Eeva Broberg

Specific serology for emerging human coronaviruses by protein microarray

The influenza season 2014/15 started in Europe in week 50 2014 with influenza A(H3N2) viruses predominating. The majority of the A(H3N2) viruses characterised antigenically and/or genetically differ from the northern hemisphere vaccine component which may result in reduced vaccine effectiveness for the season. We therefore anticipate that this season may be more severe than the 2013/14 season. Treating influenza with antivirals in addition to prevention with vaccination will be important.

Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting

Please cite this paper as: Laurie et al. (2013) Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting. Influenza and Other Respiratory Viruses 7(2) 211–224.

The consortium for the standardization of influenza seroepidemiology (CONSISE): a global partnership to standardize influenza seroepidemiology and develop influenza investigation protocols to inform public health policy

CONSISE – The consortium for the Standardization of Influenza Seroepidemiology – is a global partnership to develop influenza investigation protocols and standardize seroepidemiology to inform health policy. This international partnership was formed in 2011 and was created out of a need, identified during the 2009 H1N1 pandemic, for timely seroepidemiological data to better estimate pandemic virus infection severity and attack rates to inform policy decisions. CONSISE has developed into a consortium of two interactive working groups: epidemiology and laboratory, with a steering committee composed of individuals from several organizations. CONSISE has had two international meetings with more planned for 2013. We seek additional members from public health agencies, academic institutions and other interested parties.

Guidance for clinical and public health laboratories testing for influenza virus antiviral drug susceptibility in Europe

Two classes of antiviral drugs are licensed in Europe for treatment and prophylaxis of influenza; the M2 ion-channel blockers amantadine and rimantadine acting against type A influenza viruses only and the neuraminidase enzyme inhibitors zanamivir and oseltamivir acting against type A and type B influenza viruses. This guidance document was developed for but not limited to the European Union (EU) and other European Economic Area (EEA) countries on how and when to test for influenza virus antiviral drug susceptibility. It is aimed at clinical and influenza surveillance laboratories carrying out antiviral drug susceptibility testing on influenza viruses from patients suspected of harbouring viruses with reduced susceptibility or for the monitoring of the emergence of such among circulating viruses, respectively. Therefore, the guidance should not be read as a directive or an algorithm for treatment. Monitoring for emergence of influenza viruses with reduced drug susceptibility in hospitalized cases is crucial for decision making on possible changes to antiviral treatment. Therefore, it is important to test for antiviral susceptibility in certain patient groups, such as patients treated with influenza antiviral drugs. It is also important to determine the frequency of viruses with natural (not related to drug use) reduced susceptibility among community and hospitalized cases, as this knowledge is essential for making empirical antiviral treatment decisions. Furthermore, testing of specimens from community influenza patients is needed to determine the frequency of viruses with reduced susceptibility and good viral fitness that are readily transmissible, as they may become dominant among circulating viruses. Phenotypic neuraminidase enzyme inhibition assays are recommended to determine the level of inhibition of the neuraminidase enzyme by antiviral drugs as a measure of drug susceptibility of the virus. Genotypic assays are recommended to identify amino acid substitutions in the neuraminidase and M2 ion-channel proteins that have been associated with reduced antiviral susceptibility previously. By 2012 all circulating seasonal influenza A(H1N1)pdm09 and A(H3N2) viruses were naturally resistant to the M2 ion-channel blockers, so priority should be given to testing for neuraminidase inhibitor susceptibility.

Predominance of influenza A(H1N1)pdm09 virus genetic subclade 6B.1 and influenza B/Victoria lineage viruses at the start of the 2015/16 influenza season in Europe

Influenza A(H1N1)pdm09 viruses predominated in the European influenza 2015/16 season. Most analysed viruses clustered in a new genetic subclade 6B.1, antigenically similar to the northern hemisphere vaccine component A/California/7/2009. The predominant influenza B lineage was Victoria compared with Yamagata in the previous season. It remains to be evaluated at the end of the season if these changes affected the effectiveness of the vaccine for the 2015/16 season.

Influenza season 2012–2013 in Europe: moderate intensity, mixed (sub)types

SUMMARY This paper summarizes influenza activity in the European Union/European Economic Area (EU/EEA) in 2012–2013. The influenza season 2012–2013 in Europe lasted from early December to late April. Overall the severity of the season could be described as moderate, based on the ILI/ARI consultation rates and the percentage of sentinel specimens positive for influenza compared to previous seasons. Both influenza A and B viruses circulating accounted for 47% and 53% of positive sentinel specimens, respectively, with both A(H1) and A(H3) varying for dominance. Compared to outpatients, the proportion of laboratory-confirmed influenza hospitalized cases infected by A(H1N1)pdm09 was significantly higher in middle-aged patients (33% vs. 17%, χ2 = 66·6, P < 0·01). Despite a relatively good match between vaccine and circulating strains, vaccine effectiveness was estimated to be moderate.

Age-specific differences in influenza virus type and subtype distribution in the 2012/2013 season in 12 European countries

SUMMARY The epidemiology of seasonal influenza is influenced by age. During the influenza season, the European Influenza Surveillance Network (EISN) reports weekly virological and syndromic surveillance data [mostly influenza-like illness (ILI)] based on national networks of sentinel primary-care providers. Aggregated numbers by age group are available for ILI, but not linked to the virological data. At the end of the influenza season 2012/2013, all EISN laboratories were invited to submit a subset of their virological data for this season, including information on age. The analysis by age group suggests that the overall distribution of circulating (sub)types may mask substantial differences between age groups. Thus, in cases aged 5–14 years, 75% tested positive for influenza B virus whereas all other age groups had an even distribution of influenza A and B viruses. This means that the intepretation of syndromic surveillance data without age group-specific virological data may be misleading. Surveillance at the European level would benefit from the reporting of age-specific influenza data.

Surveillance of hospitalised severe cases of influenza A(H1N1)pdm09 and related fatalities in nine EU countries in 2010–2011

Please cite this paper as: Snacken et al. (2012) Surveillance of hospitalised severe cases of Influenza A(H1N1)pdm09 and related fatalities in nine EU countries in 2010–2011. Influenza and Other Respiratory Viruses 6(601), e93–e96.

Laboratory preparedness in EU/EEA countries for detection of novel avian influenza A(H7N9) virus, May 2013.

Following human infections with novel avian influenza A(H7N9) viruses in China, the European Centre for Disease Prevention and Control, the World Health Organization (WHO) Regional Office for Europe and the European Reference Laboratory Network for Human Influenza (ERLI-Net) rapidly posted relevant information, including real-time RT-PCR protocols. An influenza RNA sequence-based computational assessment of detection capabilities for this virus was conducted in 32 national influenza reference laboratories in 29 countries, mostly WHO National Influenza Centres participating in the WHO Global Influenza Surveillance and Response System (GISRS). Twenty-seven countries considered their generic influenza A virus detection assay to be appropriate for the novel A(H7N9) viruses. Twenty-two countries reported having containment facilities suitable for its isolation and propagation. Laboratories in 27 countries had applied specific H7 real-time RT-PCR assays and 20 countries had N9 assays in place. Positive control virus RNA was provided by the WHO Collaborating Centre in London to 34 laboratories in 22 countries to allow evaluation of their assays. Performance of the generic influenza A virus detection and H7 and N9 subtyping assays was good in 24 laboratories in 19 countries. The survey showed that ERLI-Net laboratories had rapidly developed and verified good capability to detect the novel A(H7N9) influenza viruses.

Evaluation of influenza virus antiviral susceptibility testing in Europe: Results from the first external quality assessment exercise

BACKGROUND The first antiviral susceptibility testing external quality assessment (EQA) was held for European influenza reference laboratories during winter 2010/11. OBJECTIVES To assess European network influenza antiviral susceptibility testing capability and provide participants with an independent performance evaluation. STUDY DESIGN The EQA panel contained ten coded specimens of inactivated human influenza A and B viruses with reduced susceptibility to neuraminidase inhibitors (NAI), or adamantanes. Twenty-four laboratories from 19 member states of the WHO European region analysed the panel using phenotypic (determination of 50% inhibitory concentration (IC(50)) values by neuraminidase (NA) enzyme inhibition assay) and/or genotypic methods. RESULTS All 24 laboratories returned genotypic data for A(H1N1)pdm09 influenza virus, 18 (75%) for former seasonal A(H1N1), 16 (67%) for A(H3N2) and 15 (63%) for influenza B virus, correctly identifying NAI or adamantane reduced susceptibility-associated substitutions in the NA (mean 84%; range 52-100%) or M2 (mean 85%; range 73-94%), respectively. Thirteen laboratories (54%) returned phenotypic NAI susceptibility data. Despite inter-laboratory and inter-assay IC(50) value variation, all 13 laboratories correctly identified oseltamivir reduced susceptibility/resistance in pure preparations of A(H1N1) oseltamivir-resistant viruses. However, only 11 (85%) identified oseltamivir reduced susceptibility/resistance in a mixture of A(H1N1)pdm09 oseltamivir-sensitive/-resistant viruses. Furthermore, 3 laboratories (23%) considered oseltamivir-sensitive influenza B virus reduced susceptible/resistant. CONCLUSIONS Detection of NA-H275Y in A(H1N1) viruses was achieved by most laboratories. IC(50) values and interpretation thereof varied for a sensitive/resistant virus mixture and for influenza B virus. The results of this exercise will assist harmonisation of antiviral susceptibility testing, interpretation and reporting within the European network through targeted training.