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Clin Microbiol Infect 2012; 18: 177-183 Abstract We looked for evidence of antibodies to the 2009 influenza A/H1N1 pandemic virus in panels of sera from individuals living in metropolitan France, obtained either before, during or after the epidemic, using standard haemagglutination inhibition and microneutralization tests. The difference between seroprevalence values measured in post- and pre-epidemic panels was used as an estimate of seroconversion rate in different age groups (23.4% (0-24 years, age-group 0); 16.5% (25-34); 7.9% (35-44); 7.2% (45-54); 1.6% (55-64); and 3.1% (>65)), confirming that the distribution of cases in different age groups was similar to that of the seasonal H1N1 virus. During the pre-pandemic period low-titre cross-reactive antibodies were present in a large proportion of the population (presumably acquired against seasonal H1N1) whereas cross-reactive antibodies were detected in individuals over the age of 65 years with significantly higher prevalence and serological titres (presumably acquired previously against Spanish flu-related H1N1 strains). Clinical data and analysis of post-pandemic seroprevalence showed that few of these latter patients were infected by the influenza virus during the epidemic. In contrast, the majority of both clinical cases and seroconversions were recorded in the 0-24 age group and a global inverse relationship between prevalence of antibodies to pH1N1 in the pre-pandemic period and rate of seroconversion was observed amongst age groups. Our results emphasize the complex relationships involved in antigenic reactivity to pandemic and seasonal H1N1 viral antigens; hence the difficulty in distinguishing between low-titre specific and cross-reactive antibodies, establishing precise seroprevalence numbers and fully understanding the relationship between previous immunity to seasonal viruses and protection against the novel variant. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: E81-E83 Abstract Rapid documentation of respiratory specimens can have an impact on the management of patients and their relatives in terms of preventive and curative measures. We compared the results of the Xpert® Flu assay (Cepheid) with three real-time RT-PCR assays using 127 nasopharyngeal samples, of which 75 were positive for influenza A (with 52 identified as A/H1N1-2009) and 52 were positive for influenza B. The Xpert® Flu assay presented a quasi-absence of non-interpretable tests, and showed sensitivity and specificity of 100% and 100% for Flu A, 98.4% and 100% for A/H1N1-2009, and 80.7% and 100% for Flu B. [ABSTRACT FROM AUTHOR]

Introduction: Haemagglutination-inhibition (HI) antibody titer is a correlate of protection against influenza; its persistence after infection or vaccination is important to determining susceptibility to subsequent infection. Few studies, however, have reported longitudinal data regarding the magnitude and duration of HI protection following natural seasonal influenza A infection., Methods: Using French influenza cohort study data collected from 2008 to 2010, we investigated persistence of serological protection among subjects according to influenza-like illness (ILI) and laboratory-confirmed seasonal 2007 influenza A(H1N1) infection status at inclusion in 2008 (ILI-A(H1N1) positive, ILI-A(H1N1) negative, or no-ILI). Antibody titers against seasonal 2007 A(H1N1) were determined using the HI technique for sera. Regression models for interval-censored data were used to estimate geometric mean titers (GMT) for HI assays. A logistic regression model adjusted for age group (subjects <30, 30-50 and >50 years old) was used to quantify the association between HI titer and protection against infection., Results: Based on 310 total subjects, influenza A(H1N1) infection was confirmed in 39 of 115 ILI subjects at inclusion. GMT associated with 50% probability of protection among ILI subjects decreased with age group (subjects <30 yo: GMT of 40.8 was associated with 50% [95CI: 29.3%; 70.7%] probability of protection, subjects 30-50 yo: 26.8 [95CI: 34.4%; 65.6%] and subjects >50 yo: 8.9 [95CI: 15.3%; 84.7%]). GMT declined after the first annual study visit among ILI-A(H1N1) positive subjects but remained higher compared to inclusion at the 2010 study visit (41.5 [95CI: 34.8; 49.5], p=0.0157). GMT remained stable among ILI-A(H1N1) negative subjects (p=0.7502), but decreased among no-ILI subjects (p<0.0001)., Conclusion: Our results confirm the positive relationship between HI titer and probability of protection among naturally infected subjects, and provides evidence that protection associated with HI titer varies with age. This longitudinal analysis suggests the rise in HI titers following seasonal 2007 influenza A(H1N1) infection may persist into subsequent influenza seasons., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Obtaining a comprehensive quantitative figure of the determinants of influenza infection will help identify priority targets for future influenza mitigation interventions. We developed an original causal model integrating highly diverse factors and their dependencies, to identify the most critical determinants of pandemic influenza infection (H1N1pdm09) during the 2010-2011 influenza season., Methods: We used data from 601 households (1450 participants) included in a dedicated cohort. Structural equations were used to model direct and indirect relationships between infection and risk perception, compliance with preventive behaviours, social contacts, indoor and outdoor environment, sociodemographic factors and pre-epidemic host susceptibility. Standardised estimates (βstd) were used to assess the strength of associations (ranging from -1 for a completely negative association to 1 for a completely positive association)., Results: Host susceptibility to H1N1pdm09 and compliance with preventive behaviours were the only two factors directly associated with the infection risk (βstd=0.31 and βstd=-0.21). Compliance with preventive behaviours was influenced by risk perception and preventive measures perception (βstd=0.14 and βstd=0.27). The number and duration of social contacts were not associated with H1N1pdm09 infection., Conclusions: Our findings suggest that influenza vaccination in addition to public health communication campaigns focusing on personal preventive measures should be prioritised as potentially efficient interventions to mitigate influenza epidemics., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The CoPanFlu-France household cohort was set up in 2009 to identify risk factors of infection by the pandemic A/H1N1 (H1N1pdm09) virus in the general population., Objectives: To investigate the determinants of infection during the 2010-2011 season, the first complete influenza season of study follow-up for this cohort., Patients/methods: Pre- and post-epidemic blood samples were collected for all subjects, and nasal swabs were obtained in all subjects from households where an influenza-like illness was reported. Cases were defined as either a fourfold increase in the serological titer or a laboratory-confirmed H1N1pdm09 on a nasal swab, with either RT-PCR or multiplex PCR. Risk factors for H1N1pdm09 infections were explored, without any pre-specified hypothesis, among 167 individual, collective and environmental covariates via generalized estimating equations modeling. We adopted a multimodel selection procedure to control for model selection uncertainty., Results: This analysis is based on a sample size of 1121 subjects. The final multivariable model identified one risk factor (history of asthma, OR = 2.17; 95% CI: 1.02-4.62) and three protective factors: pre-epidemic serological titer (OR = 0.51 per doubling of the titer; 95% CI: 0.39-0.67), green tea consumption a minimum of two times a week (OR = 0.39; 95% CI: 0.18-0.84), and proportion of subjects in the household always covering their mouth while coughing/sneezing (OR = 0.93 per 10% increase; 95% CI: 0.86-1.00)., Conclusion: This exploratory study provides further support of previously reported risk factors and highlights the importance of collective protective behaviors in the household. Further analyses will be conducted to explore these findings., (© 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Pilgrims returning from the Hajj might contribute to international spreading of respiratory pathogens. Nasal and throat swab specimens were obtained from 129 pilgrims in 2013 before they departed from France and before they left Saudi Arabia, and tested by PCR for respiratory viruses and bacteria. Overall, 21.5% and 38.8% of pre-Hajj and post-Hajj specimens, respectively, were positive for ≥1 virus (p = 0.003). One third (29.8%) of the participants acquired ≥1 virus, particularly rhinovirus (14.0%), coronavirus E229 (12.4%), and influenza A(H3N2) virus (6.2%) while in Saudi Arabia. None of the participants were positive for the Middle East respiratory syndrome coronavirus. In addition, 50.0% and 62.0% of pre-Hajj and post-Hajj specimens, respectively, were positive for Streptococcus pneumoniae (p = 0.053). One third (36.3%) of the participants had acquired S. pneumoniae during their stay. Our results confirm high acquisition rates of rhinovirus and S. pneumoniae in pilgrims and highlight the acquisition of coronavirus E229.

The 2011-2012 and 2012-2013 post-pandemic influenza outbreaks were characterized by variability in the A(H3N2) influenza viruses, resulting in low to moderate vaccine effectiveness (VE). The aim of this study was to investigate the molecular evolution and vaccine strain match of the A(H3N2) influenza viruses, having been circulated throughout the population of the French Corsica Island in 2011-2012 and again in 2012-2013. Clinical samples from 31 patients with confirmed A(H3N2) influenza viruses were collected by general practitioners (GPs) over these two consecutive seasons. An analysis of genetic distance and antigenic drift was conducted. Based on a hemagglutinin (HA) aminoacid sequence analysis, the Corsican A(H3N2) viruses fell into the A/Victoria/208/2009 genetic clade, group 3. All influenza viruses were characterized by at least four fixed amino acid mutations which were: N145S (epitope A); Q156H and V186G (epitope B) Y219S (epitope D), with respect to the A/Perth/16/2009 (reference vaccine strain for the 2011-2012) and the A/Victoria/361/2011 (reference vaccine strain for the 2012-2013). Using the p(epitope) model, the percentages of the perfect match VE estimated against circulated strains declined within and between seasons, with estimations of <50%. Overall, these results seem to indicate an antigenic drift of the A(H3N2) influenza viruses which were circulated in Corsica. These findings highlight the importance of the continuous and careful surveillance of genetic changes in the HA domain during seasonal influenza epidemics, in order to provide information on newly emerging genetic variants., (© 2013 Wiley Periodicals, Inc.)

Background: Homeless shelters are identified as places where humans are at high risk of acquiring respiratory disease. We previously reported the prevalence of the main respiratory diseases affecting a population of homeless in Marseille, France. Here, we investigated the prevalence of 10 respiratory viruses in a similar homeless population during 2 successive winter seasons., Findings: Following a clinical examination, we collected nasal specimens from which the RT-PCR detection of 10 respiratory viruses was performed through snapshot investigations. Among the 265 patients included, 150 (56.6%) reported at least one respiratory symptom of which 13 (8.7%) had positive swabs for at least one respiratory virus, and 115 patients reported any respiratory symptom of which 10 (8.7%) had positive swabs for respiratory virus. Overall, 23 patients had positive swabs for at least one respiratory virus. Human rhinovirus (HRV) was the predominant virus (13 isolates) followed by enteroviruses (3), human metapneumovirus (2), human coronavirus OC43 (2), 229E virus (2) and human respiratory syncytial virus subtype B (1). Among the patients infected with HRV, 10 were collected during the same snapshot., Conclusions: Although one half of the patients reported respiratory symptoms, the prevalence of respiratory viruses was within the range of that previously described in adult asymptomatic patients outside the homeless community. Most HRV-positive swabs were collected during the same snapshot suggesting a local outbreak. No influenza viruses were found despite the fact that one half of the patients were investigated during the peak of the seasonal influenza epidemic in Marseille.

The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households). The GMT for the general population was 47.1 (95% confidence interval (CI): 45.1, 49.2). According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.

Five persons in France were infected with Orf virus after skin wounds were exposed to infected sheep tissues during Eid al-Adha, the Muslim Feast of Sacrifice. Infections were confirmed by electron microscopy, PCR, and sequence analysis. Prevention and control of this underdiagnosed disease can be achieved by educating physicians, slaughterhouse workers, and persons participating in Eid al-Adha.

Background: The risk of influenza infection depends on biological characteristics, individual or collective behaviors and the environmental context. The Cohorts for Pandemic Influenza (CoPanFlu) France study was set up in 2009 after the identification of the novel swine-origin A/H1N1 pandemic influenza virus. This cohort of 601 households (1450 subjects) representative for the general population aims at using an integrative approach to study the risk and characteristics of influenza infection as a complex combination of data collected from questionnaires regarding sociodemographic, medical, behavioral characteristics of subjects and indoor environment, using biological samples or environmental databases., Methods/design: Households were included between December 2009 and July 2010. The design of this study relies on systematic follow-up visits between influenza seasons and additional visits during influenza seasons, when an influenza-like illness is detected in a household via an active surveillance system. During systematic visits, a nurse collects individual and environmental data on questionnaires and obtains blood samples from all members of the household. When an influenza-like-illness is detected, a nurse visits the household three times during the 12 following days, and collects data on questionnaires regarding exposure and symptoms, and biological samples (including nasal swabs) from all subjects in the household. The end of the follow-up period is expected in fall 2012., Discussion: The large amount of data collected throughout the follow-up will permit a multidisciplinary study of influenza infections. Additional data is being collected and analyzed in this ongoing cohort. The longitudinal analysis of these households will permit integrative analyses of complex phenomena such as individual, collective and environmental risk factors of infection, routes of transmission, or determinants of the immune response to infection or vaccination.

Background: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season., Methodology/principal Findings: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥ 1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20-59 years) and 73.3% in the elderly (≥ 60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive., Conclusions: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥ 1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.

Background: In April 2009, the first cases of pandemic (H1N1)-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones., Methodology/principal Findings: We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i) Nasal swabs were tested using rapid influenza diagnostic test (RIDT) and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus) and distribution in age groups and results of RIDT were analyzed. (ii) 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii) One early (May 2009) and one late (July 2009) viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii) Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed., Conclusions/significance: This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1)-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in children, especially in the context of the investigation of grouped cases.

In early 2009, four human cases of cowpox virus cutaneous infection in northern France, resulting from direct contact with infected pet rats (Rattus norvegicus), were studied. Pet rats, originating from the same pet store, were shown to be infected by a unique virus strain. Infection was then transmitted to humans who purchased or had contact with pet rats.