Seasonal and pandemic influenza surveillance considerations for constructing multicomponent systems

Abstract Surveillance for influenza is essential for the selection of influenza vaccine components and detection of human infections with novel influenza A viruses that may signal the start of a pandemic. Virologic surveillance provides the foundation from which this information can be obtained. However, morbidity and mortality data are needed to better understand the burden of disease, which, in turn, can provide useful information for policy makers relevant to the allocation of resources for prevention and control efforts. Data on the impact of influenza can be used to identify groups at increased risk for severe influenza‐related complications, develop prevention and control policies, and monitor the effect of these policies. Influenza surveillance systems frequently monitor outpatient illness, hospitalizations, and deaths, but selection of influenza surveillance components should be based on the surveillance goals and objectives of the jurisdiction.     

Influenza surveillance and immunisation in New Zealand, 1997–2006

Background The national influenza surveillance in New Zealand is an essential public health component for assessing and implementing strategies to control influenza. Objective The aim of this study is to report the national influenza surveillance data collected during 1997–2006 in terms of the community disease burden, circulating viral strains, hospitalisations, mortality, and immunisation coverage. Methods The national influenza surveillance system includes sentinel general practice surveillance, laboratory‐based surveillance, and hospital admission and mortality surveillance and immunisation coverage. The results obtained during 1997–2006 were analysed. Results When the last 10 years were compared to the previous years, sentinel general practice surveillance recorded a decreasing trend of influenza‐like illness rates in the community. Sentinel surveillance also showed that children aged 0–4 years were the most affected. Influenza‐related hospitalisation surveillance reported an increasing trend of hospital admissions particularly in children aged 0–19 years. Introduction of routine influenza vaccination among the New Zealand elderly was associated with a significant decrease of influenza‐related mortality. Conclusions This report demonstrates that an integrated virological and epidemiological surveillance system for influenza is essential for monitoring the disease burden, identifying circulating strains, guiding effective vaccination and planning for a potential pandemic.     

Surveillance of Influenza in Indonesia, 2003–2007

Background Longitudinal data are limited about the circulating strains of influenza viruses and their public health impact in Indonesia. We conducted influenza surveillance among outpatients and hospitalized patients with influenza‐like illness (ILI) across the Indonesian archipelago from 2003 through 2007. Methodology Demographic, clinical data, and respiratory specimens were collected for 4236 ILI patients tested for influenza virus infection by RT‐PCR and viral culture. Principal Findings Influenza A and B viruses co‐circulated year‐round with seasonal peaks in influenza A virus activity during the rainy season (December–January). During 2003–2007, influenza viruses were identified in 20·1% (4236/21 030) of ILI patients, including 20·1% (4015/20 012) of outpatients, and 21·7% (221/1018) of inpatients. One H5N1 case was identified retrospectively in an outpatient with ILI. Antigenic drift in circulating influenza A and B virus strains was detected during the surveillance period in Indonesia. In a few instances, antigenically drifted viruses similar to the World Health Organization (WHO) vaccine strains were detected earlier than the date of their designation by WHO. Conclusions Influenza A and B virus infections are an important cause of influenza‐like illness among outpatients and hospitalized patients in Indonesia. While year‐round circulation of influenza viruses occurs, prevention and control strategies should be focused upon the seasonal peak during rainy season months. Ongoing virologic surveillance and influenza disease burden studies in Indonesia are important priorities to better understand the public health impact of influenza in South‐East Asia and the implications of influenza viral evolution and global spread.     

Preliminary results of 2009 pandemic influenza surveillance in the United States using the Aggregate Hospitalization and Death Reporting Activity

Please cite this paper as: Jhung et al. (2011) Preliminary results of 2009 pandemic influenza surveillance in the United States using the Aggregate Hospitalization and Death Reporting Activity. Influenza and Other Respiratory Viruses 5(5), 321–327. Background To augment established influenza surveillance systems in the United States, the Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists implemented the Aggregate Hospitalization and Death Reporting Activity (AHDRA) in August 2009. The AHDRA was designed to meet increased demands for timely and detailed information describing illness severity during the 2009 H1N1 influenza A (pH1N1) pandemic response. Objectives We describe the implementation of AHDRA and provide preliminary results from this new surveillance activity. Methods All 50 US states were asked to report influenza‐associated hospitalizations and deaths to AHDRA each week using either a laboratory‐confirmed or syndromic surveillance definition. Aggregate counts were used to calculate age‐specific weekly and cumulative rates per 100 000, and laboratory‐confirmed reports were used to estimate the age distribution of pH1N1 influenza‐associated hospitalizations and deaths. Results From August 30, 2009, through April 6, 2010, AHDRA identified 41 689 laboratory‐confirmed influenza‐associated hospitalizations and 2096 laboratory‐confirmed influenza‐associated deaths. Aggregate Hospitalization and Death Reporting Activity rates peaked earlier than hospitalization and death rates seen in previous influenza seasons with other surveillance systems, and the age distribution of cases revealed a tendency for hospitalizations and deaths to occur in persons <65 years for age. Conclusions Aggregate Hospitalization and Death Reporting Activity laboratory‐confirmed reports provided important information during the 2009 pandemic response. Aggregate Hospitalization and Death Reporting Activity syndromic reports were marked by low representativeness and specificity and were therefore less useful. The AHDRA was implemented quickly and may be a useful surveillance system to monitor severe illness during future influenza pandemics.     

Comparison of a live attenuated 2009 H1N1 vaccine with seasonal influenza vaccines against 2009 pandemic H1N1 virus infection in mice and ferrets

The role of seasonal influenza vaccination in pandemic influenza A H1N1 disease is important to address, because a large segment of the population is vaccinated annually. We administered 1 or 2 doses of pandemic H1N1 vaccine (CA/7 ca), a seasonal trivalent inactivated (s-TIV), or live attenuated influenza vaccine (s-LAIV) to mice and ferrets and subsequently challenged them with a pandemic H1N1 virus. In both species, CA/7 ca was immunogenic and conferred complete protection against challenge. s-TIV did not confer protection in either animal model, and s-LAIV did not confer any protection in ferrets. In mice, 2 doses of s-LAIV led to complete protection in the upper respiratory tract and partial protection in the lungs. Our data indicate that vaccination with the seasonal influenza vaccines did not confer complete protection in the lower respiratory tract in either animal model, whereas the CA/7 ca vaccine conferred complete protection in both animal models.     

The burden of influenza in East and South‐East Asia: a review of the English language literature

Abstract While human infections with avian influenza A (H5NI) viruses in Asia have prompted concerns about an influenza pandemic, the burden of human influenza in East and Southeast Asia has received far less attention. We conducted a review of English language articles on influenza in 18 countries in East and Southeast Asia published from 1980 to 2006 that were indexed on PubMed. Articles that described human influenza‐associated illnesses among outpatients or hospitalized patients, influenza‐associated deaths, or influenza‐associated socioeconomic costs were reviewed. We found 35 articles from 9 countries that met criteria for inclusion in the review. The quality of articles varied substantially. Significant heterogeneity was noted in case definitions, sampling schemes and laboratory methods. Early studies relied on cell culture, had difficulties with specimen collection and handling, and reported a low burden of disease. The recent addition of PCR testing has greatly improved the proportion of respiratory illnesses diagnosed with influenza. These more recent studies reported that 11–26% of outpatient febrile illness and 6‐14% of hospitalized pneumonia cases had laboratory‐confirmed influenza infection. The influenza disease burden literature from East and Southeast Asia is limited but expanding. Recent studies using improved laboratory testing methods and indirect statistical approaches report a substantial burden of disease, similar to that of Europe and North America. Current increased international focus on influenza, coupled with unprecedented funding for surveillance and research, provide a unique opportunity to more comprehensively describe the burden of human influenza in the region.     

MF59®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Abstract Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross‐reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non‐adjuvanted pre‐pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre‐pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross‐reactive immunogenicity. MF59^®, the first oil‐in‐water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59‐adjuvanted seasonal influenza vaccine (Fluad^®) has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non‐adjuvanted vaccines, and to provide cross‐reactive immunity against divergent influenza strains. Similar results have been generated with a MF59‐adjuvanted H5N1 pre‐pandemic vaccine, which showed higher and broader immunogenicity compared with non‐adjuvanted pre‐pandemic vaccines.     

Antibody responses against influenza A(H1N1)pdm09 virus after sequential vaccination with pandemic and seasonal influenza vaccines in Finnish healthcare professionals

Background Influenza A(H1N1)pdm09 virus has been circulating in human population for three epidemic seasons. During this time, monovalent pandemic and trivalent seasonal influenza vaccination against this virus have been offered to Finnish healthcare professionals. It is, however, unclear how well vaccine‐induced antibodies recognize different strains of influenza A(H1N1)pdm09 circulating in the population and whether the booster vaccination with seasonal influenza vaccine would broaden the antibody cross‐reactivity. Objectives Influenza vaccine‐induced humoral immunity against several isolates of influenza A(H1N1)pdm09 virus was analyzed in healthcare professionals. Age‐dependent responses were also analyzed. Methods Influenza viruses were selected to represent viruses that circulated in Finland during two consecutive influenza epidemic seasons 2009–2010 and 2010–2011. Serum samples from vaccinated volunteers, age 20–64 years, were collected before and after vaccination with AS03‐adjuvanted pandemic and non‐adjuvanted trivalent seasonal influenza vaccine that was given 1 year later. Results Single dose of pandemic vaccine induced a good albeit variable antibody response. On day 21 after vaccination, depending on the virus strain, 14–75% of vaccinated had reached antibody titers (≥1:40) considered seroprotective. The booster vaccination 1 year later with a seasonal vaccine elevated the seroprotection rate to 57–98%. After primary immunization, younger individuals (20–48 years) had significantly higher antibody titers against all tested viruses than older persons (49–64 years) but this difference disappeared after the seasonal booster vaccination. Conclusions Even a few amino acid changes in influenza A HA may compromise the vaccine‐induced antibody recognition. Older adults (49 years and older) may benefit more from repeated influenza vaccinations.     

Influenza: epidemiology, clinical features, therapy, and prevention

Influenza A and B are important causes of respiratory illness in all age groups. Influenza causes seasonal outbreaks globally and, less commonly, pandemics. In the United States, seasonal influenza epidemics account for >200,000 hospitalizations and >30,000 deaths annually. More than 90% of deaths occur in the elderly population. Interestingly, in the novel 2009 H1N1 influenza pandemic, attack rates were highest among children and young adults. Fewer than 10% of cases occurred in adults >60 years old, likely because preexisting antibodies against other H1N1 viruses afforded protection. Despite concerns about a high lethality rate with the novel 2009 H1N1 strain, most illnesses caused by the 2009 H1N1 viruses were mild (overall case fatality rate <0.5%). Clinical features of influenza infection overlap with other respiratory pathogens (particularly viruses). The diagnosis is often delayed due to low suspicion and the limited use of specific diagnostic tests. Rapid diagnostic tests are widely available and allow detection of influenza antigen in respiratory secretions within 1 hour; however, sensitivity ranges from 50 to 90%. Neuraminidase inhibitors (NAIs) (eg, oseltamivir and zanamivir) are effective for treating influenza A or B and for prophylaxis in selected adults and children. Resistance to NAIs is rare, but influenza strains resistant to oseltamivir have been detected. Vaccines are the cornerstone of influenza control. Currently, trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available. These agents reduce mortality and morbidity in high-risk patients (i.e., the elderly or patients with comorbidities), and expanding the use of vaccines to healthy children and adults reduces the incidence of influenza, pneumonia, and hospitalizations due to respiratory illnesses in the community.     

An early report from newly established laboratory-based influenza surveillance in Lao PDR

Please cite this paper as: Vongphrachanh P, Simmerman JM, Phonekeo D, Pansayavong V, Sisouk T, Ongkhamme S, Bryce GT, Corwin A, Bryant JE. An early report from newly established laboratory-based influenza surveillance in Lao PDR. Influenza and Other Respiratory Viruses 4(2), 47–52. Background Prior to 2007, little information was available about the burden of influenza in Laos. We report data from the first laboratory-based influenza surveillance system established in the Lao People’s Democratic Republic. Methods Three hospitals in the capital city of Vientiane began surveillance for influenza-like illness (ILI) in outpatients in 2007 and expanded to include hospitalized pneumonia patients in 2008. Nasal/throat swab specimens were collected and tested for influenza and other respiratory viruses by multiplex ID-Tag^TM respiratory viral panel (RVP) assay on a Luminex® 100× MAP IS instrument (Qiagen, Singapore). Results During January 2007 to December 2008, 287 of 526 (54·6%) outpatients with ILI were positive for at least one respiratory virus. Influenza was most commonly identified, with 63 (12·0%) influenza A and 92 (17·5%) influenza B positive patients identified. In 2008, six of 79 (7·6%) hospitalized pneumonia patients were positive for influenza A and four (5·1%) were positive for influenza B. Children <5 years represented 19% of viral infections in outpatients and 38% of pneumonia inpatients. Conclusion Our results provide the first documentation of influenza burden among patients with febrile respiratory illness and pneumonia requiring hospitalization in Laos. Implementing laboratory-based influenza surveillance requires substantial investments in infrastructure and training. However, continuing outbreaks of avian influenza A/H5N1 in poultry and emergence of the 2009 influenza A(H1N1) pandemic strain further underscore the importance of establishing and maintaining influenza surveillance in developing countries.     

Hospitalization of influenza‐like illness patients recommended by general practitioners in France between 1997 and 2010

Please cite this paper as: Pelat et al. (2012) Hospitalization of influenza‐like illness patients recommended by general practitioners in France between 1997 and 2010. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00356.x. Background The case–hospitalization ratio (CHR) is a key quantity for the management of emerging pathogens such as pandemic influenza. Yet, few running surveillance systems prospectively monitor the CHR during influenza epidemics. Here, we analyze the proportion of recommended hospitalizations (PRH) among influenza‐like illness (ILI) patients attended in general practice in France and compare the PRH observed during the 2009–2010 A(H1N1) pandemic with the one of the twelve previous seasons. Methods ILI cases were recorded by general practitioners (GPs) involved in surveillance, who indicated for each case whether they recommended hospitalization. We stratify the analysis by age, sex, and viral subtype. We investigate the reasons why GPs recommended hospitalization and the presence of risk factors for pandemic A(H1N1) complications. Results The average PRH over the seasons 1997–1998 to 2008–2009 was 3·4‰ (3–3·9). It was three times higher during the 2009–2010 pandemic than during seasonal influenza epidemics (OR = 2·89, 95% CI: 2·28–3·64). The highest increase was among 20–39‐year‐old women: OR = 11·8 (5·04–29·59). Overall, the principal reasons for recommending hospitalization were “respiratory problems” and “bad general condition.” However, during the pandemic, “age” (mainly associated with infants), “pregnancy,” and “diagnostic” became more frequent than before (P < 0·001). Finally, pregnancy was the reported risk factor for pandemic A(H1N1) complications that had the largest impact on hospitalization recommendation during the pandemic (OR = 38·62, P < 0·001). Conclusion Easily implemented in surveillance systems, this protocol has the potential to reveal changes in hospitalization recommendation by GPs. Moreover, if the right data are collected alongside, it could give timely insights into epidemic severity.     

Socio‐demographic differences in opinions about 2009 pandemic influenza A (H1N1) and seasonal influenza vaccination and disease among adults during the 2009–2010 influenza season

Background In April 2009, a novel influenza A virus emerged in the United States. By the end of July, influenza A (H1N1) 2009 monovalent (2009 H1N1) vaccine had been developed, licensed, and recommended by the Advisory Committee on Immunization Practices. Initial target groups for vaccination were identified and the first vaccine was publicly available in early October 2009. Objective This study examines socio‐demographic differences in opinions about 2009 pandemic influenza A (H1N1) (pH1N1) and seasonal influenza disease and vaccines and the association with receipt of influenza vaccinations during the 2009–2010 influenza season. Changes in opinions over the course of the pH1N1 pandemic were also examined. Methods Data from the 2009 National H1N1 Flu Survey (NHFS) were analyzed. The NHFS was a CDC‐sponsored telephone survey initiated in response to the 2009 pH1N1 pandemic to obtain weekly within‐season estimates of vaccination coverage, opinions, and other information. Results Opinions about influenza vaccine and disease varied significantly by race/ethnicity, income, and education level. In multivariable logistic regression analysis, adjusted 2009 H1N1 vaccination coverage was most strongly associated with opinions about the effectiveness of the vaccine and personal risk of disease, varying from 7 to 11% among adults who believed the vaccine to have low effectiveness and themselves at low risk of influenza, to 50–53% among those who thought vaccine effectiveness to be high and themselves at high risk of influenza. Conclusion Improving communication about personal risk and the effectiveness of influenza vaccines may improve vaccination coverage. The findings of difference in opinions could be used to target communication.     

The relative clinical impact of 2009 pandemic influenza A (H1N1) in the community compared to seasonal influenza in the Netherlands was most marked among 5-14 year olds

Please cite this paper as: van Gageldonk‐Lafeber et al. (2011) The relative clinical impact of 2009 pandemic influenza A (H1N1) in the community compared to seasonal influenza in the Netherlands was most marked among 5–14 year olds. Influenza and Other Respiratory Viruses 5(6), e513–e520. Background So far, most pandemic influenza reports were based on case studies focusing on severe disease. For public health policy, it is essential to consider the overall impact of the pandemic, including mild diseases. Objectives The aim of our study is to gain insight into the epidemiology of 2009 pandemic influenza in the community and to estimate the relative impact of pandemic compared to seasonal influenza. Methods The relative impact of pandemic influenza in the general population was assessed as the influenza‐like illness (ILI) incidence during the pandemic season compared with that during regular seasons. Influenza‐like illness incidences and virus diagnostics were derived from continuous sentinel surveillance systems. The incidence of hospital admissions, based on the mandatory notification of pandemic influenza, was used to relate the impact of severe disease to that in the community. Results The overall incidence of general practitioners‐attended ILI was 96 consultations per 10 000 persons. Highest incidences were reported in children and lowest in persons aged ≥65 years. For 5–14 year olds, the incidence during the pandemic was higher than during all preceding seasons. Samples originating from 5 to 19 year olds were statistically significant more often positive for pandemic influenza A (H1N1) 2009 virus as compared with samples from 0 to 4 year olds. Moreover, the incidence of hospital admission owing to pandemic influenza was highest in the youngest children. Conclusions Our study showed that while the absolute incidences of 2009 pandemic influenza were highest in children aged 0–4 years, the relative clinical impact in the community compared to seasonal influenza in previous years was most noticeable in healthy children 5–14 years of age.     

Improving seasonal and pandemic influenza vaccines

Abstract Challenges facing seasonal and pandemic influenza vaccination include: increasing the immunogenicity of seasonal vaccines for the most vulnerable, increasing vaccination coverage against seasonal influenza, and developing vaccines against pandemic strains that are immunogenic with very low quantities of antigen to maximize the number of people who can be vaccinated with a finite production capacity. We review Sanofi Pasteur’s epidemic and pandemic influenza research and development programmes with emphasis on two key projects: intradermal influenza vaccine for seasonal vaccination of both elderly and younger adults, and pandemic influenza vaccine.     

The potential economic value of influenza vaccination for healthcare workers in The Netherlands

Background

Despite the clinical evidence, influenza vaccination coverage of healthcare workers remains low. To assess the health economic value of implementing an influenza immunization program among healthcare workers (HCW) in University Medical Centers (UMCs) in the Netherlands, a cost‐benefit model was developed using a societal perspective.

Methods/Patients

The model was based on a trial performed among all UMCs in the Netherlands that included both hospital staff and patients admitted to the pediatrics and internal medicine departments. The model structure and parameters estimates were based on the trial and complemented with literature research, and the impact of uncertainty explored with sensitivity analyses.

Results

In a base‐case scenario without vaccine coverage, influenza‐related annual costs were estimated at € 410 815 for an average UMC with 8000 HCWs and an average occupancy during the influenza period of 6000 hospitalized patients. Of these costs, 82% attributed to the HCWs and 18% were patient‐related. With a vaccination coverage of 15.47%, the societal program’s savings were € 2861 which corresponds to a saving of € 270.53 per extended hospitalization. Univariate sensitivity analyses show that the results are most sensitive to changes in the model parameters vaccine effectiveness in reducing influenza‐like illness (ILI) and the vaccination‐related costs.

Conclusion

In addition to the decreased burden of patient morbidity among hospitalized patients, the effects of the hospital immunization program slightly outweigh the economic investments. These outcomes may support healthcare policymakers’ recommendations about the influenza vaccination program for healthcare workers.     

MOLECULAR CHARACTERIZATION OF INFLUENZA B VIRUS OUTBREAK ON A CRUISE SHIP IN BRAZIL 2012

In February 2012, an outbreak of respiratory illness occurred on the cruise ship MSC Armonia in Brazil. A 31-year-old female crew member was hospitalized with respiratory failure and subsequently died. To study the etiology of the respiratory illness, tissue taken at necropsy from the deceased woman and respiratory specimens from thirteen passengers and crew members with respiratory symptoms were analyzed. Influenza real-time RT-PCR assays were performed, and the full-length hemagglutinin (HA) gene of influenza-positive samples was sequenced. Influenza B virus was detected in samples from seven of the individuals, suggesting that it was the cause of this respiratory illness outbreak. The sequence analysis of the HA gene indicated that the virus was closely related to the B/Brisbane/60/2008-like virus, Victoria lineage, a virus contained in the 2011-12 influenza vaccine for the Southern Hemisphere. Since the recommended composition of the influenza vaccine for use during the 2013 season changed, an intensive surveillance of viruses circulating worldwide is crucial. Molecular analysis is an important tool to characterize the pathogen responsible for an outbreak such as this. In addition, laboratory disease surveillance contributes to the control measures for vaccine-preventable influenza.     

Epidemiologic and virologic assessment of the 2009 influenza A (H1N1) pandemic on selected temperate countries in the Southern Hemisphere: Argentina, Australia, Chile, New Zealand and South Africa

Please cite this paper as: Van Kerkhove et al. (2011) Epidemiologic and virologic assessment of the 2009 influenza A (H1N1) pandemic on selected temperate countries in the Southern Hemisphere: Argentina, Australia, Chile, New Zealand and South Africa. Influenza and Other Respiratory Viruses 5(6), e487–e498. Introduction and Setting Our analysis compares the most comprehensive epidemiologic and virologic surveillance data compiled to date for laboratory‐confirmed H1N1pdm patients between 1 April 2009 ‐ 31 January 2010 from five temperate countries in the Southern Hemisphere–Argentina, Australia, Chile, New Zealand, and South Africa. Objective We evaluate transmission dynamics, indicators of severity, and describe the co‐circulation of H1N1pdm with seasonal influenza viruses. Results In the five countries, H1N1pdm became the predominant influenza strain within weeks of initial detection. South Africa was unique, first experiencing a seasonal H3N2 wave, followed by a distinct H1N1pdm wave. Compared with the 2007 and 2008 influenza seasons, the peak of influenza‐like illness (ILI) activity in four of the five countries was 3‐6 times higher with peak ILI consultation rates ranging from 35/1,000 consultations/week in Australia to 275/100,000 population/week in New Zealand. Transmission was similar in all countries with the reproductive rate ranging from 1.2–1.6. The median age of patients in all countries increased with increasing severity of disease, 4–14% of all hospitalized cases required critical care, and 26–68% of fatal patients were reported to have ≥1 chronic medical condition. Compared with seasonal influenza, there was a notable downward shift in age among severe cases with the highest population‐based hospitalization rates among children <5 years old. National population‐based mortality rates ranged from 0.8–1.5/100,000. Conclusions The difficulty experienced in tracking the progress of the pandemic globally, estimating its severity early on, and comparing information across countries argues for improved routine surveillance and standardization of investigative approaches and data reporting methods.     

Vaccines for seasonal and pandemic influenza

Seasonal influenza continues to have a huge annual impact in the United States, accounting for tens of millions of illnesses, hundreds of thousands of excess hospitalizations, and tens of thousands of excess deaths. Vaccination remains the mainstay for the prevention of influenza. In the United States, 2 types of influenza vaccine are currently licensed: trivalent inactivated influenza vaccine and live attenuated influenza vaccine. Both are safe and effective in the populations for which they are approved for use. Children, adults <65 years of age, and the elderly all receive substantial health benefits from vaccination. In addition, vaccination appears to be cost-effective, if not cost saving, across the age spectrum. Despite long-standing recommendations for the routine vaccination of persons in high-priority groups, US vaccination rates remain too low across all age groups. Important issues to be addressed include improving vaccine delivery to current and expanded target groups, ensuring timely availability of adequate vaccine supply, and development of even more effective vaccines. Development of a vaccine against potentially pandemic strains is an essential part of the strategy to control and prevent a pandemic outbreak. The use of existing technologies for influenza vaccine production would be the most straightforward approach, because these technologies are commercially available and licensing would be relatively simple. Approaches currently being tested include subvirion inactivated vaccines and cold-adapted, live attenuated vaccines. Preliminary results have suggested that, for some pandemic antigens, particularly H5, subvirion inactivated vaccines are poorly immunogenic, for reasons that are not clear. Data from evaluation of live pandemic vaccines are pending. Second-generation approaches designed to provide improved immune responses at lower doses have focused on adjuvants such as alum and MF59, which are currently licensed for influenza or other vaccines. Additional experimental approaches are required to achieve the ultimate goal for seasonal and pandemic influenza prevention--namely, the ability to generate broadly cross-reactive and durable protection in humans.