Is the onset of influenza in the community age-related?

We studied the spread of influenza in the community between 1993 and 2009 using primary-care surveillance data to investigate if the onset of influenza was age-related. Virus detections [A(H3N2), B, A(H1N1)] and clinical incidence of influenza-like illness (ILI) in 12·3 million person-years in the long-running Royal College of General Practitioners-linked clinical-virological surveillance programme in England & Wales were examined. The number of days between symptom onset and the all-age peak ILI incidence were compared by age group for each influenza type/subtype. We found that virus detection and ILI incidence increase, peak and decrease were in unison. The mean interval between symptom onset to peak ILI incidence in virus detections (all ages) was: A(H3N2) 20·5 [95% confidence interval (CI) 19·7-21·6] days; B, 18·8 (95% CI 15·8·0-21·7) days; and A(H1N1) 17·0 (95% CI 15·6-18·4) days. Differences by age group were examined using the Kruskal-Wallis test. For A(H3N2) and A(H1N1) viruses the interval was similar in each age group. For influenza B there were highly significant differences by age group (P = 0·0001). Clinical incidence rates of ILI reported in the 8 weeks preceding the period of influenza virus activity were used to estimate a baseline incidence and threshold value (upper 95% CI of estimate) which was used as a marker of epidemic progress. Differences between the age groups in the week in which the threshold was reached were small and not localized to any age group. In conclusion we found no evidence to suggest that influenza A(H3N2) and A(H1N1) occurs in the community in one age group before another. For influenza B, virus detection was earlier in children aged 5-14 years than in persons aged ⩾25 years.

Influenza-attributable burden in United Kingdom primary care.

Influenza is rarely laboratory-confirmed and the outpatient influenza burden is rarely studied due to a lack of suitable data. We used the Clinical Practice Research Datalink (CPRD) and surveillance data from Public Health England in a linear regression model to assess the number of persons consulting UK general practitioners (GP episodes) for respiratory illness, otitis media and antibiotic prescriptions attributable to influenza during 14 seasons, 1995-2009. In CPRD we ascertained influenza vaccination status in each season and risk status (conditions associated with severe influenza outcomes). Seasonal mean estimates of influenza-attributable GP episodes in the UK were 857 996 for respiratory disease including 68 777 for otitis media, with wide inter-seasonal variability. In an average season, 2·4%/0·5% of children aged <5 years and 1·3%/0·1% of seniors aged ⩾75 years had a GP episode for respiratory illness attributed to influenza A/B. Two-thirds of influenza-attributable GP episodes were estimated to result in prescription of antibiotics. These estimates are substantially greater than those derived from clinically reported influenza-like illness in surveillance programmes. Because health service costs of influenza are largely borne in general practice, these are important findings for cost-benefit assessment of influenza vaccination programmes.

Self-sampling for community respiratory illness: a new tool for national virological surveillance.

This report aims to evaluate the usefulness of self-sampling as an approach for future national surveillance of emerging respiratory infections by comparing virological data from two parallel surveillance schemes in England. Nasal swabs were obtained via self-administered sampling from consenting adults (≥ 16 years-old) with influenza symptoms who had contacted the National Pandemic Flu Service (NPFS) health line during the 2009 influenza pandemic. Equivalent samples submitted by sentinel general practitioners participating in the national influenza surveillance scheme run jointly by the Royal College of General Practitioners (RCGP) and Health Protection Agency were also obtained. When comparable samples were analysed there was no significant difference in results obtained from self-sampling and clinician-led sampling schemes. These results demonstrate that self-sampling can be applied in a responsive and flexible manner, to supplement sentinel clinician-based sampling, to achieve a wide spread and geographically representative way of assessing community transmission of a known organism.

Vaccine effectiveness of 2011/12 trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: evidence of waning intra-seasonal protection.

The 2011/12 season was characterised by unusually late influenza A (H3N2) activity in the United Kingdom (UK). We measured vaccine effectiveness (VE) of the 2011/12 trivalent seasonal influenza vaccine (TIV) in a test-negative case­control study in primary care. Overall VE against confirmed influenza A (H3N2) infection, adjusted for age, surveillance scheme and month, was 23% (95% confidence interval (CI): -10 to 47). Stratified analysis by time period gave an adjusted VE of 43% (95% CI: -34 to 75) for October 2011 to January 2012 and 17% (95% CI: -24 to 45) for February 2012 to April 2012. Stratified analysis by time since vaccination gave an adjusted VE of 53% (95% CI: 0 to 78) for those vaccinated less than three months, and 12% (95% CI: -31 to 41) for those vaccinated three months or more before onset of symptoms (test for trend: p=0.02). For confirmed influenza B infection, adjusted VE was 92% (95% CI: 38 to 99). A proportion (20.6%) of UK influenza A(H3N2) viruses circulating in 2011/12 showed reduced reactivity (fourfold difference in haemagglutination inhibition assays) to the A/Perth/16/2009 2011/12 vaccine component, with no significant change in proportion over the season. Overall TIV protection against influenza A(H3N2) infection was low, with significant intraseasonal waning.

Age-specific vaccine effectiveness of seasonal 2010/2011 and pandemic influenza A(H1N1) 2009 vaccines in preventing influenza in the United Kingdom.

An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42-66); age-specific adjusted VE was 87% (95% CI 45-97) in <5-year-olds and 84% (95% CI 27-97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI -6 to 51) overall and 72% (95% CI 15-91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42-68) and in 5- to 14-year-olds 75% (95% CI 32-91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.

Effectiveness of pandemic and seasonal influenza vaccine in preventing pandemic influenza A(H1N1)2009 infection in England and Scotland 2009-2010.

Following the global spread of pandemic influenza A(H1N1)2009, several pandemic vaccines have been rapidly developed. The United Kingdom and many other countries in the northern hemisphere implemented seasonal and pandemic influenza vaccine programmes in October 2009. We present the results of a case­control study to estimate effectiveness of such vaccines in preventing confirmed pandemic influenza infection. Some 5,982 individuals with influenza-like illness seen in general practices between November 2009 and January 2010 were enrolled. Those testing positive on PCR for pandemic influenza were assigned as cases and those testing negative as controls. Vaccine effectiveness was estimated as the relative reduction in odds of confirmed infection between vaccinated and unvaccinated individuals. Fourteen or more days after immunisation with the pandemic vaccine, adjusted vaccine effectiveness (VE) was 72% (95% confidence interval (CI): 21% to 90%). If protection was assumed to start after seven or more days, the adjusted VE was 71% (95% CI: 37% to 87%). Pandemic influenza vaccine was highly effective in preventing confirmed infection with pandemic influenza A(H1N1)2009 from one week after vaccination. No evidence of effectiveness against pandemic influenza A(H1N1)2009 was found for the 2009/10 trivalent seasonal influenza vaccine (adjusted VE of -30% (95% CI: -89% to 11%)).

An assessment of the effect of statin use on the incidence of acute respiratory infections in England during winters 1998-1999 to 2005-2006.

Statins reduce cardiovascular mortality and related risks associated with pneumonia suggesting potentially beneficial use in influenza pandemics. We investigated the effect of current statin use on acute respiratory infections in primary care. Data from anonymized electronic medical records of persons aged 45 years were examined for statin use, chronic morbidity, respiratory diagnoses, vaccination procedures, and immune suppression. Logistic regression models were used to calculate odds ratios (ORs) for statin users vs. non-users in respiratory infection outcomes. A total of 329 881 person-year observations included 18% statin users and 46% influenza vaccinees. Adjusted ORs for statin users vs. non-users were: influenza-like illness, 1.05 (95% CI 0.92-1.20); acute bronchitis, 1.08 (95% CI 1.01-1.15); pneumonia, 0.91 (95% CI 0.73-1.13); all acute respiratory infections, 1.03 (95% CI 0.98-1.07); and urinary tract infections, 0.91 (95% CI 0.85-0.98). We found no benefit in respiratory infection outcomes attributable to statin use, although uniformly higher ORs in non-vaccinated statin users might suggest synergism between statins and influenza vaccination.

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.

The representativeness of sentinel practice networks.

BACKGROUND: The representativeness of practice networks is important when using the information obtained to guide health policy. AIM: To develop a model for examining the representativeness of practice networks. METHODS: Comparison of surveyed population, practice structure and prescribing characteristics with the national data using the Weekly Returns Service (WRS) for 2006 as an example of practice network. The population monitored was compared with the national PCT population. The practice postcode was linked to the Index of Multiple Deprivation and the distribution compared with the national equivalents. Doctor and practice-specific structural data (obtained by questionnaire) and practice-prescribing data were compared with the national equivalents. The significance of differences was evaluated using non-parametric tests. RESULTS: The WRS population was closely matched with the national data by age, gender and deprivation index. Compared with the national equivalents, WRS practices, included more younger GPs, had a larger average list per GP and fewer practices with a list of less than 1499 per GP. Prescribing patterns were similar to their PCT equivalents excepting for small reductions of antibacterial prescribing (items 7% and cost 5%). CONCLUSION: We demonstrate a low-cost model methodology for examining the representativeness of practice networks using independent data with minimum practice input.

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 > or =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 > or =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.