BackgroundGrowing evidence suggests respiratory syncytial virus (RSV) is an important cause of respiratory disease in adults. However, the adult burden remains largely uncharacterized as most RSV studies focus on children, and population-based studies with laboratory-confirmation of infection are difficult to implement. Indirect modelling methods, long used for influenza, can further our understanding of RSV burden by circumventing some limitations of traditional surveillance studies that rely on direct linkage of individual-level exposure and outcome data.MethodsMultiple linear time-series regression was used to estimate RSV burden in the United Kingdom (UK) between 1995 and 2009 among the total population and adults in terms of general practice (GP) episodes (counted as first consultation ≥28 days following any previous consultation for same diagnosis/diagnostic group), hospitalisations, and deaths for respiratory disease, using data from Public Health England weekly influenza/RSV surveillance, Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics. The main outcome considered all ICD-listed respiratory diseases and, for GP episodes, related symptoms. Estimates were adjusted for non-specific seasonal drivers of disease using secular cyclical terms and stratified by age and risk group (according to chronic conditions indicating severe influenza risk as per UK recommendations for influenza vaccination). Trial registration NCT01706302. Registered 11 October 2012.ResultsAmong adults aged 18+ years an estimated 487,247 GP episodes, 17,799 hospitalisations, and 8,482 deaths were attributable to RSV per average season. Of these, 175,070 GP episodes (36 %), 14,039 hospitalisations (79 %) and 7,915 deaths (93 %) were in persons aged 65+ years. High- versus low-risk elderly were two-fold more likely to have a RSV-related GP episode or death and four-fold more likely be hospitalised for RSV. In most seasons since 2001, more GP episodes, hospitalisations and deaths were attributable to RSV in adults than to influenza.ConclusionRSV is associated with a substantial disease burden in adults comparable to influenza, with most of the hospitalisation and mortality burden in the elderly. Treatment options and measures to prevent RSV could have a major impact on the burden of RSV respiratory disease in adults, especially the elderly.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1218-z) contains supplementary material, which is available to authorized users.

BackgroundInfluenza and respiratory syncytial virus (RSV) cause substantial mortality from respiratory and other causes in the USA, especially among people aged 65 and older.ObjectivesWe estimated the influenza-attributable mortality and RSV-attributable mortality in the USA, stratified by age and risk status, using outcome definitions with different sensitivity and specificity.MethodsInfluenza- and RSV-associated mortality was assessed from October 1997–March 2009 using multiple linear regression modeling on data obtained from designated government repositories.ResultsThe main outcomes and measures included mortality outcome definitions—pneumonia and influenza, respiratory broad, and cardiorespiratory disease. A seasonal average of 10 682 (2287–16 363), 19 100 (4862–29 245), and 28 169 (6797–42 316) deaths was attributed to influenza for pneumonia and influenza, respiratory broad, and cardiorespiratory outcome definitions, respectively. Corresponding values for RSV were 6211 (4584–8169), 11 300 (8546–14 244), and 17 199 (13 384–21 891), respectively. A/H3N2 accounted for seasonal average of 71% influenza-attributable deaths; influenza B accounted for most (51–95%) deaths during four seasons. Approximately 70% influenza-attributable deaths occurred in individuals ≥75 years, with increasing mortality for influenza A/H3N2 and B, but not A/H1N1. In children aged 0–4 years, an average of 97 deaths was attributed to influenza (A/H3N2 = 49, B = 33, A/H1N1 = 15) and 165 to respiratory broad outcome definition (RSV). Influenza-attributable mortality was 2·94-fold higher in high-risk individuals.ConclusionsInfluenza-attributable mortality was highest in older and high-risk individuals and mortality in children was higher than reported in passive Centers for Disease Control and Prevention surveillance. Influenza B-attributable mortality was higher than A in four of 12 seasons. Our estimates represent an updated assessment of influenza-attributable mortality in the USA.

BackgroundBuruli ulcer is an infectious disease involving the skin, caused by Mycobacterium ulcerans. This disease is associated with areas where the water is slow-flowing or stagnant. However, the exact mechanism of transmission of the bacillus and the development of the disease through human activities is unknown.Methodology/Principal FindingsA case-control study to identify Buruli ulcer risk factors in Cameroon compared case-patients with community-matched controls on one hand and family-matched controls on the other hand. Risk factors identified by the community-matched study (including 163 pairs) were: having a low level of education, swamp wading, wearing short, lower-body clothing while farming, living near a cocoa plantation or woods, using adhesive bandages when hurt, and using mosquito coils. Protective factors were: using bed nets, washing clothes, and using leaves as traditional treatment or rubbing alcohol when hurt. The family-matched study (including 118 pairs) corroborated the significance of education level, use of bed nets, and treatment with leaves.Conclusions/SignificanceCovering limbs during farming activities is confirmed as a protective factor guarding against Buruli ulcer disease, but newly identified factors including wound treatment and use of bed nets may provide new insight into the unknown mode of transmission of M. ulcerans or the development of the disease.

BackgroundEstimates of influenza and respiratory syncytial virus (RSV) burden must be periodically updated to inform public health strategies. We estimated seasonal influenza- and RSV-attributable hospitalizations in the US from 1997 to 2009 according to age and risk status (NCT01599390).MethodsMultiple linear regression modelling was used to attribute hospitalizations to influenza or RSV using virological surveillance and hospitalization data. Hospitalization data were obtained from the US Nationwide Inpatient Sample and virology data were obtained from FluView (Centers for Disease Control and Prevention). Outcomes included any mention of ICD-coded respiratory disease and cardiorespiratory disease diagnoses. We also explored a broader definition of respiratory disease that included mention of relevant respiratory sign/symptoms and viral infection (“respiratory broad”).ResultsApplying the respiratory broad outcome, our model attributed ~300,000 and ~200,000 hospitalizations to influenza and RSV, respectively. Influenza A/H3N2 was the predominant cause of influenza-related hospitalizations in most seasons, except in three seasons when influenza B was dominant; likewise, A/H3N2 caused most influenza-related hospitalizations in all age segments, except in children <18 years where the relative contribution of A/H3N2 and B was similar. Most influenza A- and B-related hospitalizations occurred in seniors while approximately one half and one third of all RSV-related events occurred in children 0–4 years and seniors 65+ years, respectively. High-risk status was associated with higher risk of both influenza- and RSV-attributable hospitalizations in adults, but not in children.ConclusionsOur study assessed the burden of influenza and RSV, information that is important for both cost effectiveness studies and for prioritization of the development of antivirals and vaccines. For seniors, we found that the burdens of influenza and RSV were both substantial. Among children <18 years, about half of all influenza hospitalizations were due to influenza B, most occurring in children without noted risk conditions. RSV hospitalizations among children were confined to those 0–4 years. Our study also demonstrated the importance of the outcome used to estimate hospitalization burden. Our findings highlight the burden of influenza among children regardless of risk status and underscore the prevalence of RSV infections among both young children and older adults.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-017-4177-z) contains supplementary material, which is available to authorized users.

ObjectiveThe burden of respiratory syncytial virus (RSV) illness is not well characterised in primary care. We estimated the burden of disease attributable to RSV in children in the UK between 1995 and 2009.DesignTime-series regression modelling.SettingA multiple linear regression model based on weekly viral surveillance (RSV and influenza, Public Health England), and controlled for non-specific seasonal drivers of disease, estimated the proportion of general practitioner (GP) episodes of care (counted as first visit in a series within 28 days; Clinical Practice Research Datalink, CPRD), hospitalisations (Hospital Episode Statistics, HES) and deaths (Office of National Statistics, ONS) attributable to RSV each season.ParticipantsChildren 0–17 years registered with a GP in CPRD, or with a respiratory disease outcome in the HES or ONS databases.Primary outcome measuresRSV-attributable burden of GP episodes, hospitalisations and deaths due to respiratory disease by age. RSV-attributable burden associated with selected antibiotic prescriptions.ResultsRSV-attributable respiratory disease in the UK resulted in an estimated 450 158 GP episodes, 29 160 hospitalisations and 83 deaths per average season in children and adolescents, with the highest proportions in children <6 months of age (14 441/100 000 population, 4184/100 000 and 6/100 000, respectively). In an average season, there were an estimated 125 478 GP episodes for otitis media and 416 133 prescriptions for antibiotics attributable to RSV. More GP episodes, hospitalisations and deaths from respiratory disease were attributable to RSV than to influenza in children under 5 years.ConclusionsThe burden of RSV in children in the UK exceeds that of influenza. RSV in children and adolescents contributes substantially to GP office visits for a diverse range of illnesses, and was associated with an average 416 133 prescribed antibiotic courses per season. Effective antiviral treatments and preventive vaccines are urgently needed for the management of RSV infection in children.Trial registration numberNCT01706302.

BackgroundInfluenza is rarely confirmed with laboratory testing and accurate assessment of the overall burden of influenza is difficult. We used statistical modelling methods to generate updated, granular estimates of the number/rate of influenza-attributable hospitalisations and deaths in the United Kingdom. Such data are needed on a continuing basis to inform on cost-benefit analyses of treatment interventions, including vaccination.MethodsWeekly age specific data on hospital admissions (1997–2009) and on deaths (1997–2009) were obtained from national databases. Virology reports (1996–2009) of influenza and respiratory syncytial virus detections were provided by Public Health England. We used an expanded set of ICD-codes to estimate the burden of illness attributable to influenza which we refer to as ‘respiratory disease broadly defined’. These codes were chosen to optimise the balance between sensitivity and specificity. A multiple linear regression model controlled for respiratory syncytial virus circulation, with stratification by age and the presence of comorbid risk status (conditions associated with severe influenza outcomes).ResultsIn the United Kingdom there were 28,516 hospitalisations and 7163 deaths estimated to be attributable to influenza respiratory disease in a mean season, with marked variability between seasons. The highest incidence rates of influenza-attributable hospitalisations and deaths were observed in adults aged 75+ years (252/100,000 and 131/100,000 population, respectively). Influenza B hospitalisations were highest among 5–17 year olds (12/100,000 population). Of all estimated influenza respiratory deaths in 75+ year olds, 50 % occurred out of hospital, and 25 % in 50–64 year olds. Rates of hospitalisations and death due to influenza-attributable respiratory disease were increased in adults identified as at-risk.ConclusionsOur study points to a substantial but highly variable seasonal influenza burden in all age groups, particularly affecting 75+ year olds. Effective influenza prevention or early intervention with anti-viral treatment in this age group may substantially impact the disease burden and associated healthcare costs. The high burden of influenza B hospitalisation among 5–17 year olds supports current United Kingdom vaccine policy to extend quadrivalent seasonal influenza vaccination to this age group.Trial registrationClinicalTrial.gov, NCT01520935Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3128-4) contains supplementary material, which is available to authorized users.

SUMMARYInfluenza 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.

The contribution of influenza B to the seasonal influenza burden varies from year-to-year. Although 2 antigenically distinct influenza B virus lineages have co-circulated since 2001, trivalent influenza vaccines (TIVs) contain antigens from only one influenza B virus. B-mismatch or co-circulation of both B lineages results in increased morbidity and mortality attributable to the B lineage absent from the vaccine. Quadrivalent vaccines (QIVs) contain both influenza B lineages. We reviewed currently licensed QIVs and their value by focusing on the preventable disease burden. Modeling studies support that QIVs are expected to prevent more influenza cases, hospitalisations and deaths than TIVs, although estimates of the case numbers prevented vary according to local specificities. The value of QIVs is demonstrated by their capacity to broaden the immune response and reduce the likelihood of a B-mismatched season. Some health authorities have preferentially recommended QIVs over TIVs in their influenza prevention programmes.