French National Diagnostic and Care Protocol for antiphospholipid syndrome in adults and children.

Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features. APS may be rapidly progressive with multiple, often synchronous thromboses, resulting in life-threatening multiple organ failure. This form is known as "catastrophic antiphospholipid syndrome" (CAPS). It may be primary or associated with systemic lupus erythematosus (associated APS) and in very rare cases with other systemic autoimmune diseases. General practitioners and paediatricians may encounter APS in patients with one or more vascular thromboses. Because APS is so rare and difficult to diagnosis (risk of overdiagnosis) any suspected case should be confirmed rapidly and sometimes urgently by an APS specialist. First-line treatment of thrombotic events in APS includes heparin followed by long-term anticoagulation with a VKA, usually warfarin. Except in the specific case of stroke, anticoagulants should be started as early as possible. Any temporary discontinuation of anticoagulants is associated with a high risk of thrombosis in APS. A reference/competence centre specialised in autoimmune diseases must be urgently consulted for the therapeutic management of CAPS.

Strengths and limitations of a policy for handling and following up suspected pediatric cases of SARS-CoV-2 infection.

To compensate for the poor initial knowledge about pediatric SARS-CoV-2 infections and the limited access to non-urgent medical care during lockdown, a local telephone follow-up program was set up to remotely monitor children with confirmed or suspected SARS-CoV-2 infection at the pediatric emergency department of a French tertiary hospital. We retrospectively assessed 131 children. A total of 488 phone call attempts resulted in 293 (60%) teleconsultations. This telephone follow-up program was simple and appeared necessary in the first stage of the pandemic with an emergent pathogen. However, it was time-consuming and should be improved for further use.

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.

Impact of social deprivation on length of stay for common infectious diseases in two French university-affiliated general pediatric departments.

BACKGROUND: Adult deprived patients consume more healthcare resources than others, particularly in terms of increased length of stay (LOS) and costs. Very few pediatric studies have focused on LOS, although the effect of deprivation could be greater in children due to the vulnerability of this population. Our objective was to compare LOS between deprived and nondeprived children hospitalized for acute infectious diseases in two university-affiliated pediatric departments located in a low-income area of northern Paris. METHODS: We performed a prospective observational multicenter study in two university-affiliated hospitals, Hôpital Robert-Debré and Hôpital Jean-Verdier. All the patients under 15 years of age admitted to the general pediatric department for pneumonia, bronchiolitis, gastroenteritis, or pyelonephritis between 20 October 2016 and 20 March 2017 were included. Deprivation was assessed with an individual questionnaire and score (EPICES). Endpoints included length of stay, costs, and readmission rates at 15 days in each quintile of deprivation. Multivariate regression assessed the association between deprivation and each endpoint. RESULTS: A total of 556 patients were included in the study and 540 were analyzed. Sixty percent were boys and the mean age was 9 months±18. Bronchiolitis was the most frequent diagnosis (67.8%). Fifty-six percent of patients were considered to be deprived based on the EPICES questionnaire. Mean LOS was 4.6±3.5 days and we found no significant difference in LOS between the different deprivation quintiles (P=0.83). Multivariate regression did not show an association between LOS and deprivation. CONCLUSION: There was no difference between deprived and nondeprived patients in terms of LOS. Deprivation may therefore impact hospitals in other ways such as admission rates. The impact of deprivation during hospitalization for chronic diseases should also be investigated.

The association of severe encephalopathy and question mark ear is highly suggestive of loss of MEF2C function.

Auriculocondylar syndrome and isolated question mark ear result from dysregulation of the endothelin 1-endothelin receptor type A signaling pathway. Animal models have highlighted the role of the transcription factor MEF2C as an effector of this pathway. We report heterozygous MEF2C loss-of-function as a possible cause of question mark ear associated with intellectual deficiency.

[Iron and susceptibility to infections]. / Fer et prédisposition aux infections.

Iron is essential for proper functioning of the host immune system as well as an essential nutrient for growth of various pathogens. Iron deficiency increases infection susceptibility, specially those due to intracellular pathogens. At the opposite, excess iron stores could increase the virulence of some pathogens. Hepcidin synthesis is increased during the acute inflammation phase; leading to decreased iron intestinal absorption and retention of the metal within macrophages. This is considered to result from a defense mechanism of the child to limit the availability of iron for extracellular pathogens. On the other hand, iron affect innate immune responses by influencing IFN-γ or NF-kB pathways in macrophages. Consequently, iron enhances host resistance to intracellular pathogens but excess iron may alter immune system.

[Kikuchi-Fujimoto disease mimicking malignant lymphoma in adolescents]. / La maladie de Kikuchi-Fujimoto ; un diagnostic différentiel méconnu du lymphome chez l'adolescent.

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a rare cause of lymphadenopathy in children. This benign disease can mimic lymphoma and misleads doctors. It was first described in Asia, where it occurred especially in young women. Recent publications show that it can also affect teenagers and young adults in Caucasian populations. The pathophysiology remains unknown. Three hypotheses have been raised for this disease: the role of viruses (in particular HHV-8), genetic predisposition (two alleles in HLA class II genes were found more frequently in patients with Kikuchi disease), and an autoimmune cause because of the correlation with lupus erythematosus. Few cases have been reported in Europe so far. In this article, we report three cases of Kikuchi disease observed in less than 2 months in a single hospital in France. All three patients were teenagers who presented with lymphadenopathy, either isolated or combined with fever, weakness, and weight loss. In all of them, the hypermetabolic activity of the lymph node on the PET scanner misled us to suspect lymphoma. The diagnosis of Kikuchi disease was finally made, for all patients, after 2 weeks in the hospital based on lymph node biopsy. Based on this report, we highlight that early biopsy in presence of lymphadenopathy can avoid unnecessary extensive investigations. Moreover, in this rare disease, it is very surprising to come across three cases that are not family-related, in such a short period of time. This strengthens the hypothesis of the possible implication of an environmental factor in the pathophysiology of Kikuchi disease.

Antimicrobial treatment of infrequent bacterial species isolated in children.

This section summarizes the empirical antimicrobial treatment according to the less frequent bacterial species responsible for infection whether community-acquired or nosocomial. It specifies their role in diseases and the recommended antibiotics, taking into account their natural and most common acquired resistance and the pharmacokinetic-pharmacodynamic parameters. The advice of an infectious disease specialist or bacteriologist is recommended.

Outcomes of bacterial meningitis in children.

OBJECTIVE: Pediatricians are well aware of the immediate risks of bacterial meningitis in children. However, the long-term outcome of the disease has not been extensively studied. We aimed: (i) to evaluate the duration and quality of the long-term follow-up of children diagnosed with bacterial meningitis in a general pediatric department, (ii) to estimate the incidence of sequelae at the various stages of follow-up, and (iii) to compare our data with that of other studies. METHODS: We conducted a retrospective study and included 34 children (3 months-15 years) who had been hospitalized for bacterial meningitis in the pediatric department of a University Hospital between January 1st, 2001 and December 31st, 2013. RESULTS: Overall, 32% of patients presented with sequelae and 15% with seizures. Only one patient presented with hearing loss, but 23.5% of patients did not have any hearing test performed. Seven patients had a neuropsychological assessment performed and no severe neuropsychological sequela was observed in this group. The average follow-up duration increased during the study period (from 23 to 49months). The long-term follow-up modalities observed in other studies were highly variable. Assessing the incidence and severity of sequelae was therefore difficult. CONCLUSION: A standardized follow-up should be implemented by way of a national surveillance network of children presenting with bacterial meningitis.

[Visceral leishmaniasis without splenomegaly. A pediatric case report]. / Leishmaniose viscérale sans splénomégalie. À propos d'un cas chez un nourrisson.

Pediatric visceral leishmaniasis is caused by Leishmania infantum, a dog parasite transmitted to humans by the bite of the female phlebotomine sand fly. The well-known clinical triad is fever, pallor, and splenomegaly. A secondary macrophage activation syndrome (MAS) can complicate this infection, which is lethal when not treated. When MAS is observed without any explanation, a visceral leishmaniasis is highly recommended. We report a case of visceral leishmaniasis in a 21-month-old child complicated by a macrophage activation syndrome without splenomegaly. No immunodeficiency was diagnosed that could explain this unusual clinical condition. To our knowledge, this is the first case of visceral leishmaniasis without splenomegaly reported to date.

[Association between the presence of antiphospholipid antibodies and the occurrence of autism spectrum disorder in childhood]. / Lien entre trouble du spectre autistique de l'enfant et anticorps antiphospholipides : une étude cas-témoin.

OBJECTIVES: To evaluate the association between the presence of antiphospholipid (APL) antibodies and the occurrence of autism spectrum disorder (ASD) in childhood. METHODS: A prospective, monocentric case-control study from February 2012 to August 2014 comparing the APL antibodies of children with ASD (group 1) and children without ASD (group 2). RESULTS: Group 1 consisted of 44 children with ASD defined by clinical, genetic, metabolic, and morphological criteria. Group 2 consisted of 26 control children without ASD. One of children with ASD (2.3 %) had persistent anticardiolipin (ACL) antibodies, five of them (11.4 %) had persistent APL antibodies, one of them (2.3 %) had antiannexin V (AAV) antibodies, and two of them (4.5 %) had antiphosphatidylethanolamine (APE) antibodies. Two of the control children (7.7 %) had persistent APL antibodies. None of them had persistent ACL, AAV, or APE antibodies. Comparing group 1 and 2 children, no significant difference was found between the presence and the titers of conventional and non conventional antibodies (P<0.05). Furthermore, one mother of an autistic child (3 %) had persistent APL antibodies. CONCLUSION: ASD had no significant relation with the presence of APL antibodies.

[Complement terminal fraction deficiency revealed at first invasive meningococcal infection]. / Déficit en fraction terminale du complément révélé dès le premier épisode d'infection invasive à méningocoque.

Prevalence of complement protein deficiency in the general population is rare and its association with an increased risk of meningococcal infection is well established. However, management of these patients with potentially serious infections and indications warranting a search for such a deficiency have not met with consensus. We report the case of a 3-year-old child with no significant medical history who consulted in an emergency department for a fever after a stay in Senegal. Medical explorations concluded in septicemia and meningococcal W meningitis with a favorable outcome. Secondarily, we highlighted a complete deficiency of complement component C6. We diagnosed the same deficit in his twin sister who presented no infection. A long-term prophylactic antibiotic therapy and a meningococcal conjugate vaccine A,C,Y,W were set up for the twins. Recurrent invasive meningococcal infections and highlighting certain meningococcal serogroups are currently indications for complement protein exploration. We suggest expanding the search criteria for a complement protein deficiency after a single event of invasive meningococcal infection. This is an easy, rapid, and cost-effective screening system by dosage of CH50, C3, C4, and AP50. The arrival of the new meningococcal B vaccine will contribute to improving these patients' care. Family screening is necessary for prophylactic therapy.

Survey of vaccination policies in French healthcare institutions.

OBJECTIVE: The survey was implemented to describe vaccination policies for healthcare professionals in French healthcare institutions. METHODS: A cross-sectional survey based on questionnaires was sent to occupational physicians and chairpersons of hospital infection prevention and control committees (HIPC) of 38 institutions between November 2010 and January 2011. RESULTS: Twenty-nine occupational physicians and 26 hospital infection prevention and control committees chairpersons (HIPC), from 30 institutions answered (response rate: 79%), 70% of the institutions were university hospitals. Overall, 76% of occupational physicians and 85% of HIPC chairpersons reported that information and awareness campaigns about vaccination recommendations for healthcare professionals were usually conducted in their establishment. Fifty-nine percent of occupational physicians and 31% of HIPC chairpersons reported that they were aware of the vaccine coverage rates of professionals in their institution. The occupational physicians reported that they suggested diphtheria, tetanus, polio, influenza, and acellular pertussis vaccination to all staff at their annual visit in 100%, 97%, and 62% of cases, respectively. Varicella and measles vaccinations were never suggested in 31% and 17% of cases, respectively. Among respondents, 55% of physicians reported that they had already managed a pertussis epidemic, and 42% a measles epidemic, and in both of these cases an awareness campaigns were usually conducted (93% and 96%). CONCLUSIONS: The vaccine coverage rates of healthcare professionals in French healthcare institutions remain insufficiently documented and could be improved.

[Severe bacterial infections and sudden death in children less than 4-years-old: 3 case reports]. / Infections bactériennes sévères et morts inattendues de l'enfant de moins de 4ans: à propos de 3 observations.

Infectious factors contribute to sudden infant death in about 1 case out of 3. We report 3 children less than 4-years-old who died suddenly of bacterial infection due to Neisseria meningitidis, Streptococcus pneumoniae, and Staphylococcus aureus. The bacteria were isolated from central and peripheral samples. A bacterial origin should be sought in all cases of sudden death in children. When a bacterial origin is confirmed, the question of immunodeficiency should be raised.

[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.

[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.

[Malformation syndromes associated with childhood cancer: an update]. / Anomalies de développement et prédisposition aux tumeurs de l'enfant.

Biology, genetics and environment of childhood solid tumours set them apart from adult solid tumours. The nature of the progenitor cells from which these tumours arise, and their immature tissue environment, allows childhood solid tumours to develop with fewer defects in cell regulatory processes. Constitutional molecular defects are known to play a role in childhood solid tumours, as shown by the increased incidence of embryonic cancers in children carrying malformations associated with childhood cancer. These rare diagnoses are commonly missed. In this article, we reviewed the spectrum of these tumour predisposition syndromes.