoassay with fluorescent Eu-nanoparticle reporters was developed for the detection of anti-pertussis toxin (PT) and adenylate cyclase toxin (ACT) antibodies from oral fluid samples (=100), from suspected pertussis cases with respiratory symptoms.

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Determination of serotypes of is essential for monitoring current vaccine programmes. Since October 2017, pneumococcal serotypes in England have been derived from whole genome sequencing (WGS) data using our bioinformatic tool PneumoCaT. That tool was designed for serotype determination from pure cultures in a reference laboratory.

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Background: England's third-trimester maternal pertussis vaccination, introduced in October 2012, was extended to the second trimester in 2016. Maternal vaccination provides high protection against infant disease, but routine second-trimester vaccination has not previously been assessed.

Methods: National laboratory-confirmed pertussis case surveillance determined vaccination history, maternal vaccination history and hospitalization.

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During July-December 2021, after COVID-19 restrictions were removed in England, invasive pneumococcal disease incidence in children <15 years of age was higher (1.96/100,000 children) than during the same period in 2020 (0.7/100,000 children) and in prepandemic years 2017-2019 (1.

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Background: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet).

Methods: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018.

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Background: The specificity of molecular methods for the detection of carriage is under debate. We propose a procedure for carriage surveillance and vaccine impact studies that increases the accuracy of molecular detection of live pneumococci in polymicrobial respiratory samples.

Methods: Culture and qPCR methods were applied to detect pneumococcus and pneumococcal serotypes in 1,549 nasopharyngeal samples collected in the Netherlands ( = 972) and England ( = 577) from 946 toddlers and 603 adults, and in paired oropharyngeal samples collected exclusively from 319 Dutch adults.

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As with other pathogens, competitive interactions between strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.

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Background: In March 2020, England went into its first lockdown in response to the COVID-19 pandemic. Restrictions eased temporarily, followed by second and third waves in October 2020 and January 2021. Recent data showed that the COVID-19 pandemic resulted in reduced transmission of some invasive diseases.

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