Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption. OBJECTIVES: To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations. METHODS: We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression. RESULTS: We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (-0.5% per month; 95% CI -0.9 to -0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (-22.2%; 95% CI -33.0 to -11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence. CONCLUSIONS: In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved.

Surveillance of noninvasive group A Streptococcus infections in French ambulatory pediatrics before and during the COVID-19 pandemic: a prospective multicenter study from 2018-2022.

OBJECTIVES: We evaluated the burden of noninvasive group A Streptococcus (GAS) infections in ambulatory pediatrics before and during the COVID-19 pandemic in France. METHODS: We analyzed data from a national network of ambulatory pediatricians between 2018 and 2022. Clinicians evaluating children ≤15 years old for tonsillopharyngitis, perianal infections, paronychia/blistering dactylitis, and scarlet fever were invited to perform a rapid antigen detection test (RADT) for GAS. Monthly incidence of noninvasive GAS infections per 10,000 visits was modeled using time series analysis, considering two breakpoints: March 2020 (first national lockdown) and March 2022 (end of mandatory mask-wearing in schools). RESULTS: Over the study period, 125 pediatricians recorded 271,084 infectious episodes. GAS-related illnesses represented 4.3% of all infections. In March 2020, the incidence of GAS diseases decreased by 84.5% (P <0.001), with no significant trend until March 2022. After March 2022, the incidence significantly increased (+23.8% per month, P <0.001), with similar patterns across all monitored GAS-related diseases. CONCLUSION: By using routine clinical data and RADTs, we have monitored changes in the incidence of noninvasive GAS infections in ambulatory pediatrics. COVID-19 mitigation measures have had a major impact on the epidemiology of noninvasive GAS infections, but their relaxation was followed by a surge above baseline levels.

Respiratory Syncytial Virus in Outpatient Children with Bronchiolitis: Continuous Virus Circulation During the Nonepidemic Period.

We aimed to estimate the respiratory syncytial virus positivity rate among ambulatory children with bronchiolitis according to the bronchiolitis epidemic period as defined by the French Public Health Institute. The positivity rate was 28.9% during the nonepidemic period and 50.6% during the epidemic period, which suggests continuous virus circulation between bronchiolitis annual peaks.

Trends in pediatric ambulatory community acquired infections before and during COVID-19 pandemic: A prospective multicentric surveillance study in France.

Background: Covid-19 pandemic control has imposed several non-pharmaceutical interventions (NPIs). Strict application of these measures has had a dramatic reduction on the epidemiology of several infectious diseases. As the pandemic is ongoing for more than 2 years, some of these measures have been removed, mitigated, or less well applied. The aim of this study is to investigate the trends of pediatric ambulatory infectious diseases before and up to two years after the onset of the pandemic. Methods: We conducted a prospective surveillance study in France with 107 pediatricians specifically trained in pediatric infectious diseases. From January 2018 to April 2022, the electronic medical records of children with an infectious disease were automatically extracted. The annual number of infectious diseases in 2020 and 2021 was compared to 2018-2019 and their frequency was compared by logistic regression. Findings: From 2018 to 2021, 185,368 infectious diseases were recorded. Compared to 2018 (n=47,116) and 2019 (n=51,667), the annual number of cases decreased in 2020 (n=35,432) by about a third. Frequency of scarlet fever, tonsillopharyngitis, enteroviral infections, bronchiolitis, and gastroenteritis decreased with OR varying from 0·6 (CI95% [0·5;0·7]) to 0·9 (CI95% [0·8;0·9]), p<0·001. In 2021, among the 52,153 infectious diagnoses, an off-season rebound was observed with increased frequency of enteroviral infections, bronchiolitis, gastroenteritis and otitis with OR varying from 1·1 (CI95% [1·0;1·1]) to 1·5 (CI95% [1·4;1·5]), p<0·001. Interpretation: While during NPIs strict application, the overall frequency of community-acquired infections was reduced, after relaxation of these measures, a rebound of some of them (enteroviral infections, bronchiolitis, gastroenteritis, otitis) occurred beyond the pre-pandemic level. These findings highlight the need for continuous surveillance of infectious diseases, especially insofar as future epidemics are largely unpredictable. Funding: ACTIV, AFPA, GSK, MSD, Pfizer and Sanofi.

New Approach to the Surveillance of Pediatric Infectious Diseases From Ambulatory Pediatricians in the Digital Era.

BACKGROUND: Many ambulatory networks in several countries have established syndromic surveillance systems to detect outbreaks of different illnesses. Here, we describe a new Pediatric and Ambulatory Research in Infectious diseases network that combined automated data extraction from the computers of primary care pediatricians. METHODS: Pediatricians who used the same software, AxiSanté 5-Infansoft for electronic medical records were specially trained in infectious diseases, encouraged to comply with French treatments' recommendations, use of point-of-care tests and vaccination guidelines. Infectious disease diagnoses in children <16 years old in the records triggered automatic data extraction of complete records. A quality control process and external validation were developed. RESULTS: From September 2017 to February 2020, 107 pediatricians enrolled 57,806 children (mean age 2.9 ± 2.6 years at diagnosis) with at least one infectious disease diagnosis among those followed by the network. Among the 118,193 diagnoses, the most frequent were acute otitis media (n = 44,924, 38.0%), tonsillopharyngitis (n = 13,334, 11.3%), gastroenteritis (n = 12,367, 10.5%), influenza (n = 11,062, 9.4%), bronchiolitis (n = 10,531, 8.9%), enteroviral infections (n = 8474, 7.2%) and chickenpox (n = 6857, 5.8%). A rapid diagnostic test was performed in 84.7% of cases of tonsillopharyngitis and was positive in 44%. The antibiotic recommendations from French guidelines were strictly followed: amoxicillin was the most prescribed antibiotic and less than 10% of presumed viral infections were treated. CONCLUSIONS: This "tailor-made" network set up with quality controls and external validation represents a new approach to the surveillance of pediatric infectious diseases in the digital era and could highly optimize pediatric practices.

[Preventing cancer: The role of Papillomavirus vaccination in the general population]. / Prévenir les cancers : place de la vaccination Papillomavirus en population générale.

Papillomavirus (HPV), the first sexually transmitted disease in the world, is the main infectious agent responsible for cancer (6300 per year, in France). The cycle of HPV infection - >precancerous lesions - >cancer is well documented with regard to the cervix (cf. Nobel Prize in 2008). While this area is the most frequent (3000), it is far from being the only one. Other cancers include the anus, oropharyngeal sphere, glans and vulva. The sum of these other induced HPV cancers is greater than the total number of cervical cancers and also concerns boys. Screening is essential but insufficient and only concerns the cervix. Only vaccination can provide primary and general prevention. Since 2007, there have been many studies demonstrating its excellent efficacy and tolerance. However, France lags behind other countries with a vaccination coverage (<30 %) that does not allow for an epidemiological impact.

Timeliness of vaccination in infants followed by primary-care pediatricians in France.

Vaccination status is more often evaluated by up-to-date vaccination coverage rather than timeliness of immunization. Delaying vaccination may be dangerous during infancy. The aim of this study was to identify the importance of potentially dangerous vaccination delay (previously defined) and determinants of these delays. We conducted a national, prospective, vaccination survey in June 2014, with primary care pediatricians. Children, 2 to 24 months of age, were included. Data about vaccination were extracted from their health books. Additional data were collected through a standardized questionnaire. Vaccine coverage rate and timeliness were calculated. Variables associated with a potentially dangerous vaccination delay as previously defined were determined by a multivariable analysis. Among the 443 included children (mean age 10.8 months, 49% males), 13% to 58% of vaccine doses according to vaccine type were done with a potentially dangerous delay. Globally, 47% of children had at least one potentially dangerous immunization delay. We identified two risk factors of potentially dangerous delayed immunization globally: an increasing age of the child (adjusted odds ratio: 1.2, 95% confidence interval [CI]: 1.1-1.3, p < 10-3), and a working mother (adjusted OR: 2.4, 95% CI: 1.2-4.7, p = 0.01). Despite a good vaccine coverage rate, a large number of children had a potentially dangerous vaccination delay. A high level of vigilance regarding these immunization delays, and particularly to the patients sharing the risk factors of immunization delay identified here, can increase quality and effectiveness of the vaccine protection.

Antibiotic Resistance of Potential Otopathogens Isolated From Nasopharyngeal Flora of Children With Acute Otitis Media Before, During and After Pneumococcal Conjugate Vaccines Implementation.

BACKGROUND: To re-evaluate antibiotic strategies for acute otitis media (AOM) in young children, we analyzed the trends of nasopharyngeal carriage and antibiotic resistance of Streptococcus pneumoniae (Sp), Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) isolated from young children with AOM during a 16-year period. METHODS: This cross-sectional study analyzed from 2001 to 2016 the nasopharyngeal carriage of Sp, Hi and Mc of young children with AOM. Medical history and physical findings were reported. Periods were defined by pneumococcal conjugate vaccine (PCV) introduction. We separately analyzed the 13-valent PCV (PCV13) period, which started after 2013. RESULTS: During the study, 12,973 children with AOM were enrolled by 138 pediatricians. By comparing the first and last PCV periods, the proportion of children in day care centers and that of AOM with conjunctivitis significantly increased. The proportion of penicillin nonsusceptible Sp carriage significantly decreased during the study, with 0.8% of penicillin-resistant strains isolated in the PCV13 period, but that of ß-lactamase-producing Hi continually increased to 23.6% in 2016. The level of Mc ß-lactamase-producing strains remained high (>97%). In the PCV13 period, the main predictors of ß-lactamase-producing Hi carriage were conjunctivitis (adjusted odds ratio = 6.0, 95% confidence interval [4.7-7.7]) and attending a day care center (2.4 [1.7-3.5]). CONCLUSIONS: In the PCV13 period, the proportion of penicillin-resistant Sp carriage was very low and that of ß-lactamase-producing Hi carriage did not exceed 20% among children with AOM and without conjunctivitis. Our results suggest that amoxicillin may remain the first-line antibiotic treatment for AOM in young children except for those with conjunctivitis, for which amoxicillin-clavulanate is still the best antibiotic.