Alessandra Falchi

Field effectiveness of pandemic and 2009-2010 seasonal vaccines against 2009-2010 A(H1N1) influenza: estimations from surveillance data in France.

Background In this study, we assess how effective pandemic and trivalent 2009-2010 seasonal vaccines were in preventing influenza-like illness (ILI) during the 2009 A(H1N1) pandemic in France. We also compare vaccine effectiveness against ILI versus laboratory-confirmed pandemic A(H1N1) influenza, and assess the possible bias caused by using non-specific endpoints and observational data. Methodology and Principal Findings We estimated vaccine effectiveness by using the following formula: VE  =  (PPV-PCV)/(PPV(1-PCV)) × 100%, where PPV is the proportion vaccinated in the population and PCV the proportion of vaccinated influenza cases. People were considered vaccinated three weeks after receiving a dose of vaccine. ILI and pandemic A(H1N1) laboratory-confirmed cases were obtained from two surveillance networks of general practitioners. During the epidemic, 99.7% of influenza isolates were pandemic A(H1N1). Pandemic and seasonal vaccine uptakes in the population were obtained from the National Health Insurance database and by telephonic surveys, respectively. Effectiveness estimates were adjusted by age and week. The presence of residual biases was explored by calculating vaccine effectiveness after the influenza period. The effectiveness of pandemic vaccines in preventing ILI was 52% (95% confidence interval: 30–69) during the pandemic and 33% (4–55) after. It was 86% (56–98) against confirmed influenza. The effectiveness of seasonal vaccines against ILI was 61% (56–66) during the pandemic and 19% (−10–41) after. It was 60% (41–74) against confirmed influenza. Conclusions The effectiveness of pandemic vaccines in preventing confirmed pandemic A(H1N1) influenza on the field was high, consistently with published findings. It was significantly lower against ILI. This is unsurprising since not all ILI cases are caused by influenza. Trivalent 2009-2010 seasonal vaccines had a statistically significant effectiveness in preventing ILI and confirmed pandemic influenza, but were not better in preventing confirmed pandemic influenza than in preventing ILI. This lack of difference might be indicative of selection bias.

Evaluating the feasibility and participants' representativeness of an online nationwide surveillance system for influenza in France.

The increasing Internet coverage and the widespread use of digital devices offer the possibility to develop new digital surveillance systems potentially capable to provide important aid to epidemiological and public health monitoring and research. In France, a new nationwide surveillance system for influenza-like illness, GrippeNet.fr, was introduced since the 2011/2012 season based on an online participatory mechanism and open to the general population. We evaluate the recruitment and participation of users to the first pilot season with respect to similar efforts in Europe to assess the feasibility of establishing a participative network of surveillance in France. We further investigate the representativeness of the GrippeNet.fr population along a set of indicators on geographical, demographic, socio-economic and health aspects. Participation was widespread in the country and with rates comparable to other European countries with partnered projects running since a longer time. It was not representative of the general population in terms of age and gender, however all age classes were represented, including the older classes (65+ years old), generally less familiar with the digital world, but considered at high risk for influenza complications. Once adjusted on demographic indicators, the GrippeNet.fr population is found to be more frequently employed, with a higher education level and vaccination rate with respect to the general population. A similar propensity to commute for work to different regions was observed, and no significant difference was found for asthma and diabetes. Results show the feasibility of the system, provide indications to inform adjusted epidemic analyses, and highlight the presence of specific population groups that need to be addressed by targeted communication strategies to achieve a higher representativeness in the following seasons.

Morphological, chemical and genetic differentiation of two subspecies of Cistus creticus L. (C. creticus subsp. eriocephalus and C. creticus subsp. corsicus).

Cistus creticus L., an aromatic species from the Mediterranean area, contains various diterpenes bearing the labdane skeleton. The production of essential oil from this species has potential economic value, but so far, it has not been optimized. In order to contribute to a better knowledge of this species and to its differentiation, the morphological characters, volatile chemical composition and genetic data of two subspecies (C. creticus subsp. eriocephalus and C. creticus subsp. corsicus) were investigated. The leaf trichomes were studied using scanning electron microscopy. The chemical composition of Corsican essential oil (C. creticus subsp. corsicus) has been reported using GC, GC/MS and 13C NMR; the main constituents were oxygenated labdane diterpenes (33.9%) such as 13-epi-manoyl oxide (18.5%). Using plant material (54 samples) collected from 18 geographically distinct areas of the islands of Corsica and Sardinia, the basis of variation in the headspace solid-phase microextraction volatile fraction and an inter-simple sequence repeat genetic analysis were also examined. It was shown that the two subspecies of C. creticus differed in morphology, essential oil production, volatile fraction composition and genetic data.

Age Distribution of Influenza Like Illness Cases during Post-Pandemic A(H3N2): Comparison with the Twelve Previous Seasons, in France

In France, the 2011–2012 influenza epidemic was characterized by the circulation of antigenically drifted influenza A(H3N2) viruses and by an increased disease severity and mortality among the elderly, with respect to the A(H1N1)pdm09 pandemic and post-pandemic outbreaks. Whether the epidemiology of influenza in France differed between the 2011–2012 epidemic and the previous outbreaks is unclear. Here, we analyse the age distribution of influenza like illness (ILI) cases attended in general practice during the 2011–2012 epidemic, and compare it with that of the twelve previous epidemic seasons. Influenza like illness data were obtained through a nationwide surveillance system based on sentinel general practitioners. Vaccine effectiveness was also estimated. The estimated number of ILI cases attended in general practice during the 2011–2012 was lower than that of the past twelve epidemics. The age distribution was characteristic of previous A(H3N2)-dominated outbreaks: school-age children were relatively spared compared to epidemics (co-)dominated by A(H1N1) and/or B viruses (including the 2009 pandemic and post-pandemic outbreaks), while the proportion of adults over 30 year-old was higher. The estimated vaccine effectiveness (54%, 95% CI (48, 60)) was in the lower range for A(H3N2) epidemics. In conclusion, the age distribution of ILI cases attended in general practice seems to be not different between the A(H3N2) pre-pandemic and post-pandemic epidemics. Future researches including a more important number of ILI epidemics and confirmed virological data of influenza and other respiratory pathogens are necessary to confirm these results.

Rates of immunization against pandemic and seasonal influenza in persons at high risk of severe influenza illness: a cross-sectional study among patients of the French Sentinelles general practitioners

BackgroundThree main categories of persons are targeted by the French influenza vaccination strategy: all persons aged 65 years or over, those aged less than 65 years with certain underlying medical conditions and health care workers. The main objective of this study was to estimate rates of influenza immunization in these target groups attending a medical consultation for two consecutive influenza seasons: 2009–2010 (seasonal and pandemic vaccines) and 2010–2011 (seasonal vaccine).MethodsA standardized questionnaire was mailed to 1323 general practitioners (GPs) of the Sentinelles Network, collecting data on all patients seen on a randomly assigned day. For every patient, following information was collected: age, gender, BMI, presence of any medical condition that increases risk of severe influenza illness, and vaccination status for the three vaccines mentioned.ResultsTwo hundred and three GPs agreed to participate and included 4248 patients. Overall, in persons with high risk of severe influenza, the estimated vaccine coverages (VC) were 60%, (95% CI = 57%; 62%) for the seasonal vaccine in 2010–2011, 61% (59%; 63%) for the seasonal vaccine in 2009–2010 and 23% (21%; 25%), for the pandemic vaccine in 2009–2010. Among people aged 65 years and over (N=1259, 30%) VC was estimated for seasonal vaccines at 72% (70%; 75%) in 2010–2011 and 73% (71%; 76%) in 2009–2010, and 24% (22%; 26%) for the pandemic vaccine. The lowest seasonal VC were observed in younger persons (<65 years) with underlying medical conditions, in particular pregnant women (<10%) and overweight persons (<30%).ConclusionsOur study shows that influenza vaccination coverage among patients of the French Sentinelles general practitioners remains largely below the target of 75% defined by the 2004 French Public Health Law, and underscores the need for the implementation of public health interventions likely to increase vaccination uptake.

Nationwide Surveillance of 18 Respiratory Viruses in Patients With Influenza-Like Illnesses: A Pilot Feasibility Study in the French Sentinel Network

The aim of the present study was to test the feasibility of integrating the diagnosis of 18 respiratory viruses into clinical surveillance of influenza‐like illness using a PCR‐DNA microarray detection assay. The study took place in the French Sentinel Network, a nationwide surveillance network of General Practitioners (GPs) representative of French GPs in terms age, location, and type of practice (urban/rural). Three virological laboratories also participated in the study. The study was planned for 5 weeks from January 25, 2010 to February 27, 2010. A subset of 150 Sentinel GPs, located in mainland France, was enrolled to collect clinical data and nasopharyngeal samples from every first patient of the week having a medical visit for influenza‐like illness defined as a sudden fever of 39°C or more with respiratory symptoms and myalgia. Sixty‐three GPs (42%) collected 103 samples while 87 GPs (58%) did not. GPs did not differ with respect to their age, gender, urban/rural distribution, or years of inscription in the Sentinel Network. Patients included were of a similar age and had similar vaccination characteristics, but were more frequently men than influenza‐like illness patients reported to the network during the study period. Sixty‐one viruses were detected from 56 of 96 (58%) interpretable samples. The respiratory viruses detected most frequently were metapneumovirus and respiratory syncytial virus. This study showed that virological diagnosis of 18 respiratory viruses can be combined with surveillance of clinical influenza‐like illness in general practice. Although feasibility has not been demonstrated yet, it will be evaluated over the winter of 2010–2011. J. Med. Virol. 83:1451–1457, 2011.

Human CHIT1 gene distribution: new data from Mediterranean and European populations

AbstractA 24 bp duplication in the CHIT1 gene (H allele) is associated with a deficiency in the activity of chitotriosidase, an enzyme with the capability to hydrolyse chitin. A recent study in European and two sub-Saharan populations suggested a relationship between the presence of the mutation, improved environmental conditions, and the disappearance of parasitic diseases, including Plasmodium falciparum malaria. This result was not supported by the high frequency of the 24 bp duplication in a sample from Taiwan, an area with high malaria endemicity until 40 years ago. In this study, we analysed the frequency variability of the H allele in Mediterranean populations and its internal variability in Sardinia (Italy) with respect to malaria, which had been endemic on the island until its eradication during 1946–1950. The pattern of H frequency distributions is not consistent with the hypothesis of selective pressures acting on CHIT1 gene. The Morans index coefficient and correlogram seem to indicate, indeed, that allele distribution was determined by random factors. The pattern of frequency distribution suggests a possible Asiatic origin of the H allele, but it could be possible also that the mutant allele had diffused out of Africa, and was subsequently lost from African populations.

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

BackgroundData 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.MethodsThe 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.ResultsDuring 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.ConclusionsDuring 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.

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.

Early estimates of 2014/15 seasonal influenza vaccine effectiveness in preventing influenza-like illness in general practice using the screening method in France

The ongoing influenza epidemic is characterized by intense activity with most influenza infections due to the A (H3N2) viruses. Using the screening method, mid-season vaccine effectiveness (VE) in preventing influenza-like illness in primary care was estimated to 32% (95% CI; 23 to 40) among risk groups and was 11% (95% CI; −4 to 23) among the elderly (≥ 65 y). The VE in ≥ 65 y was the lowest estimate regarding the 4 previous seasonal influenza epidemics.