Accuracy of prenatal ultrasound screening to identify fetuses infected by cytomegalovirus which will develop severe long-term sequelae.

OBJECTIVES: To compare the ability of detailed routine ultrasound examination, performed without knowledge of maternal serology and fetal status, with that of targeted prenatal imaging performed in prenatal diagnostic units in cases of known fetal infection to identify cytomegalovirus (CMV)-infected fetuses that will develop long-term sequelae. METHODS: All prenatal imaging reports were collected for 255 children with congenital CMV in a registered cohort between 2013 and 2017 (NCT01923636). All women had undergone detailed routine fetal ultrasound examination at 20-24 and 30-34 weeks as part of routine antenatal care. All cases of known fetal CMV infection had also undergone targeted prenatal ultrasound examination. Postnatal structured follow-up for up to 48 months of age involved clinical, audiological and neurological assessment, including Brunet-Lezine scoring. Long-term sequelae (> 12 months) were considered to be mild in cases with isolated unilateral hearing loss and/or vestibular disorders, and severe in cases with bilateral hearing loss and/or neurological sequelae. All imaging reports were analyzed retrospectively with the knowledge of congenital CMV infection, searching for reference to findings that were, or could have been, related to fetal infection. Findings were analyzed in relation to whether the cases were diagnosed with CMV in utero or only postnatally. RESULTS: There were 237 children with complete follow-up data (> 12 months), for a median of 24 (range, 12-48) months. Of these, 30% (71/237) were diagnosed with CMV prenatally and 70% (166/237) were diagnosed within 3 weeks after birth. 72.5% (29/40) of children with long-term sequelae, including 74% (14/19) with severe long-term sequelae, were not identified in the prenatal period. Among those diagnosed prenatally, the sensitivity of prenatal imaging for predicting long-term sequelae and severe long-term sequelae was 91% and 100%, respectively, while, in the group diagnosed only postnatally, non-specific infection-related ultrasound findings had been reported without raising suspicion in 48% of cases with long-term sequelae and 64% of those with severe long-term sequelae. CONCLUSIONS: Routine detailed ultrasound examination in pregnancy is not an appropriate screening tool for congenital CMV infection that leads to long-term sequelae, in contrast with the high performance of targeted prenatal imaging in known cases of fetal infection. The non-specific nature of ultrasound features of CMV and their evolution, and a lack of awareness of caregivers about congenital CMV, are likely explanations. Awareness of the sonologist regarding congenital CMV and knowledge of the maternal serological status in the first trimester seem key to the performance of prenatal ultrasound. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Maternity staff immunization coverage against pertussis and maternal vaccination practices: Results of a 2017 cross-sectional survey in five public maternity hospitals.

OBJECTIVES: To conduct an audit of vaccination practices against pertussis in maternity wards to assess immunization practices targeting women, knowledge and awareness among health professionals and their involvement in the vaccination process, and to estimate their vaccine coverage. MATERIALS AND METHODS: 2017 cross-sectional descriptive survey using a data collection sheet of immunization practices targeting women and an anonymous questionnaire for health professionals whose vaccine coverage had been documented by the occupational health service. RESULTS: Five public maternity wards participated: one had a vaccination policy for women; 426 of 822 health professionals completed the questionnaire, 76% (from 50% of all residents to 83% of nurses) declared their vaccination status as up to date. Staff files in occupational health services showed that 69% of 822 health professionals received at least one vaccine booster during adulthood (57% less than 10 years before the survey); documented vaccination coverage rates ranged from 75% for residents to 91% for senior physicians. Occupational physicians and family physicians respectively performed 41% and 34% of vaccinations. While knowledge regarding vaccines was good, only 47% of health professionals declared prescribing them and 18% declared administering the anti-pertussis vaccine "often" or "very often". CONCLUSIONS: Updated data is needed to confirm the reported increase as participating centers are not representative of all birth centers. The active role of health professionals in vaccination-based pertussis prevention needs to be reinforced.

Klebsiella pneumoniae and Klebsiella oxytoca meningitis in infants. Epidemiological and clinical features.

BACKGROUND: The incidence of meningitis caused by Klebsiella pneumoniae (Kp) and Klebsiella oxytoca (Ko) in high-income countries is unknown, and no series have been published to date. METHODS: We conducted a nationwide multicenter observational study in France between 2006 and 2016. All children from the French national registry for paediatric bacterial meningitis under the age of 1 year and hospitalized for Kp or Ko meningitis were included. Virulence factors of four Klebsiella spp. strains were explored by whole genome sequencing. RESULTS: Of 1859 cases of meningitis in children under the age of 1 year, 13 cases (0.7%) of Klebsiella spp. meningitis (nine for Kp meningitis and four for Ko meningitis) were registered in the French national registry. Three of the patients died and 50% of the survivors had developmental delays. CONCLUSIONS: Prematurity, low birth weight, and congenital anomalies of the urinary tract appear to be risk factors for Klebsiella spp. meningitis as well as virulence factors of the strain.

Incidence of pertussis in subjects aged 50years and older in France in 2013-2014.

OBJECTIVE: To assess the incidence of pertussis (whooping cough) in subjects aged 50years and older in France. METHODS: Participating family physicians (FPs) using the patient record management software AxiSanté® included patients aged 50years and older, who had signed an informed consent form, presenting with persistent cough for 7 to 21days. Bordetella genetic material was detected by polymerase chain reaction (PCR) on nasopharyngeal samples collected at the FP's discretion. RESULTS: A total of 42 FPs included 129 patients from June 2013 to August 2014 (large cities: 38; medium-sized cities: 57; rural areas: 34); 106 samples were analyzed. Overall, 30 pertussis cases were diagnosed: 10 cases confirmed by PCR, 18 purely clinical cases, and two direct epidemiological cases. The crude incidence rate per 100,000 patients aged≥50years was 103.6 (95% CI: 69.9-47.9): 77.1 in large cities, 103.1 in medium-sized cities, and 143.9 in rural areas. The extrapolated incidence rate per 100,000 persons aged≥50years was 187.1 (95% CI: 126.2-67.1): 131.1 in large cities, 256.1 in medium-sized cities, and 242.2 in rural areas. CONCLUSION: The population aged 50years and older can serve as a reservoir. Its role in Bordetella pertussis circulation should be taken into account for pertussis booster vaccination programs.

Bacterial meningitis antibiotic treatment.

The implementation of pneumococal conjugate vaccines (PCVs) 7 then 13 valent (Prevenar13®) in 2010-2011 has significantly changed the profile of pneumococcal meningitis. Since 3 years, the National Pediatric Meningitis Network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have reported no cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (3GC): cefotaxime or ceftriaxone. In the light of these new data, vancomycin should no longer be prescribed at the initial phase of pneumococcal meningitis treatment (confirmed or only suspected) and this antibiotic should only be added when 3GC minimum inhibitory concentration of the strain isolated is greater than 0.5mg/L. For meningococcal meningitis, nearly 20% of strains have decreased susceptibility to penicillin and amoxicillin, but all remain susceptible to 3GC. The National Pediatric Meningitis Network is a valuable tool because it has been sufficiently exhaustive and sustainable over 15 years. Maintaining this epidemiologic surveillance will allow us to adapt, if necessary, new regimens for subsequent changes that could be induced by vaccination and/or antibiotic uses.

[Pertussis: Where do we stand 10years after the introduction of cocooning vaccination strategy in France?] / Coqueluche : où en est-on en France 10ans après la mise en place de la stratégie vaccinale du cocooning ?

The goals of this article are to review the pertussis cocooning strategy, which has been recommended in France since 2004 to protect infants not yet vaccinated from becoming infected by vaccinating their immediate entourage, and to present room for improvement. The analysis of the literature between 2004 and 2015 shows that pertussis vaccine coverage in new parents is lower than 50% and that attempts that have already been implemented to increase it are effective. Pertussis vaccine coverage improvement requires all health actors to collaborate and be trained in informing and motivating parents to get vaccinated before, during and after pregnancy (the parents then will act as relays to their relatives); generalization in maternity wards of systematic checking of the vaccination card; extension to the midwives of the right to prescribe and administer pertussis vaccine to spouses; vaccination facilitation in maternity wards with the support of health organizations. Exchange and sharing of experiences between health care professionals are essential. Pregnancy is the ideal period to promote pertussis vaccination.

[Is the new vaccination schedule recommended in France adapted to premature babies?]. / Le nouveau calendrier vaccinal est-il adapté à l'ancien prématuré ?

The French 2013 immunization schedule having a goal of simplification with comparable efficacy, has decreased the number of injections and removed the injection performed at three months of age in the general population. Apart from the prevention of invasive pneumococcal infections for which it is recommended to maintain three dose primary immunization, vaccination of premature is not addressed in this new calendar. Can the extremely preterm infants (<33 weeks of gestational age) benefit from this new schedule or should we keep them in three injections schedule? The objective of this paper is to clarify this point through the data available in the literature. Children born prematurely and especially the "extremely premature" born before 33 weeks are at high risk of infections, some of them are preventable by immunization. Although there is no clinical evidence, for pertussis, pneumococcus, Haemophilus influenzae b, hepatitis B, whatever the immunogenicity criteria, immunogenicity is significantly lower in preterm than in term newborn after 3 doses primary schedule. This lower immunogenicity raises concerns about the transition to two doses, about the ability to give short term protection and booster responses. Given these data, GPIP takes the position for maintaining a primary 3-dose vaccination at 2.3 and 4 months for premature infants less than 33 weeks.

Respiratory morbidity of preterm infants of less than 33 weeks gestation without bronchopulmonary dysplasia: a 12-month follow-up of the CASTOR study cohort.

The aim of this study was to describe the incidence and risk factors for respiratory morbidity during the 12-month period following the first respiratory syncytial virus (RSV) season in 242 preterm infants [<33 weeks gestational age (GA)] without bronchopulmonary dysplasia and 201 full-term infants (39-41 weeks GA) from the French CASTOR study cohort. Preterm infants had increased respiratory morbidity during the follow-up period compared to full-terms; they were more likely to have wheezing (21% vs. 11%, P = 0·007) and recurrent wheezing episodes (4% vs. 1%, P = 0·049). The 17 infants (14 preterms, three full-terms) who had been hospitalized for RSV-confirmed bronchiolitis during their first RSV season had significantly more wheezing episodes during the follow-up period than subjects who had not been hospitalized for RSV-confirmed bronchiolitis (odds ratio 4·72, 95% confidence interval 1·71-13·08, P = 0·003). Male gender, birth weight <3330 g and hospitalization for RSV bronchiolitis during the infant's first RSV season were independent risk factors for the development of wheezing episodes during the subsequent 12-month follow-up period.

[Update on vaccine research. Proceedings of the 15th annual conference on vaccine research organized by the National Foundation for Infectious Diseases]. / Actualités en matière de recherche vaccinale. Compte-rendu de la 15(e) conférence annuelle sur la recherche vaccinale organisée par la National Foundation for Infectious Diseases.

Every year, the National Foundation for Infectious Diseases brings together more than 300 participants to review progress in vaccine research and development and identify the most promising avenues of research. These conferences are among the most important scientific meetings entirely dedicated to vaccine research for both humans and animals, and provide a mix of plenary sessions with invited presentations by acknowledged international experts, parallel sessions, poster sessions, and informal exchanges between experts and young researchers. During the Fifteenth Conference that took place in Baltimore in May 2012, various topics were addressed, including the scientific basis for vaccinology; exploration of the immune response; novel vaccine design; new adjuvants; evaluation of the impact of newly introduced vaccines (such as rotavirus, HPV vaccines); vaccine safety; and immunization strategies. The new techniques of systems biology allow for a more comprehensive approach to the study of immune responses in order to identify correlates of protection and to design novel vaccines against chronic diseases such as AIDS or malaria, against which natural immunity is incomplete.

[Epidemiological study of very preterm infants at Rouen University Hospital: changes in mortality, morbidity, and care over 11 years]. / Évolution de la mortalité, de la morbidité et de la prise en charge des grands prématurés dans un centre de niveau III : comparaison des années 2000, 2005 et 2010.

The very preterm birth rate has increased in the past few years. Despite advances in neonatal medicine, neurodevelopmental sequelae have not decreased, despite a perinatal plan published in France in 1994. We conducted an epidemiological comparative survey at Rouen University Hospital in order to analyze morbidity, mortality, and care of very of premature infants by comparing the years 2000, 2005, and 2010. This hospital draws on an area of 17,000 births per year. Our survey was a single-center prospective, descriptive, and comparative study. The three cohorts had the same characteristics and the mortality rate was constant for 11 years. Use of medically assisted procreation and maternal age increased over this period. Chorioamnionitis halved, whereas duration of intrapartum antibiotic therapy increased. Neonatal morbidity was stable for hyaline membrane disease, bronchopulmonary dysplasia, maternofetal or nosocomial infections, and necrotizing enterocolitis. Regarding neurological complications, intraventricular hemorrhages decreased and white matter lesions remained constant. The rate of severe retinopathy remained low. The duration of parenteral nutrition and assisted ventilation, use of postnatal corticosteroids, and length of hospitalization decreased. The breastfeeding rate has increased since 2000 in parallel with postnatal growth restriction : 39% of the premature infants had a weight under the 10th percentile at hospital discharge. Our study allowed us to follow up the changes in neonatal epidemiological characteristics, the mortality and morbidity of extreme premature infants over a period of 11 years and showed few significant changes. Knowledge of medical practices is essential to improve the short- and long-term outcome of premature infants.

Hospitalizations for respiratory syncytial virus bronchiolitis in preterm infants at <33 weeks gestation without bronchopulmonary dysplasia: the CASTOR study.

This study was conducted during the 2008-2009 respiratory syncytial virus (RSV) season in France to compare hospitalization rates for bronchiolitis (RSV-confirmed and all types) between very preterm infants (<33 weeks' gestational age, WGA) without bronchopulmonary dysplasia and full-term infants (39-41 WGA) matched for date of birth, gender and birth location, and to evaluate the country-specific risk factors for bronchiolitis hospitalization. Data on hospitalizations were collected both retrospectively and prospectively for 498 matched infants (249 per group) aged <6 months at the beginning of the RSV season. Compared to full-term infants, preterm infants had a fourfold [95% confidence interval (CI) 1·36-11·80] and a sevenfold (95% CI 2·79-17·57) higher risk of being hospitalized for bronchiolitis, RSV-confirmed and all types, respectively. Prematurity was the only factor that significantly increased the risk of being hospitalized for bronchiolitis. The risk of multiple hospitalizations for bronchiolitis in the same infant significantly increased with male gender and the presence of siblings aged ⩾2 years.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

Pandemic A/H1N1/2009 influenza in a paediatric haematology and oncology unit: successful management of a sudden outbreak.

Viral respiratory infections are potentially life-threatening among children treated for cancer. We report a nosocomial outbreak of six cases of pandemic influenza A/H1N1/2009 on a paediatric haematology and oncology ward. Three patients developed pneumonia and two of them sustained haemodynamic collapse. The source was probably a relative of the first infected patient. The outbreak was probably spread by cross-infection between patients during communal activities. A few days' delay in identifying the outbreak promoted spread of the influenza. Infection control measures included the use of oral oseltamivir treatment for all hospitalised patients, isolation of the infected patients, strict personal protective controls and a restriction on visitors. No new cases occurred after implementation of these containment measures. At the time when the outbreak was identified, all the patients were already isolated for other reasons. We conclude that A/H1N1/2009 influenza may spread rapidly and cause severe infection in paediatric cancer patients but can be efficiently contained. Identification of isolated or clustered cases should lead to the rapid implementation of appropriate infection control measures.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.