Since the 2009 A/H1N1 pandemic, Public Health England have developed a suite of real-time statistical models utilising enhanced pandemic surveillance data to nowcast and forecast a future pandemic. ...Their ability to track seasonal influenza and predict heightened winter healthcare burden in the light of high activity in Australia in 2017 was untested.
Four transmission models were used in forecasting the 2017/2018 seasonal influenza epidemic in England: a stratified primary care model using daily, region-specific, counts and virological swab positivity of influenza-like illness consultations in general practice (GP); a strain-specific (SS) model using weekly, national GP ILI and virological data; an intensive care model (ICU) using reports of ICU influenza admissions; and a synthesis model that included all data sources. For the first 12 weeks of 2018, each model was applied to the latest data to provide estimates of epidemic parameters and short-term influenza forecasts. The added value of pre-season population susceptibility data was explored.
The combined results provided valuable nowcasts of the state of the epidemic. Short-term predictions of burden on primary and secondary health services were initially highly variable before reaching consensus beyond the observed peaks in activity between weeks 3-4 of 2018. Estimates for R
were consistent over time for three of the four models until week 12 of 2018, and there was consistency in the estimation of R
across the SPC and SS models, and in the ICU attack rates estimated by the ICU and the synthesis model. Estimation and predictions varied according to the assumed levels of pre-season immunity.
This exercise successfully applied a range of pandemic models to seasonal influenza. Forecasting early in the season remains challenging but represents a crucially important activity to inform planning. Improved knowledge of pre-existing levels of immunity would be valuable.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Estimates of health‐related quality of life (HRQoL) and work/school absences for influenza are typically based on medically attended cases or those meeting influenza‐like‐illness (ILI) ...case definitions and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited.
Objectives
To measure quality‐adjusted life days and years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza.
Patients/methods
Flu Watch was a community cohort in England from 2006 to 2011. Participants were followed up weekly. During respiratory illness, they prospectively recorded daily symptoms, work/school absences and EQ‐5D‐3L data and submitted nasal swabs for RT‐PCR influenza testing.
Results
Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases, respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 and 2.4 days, respectively. In England, community influenza cases lost 24 300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 to 2009/10.
Conclusions
Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level.
Summary Background Effective antigen-sparing vaccines are needed to confront pandemic influenza. Whole-virion and oil-in-water adjuvanted vaccines are the most effective formulations against H5N1 ...avian influenza. We assessed the safety and immunogenicity in adults in the UK of pandemic H1N1 whole-virion vaccine and oil-in-water adjuvanted vaccine purchased by the UK government in 2009. Methods In our randomised, observer-blind, parallel-group, controlled trial, healthy adults aged 18–44 years, 45–64 years, and 65 years and older (from Oct 19, to Nov 12, 2009) received two doses of vaccine given 21 days apart: either 7·5 μg of haemagglutinin formulated as whole-virion vaccine, or 3·75 μg of haemagglutinin formulated as split-virion vaccine with AS03A oil-in-water adjuvant. Assignment was by a computer-generated code, with random permuted blocks of two, four, and six. All participants and investigators were unaware of vaccine assignments. The trial was done at three hospitals in the UK. We measured antibody titres with a haemagglutination-inhibition assay at baseline; 7, 14, and 21 days after each vaccination; and at 6 months after the first dose. Primary outcome was vaccine immunogenicity of the full analysis set by the EU Committee of Human Medicinal Products licensing criteria. This study is registered with ISRCTN , number ISRCTN92328241. Findings At day 0, baseline antibody (titre ≥1/8) was detected in 44 (13%) of 347 participants. Sera from 95% to 98% of participants were assessed for immunogenicity on days 7, 14, 21, 28, 35, and 42, and at 6 months. On day 21 after one dose of adjuvanted AS03A or whole-virion vaccine, 63 (94%, 95 CI 85·4–98·4) of 67 and 50 (71%, 59·4–81·6) of 70 participants aged 18–44 years, 51 (77%, 65·3–86·7) of 66 and 26 (39%, 27·1–51·5) of 67 aged 45–64 years, and 19 (51%, 34·4–68·1) of 37 and 11 (32%, 17·4–50·5) of 34 aged 65 years or older had titres of 1:40 or greater. On day 42 (21 days after the second dose), 64 (100%, 94·4–100) of 64 and 49 (73%, 60·9–83·2) of 67 participants aged 18–44 years, 59 (91%, 81·0–96·5) of 65 and 29 (43·9%, 31·7–56·7) of 66 aged 45–64 years, and 28 (76%, 58·8–88·2) of 37 and 12 (36%, 20·4–54·9) of 33 aged 65 years or older had titres of 1/40 or greater. At 6 months, 62 (98%, 91·5–100) of 63 and 54 (78%, 66·7–87·3) of 69 participants aged 18–44 years, 54 (82%, 70·4–90·2) of 66 and 37 (55%, 42·6–67·4) of 67 aged 45–64 years, and 21 (57%, 39·5–72·9) of 37 and 10 (29%, 15·1–47·5) of 34 aged 65 years or older had titres of 1/40 or greater. There were no vaccine-related serious adverse events. Whole-virion vaccine was associated with fewer local and systemic reactions than adjuvanted vaccine. Interpretation AS03A -adjuvanted vaccine was more immunogenic against pandemic influenza A H1N1 virus than whole-virion vaccine and offers greater antigen-sparing capacity. A two-dose strategy should be considered for older people. Funding Department of Health, National Institute for Health Research Evaluation, Trials and Studies Coordinating Centre.
The authors discuss the implications of a new study that presents compelling data to show that norovirus evolution is driven by immune selection pressure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Western industrialised nations face a large increase in the number of older people. People over the age of 60 years account for almost half of the 16.8 million hospital admissions in England from ...2009 to 2010. During 2009-10, respiratory infections accounted for approximately 1 in 30 hospital admissions and 1 in 20 of the 51.5 million bed-days.
To determine the diagnostic accuracy and clinical effectiveness and cost-effectiveness of rapid molecular and near-patient diagnostic tests for influenza, respiratory syncytial virus (RSV) and Streptococcus pneumoniae infections in comparison with traditional laboratory culture.
We carried out a randomised controlled trial (RCT) to evaluate impact on prescribing and clinical outcomes of point-of-care tests (POCTs) for influenza A and B and pneumococcal infection, reverse transcriptase-polymerase chain reaction (RT-PCR) tests for influenza A and B and RSV A and B, and conventional culture for these pathogens. We evaluated diagnostic accuracy of POCTs for influenza and pneumococcal infection, RT-PCR for influenza and sputum culture for S. pneumoniae using samples collected during the RCT. We did a systematic review and meta-analysis of POCTs for influenza A and B. We evaluated ease and speed of use of each test, process outcomes and cost-effectiveness.
There was no evidence of association between diagnostic group and prescribing or clinical outcomes. Using PCR as 'gold standard', Quidel Influenza A + B POCT detected 24.4% 95% confidence interval (CI) 16.0% to 34.6% of influenza infections (specificity 99.7%, 95% CI 99.2% to 99.9%); viral culture detected 21.6% (95% CI 13.5% to 31.6%; specificity 99.8%, 95% CI 99.4% to 100%). Using blood culture as 'gold standard', BinaxNOW pneumococcal POCT detected 57.1% (95% CI 18.4% to 90.1%) of pneumococcal infections (specificity 92.5%; 95% CI 90.6% to 94.1%); sputum culture detected 100% (95% CI 2.5% to 100%; specificity 97.2%, 95% CI 94.3% to 98.9%). Overall, pooled estimates of sensitivity and specificity of POCTs for influenza from the literature were 74% (95% CI 67% to 80%) and 99% (95% CI 98% to 99%), respectively. Median intervals from specimen collection to test result were 15 minutes interquartile range (IQR) 10-23 minutes) for Quidel Influenza A + B POCT, 20 minutes (IQR 15-30 minutes) for BinaxNOW pneumococcal POCT, 50.8 hours (IQR 44.3-92.6 hours) for semi-nested conventional PCR, 29.2 hours (IQR 26-46.9 hours) for real-time PCR, 629.6 hours (IQR 262.5-846.7 hours) for culture of influenza and 84.4 hours (IQR 70.7-137.8 hours) and 71.4 hours (IQR 69.15-84.0 hours) for culture of S. pneumoniae in blood and sputum, respectively. Both POCTs were rated straightforward and undemanding; blood culture was moderately complex and all other tests were complex. Costs and quality-adjusted life-years (QALYs) of each diagnostic strategy were similar. Incrementally, PCR was most cost-effective (78.3% probability at a willingness to pay of £20,000/QALY). Few patients were admitted within a timescale conducive to treatment with a neuraminidase inhibitor according to National Institute for Health and Care Excellence guidance.
The accuracy study was limited by inadequate gold standards.
All tests had limitations. We found no evidence that POCTs for influenza or S. pneumoniae, or PCR for influenza or RSV influenced antimicrobial prescribing or clinical outcomes. The total costs and QALYs of each diagnostic strategy were similar, although, incrementally, PCR was the most cost-effective strategy. The analysis does not support routine use of POCTs for either influenza or pneumococcal antigen for adults presenting with acute cardiopulmonary conditions, but suggests that conventional viral culture for clinical diagnosis should be replaced by PCR.
Current Controlled Trials ISRCTN21521552.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 36. See the NIHR Journals Library website for further project information.
Surveillance for antiviral resistance Zambon, Maria C.
Influenza and other respiratory viruses,
January 2013, Letnik:
7, Številka:
s1
Journal Article
Recenzirano
Odprti dostop
Please cite this paper as: Zambon. (2012) Surveillance for antiviral resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 37–43.
In the 10 years since licensure of neuraminidase inhibitor ...drugs, their use has steadily increased, especially during the pandemic of 2009. Experience now indicates that factors which influence the emergence of high level resistance include the nature of drug binding to target, viral subtype, the use of post exposure prophylaxis and a lack of immunity in the host as seen in children and immunocompromised individuals. These factors point towards targetted surveillance programmes for the early identification of transmissible drug resistance.
Influenza vaccines are the main tool to prevent morbidity and mortality of the disease; however, egg adaptations associated with the choice of the manufacturing process may reduce their ...effectiveness. This study aimed to estimate the impact of egg adaptations and antigenic drift on the effectiveness of trivalent (TIV) and quadrivalent (QIV) influenza vaccines.
Nine experts in influenza virology were recruited into a Delphi-style exercise. In the first round, the experts were asked to answer questions on the impact of antigenic drift and egg adaptations on vaccine match (VM) and influenza vaccine effectiveness (IVE). In the second round, the experts were presented with the data from a systematic literature review on the same subject and aggregated experts' responses to round one questions. The experts were asked to review and confirm or amend their responses before the final summary statistics were calculated.
The experts estimated that, across Europe, the egg adaptations reduce, on average, VM to circulating viruses by 7-21% and reduce IVE by 4-16%. According to the experts, antigenic drift results in a similar impact on VM (8-24%) and IVE (5-20%). The highest reduction in IVE was estimated for the influenza virus A(H3N2) subtype for the under 65 age group. When asked about the frequency of the phenomena, the experts indicated that, on average, between the 2014 and 19 seasons, egg adaptation and antigenic drift were significant enough to impact IVE that occurred in two and three out of five seasons, respectively. They also agreed that this pattern is likely to reoccur in future seasons.
Expert estimates suggest there is a potential for 9% on average (weighted average of "All strains" over three age groups adjusted by population size) and up to a 16% increase in IVE (against A(H3N2), the <65 age group) if egg adaptations that arise when employing the traditional egg-based manufacturing process are avoided.
PURPOSE OF REVIEWCases of severe influenza may occur during seasonal epidemics, following sporadic zoonotic influenza A transmission from animal reservoirs or on a massive scale with the ...unpredictable emergence of a new pandemic influenza strain. Clinical experience identifies unmet medical need for additional therapies for influenza, in particular to treat severely unwell adults and children. During and following the pandemic of 2009, a wealth of data from hospitalized cases of influenza from many different countries accumulated and are now starting to emerge. Observational clinical data provide information about the efficacy of existing antiviral drugs in severely ill patients. The development pipeline for new therapies contains several promising agents which are focussed on a range of viral targets, and opens the possibility of combination antiviral therapy for the first time, which may be especially useful in clinically challenging cases. Advances in immunological methods and recombinant protein engineering support the potential for use of immunomodulating therapies as adjuncts in treatment of severe influenza.
RECENT FINDINGSThe main themes are the importance of treating severe influenza early, considering multiple therapy options and the relevance of observational clinical data to treatment of severely ill and risk groups.
SUMMARYClinicians, who may have only seen the media headlines following discussion of reviews which deal with randomized controlled trials of neuraminidase inhibitor drug use in mild uncomplicated influenza in the community, may be hesitant to prescribe these drugs. Observational data arising from treatment of severely ill individuals support use of these drugs early in illness and show improvement in outcomes associated with drug use.
Care homes have been disproportionately affected by the COVID-19 pandemic. We investigated the potential role of asymptomatic infection and silent transmission in London care homes that reported no ...cases of COVID-19 during the first wave of the pandemic.
Five care homes with no cases and two care homes reporting a single case of COVID-19 (non-outbreak homes) were investigated with nasal swabbing for SARS-CoV-2 RT-PCR and serology for SARS-CoV-2 antibodies five weeks later. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. Serology results were compared with those of six care homes with recognised outbreaks.
Across seven non-outbreak homes, 718 (387 staff, 331 residents) individuals had a nasal swab and 651 (386 staff, 265 residents) had follow-up serology. Sixteen individuals (13 residents, 3 staff) in five care homes with no reported cases were RT-PCR positive (care home positivity rates, 0 to 7.6%) compared to 13 individuals (3.0 and 10.8% positivity) in two homes reporting a single case.
Seropositivity across these seven homes varied between 10.7-56.5%, with four exceeding community seroprevalence in London (14.8%). Seropositivity rates for staff and residents correlated significantly (rs 0.84, 95% CI 0.51-0.95 p <0.001) across the 13 homes. WGS identified multiple introductions into some homes and silent transmission of a single lineage between staff and residents in one home.
We found high rates of asymptomatic infection and transmission even in care homes with no COVID-19 cases. The higher seropositivity rates compared to RT-PCR positivity highlights the true extent of the silent outbreak.
PHE
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