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.

Structured surveillance of infectious intestinal disease in pre-school children in the community: 'The Nappy Study'.

The incidence and causes of infectious intestinal disease (IID) in children aged <5 years presenting to general practitioners (GPs) were estimated. During a 12-month period, soiled nappies were collected from children presenting with symptoms suggestive of IID in a network of 65 GPs located across England. Molecular methods were used to detect a range of enteric pathogens including viruses, bacteria and parasites. Genotyping was performed on rotavirus and norovirus isolates. A total of 583 nappies were collected from 554 children; a pathogen was detected in 361 (62%) specimens. In the 43 practices 1584 new episodes of IID were recorded in a population averaging 19774; the specimen capture rate was 28%. IID incidence peaked during March and April. Norovirus (24.5%), rotavirus (19.0%) and sapovirus (12.7%) were most commonly detected, and mixed infections were detected in 11.7% of cases. Strain characterization revealed G1P[8] (65.8%), G4P[4] (8.1%) and G9P[8] (8.1%) as the most common rotavirus genotypes, similar to the UK national distribution. GII-3 (42.9%) and GII-4 (39.7%) were the most common norovirus genotypes; this was significantly different (P<0.005) to the national distribution.

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.

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.

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.

Surveillance of influenza-like illness in England and Wales during 1966-2006.

We report surveillance data collected since 1966 from a general practice database in England and Wales. Incidence rates of influenza-like illness (ILI) peaked during the winter of 1969/70, and were then followed by a decade of heightened activity. There has since been a gradual downward trend of ILI, interspersed with winters of heightened activity; since 1999/2000, the incidence of ILI has been at its lowest for 40 years. We argue that the decade following the herald waves of the pandemic could be equally important for the planning of healthcare services in the community.

Surveillance of sexually transmitted diseases in general practice: a description of trends in the Royal College of General Practitioners Weekly Returns Service between 1994 and 2001.

This paper describes the incidence of sexually transmitted infections (STIs) recorded in the Weekly Returns Service (WRS) between 1994 and 2001. There were approximately 76,500 new diagnoses of STIs (7500 males, 71,000 females) and associated syndromes. Candidiasis was the commonest condition reported in males and females followed by pelvic inflammatory disease. The ratio of males to females was 7.1 for non-specific urethritis, and 9.1 and 2.1 for Reiter's syndrome and pediculosis pubis, respectively. The incidence of anogenital warts and genital herpes changed little over time. New diagnoses of genital herpes were higher in females than in males (ratio 2.8:1), whereas the mean annual incidence of genital warts was similar in males and females. The WRS provides an insight into the burden of STI diagnoses, and diagnoses related to STIs that are managed in general practice, and as such has the potential to make a substantial contribution to STI surveillance in England.

The incidence of molluscum contagiosum, scabies and lichen planus.

We aimed to describe the incidence of new episodes of molluscum contagiosum, scabies and lichen planus presenting to general practitioners in England and Wales. We examined data collected in a sentinel practice network (the Weekly Returns Service of the Royal College of General Practitioners) in which about half a million persons were observed each year over the period 1994-2003. The incidence of molluscum contagiosum in males was 243/100,000 person-years and in females 231; of scabies, males 351, females 437; of lichen planus, males 32, females 37. Incidence varied by year and age. Ninety per cent of molluscum contagiosum episodes were reported in children aged 0-14 years, where incidence in 2000 (midpoint of a 6-year period of stable incidence) was 1265/100,000 (95% CI 1240-1290). Scabies affected all ages and annual incidence ranged between 233 (95% CI 220-246) in 2003 and 470 (95% CI 452-488) in 2000. Lichen planus occurred chiefly in persons aged over 45 years: incidence (all ages) ranged between 27 (95% CI 23-31) in 2003 and 43 (95% CI 37-49) in 1998. The relative risk of female to male incidence (all ages) of molluscum contagiosum was 0.95 (95% CI 0.91-0.99); of scabies 1.25 (95% CI 1.21-1.28); and of lichen planus 1.19 (95% CI 1.08-1.13).

Influenza and its relationship to circulatory disorders.

Three sources of data (general practice episode data from the Weekly Returns Service of the Royal College of General Practitioners, national hospital admission data for England and national mortality data by date of death) were examined separately in each winter (1994/1995 to 1999/2000) to investigate the impact of influenza on circulatory disease. Weekly data on incidence (clinical new episodes) hospital emergency admissions and deaths certified to circulatory disorders and to respiratory diseases (chapters VII and VIII of ICD9) during influenza epidemic periods (defined from combined clinical/virological surveillance) were examined in age groups 45-64, 65-74 and > or =75 years. Data collected in the four winters in which there were substantial influenza A epidemics were consolidated for the period 6 weeks before to 6 weeks after each peak of the epidemic, and associations between the variables at different time lags examined by calculating cross-correlation coefficients. We also examined deaths due to ischaemic heart disease (IHD) as a proportion of all circulatory deaths and deaths due to influenza/pneumonia as a proportion of all respiratory deaths. There were no increases of GP episodes nor of emergency admissions for circulatory disorders in any of the three age groups during epidemic periods. Increased circulatory deaths occurred in all age groups and particularly in the oldest group. The large cross-correlation coefficients of deaths (circulatory and respiratory) with GP respiratory episodes at weekly lags of 0, -1 and 1 were evidence that the deaths and episode distributions were contemporaneous. The ratios of excess circulatory deaths relative to excess respiratory deaths during epidemic periods were 0.74 (age 45-64), 0.72 (65-74) and 0.57 (> or =75 years). Increased circulatory deaths contemporary with new incident cases of respiratory episodes but with no concomitant increase in admissions suggests rapid death during the acute phase of illness. Influenza contingency planning needs to take account of these deaths in determining policy for prophylaxis and in providing facilities for cardio-respiratory resuscitation.