Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

This study provides solid evidence that among infants for whom a source case was identified, household members were responsible for 76%-83% of transmission of Bordetella pertussis to this high-risk group. Vaccination of adolescents and adults in close contact with young infants may thus eliminate a substantial proportion of infant pertussis if high coverage rates can be achieved.

NALP proteins, also known as NLRPs, belong to the CATERPILLER protein family involved, like Toll-like receptors, in the recognition of microbial molecules and the subsequent activation of inflammatory and immune responses. Current advances in the function of NALPs support the recently proposed model of a disease continuum bridging autoimmune and autoinflammatory disorders. Among these diseases, hereditary periodic fevers (HPFs) are Mendelian disorders associated with sequence variations in very few genes; these variations are mostly missense mutations whose deleterious effect, which is particularly difficult to assess, is often questionable. The growing number of identified sporadic cases of periodic fever syndrome, together with the lack of discriminatory clinical criteria, has greatly hampered the identification of new disease-causing genes, a step that is, however, essential for appropriate management of these disorders. Using a candidate gene approach, we identified nonambiguous mutations in NALP12 (i.e., nonsense and splice site) in two families with periodic fever syndromes. As shown by means of functional studies, these two NALP12 mutations have a deleterious effect on NF-B signaling. Overall, these data identify a group of HPFs defined by molecular defects in NALP12, opening up new ways to manage these disorders. The identification of these first NALP12 mutations in patients with autoinflammatory disorder also clearly demonstrates the crucial role of NALP12 in inflammatory signaling pathways, thereby assigning a precise function to this particular member of an emerging family of proteins whose putative biological properties are currently inferred essentially through in vitro means.genetics ͉ Mendelian disorder ͉ NLRP ͉ autoinflammatory disorder ͉ CATERPILLER

Since the beginning of the COVID-19 pandemic, reduced incidence of many viral and bacterial infections has been reported in children: bronchiolitis, varicella, measles, pertussis, pneumococcal and meningococcal invasive diseases. The purpose of this opinion paper is to discuss various situations that could lead to larger epidemics when the non-pharmaceutical interventions (NPI) imposed by the SARS-CoV-2 epidemic will no longer be necessary. While NPIs limited the transmission of SARS-CoV-2, they also reduced the spread of other pathogens during and after lockdown periods, despite the re-opening of schools since June 2020 in France. This positive collateral effect in the short term is welcome as it prevents additional overload of the healthcare system. The lack of immune stimulation due to the reduced circulation of microbial agents and to the related reduced vaccine uptake induced an "immunity debt" which could have negative consequences when the pandemic is under control and NPIs are lifted. The longer these periods of "viral or bacterial low-exposure" are, the greater the likelihood of future epidemics. This is due to a growing proportion of "susceptible" people and a declined herd immunity in the population. The observed delay in vaccination program without effective catch-up and the decrease in viral and bacterial exposures lead to a rebound risk of vaccine-preventable diseases. With a vaccination schedule that does not include vaccines against rotavirus, varicella, and serogroup B and ACYW Neisseria meningitidis , France could become more vulnerable to some of these rebound effects.

Intussusception, a potentially lethal condition with poorly understood etiology, is the most common cause of acute intestinal obstruction in children younger than 5 years old. In some cases, the condition has been associated with administration of the first licensed rotavirus vaccine, the reassortant rhesus-human tetravalent rotavirus vaccine (RRV-TV; RotaShield). No such association has to date been reported from large phase III safety trials with new rotavirus vaccines. As 2 new, live-attenuated oral rotavirus vaccines are currently under review for approval by the European Union regulatory authorities, a review of the clinical, etiologic and epidemiologic aspects of intussusception in Europe is urgently needed. We conducted a review of Medline literature, published from 1995 onwards on intussusception in the World Health Organization's European Region. The results are compared with data from previous reviews and other regions. The classic triad of intussusception symptoms (abdominal pain, abdominal mass, bloody stools) was present in 29-33% of patients according to the medical literature reviewed. Conservative treatment (barium, air or saline enema) was the rule (81% of cases), and few complications were observed during treatment. Treatment outcome was generally favorable, with recurrence occurring in approximately 1 in 10 patients, and only 1 death reported. Structural lead points were seen in 3% of patients; no other reliable data on the etiology of intussusception were found. The incidence of acute intussusception in young children in Europe, according to 6 heterogeneous hospital-based studies, ranged from 0.66 to 2.24 per 1000 children in inpatient departments and from 0.75 to 1.00 per 1000 children in emergency departments. Peak incidences were found in children 3-9 months of age. There are still gaps in our knowledge of intussusception with respect to its etiology and especially by which mechanisms RRV-TV might have caused it to occur. Data from regions outside Europe showed that rotavirus infection and disease are not associated with intussusception. As new rotavirus vaccines become available for use in Europe, postlicensure surveillance for intussusception is indicated and may be instrumental in further understanding the epidemiology of this condition and in further assessing the safety of future vaccines.

Children with IPD should undergo immunological investigations, particularly those aged >2 years, as PIDs may be discovered in up to 26% of cases.

Although pertussis vaccination coverage is very high in France, the organism is still circulating, affecting, within the pediatric population, mostly non- or incompletely vaccinated infants. These results strongly support the importance of adhering to the immunization schedule and suggest introducing booster dose(s) to prolong vaccine immunity and reduce the exposure to Bordetella pertussis of infants too young to be immunized.

IgM immunoblotting and polymerase chain reaction (PCR) were evaluated for use in diagnosing congenital syphilis, and the prevalence of central nervous system (CNS) invasion by Treponema pallidum during congenital infection was examined. The results of rabbit infectivity testing (RIT) on serum and cerebrospinal fluid (CSF) of 19 infants born to mothers with untreated early syphilis were compared with results of PCR and IgM immunoblotting. Seven infants had clinical evidence of congenital syphilis supported by positive serum IgM immunoblot (7/7), PCR (6/7), and RIT (3/3). Six symptomatic infants (86%) had T. pallidum isolated from CSF by RIT; 5 of 6 RIT-positive CSF samples were positive by PCR, and 2 also were reactive by IgM immunoblot. In 12 asymptomatic infants, 5 (42%) had a reactive serum IgM immunoblot and in 4 of these IgM reactivity was the only evidence of congenital infection. CNS invasion by T. pallidum was uncommon among asymptomatic infants; only 1 (8%) was positive by CSF RIT. The excellent agreement between RIT and PCR further substantiates the use of PCR as a surrogate for RIT. Our data indicate that the diagnosis of asymptomatically infected neonates will require a comprehensive approach using assays for both specific neonatal IgM and T. pallidum DNA in serum and CSF.