Showing papers in "Influenza and Other Respiratory Viruses in 2012"

Influenza research database: an integrated bioinformatics resource for influenza research and surveillance.

Abstract: Author(s): Squires, R Burke; Noronha, Jyothi; Hunt, Victoria; Garcia-Sastre, Adolfo; Macken, Catherine; Baumgarth, Nicole; Suarez, David; Pickett, Brett E; Zhang, Yun; Larsen, Christopher N; Ramsey, Alvin; Zhou, Liwei; Zaremba, Sam; Kumar, Sanjeev; Deitrich, Jon; Klem, Edward; Scheuermann, Richard H | Abstract: BackgroundThe recent emergence of the 2009 pandemic influenza A/H1N1 virus has highlighted the value of free and open access to influenza virus genome sequence data integrated with information about other important virus characteristics.DesignThe Influenza Research Database (IRD, http://www.fludb.org) is a free, open, publicly-accessible resource funded by the U.S. National Institute of Allergy and Infectious Diseases through the Bioinformatics Resource Centers program. IRD provides a comprehensive, integrated database and analysis resource for influenza sequence, surveillance, and research data, including user-friendly interfaces for data retrieval, visualization and comparative genomics analysis, together with personal log in-protected 'workbench' spaces for saving data sets and analysis results. IRD integrates genomic, proteomic, immune epitope, and surveillance data from a variety of sources, including public databases, computational algorithms, external research groups, and the scientific literature.ResultsTo demonstrate the utility of the data and analysis tools available in IRD, two scientific use cases are presented. A comparison of hemagglutinin sequence conservation and epitope coverage information revealed highly conserved protein regions that can be recognized by the human adaptive immune system as possible targets for inducing cross-protective immunity. Phylogenetic and geospatial analysis of sequences from wild bird surveillance samples revealed a possible evolutionary connection between influenza virus from Delaware Bay shorebirds and Alberta ducks.ConclusionsThe IRD provides a wealth of integrated data and information about influenza virus to support research of the genetic determinants dictating virus pathogenicity, host range restriction and transmission, and to facilitate development of vaccines, diagnostics, and therapeutics.

Influenza neuraminidase: Influenza neuraminidase

Abstract: Please cite this paper as: Air. (2012) Influenza neuraminidase. Influenza and Other Respiratory Viruses 6(4), 245–256.

Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children

Abstract: Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71–77. Background Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods Eight hundred and ninety-three residual nasal wash samples from children treated for respiratory illness at Children’s Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results Coinfections were identified in 103 (18%) of 566 virus-positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV-1, multiple virus illnesses had a significantly lower viral load (log10 copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu-A, PIV-3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections.

The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence

Abstract: There are limited data on the use of masks and respirators to reduce transmission of influenza A systematic review was undertaken to help inform pandemic influenza guidance in the United Kingdom The initial review was performed in November 2009 and updated in June 2010 and January 2011 Inclusion criteria included randomised controlled trials and quasi-experimental and observational studies of humans published in English with an outcome of laboratory-confirmed or clinically-diagnosed influenza and other viral respiratory infections There were 17 eligible studies Six of eight randomised controlled trials found no significant differences between control and intervention groups (masks with or without hand hygiene; N95/P2 respirators) One household trial found that mask wearing coupled with hand sanitiser use reduced secondary transmission of upper respiratory infection/influenza-like illness/laboratory-confirmed influenza compared with education; hand sanitiser alone resulted in no reduction One hospital-based trial found a lower rate of clinical respiratory illness associated with non-fit-tested N95 respirator use compared with medical masks Eight of nine retrospective observational studies found that mask and/or respirator use was independently associated with a reduced risk of severe acute respiratory syndrome (SARS) Findings, however, may not be applicable to influenza and many studies were suboptimal None of the studies established a conclusive relationship between mask/respirator use and protection against influenza infection Some evidence suggests that mask use is best undertaken as part of a package of personal protection especially hand hygiene The effectiveness of masks and respirators is likely linked to early, consistent and correct usage

Comparison of clinical features and outcomes of medically attended influenza A and influenza B in a defined population over four seasons: 2004–2005 through 2007–2008

Abstract: Please cite this paper as: Irving et al. (2012) Comparison of clinical features and outcomes of medically attended influenza A and influenza B in a defined population over four seasons: 2004–2005 through 2007–2008. Influenza and Other Respiratory Viruses 6(1), 37–43. Background There are few prospectively collected data comparing illnesses caused by different subtypes of influenza. We compared the clinical presentation and outcomes of subjects with primarily outpatient‐attended influenza A and B infections during four consecutive influenza seasons (2004–2005 through 2007–2008). Methods Patients were prospectively enrolled and tested for influenza following an encounter for acute respiratory illness. Influenza infections were confirmed by culture or reverse transcription polymerase chain reaction; subtype was determined for a sample of influenza A isolates each season. Clinical characteristics of influenza A and B infections were compared across and within individual seasons. Results We identified 901 cases of influenza A and 284 cases of influenza B; 98% of cases were identified through an outpatient medical encounter. Thirty‐six percent of patients with each strain had received seasonal influenza vaccine prior to illness onset. There were no consistent differences in symptoms associated with influenza A and B. Influenza A infection was associated with earlier care seeking compared with influenza B during the 2005–2006 and 2007–2008 seasons, when H3N2 was the dominant type A virus, and in a combined analysis that included all seasons. Twenty‐six (2·2%) of 1185 cases were diagnosed with radiographically confirmed pneumonia, and 59 (5%) of 1185 patients were hospitalized within 30 days of illness onset. Conclusions Over four influenza seasons, aside from shorter intervals from illness onset to clinical encounter for infections with the A(H3N2) subtype, clinical symptoms and outcomes were similar for patients with predominantly outpatient‐attended influenza A and B infections.

A plant-based system for rapid production of influenza vaccine antigens.

Abstract: Please cite this paper as: Shoji et al. (2011) A plant-based system for rapid production of influenza vaccine antigens. Influenza and Other Respiratory Viruses 6(3), 204–210. Background Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is to manufacture and administer pandemic vaccines in sufficient quantities and to do so in a timely manner without impacting the regular seasonal influenza vaccine capacity. Current, egg-based, influenza vaccine production is well established and provides an effective product, but has limited capacity and speed. Objectives To satisfy the additional global demand for emerging influenza vaccines, high-performance cost-effective technologies need to be developed. Plants have a potential as an economic and efficient large-scale production platform for vaccine antigens. Methods In this study, a plant virus-based transient expression system was used to produce hemagglutinin (HA) proteins from the three vaccine strains used during the 2008–2009 influenza season, A/Brisbane/59/07 (H1N1), A/Brisbane/10/07 (H3N2), and B/Florida/4/06, as well as from the recently emerged novel H1N1 influenza A virus, A/California/04/09. Results The recombinant plant-based HA proteins were engineered and produced in Nicotiana benthamiana plants within 2 months of obtaining the genetic sequences specific to each virus strain. These antigens expressed at the rate of 400–1300 mg/kg of fresh leaf tissue, with >70% solubility. Immunization of mice with these HA antigens induced serum anti-HA IgG and hemagglutination inhibition antibody responses at the levels considered protective against these virus infections. Conclusions These results demonstrate the feasibility of our transient plant expression system for the rapid production of influenza vaccine antigens.

Sensitivity of oral fluids for detecting influenza A virus in populations of vaccinated and non‐vaccinated pigs

Abstract: Please cite this paper as: Romagosa et al. (2011) Sensitivity of oral fluids for detecting influenza A virus in populations of vaccinated and non-vaccinated pigs. Influenza and Other Respiratory Viruses. Background/objective We evaluated the sensitivity of PCR on oral fluids in detecting influenza virus in vaccinated and non-vaccinated pigs. Methods Three-week-old influenza-free pigs were divided into three groups: (i) control, non-vaccinated, (ii) vaccinated with a commercial, heterologous vaccine, and (iii) vaccinated with an experimental, homologous vaccine. After vaccination, an influenza-infected pig was placed in contact with each of the groups. Individual nasal swabs and pen oral fluids were collected daily. Viral RNA was tested for the presence of influenza by RRT-PCR and virus isolation attempted from oral fluids. A pen was considered positive if at least one nasal swab was positive. Results Based on nasal swab results, 43·8% of pens were detected positive but only 35% based on oral fluids. Overall sensitivity of oral fluids was 80%, and virus was isolated from 51% of RRT-PCR-positive oral fluids. The kappa coefficient for agreement (ĸ) between oral fluids and nasal swabs was 0·82. Among groups, ĸ was 1 (95% CI, 1–1), 0·74 (95% CI, 0·55–0·92), and 0·76 (95% CI, 0·5–1) for control, heterologous, and homologous-vaccinated groups, respectively. There was less agreement when within pen prevalence was 10% or less. Probability of detecting influenza virus in oral fluids was 99% when within pen prevalence was higher than 18% and decreased to 69% when prevalence was 9%. Conclusions Results indicated that pen-based collection of oral fluids is a sensitive method to detect influenza even when within pen prevalence is low and when pigs have been vaccinated and highlight the potential use of oral fluids for influenza surveillance.

Liver involvement during influenza infection: perspective on the 2009 influenza pandemic

Abstract: Please cite this paper as: Papic et al. (2011) Liver involvement during influenza infection: perspective on the 2009 influenza pandemic. Influenza and Other Respiratory Viruses 6(3), e2–e5. Elevation of liver transaminase levels is a frequent observation during systemic infections. The aim of our study was to investigate liver damage during pandemic 2009 influenza A/H1N1 infection in comparison with seasonal influenza. Serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase (GGT) were significantly higher in patients with pandemic influenza compared to seasonal influenza, which was strongly correlated with hypoxia. Moreover, a positive correlation between C-reactive protein and serum GGT, alkaline phosphatase, and lactate dehydrogenase was noticed. Our findings support the hypothesis that the pandemic 2009 influenza A/H1N1 is an illness with a significant immune response to infection leading to hepatocellular injury.

Multisite virological influenza surveillance in India: 2004–2008

Abstract: Please cite this paper as: Chadha et al. (2011) Multi site Virological Influenza Surveillance in India: 2004–2008. Influenza and Other Respiratory Viruses 6(3), 196–203. Background Influenza surveillance is important to identify circulating, emerging/reemerging strains and unusual epidemiological trends. With these objectives, a multisite human influenza surveillance network was initiated in India in 2004. Methods Epidemiologic data and throat swabs for laboratory testing were collected from patients with influenza-like illness (ILI) and severe acute respiratory infections (SARI). Virus isolation was carried out in Madin–Darby canine kidney cells and strains identified by hemagglutination inhibition assay. Meteorological data were collected. Results From September 2004 to December 2008, 617 (4·43%) of 13928 cases yielded isolates: 27·8% were influenza A(H1N1), 29·8% were type A(H3N2), and 42·3% were type B. The yearly type and subtype distribution varied significantly from site to site. Peak influenza activity was observed from June to August in Delhi, Pune, and Kolkata and October to December in Chennai. Maximum influenza activity was seen during the rains in Delhi, Pune, Chennai, and Kolkata in correlation with virus isolations. Multivariate analysis of ILI cases showed chill/rigors, cough, fatigue, and ILI in family, correlated positively with isolation. Genetic analysis of Indian isolates revealed that viruses matched with vaccine strains by and large. Overlapping between circulating and vaccine component strains of consecutive years was also observed. Conclusions Seasonal influenza A(H1N1), H3N2, and type B co-circulated in all regions without any particular pattern of movement of any subtype. Year-round limited influenza activity with peaks during rains was observed. Genetic drifts and varying seasonality in different parts of the country suggest that a staggered timing of vaccination may be appropriate for India.

The impact of pandemic influenza A (H1N1) 2009 on the circulation of respiratory viruses 2009–2011

Abstract: Surveillance of respiratory viruses has been conducted for many years at the public health laboratory in Hong Kong. With the occurrence of pandemic influenza A (H1N1) 2009, we observed a change in the seasonality of influenza activity with a seemingly corresponding change in the activity of respiratory syncytial virus, parainfluenza virus, and adenovirus during 2009-2011. This phenomenon could most likely be explained by virus interference.

Review on the impact of pregnancy and obesity on influenza virus infection.

Abstract: A myriad of risk factors have been linked to an increase in the severity of the pandemic H1N1 2009 influenza A virus [A(H1N1)pdm09] including pregnancy and obesity where death rates can be elevated as compared to the general population. The goal of this review is to provide an overview of the influence of pregnancy and obesity on the reported cases of A(H1N1)pdm09 virus infection and of how the concurrent presence of these factors may have an exacerbating effect on infection outcome. Also, the hypothesized immunologic mechanisms that contribute to A(H1N1)pdm09 virus severity during pregnant or obese states are outlined. Identifying the mechanisms underlying the increased disease severity in these populations may result in improved therapeutic approaches and future pandemic preparedness.

Improving influenza vaccine virus selectionReport of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14-16 June 2010: Improving influenza vaccine virus selection

Abstract: • For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. • The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy‐making community of the complexity of influenza vaccine virus selection. • The selection process is highly coordinated and involves continual year‐round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). • Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non‐antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints. • Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines. • Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas. • Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays – for example based upon advanced recombinant DNA and protein technologies – may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development. • Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large‐scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity. • Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well‐characterized banks of age‐stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. • Advances in high‐throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X‐ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. • Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non‐mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. • The adoption of alternative vaccine technologies – such as live‐attenuated, quadrivalent or non‐HA‐based vaccines – has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high‐growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. • The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations.

Influenza viruses in Thailand: 7 years of sentinel surveillance data, 2004–2010

Abstract: Please cite this paper as: Chittaganpitch et al. (2012) Influenza viruses in Thailand: 7 years of sentinel surveillance data, 2004–2010. Influenza and Other Respiratory Viruses 6(4), 276–283. Background The re-emergence of avian influenza A (H5N1) in 2004 and the pandemic of influenza A (H1N1) in 2009 highlight the need for routine surveillance systems to monitor influenza viruses, particularly in Southeast Asia where H5N1 is endemic in poultry. In 2004, the Thai National Institute of Health, in collaboration with the US Centers for Disease Control and Prevention, established influenza sentinel surveillance throughout Thailand. Objectives To review routine epidemiologic and virologic surveillance for influenza viruses for public health action. Methods Throat swabs from persons with influenza-like illness and severe acute respiratory illness were collected at 11 sentinel sites during 2004–2010. Influenza viruses were identified using the standard protocol for polymerase chain reaction. Viruses were cultured and identified by immunofluorescence assay; strains were identified by hemagglutination inhibition assay. Data were analyzed to describe frequency, seasonality, and distribution of circulating strains. Results Of the 19 457 throat swabs, 3967 (20%) were positive for influenza viruses: 2663 (67%) were influenza A and able to be subtyped [21% H1N1, 25% H3N2, 21% pandemic (pdm) H1N1] and 1304 (33%) were influenza B. During 2009–2010, the surveillance system detected three waves of pdm H1N1. Influenza annually presents two peaks, a major peak during the rainy season (June–August) and a minor peak in winter (October–February). Conclusions These data suggest that March–April may be the most appropriate months for seasonal influenza vaccination in Thailand. This system provides a robust profile of the epidemiology of influenza viruses in Thailand and has proven useful for public health planning.

Influenza viral infections among the Iranian Hajj pilgrims returning to Shiraz, Fars province, Iran.

Abstract: Please cite this paper as: Moattari et al. (2012) Influenza viral infections among the Iranian Hajj pilgrims returning to Shiraz, Fars province, Iran. Influenza and Other Respiratory Viruses 6(601), e77–e79 Background Annually over two million Muslims from across the world converge on Mecca to perform the Hajj pilgrimage. Overcrowding at the Hajj facilitates spread of communicable diseases, especially respiratory infections. The aim of this study was to determine the attack rate of seasonal and pandemic influenza among returning Iranian pilgrims after the 2009 Hajj. Methods Clinical data and throat swabs were collected at Shiraz airport from symptomatic Iranian pilgrims of Fars province who were returning from the Hajj between 15 and 21 December 2009. The specimens were tested at the Shiraz University of Medical Sciences Influenza Research Center for influenza viruses by cell culture and real-time reverse transcriptase polymerase chain reaction (RTrtPCR) according to standard protocol. Findings Out of 3000 pilgrims from Fars province who attended the Hajj 2009, 275 symptomatic pilgrims were recruited into this study. Pilgrims had fever, cough, muscle ache and sore throat in various combinations. Twenty-five (9·1%) pilgrims had influenza by virus culture and these were as follows: influenza B (n = 17), influenza A H3N2 (n = 8) and pandemic H1N1 (n = 5), whereas 33 (12%) had influenza by RTrtPCR: influenza B (n = 20), influenza A H3N2 (n = 8) and pandemic H1N1 (n = 5). Interpretation Both seasonal and pandemic influenza infections occurred among the Iranian Hajj pilgrims; seasonal viruses were more common than the pandemic viruses even though all pilgrims were vaccinated against seasonal influenza.

Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings.

Abstract: Please cite this paper as: Burns et al. (2011) Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings. Influenza and Other Respiratory Viruses 6(3), 218–223. Background Viral detection from different respiratory sample types in children with cystic fibrosis (CF) is facilitated by available molecular methods, but optimum sampling strategies have not been identified. In addition, associations between viral detection and respiratory symptoms are not well described. Objectives Study goals were to compare molecular detection of viruses from concurrent upper airway and sputum samples in children with CF and to describe relative frequency of respiratory viral infections and identify potential clinical associations. Methods We conducted a 2-year prospective surveillance study in 44 children with CF aged 6–18 years. Upper airway and sputum samples were collected quarterly and during pulmonary exacerbations and tested for respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses types 1–4, human metapneumovirus, coronaviruses, rhinoviruses, and adenoviruses. Physical exams and symptom surveys were used to identify respiratory signs and symptoms. Results Upper airway samples were collected at 359 visits; concordance of PCR-based viral detection was examined in a subset of paired upper airway and sputum samples from 21 participants at 92 visits. Rhinovirus was the most commonly detected virus (23·1% overall), and rhinovirus detection was the same for both sample types (21·7% each). Sensitivity and specificity for the detection of rhinovirus in sputum relative to upper airway sampling were 70% and 91·7%, respectively. Respiratory symptoms associated with rhinovirus detection included increased cough, increased nasal congestion, increased sputum production, and wheezing. Conclusions A relatively high frequency of rhinovirus detection was observed by either upper airway or sputum samples, and clinical findings suggest a significant-associated symptom burden.

Intensive care unit patients with 2009 pandemic influenza A (H1N1pdm09) virus infection - United States, 2009.

Abstract: Please cite this paper as: Bramley et al. Intensive care unit patients with 2009 pandemic influenza A (H1N1pdm09) virus infection – United States, 2009. Influenza and Other Respiratory Viruses 6(601), e134–e142. Background The influenza A (H1N1pdm09) [pH1N1] virus resulted in intensive care unit (ICU) admissions, acute respiratory distress syndrome (ARDS), and death. Objectives To describe the characteristics of ICU patients with pH1N1 virus infection in the United States during the spring and fall of 2009 and to describe the factors associated with severe complications including ARDS and death. Patients/Methods Through two national case-series conducted during spring and fall of 2009, medical charts were reviewed on ICU patients with laboratory-confirmed pH1N1 infection by real-time reverse-transcriptase polymerase chain reaction. Results The majority (77%) of 154 patients hospitalized in an ICU were <50 years of age, and 65% had at least one underlying medical condition. One hundred and twenty-eight (83%) patients received influenza antiviral agents; 29% received treatment ≤2 days after illness onset. Forty-eight (38%) patients developed ARDS and 37 (24%) died. Patients with ARDS were more likely to be morbidly obese (36% versus 19%, P = 0·04) and patients who died were less likely to have asthma (11% versus 28%, P = 0.05). Compared with patients who received treatment ≥6 days after illness onset, patients treated ≤2 days after illness onset were less likely to develop ARDS (17% versus 37%, P < 0.01) or die (7% versus 35%, P < 0·01). Conclusions Among patients hospitalized in an ICU with pH1N1 virus infection, ARDS was a common complication, and one-quarter of patients died. Patients with asthma had less severe outcomes. Early treatment with influenza antiviral agents was likely beneficial, especially when initiated ≤2 days after illness onset.

Quantitative review of antibody response to inactivated seasonal influenza vaccines.

Abstract: Please cite this paper as: Seidman et al. (2012) Quantitative review of antibody response to inactivated seasonal influenza vaccines. Influenza and Other Respiratory Viruses 6(1), 52–62. Background Seasonal influenza epidemics are associated with significant morbidity and mortality each year, particularly amongst young children and the elderly. Seasonal influenza vaccines have been available for decades, yet influenza remains a major public health threat in the US, sparking interest in studies evaluating the effectiveness of vaccination. Objectives We sought to identify determinants of serological responses to inactivated seasonal influenza vaccines including number of doses, adjuvant, and subject characteristics. Methods We reviewed 60 articles published between 1987 and 2006. We used weighted multiple logistic regression and random-effects models to evaluate how seroconversion and seroprotection rates varied with host and vaccine factors. Results Both children and seniors tended to have poorer immune responses compared to adults whereas use of adjuvant and a second vaccine dose tended to improve immune response. Pre-vaccination serological status had a large impact on the immune response to vaccination. We found substantial heterogeneity among studies, even with similar population settings and vaccination regimen. Conclusions Future studies should stratify their results by pre-vaccination serological status in an effort to produce more precise summary estimates of vaccine response.

Pandemic 2009 influenza A (H1N1) infection among 2009 Hajj Pilgrims from Southern Iran: a real-time RT-PCR-based study

Abstract: Please cite this paper as: Ziyaeyan et al. (2012) Pandemic 2009 influenza A H1N1 infection among 2009 Hajj Pilgrims from Southern Iran: a real-time RT-PCR-based study. Influenza and Other Respiratory Viruses 6(601), e80–e84. Background Hajj is a mass gathering undertaken annually in Mecca, Saudi Arabia. The 2009 Hajj coincided with both the pandemic influenza A/H1N1 2009 (A(H1N1)pdm09) and seasonal types of influenza A viruses. The interaction between pandemic influenza and Hajj could cause both a high level of mortality among the pilgrims and the spread of infection in their respective countries upon their return home. Objective The present study attempted to determine the point prevalence of A(H1N1)pdm09 among returning Iranian pilgrims, most of whom had been vaccinated for seasonal influenza but not A(H1N1)pdm09. Methods Pharyngeal swabs were collected from 305 pilgrims arriving at the airport in Shiraz, Iran. RNA was extracted from the samples and A(H1N1)pdm09 and other seasonal influenza A viruses were detected using TaqMan real-time PCR. For A(H1N1)pdm09-positive samples, the sensitivity to oseltamivir was also evaluated. Results Subjects included 132 (43·3%) men and 173 (56·7%) women, ranging in age from 24 to 65 years. The A(H1N1)pdm09 virus was detected in five (1·6%) pilgrims and other influenza A viruses in eight (2·6%). All the A(H1N1)pdm09 were sensitive to oseltamivir. Conclusions Only five cases were found to be positive for A(H1N1)pdm09, and it seems unlikely that the arrival of infected pilgrims to their homelands would cause an outbreak of a new wave of infection there. Thus, the low morbidity and mortality rates among the pilgrims could be attributed to the characteristics of A(H1N1)pdm09, which causes morbidity and mortality in a way similar to the seasonal influenza infections, absence of high-risk individuals among the Iranian pilgrims, and the instructions given to them about contact and hand hygiene, and respiratory etiquette.

Isolation of novel triple‐reassortant swine H3N2 influenza viruses possessing the hemagglutinin and neuraminidase genes of a seasonal influenza virus in Vietnam in 2010

Abstract: Please cite this paper as: Ngo et al. (2012) Isolation of novel triple-reassortant swine H3N2 influenza viruses possessing the hemagglutinin and neuraminidase genes of a seasonal influenza virus in Vietnam in 2010. Influenza and Other Respiratory Viruses 6(1), 6–10. Surveillance of swine influenza viruses (SIVs) in 31 pig farms in northern and southern parts of Vietnam was conducted. Six H3N2 influenza A viruses were isolated from a pig farm in southern Vietnam. They were novel genetic reassortants between a triple–reassortant SIV and a human seasonal H3N2 virus. Their hemagglutinin and neuraminidase genes were derived from a human virus circulating around 2004–2006 and the remaining genes from a triple-reassortant SIV that originated in North America. This is the first report describing the isolation of a novel triple-reassortant SIV in Vietnam.

Transmission of pandemic influenza H1N1 (2009) in Vietnamese swine in 2009-2010.

Abstract: Please cite this paper as: Trevennec et al. (2012) Transmission of pandemic influenza H1N1 (2009) in Vietnamese swine in 2009–2010. Influenza and Other Respiratory Viruses 6(5), 348–357. Background The pandemic of 2009 was caused by an H1N1 (H1N1pdm) virus of swine origin. This pandemic virus has repeatedly infected swine through reverse zoonosis, although the extent of such infection in swine remains unclear. Objective This study targets small and commercial pig producers in North Vietnam, in order to estimate the extent of H1N1pdm infection in swine and to identify the risk factors of infection. Methods Virologic and serologic surveillance of swine was carried out in 2009–2010 in pig farms (38 swabs and 1732 sera) and at a pig slaughterhouse (710 swabs and 459 sera) in North Vietnam. The sera were screened using a influenza type A‐reactive ELISA assay, and positive sera were tested using hemagglutination inhibition tests for antibody to a panel of H1‐subtype viruses representing pandemic (H1N1) 2009 (H1N1pdm), triple reassortant (TRIG), classical swine (CS), and Eurasian avian‐like (EA) swine lineages. Farm‐level risk factors were identified using a zero‐inflated negative binomial model. Results We found a maximal seroprevalence of H1N1pdm of 55·6% [95% CI: 38·1–72·1] in the slaughterhouse at the end of December 2009, 2 weeks after the peak of reported human fatalities with H1N1pdm. Farm‐level seroprevalence was 29% [95% CI: 23·2–35·7]. In seropositive farms, within‐herd seroprevalence ranged from 10 to 100%. We identified an increased risk of infection for farms that specialized in fattening and a decreased risk of infection in farms hiring external swine workers. Conclusions Our findings suggest extensive reverse‐zoonotic transmission from humans to pigs with subsequent onward transmission within pig herds.

Body mass index and the incidence of influenza-associated pneumonia in a UK primary care cohort

Abstract: Please cite this paper as: Blumentals WA. et al. (2012) Body mass index and the incidence of influenza-associated pneumonia in a UK primary care cohort. Influenza and Other Respiratory Viruses 6(1), 28–36. Background Accumulating data suggest an association between increased BMI/obesity and morbidity in patients with pandemic (H1N1) 2009 influenza. Information on metabolic status and prognosis in seasonal influenza is lacking, however. Methods A retrospective cohort study was carried out using the UK General Practice Research Database. Patients aged ≥18 with ≥1 recorded BMI in the 12–58 kg/m2 range between January 1, 2000, and December 31, 2007, were observed for an influenza-associated pneumonia diagnosis after the date of baseline BMI, including ‘influenza with pneumonia’ or a diagnosis of ‘pneumonia’ up to 30 days after a diagnosis of ‘influenza’. Results A total of 1 074 315 patients were included, of whom 73·2% were within the reference BMI range or overweight and 2·2% were underweight (<18·5 kg/m2). Pneumonia rates were 32·33–37·48/100 000 in all BMI categories except the underweight (98·29/100 000). Relative to patients with acceptable weight, those who were underweight had an increased pneumonia rate [adjusted IRR = 2·32 (95% CI 1·80–2·94)], while being overweight (BMI = 25·0–29·9 kg/m2) or obese (BMI ≥ 30·0 kg/m2) was associated with a decreased pneumonia rate [adjusted IRR = 0·77 (95% CI 0·68–0·86) and 0·85 (95% CI 0·73–1·00), respectively]. On the other hand, women and obese women with type 2 diabetes had increased pneumonia rates [adjusted IRR = 1·37 (95% CI 1·08–1·72) and 1·47 (95%CI 1·01–2·06), respectively]. Conclusions In contrast to initial data from pandemic influenza, influenza pneumonia, and pneumonia following influenza were the most common in underweight persons, and an apparent decreased rate of pneumonia was noted with increasing BMI categories. Women with type 2 diabetes had increased rates of pneumonia.

Environment: a potential source of animal and human infection with influenza A (H5N1) virus.

Abstract: Please cite this paper as: Horm et al. (2012) Environment: a potential source of animal and human infection with influenza A (H5N1) virus. Influenza and Other Respiratory Viruses 6(6), 442–448. Background Very little is known regarding the persistence of highly pathogenic avian influenza H5N1 viruses in natural settings during outbreaks in tropical countries, although environmental factors may well play a role in the persistence and in the transmission of H5N1 virus. Objective To investigate various environmental compartments surrounding outbreak areas as potential sources for H5N1 virus transmission. Methods Environmental specimens were collected following outbreaks of avian influenza in Cambodia between April 2007 and February 2010. The methods used to concentrate H5N1 virus from water samples were based either on agglutination of the virus with chicken red blood cells or on adsorption on glass wool, followed by an elution-concentration step. An elution-concentration method was used for mud specimens. All samples that tested positive by real-time RT-PCRs (qRT-PCRs) targeting the HA5, M and NA1 genes were inoculated into embryonated hen eggs for virus isolation. Results Of a total of 246 samples, 46 (19%) tested positive for H5N1 by qRT-PCRs. Viral RNA was frequently detected in dust, mud and soil samples from the farms’ environment (respectively, 46%, 31% and 15%). Samples collected from ponds gave a lower proportion of positive samples (6%) as compared to those collected from the farms (24%). In only one sample, infectious virus particles were successfully isolated. Conclusion During H5N1 virus outbreaks, numerous environmental samples surrounding outbreak areas are contaminated by the virus and may act as potential sources for human and/or animal contamination.

Performance of rapid influenza H1N1 diagnostic tests: a meta-analysis

Abstract: Please cite this paper as: Chu et al. (2011) Performance of rapid influenza H1N1 diagnostic tests: a meta-analysis. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00284.x. Background Following the outbreaks of 2009 pandemic H1N1 infection, rapid influenza diagnostic tests have been used to detect H1N1 infection. However, no meta-analysis has been undertaken to assess the diagnostic accuracy when this manuscript was drafted. Methods The literature was systematically searched to identify studies that reported the performance of rapid tests. Random effects meta-analyses were conducted to summarize the overall performance. Results Seventeen studies were selected with 1879 cases and 3477 non-cases. The overall sensitivity and specificity estimates of the rapid tests were 0·51 (95%CI: 0·41, 0·60) and 0·98 (95%CI: 0·94, 0·99). Studies reported heterogeneous sensitivity estimates, ranging from 0·11 to 0·88. If the prevalence was 30%, the overall positive and negative predictive values were 0·94 (95%CI: 0·85, 0·98) and 0·82 (95%CI: 0·79, 0·85). The overall specificities from different manufacturers were comparable, while there were some differences for the overall sensitivity estimates. BinaxNOW had a lower overall sensitivity of 0·39 (95%CI: 0·24, 0·57) compared with all the others (P-value <0·001), whereas QuickVue had a higher overall sensitivity of 0·57 (95%CI: 0·50, 0·63) compared with all the others (P-value = 0·005). Conclusions Rapid tests have high specificity but low sensitivity and thus limited usefulness.

Transmission of influenza A(H1N1) 2009 pandemic viruses in Australian swine.

Abstract: Please cite this paper as: Deng et al (2012) Transmission of influenza A(H1N1) 2009 pandemic viruses in Australian swine Influenza and Other Respiratory Viruses 6(3), e42–e47 Background Swine have receptors for both human and avian influenza viruses and are a natural host for influenza A viruses The 2009 influenza A(H1N1) pandemic (H1N1pdm) virus that was derived from avian, human and swine influenza viruses has infected pigs in various countries Objectives To investigate the relationship between the H1N1pdm viruses isolated from piggery outbreaks in Australia and human samples associated with one of the outbreaks by phylogenetic analysis, and to determine whether there was any reassortment event occurring during the human-pig interspecies transmission Methods Real-time RT-PCR and full genome sequencing were carried out on RNA isolated from nasal swabs and/or virus cultures Phylogenetic analysis was performed using the Geneious package Results The influenza H1N1pdm outbreaks were detected in three pig farms located in three different states in Australia Further analysis of the Queensland outbreak led to the identification of two distinct virus strains in the pigs Two staff working in the same piggery were also infected with the same two strains found in the pigs Full genome sequence analysis on the viruses isolated from pigs and humans did not identify any reassortment of these H1N1pdm viruses with seasonal or avian influenza A viruses Conclusions This is the first report of swine infected with influenza in Australia and marked the end of the influenza-free era for the Australian swine industry Although no reassortment was detected in these cases, the ability of these viruses to cross between pigs and humans highlights the importance of monitoring swine for novel influenza infections

Journalists’ views about reporting avian influenza and a potential pandemic: a qualitative study

Abstract: Please cite this paper as: Hooker et al. (20XX) Journalists’ views about reporting avian influenza and a potential pandemic: a qualitative study. Influenza and Other Respiratory Viruses 6(3), 224–229. Background The mass media is a key component of any public communication strategy for influenza or other respiratory illnesses, but coverage can be variable. In this study, we explored the factors that influenced journalists’ coverage of avian influenza as a model for coverage of a potential influenza pandemic. Methods This study involved semi-structured interviews with 16 journalists from major Australian print, radio and television media organisations reporting on avian influenza and pandemic planning. Journalists, including reporters, editors and producers, were interviewed between October 2006 and August 2007. Thematic analysis was used to draw out major lessons for health communicators. Results Coverage of avian influenza was influenced by a small set of news values: catastrophic potential, cultural and geographical proximity, unfamiliarity and uncertainty. Lack of novelty and the absence of compelling images led to a decline in coverage. Journalists expressed concerns about the accuracy and impacts of reporting, but saw as critically important, their primary role as informants. They hence emphasised the importance of journalistic independence. Journalists all intended to continue working in a pandemic. Conclusions Health experts need to adapt their timetables and resources to journalists’ needs to improve their mutual communication. In crisis situations, journalists communicate with the public efficiently and effectively, but expert and journalistic views on the role and content of coverage may diverge in the post-acute, reflective phase of a crisis.

Is abdominal obesity associated with the 2009 influenza A (H1N1) pandemic in Korean school-aged children?

Abstract: Please cite this paper as: Kim et al. (2012) Is abdominal obesity associated with the 2009 influenza A (H1N1) pandemic in Korean school-aged children? Influenza and Other Respiratory Viruses 6(5), 313–317. Objective Given their medical vulnerabilities, we investigated the epidemiological factors related to H1N1 infection in school-aged children. Methods This study analyzed data collected on 7448 school-aged children in South Korea between 18 November and 8 December 2009. Results We found that H1N1 infection was associated with body mass index (BMI), waist circumference (WC), the use of facemasks, contact history with H1N1-infected persons, and overseas travel history (P < 0·05). In addition, WC quartiles were significantly associated with H1N1 infection after adjusting for BMI and other confounding variables [OR (95% CI): 1·00, 1·10 (0·72–1·45), 1·13 (0·76–1·67), and 2·71 (1·74–4·24), respectively). Conclusions Abdominal obesity and the use of facemasks appear to be independently associated with H1N1 infection in school-aged children. We infer that providing education on wearing facemasks and specific planning for abdominally obese children and adolescents may be effective means of reducing the spread of the influenza pandemic in school-aged children.

Maternal outcomes among pregnant women receiving live attenuated influenza vaccine.

Abstract: Please cite this paper as: Toback et al. (2012) Maternal outcomes among pregnant women receiving live attenuated influenza accine. Influenza and Other Respiratory Viruses 6(1), 44–51. Background Although the live attenuated influenza vaccine (LAIV) prescribing information contains warnings/precautions against use during pregnancy, administration of LAIV to pregnant women does occur. Data regarding maternal outcomes after LAIV administration during pregnancy are limited. Objectives Maternal outcomes after LAIV vaccination during pregnancy were examined. Methods Data from a health insurance claims database that covers approximately 50 million individuals were analyzed for the six influenza seasons from 2003–2004 through 2008–2009. Emergency department (ED) visits and hospitalizations occurring within 42 days of vaccination were analyzed by primary diagnosis; outcomes were categorized as cardiopulmonary, obstetric, and other. Cohort characteristics were analyzed using descriptive statistics. Results Of 834 999 pregnancies identified, 138 (0·017%) were among women who received LAIV vaccinations. Of the 138 pregnant women, 13% were ≤19 years, 67% were 20–34 years, and 20% were ≥35 years of age. Eight events occurred within 42 days of vaccination: one ED visit for bronchitis, two hospitalizations for hyperemesis gravidarum and premature labor, and five ED visits/hospitalizations for common medical conditions. All outcomes identified after LAIV exposure occurred at rates similar to rates in unvaccinated pregnant women reported in the medical literature. Conclusions Administration of LAIV to pregnant women is rare; the rate has remained constant since 2004–2005. In this cohort, there was no evidence of significant maternal adverse outcomes after receipt of LAIV. These data may offer some reassurance to providers and pregnant women in the event of inadvertent LAIV administration, but do not support the routine use of LAIV in pregnant women.

The mucosal and systemic immune responses elicited by a chitosan-adjuvanted intranasal influenza H5N1 vaccine.

Abstract: Please cite this paper as: Svindland et al. The mucosal and systemic immune responses elicited by a chitosan-adjuvanted intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750-2659.2011.00271.x. Background Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority (Vaccine 2005;23:1529). Dose-sparing strategies and an efficient mass-vaccination regime will be paramount to reduce the morbidity and mortality of a future H5N1 pandemic. Objectives This study has investigated the immune response and the dose-sparing potential of a chitosan-adjuvanted intranasal H5N1 (RG-14) subunit (SU) vaccine in a mouse model. Methods Groups of mice were intranasally immunised once or twice with a chitosan (5 mg/ml)-adjuvanted SU vaccine [7·5, 15 or 30 μg haemagglutinin (HA)] or with a non-adjuvanted SU vaccine (30 μg HA). For comparison, another group of mice were intranasally immunised with a whole H5N1 (RG-14) virus (WV) vaccine (15 μg HA), and the control group consisted of unimmunised mice. Results The chitosan-adjuvanted SU vaccine induced an immune response superior to that of the non-adjuvanted SU vaccine. Compared with the non-adjuvanted SU group, the chitosan-adjuvanted SU vaccine elicited higher numbers of influenza-specific antibody-secreting cells (ASCs), higher concentrations of local and systemic antibodies and correspondingly an improved haemagglutination inhibition (HI) and single radial haemolysis (SRH) response against both the homologous vaccine strain and drifted H5 strains. We measured a mixed T-helper 1/T-helper 2 cytokine response in the chitosan-adjuvanted SU groups, and these groups had an increased percentage of virus-specific CD4+ T cells producing two Thelper 1 (Th1) cytokines simultaneously compared with the non-adjuvanted SU group. Overall, the WV vaccine induced higher antibody concentrations in sera and an HI and SRH response similar to that of the chitosan-adjuvanted SU vaccine. Furthermore, the WV vaccine formulation showed a stronger bias towards a T-helper 1 profile than the SU vaccine and elicited the highest frequencies of CD4+ Th1 cells simultaneously secreting three different cytokines (INFγ+, IL2+ and INFα+). As expected, two immunisations gave a better immune response than one in all groups. The control group had very low or not detectable results in the performed immunoassays. Conclusion The cross-clade serum reactivity, improved B- and T-cell responses and dose-sparing potential of chitosan show that a chitosan-adjuvanted intranasal influenza vaccine is a promising candidate vaccine for further preclinical development.

Circulation of avian influenza viruses in wild birds in Inner Niger Delta, Mali

Abstract: Background Avian influenza viruses (AIV) have been detected in wild birds in West Africa during the northern winter, but no information is available on a potential year-round circulation of AIV in West Africa. Such year-round circulation would allow reassortment opportunities between strains circulating in Afrotropical birds and strains imported by migratory birds wintering in West Africa. Objective and Method A 2-year longitudinal survey was conducted in the largest continental wetland of West Africa, the Inner Niger Delta in Mali, to determine the year-round circulation of AIV in wild birds. Results and Conclusions Avian influenza virus RNA was detected during all periods of the year. Very low prevalence was detected during the absence of the migratory wild birds. However, a year-round circulation of AIV seems possible in West Africa, as shown in other African regions. West Africa may hence be another potential site of reassortment between AIV strains originating from both Afro-tropical and Eurasian regions. (Resume d'auteur)

Viral load at diagnosis and influenza A H1N1 (2009) disease severity in children.

Abstract: To assess viral load at diagnosis (VLAD) as a biomarker of novel influenza disease severity, epidemiologic and clinical data of admitted patients <18 years old with Influenza A H1N1 (2009) infection and respiratory symptoms were prospectively collected in a single pediatric tertiary hospital, from weeks 30-51 of 2009. Seventy patients were included. VLAD in children who had symptoms for ≥ 5 days was an accurate parameter distinguishing the patients who required mechanical ventilation (MV) from those who did not required it (area under the ROC curve: 0.73; P=0.03). Having <4.5 log10 copies/ml with ≥ 5 days of symptoms was associated with a lower risk of requiring MV.