Publications by authors named "Ezra Linley"

20 Publications

  • Page 1 of 1

Seroprevalence of SARS-CoV-2 among Blood Donors and Changes after Introduction of Public Health and Social Measures, London, UK.

Emerg Infect Dis 2021 07;27(7):1795-1801

We describe results of testing blood donors in London, UK, for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) IgG before and after lockdown measures. Anonymized samples from donors 17-69 years of age were tested using 3 assays: Euroimmun IgG, Abbott IgG, and an immunoglobulin receptor-binding domain assay developed by Public Health England. Seroprevalence increased from 3.0% prelockdown (week 13, beginning March 23, 2020) to 10.4% during lockdown (weeks 15-16) and 12.3% postlockdown (week 18) by the Abbott assay. Estimates were 2.9% prelockdown, 9.9% during lockdown, and 13.0% postlockdown by the Euroimmun assay and 3.5% prelockdown, 11.8% during lockdown, and 14.1% postlockdown by the receptor-binding domain assay. By early May 2020, nearly 1 in 7 donors had evidence of past SARS-CoV-2 infection. Combining results from the Abbott and Euroimmun assays increased seroprevalence by 1.6%, 2.3%, and 0.6% at the 3 timepoints compared with Euroimmun alone, demonstrating the value of using multiple assays.
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http://dx.doi.org/10.3201/eid2707.203167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237903PMC
July 2021

Post-vaccination HPV seroprevalence among female sexual health clinic attenders in England.

Vaccine 2021 Jul 12;39(30):4210-4218. Epub 2021 Jun 12.

Blood Safety, Hepatitis, Sexually Transmitted Infections (STI) and HIV Service, Public Health England, London, UK.

Background: The National HPV Immunisation Programme was introduced in England in September 2008 using the HPV16/18 bivalent vaccine. We conducted serological surveillance to explore vaccination coverage levels. We also conducted a case-control study to investigate a hypothesised cross-protective effect of the HPV16/18 vaccine against genital warts.

Methods: Residual serum specimens from 16 to 20 year-old women attending six specialist sexual health services (SSHS) between 2011 and 2015 in England were tested for antibodies against HPV16 and HPV18 using a virus-like particle (VLP)-based multiplex serology assay. Patients were classified as having vaccine-induced seropositivity if they were seropositive for both HPV types and either had high antibody levels for at least one HPV type, or moderately high levels for both HPV types. Differences in vaccine-induced seropositivity by patient characteristics were investigated using logistic regression. Vaccine-induced seropositivity was then compared for patients with genital warts (cases) and matched patients without (controls).

Results: Of 3,973 serum specimens collected, 3,870 (97.4%) had a valid result. The proportion of women with vaccine-induced seropositivity decreased with age (from 78.1% in 16-year-olds to 52.6% in 20-year-olds). Vaccine-induced seropositivity was lower among women born outside the UK, from more deprived areas and with a history of chlamydia diagnosis. A difference in uptake by ethnic group was also seen but this was largely confounded by differences in deprivation and country of birth. Among 537 cases and 1,515 controls, there was little evidence of a protective effect of the bivalent HPV vaccine against genital warts (adjusted odds ratio 0.93; 95% CI: 0.74-1.18).

Discussion: Vaccine-induced seropositivity in this high-risk population was in line with vaccination coverage in the general population although was lower in some at-risk sub-groups. This study does not provide evidence to support a cross-protective effect of the HPV16/18 vaccine against genital warts.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.018DOI Listing
July 2021

Impact of COVID-19 vaccination program on seroprevalence in blood donors in England, 2021.

J Infect 2021 May 11. Epub 2021 May 11.

Immunisation and Countermeasures Division, National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.

The COVID-19 vaccination programme commenced in England on 8th December 2020 primarily based on age; by 7th March 2021 approximately 93% of the English population aged 70+ years had received at least 1 dose of either the Pfizer BioNTech or AstraZeneca vaccines. Using a nucleoprotein assay that detects antibodies following natural infection only and a spike assay that detects infection and vaccine-induced responses, we aim to describe the impact of vaccination on SARS-CoV-2 antibody prevalence in English blood donors.
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http://dx.doi.org/10.1016/j.jinf.2021.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110696PMC
May 2021

Seroprevalence of SARS-CoV-2 antibodies in university students: Cross-sectional study, December 2020, England.

J Infect 2021 07 29;83(1):104-111. Epub 2021 Apr 29.

Immunisation and Countermeasures Division, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.

Background: In England, the reopening of universities in September 2020 coincided with a rapid increase in SARS-CoV-2 infection rates in university aged young adults. This study aimed to estimate SARS-CoV-2 antibody prevalence in students attending universities that had experienced a COVID-19 outbreak after reopening for the autumn term in September 2020.

Methods: A cross-sectional serosurvey was conducted during 02-11 December 2020 in students aged ≤ 25 years across five universities in England. Blood samples for SARS-CoV-2 antibody testing were obtained using a self-sampling kit and analysed using the Abbott SARS-CoV-2 N antibody and/or an in-house receptor binding domain (RBD) assay.

Findings: SARS-CoV-2 seroprevalence in 2,905 university students was 17.8% (95%CI, 16.5-19.3), ranging between 7.6%-29.7% across the five universities. Seropositivity was associated with being younger likely to represent first year undergraduates (aOR 3.2, 95% CI 2.0-4.9), living in halls of residence (aOR 2.1, 95% CI 1.7-2.7) and sharing a kitchen with an increasing number of students (shared with 4-7 individuals, aOR 1.43, 95%CI 1.12-1.82; shared with 8 or more individuals, aOR 1.53, 95% CI 1.04-2.24). Seropositivity was 49% in students living in halls of residence that reported high SARS-CoV-2 infection rates (>8%) during the autumn term.

Interpretation: Despite large numbers of cases and outbreaks in universities, less than one in five students (17.8%) overall had SARS-CoV-2 antibodies at the end of the autumn term in England. In university halls of residence affected by a COVID-19 outbreak, however, nearly half the resident students became infected and developed SARS-CoV-2 antibodies.
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http://dx.doi.org/10.1016/j.jinf.2021.04.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081745PMC
July 2021

Association between self-reported signs and symptoms and SARS-CoV-2 antibody detection in UK key workers.

J Infect 2021 05 26;82(5):151-161. Epub 2021 Mar 26.

Field Service, East of England, National Infection Service, Public Health England, Cambridge, United Kingdom; NIHR Health Protection Research Unit (HPRU) in Genomics and Data Enabling, University of Warwick, Warwick, United Kingdom. Electronic address:

Background: Screening for SARS-CoV-2 antibodies is under way in some key worker groups; how this adds to self-reported COVID-19 illness is unclear. In this study, we investigate the association between self-reported belief of COVID-19 illness and seropositivity.

Methods: Cross-sectional study of three key worker streams comprising (A) Police and Fire & Rescue (2 sites) (B) healthcare workers (1 site) and (C) healthcare workers with previously positive PCR result (5 sites). We collected self-reported signs and symptoms of COVID-19 and compared this with serology results from two SARS-CoV-2 immunoassays (Roche Elecsys® and EUROIMMUN).

Results: Between 01 and 26 June, we recruited 2847 individuals (Stream A: 1,247, Stream B: 1,546 and Stream C: 154). Amongst those without previous positive PCR tests, 687/2,579 (26%) reported belief they had COVID-19, having experienced compatible symptoms; however, only 208 (30.3%) of these were seropositive on both immunoassays. Both immunoassays had high sensitivities relative to previous PCR positivity (>93%); there was also limited decline in antibody titres up to 110 days post symptom onset. Symptomatic but seronegative individuals had differing symptom profiles and shorter illnesses than seropositive individuals.

Conclusion: Non-COVID-19 respiratory illness may have been mistaken for COVID-19 during the outbreak; laboratory testing is more specific than self-reported key worker beliefs in ascertaining past COVID-19 disease.
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http://dx.doi.org/10.1016/j.jinf.2021.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997203PMC
May 2021

Serological surveillance of SARS-CoV-2: Six-month trends and antibody response in a cohort of public health workers.

J Infect 2021 05 22;82(5):162-169. Epub 2021 Mar 22.

Immunisation and Countermeasures Division, PHE Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK; Paediatric Infectious Diseases Research Group (PIDRG), St. Georges University of London (SGUL), London, UK. Electronic address:

Background: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.

Methods: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression.

Findings: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) < 2% Roche (S).

Interpretation: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.
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http://dx.doi.org/10.1016/j.jinf.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982645PMC
May 2021

SARS-CoV-2 infection and transmission in primary schools in England in June-December, 2020 (sKIDs): an active, prospective surveillance study.

Lancet Child Adolesc Health 2021 06 17;5(6):417-427. Epub 2021 Mar 17.

National Infection Service, Public Health England, London, UK.

Background: Little is known about the risk of SARS-CoV-2 infection and transmission in educational settings. Public Health England initiated a study, COVID-19 Surveillance in School KIDs (sKIDs), in primary schools when they partially reopened from June 1, 2020, after the first national lockdown in England to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, seroprevalence, and seroconversion in staff and students.

Methods: sKIDs, an active, prospective, surveillance study, included two groups: the weekly swabbing group and the blood sampling group. The swabbing group underwent weekly nasal swabs for at least 4 weeks after partial school reopening during the summer half-term (June to mid-July, 2020). The blood sampling group additionally underwent blood sampling for serum SARS-CoV-2 antibodies to measure previous infection at the beginning (June 1-19, 2020) and end (July 3-23, 2020) of the summer half-term, and, after full reopening in September, 2020, and at the end of the autumn term (Nov 23-Dec 18, 2020). We tested for predictors of SARS-CoV-2 antibody positivity using logistic regression. We calculated antibody seroconversion rates for participants who were seronegative in the first round and were tested in at least two rounds.

Findings: During the summer half-term, 11 966 participants (6727 students, 4628 staff, and 611 with unknown staff or student status) in 131 schools had 40 501 swabs taken. Weekly SARS-CoV-2 infection rates were 4·1 (one of 24 463; 95% CI 0·1-21·8) per 100 000 students and 12·5 (two of 16 038; 1·5-45·0) per 100 000 staff. At recruitment, in 45 schools, 91 (11·2%; 95% CI 7·9-15·1) of 816 students and 209 (15·1%; 11·9-18·9) of 1381 staff members were positive for SARS-CoV-2 antibodies, similar to local community seroprevalence. Seropositivity was not associated with school attendance during lockdown (p=0·13 for students and p=0·20 for staff) or staff contact with students (p=0·37). At the end of the summer half-term, 603 (73·9%) of 816 students and 1015 (73·5%) of 1381 staff members were still participating in the surveillance, and five (four students, one staff member) seroconverted. By December, 2020, 55 (5·1%; 95% CI 3·8-6·5) of 1085 participants who were seronegative at recruitment (in June, 2020) had seroconverted, including 19 (5·6%; 3·4-8·6) of 340 students and 36 (4·8%; 3·4-6·6) of 745 staff members (p=0·60).

Interpretation: In England, SARS-CoV-2 infection rates were low in primary schools following their partial and full reopening in June and September, 2020.

Funding: UK Department of Health and Social Care.
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http://dx.doi.org/10.1016/S2352-4642(21)00061-4DOI Listing
June 2021

Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection.

Nat Immunol 2021 05 5;22(5):620-626. Epub 2021 Mar 5.

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

The immune response to SARS-CoV-2 is critical in controlling disease, but there is concern that waning immunity may predispose to reinfection. We analyzed the magnitude and phenotype of the SARS-CoV-2-specific T cell response in 100 donors at 6 months following infection. T cell responses were present by ELISPOT and/or intracellular cytokine staining analysis in all donors and characterized by predominant CD4 T cell responses with strong interleukin (IL)-2 cytokine expression. Median T cell responses were 50% higher in donors who had experienced a symptomatic infection, indicating that the severity of primary infection establishes a 'set point' for cellular immunity. T cell responses to spike and nucleoprotein/membrane proteins were correlated with peak antibody levels. Furthermore, higher levels of nucleoprotein-specific T cells were associated with preservation of nucleoprotein-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T cell responses are retained at 6 months following infection.
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http://dx.doi.org/10.1038/s41590-021-00902-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610739PMC
May 2021

Use of dried blood spot samples for SARS-CoV-2 antibody detection using the Roche Elecsys ® high throughput immunoassay.

J Clin Virol 2021 03 19;136:104739. Epub 2021 Jan 19.

Field Service, Public Health England, United Kingdom.

Dried blood spot samples (DBS) provide an alternative sample type to venous blood samples for antibody testing. DBS are used by NHS for diagnosing Hepatitis C and by Public Health England for large scale HIV and Hepatitis C serosurveillance; the applicability of DBS based approaches for SARS-CoV-2 antibody detection is uncertain. The study aimed to compare antibody detection in DBS eluates using the Roche Elecsys ® immunoassay with antibody detection in paired plasma samples, using the same assay. The study was in one Police and one Fire & Rescue facility in England; it comprised of 195 participants within a larger sample COVID-19 serodiagnostics study of keyworkers, EDSAB-HOME. Outcome measures were sensitivity and specificity of DBS (the index test) relative to plasma (the reference test), at an experimental cut-off; quality of DBS sample collected; estimates of relative sensitivity of DBS vs. plasma immunoassay in a larger population. 18/195 (9.2%) participants tested positive using plasma samples. DBS sample quality varied markedly by phlebotomist, and low sample volume significantly reduced immunoassay signals. Using an experimental cut-off, sensitivity and specificity of DBS were 89.0% (95% CI 67.2, 96.9%) and 100.0% (95% CI 97.9, 100%) respectively compared with using plasma. The limit of detection for DBS is about 30 times higher than for plasma. DBS use for SARS-CoV-2 serology, though feasible, is insensitive relative to immunoassays on plasma. Sample quality impacts on assay performance. Alternatives, including the collection of capillary blood samples, should be considered for screening programs.
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http://dx.doi.org/10.1016/j.jcv.2021.104739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817498PMC
March 2021

Rapid community point-of-care testing for COVID-19 (RAPTOR-C19): protocol for a platform diagnostic study.

Diagn Progn Res 2021 Feb 8;5(1). Epub 2021 Feb 8.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK.

Background: The aim of RApid community Point-of-care Testing fOR COVID-19 (RAPTOR-C19) is to assess the diagnostic accuracy of multiple current and emerging point-of-care tests (POCTs) for active and past SARS-CoV2 infection in the community setting. RAPTOR-C19 will provide the community testbed to the COVID-19 National DiagnOstic Research and Evaluation Platform (CONDOR).

Methods: RAPTOR-C19 incorporates a series of prospective observational parallel diagnostic accuracy studies of SARS-CoV2 POCTs against laboratory and composite reference standards in patients with suspected current or past SARS-CoV2 infection attending community settings. Adults and children with suspected current SARS-CoV2 infection who are having an oropharyngeal/nasopharyngeal (OP/NP) swab for laboratory SARS-CoV2 reverse transcriptase Digital/Real-Time Polymerase Chain Reaction (d/rRT-PCR) as part of clinical care or community-based testing will be invited to participate. Adults (≥ 16 years) with suspected past symptomatic infection will also be recruited. Asymptomatic individuals will not be eligible. At the baseline visit, all participants will be asked to submit samples for at least one candidate point-of-care test (POCT) being evaluated (index test/s) as well as an OP/NP swab for laboratory SARS-CoV2 RT-PCR performed by Public Health England (PHE) (reference standard for current infection). Adults will also be asked for a blood sample for laboratory SARS-CoV-2 antibody testing by PHE (reference standard for past infection), where feasible adults will be invited to attend a second visit at 28 days for repeat antibody testing. Additional study data (e.g. demographics, symptoms, observations, household contacts) will be captured electronically. Sensitivity, specificity, positive, and negative predictive values for each POCT will be calculated with exact 95% confidence intervals when compared to the reference standard. POCTs will also be compared to composite reference standards constructed using paired antibody test results, patient reported outcomes, linked electronic health records for outcomes related to COVID-19 such as hospitalisation or death, and other test results.

Discussion: High-performing POCTs for community use could be transformational. Real-time results could lead to personal and public health impacts such as reducing onward household transmission of SARS-CoV2 infection, improving surveillance of health and social care staff, contributing to accurate prevalence estimates, and understanding of SARS-CoV2 transmission dynamics in the population. In contrast, poorly performing POCTs could have negative effects, so it is necessary to undertake community-based diagnostic accuracy evaluations before rolling these out.

Trial Registration: ISRCTN, ISRCTN14226970.
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http://dx.doi.org/10.1186/s41512-021-00093-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868893PMC
February 2021

HPV16 and HPV18 seropositivity and DNA detection among men who have sex with men: a cross-sectional study conducted in a sexual health clinic in London.

Sex Transm Infect 2021 Aug 23;97(5):382-386. Epub 2020 Dec 23.

Institute for Global Health, University College London, London, UK

Objectives: Men who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection and related diseases compared with men who have sex exclusively with women. From April 2018, there has been a phased roll-out of HPV vaccination offered to MSM aged up to 45 years old who are attending sexual health clinics and HIV clinics in England. The vaccine is most effective if delivered prior to HPV infection. We estimated the proportion of MSM with no current vaccine-type infection and no serological evidence of prior infection, in a study undertaken prior to vaccine introduction.

Methods: We conducted a cross-sectional study among 484 MSM aged 18-40 years old who attended a sexual health clinic in London between 2010 and 2012. We estimated the prevalence of current and past infection by testing for HPV DNA in anogenital samples and for serum antibodies to HPV16 and HPV18.

Results: The median age was 30 years (IQR 25-35). The prevalence of HPV16 and HPV18 DNA was 13.2% and 6.2%, respectively. Seropositivity for HPV16 and HPV18 was 28.5% and 17.1%, respectively, with 11.4% seropositive for both types. Seropositivity for the same HPV type was strongly associated with anogenital DNA detection. 279 MSM (57.6%) tested negative for both HPV16 and HPV18 serology and were DNA negative for these two types; only 5 MSM (1.0%) were seropositive and DNA positive for both HPV types.

Conclusions: This is the first study to determine both the prevalence of HPV DNA in anogenital samples and HPV seroprevalence among MSM attending a sexual health clinic in the UK. Over half of MSM in this study had no evidence of a previous or current infection with either of the high-risk HPV types included in the quadrivalent vaccine, which supports the rationale for opportunistic HPV vaccination of MSM attending sexual health clinics.
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http://dx.doi.org/10.1136/sextrans-2020-054726DOI Listing
August 2021

Emergence of a Novel Coronavirus (COVID-19): Protocol for Extending Surveillance Used by the Royal College of General Practitioners Research and Surveillance Centre and Public Health England.

JMIR Public Health Surveill 2020 04 2;6(2):e18606. Epub 2020 Apr 2.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.

Background: The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) have successfully worked together on the surveillance of influenza and other infectious diseases for over 50 years, including three previous pandemics. With the emergence of the international outbreak of the coronavirus infection (COVID-19), a UK national approach to containment has been established to test people suspected of exposure to COVID-19. At the same time and separately, the RCGP RSC's surveillance has been extended to monitor the temporal and geographical distribution of COVID-19 infection in the community as well as assess the effectiveness of the containment strategy.

Objectives: The aims of this study are to surveil COVID-19 in both asymptomatic populations and ambulatory cases with respiratory infections, ascertain both the rate and pattern of COVID-19 spread, and assess the effectiveness of the containment policy.

Methods: The RCGP RSC, a network of over 500 general practices in England, extract pseudonymized data weekly. This extended surveillance comprises of five components: (1) Recording in medical records of anyone suspected to have or who has been exposed to COVID-19. Computerized medical records suppliers have within a week of request created new codes to support this. (2) Extension of current virological surveillance and testing people with influenza-like illness or lower respiratory tract infections (LRTI)-with the caveat that people suspected to have or who have been exposed to COVID-19 should be referred to the national containment pathway and not seen in primary care. (3) Serology sample collection across all age groups. This will be an extra blood sample taken from people who are attending their general practice for a scheduled blood test. The 100 general practices currently undertaking annual influenza virology surveillance will be involved in the extended virological and serological surveillance. (4) Collecting convalescent serum samples. (5) Data curation. We have the opportunity to escalate the data extraction to twice weekly if needed. Swabs and sera will be analyzed in PHE reference laboratories.

Results: General practice clinical system providers have introduced an emergency new set of clinical codes to support COVID-19 surveillance. Additionally, practices participating in current virology surveillance are now taking samples for COVID-19 surveillance from low-risk patients presenting with LRTIs. Within the first 2 weeks of setup of this surveillance, we have identified 3 cases: 1 through the new coding system, the other 2 through the extended virology sampling.

Conclusions: We have rapidly converted the established national RCGP RSC influenza surveillance system into one that can test the effectiveness of the COVID-19 containment policy. The extended surveillance has already seen the use of new codes with 3 cases reported. Rapid sharing of this protocol should enable scientific critique and shared learning.

International Registered Report Identifier (irrid): DERR1-10.2196/18606.
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http://dx.doi.org/10.2196/18606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124955PMC
April 2020

Plans for Nationwide Serosurveillance Network in Vietnam.

Emerg Infect Dis 2020 01;26(1)

In recent years, serosurveillance has gained momentum as a way of determining disease transmission and immunity in populations, particularly with respect to vaccine-preventable diseases. At the end of 2017, the Oxford University Clinical Research Unit and the National Institute of Hygiene and Epidemiology held a meeting in Vietnam with national policy makers, researchers, and international experts to discuss current seroepidemiologic projects in Vietnam and future needs and plans for nationwide serosurveillance. This report summarizes the meeting and the plans that were discussed to set up nationwide serosurveillance in Vietnam.
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http://dx.doi.org/10.3201/eid2601.190641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924907PMC
January 2020

Serological surveillance of influenza in an English sentinel network: pilot study protocol.

BMJ Open 2019 03 8;9(3):e024285. Epub 2019 Mar 8.

Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.

Background: Rapidly undertaken age-stratified serology studies can produce valuable data about a new emerging infection including background population immunity and seroincidence during an influenza pandemic. Traditionally seroepidemiology studies have used surplus laboratory sera with little or no clinical information or have been expensive detailed population based studies. We propose collecting population based sera from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), a sentinel network with extensive clinical data.

Aim: To pilot a mechanism to undertake population based surveys that collect serological specimens and associated patient data to measure seropositivity and seroincidence due to seasonal influenza, and create a population based serology bank. METHODS AND ANALYSIS: We will recruit 6 RCGP RSC practices already taking nasopharyngeal virology swabs. Patients who attend a scheduled blood test will be consented to donate additional blood samples. Approximately 100-150 blood samples will be collected from each of the following age bands - 18- 29, 30- 39, 40- 49, 50- 59, 60- 69 and 70+ years.

Methods: We will send the samples to the Public Health England (PHE) Seroepidemiology Unit for processing and storage. These samples will be tested for influenza antibodies, using haemagglutination inhibition assays. Serology results will be pseudonymised, sent to the RCGP RSC and combined using existing processes at the RCGP RSC secure hub. The influenza seroprevalence results from the RCGP cohort will be compared against those from the annual PHE influenza residual serosurvey.

Ethics And Dissemination: Ethical approval was granted by the Proportionate Review Sub- Committee of the London - Camden & Kings Cross on 6 February 2018. This study received approval from Health Research Authority on 7 February 2018. On completion the results will be made available via peer-reviewed journals.
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http://dx.doi.org/10.1136/bmjopen-2018-024285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429844PMC
March 2019

Serogroup C disease epidemiology, seroprevalence, vaccine effectiveness and waning immunity, England, 1998/99 to 2015/16.

Euro Surveill 2019 Jan;24(1)

University of Manchester, Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Stopford Building, Manchester, United Kingdom.

BackgroundIn 1999, the United Kingdom (UK) was the first country to introduce meningococcal group C (MenC) conjugate vaccination. This vaccination programme has evolved with further understanding, new vaccines and changing disease epidemiology.AimTo characterise MenC disease and population protection against MenC disease in England.MethodsBetween 1998/99-2015/16, surveillance data from England for laboratory-confirmed MenC cases were collated; using the screening method, we updated vaccine effectiveness (VE) estimates. Typing data and genomes were obtained from the Meningitis Research Foundation Meningococcus Genome Library and PubMLST database. Phylogenetic network analysis of MenC cc11 isolates was undertaken. We compared bactericidal antibody assay results using anonymised sera from 2014 to similar data from 1996-1999, 2000-2004 and 2009.ResultsMenC cases fell from 883 in 1998/99 (1.81/100,000 population) to 42 cases (0.08/100,000 population) in 2015/16. Lower VE over time since vaccination was observed after infant immunisation (p = 0.009) and a single dose at 1-4 years (p = 0.03). After vaccination at 5-18 years, high VE was sustained for ≥ 8 years; 95.0% (95% CI: 76.0- 99.5%). Only 25% (75/299) children aged 1-14 years were seroprotected against MenC disease in 2014. Recent case isolates mostly represented two cc11 strains.ConclusionHigh quality surveillance has furthered understanding of MenC vaccines and improved schedules, maximising population benefit. The UK programme provides high direct and indirect protection despite low levels of seroprotection in some age groups. High-resolution characterisation supports ongoing surveillance of distinct MenC cc11 lineages.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.1.1700818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325668PMC
January 2019

Should Pneumococcal Serotype 3 Be Included in Serotype-Specific Immunoassays?

Vaccines (Basel) 2019 Jan 3;7(1). Epub 2019 Jan 3.

Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.

Since the introduction of the 13-valent pneumococcal conjugate vaccine, a number of studies have demonstrated the limited efficacy of the pneumococcal serotype 3 component of this vaccine. Evidence from seven countries (Denmark, France, Greece, Portugal, Sweden, UK, US) shows limited or no effectiveness of the 13-valent pneumococcal conjugate vaccine against serotype 3 invasive pneumococcal disease and carriage. The serotype 3 capsule has some unique characteristics that may serve to explain this lack of efficacy-capsular polysaccharide is abundantly expressed, leading to a greater thickness of capsule, and free capsular polysaccharide may be released during growth. The serotype 3 component of the Luminex multiplex assay demonstrates inferior inter-laboratory reproducibility than other components and results may not be reliable. This communication outlines this evidence and discusses whether it is necessary to include serotype 3 in the assay in the future.
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http://dx.doi.org/10.3390/vaccines7010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466091PMC
January 2019

Haemophilus influenzae type b (Hib) seroprevalence and current epidemiology in England and Wales.

J Infect 2018 04 28;76(4):335-341. Epub 2017 Dec 28.

Immunisation Department, Public Health England, London, UK; Paediatric Infectious Diseases Research Group, St. George's University of London, London, UK. Electronic address:

Introduction: The implementation of the Hib conjugate vaccine in the United Kingdom in 1992 resulted in a rapid decline in invasive Hib disease across all age groups. However, a resurgence in 2000-2002 prompted the introduction of additional control measures, including a routine 12-month booster in 2006. Here we describe results from a national serosurvey in children eligible for the 12-month booster and recent Haemophilus influenzae epidemiology in England and Wales.

Methods: A national serosurvey was performed to determine the prevalence of anti-polyribosyl-phosphate (anti-PRP) IgG antibodies in 1000 residual samples from children up to 8 years of age in 2013-2014. Data were compared to previous national serosurveys performed by the same laboratory. Current epidemiology of invasive H. influenzae disease in England and Wales is also reported.

Results: Median anti-PRP IgG concentrations were highest among 1 year olds at 4.4 µg/mL (IQR, 1.3-14.9; n = 99) and then declined rapidly but remained ≥1.0 µg/mL across the age-groups in the cohort eligible for the 12-month booster. Overall, 89% of children (719/817) had anti-PRP concentrations ≥0.15 µg/mL, the putative threshold for short-term protection against invasive Hib disease. During 2012-2016, annual Hib disease incidence remained below one case per million population, responsible for only 67 of 3523 laboratory-confirmed H. influenzae cases, including one case of Hib meningitis during the 5-year period. There were only two deaths within 30 days over the five-year period (case fatality rate, 3.0%).

Conclusions: Hib control in England and Wales is currently the best achieved since the vaccine was introduced more than two decades ago. However, Hib antibodies wane rapidly after the 12 months booster. Although most children remain protected against disease, antibody levels may not be high enough to prevent carriage among toddlers. Ongoing monitoring is essential to inform future vaccination policy.
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http://dx.doi.org/10.1016/j.jinf.2017.12.010DOI Listing
April 2018

Use of hydrogen peroxide as a biocide: new consideration of its mechanisms of biocidal action.

J Antimicrob Chemother 2012 Jul 24;67(7):1589-96. Epub 2012 Apr 24.

Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.

Hydrogen peroxide is extensively used as a biocide, particularly in applications where its decomposition into non-toxic by-products is important. Although increasing information on the biocidal efficacy of hydrogen peroxide is available, there is still little understanding of its biocidal mechanisms of action. This review aims to combine past and novel evidence of interactions between hydrogen peroxide and the microbial cell and its components, while reflecting on alternative applications that make use of gaseous hydrogen peroxide. It is currently believed that the Fenton reaction leading to the production of free hydroxyl radicals is the basis of hydrogen peroxide action and evidence exists for this reaction leading to oxidation of DNA, proteins and membrane lipids in vivo. Investigations of DNA oxidation suggest that the oxidizing radical is the ferryl radical formed from DNA-associated iron, not hydroxyl. Investigations of protein oxidation suggest that selective oxidation of certain proteins might occur, and that vapour-phase hydrogen peroxide is a more potent oxidizer of protein than liquid-phase hydrogen peroxide. Few studies have investigated membrane damage by hydrogen peroxide, though it is suggested that this is important for the biocidal mechanism. No studies have investigated damage to microbial cell components under conditions commonly used for sterilization. Despite extensive studies of hydrogen peroxide toxicity, the mechanism of its action as a biocide requires further investigation.
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http://dx.doi.org/10.1093/jac/dks129DOI Listing
July 2012

Mode of action of hydrogen peroxide and other oxidizing agents: differences between liquid and gas forms.

J Antimicrob Chemother 2010 Oct 16;65(10):2108-15. Epub 2010 Aug 16.

Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3NB, UK.

Objectives: Antimicrobials such as chlorine dioxide, peracetic acid and hydrogen peroxide (H(2)O(2)) share a basic mechanism of action (chemical oxidation of cellular components), but profound differences arise in their efficacy against microorganisms. Optimization of activity requires an understanding of their interaction with microbial targets and a clear differentiation between the chemical efficacies of each oxidative biocide. This study aimed to elucidate the biochemical mechanisms of action of oxidizing biocides at a macromolecular level, using amino acids, protein and an enzyme as model substrates for the action of each biocide.

Methods: The interactions of a number of oxidising agents (liquid and gaseous H(2)O(2), ClO(2), peracetic acid formulations) with amino acids, proteins (bovine serum albumin and aldolase) and enzymes were investigated by spectrophotometry, SDS-PAGE and alkaline phosphatase activity measurements.

Results: Biocide reactions yielded different types of oxidative structural change and different degrees of oxidation to amino acids and proteins, and differences in activity against a microbial enzyme. In particular there was a marked difference in the interactions of liquid H(2)O(2) and gaseous H(2)O(2) with the macromolecules, the latter causing greater oxidation; these results explain the dramatic differences in antimicrobial efficacy between liquid and gas peroxide.

Conclusions: These results provide a comprehensive understanding of the differences in interactions between a number of oxidizing agents and macromolecules commonly found in microbial cells. Biochemical mechanistic differences between these oxidative biocides do exist and lead to differential effects on macromolecules. This in turn could provide an explanation as to their differences in biocidal activity, particularly between liquid and gas peroxide.
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http://dx.doi.org/10.1093/jac/dkq308DOI Listing
October 2010
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