Genetic drift of influenza A(H3N2) viruses during two consecutive seasons in 2011-2013 in Corsica, France.

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.

Acute diarrhea in adults consulting a general practitioner in France during winter: incidence, clinical characteristics, management and risk factors.

BACKGROUND: Data describing the epidemiology and management of viral acute diarrhea (AD) in adults are scant. The objective of this study was to identify the incidence, clinical characteristics, management and risk factors of winter viral AD in adults. METHODS: The incidence of AD in adults during two consecutive winters (from December 2010 to April 2011 and from December 2011 to April 2012) was estimated from the French Sentinelles network. During these two winters, a subset of Sentinelles general practitioners (GPs) identified and included adult patients who presented with AD and who filled out a questionnaire and returned a stool specimen for virological examination. All stool specimens were tested for astrovirus, group A rotavirus, human enteric adenovirus, and norovirus of genogroup I and genogroup II. Age- and sex-matched controls were included to permit a case-control analysis with the aim of identifying risk factors for viral AD. RESULTS: During the studied winters, the average incidence of AD in adults was estimated to be 3,158 per 100,000 French adults (95% CI [2,321 - 3,997]). The most reported clinical signs were abdominal pain (91.1%), watery diarrhea (88.5%), and nausea (83.3%). GPs prescribed a treatment in 95% of the patients with AD, and 80% of the working patients with AD could not go to work. Stool examinations were positive for at least one enteric virus in 65% (95% CI [57 - 73]) of patients with AD with a predominance of noroviruses (49%). Having been in contact with a person who has suffered from AD in the last 7 days, whether within or outside the household, and having a job (or being a student) were risk factors significantly associated with acquiring viral AD. CONCLUSIONS: During the winter, AD of viral origin is a frequent disease in adults, and noroviruses are most often the cause. No preventable risk factor was identified other than contact with a person with AD. Thus, at the present time, reinforcement of education related to hand hygiene remains the only way to reduce the burden of disease.

Simultaneous investigation of influenza and enteric viruses in the stools of adult patients consulting in general practice for acute diarrhea.

BACKGROUND: Gastrointestinal symptoms are not an uncommon manifestation of an influenza virus infection. In the present study, we aimed to investigate the presence of influenza viruses in the stools of adult patients consulting their general practitioner for uncomplicated acute diarrhea (AD) and the proportion of concurrent infections by enteric and influenza viruses. METHOD: A case-control study was conducted from December 2010 to April 2011. Stool specimens were collected and tested for influenza viruses A (seasonal A/H3N2 and pandemic A/H1N1) and B, and for four enteric viruses (astrovirus, group A rotavirus, human enteric adenovirus, norovirus of genogroups I - NoVGI - and genogroup II - NoVGII). RESULTS: General practitioners enrolled 138 cases and 93 controls. Of the 138 stool specimens collected, 92 (66.7%) were positive for at least one of the four enteric viruses analysed and 10 (7.2%) tested positive for one influenza virus. None of these 10 influenza positive patients reported respiratory symptoms. In five influenza-positive patients (3.6%), we also detected one enteric virus, with 4 of them being positive for influenza B (2 had co-detection with NoVGI, 1 with NoVGII, and 1 with astrovirus). None of the 93 controls tested positive for one of the enteric and/or other influenza viruses we investigated. CONCLUSIONS: In this study we showed that the simultaneous detection of influenza and enteric viruses is not a rare event. We have also reported, for the first time in general practice, the presence of seasonal and pandemic influenza viruses in the stools of adult patients consulting for uncomplicated AD. A simultaneous investigation of enteric and influenza viruses in patients complaining of gastrointestinal symptoms could be useful for future studies to better identify the agents responsible for AD.

A phenylalanine-arginine beta-naphthylamide sensitive multidrug efflux pump involved in intrinsic and acquired resistance of Campylobacter to macrolides.

The macrolide erythromycin is the antibiotic of choice in the management of Campylobacter infections. Although mutation has been reported to account for resistance to the antibiotic, resistance may also be due to an efflux pump that extrudes the drug prior to reaching its target. Moreover, the efflux pump may be one that accommodates resistance to other related or unrelated drugs (multidrug resistance). We examined the possibility that resistance to erythromycin may involve an efflux pump whose presence may be identified by the use of the unique commercial inhibitor of the previously described efflux pumps phenylalanine-arginine beta-naphtylamide (PAbetaN). We showed that PAbetaN is able to significantly increase the susceptibility of the reference strain NCTC 11168 to erythromycin, suggesting that an efflux pump functions at a basal level in the reference wild type strain. Erythromycin-resistant isolates were tested for their response to PAbetaN treatment. Among the strains tested, resistance of three isolates to erythromycin was reduced to a level comparable to that of the susceptible strain when the strains were grown in the presence of this inhibitor. To conclude, besides mutations, erythromycin resistance in Campylobacter may also be due to an efflux mechanism sensitive to PAbetaN.

Epidemiology and viral etiology of the influenza-like illness in corsica during the 2012-2013 Winter: an analysis of several sentinel surveillance systems.

Influenza-like illness (ILI) surveillance is important to identify circulating and emerging/reemerging strains and unusual epidemiological trends. The present study aimed to give an accurate picture of the 2012-2013 ILI outbreak in Corsica by combining data from several surveillance systems: general practice, emergency general practice, hospital emergency units, intensive care units, and nursing homes. Twenty-eight respiratory viruses were retrospectively investigated from patients in general practice with ILI. Sequence analysis of the genetic changes in the hemagglutinin gene of influenza viruses (A(H1N1)pdm2009, A(H3N2) and B) was performed. The trends in ILI/influenza consultation rates and the relative illness ratios (RIRs) of having an ILI consultation were estimated by age group for the different surveillance systems analyzed. Of the 182 ILI patients enrolled by general practitioners, 57.7% tested positive for influenza viruses. Phylogenetic analyses suggested a genetic drift for influenza B and A(H3N2) viruses. The ILI/influenza surveillance systems showed similar trends and were well correlated. In accordance with virological data, the RIRs of having an ILI consultation were highest among the young (<15 years old) and decreased with age. No clusters of acute respiratory illness were declared by the sentinel nursing homes. This study is noteworthy in that it is the first extensive description of the 2012-2013 ILI outbreak in Corsica as monitored through several surveillance systems. To improve ILI surveillance in Corsica, a consortium that links together the complementary regional surveillance ILI systems described here is being implemented.

Genetic structure of human A/H1N1 and A/H3N2 influenza virus on Corsica Island: phylogenetic analysis and vaccine strain match, 2006-2010.

BACKGROUND: The aim of this study was to analyse the genetic patterns of Hemagglutinin (HA) genes of influenza A strains circulating on Corsica Island during the 2006-2009 epidemic seasons and the 2009-2010 pandemic season. METHODS: Nasopharyngeal samples from 371 patients with influenza-like illness (ILI) were collected by General Practitioners (GPs) of the Sentinelles Network through a randomised selection routine. RESULTS: Phylogenetic analysis of HA revealed that A/H3N2 strains circulating on Corsica were closely related to the WHO recommended vaccine strains in each analyzed season (2006-2007 to 2008-2009). Seasonal Corsican influenza A/H1N1 isolated during the 2007-2008 season had drifted towards the A/Brisbane/59/2007 lineage, the A/H1N1 vaccine strain for the 2008-2009 season. The A/H1N1 2009 (A/H1N1pdm) strains isolated on Corsica Island were characterized by the S220T mutation specific to clade 7 isolates. It should be noted that Corsican isolates formed a separate sub-clade of clade 7 as a consequence of the presence of the fixed substitution D222E. The percentages of the perfect match vaccine efficacy, estimated by using the p(epitope) model, against influenza viruses circulating on Corsica Island varied substantially across the four seasons analyzed, and tend to be highest for A/H1N1 compared with A/H3N2 vaccines, suggesting that cross-immunity seems to be stronger for the H1 HA gene. CONCLUSION: The molecular analysis of the HA gene of influenza viruses that circulated on Corsica Island between 2006-2010 showed for each season the presence of a dominant lineage characterized by at least one fixed mutation. The A/H3N2 and A/H1N1pdm isolates were characterized by multiples fixation at antigenic sites. The fixation of specific mutations at each outbreak could be explained by the combination of a neutral phenomenon and a founder effect, favoring the presence of a dominant lineage in a closed environment such as Corsica Island.

Co-circulation of two genetically distinct sub-groups of A/H3N2 influenza strains during the 2006-2007 epidemic season in Corsica Island, France.

BACKGROUND: Influenza virus is one of the major viral respiratory pathogens infecting human beings. OBJECTIVES: To determine the influenza A virus variants responsible for the 2006-2007 epidemic season in Corsica Island, France. STUDY DESIGN: Of 134 nasal samples of adult patients tested by culture and RT-PCR assays, 85 influenza A strains were identified; 81 (95%) were sub-typed as A/H3N2 and 4 (5%) were sub-typed as A/H1N1. RESULTS: All of the HA sequences of the A/H3N2 viruses circulating in Corsica Island appeared to be closely related to the A/Wisconsin/67/2005 vaccine strain and segregated into two sub-groups that were genetically distinct from other viruses circulating in other countries during 2006/2007. One of these sub-groups was distinguished by the substitution H156Q whereas the second demonstrated at least one of the 3 other additional mutations (R142G, L157S and K173E) common to the HA1 sequence of A/Nepal/921/2006 reference strain. Among the 14 strains of this second sub-group, 10 viral strains had been isolated from vaccinated adult patients. CONCLUSION: These findings suggest that a prospective analysis of the HA sequences of influenza isolates may allow an early detection of newly evolved variants with potential epidemiological inference.