Douglas M. Fleming

Contribution of influenza and respiratory syncytial virus to community cases of influenza-like illness: an observational study

BACKGROUND Respiratory syncytial virus (RSV) is an important cause of lower-respiratory-tract infection in children and elderly people, but its effect in other age-groups is uncertain. We did a community-based observational study of RSV infection in community-dwelling individuals of all ages who presented to general practices in the UK with influenza-like illnesses during three successive winters (1995-96, 1996-97, and 1997-98). METHODS Nasopharyngeal swabs routinely submitted for virological surveillance were examined by multiplex reverse transcription PCR for influenza A and B viruses and RSV A and B, and findings were related to the clinical incidence of influenza-like illness and acute bronchitis at that time. RSV strains identified were compared with those obtained from hospital admissions. FINDINGS 480 RSV and 709 influenza viruses were identified from a total of 2226 swabs submitted. Both types of virus were found in all age-groups for between 12 and 20 weeks in each winter. RSV A accounted for 60% of RSV detections. Similar strains of RSV were present in hospital and community patients within the same year, but there were different lineages each year. INTERPRETATION In individuals diagnosed with influenza-like illness, there is a substantial potential for confusion between illnesses caused by influenza and those caused by RSV. The burden of illness attributable to each needs to be clarified to define optimum management routines.

Human Metapneumovirus as a Cause of Community-Acquired Respiratory Illness

Human metapneumovirus (HMPV) is a recently identified Paramyxovirus first isolated from hospitalized children with acute respiratory tract infections (ARTI). We sought evidence of HMPV infection in patients who had visited general practitioners, had influenzalike illnesses (ILI), and had negative tests for influenza and Human respiratory syncytial virus (HRSV). As part of national virologic surveillance, sentinel general practices in England and Wales collected samples from patients of all ages with ILI during winter 2000–01. Reverse transcriptase-polymerase chain reaction (PCR) for HMPV, influenza A (H1 and H3), influenza B, and HRSV was used to screen combined nose and throat swabs. PCR products from the HMPV-positive samples were sequenced to confirm identity and construct phylogenetic trees. Of 711 swabs submitted, 408 (57.3%) were negative for influenza and HRSV; HMPV was identified in 9 (2.2%) patients. HMPV appears to be associated with community-acquired ARTI. The extent of illness and possible complications related to this new human virus need to be clarified

Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma.

Background: Despite their potential for increased morbidity, 75% to 90% of asthmatic children do not receive influenza vaccination. Live attenuated influenza vaccine (LAIV), a cold-adapted, temperature-sensitive, trivalent influenza vaccine, is approved for prevention of influenza in healthy children 5 to 19 years of age. LAIV has been studied in only a small number of children with asthma. Methods: Children 6 to 17 years of age, with a clinical diagnosis of asthma, received a single dose of either intranasal CAIV-T (an investigational refrigerator-stable formulation of LAIV; n = 1114) or injectable trivalent inactivated influenza vaccine (TIV; n = 1115) in this randomized, open-label study during the 2002–2003 influenza season. Participants were followed up for culture-confirmed influenza illness, respiratory outcome, and safety. Results: The incidence of community-acquired culture-confirmed influenza illness was 4.1% (CAIV-T) versus 6.2% (TIV), demonstrating a significantly greater relative efficacy of CAIV-T versus TIV of 34.7% (90% confidence interval [CI] 9.4%–53.2%; 95% CI = 3.9%–56.0%). There were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate findings, asthma symptom scores, or nighttime awakening scores. The incidence of runny nose/nasal congestion was higher for CAIV-T (66.2%) than TIV (52.5%) recipients. Approximately 70% of TIV recipients reported injection site reactions. Conclusions: CAIV-T was well tolerated in children and adolescents with asthma. There was no evidence of a significant increase in adverse pulmonary outcomes for CAIV-T compared with TIV. CAIV-T had a significantly greater relative efficacy of 35% compared with TIV in this high-risk population.

Potential Impact of Antiviral Drug Use during Influenza Pandemic

Impact of different antiviral treatment strategies on hospitalizations during an influenza pandemic is evaluated.

Safety, Efficacy, and Effectiveness of Cold-Adapted Influenza Vaccine-Trivalent Against Community-Acquired, Culture-Confirmed Influenza in Young Children Attending Day Care

OBJECTIVE. The goal was to evaluate the safety, tolerability, and efficacy of an investigational, refrigerator-stable formulation of live attenuated influenza vaccine (cold-adapted influenza vaccine-trivalent) against culture-confirmed influenza, acute otitis media, and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons. METHODS. Children 6 to <36 months of age who were attending day care were assigned randomly in year 1 to receive 2 doses of vaccine or placebo intranasally, 35 ± 7 days apart. In year 2, subjects received 1 dose of the same treatment as in year 1. RESULTS. A total of 1616 subjects (vaccine: 951 subjects; placebo: 665 subjects) in year 1 and 1090 subjects (vaccine: 640 subjects; placebo: 450 subjects) in year 2 were able to be evaluated for efficacy. The mean age at first vaccination was 23.4 ± 7.9 months. In year 1, the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4%; efficacy was 91.8% against A/H1N1 and 72.6% against B. In year 2, the overall efficacy was 88.7%; efficacy was 90.0% against H1N1, 90.3% against A/H3N2, and 81.7% against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6% in year 1 and 97.0% in year 2. Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent (82.3%) than placebo (75.4%). CONCLUSIONS. Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care.

Zanamivir Prophylaxis: An Effective Strategy for the Prevention of Influenza Types A and B within Households

A double-blind, randomized study of inhaled zanamivir for the prevention of influenza in families was conducted. Once a person with a suspected case of influenza was identified (index patient), treatment of all other household members (contacts) > or =5 years old was initiated. Contacts received either 10 mg zanamivir or placebo inhaled once daily for 10 days. Index patients received relief medication only. In total, 487 households (242 placebo and 245 zanamivir) were enrolled, with 1291 contacts randomly assigned to receive prophylaxis. Four percent of zanamivir versus 19% of placebo households (P<.001) had at least 1 contact who developed symptomatic, laboratory-confirmed influenza, representing 81% protective efficacy (95% confidence interval, 64%-90%). Protective efficacy was similarly high for individuals (82%) and against both influenza types A and B (78% and 85%, respectively, for households). Zanamivir was well tolerated and was effective in preventing influenza types A and B within households where the index patient was not treated.

Effectiveness of trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2012/13 end of season results.

In 2015/16, the influenza season in the United Kingdom was dominated by influenza A(H1N1)pdm09 circulation. Virus characterisation indicated the emergence of genetic clusters, with the majority antigenically similar to the current influenza A(H1N1)pdm09 vaccine strain. Mid-season vaccine effectiveness (VE) estimates show an adjusted VE of 41.5% (95% confidence interval (CI): 3.0-64.7) against influenza-confirmed primary care consultations and of 49.1% (95% CI: 9.3-71.5) against influenza A(H1N1)pdm09. These estimates show levels of protection similar to the 2010/11 season, when this strain was first used in the seasonal vaccine.

The duration and magnitude of influenza epidemics: A study of surveillance data from sentinel general practices in England, Wales and the Netherlands

Weekly incidence data for influenza-like illness, routinely collected in sentinel general practices in England and Wales and in the Netherlands over 10 winter periods (week 37 in one year to week 20 in the next, 1987/1988–1996/1997) were examined in conjunction with matching virus isolate data to define epidemic periods of influenza in the two countries. We first defined the background rates of recording influenza-like illness which occurred at times when only sporadic or no isolations of virus were reported. The background rates were similar in the two networks with mean weekly incidence in England and Wales of 28.1 per 100,000 (all ages) and in the Netherlands 29.8. Epidemic periods defined as lying above the upper 95% confidence level of the background rate lasted on an average of about 10 weeks. Once epidemics were recognised, peak incidence was generally achieved within 4 weeks. The excess population (all ages) consulting general practitioners during influenza epidemic periods was calculated from the difference between the observed and background incidence rates, and expressed as a percentage of the total population. In the 10 periods surveyed, the percentage of the population consulting and diagnosed with influenza-like illness in England and Wales ranged from 0.4% in 1991/1992 to 1.7% in 1989/1990 and in the Netherlands from 0.5% in 1990/1991 to 2.1% in 1989/1990. The duration and epidemic periods were broadly similar in the two countries though the excess consulting population during the 10 epidemics studied averaged 0.85% in England and Wales compared with 1.39% in the Netherlands. There were substantial differences between the two countries in the impact of influenza in individual years, as measured in the consulting population even though the predominant virus (sub)types were similar.

Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989-90 using a general practice database.

The effectiveness of influenza vaccination in preventing serious illness and death was determined in an elderly population during the influenza epidemic of was determined in an elderly population during the influenza epidemic of was determined in an elderly population during the influenza epidemic of 1989-90. A retrospective cohort study was carried out using computerized general practitioner records on nearly 10,000 patients aged 55 years and over. After adjustment for potential confounding factors, recent immunization was found to have a protective effect of 75% (95% confidence intervals: 21-92%) against death. Protection did not appear to vary with either age or the presence of underlying chronic disease. As the complications of influenza are most common in those with underlying chronic disease, the study findings are consistent with the recommended policy for the use of influenza vaccine in the UK. Further work is necessary to determine the cost-effectiveness of extending immunization to other groups.

Mortality in children from influenza and respiratory syncytial virus

Study objective: To quantify mortality attributable to influenza and respiratory syncytial virus (RSV) infection in children. Design and methods: Comparison of death rates (all cause and certified respiratory) in England over winters 1989/90 to 1999/00 during and outside influenza and RSV circulation periods. Virus active weeks were defined from clinical and virological surveillance data. Excess deaths associated with weeks of either influenza or RSV activity over virus non-active weeks were estimated in each winter for age groups 1–12 months, 1–4, 5–9, and 10–14 years. The estimate obtained was allotted to influenza and RSV in the proportion derived from independent separate calculations for each virus. Main results: Average winter respiratory deaths attributed to influenza in children 1 month–14 years were 22 and to RSV 28; and all cause deaths to influenza 78 and to RSV 79. All cause RSV attributed deaths in infants 1–12 months exceeded those for influenza every year except 1989/90; the average RSV and influenza attributed death rates were 8.4 and 6.7 per 100 000 population respectively. Corresponding rates for children 1–4 years were 0.9 and 0.8 and for older children all rates were 0.2 or less, except for an influenza rate of 0.4 in children 10–14 years. Conclusions: Influenza and RSV account for similar numbers of deaths in children. The impact varies by winter and between age groups and is considerably underestimated if analysis is restricted to respiratory certified deaths. Summing the impact over the 11 winters studied, compared with influenza RSV is associated with more deaths in infants less than 12 months, almost equal numbers in children 1–4 years, and fewer in older children. Improved information systems are needed to investigate paediatric deaths.