Surveillance for severe acute respiratory infections (SARI) in hospitals in the WHO European region - an exploratory analysis of risk factors for a severe outcome in influenza-positive SARI cases.

BACKGROUND: The 2009 H1N1 pandemic highlighted the need to routinely monitor severe influenza, which lead to the establishment of sentinel hospital-based surveillance of severe acute respiratory infections (SARI) in several countries in Europe. The objective of this study is to describe characteristics of SARI patients and to explore risk factors for a severe outcome in influenza-positive SARI patients. METHODS: Data on hospitalised patients meeting a syndromic SARI case definition between 2009 and 2012 from nine countries in Eastern Europe (Albania, Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Romania, Russian Federation and Ukraine) were included in this study. An exploratory analysis was performed to assess the association between risk factors and a severe (ICU, fatal) outcome in influenza-positive SARI patients using a multivariate logistic regression analysis. RESULTS: Nine countries reported a total of 13,275 SARI patients. The majority of SARI patients reported in these countries were young children. A total of 12,673 SARI cases (95%) were tested for influenza virus and 3377 (27%) were laboratory confirmed. The majority of tested SARI cases were from Georgia, the Russian Federation and Ukraine and the least were from Kyrgyzstan. The proportion positive varied by country, season and age group, with a tendency to a higher proportion positive in the 15+ yrs age group in six of the countries. ICU admission and fatal outcome were most often recorded for influenza-positive SARI cases aged > 15 yrs. An exploratory analysis using pooled data from influenza-positive SARI cases in three countries showed that age > 15 yrs, having lung, heart, kidney or liver disease, and being pregnant were independently associated with a fatal outcome. CONCLUSIONS: Countries in Eastern Europe have been able to collect data through routine monitoring of severe influenza and results on risk factors for a severe outcome in influenza-positive SARI cases have identified several risk groups. This is especially relevant in the light of an overall low vaccination uptake and antiviral use in Eastern Europe, since information on risk factors will help in targeting and prioritising vulnerable populations.

The community impact of the 2009 influenza pandemic in the WHO European region: a comparison with historical seasonal data from 28 countries.

BACKGROUND: The world has recently experienced the first influenza pandemic of the 21st century that lasted 14 months from June 2009 to August 2010. This study aimed to compare the timing, geographic spread and community impact during the winter wave of influenza pandemic A (H1N1) 2009 to historical influenza seasons in countries of the WHO European region. METHODS: We assessed the timing of pandemic by comparing the median peak of influenza activity in countries of the region during the last seven influenza seasons. The peaks of influenza activity were selected by two independent researchers using predefined rules. The geographic spread was assessed by correlating the peak week of influenza activity in included countries against the longitude and latitude of the central point in each country. To assess the community impact of pandemic influenza, we constructed linear regression models to compare the total and age-specific influenza-like-illness (ILI) or acute respiratory infection (ARI) rates reported by the countries in the pandemic season to those observed in the previous six influenza seasons. RESULTS: We found that the influenza activity reached its peak during the pandemic, on average, 10.5 weeks (95% CI 6.4-14.2) earlier than during the previous 6 seasons in the Region, and there was a west to east spread of pandemic A(H1N1) influenza virus in the western part of the Region. A regression analysis showed that the total ILI or ARI rates were not higher than historical rates in 19 of the 28 countries. However, in countries with age-specific data, there were significantly higher consultation rates in the 0-4 and/or 5-14 age groups in 11 of the 20 countries. CONCLUSIONS: Using routine influenza surveillance data, we found that pandemic influenza had several differential features compared to historical seasons in the region. It arrived earlier, caused significantly higher number of outpatient consultations in children in most countries and followed west to east spread that was previously observed during some influenza seasons with dominant A (H3N2) ifluenza viruses. The results of this study help to understand the epidemiology of 2009 influenza pandemic and can be used for pandemic preparedness planning.

Influenza in long-term care facilities.

Long-term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long-term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence.

Improving the representativeness of influenza viruses shared within the WHO Global Influenza Surveillance and Response System.

BACKGROUND: Sharing influenza viruses within the WHO Global Influenza Surveillance and Response System is crucial for monitoring evolution of influenza viruses. OBJECTIVES: Analysis of timeliness and geographic representativeness of viruses shared by National Influenza Centres (NICs) in the WHO European Region with the London WHO Collaborating Centre for Reference and Research on Influenza for the Northern Hemisphere's 2010-2011 and 2011-2012 influenza seasons. MATERIALS AND METHODS: Data from NICs on influenza-positive specimens shared with WHO CC London for the above-mentioned influenza seasons were analyzed for timeliness of sharing with respect to the February deadline (31 January) for inclusion in the WHO consultations on the composition of influenza virus vaccines for the Northern Hemisphere and geographic representativeness. RESULTS: The 2010-2011 and 2011-2012 seasons were different in terms of the seasonal pattern, the timing of the epidemic, and the dominant virus. Consistent patterns of virus sharing across the seasons were observed. Approximately half the viruses collected before the deadline were not shared within the deadline; the average delay between date of specimen collection and shipment receipt was 3 and 1·5 months for the first and second season, respectively. CONCLUSION: A baseline was provided for future work on enhancement of specimen sharing in the WHO European Region and improving the vaccine virus selection process. Greater insight into virus selection criteria applied by countries and the causes of delays in shipment are needed to understand the representativeness of viruses shared and to assess the importance of this for vaccine strain selection.

Production of recombinant H1 parvovirus stocks devoid of replication-competent viruses.

Vector and helper plasmids for the production of recombinant H1 (rH1) parvovirus, an oncolytic virus and candidate vector for cancer gene therapy, were constructed with the aim of reducing the contamination of these preparations with replication-competent viruses (RCV). Split-helper plasmids were constructed by manipulating the splicing signals for the capsid proteins such that VP1 and VP2 were expressed from separate plasmids. H1 vectors with similarly mutated splice sites were packaged, using the split-helper plasmids, and the resulting recombinant H1 viruses were completely free of RCV because the generation of recombinants expressing both capsid proteins was prevented. Vector yields of rH1 produced with split-helper plasmids in combination with splice site-modified vectors were similar (in the range of 10(7) replication units/ml) to yields of rH1 produced with the standard vector/helper pair, in which case significant levels of RCV were generated (10(4)-10(5) plaque-forming units/ml). To assess the functionality of this approach in vivo, rH1 was produced that contained the human interleukin 2 (IL-2) transgene and that was devoid of RCV. This IL-2-carrying rH1 vector expressed IL-2 efficiently in human tumor cells (HeLa) in vitro and generated antitumor responses in nude mice xenografted with HeLa cells that had been infected ex vivo with this virus. These results should allow the large-scale production of recombinant oncotropic parvoviruses and their assessment for the gene therapy of cancer in a clinical setting.

Risk factors associated with fatal influenza, Romania, October 2009-May 2011.

BACKGROUND: Limited data are available from Central and Eastern Europe on risk factors for severe complications of influenza. Such data are essential to prioritize prevention and treatment resources and to adapt influenza vaccination recommendations. OBJECTIVES: To use sentinel surveillance data to identify risk factors for fatal outcomes among hospitalized patients with severe acute respiratory infections (SARI) and among hospitalized patients with laboratory-confirmed influenza. METHODS: Retrospective analysis of case-based surveillance data collected from sentinel hospitals in Romania during the 2009/2010 and 2010/2011 winter influenza seasons was performed to evaluate risk factors for fatal outcomes using multivariate logistic regression. RESULTS: During 2009/2010 and 2010/2011, sentinel hospitals reported 661 SARI patients of which 230 (35%) tested positive for influenza. In the multivariate analyses, infection with influenza A(H1N1)pdm09 was the strongest risk factor for death among hospitalized SARI patients (OR: 6·6; 95% CI: 3·3-13·1). Among patients positive for influenza A(H1N1)pdm09 virus infection (n = 148), being pregnant (OR: 7·1; 95% CI: 1·6-31·2), clinically obese (OR: 2·9;95% CI: 1·6-31·2), and having an immunocompromising condition (OR: 3·7;95% CI: 1·1-13·4) were significantly associated with fatal outcomes. CONCLUSION: These findings are consistent with several other investigations of risk factors associated with influenza A(H1N1)pdm09 virus infections. They also support the more recent 2012 recommendations by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) that pregnant women are an important risk group for influenza vaccination. Ongoing sentinel surveillance can be useful tool to monitor risk factors for complications of influenza virus infections during each influenza season, and pandemics as well.