Case registry systems for pandemic influenza A(H1N1)pdm09 in Europe: are there lessons for the future?

Countries across Europe developed a range of database systems to register pandemic influenza A(H1N1)pdm09 cases. Anecdotal reports indicate that some systems were not as useful as expected. This was a cross-sectional, semi-structured survey of health professionals who collected and reported pandemic influenza A(H1N1)pdm09 cases in 23 countries within the 27 European Union (EU) Member States plus Norway. We describe here the experiences of using pandemic case register systems developed before and during the pandemic, whether the systems were used as intended and, what problems, if any, were encountered. We conducted the survey to identify improvements that could be made to future pandemic case registers at national and EU level. Despite many inter-country differences, 17 respondents felt that a standardised case register template incorporating a limited number of simple standard variables specified in advance and agreed between the World Health Organization and the European Centre for Disease Prevention and Control could be useful. Intra- and inter-country working groups could facilitate information exchange, clearer system objectives and improved interoperability between systems

Parallel evolution in the emergence of highly pathogenic avian influenza A viruses

Abstract: Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here, we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs evolve independently from low-pathogenic ancestors via acquisition of polybasic cleavage sites. Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the viral genome. We combine phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein structure. Our resulting mutational panel may help to reveal new links between virulence evolution and other traits, and raises the possibility of predicting aspects of AIV evolution

High probability of avian influenza virus (H7N7) transmission from poultry to humans active in disease control on infected farms

textabstractAn epizootic of avian influenza (H7N7) caused a large number of human infections in The Netherlands in 2003. We used data from this epizootic to estimate infection probabilities for persons involved in disease control on infected farms. Analyses were based on databases containing information on the infected farms, person-visits to these farms, and exposure variables (number of birds present, housing type, poultry type, depopulation method, period during epizootic). Case definition was based on self-reported conjunctivitis and positive response to hemagglutination inhibition assay. A high infection probability was associated with clinical inspection of poultry in the area surrounding infected flocks (7.6%; 95% confidence interval [CI], 1.4%-18.9%) and active culling during depopulation (6.2%; 95% CI, 3.7%-9.6%). Low probabilities were estimated for management of biosecurity (0.0%; 95% CI, 0.0%-1.0%) and cleaning assistance during depopulation (0.0%; 95% CI, 0.0%-9.2%). No significant association was observed between the probability of infection and the exposure variables

Human to human transmission of avian influenza A/H7N7, The Netherlands, 2003.

An outbreak of highly pathogenic avian influenza A virus subtype H7N7 began in poultry farms in the Netherlands in 2003. Virus infection was detected by RT-PCR in 86 poultry workers and three household contacts of PCR-positive poultry workers, mainly associated with conjunctivitis. To determine the magnitude of and risk factors for human-to-human transmission of influenza A/H7N7 in the Netherlands, a retrospective cohort study among household members of infected poultry workers was undertaken. In total, 33 (58.9%) of 56 (among 62) participants who provided blood samples had positive H7 serology, using single convalescent serum samples obtained at least 3 weeks after onset of symptoms of the index case. Eight household members (12.9%) reported symptoms (conjunctivitis and/or ILI), of which four of five (80.0%) tested seropositive. On univariate analysis, significant risk factors for seropositivity included having at least two toilets, a pet bird, and using cloth handkerchiefs. It was not possible to obtain a stable model for binomial regression for the outcome of A/H7N7 infection. Further seroprevalence studies among contacts of asymptomatic H7 cases should be conducted. (aut.ref.

High probability of avian influenza virus (H7N7) transmission from poultry to humans active in disease control on infected farms

An epizootic of avian influenza (H7N7) caused a large number of human infections in The Netherlands in 2003. We used data from this epizootic to estimate infection probabilities for persons involved in disease control on infected farms. Analyses were based on databases containing information on the infected farms, person-visits to these farms, and exposure variables (number of birds present, housing type, poultry type, depopulation method, period during epizootic). Case definition was based on self-reported conjunctivitis and positive response to hemagglutination inhibition assay. A high infection probability was associated with clinical inspection of poultry in the area surrounding infected flocks (7.6%; 95% confidence interval [CI], 1.4%-18.9%) and active culling during depopulation (6.2%; 95% CI, 3.7%-9.6%). Low probabilities were estimated for management of biosecurity (0.0%; 95% CI, 0.0%-1.0%) and cleaning assistance during depopulation (0.0%; 95% CI, 0.0%-9.2%). No significant association was observed between the probability of infection and the exposure variables

Measurement of antibodies to avian influenza virus A(H7N7) in humans by hemagglutination inhibition test.

During the epizootic of highly pathogenic avian influenza A(H7N7) in 2003 in The Netherlands, RT-PCR and culture confirmed infection was detected in 89 persons who were ill. A modified hemagglutination inhibition (HI) test using horse erythrocytes and 2 hemagglutinating units of virus was applied to assess retrospectively the extent of human (subclinical) infection. Validation of the HI-test with sera from 34 RT-PCR and culture confirmed A(H7) infected persons and sera from 100 persons from a human influenza vaccine trial in autumn 2002 showed that this HI-test had a sensitivity of 85% and a specificity of 100% when using a cut-off titer of > or =10. Using this cut-off value, A(H7) specific antibodies were detected in 49% of 508 persons exposed to poultry and in 64% of 63 persons exposed to A(H7) infected persons. Correlation of seropositivity with the occurrence of eye symptoms in exposed persons who had not received antiviral prophylaxis and of reduced seropositivity with taking antiviral prophylaxis provided further evidence that the A(H7) HI antibody titers were real. In conclusion, by applying an HI-test using horse erythrocytes human antibodies against the avian A(H7N7) virus were detected with high sensitivity and specificity in an unexpectedly high proportion of exposed persons