Surveillance of adverse events following vaccination in the French armed forces, 2011-2012.

OBJECTIVES: French military personnel are subject to a compulsory vaccination schedule. The aim of this study was to present the results of surveillance of vaccine adverse events (VAEs) reported from 2011 to 2012 in the French armed forces. STUDY DESIGN: VAEs were surveyed among all French armed forces from 2011 to 2012 by the epidemiological departments of the military health service. For each case, a notification form providing patient and clinical information was provided. METHODS: Case definitions were derived from the French drug safety guidelines. Three types of VAE were considered: non-serious, serious and unexpected. Incidence rates were calculated by relating VAEs to the number of vaccine doses delivered. RESULTS: In total, 161 VAE cases were reported. The overall VAE reporting rate was 24.6 VAEs per 100,000 doses, and the serious VAE rate was 1.3 per 100,000 doses (nine cases). The serious VAEs included two cases of Guillain-Barré syndrome, one case of optic neuritis, one case of a meningeal-like syndrome, one case of rheumatoid purpura, one case of acute asthma and three cases of fainting. The highest rates of VAE were observed with the Bacille Calmette-Guérin vaccine (BCG) (482.3 per 100,000 doses), inactivated diphtheria-tetanus-poliovirus with acellular pertussis vaccine (dTap-IPV) (106.1 per 100,000 doses) and meningococcal quadrivalent glycoconjugate vaccine (MenACWY-CRM) (39.3 per 100,000 doses). CONCLUSIONS: The global rates of VAE observed in 2011 and 2012 confirm the increase that has been observed since 2009 in the French armed forces, which could reflect improved practitioner awareness about VAEs and the use of certain vaccines added to the vaccination schedule recently (dTap-IPV in 2008 and MenACWY-CRM in 2010). VAEs appear to be relatively rare, particularly serious VAEs, which indicates acceptable tolerance of vaccines.

Feedback on the management of the 2011 measles outbreak by French military general practitioners: an evaluation study.

OBJECTIVE: Preventive measures were implemented in the French armed forces to limit the measles outbreak that occurred in 2010 and 2011. This study aimed to obtain feedback concerning the management of this outbreak by the French military general practitioners. METHOD: A cross-sectional study was conducted among the general practitioners (GPs) in military units located in metropolitan France. The 60 military units that reported at least one measles case in 2011 were included. Data were collected using self-administered questionnaires. RESULTS: The acceptance of preventive measures against measles was good (measures "totally justified" for 77.8%) and most of the military GPs considered that the outbreak had no significant impact on their activities. The management of measles cases was perceived as not very problematic but difficulties were encountered in the identification of contacts around cases (48.1% of respondents) and in the identification of vaccine recipients among these contacts (more than 80% of respondents reporting difficulties in the collection of measles and vaccination histories). The organization of vaccination around cases was also perceived as difficult. CONCLUSIONS: Preventive measures around measles cases were well accepted by the military GPs, which could reflect their preparedness in the face of the outbreak. However, vaccination did not seem to be well understood or accepted by military patients, underlining the essential role of military GPs in patient information. Difficulties in the collection of vaccination and measles histories among contacts could be overcome by an early transcription of individual medical records in the military medical files of newly enlisted personnel. A more generalized use of oral fluid testing devices, which can be shipped at ambient temperature, would simplify diagnosis in the armed forces.

Cumulative incidence rate of medical consultation for fecundity problems--analysis of a prevalent cohort using competing risks.

STUDY QUESTION: What is the incidence of medical consultation for fecundity problems in the French population, taking into account pregnancy occurrence and resumption of contraceptive use?. SUMMARY ANSWER: Considering the occurrence of a pregnancy and resumption of use of contraception as competing risks, the cumulative incidence rate of medical consultation for fecundity problems was 9.0% [95% confidence interval (CI): 6.5%; 11.9%] after 12 months of unprotected intercourse and 12.2% [95% CI: 9.6%; 15.3%] after 24 months. WHAT IS KNOWN ALREADY: Estimates of the prevalence of medical consultation due to involuntary infertility among couples who have sought a pregnancy for more than 12 months range from 25 to 50%. Most of the studies however are limited by retrospective data collection, without considering the duration of time since the beginning of the period of unprotected intercourse (PUI) and without considering medical consultation for fecundity problems as a competing risk. STUDY DESIGN, SIZE, DURATION: This study is based on the Observatory of Fecundity in France survey, a population-based probability survey designed to estimate the frequency of involuntary infertility on a nationwide basis and to explore the associations with environmental factors. Women answered two telephone questionnaires, the first at the time of enrolment in 2007, the second at follow-up 1 year later. The current analysis was performed among a subsample of 6577 women recruited before or during a PUI and followed-up for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study sample comprised 940 women aged 18-44 years who had a PUI between the time of enrolment and the 1-year follow-up, and who had not consulted a physician for fecundity problems for the current PUI prior to enrolment. Women reported all the medical consultations they had because of difficulties becoming pregnant during the current PUI. The date of each consultation was carefully assessed. In France, women can consult a gynaecologist directly without referral by their general practitioner. The occurrence of a pregnancy and resumption of contraceptive use were considered as informative censoring events, using a competing risk model. MAIN RESULTS AND THE ROLE OF CHANCE: Using the competing risk survival model, the cumulative incidence rate of first consultation was 9.0% [95% CI: 6.5%; 11.9%] 12 months after the start of the PUI and 12.2% [95% CI: 9.6%; 15.3%] after 24 months. The Kaplan-Meier method, which does not take competing risks into account, yielded substantially higher estimates: 26.0% [95% CI: 18.8%; 32.5%] at 12 months and 56.8% [95% CI: 44.2%; 66.6%] at 24 months. Among the 219 women who had attempted to become pregnant for at least 12 months, cumulative incidences of first medical consultations were 28.2% [18.7-38.9%] 24 months after the start of the PUI, and 31.2% [21.3- 42.4%] after 36 months. The rates were higher among nulliparous but non-nulligravid women, followed by nulligravid women, as compared with parous women. Age was not strongly related to the occurrence of medical consultation. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is the number of women lost to follow-up (29.7%). In addition, results regarding the absence of an age effect should be taken with caution as few women in our study were aged over 35 years. Although such an attrition rate is commonly observed in prospective studies in the general population, it could have induced a selection bias that may have led to an underestimation of the rates of medical consultation. Sensitivity analyses, using the inverse probability weighting method suggest that our results are unlikely to be biased. WIDER IMPLICATIONS OF THE FINDINGS: This study reveals frequencies of medical consultation for fertility problems, which, after considering competing events such as pregnancy in a relevant statistical model, are lower than generally reported in the literature. The results also indicate the existence of a difference between the potential need and the actual use of medical care for fecundity problems. This suggests a need for studies to look for factors other than medical recommendations that may play a role in the patterns of medical seeking behaviours for fecundity problems, such as women's reproductive history, socio-economic characteristics or accessibility to infertility services. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by grants from ANR (French Agency for Research, SEST call on Environmental and Occupational Health), ANSES (French Agency for Food, environmental and Occupational Health Safety, EST call on Environmental and Occupational Health), InVS (French Institute for Public Health Surveillance). The team of Environmental Epidemiology applied to Fecundity and Reproduction has been funded by an AVENIR grant from Inserm (2007). Authors declare no conflict of interest.

Increase in reported adverse events following seasonal influenza vaccination among the French armed forces, 2008-2009: possible role of stimulated reporting and background cases of influenza-like infection.

OBJECTIVES: In September 2009, an increase in seasonal influenza vaccine adverse events (VAE), compared with reports for previous years, was detected among the French armed forces in the setting of an extended immunization campaign. This work presents the results of this investigation. STUDY DESIGN: VAE were surveyed among all French military personnel from 2008 to 2009 by Epidemiological Departments of the French Military Health Service. For each case, a notification form was completed, providing patient and clinical information. METHODS: Case definitions were derived from the French drug vigilance guidelines. Three types of VAE were considered: non-serious, serious and unexpected. Incidence rates were calculated by relating VAE to the number of vaccine doses injected. RESULTS: Forty-seven seasonal influenza VAE were reported in continental France: 18 in 2008 and 29 in 2009. The annual reporting rate was higher in 2009 (31.6 vs 16.6 VAE per 100,000 injections, respectively). The highest monthly incidence was observed in September 2009 (60.8 events per 100,000 injections). Two other peaks were observed in February 2008 and March 2009. The incidence in September 2009 was not significantly different from the incidences in February 2008 and March 2009. It was observed that incidence peaks occurred during influenza epidemic periods. One serious neurological VAE was observed. CONCLUSIONS: The increase in seasonal influenza VAE in late 2009 mainly involved non-serious events, and could reflect stimulated reporting in the context of the A(H1N1)pdm09 pandemic. VAE reporting rates were highest during influenza epidemic periods, which could be explained by VAE being wrongly attributed to the vaccine when symptoms could reflect coincident background cases of viral infection.

Resurgence of measles in the French military forces in 2010.

Since the start of 2010 there has been a flare-up of measles in France, following on the resurgence observed in 2008. The aim of this study was to present results of the epidemiological surveillance of measles in the French armed forces and to describe the increase in incidence. Measles was surveyed from 1992 to 2010. Criteria for report were those used for French national compulsory notification. The data, concerning active military personnel, were provided by the physicians in the armed forces using anonymous data collection forms. Between 1992 and July 2010, 689 cases of measles were notified. Since 2002, the mean incidence rate was 1 case per 100,000. A significant increase has been observed for 2010 (13.9 cases per 100,000 in 2010 versus 1.8 in 2009). The 28 cases reported in 2010 involved five clusters and three isolated cases. The mean age of affected subjects was 27 years. Only 30% of cases had been vaccinated. The epidemic resurgence of measles observed in 2010 in the French armed forces follows the same pattern as that observed nationally and at European level, and can be seen as the likely consequence of inadequate vaccination cover.

Novel influenza A(H1N1) outbreak among French armed forces in 2009: results of Military Influenza Surveillance System.

OBJECTIVES: An outbreak of novel A(H1N1) virus influenza, detected in Mexico in April 2009, spread worldwide in 9 weeks. The aim of this paper is to present the monitoring results of this influenza outbreak among French armed forces. STUDY DESIGN: The period of monitoring by the Military Influenza Surveillance System (MISS) was 9 months, from May 2009 to April 2010. METHODS: The main monitored events were acute respiratory infection (ARI), defined by oral temperature ≥38.5 °C and cough, and laboratory-confirmed influenza. Weekly incidence rates were calculated by relating cases to the number of servicepersons monitored. RESULTS: In continental France, the incidence of ARI increased from September 2009, with a weekly maxima of 401 cases per 100,000 in early December 2009 according to MISS. Estimations of the incidence of consultations which could be related to novel A(H1N1) influenza ranged from 48 to 57 cases per 100,000. CONCLUSIONS: The trends observed by MISS are compatible with French national estimations. The incidence of consultations which could be related to A(H1N1) influenza at the peak of the epidemic (194 cases per 100,000) was much lower than the national estimate (1321 cases per 100,000). This may be due to servicepersons who consulted in civilian facilities and were not monitored. Other explanations are the healthy worker effect and the younger age of the military population.

High acquisition rate of extended-spectrum ß-lactamase-producing Enterobacteriaceae among French military personnel on mission abroad, without evidence of inter-individual transmission.

OBJECTIVES: Acquisition of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) by Europeans travelling individually in high-endemicity countries is common. However, how the different ESBL-E strains circulate in groups of travellers has not been studied. We investigated ESBL-E transmission within several groups of French military personnel serving overseas for 4-6 months. METHODS: We conducted a prospective study among French military personnel assigned to Afghanistan, French Guiana or Côte d'Ivoire for 4-6 months. Faecal samples provided by volunteers before leaving and after returning were screened for ESBL-E isolates. ESBL Escherichia coli from each military group was characterized by repetitive element palindromic polymerase chain reaction (rep-PCR) fingerprinting followed, in the Afghanistan group, by whole-genome sequencing (WGS) if similarity was ≥97%. RESULTS: Among the 189 volunteers whose samples were negative before departure, 72 (38%) were positive after return. The highest acquisition rates were observed in the Afghanistan (29/33, 88%) and Côte d'Ivoire (39/80, 49%) groups. Acquisition rates on return from French Guiana were much lower (4/76, 5%). WGS of the 20 strains from the Afghanistan group that clustered by rep-PCR identified differences in sequence type, serotype, resistance genes and plasmid replicons. Moreover, single-nucleotide polymorphism (SNP) differences across acquired strains from a given cluster ranged from 30 to 3641, suggesting absence of direct transmission. CONCLUSIONS: ESBL-E. coli acquisition was common among military personnel posted overseas. Many strains clustered by rep-PCR but differed by WGS and SNP analysis, suggesting acquisition from common external sources rather than direct person-to-person transmission.

[A French soldier returns from the Central Africa Republic with hepatitis A: Vaccination failure is possible!]. / Hépatite A au retour de Centrafrique chez un militaire français : les échecs vaccinaux sont possibles !

In stays in tropical countries, the French military, and travelers in general, are exposed to diseases transmitted by the fecal-oral route, some of which are vaccine-preventable. Here we report a 42-yer-old soldier with hepatitis A, which first appeared on his return from a military operation in the Central African Republic. Despite its excellent immunogenicity and a duration of seroprotection extending beyond 20 years in the vast majority of cases, the hepatitis A vaccine can fail. This reminds us of the importance of combining vaccine and non-vaccine prevention in tropical countries, especially in precarious living conditions.

Synthesis and determination of absolute configuration of the bicyclic guanidine core of batzelladine A.

[reaction: see text] The synthesis of a selectively protected form of the bicyclic guanidine fragment of batzelladine A from L-aspartic acid is reported, thereby establishing the absolute configuration of the bicyclic guanidine ring system within the natural product.

[Adolescents' knowledge and behavior on sexuality, infectious transmitted diseases, and human papillomavirus vaccination: results of a survey in a French high school]. / Connaissances et comportements des adolescents en matière de sexualité, infections sexuellement transmissibles et vaccination contre le papillomavirus humain : résultats d'une enquête transversale dans un lycée.

UNLABELLED: Teenager sexuality is a public health issue. In teenagers attending a high school, we assessed their knowledge and behavior on sexuality, infectious transmitted diseases, human papilloma virus (HPV) vaccination, and cervical cancer. Then in girls, we estimated the anti-HPV vaccination coverage and focused on factors associated with poor knowledge of these topics. METHODS: This was a knowledge, attitudes, and practices cross-sectional study conducted at the beginning of the 2010-2011 school year in the Saint-Cyr military high school, using an anonymous self-administered questionnaire. RESULTS: Among 669 adolescents (M/F sex-ratio, 2.3; mean age, 17 years [IC 95%, 15-20]), 40% had already had sex and 92% had used contraception. Boys and girls had a poor level of knowledge on infectious transmitted diseases. Regarding knowledge on HPV and cervical cancer, a better level was significantly associated with female gender (P=10(-4)). In multivariate analysis, male gender, age under 18 years, lack of dialogue with parents on these subjects, low socioeconomic status of parents, and absence of health education were significantly associated with poor knowledge on these topics. CONCLUSION: These data should help healthcare providers better target access and content of sexual health education training.

The measles outbreak in the French military forces--2010-2011: results of epidemiological surveillance.

OBJECTIVE: Since the start of 2010 there has been a flare-up of measles in France, following on the resurgence observed in 2008. The aim of this study was to present results of the epidemiological surveillance of measles in the French armed forces in metropolitan France and to describe the outbreak that occurred in 2010 and 2011. METHODS: Criteria for report were those used for French national compulsory notification. The data, concerning active military personnel, were derived from epidemiological surveillance from 1992 to 2011 for the incidence rates and from notification forms completed in 2010 and 2011 by the military practitioners for the description of characteristics of cases. RESULTS: Between January 1992 and July 2010, 833 cases of measles were reported. Since 2002, the mean incidence rate had been 1 case p.100,000. A significant increase in incidence was observed in 2010 (10.1 p.100,000) and in 2011 (41.4 p.100,000). Clusters of cases accounted for 72.3% of cases. Rates were much higher among subjects under 30. Only 68.6% of cases had been previously vaccinated with at least one dose of MMR vaccine. The mean vaccine coverage among contacts of cases was approximated to 54.3%. CONCLUSIONS: The outbreak of measles observed in 2010 and 2011 in the French armed forces followed the same pattern as that observed nationally and at European level, and can be seen as the likely consequence of inadequate vaccination coverage.

[Efficacy and tolerability of highly crosslinked hyaluronic acid injections in the management of the enophthalmous orbit]. / Efficacité et tolérance des injections d'acide hyaluronique hautement réticulé dans la prise en charge des énophtalmies.

OBJECTIVE: Evaluation of the efficacy and tolerability of highly crosslinked hyaluronic acid injections in treating the enophthalmous orbit. METHODS: Retrospective study of 11 enophthalmic patients who received an intraorbital injection of Juvederm(®) Voluma between June 2007 and October 2008. The mean follow-up was 19 months (range 12-25 months). RESULTS: Twelve orbits of 11 patients were treated, including nine with post-enucleation socket syndrome (PESS). Volume loss was corrected in 66.67% of cases (eight orbits) with only one intraorbital injection. Two patients requested an additional injection, achieving a final success rate of 83.33%. A rate of 16.67% (two orbits) developed some bruising, mild swelling and hypersensivity at the injection site within 24 hours of administration of the filler, representing minor, temporary side-effects of which the patients had been forewarned. Persistent edema was noted in 16.67% of cases, likely due to an overcorrection of ptosis, and ptosis was exacerbated in 16.67% of cases (two orbits). One ptosis was corrected after several months, with no particular difficulties related to the hyaluronic acid. No additional complications were identified. CONCLUSION: Juvederm(®) Voluma appears to be an effective filler for reduction of enophthalmos with a single intraorbital injection. In our experience, this product seems to have a longer duration of action than reported by the manufacturer and appears to perform like a semi-permanent or even permanent filler.

[Pertussis surveillance in French military forces in 2007]. / Surveillance épidémiologique de la coqueluche dans les armées françaises en 2007.

OBJECTIVES: Pertussis surveillance in the French general population was stopped in 1986. Pertussis was added to the list of illnesses surveyed by the military epidemiological surveillance network because of outbreaks having occurred among French servicepersons and in military high schools. This study had for aim to report the results of the first year of surveillance. DESIGN: Pertussis declaration criteria were those recommended in 2006 by the French council for public hygiene. The data concerning active military servicepersons was collected by physicians of all military medical units. An anonymous declaration form was used for data collection. RESULTS: In 2007, 66 cases of pertussis were reported in the military forces, 10 of which were excluded after a negative biological test. The classification of the 56 included cases was: 46% biologically confirmed cases, 20% clinically confirmed cases, 14% suspected cases, and 6% epidemiologically confirmed cases. The incidence density rate was 16.3 cases for 100,000 servicepersons-years. Age under 20 was associated with a 4.6 fold higher risk to develop pertussis. CONCLUSIONS: The high incidence rate observed in individuals under 20 years of age could reflect a shift of pertussis reservoir to young adults, as observed in industrialized countries after generalization of vaccination programs. However, several years of surveillance will be needed to confirm this hypothesis. Meanwhile, the military epidemiological network could constitute an important surveillance marker of pertussis among adults in France.

[A(H1N1) influenza surveillance in the French armed forces: adapting the surveillance systems to the pandemic setting]. / Surveillance épidémiologique de la grippe A(H1N1) 2009 dans les armées françaises: adaptation des systèmes de surveillance au contexte pandémique.

OBJECTIVES: An outbreak of A(H1N1) virus influenza, detected in Mexico during April 2009, spread around the world in nine weeks. French armed forces had to adapt their epidemiological surveillance systems to this pandemic. Our aim was to present surveillance results. DESIGN: There are two influenza surveillance systems in French armed forces: one permanent throughout the year and one seasonal, the Military influenza surveillance system (SMOG). The pandemic threat led to an early reactivation of SMOG, before the initiation of a daily surveillance system specifically dedicated to A(H1N1) influenza. RESULTS: In metropolitan France, the increase of respiratory infections was observed as of September 2009, with a maximum of 401 cases for 100,000 at the beginning of December according to SMOG. The estimated rate of consultations related to A(H1N1) influenza ranged between 46 and 65 cases for 100,000. For military units operating outside of metropolitan France, a peak of incidence was observed in August (400 cases for 100,000). CONCLUSION: The trends observed by influenza military surveillance networks were compatible with French ones. Concerning French forces in operations, the increase of incidence observed in August was the consequence of the influenza outbreak in the Southern hemisphere. Estimations of consultations rate related to A(H1N1) influenza, ranged between 127 and 194 cases for 100,000 at the beginning of December, lower than the national rate (1321 cases for 100,000), a consequence of the age pyramid in the military population.

Sulfide-mediated dehydrative glycosylation.

The development of a new method for glycosylation with 1-hydroxy glycosyl donors employing dialkyl sulfonium reagents is described. The process employs the reagent combination of a dialkyl sulfide and triflic anhydride to effect anomeric bond constructions. This controlled dehydrative coupling of various C(1)-hemiacetal glycosyl donors and nucleophilic acceptors proceeds by way of a sulfide-to-sulfoxide oxidation process in which triflic anhydride serves as the oxidant.