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 presence of marked mpox symptoms (association of fever, lymphadenopathy and extensive mucocutaneous lesions), we estimated prevalence ratios (PR) and 95% confidence intervals (CI) using Poisson regression models with robust standard errors. RESULTS: There were 1,888 confirmed mpox cases with date of symptom onset between 7 May and 31 July 2022. Overall, 7% (93/1,394) presented marked mpox symptoms. Among cases who provided information about their vaccination status, 14% (207/1,469) 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 hospitalisation due to mpox (PR 0.64, 95%CI: 0.23-1.80). CONCLUSIONS: 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 hospitalisation.

Can physicians and schools mitigate social inequalities in human papillomavirus vaccine awareness, uptake and vaccination intention among adolescents? A cross-sectional study, France, 2021 to 2022.

BackgroundIn France, human papillomavirus (HPV) vaccination coverage varies across socioeconomic levels.AimWe aimed at assessing HPV vaccine awareness, uptake and vaccination intention among adolescents in France.MethodsIn a cluster-randomised study, 13-15-year-old students in 61 French middle schools completed a web-based questionnaire. We used multivariable logistic regression to evaluate determinants of HPV vaccine awareness, self-reported uptake and vaccination intention among unvaccinated students and interaction terms to explore effects of visits to family physician and remembering school lessons on vaccination. The French deprivation index of school municipalities served as proxy for socioeconomic levels.ResultsAmong 6,992 participants, awareness was significantly associated with parental education (odds ratio (OR) = 0.82; 95% confidence interval (CI): 0.71-0.95), language spoken at home (OR = 0.59; 95% CI: 0.52-0.66) and deprivation level (OR = 0.57; 95% CI: 0.44-0.71), regardless of physician visit or school lessons. Vaccine uptake was associated with parental education without a recent physician visit (OR = 0.31; 95% CI: 0.16-0.59, vs OR = 0.64; 95% CI: 0.52-0.78 with a visit, interaction p = 0.045). Vaccination intention among unvaccinated was associated with deprivation level (moderate-low vs low) among students not remembering school lessons on vaccination (OR = 0.17; 95% CI: 0.05-0.62, vs OR = 0.93; 95% CI: 0.51-1.67 remembering school lessons, interaction p = 0.022). Parental education was associated with vaccination intention among students reporting a physician visit (OR = 0.41; 95% CI: 0.26-0.64 vs OR = 1.05; 95% CI: 0.50-2.20 without a visit, interaction p = 0.034).ConclusionOur results suggest that healthcare and school could promote vaccination and mitigate social inequalities in HPV vaccination coverage.

Anal and oropharyngeal HPV distribution in HIV-negative multipartner MSM using self-sampling kits for HIV and sexually transmitted infection screening.

Men who have sex with men (MSM) are at high risk of sexually transmitted infections, among which HPV infections are particularly prominent. We took advantage of the MémoDépistages study to evaluate HPV distribution at anal and oropharyngeal sites in HIV-negative multipartner MSM. HPV DNA was detected in 82% (n = 344) of anal and 11% (n = 45) of oropharyngeal self-collected samples taken from 421 participants. Multiple HPV types were detected in 70% of anal samples, and single HPV types in 91% of oropharyngeal samples. HPV16 was the most frequent type detected in the anus, followed by HPV6, HPV51, and HPV52. HPV6, HPV16, and HPV11 were the most prevalent types in the oropharynx. HPV targeted by the nonavalent vaccine was detected in 71% and 50% of HPV-positive anal and oropharyngeal samples, respectively. The main risk factor associated with HPV detection was frequenting gay meeting places, living in large cities, and having an anal Chlamydia trachomatis/Neisseria gonorrhoeae infection. In this cohort of highly sexually active MSM, HPV detection was highly frequent and rendered them at high risk of precancerous and cancerous lesions. Universal vaccination against HPV before sexual debut is an important public health strategy to prevent HPV-associated cancers in this highly vulnerable population of HIV-negative MSM.

Low vaccination coverage for human papillomavirus disease among young men who have sex with men, France, 2019.

BackgroundIn France, human papillomavirus (HPV) vaccination has been recommended in 2016 for men who have sex with men (MSM) up to age 26 years.AimWe aimed to estimate HPV vaccine coverage in 18-28 year-old MSM and identify uptake determinants.MethodsWe collected data on socio-demographic characteristics, sexual behaviour, sexually transmitted diseases (STI) screening and vaccination uptake using a voluntary cross-sectional online survey conducted in 2019 targeting MSM. We calculated coverage of at least one dose of HPV vaccine and prevalence ratios (PR) of determinants with 95% confidence intervals (CI) using Poisson regression.ResultsOf 9,469 respondents (age range: 18-28 years), 15% (95% CI: 14-16) reported being vaccinated for HPV. Coverage was significantly higher among MSM < 24 years (PR: 1.25; 95% CI: 1.13-1.39), with education level below university degree (PR: 1.12; 95% CI: 1.08-1.32), living in rural areas (PR: 1.21; 95% CI: 1.08-1.36), attending sex parties (PR: 1.12; 95% CI: 1.03-1.33), using HIV-related biomedical prevention methods (PR: 1.31; 95% CI: 1.12-1.54), with STI diagnosis (PR: 1.22; 95% CI: 1.08-1.38) and with hepatitis A or B vaccination (PR: 4.56; 95% CI: 3.63-5.81 vs PR: 3.35; 95% CI: 2.53-4.44).ConclusionsThe HPV vaccination uptake among MSM in France was not satisfactory. It was higher among MSM benefitting from other vaccinations and biomedical preventive methods against HIV, suggesting a synergistic effect of the national preventive sexual health recommendations for MSM. Further efforts to improve HPV vaccination coverage targeting MSM are warranted.

Targeted vaccination campaigns of teenagers after two clusters of B invasive meningococcal disease in Brittany, France, 2017.

BACKGROUND: In December 2016, three cases of serogroup B invasive meningococcal disease, including two children from the same middle school (11 to 15 years old pupils), occurred in the department (administrative district) Côtes-d'Armor (Brittany, France). They were infected by a rare strain (B:P1.7-2,4:F5-9:cc162), covered by the 4CMenB vaccine (Bexsero®). Four months later, two cases due to the same strain occurred in a high school in the same area (15 to 19 years old students). In accordance with French recommendations, vaccination was proposed to students of both schools and to all individuals aged 11-19 years living or studying in the hyperendemic area. We describe these vaccination campaigns, from the alert to the impact evaluation. METHODS: The target population included 8884 people: 579 in the middle school, 2007 in the high school and 6298 in the community. In both schools, vaccination sessions were organized directly on site. In the community, teenagers were vaccinated by general practitioners. The vaccination campaign took place from May to October 2017. An active pharmacovigilance follow-up was set up to document adverse effects of the vaccine. RESULTS: Considering the whole target population, the vaccination coverage was estimated at 43% for 1 dose and 34% for 2 doses. Higher vaccination coverage was observed in the schools (79% in the middle school and 42% in the high school for 2 doses) than in the community (27% for 2 doses). The reported adverse effects were consistent with the safety profile of the vaccine and no severe adverse effect was reported. CONCLUSIONS: This vaccination campaign was the third one implemented with Bexsero® in France and constitutes a reproducible approach for future targeted vaccination campaigns. No additional cases of the same strain have occurred since the end of the campaigns in the area.

Emergence of new genetic lineage, ST-9316, of Neisseria meningitidis group W in Hauts-de-France region, France 2013-2018.

BACKGROUND: The epidemiology of invasive meningococcal disease (IMD) is continuously changing in incidence, age distribution and/or the expansion of new strains of Neisseria meningitidis. The epidemiology of IMD due to group W (IMDW) has changed recently at a global level with the emergence of isolates belonging to the clonal complex ST-11 (CC11) derived from the South America-UK strain. A more recent change has been detected in France with the emergence of a new genotype distinct from CC11 that we aimed to analyse. METHODS: Epidemiological and microbiological surveillance data in France were used in combination with whole genome sequencing (WGS) to detect emerging phenotypes and genotypes of IMD causing strains, and their susceptibility to immunity induced by the 4CMenB vaccine. Transgenic mice expressing the human transferrin were used to analyse the virulence of emerging strain isolates by direct comparison with CC11 isolates. FINDINGS: Our data showed a local increase of IMDW isolates in north France since 2013. The isolates belonged to ST-9316 and few were ST-11 isolates. WGS clustered ST-9316 isolates together and were distantly separated from the isolates of the clonal complex ST-11 (CC11). Unlike cases due to W/CC11 isolates, cases due to W/ST-9316 isolates were mostly observed amongst infants under the age of 1 year but with lower mortality compared to W/CC11 cases. Genomic comparison showed that the W/ST-9316, unlike W/CC11 isolates, lacked the hmbR gene encoding the haemoglobin receptor that is a virulence factor involved in the acquisition of iron from haemoglobin. W/ST-9316 further showed lower virulence in mice compared to W/CC11 isolates. INTERPRETATION: We report the emergence of a novel sequence type (ST-9316) mostly associated with serogroup W, and exhibiting a lower virulence and a distinct age specific incidence profile than W/CC11 isolates. Surveillance requires powerful approaches combining WGS and pathophysiological analysis to adapt control measures.

[Challenges in the implementation of HPV vaccination for cancer prevention]. / Vaccination contre les HPV : un enjeu de prévention des cancers.

In France, every year, HPVs cause approximately 6,300 cancers -cervix, anus, oropharynx, penis, vulva, vagina, oral cavity, larynx- representing 2% of all incident cancers, 35,000 precancerous le-sions of the cervix, and at least 50,000 condylomas in the under- 30s. All 3,000 new cases of cervical cancers are attributable to HPV infections. Cervical cancer prevention is based on the combination of two complementary strategies: vaccination of 11 to 14-years-old girls against HPV and organized screening of cervical cancer for women between 25 and 65 years old. In France, the vaccination coverage rate -VCR- against HPV for 2 vaccine doses is less than 25% while it reaches more than 80% in the United Kingdom, Portugal, Australia, etc. This low level of VCR can be explained by the mistrust in these vaccines especially regarding their effectiveness and safety. However, more than 10 years after their commercialization, HPV vaccines have already demonstrated, in many countries, their effectiveness against HPV infections, genital warts and precancerous cervical lesions. In addition, no association between vaccines and autoimmune diseases has been demonstrated, either by national or international surveillance authorities, or by scientific publications, after the commercialization of 200 million doses worldwide. As the International Papillomavirus Society has declared that the combination of a high VCR against HPV and a high participation in cervical cancer screening, combined with appropriate treatment, can lead to the elimination of cervical cancer as a public health problem, it is important to better communicate the scientific findings in order to better understand vaccination's benefits.

En France, les papillomavirus -HPV- sont responsables chaque année d'environ 6 300 cancers potentiellement dus aux HPV -col de l'utérus, anus, oropharynx, pénis, vulve, vagin, cavité orale, larynx- représentant 2 % des cancers incidents, de 35 000 traitements de lésions précancéreuses du col de l'utérus, et d'au moins 50 000 condylomes chez les moins de 30 ans. Les 3 000 nouveaux cas de cancers du col de l'utérus chaque année sont attribuables à 100 % aux infections HPV. La prévention de ce cancer repose sur l'articulation de deux stratégies complémentaires: la vaccination des jeunes filles de 11 à 14 ans contre les HPV et le dépistage organisé du cancer du col de l'utérus de 25 à 65 ans. En France, la couverture vaccinale contre les HPV -2 doses- est inférieure à 25 % tandis qu'elle atteint plus de 80 % au Royaume-Uni, au Portugal, en Australie, etc. Ce faible taux peut être expliqué par l'existence d'une défiance vis-à-vis de ces vaccins alimentée par des doutes portant tant sur l'efficacité que sur la sécurité des vaccins. Pourtant, après plus de 10 ans de commercialisation, les vaccins contre les HPV ont déjà démontré, dans de nombreux pays dans le monde, une efficacité en vie réelle contre les infections HPV, les condylomes ainsi que les lésions précancéreuses du col de l'utérus. De plus, le lien entre les vaccins et les maladies auto-immunes n'a pas été démontré ni par les autorités de surveillance nationales ou internationales, ni par les publications scientifiques après la commercialisation de 200 millions de doses dans le monde. À l'heure où l' International papillomavirus society a déclaré que la combinaison d'une couverture vaccinale élevée contre les HPV et d'un fort taux de participation au dépistage du cancer du col de l'utérus, alliée à des traitements appropriés, peut conduire à l'élimination du cancer du col de l'utérus comme problème de santé publique, il est important de mieux communiquer sur les données scientifiques afin de mieux comprendre les bénéfices de la vaccination.

Assessment of the impact of the extension of vaccination mandates on vaccine coverage after 1 year, France, 2019.

One year after the extension of the childhood vaccination mandates to the 11 routine vaccinations for children under 2 years old, we estimated vaccination coverage through vaccine reimbursement data. Coverage for children born in 2018 has notably increased. Moreover, vaccine coverage for children and for vaccines not concerned by the law have also shown an increasing trend, supporting a positive impact of the ongoing communication strategy on vaccination, beyond the extension of vaccination mandates.

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.

A cluster of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup W among university students, France, February to May 2017.

Between February and May 2017, two cases of invasive meningococcal disease caused by a new, rapidly expanding serogroup W meningococci variant were reported among students of an international university in Paris. Bacteriological investigations showed that isolates shared identical genotypic formula (W:P1.5,2:F1-1:cc11) and belonged to the South American/UK lineage. A vaccination campaign was organised that aimed at preventing new cases linked to potential persistence of the circulation of the bacteria in the students.

I-MOVE multi-centre case control study 2010-11: overall and stratified estimates of influenza vaccine effectiveness in Europe.

BACKGROUND: In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. METHODS: Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination. RESULTS: We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B. CONCLUSIONS: Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe.

Estimates of pandemic influenza vaccine effectiveness in Europe, 2009-2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) multicentre case-control study.

BACKGROUND: A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009-2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1). METHODS AND FINDINGS: Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6-85.5) overall; 78.4% (95% CI 54.4-89.8) in patients <65 years; and 72.9% (95% CI 39.8-87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9-84.8), 71.3% (95% CI 29.1-88.4), and 70.2% (95% CI 19.4-89.0), respectively. The adjusted PIVE was 66.0% (95% CI -69.9 to 93.2) if vaccinated 8-14 days before ILI onset. The adjusted 2009-2010 seasonal influenza VE was 9.9% (95% CI -65.2 to 50.9). CONCLUSIONS: Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009-2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010-2011 season, when vaccination will occur before the influenza season starts.