Alex J. Elliot

Prescription of anti-influenza drugs for healthy adults: a systematic review and meta-analysis.

In publicly funded health systems with finite resources, management decisions are based on assessments of clinical effectiveness and cost-effectiveness. The UK National Institute for Health and Clinical Excellence commissioned a systematic review to inform their 2009 update to guidance on the use of antiviral drugs for the treatment of influenza. We searched databases for studies of the use of neuraminidase inhibitors for the treatment of seasonal influenza. We present the results for healthy adults (ie, adults without known comorbidities) and people at-risk of influenza-related complications. There was an overall reduction in the median time to symptom alleviation in healthy adults by 0.57 days (95% CI -1.07 to -0.08; p=0.02; 2701 individuals) with zanamivir, and 0.55 days (95% CI -0.96 to -0.14; p=0.008; 1410 individuals) with oseltamivir. In those at risk, the median time to symptom alleviation was reduced by 0.98 days (95% CI -1.84 to -0.11; p=0.03; 1252 individuals) with zanamivir, and 0.74 days (95% CI -1.51 to 0.02; p=0.06; 1472 individuals) with oseltamivir. Little information was available on the incidence of complications. In view of the advantages and disadvantages of different management strategies for controlling seasonal influenza in healthy adults recommending the use of antiviral drugs for the treatment of people presenting with symptoms is unlikely to be the most appropriate course of action.

Lessons from 40 years' surveillance of influenza in England and Wales.

The influenza virus continues to pose a significant threat to public health throughout the world. Current avian influenza outbreaks in humans have heightened the need for improved surveillance and planning. Despite recent advances in the development of vaccines and antiviral drugs, seasonal epidemics of influenza continue to contribute significantly to general practitioner workloads, emergency hospital admissions, and deaths. In this paper we review data produced by the Royal College of General Practitioners Weekly Returns Service, a sentinel general practice surveillance network that has been in operation for over 40 years in England and Wales. We show a gradually decreasing trend in the incidence of respiratory illness associated with influenza virus infection (influenza-like illness; ILI) over the 40 years and speculate that there are limits to how far an existing virus can drift and yet produce substantial new epidemics. The burden of disease caused by influenza presented to general practitioners varies considerably by age in each winter. In the pandemic winter of 1969/70 persons of working age were most severely affected; in the serious influenza epidemic of 1989/90 children were particularly affected; in the millennium winter (in which the NHS was severely stretched) ILI was almost confined to adults, especially the elderly. Serious confounders from infections due to respiratory syncytial virus are discussed, especially in relation to assessing influenza vaccine effectiveness. Increasing pressure on hospitals during epidemic periods are shown and are attributed to changing patterns of health-care delivery.

Estimating influenza vaccine effectiveness using routinely collected laboratory data

Background Estimation of influenza vaccine effectiveness (V/E) is needed early during influenza outbreaks in order to optimise management of influenza—a need which will be even greater in a pandemic situation. Objective Examine the potential of routinely collected virological surveillance data to generate estimates of V/E in real-time during winter seasons. Methods Integrated clinical and virological community influenza surveillance data collected over three winters 2004/5–2006/7 were used. We calculated the odds of vaccination in persons that were influenza-virus-positive and the odds in those that were negative and provided a crude estimate of V/E. Logistic regression was used to obtain V/E estimates adjusted for confounding variables such as age. Results Multivariable analysis suggested that adjustments to the crude V/E estimate were necessary for patient age and month of sampling. The annual adjusted V/E was 2005/6, 67% (95% CI 41% to 82%); 2006/7 55% (26% to 73%) and 2007/8 67% (41% to 82%). The adjusted V/E in persons <65 years was 70% (57% to 78%) and 65 years and over 46% (−17% to 75%). Estimates differed by small insignificant amounts when calculated separately for influenza A and B; by interval between illness onset and swab sample; by analysis for the period November to January in each year compared with February to April and according to viral load. Conclusion We have demonstrated the potential of using routine virological and clinical surveillance data to provide estimates of V/E early in season and conclude that it is feasible to introduce this approach to V/E measurement into evaluation of national influenza vaccination programs.

Seasonality and trends in the incidence and prevalence of gout in England and Wales 1994–2007

Objectives: To examine seasonality and long-term trends in the incidence and prevalence of gout. Methods: A retrospective study (1994–2007) using routinely collected surveillance data from the Royal College of General Practitioners Weekly Returns Service sentinel general practice network in England and Wales. New cases and acute attacks of gout per 10 000 population were calculated for age groups 0–44, 45–64, 65–74 and ⩾75 years. Long-term trends of annual incidence were assessed by regression analysis. Seasonality indices were calculated using 4-weekly data, and the relative risk of gout incidence during the summer was estimated. Annual prevalence was estimated from the consulting patient population (2001–7) and from prescribing data on defined daily doses (DDD) of allopurinol (2003–7). Results: The annual incidence rate of new gout cases was stable over the period 1998–2007; acute attacks decreased on average 4% per annum. New gout cases and acute attacks combined into 4-weekly incidence rates peaked during the “summer” period of each year. There was an increased risk of gout diagnosis during summer months (late April to mid-September; odds ratio 1.22, 95% CI 1.18 to 1.26). The annual prevalence of gout in 2001–7 was 0.46%, with highest rates in men ⩾75 years (2.57%). Estimated prevalence based on a DDD of 400 mg allopurinol was 0.37%. Conclusion: The incidence of gout is seasonal. This has implications for the management of patients who currently have gout, and for those who are at risk of future attacks. The decreasing trend in the incidence of acute attacks suggests that patient management is improving.

Uptake and impact of vaccinating school age children against influenza during a season with circulation of drifted influenza A and B strains, England, 2014/15

The 2014/15 influenza season was the second season of roll-out of a live attenuated influenza vaccine (LAIV) programme for healthy children in England. During this season, besides offering LAIV to all two to four year olds, several areas piloted vaccination of primary (4-11 years) and secondary (11-13 years) age children. Influenza A(H3N2) circulated, with strains genetically and antigenically distinct from the 2014/15 A(H3N2) vaccine strain, followed by a drifted B strain. We assessed the overall and indirect impact of vaccinating school age children, comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot to non-pilot areas. Uptake levels were 56.8% and 49.8% in primary and secondary school pilot areas respectively. In primary school age pilot areas, cumulative primary care influenza-like consultation, emergency department respiratory attendance, respiratory swab positivity, hospitalisation and excess respiratory mortality were consistently lower in targeted and non-targeted age groups, though less for adults and more severe end-points, compared with non-pilot areas. There was no significant reduction for excess all-cause mortality. Little impact was seen in secondary school age pilot only areas compared with non-pilot areas. Vaccination of healthy primary school age children resulted in population-level impact despite circulation of drifted A and B influenza strains.

Influenza and respiratory syncytial virus in the elderly

Respiratory infections are one of the leading causes of morbidity and mortality worldwide: influenza and respiratory syncytial virus (RSV) are the predominant pathogens responsible. Annual vaccination and the use of antiviral drugs provides both protection and treatment against influenza, particularly protecting those patients most at risk, including the elderly and individuals with chronic comorbidities. Currently, there are extremely limited options in the protection against RSV infection, making those at-risk patients vulnerable to serious disease, complications and death. This review focuses on recent trends in respiratory illness in the elderly, particularly focusing on the burden of influenza and RSV on hospitalizations and mortality. We discuss the potential benefit of influenza vaccination on these outcomes, including the recent controversial debate over the effectiveness of influenza vaccination.

Establishing an emergency department syndromic surveillance system to support the London 2012 Olympic and Paralympic Games

Background The London 2012 Olympic and Paralympic Games is a mass gathering event that will present a major public health challenge. The Health Protection Agency, in collaboration with the College of Emergency Medicine, has established the Emergency Department Sentinel Syndromic Surveillance System (EDSSS) to support the public health surveillance requirements of the Games. Methods This feasibility study assesses the usefulness of EDSSS in monitoring indicators of disease in the community. Daily counts of anonymised attendance data from six emergency departments across England were analysed by patient demographics (age, gender, partial postcode), triage coding and diagnosis codes. Generic and specific syndromic indicators were developed using aggregations of diagnosis codes recorded during each attendance. Results Over 339 000 attendances were recorded (26 July 2010 to 25 July 2011). The highest attendances recorded on weekdays between 10:00 and 11:00 and on weekends between 12:00 and 13:00. The mean daily attendance per emergency department was 257 (range 38–435). Syndromic indicators were developed including: respiratory, gastrointestinal, cardiac, acute respiratory infection, gastroenteritis and myocardial ischaemia. Respiratory and acute respiratory infection indicators peaked during December 2010, concomitant with national influenza activity, as monitored through other influenza surveillance systems. Conclusions The EDSSS has been established to provide an enhanced surveillance system for the London 2012 Olympics. Further validation of the data will be required; however, the results from this initial descriptive study demonstrate the potential for identifying unusual and/or severe outbreaks of infectious disease, or other incidents with public health impact, within the community.

Monitoring the emergence of community transmission of influenza A/H1N1 2009 in England: a cross sectional opportunistic survey of self sampled telephone callers to NHS Direct

Objective To evaluate ascertainment of the onset of community transmission of influenza A/H1N1 2009 (swine flu) in England during the earliest phase of the epidemic through comparing data from two surveillance systems. Design Cross sectional opportunistic survey. Study samples Results from self samples by consenting patients who had called the NHS Direct telephone health line with cold or flu symptoms, or both, and results from Health Protection Agency (HPA) regional microbiology laboratories on patients tested according to the clinical algorithm for the management of suspected cases of swine flu. Setting Six regions of England between 24 May and 30 June 2009. Main outcome measure Proportion of specimens with laboratory evidence of influenza A/H1N1 2009. Results Influenza A/H1N1 2009 infections were detected in 91 (7%) of the 1385 self sampled specimens tested. In addition, eight instances of influenza A/H3 infection and two cases of influenza B infection were detected. The weekly rate of change in the proportions of infected individuals according to self obtained samples closely matched the rate of increase in the proportions of infected people reported by HPA regional laboratories. Comparing the data from both systems showed that local community transmission was occurring in London and the West Midlands once HPA regional laboratories began detecting 100 or more influenza A/H1N1 2009 infections, or a proportion positive of over 20% of those tested, each week. Conclusions Trends in the proportion of patients with influenza A/H1N1 2009 across regions detected through clinical management were mirrored by the proportion of NHS Direct callers with laboratory confirmed infection. The initial concern that information from HPA regional laboratory reports would be too limited because it was based on testing patients with either travel associated risk or who were contacts of other influenza cases was unfounded. Reports from HPA regional laboratories could be used to recognise the extent to which local community transmission was occurring.

Morbidity profiles of patients consulting during influenza and respiratory syncytial virus active periods

We compared the burden of illness due to a spectrum of respiratory diagnostic categories among persons presenting in a sentinel general practice network in England and Wales during periods of influenza and of respiratory syncytial virus (RSV) activity. During all periods of viral activity, incidence rates of influenza-like illness, bronchitis and common cold were elevated compared to those in baseline periods. Excess rates per 100,000 of acute bronchitis were greater in children aged <1 year (median difference 2702, 95% CI 929-4867) and in children aged 1-4 years (994, 95% CI 338-1747) during RSV active periods rather than influenza; estimates for the two viruses were similar in other age groups. Excess rates of influenza-like illness in all age groups were clearly associated with influenza virus activity. For common cold the estimates of median excess rates were significantly higher in RSV active periods for the age groups <1 year (3728, 95% CI 632-5867) and 5-14 years (339, 95% CI 59-768); estimates were similar in other age groups for the two viruses. The clinical burden of disease associated with RSV is as great if not greater than influenza in patients of all ages presenting to general practitioners.

Acute respiratory infections and winter pressures on hospital admissions in England and Wales 1990–2005

BACKGROUND Hospitals experience winter surges in admissions due to respiratory infections. The roles of acute bronchitis and influenza-like illness (ILI) in the timing and severity of these surges are examined over the years 1990-91 to 2004-05. METHODS Respiratory admissions of persons aged > or =65 years in England and Wales were analysed in relation to patients with ILI or acute bronchitis diagnosed by community-based general practitioners from a sentinel surveillance network. RESULTS Acute bronchitis and ILI accounted for 46 and 7% of the variation in respiratory admissions, respectively: when admissions were lagged by 1 week, these estimates were 20 and 14%, respectively. Admissions peaked in weeks 52, 01 or 02 (late December to early January) in 14 of the 15 winters. Acute bronchitis peaked during weeks 01 or 02; ILI exhibited greater variability and peaks ranged from weeks 46 (mid-November) to 07 (mid-February). During winters where acute bronchitis and ILI peaked concurrently, surges on hospitals were most severe. CONCLUSIONS During each winter acute bronchitis provides a consistent and major contribution to the winter admissions surge in the elderly. The variable incidence of ILI can increase the surge in admissions, especially when ILI and acute bronchitis peak together.