Standardization and improvement of influenza surveillance: memorandum from a WHO/GEIG meeting.

The main objectives of influenza surveillance are early detection of influenza outbreaks and identification of the causative agent, collection and analysis of influenza morbidity and mortality data, and collection of influenza virus isolates and analysis of their antigenic characteristics. The true morbidity and mortality from influenza are difficult to estimate in most countries on the basis of only reports of influenza-like illnesses. Analysis and comparisons of the impact of influenza in different countries are also difficult because surveillance systems and methods vary from one country to another. This Memorandum describes generally applicable systems that could improve influenza surveillance.     

Influenza surveillance.

The main objectives of influenza surveillance are: collection of influenza virus isolates and analysis of their antigenic characteristics so that the most appropriate virus variants can be recommended as constituents of influenza vaccines for use during the next epidemiological season; collection and analysis of information on influenza morbidity and mortality; and earliest possible detection of influenza epidemics. Exact estimates of the specific morbidity and mortality due to influenza are now being carried out in only certain countries. Simple notification of clinical cases and deaths without laboratory confirmation is unsatisfactory and leads to errors in interpretation. The methods used to predict baseline mortality may be inaccurate, resulting in underestimation of mortality associated with influenza virus infection. Comparison of the impact of influenza in different countries is also difficult owing to a variety of methods used for the estimation of mortality and morbidity. Although the laboratory aspects of influenza epidemiology are more uniformly covered worldwide than the statistical aspects, it is still necessary to increase laboratory coverage of some parts of the world and to improve the techniques for the isolation and characterization of not only influenza viruses but also other acute respiratory viruses. The systems and methods for influenza surveillance should be improved and standardized.     

Impact of influenza and respiratory syncytial virus on mortality in England and Wales from January 1975 to December 1990.

The effects of influenza A and B and RSV on mortality in England and Wales were assessed by regression analysis for the period 1975-90. Morbidity data from sentinel practices were used to calculate 4-weekly rates of aggregated upper respiratory tract infections (URTI); PHLS laboratory reports were used as indices of infection, and 4-weekly death rates from all causes, excluding childbirths, were used to study relationships with mortality. Deaths correlated strongly with influenza A and B reports, temperature, and interactions between aggregated URTI and temperature, and RSV outbreaks and temperature. Estimates of ''seasonal'' 4-weekly mortality associated with URTI were made by substituting into primary regression models the mean of annual trough consultation rates for aggregated URTI and baseline values for RSV and influenza. Peak 4-weekly mortality associated with URTIs was estimated at c. 24000 and c. 28000 during combined influenza and RSV epidemics of 1975-6 and 1989-90 respectively. Secondary regression analysis was carried out with the estimated ''seasonal'' 4-weekly deaths associated with URTI as dependent variable and laboratory data as regressors. Estimated excess mortality associated with influenza was considerable even during years without major epidemics. Overall during the 15 winters the estimated mortality associated with RSV was 60-80% more than that associated with influenza. The modelling permits only a crude estimate of RSV associated mortality. None the less it suggests that RSV is an important cause of winter mortality.     

Co-ordinated approach to healthcare worker influenza vaccination in an area health service

To increase local influenza vaccination uptake among healthcare workers (HCWs), a co-ordinated, area-wide influenza vaccination campaign was undertaken in 2008 for five hospitals in the South Metropolitan Area Health Service of Perth, Western Australia (WA). The programme included standardised marketing and data collection, with a consent form completed by each recipient. Denominator data were obtained from the WA Department of Health's staff database. Vaccination coverage at each hospital was calculated and compared with that of 2007, with predictors for vaccination determined using a follow-up cross-sectional survey. A total of 6387 influenza vaccinations were administered. The coverage rate was above 55% in all but one hospital (range: 48.8–76.5%) whereas in 2007 no hospital achieved 55% (range: 29–51%). Allied health professionals attained the highest coverage (57.7%), followed by doctors (51.9%), nurses (49.6%) and patient support staff (48.6%). Of HCWs who worked half-time or more, 58.8% were vaccinated. The main reasons for vaccination were to prevent influenza, limit spread, and the programme's availability. The survey revealed that HCWs who perceived that they were susceptible to influenza, that it was a serious disease and that immunisation was effective and important were significantly more likely to be vaccinated. An area-wide approach to HCW influenza vaccination can substantially improve uptake. Regular working party meetings, consistent marketing, standardised data collection and analysis, and senior management support were key elements and could be used by others to attain good vaccination coverage among HCWs.     

A systematic review of the social and economic burden of influenza in low- and middle-income countries

ObjectivesThe economic burden of seasonal influenza outbreaks as well as influenza pandemics in lower- and middle-income countries (LMIC) has yet to be specifically systematically reviewed. The aim of this systematic review is to assess the evidence of influenza economic burden assessment methods in LMIC and to quantify the economic consequences of influenza disease in these countries, including broader opportunity costs in terms of impaired social progress and economic development.MethodsWe conducted an all language literature search across 5 key databases using an extensive list of key words for the time period 1950–2013. We included studies which explored direct costs (medical and non-medical), indirect costs (productivity losses), and broader economic impact in LMIC associated with different influenza outcomes such as confirmed seasonal influenza infection, influenza-like illnesses, and pandemic influenza.ResultsWe included 62 full-text studies in English, Spanish, Russian, Chinese languages, mostly from the countries of Latin American and the Caribbean and East Asia and Pacific with pertinent cost data found in 39 papers. Estimates for direct and indirect costs were the highest in Latin American and the Caribbean. Compared to high-income economies, direct costs in LMIC were lower and productivity losses higher. Evidence on broader impact of influenza included impact on the wider national economy, security dimension, medical insurance policy, legal frameworks, distributional impact, and investment flows.ConclusionThe economic burden of influenza in LMIC encompasses multiple dimensions such as direct costs to the health service and households, indirect costs due to productivity losses as well as broader detriments to the wider economy. Evidence from sub-Saharan Africa and in pregnant women remains very limited. Heterogeneity of methods used to estimate cost components makes data synthesis challenging. There is a strong need for standardizing research, data collection and evaluation methods for both direct and indirect cost components.     

Can routinely collected laboratory and health administrative data be used to assess influenza vaccine effectiveness? Assessing the validity of the Flu and Other Respiratory Viruses Research (FOREVER) Cohort

BackgroundLinking data on laboratory specimens collected during clinical practice with health administrative data permits highly powered vaccine effectiveness (VE) studies to be conducted at relatively low cost, but bias from using convenience samples is a concern. We evaluated the validity of using such data for estimating VE.MethodsWe created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking individual-level data on respiratory virus laboratory tests, hospitalizations, emergency department visits, and physician services. For community-dwelling adults aged > 65 years, we assessed the presence and magnitude of information and selection biases, generated VE estimates under various conditions, and compared our VE estimates with those from other studies.ResultsWe included 65,648 unique testing episodes obtained from 54,434 individuals during the 2010–11 to 2015–16 influenza seasons. To examine information bias, we found the proportion testing positive for influenza for patients with unknown interval from illness onset to specimen collection was more similar to patients for whom illness onset date was ≤ 7 days before specimen collection than to patients for whom illness onset was > 7 days before specimen collection. To assess the presence of selection bias, we found the likelihood of influenza testing was comparable between vaccinated and unvaccinated individuals, although the adjusted odds ratios were significantly greater than 1 for some healthcare settings and during some influenza seasons. Over 6 seasons, VE estimates ranged between 36% (95%CI, 27–44%) in 2010–11 and 5% (95%CI, –2, 11%) in 2014–15. VE estimates were similar under a range of conditions, but were consistently higher when accounting for misclassification of vaccination status through a quantitative sensitivity analysis. VE estimates from the FOREVER Cohort were comparable to those from other studies.ConclusionsRoutinely collected laboratory and health administrative data contained in the FOREVER Cohort can be used to estimate influenza VE in community-dwelling older adults.     

Inactivated influenza vaccine effectiveness and an analysis of repeated vaccination for children during the 2016/17 season

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age during the 2016/17 season. In addition, we estimated the impact of repeated vaccination in children on VE.MethodsOur study for VEs in preventing influenza and admission due to influenza were conducted according to a test-negative case-control design (TNCC) based on influenza rapid diagnostic test results. We also analyzed the VE by vaccine status in the current and previous seasons for the impact of repeated vaccination.ResultsDuring the 2016/17 season, the quadrivalent IIV was used in Japan. The adjusted VE in preventing influenza illness was 38% (95% CI, 29–46) against influenza A and 39% (95% CI, 18–54) against influenza B. Infants showed no significant VE. The VE in preventing hospitalization was not demonstrated. For the analysis of repeated vaccination, the vaccine was effective only when immunization occurred in the current season. The children who were immunized in two consecutive seasons were more likely to develop influenza compared to those immunized in the current season only (odds ratio, 1.58 [95% CI, 1.05–2.38], adjusted odds ratio, 1.53 [95% CI, 0.99–2.35]). However, the odds ratio of repeated vaccination was not significant when the analysis excluded those who developed influenza in the previous season.ConclusionsVE in children in the 2016/17 season was similar to values previously reported. Repeated vaccination interfered with the VE against any influenza infection in the 2016/17 season. The results of our study suggest that decreased VE by repeat vaccination phenomenon was associated with immunity by influenza infection in the previous season. However, the influenza vaccine should be recommended every season for children.     

Genetic reassortment in pandemic and interpandemic influenza viruses

The human influenza pandemics of 1957 and 1968 were caused by reassortant viruses that possessed internal gene segments from avian and human strains. Whether genetic reassortment of human and avian influenza viruses occurs during interpandemic periods and how often humans are infected with such reassortants is not known. To provide this information, we used dot-blot hybridization, partial nucleotide sequencing and subsequent phylogenetic analysis to examine the 6 internal genes of 122 viruses isolated in humans between 1933 and 1992 primarily from Asia, Europe, and the Americas. The internal genes of A/New Jersey/11/76 isolated from a human fatality at Fort Dix, New Jersey in 1976 were found to be of porcine origin. Although none of the geographically and temporally diverse collection of 122 viruses was an avian-human or other reassortant, cognizance was made of the fact that there were two isolates from children from amongst 546 influenza A isolates obtained from The Netherlands from 1989–1994 which were influenza reassortants containing genes of avian origin, viruses which have infected European pigs since 1983–1985. Thus, genetic reassortment between avian and human influenza strains does occur in the emergence of pandemic and interpandemic influenza A viruses. However, in the interpandemic periods the reassortants have no survival advantage, and the circulating interpandemic influenza viruses in humans do not appear to accumulate avian influenza virus genes.     

Estimating the undetected burden of influenza hospitalizations in children

During the 2004-2005 influenza season two independent influenza surveillance systems operated simultaneously in three United States counties. The New Vaccine Surveillance Network (NVSN) prospectively enrolled children hospitalized for respiratory symptoms/fever and tested them using culture and RT-PCR. The Emerging Infections Program (EIP) and a similar clinical-laboratory surveillance system identified hospitalized children who had positive influenza tests obtained as part of their usual medical care. Using data from these systems, we applied capture-recapture analyses to estimate the burden of influenza related-hospitalizations in children aged<5 years. During the 2004-2005 influenza season the influenza-related hospitalization rate estimated by capture-recapture analysis was 8.6/10,000 children aged<5 years. When compared to this estimate, the sensitivity of the prospective surveillance system was 69% and the sensitivity of the clinical-laboratory based system was 39%. In the face of limited resources and an increasing need for influenza surveillance, capture-recapture analysis provides better estimates than either system alone.     

Influenza vaccination: A qualitative study of practice level barriers from medical practitioners caring for children with special risk medical conditions

BackgroundUnderstanding the influenza vaccination practices of general practitioners (GP) and paediatric hospital specialists caring for children with special risk medical conditions (SRMC) is imperative for designing interventions to improve uptake. This study aimed to identify the vaccination decision making, provider practices and perceived barriers and facilitators to recommending or delivering influenza vaccine for children with SRMCs at the tertiary and primary care levels.MethodsNominated GPs and hospital specialists from a single tertiary hospital were interviewed to explore influenza vaccination practices and challenges for children with confirmed SRMCs. Interviews were digitally recorded, transcribed verbatim and thematic analysis was used to inductively code these data. Resulting themes were mapped across the COM-B ('capability', 'opportunity', 'motivation' and 'behaviour') theoretical framework to understanding barriers and potential interventions.ResultsTwenty-six medical practitioners (21 GPs and 5 hospital specialists) completed semi-structured interviews. Barriers, and facilitators for influenza vaccine recommendation (the intended behaviour) were thematically grouped. Opportunity themes included structural barriers (e.g. limited use of systems and processes to support the identification of children with SRMCs); recommendation as standard practice; vaccination inconvenience; lack of communication and educational resources; social acceptance and normalisation; and media messaging. Capability themes included provider communication with parents; knowledge of influenza vaccine recommendations; and professional boundaries to implement the recommendation. Themes in the Motivation category included provider clinical prioritisation and responsibility towards providing a recommendation.ConclusionsThe main barriers to influenza recommendation raised by our study participants were structural. These included lack of processes to identify children with SRMCs, limited use of reminder systems and unclear delineation of role responsibility between hospital specialists and GPs. An important driver that emerged was GPs’ responsibility for providing a recommendation. To increase influenza vaccine coverage for children with SRMCs, consideration should be given to addressing practice level structural barriers and improving collaboration.     

Promoting influenza vaccination: Insights from a qualitative meta-analysis of 14 years of influenza-related communications research by U.S. Centers for Disease Control and Prevention (CDC)

IntroductionA primary mission of the U.S. Centers for Disease Control and Prevention's (CDC) is promoting immunization against seasonal influenza. As with most education efforts, CDC's influenza-related communications are often informed by formative research.MethodsA qualitative meta-analysis of 29 unpublished, primarily qualitative CDC-sponsored studies related to flu and flu vaccination knowledge, attitudes and beliefs (KABs). The studies, undertaken between 2000 and 2013, involved focus groups, in-depth interviews, message testing and surveys. Some involved health care professionals, while others involved members of the public, including sub-populations at risk for severe illness.FindingsThe themes that emerged suggested progress in terms of KABs related to influenza and influenza vaccination, but also the persistence of many barriers to vaccine acceptance. With respect to the public, recurring themes included limited understanding of influenza and immunization recommendations, indications of greater sub-group recognition of the value of flu vaccination, continued resistance to vaccination among many, and overestimation of the effectiveness of non-vaccine measures. Seven cognitive facilitators of vaccination were identified in the studies along with six cognitive barriers. For health care providers, the analysis suggests greater knowledge and more favorable beliefs, but many misperceptions persist and are similar to those held by the public. KABs often differed by type or category of health care provider.ConclusionsThe themes identified in this qualitative analysis illustrate the difficulty in changing KABs related to influenza and influenza vaccine, particularly on the scope and scale needed to greatly improve uptake. Even with an influenza pandemic and more vaccine options available, public and some health care provider perceptions and beliefs are difficult and slow to change. This meta-analysis does, however, provide important insights from previously unpublished information that can help those who are promoting influenza vaccination to health care providers, the general public and specific populations within the general population.     

CC及CXC趋化因子在流感病毒感染过程中调控不同免疫细胞的作用研究进展

流行性感冒(简称流感)是由流感病毒感染引起的急性呼吸道传染病。流感病毒经呼吸道侵袭人体后,呼吸道上皮细胞首先作出反应,产生多种细胞因子诱导机体发挥免疫应答,其中CC趋化因子及CXC趋化因子在流感病毒感染过程中调控多种免疫细胞,在流感病毒感染早期控制炎症反应,维持机体稳态过程中发挥重要作用。分析宿主体内趋化因子调控免疫细胞在流感病毒感染过程中的作用机制,从而为治疗流感提供新的策略。本文主要针对流感病毒感染过程中发挥主要作用的CC趋化因子、CXC趋化因子及其相关受体对各类型免疫细胞的调节作用进行综述。     

CDC Pregnancy Flu Line: Monitoring Severe Illness Among Pregnant Women with Influenza

The Centers for Disease Control and Prevention implemented the Pregnancy Flu Line (PFL) during the influenza A(H1N1)pdm09 (pH1N1) pandemic and continued operation through the 2010–2011 influenza season to collect reports of intensive care unit (ICU) admissions and deaths among pregnant women with influenza. The system documented the severe impact of influenza on pregnant women during both seasons with 181 ICU/survivals and 37 deaths reported during the 2009 fall pandemic wave and 69 ICU/survivals and ten deaths reported in the subsequent influenza season (2010–2011). A health department survey suggests PFL participants perceived public health benefits and minimum time burdens.     

Influenza vaccine effectiveness estimates for Western Australia during a period of vaccine and virus strain stability, 2010 to 2012

During 2010–2012 the strain composition of the influenza vaccine in the Southern Hemisphere did not change, but the circulating virus type/subtype did. We pooled data for these years from the Western Australian sentinel medical practice surveillance system for influenza to estimate vaccine effectiveness (VE) by influenza virus type and subtype. A case test-negative design was used with VE estimated as (1-odds ratio) × 100%. There were 2182 patients included in the analysis across the 3 years studied. The predominant subtype was A/H1pdm09 in 2010 and 2011, and A/H3 in 2012. The overall adjusted VE estimate against all influenza for 2010–2012 was 51% (95% CI: 36, 63). Estimates were highest against A/H1pdm09 at 74% (95% CI: 47, 87), followed by 56% (95% CI: 33, 71) for influenza B and lowest against A/H3 at 39% (95% CI: 13, 57). When analyses were restricted to compare influenza-positive patients with patients who tested positive for a non-influenza virus, overall adjusted VE was 59% (95% CI: 39, 72). These results suggest moderate protection against influenza by vaccination in Western Australia over the period 2010–2012, and are consistent with findings from other settings.     

Place of influenza vaccination among children—United States, 2010–11 through 2013–14 influenza seasons

BackgroundStudies are published on settings adults receive influenza vaccination but few have reported on settings children are vaccinated and how this might be changing over time or vary by socio-demographics.MethodsData from the National Immunization Survey-Flu were analyzed to assess place of influenza vaccination among vaccinated children 6 months–17 years during the 2010–11, 2011–12, 2012–13, and 2013–14 influenza seasons. The percentage of children vaccinated at each place was calculated overall and by age, race/ethnicity, income, and Metropolitan Statistical Area (MSA).ResultsThe places children received influenza vaccination varied little over four recent influenza seasons. From the 2010–11 through 2013–14 influenza seasons the percentage of vaccinated children receiving influenza vaccination at a doctor's office was 64.1%, 65.1%, 65.3%, and 65.3%, respectively with no differences from one season to the next. Likewise, for vaccination at clinics or health centers (17.8%, 17.5%, 17.0%. 18.0%), health departments (3.2%, 3.6%, 3.0%, 2.8%), and other non-medical places (1.6%, 1.4%, 1.2%, 1.1%), there were no differences from one season to the next. There were some differences for vaccinations at hospitals, pharmacies, and schools. There was considerable variability in the place of influenza vaccination by age, race/ethnicity, income, and MSA. Fewer Hispanic children were vaccinated at a doctor's office than black, white, and other or multiple race children and fewer black children and children of other or multiple races were vaccinated at a doctor's office than white children. More children at or below the poverty level were vaccinated at a clinic or health center than all of the other income groups.ConclusionMost vaccinated children receive their influenza vaccination at a doctor's office. Place of vaccination changed little over four recent influenza seasons. Large variability in place of vaccination exists by age, race/ethnicity, income, and MSA. Monitoring place of vaccination can help shape future immunization programs.     

Nine-year study of WHO virus reports on fatal viral infections.

In 1963, the World Health Organization established a system for the collection and distribution of information on viruses. The present study is based on 2737 reports of fatal viral infections received from laboratories in 39 out of a total of 47 countries participating in the scheme. In the industrially developed countries, from which most of the reports came, more than one-third of the total number of deaths were associated with influenza A virus, while in the developing countries, the enteroviruses, and in particular poliovirus, came high on the list.