Consensus statements on the information to deliver after a febrile seizure.

Febrile seizures (FS) are usually self-limiting and cause no morbidity. Nevertheless they represent very traumatic events for families. There is a need to identify key messages that reassure carers and help to prevent inappropriate, anxiety-driven behaviors associated with "fever phobia." No recommendations have been proposed to date regarding the content of such messages. Using a Delphi process, we have established a consensus regarding the information to be shared with families following a FS. Twenty physicians (child neurologists and pediatricians) from five European countries participated in a three-step Delphi process between May 2018 and October 2019. In the first step, each expert was asked to give 10 to 15 free statements about FS. In the second and third steps, statements were scored and selected according to the expert ranking of importance. A list of key messages for families has emerged from this process, which offer reassurance about FS based on epidemiology, underlying mechanisms, and the emergency management of FS should they recur. Interestingly, there was a high level of agreement between child neurologists and general pediatricians.Conclusion: We propose key messages to be communicated with families in the post-FS clinic setting. What is Known: • Febrile seizures (FS) are traumatic events for families. • No guidelines exist on what information to share with parents following a FS. What is New: • A Delphi process involving child neurologists and pediatricians provides consensual statement about information to deliver after a febrile seizure. • We propose key messages to be communicated with families in the post-FS clinic setting.

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.

Biofilm production by Haemophilus influenzae and Streptococcus pneumoniae isolated from the nasopharynx of children with acute otitis media.

BACKGROUND: Biofilm production by Haemophilus influenzae and Streptococcus pneumoniae has been implicated in the pathogenesis of otitis media, mainly in chronic and recurrent cases. We studied the "in vitro" biofilm production by these 2 species isolated alone or together from the nasopharynx of children with acute otitis media. METHODS: The studied strains were from 3 pneumococcal conjugate vaccine (PCV) periods: pre-PCV7, post-PCV7/pre-PCV13 and post-PCV13. A modified microtiter plate assay with crystal violet stain was used to study the biofilm production of 182 H. influenzae and 191 S. pneumoniae strains. RESULTS: Overall, 117/181 (64.6%) H. influenzae and 128/191 (66.8%) S. pneumoniae strains produced biofilm. The proportion of biofilm-producing H. influenzae strains was greater with than without the isolation of S. pneumoniae in the same sample (75.5% vs 52.3%, p = 0.001). Conversely, the proportion of biofilm-producing S. pneumoniae strains was not affected by the presence or not of H. influenzae (66.3% vs 67.4%). S. pneumoniae serotypes 6B, 15B/C, 19A, 35F and 35B were the better biofilm producers (80%). Serotypes 11A, 14, 15A, 19F and 19A were more associated with H. influenzae biofilm-producing strains. Overall, 89/94 (94.6%) of cases with combined isolation showed biofilm production by S. pneumoniae or H. influenzae. CONCLUSION: This study emphasizes the high proportion of biofilm production by H. influenzae and S. pneumoniae strains isolated from the nasopharynx of children with acute otitis media, which reinforces the results of studies suggesting the importance of biofilm in the pathogenesis of acute otitis media.

Tuberculin skin test negativity is under tight genetic control of chromosomal region 11p14-15 in settings with different tuberculosis endemicities.

A substantial proportion of subjects exposed to a contagious tuberculosis case display lack of tuberculin skin test (TST) reactivity. We previously mapped a major locus (TST1) controlling lack of TST reactivity in families from an area in South Africa where tuberculosis is hyperendemic. Here, we conducted a household tuberculosis contact study in a French area where the endemicity of tuberculosis is low. A genome-wide analysis of TST negativity identified a significant linkage signal (P < 3 × 10(-5)) in close vicinity of TST1. Combined analysis of the 2 samples increased evidence of linkage (P = 2.4 × 10(-6)), further implicating genetic factors located on 11p14-15. This region overlaps the TNF1 locus controlling mycobacteria-driven tumor necrosis factor α production.

Rapid-antigen detection tests for group a streptococcal pharyngitis: revisiting false-positive results using polymerase chain reaction testing.

We investigated mechanisms of the false-positive test results on rapid-antigen detection test (RADT) for group A Streptococcal (GAS) pharyngitis. Most RADT false-positives (76%) were associated with polymerase chain reaction-positive GAS results, suggesting that RADT specificity could be considered close to 100%. Finding that 61% of GAS culture-negative but RADT-positive cases were positive on both GAS polymerase chain reaction and Staphylococcus aureus testing, we posit bacterial inhibition as causative.

Food intake during the previous 24 h as a percentage of usual intake: a marker of hypoxia in infants with bronchiolitis: an observational, prospective, multicenter study.

BACKGROUND: Hypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24 hours (bottle and spoon feeding), as a percentage of usual intake (24h FI), as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs. METHODS: In this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6 months, with bronchiolitis (rhinorrhea + dyspnea + cough + expiratory sounds). Infants with risk factors (history of prematurity, chronic heart or lung disorders), breast-fed infants, and infants having previously been treated for bronchial disorders were excluded.The 24h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO2) was recorded. Hypoxia was noted if SpO2 was below 95% and verified. RESULTS: 24h FI ≥ 50% was associated with a 96% likelihood of SpO2 ≥ 95% [95% CI, 91-99]. In univariate analysis, 24h FI < 50% had the highest odds ratio (13.8) for SpO2 < 95%, compared to other 24h FI values and other clinical signs, as well as providing one of the best compromises between specificity (90%) and sensitivity (60%) for identifying infants with hypoxia. In multivariate analysis with adjustment for age, SpO2 < 95% was related to the presence of intercostal retractions (OR = 9.1 [95% CI, 2.4-33.8%]) and 24h FI < 50% (OR = 10.9 [95% CI, 3.0-39.1%]). Hospitalization (17 infants) was strongly related to younger age, 24h FI and intercostal retractions. CONCLUSION: In practice, the measure of 24 h FI may be useful in identifying hypoxia and deserves further study.

Antibiotic Resistance of Haemophilus influenzae in Nasopharyngeal Carriage of Children with Acute Otitis Media and in Middle Ear Fluid from Otorrhea.

Haemophilus influenzae (Hi) is one of the leading bacteria implicated in childhood acute otitis media (AOM). Recent concerns have been raised about the emergence of Hi-resistant strains. We aimed to analyze the evolution of ß-lactam resistance to Hi among strains isolated from nasopharyngeal carriage in children with AOM and in mild ear fluid (MEF) after the spontaneous perforation of the tympanic membrane (SPTM) in France. In this national ambulatory-based cohort study over 16 years, we analyzed the rate of Hi nasopharyngeal carriage and the proportion of ß-lactam-resistant Hi strains over time using a segmented linear regression model. Among the 13,865 children (median [IQR] age, 12.7 [9.3-17.3] months; 7400 [53.4%] male) with AOM included from November 2006 to July 2022, Hi was isolated in 7311 (52.7%) children by nasopharyngeal sampling. The proportion of ß-lactamase-producing and ß-lactamase-negative, ampicillin-resistant (BLNAR) Hi strains in nasopharyngeal carriage remained stable during the study period. Among the 783 children (median [IQR] age, 20 [12.3-37.8] months; 409 [52.2%] male) with SPTM included from October 2015 to July 2022, Hi was isolated in 177 (22.6%) cases by MEF sampling. The proportions of ß-lactamase-producing and BLNAR Hi strains did not significantly differ between nasopharyngeal (17.6% and 8.8%, respectively) and MEF (12.6% and 7.4%) samples. Accordingly, amoxicillin remains a valid recommendation as the first-line drug for AOM in France.

Assessment of SARS-CoV-2 infection by Reverse transcription-PCR and serology in the Paris area: a cross-sectional study.

BACKGROUND: Several studies indicated that children seem to be less frequently infected with SARS-CoV-2 and are potentially less contagious than adults. To examine the spread of SARS-CoV-2, we combined both Reverse transcription-PCR testing and serology in children in the most affected region in France, Paris, during the COVID-19 epidemic. METHODS: From 14 April 2020 to 12 May 2020, we conducted a cross-sectional, prospective, multicentre study. Healthy controls and pauci-symptomatic children from birth to age 15 years were enrolled by 27 ambulatory paediatricians. A nasopharyngeal swab was taken for detection of SARS-CoV-2 by Reverse transcription-PCR and a microsample of blood for micromethod serology. RESULTS: Among the 605 children, 322 (53.2%) were asymptomatic and 283 (46.8%) were symptomatic. Reverse transcription-PCR and serology results were positive for 11 (1.8%) and 65 (10.7%) children, respectively, with no significant difference between asymptomatic and pauci-symptomatic children. Only three children were Reverse transcription-PCR-positive without any antibody response detected. The frequency of Reverse transcription-PCR SARS-CoV-2 positivity was significantly higher for children with positive than negative serology results (12.3% vs 0.6%, p<0.001). Contact with a person with confirmed COVID-19 increased the odds of Reverse transcription-PCR positivity (OR 7.8, 95% CI 1.5 to 40.7) and serology positivity (OR 15.1, 95% CI 6.6 to 34.6). CONCLUSION: In an area heavily affected by COVID-19, after the peak of the first epidemic wave and during the lockdown, the rate of children with Reverse transcription-PCR SARS-CoV-2 positivity was very low (1.8%), but that of serology positivity was higher (10.7%). Most children with positive Reverse transcription-PCR results also had positive serology results. TRIAL REGISTRATION NUMBER: NCT04318431.

Bacterial causes of otitis media with spontaneous perforation of the tympanic membrane in the era of 13 valent pneumococcal conjugate vaccine.

After pneumococcal conjugate vaccine (PCV) implementation, the number of acute otitis media (AOM) episodes has decreased, but AOM still remains among the most common diagnoses in childhood. From 2% to 17% of cases of AOM feature spontaneous perforation of the tympanic membrane (SPTM). The aim of this study was to describe the bacteriological causes of SPTM 5 to 8 years years after PCV13 implementation, in 2010. From 2015 to 2018, children with SPTM were prospectively enrolled by 41 pediatricians. Middle ear fluid was obtained by sampling spontaneous discharge. Among the 470 children with SPTM (median age 20.8 months), no otopathogen was isolated for 251 (53.4% [95% CI 48.8%;58.0%]): 47.1% of infants and toddlers, 68.3% older children (p<0.001). Among children with isolated bacterial otopathogens (n = 219), non-typable Haemophilus influenzae (NTHi) was the most frequent otopathogen isolated (n = 106, 48.4% [95% CI 41.6%;55.2%]), followed by Streptoccocus pyogenes (group A streptococcus [GAS]) (n = 76, 34.7% [95% CI 28.4%;41.4%]) and Streptococcus pneumoniae (Sp) (n = 61, 27.9% [95% Ci 22.0%;34.3%]). NTHi was frequently isolated in infants and toddlers (53.1%), whereas the main otopathogen in older children was GAS (52.3%). In cases of co-infection with at least two otopathogens (16.9%, n = 37/219), NTHi was frequently involved (78.4%, n = 29/37). When Sp was isolated, PCV13 serotypes accounted for 32.1% of cases, with serotype 3 the main serotype (16.1%). Among Sp strains, 29.5% were penicillin-intermediate and among NTHi strains, 16.0% were ß-lactamase-producers. More than 5 years after PCV13 implementation, the leading bacterial species recovered from AOM with SPTM was NTHi for infants and toddlers and GAS for older children. In both age groups, Sp was the third most frequent pathogen and vaccine serotypes still played an important role. No resistant Sp strains were isolated, and the frequency of ß-lactamase-producing NTHi did not exceed 16%.

Sickness behavior in feverish children is independent of the severity of fever. An observational, multicenter study.

BACKGROUND. OBJECTIVES: Behavioral changes in a febrile child are usually considered to stem from the fever. We studied sickness behavior (SB) in terms of its clinical components and its relation to fever. METHODS: This observational, multicenter study included children aged 6 months to 3 years who were either febrile (fever ≥12 hours, ≥ 39°C and ≥38°C at inclusion) or non-febrile and well. The child had to have been awake for the 2 hours preceding the consultation and cared for by the parent who brought him/her to the doctor. SB was evaluated according to 6 parameters over this 2-hour period: time spent playing, distance covered, time spent seeking comfort, time spent whining or crying, time spent in a state of irritation or of anger, most distorted facial expression. Two parameters were assessed for the 24-hour period preceding the consultation: time spent sleeping and appetite. The parent reported the degree of change in these parameters compared with the usual situation, using rating scales. RESULTS: 200 febrile children (most with nonspecific upper respiratory infections) and 200 non-febrile children were included. The mean values of the 8 parameters differed significantly (p<0.001) between the 2 groups and were independent of the height of fever at inclusion in the febrile children. In the study conditions, paracetamol failed to improve SB when the child was still feverish. CONCLUSION: The 8 parameters suggested that SB and fever are two independent manifestations that are activated simultaneously during an infection. This independence is in harmony with recommendations to treat the discomfort of SB and not the fever.