History of smallpox vaccination and marked clinical expression of mpox among cases notified in France from May to July 2022.

OBJECTIVES: The aim was to estimate the effect of reported history of smallpox vaccination prior to 1980 on clinical expression of mpox. METHODS: We included all confirmed mpox cases identified by the national mpox surveillance system in France between May and July 2022. Cases tested positive for monkeypox virus or orthopoxviruses by PCR. Cases were interviewed by phone using a questionnaire documenting demographics, symptoms and exposures. To estimate the effect of smallpox vaccination on the presence of marked mpox symptoms (association of fever, lymphadenopathy and extensive mucocutaneous lesions), we estimated prevalence ratios (PRs) and 95% CIs using Poisson regression models with robust standard errors. RESULTS: There were 1888 confirmed mpox cases with date of symptom onset between 7 May and 31 July 2022. Overall, 7% (93/1394) presented marked mpox symptoms. Among patients who provided information about their vaccination status, 14% (207/1469) reported smallpox vaccination prior to 1980. The proportion of cases with marked symptoms was 2% (3/170) among those reporting smallpox vaccination prior to 1980 and 8% (76/974) among those who reported no vaccination. The proportion of marked symptoms was four times lower among cases reporting previous smallpox vaccination than in cases reporting no vaccination (PR, 0.24; 95% CI: 0.08-0.76). There was no evidence of an effect of smallpox vaccination on development of complications (PR, 0.65; 95% CI: 0.35-1.22) or hospitalization due to mpox (PR, 0.64; 95% CI: 0.23-1.80). DISCUSSION: Our results suggest that smallpox vaccination during childhood attenuated the clinical expression of monkeypox virus infection, but there was no evidence of an effect on complications or hospitalization.

Impact of vaccination against severe COVID-19 in the French population aged 50 years and above: a retrospective population-based study.

BACKGROUND: Given the widespread implementation of COVID-19 vaccination to mitigate the pandemic from the end of 2020, it is important to retrospectively evaluate its impact, in particular by quantifying the number of severe outcomes prevented through vaccination. METHODS: We estimated the number of hospitalizations, intensive care unit (ICU) admissions and deaths directly averted by vaccination in France, in people aged ≥ 50 years, from December 2020 to March 2022, based on (1) the number of observed events, (2) vaccination coverage, and (3) vaccine effectiveness. We accounted for the effect of primary vaccination and the first booster dose, the circulating variants, the age groups, and the waning of vaccine-induced protection over time. RESULTS: An estimated 480,150 (95% CI: 260,072-582,516) hospitalizations, 132,156 (50,409-157,767) ICU admissions and 125,376 (53,792-152,037) deaths were directly averted by vaccination in people aged ≥ 50 years, which corresponds to a reduction of 63.2% (48.2-67.6), 68.7% (45.6-72.4) and 62.7% (41.9-67.1) respectively, compared to what would have been expected without vaccination over the study period. An estimated 5852 (2285-6853) deaths were directly averted among the 50-59 years old, 16,837 (6568-19,473) among the 60-69 years old, 32,136 (13,651-36,758) among the 70-79 years old and 70,551 (31,288-88,953) among the ≥ 80 years old. CONCLUSIONS: The vaccination campaign in France considerably reduced COVID-19 morbidity and mortality, as well as stress on the healthcare system.

Protection against symptomatic SARS-CoV-2 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original monovalent vaccines - A matched cohort study in France.

This cohort study evaluated the protection against symptomatic Omicron BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to mRNA Original monovalent vaccines (Pfizer- BioNTech or Moderna). Individuals of ≥60 years old, who received a booster dose between 03/10/2022 and 06/11/2022, when both bivalent and monovalent vaccines were used in France, were included and matched according to the type of booster vaccine received. The outcome of interest was a positive SARS-CoV-2 RT-PCR or antigenic test associated to self-reported symptoms, ≥ seven days after receiving the booster dose. Data were analysed with a Cox Proportional-Hazards model adjusted for the presence of previous infection, age, sex, and the presence of medium risk comorbidities. A total of 136,852 individuals were included and followed for a median period of 77 days. The bivalent vaccine conferred an additional protection of 8 % [95 % CI: 0 %-16 %, p = 0.045] against symptomatic Omicron BA.5infection compared to the monovalent vaccines.

Vaccine effectiveness and duration of protection of COVID-19 mRNA vaccines against Delta and Omicron BA.1 symptomatic and severe COVID-19 outcomes in adults aged 50 years and over in France.

The emergence of SARS-CoV-2 variants calls for continuous monitoring of vaccine effectiveness (VE). We estimated the absolute effectiveness of complete 2-dose primary vaccination and booster vaccination with COVID-19 mRNA vaccines, and the duration of protection against Delta and Omicron BA.1 symptomatic infection and severe outcomes. French residents aged ≥50 years, who presented with SARS-CoV-2-like symptoms and tested for SARS-CoV-2 between June 6, 2021 and February 10, 2022 were included. A test-negative study was conducted to estimate VE against symptomatic infection, using conditional logistic regression models. Cox proportional hazard regressions were performed to assess additional protection against severe COVID-19 outcomes (any hospitalization, and intensive care units [ICU] admission or in-hospital death). In total, 273732 cases and 735 919 controls were included. VE against symptomatic infection after 2-doses vaccination was 86% (95% CI: 75-92%) for Delta and 70% (58-79%) for Omicron, 7-30 days post vaccination. Protection waned over time, reaching 60% (57-63%) against Delta and 20% (16.-24%) for Omicron BA.1 > 120 days after vaccination. The booster dose fully restored protection against symtpomatic Delta infection (95% [81-99%]) but only partially against symptomatic Omicron BA.1 infection (63% [59-67%]). VE against Delta-related severe outcomes was above 95% with 2 doses, and persisted for at least four months. Protection against any Omicron BA.1-hospitalization was 92% (65%-99%) at 8-30 days, and 82% (67%-91%) > 120 days from the second dose. Against BA.1 ICU admission or in-patient death, VE stood at 98% (0-100%) at 8-30 days, and was 90% (40-99%) > 120 days from the second dose. Protection confered by mRNA vaccines against severe disease caused by either Delta or Omicron BA.1 appeared high and sustained over time. Protection against symptomatic diseases after 2 doses decreased rapidly, especially against Omicron BA.1. A booster dose restored high protection against Delta but only a partial one against Omicron BA.1.

Effectiveness of second booster compared to first booster and protection conferred by previous SARS-CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France.

In face of evidence of rapid waning of vaccine effectiveness against Omicron and its sub-lineages, a second booster with mRNA vaccines was recommended for the most vulnerable in France. We used a test negative design to estimate the effectiveness of the second booster relative to the first booster and the protection conferred by a previous SARS-CoV-2 infection, against symptomatic Omicron BA.2 or BA.4/5. We included symptomatic ≥60 years old individuals tested for SARS-CoV-2 in March 21-October 30, 2022. Compared to a 181-210 days old first booster, a second booster restored protection with a relative effectiveness of 41% [95%CI: 39-42%], 7-30 days post-vaccination. This gain in protection was lower than the one observed with the first booster, at equal time points since vaccination. High levels of protection were associated to previous SARS-CoV-2 infection, especially when the infection was recent and occurred when an antigenic-related variant was dominant.

Bronchiolitis epidemics in France during the SARS-CoV-2 pandemic: The 2020-2021 and 2021-2022 seasons.

OBJECTIVES: We described bronchiolitis epidemics during the 2020-2021 and 2021-2022 seasons in France and their interaction with the COVID outbreak. PATIENTS AND METHODS: Data on family physician (FP) visits, emergency department (ED) visits, hospitalizations for bronchiolitis for children˂2 years, and hospital virological data were analyzed and compared with previous seasons (2015-2020). RESULTS: The 2020-2021 epidemic arrived very late, and its impact was lower than in previous seasons (2015-2020) (FP visits: -23%, ED visits: -38%, and hospitalizations: -30%). The 2021-2022 epidemic started early (week 40) and lasted for a relatively long time (13 weeks). The impact was higher than in 2015-2020 (FP visits: +13%, ED visits: +34%, hospitalizations: +28%). CONCLUSION: Findings from the 2020-2021 epidemic may be linked to the implementation of non-pharmaceutical COVID-19 prevention measures. For 2021-2022, findings may be linked to an "immunity debt" resulting from the lower impact of the previous season.

Severe hospital events following symptomatic infection with Sars-CoV-2 Omicron and Delta variants in France, December 2021-January 2022: A retrospective, population-based, matched cohort study.

Background: A rapid increase in incidence of the SARS-CoV-2 Omicron variant (sub-lineage BA.1) occurred in France in December 2021, while the Delta variant was prevailing since July 2021. We aimed to determine whether the risk of a severe hospital event following symptomatic SARS-CoV-2 infection differs for Omicron versus Delta. Methods: We conducted a retrospective cohort study to compare severe hospital events (admission to intensive care unit or death) between Omicron and Delta symptomatic cases matched according to week of virological diagnosis and age. The analysis was adjusted for age, sex, vaccination status, presence of comorbidities and region of residence, using Cox proportional hazards model. Findings: Between 06/12/2021-28/01/2022, 184 364 cases were included, of which 931 had a severe hospital event (822 Delta, 109 Omicron). The risk of severe event was lower among Omicron versus Delta cases; the difference in severity between the two variants decreased with age (adjusted Hazard Ratio (aHR)=0·13 95%CI: 0·08-0·20 among 40-64 years, aHR=0·50 95%CI: 0·26-0.98 among 80+ years). The risk of severe event increased with the presence of comorbidities (for very-high-risk comorbidity, aHR=4·15 95%CI: 2·86-6·01 among 40-64 years) and in males (aHR=2·28 95%CI: 1·82-2·85among 40-64 years) and was higher in unvaccinated compared to primo-vaccinated (aHR=7·29 95%CI: 5·58-9·54 among 40-64 years). A booster dose reduced the risk of severe hospital event in 80+ years infected with Omicron (aHR=0·29; 95%CI: 0·12-0·69). Interpretation: This study confirms the lower severity of Omicron compared to Delta. However, the difference in disease severity is less marked in the elderly. Further studies are needed to better understand the interactions between age and severity of variants. Funding: The study was performed as part of routine work at Public Health France.

Impact of the Omicron variant on SARS-CoV-2 reinfections in France, March 2021 to February 2022.

Since the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021.

Community outbreak of serogroup B invasive meningococcal disease in Beaujolais, France, February to June 2016: from alert to targeted vaccination.

In February and March 2016, four cases of serogroup B invasive meningococcal disease (IMD) occurred over 3 weeks in a small area north of Lyon in the Auvergne-Rhône-Alpes region, France. There were no deaths but two cases had sequelae. This community outbreak was caused by a rare meningococcal strain of the clonal complex ST-32, covered by the 4CMenB/Bexsero vaccine. The incidence rate for serogroup B IMD in this area was 22.5 per 100,000 inhabitants, which is above the epidemic threshold (10/100,000). The number of cases observed was significantly higher than expected in the age group of 0-24 year-olds (standardised incidence ratio: 96). These results suggested the potential emergence of this invasive strain in this sub-population. In accordance with French recommendations, it was decided to vaccinate the population aged between 2 months and 24 years, living, working or studying in the epidemic area. The vaccination campaign took place from April to September 2016. Vaccination coverage was estimated at 47% for one dose and 40% for two doses. The lowest coverage estimations were observed for the age groups younger than 3 and 15-19 years. Enhanced epidemiological and microbiological surveillance reported a fifth case in June 2016, outside the epidemic area.

[Supply disruptions and drug shortages: the example of benzathine benzylpenicillin]. / Tensions d'approvisionnement et ruptures de stock des médicaments : l'exemple de la benzathine benzylpénicilline.

Supply disruptions and drug shortages : the example of benzathine benzylpenicillin. Despite collective mobilisation, drug shortages have increased in recent years, creating a strong impact on public health. Anti-infective drugs, mainly injectable antibiotics, are particularly affected by these shortages. Although the causes of these ruptures are multiple, they are mainly related to the effects of globalisation and industrial strategies of rationalisation of production costs. The shortage of benzathine benzylpenicillin illustrates the action of the French Medicines Agency (ANSM), and the various actors to guarantee access to care and limit the consequences for the patient. Beyond measures taken at national level by the regulatory authorities in connection with the pharmaceutical companies, it is necessary to set up a concerted action at European level to fight effectively against drug shortages.

Tensions d'approvisionnement et ruptures de stock des médicaments : l'exemple de la benzathine benzylpénicilline. Malgré une mobilisation collective, les ruptures de stock des médicaments se sont multipliées ces dernières années, créant un fort retentissement en matière de santé publique. Les médicaments anti-infectieux, principalement les antibiotiques injectables, sont particulièrement impactés par ces pénuries. Bien que les causes de ces ruptures soient multiples, elles sont principalement liées aux effets de la mondialisation et des stratégies industrielles de rationalisation des coûts de production. La rupture de la benzathine benzylpénicilline illustre l'action de l'Agence nationale de sécurité du médicament et des produits de santé et des différents acteurs pour garantir l'accès aux soins et limiter les conséquences pour le patient. Au-delà des mesures prises au plan national par les autorités sanitaires en lien avec les laboratoires pharmaceutiques, il est nécessaire de mettre en place une action concertée au niveau européen pour lutter efficacement contre les pénuries de médicaments.

Clonal replacement and expansion among invasive meningococcal isolates of serogroup W in France.

BACKGROUND: Neisseria meningitidis group W (NmW) belonging to the clonal complex ST-11 (NmW/cc11) spread in Europe and in France in 2000 and declined thereafter. In France, invasive meningococcal disease (IMD) due to NmW increased again in 2012 and thereafter since 2015. Several sub-lineages of NmW/cc11 are circulating worldwide with successive epidemic waves. We aimed to describe recent epidemiological trends of NmW in France and to explore the microbiological and epidemiological characteristics associated with different NmW/cc11 sub-lineages. METHODS: The epidemiology of NmW was described based on data collected through mandatory notification of IMD and strain typing data for culture-confirmed and PCR-confirmed cases for the period 2000-2016. All culture-confirmed cases due to NmW from the period 2010-2016 were characterised by whole genome sequencing (WGS). A detailed epidemiological analysis was performed for culture-confirmed cases on the basis of WGS data. FINDINGS: During the period 2010-2016, genotyping was obtained for 148 cases including all the 132 culture-confirmed cases, among which 127 were matched with epidemiological data, and 16 PCR-confirmed cases (out of a total of 47 PCR-confirmed cases). An increase in IMD was observed in 2012 and was linked to isolates belonging to the "Anglo-French-Hajj" sub-lineage. These isolates have decreased significantly since 2013 and have been replaced by NmW/cc11 isolates related to the "South American - UK" sub-lineage which caused a marked increase in the number of cases of NmW in 2016. In this sub-lineage, the "original UK strain" was first detected in 2012 and increased thereafter, followed by the recently described "UK 2013-strain". Isolates related to the "South American-UK" sub-lineage represented 45% of all NmW cultured isolates from the whole period 2010-2016 but were the most frequent isolates in 2016, representing 76% of the total NmW typed isolates and 94% of the typed NmW/cc11 isolates. A changing pattern in the epidemiology of NmW has been observed in 2015-2016 in relation to the spread of the "UK 2013-strain" with a sharp increase in the number of cases among persons aged 15 years and over and a high case fatality rate (CFR). Among cases due to the "UK 2013-strain", 94% of cases were aged 15 years and over and the CFR was 28%. INTERPRETATION: Our data suggest a recent clonal replacement among NmW/cc11 isolates with the expansion of the "South American-UK" sub-lineage in France and particularly the "UK 2013-strain" which was predominant in 2015 and 2016. A shift in the age-distribution of IMD due to NmW to older ages and the high CFR are consistent with the expansion of a new virulent clone in a naive population. These data may have an impact on tailoring vaccination strategies against NmW.

Effectiveness of Human Papillomavirus Vaccination on Prevalence of Vaccine Genotypes in Young Sexually Active Women in France.

Background: Effectiveness of human papillomavirus (HPV) vaccines in the context of both guidelines, which recommend vaccination at 14 years and modest vaccine coverage, is poorly documented. Methods: Residual specimens from females aged <25 years undergoing chlamydia testing were collected, together with demographic, sexual behavior, and vaccine status data. Human pappilomavirus genotypes were determined using the PapilloCheck test system. We compared vaccine type (VT; types 6, 11, 16, 18) prevalence according to vaccination status and identified factors associated with VT prevalence. Results: Of 3736 eligible samples, 822 were from vaccinated women according to immunization record, 1021 from women self-reporting vaccination, and 1893 from unvaccinated women. Adjusted vaccine effectiveness for confirmed vaccinated compared with unvaccinated women was 95.93% (95% confidence interval [CI] = 90.22-98.32) against VT HPV and 38.37% (95% CI = 12.68-56.51) against cross-reactive genotypes (HPV 31, 33, 45), respectively. Vaccine type HPV prevalence was significantly lower (0.61%) among confirmed-vaccinated women than among those who self-reported vaccination or unvaccinated women (1.76% and 15.0%, respectively). Factors associated with prevalent VT in multivariable analysis were vaccine status, positive Chlamydia trachomatis and ≥4 partners in the preceding year. Conclusion: Our study demonstrates evidence of high effectiveness of HPV prophylactic vaccines at an individual level, supporting that wider implementation will help to reduce cervical cancer and precursors incidence.

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men.

Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract.

Epidemiological impact and cost-effectiveness of introducing vaccination against serogroup B meningococcal disease in France.

INTRODUCTION: Despite its low incidence in France, invasive serogroup B meningococcal disease remains a public health concern. A new vaccine against the disease, Bexsero(®), has been licensed in the EU. We studied the epidemiological impact and cost-effectiveness of routine vaccination using Bexsero(®) in order to inform the decision-making process regarding its potential inclusion in the vaccination schedule. METHODS: A multi-generational Markov model was used. Time horizon was set to 100 years. Five vaccination strategies were evaluated: infants at 3, 5, 6 and 13 months, toddlers at 13, 15 and 27 months and adolescents at 15 years provided 2 doses one month apart. A booster dose at 15 years old and a catch-up for 15 years old subjects during the first 15 years of the programme were added to the infant and toddler strategies. Costs per QALY gained were computed from a restricted societal perspective including direct costs only. Herd immunity was simulated in an alternative base-case scenario and sensitivity analyses. RESULTS: In the base-case analysis without herd immunity and with all cohorts vaccinated, at € 40 per vaccine dose, routine infant vaccination would provide the lowest cost per QALY gained (€ 380,973) despite only preventing 18% of cases. Under the assumption of herd immunity, the adolescent vaccination would provide the lowest cost per QALY gained (€ 135,902) preventing 24% of cases. Infant vaccination with a late booster and catch-up would prevent 51% of cases with a cost of € 188,511 per QALY gained. CONCLUSIONS: Given current meningococcal epidemiology in France and the available data on the protection provided by Bexsero(®), our modelling work showed that routine vaccination against serogroup B meningococcal disease is not cost-effective.

The use of reimbursement data for timely monitoring of vaccination coverage: the example of human papillomavirus vaccine following public concerns about vaccine safety.

BACKGROUND: Since 2011 public concerns about Human Papillomavirus (HPV) vaccination safety and efficacy arose in France. We explored the relevance of using vaccines reimbursement data to assess the impact of those public concerns on vaccination coverage. METHODS: We used the Permanent Sample of Beneficiaries which was, at the time of the study, a representative sample of 1/97(th) health insurance beneficiaries of the main Social Security scheme, the General Health Insurance Scheme, covering approximately 77 % of the French resident population. We estimated HPV vaccination coverage among girls born between 1995 and 1999 at their 15(th), 16(th) and 17(th) birthday. RESULTS: The coverage for complete vaccination among 16 years old girls decreased from 26.5 % in the first semester of 2011 to 18.6 % in the first semester of 2014. CONCLUSIONS: HPV vaccination coverage was already low in 2011 and continued to decrease thereafter. Vaccines reimbursement data allowed us to reactively monitor the impact of the controversy on vaccination coverage and design counteracting measures.

Measles elimination efforts and 2008-2011 outbreak, France.

Although few measles cases were reported in France during 2006 and 2007, suggesting the country might have been close to eliminating the disease, a dramatic outbreak of >20,000 cases occurred during 2008-2011. Adolescents and young adults accounted for more than half of cases; median patient age increased from 12 to 16 years during the outbreak. The highest incidence rate was observed in children <1 year of age, reaching 135 cases/100,000 infants during the last epidemic wave. Almost 5,000 patients were hospitalized, including 1,023 for severe pneumonia and 27 for encephalitis/myelitis; 10 patients died. More than 80% of the cases during this period occurred in unvaccinated persons, reflecting heterogeneous vaccination coverage, where pockets of susceptible persons still remain. Although vaccine coverage among children improved, convincing susceptible young adults to get vaccinated remains a critical issue if the target to eliminate the disease by 2015 is to be met.

[Measles in France]. / La rougeole en France.

From January 2008 to May 2012, over 22,000 cases of measles were reported in France. The highest incidence rate was observed in children below one year of age. Over 50% of cases were reported in young adults. Almost 5,000 patients were hospitalised including 1,023 with severe pneumonia, 27 with encephalitis and/or myelitis : 10 died. This situation is linked to insufficient and heterogeneous vaccination coverage with pockets of susceptible people allowing virus circulation. Although the vaccine coverage in children has now improved for both doses, the issue of convincing young susceptible adults to catch up for measles vaccination remains critical, if the elimination target is to be met, and in order to protect the most vulnerable population unable to benefit from this vaccination (children below 1 year, immunodeficient people, pregnant women).

[Measles and its virus]. / La rougeole et son virus.

After the huge decrease of measles thanks to vaccination, measles reappeared in 2008, with 604 cases reported at the Institut national de veille sanitaire (InVS), then 1,544 cases in 2009 and 2,605 cases up to 2010, June. At the same time, 86 viral strains were detected from saliva samples at the Centre national de référence de la rougeole et des Paramyxoviridae respiratoires (CNR) in 2008, 316 in 2009 and 946 up to August 2010. The reality of the outbreak was confirmed by the increase of the endemic cases: 0.0009% cases in 2008 and 0.004% in 2010, the diffusion to all parts of France, and the more specific attack of infants: 4% in 2008 and 9% in 2010, and of young adults: 17% in 2008 and 38% in 2010. Most of the cases (82%) occurred in non-vaccinated people. The number of hospitalised cases has increased as well, going from 18% in 2008 to 34% in 2010. The strain of this outbreak is a genotype D4. It appeared in 2008 then it spread in 2009 and 2010, representing 19, 75 and 99% of the strains, respectively. All the viruses in this genotype belonged to the Montreal-like cluster described in 1989: Montréal.CAN/89xD4. At the beginning of the outbreak some were closed to a variant which appeared in England in 2007 MVs/Enfield.GBR/14.07(D4), but most of them (95%) are nowidentical to a strain which caused a small focus of measles in the region Vendee at the last trimester 2008: MVs/Montaigu.FRA/43.08(D4). The salivary diagnosis of measles, which was introduced in France in 2005, in parallel to the obligation of reporting measles cases, has been proved very efficient: 75% of saliva are collected in the first four days, and viral RNA was detected in 536 (81%) out the 660 samples received at the CNR up to now in 2010; 136 (21%) saliva had IgM specific antibodies and 18% had neither RNA, nor IgM.

Emergence of new virulent Neisseria meningitidis serogroup C sequence type 11 isolates in France.

In France, there have been variations in the incidence of invasive meningococcal infection due to serogroup C isolates. Infection peaks were observed in 1992 and 2003 that involved isolates of phenotypes C:2a:P1.5,2 and/or C:2a:P1.5, which belong to the sequence type 11 (ST-11) clonal complex. We report an emergence of isolates belonging to the ST-11 clonal complex since 2003. These isolates displayed a new phenotype, C:2a:P1.7,1, caused infections that occurred as clusters, and were associated with increased infection severity and high virulence in mice. These isolates may be responsible for a peak in the incidence of serogroup C meningococcal infection in France, for which there is no routine vaccination to date.

Phylogenetic analysis of rubella viruses involved in congenital rubella infections in France between 1995 and 2009.

Rubella is an acute infectious disease that normally has a mild clinical course. However, infections during pregnancy, especially before week 12 of gestation (WG), can cause severe birth defects known as congenital rubella syndrome (CRS). The aim of this study was to perform genotyping and molecular characterization of rubella viruses involved in congenital infections in France over the past 15 years (1995 to 2009). Amniotic fluid (AF) specimens (n = 80) from pregnant women with congenital rubella infections (CRI) before week 20 of gestation, and a few other samples available from children/newborns with CRS (n = 26), were analyzed. The coding region of the rubella virus E1 gene was amplified directly from clinical specimens by reverse transcriptase PCR, and the resulting DNA fragments were sequenced. Sequences were assigned to genotypes by phylogenetic analysis with rubella virus reference sequences. Sufficient E1 gene sequences were obtained from 56 cases. Phylogenetic analysis of the sequences showed that at least five different genotypes (1E, 1G, 1B, 2B, and 1h) were present in France and were involved in congenital infections, with a strong predominance of genotype 1E (87%). This is one of the very few comprehensive studies of rubella viruses involved in CRI. The results indicated that over the past 15 years, multiple introductions of the dominant genotype E caused most of the CRI cases in France. A few sporadic cases were due to other genotypes (1B, 1G, 1h, 2B).