[Epidemiology and the burden of RSV]. / Épidémiologie et fardeau du VRS.

RSV is an almost obligatory virus responsible for upper (rhinitis and otitis) and lower (bronchiolitis and asthma attack) respiratory infections in children under 5 years of age. Reinfections are frequent at all ages because immunity is only partial and does not last long. Young children under the age of 1 are the most affected. The majority of these children are healthy. Having a risk factor (premature birth, heart disease, bronchopulmonary dysplasia, but also passive smoking) increases the severity of RSV pathology. Very few children currently benefit from prevention by anti-RSV monoclonal antibodies. The annual cost of care, the various socio-economic costs are a public health reality in three care sectors: out-patient, pediatric emergencies, hospitalization. Subsequent consequences: repeated wheezing and asthma, should also be taken into consideration and integrated into public health decisions. Progress in recognizing this pathology is desirable: distribution of diagnostic tests in the city; providing parents with information.

Le VRS est un virus quasi obligatoire responsable d'infections respiratoires hautes (rhinite et otite) et basses (bronchiolite et crise d'asthme) chez l'enfant de moins de 5 ans. Les réinfections sont fréquentes du fait d'une immunité partielle, peu durable, à tous les âges de la vie. Les jeunes enfants de moins de 1 an sont les plus touchés. La majorité de ces enfants sont bien portants. Avoir un facteur de risque (prématurité, cardiopathie, dysplasie bronchopulmonaire mais aussi tabagisme passif) majore la sévérité de la pathologie à VRS. Très peu d'enfants bénéficient actuellement d'une prévention par les anticorps monoclonaux anti-VRS. La charge annuelle en soins, les coûts socioéconomiques variés constituent une réalité de santé publique portant sur les trois secteurs de soins : ambulatoire, urgences pédiatriques, hospitalisation.Les conséquences ultérieures : répétition de wheezing, asthme, devraient aussi être pris en considération et intégrés dans les décisions de santé publique.Des progrès dans la reconnaissance de cette pathologie sont souhaitables : diffusion des tests diagnostiques en ville ; information aux parents.

A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. METHODS: To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. FINDINGS: The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. CONCLUSIONS: These results provide potential for a better understanding of disease pathophysiology. FUNDING: Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d'Excellence ''Milieu Intérieur," grant ANR-10-LABX-69-01; ANR-flash Covid19 "AIROCovid" and "CoVarImm"), Institut National de la Santé et de la Recherche Médicale (INSERM), and the "URGENCE COVID-19" fundraising campaign of Institut Pasteur.

Persistent osteoarticular pain in children: early clinical and laboratory findings suggestive of acute lymphoblastic leukemia (a multicenter case-control study of 147 patients).

BACKGROUND: The aim of this study was to identify early clinical and laboratory features that distinguish acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA) in children presenting with persistent bone or joint pain for at least 1 month. METHODS: We performed a multicenter case-control study and reviewed medical records of children who initially presented with bone or joint pain lasting for at least 1 month, all of whom were given a secondary diagnosis of JIA or ALL, in four French University Hospitals. Each patient with ALL was paired by age with two children with JIA. Logistic regression was used to compare clinical and laboratory data from the two groups. RESULTS: Forty-nine children with ALL and 98 with JIA were included. The single most important feature distinguishing ALL from JIA was the presence of hepatomegaly, splenomegaly or lymphadenopathy; at least one of these manifestations was present in 37 cases with ALL, but only in 2 controls with JIA, for an odds ratio (OR) of 154 [95%CI: 30-793] (regression coefficient: 5.0). If the presence of these findings is missed or disregarded, multivariate analyses showed that non-articular bone pain and/or general symptoms (asthenia, anorexia or weight loss) (regression coefficient: 4.8, OR 124 [95%CI: 11.4-236]), neutrophils < 2 × 109/L (regression coefficient: 3.9, OR 50 [95%CI: 4.3-58]), and platelets < 300 × 109/L (regression coefficient: 2.6, OR 14 [95%CI: 2.3-83.9]) were associated with the presence of ALL (area under the ROC curve: 0.96 [95%CI: 0.93-0.99]). CONCLUSIONS: Based on our findings we propose the following preliminary decision tree to be tested in prospective studies: in children presenting with at least 1 month of osteoarticular pain and no obvious ALL in peripheral smear, perform a bone marrow examination if hepatomegaly, splenomegaly or lymphadenopathy is present. If these manifestations are absent, perform a bone marrow examination if there is fever or elevated inflammatory markers associated with non-articular bone pain, general symptoms (asthenia, anorexia or weight loss), neutrophils < 2 × 109/L or platelets < 300 × 109/L.

An update on new antibiotic prophylaxis and treatment for urinary tract infections in children.

INTRODUCTION: This review focuses on the treatment of urinary tract infections (UTI) in children and in particular its recent changes. Areas covered: Acute pyelonephritis, acute cystitis and asymptomatic bacteriuria or asymptomatic infections have to be clearly distinguished. Prompt treatment is required in pyelonephritis and cystitis, but not in asymptomatic bacteriuria or infection, in order to avoid selection of more virulent strains. This concept should be considered even in immunocompromised or bedridden children. In case of pyelonephritis, there should be no delay in beginning the antibiotic treatment in order to decrease the risk of long term complication, such as renal scars. Predisposing conditions for UTI, such as voiding anomalies and urinary tract malformation should be carefully evaluated. Expert opinion: One major concern is the increasing resistance to 3rd generation cephalosporins. Therefore overconsumption in low-risk settings should be absolutely avoided. The prevalence of infections with E. coli producing extended spectrum ß-lactamase (ESBL) is increasing and pediatricians should be aware about the specific treatment options. Any recommendation about (initial) antibiotic treatment should be regularly updated and adapted to local resistance profiles and to economic factors in different health systems.

Arthritis in children: comparison of clinical and biological characteristics of septic arthritis and juvenile idiopathic arthritis.

AIM: Childhood arthritis arises from several causes. The aim of this observational study is to compare the clinical and biological features and short-term outcome of different types of arthritis because they have different treatment and prognoses. METHODS: Children <16 years of age hospitalised in a French tertiary care centre for a first episode of arthritis lasting for less than 6 weeks who underwent joint aspiration were retrospectively included. We performed non-parametrical tests to compare groups (septic arthritis (SA), juvenile idiopathic arthritis (JIA) and arthritis with no definitive diagnosis). The time before apyrexia or C reactive protein (CRP) <10 mg/L was analysed using the Kaplan-Meier method. RESULTS: We studied 125 children with a sex ratio (M/F) of 1.1 and a median age of 2.2 years (range 0.3 to 14.6). SA was associated with a lower age at onset (1.5 years, IQR 1.2-3.0 vs 3.6 years, IQR 2.2-5.6), shorter duration of symptoms before diagnosis (2 days, IQR 1-4 vs 7 days, IQR 1-19) and higher synovial white blood cell count (147 cells ×103/mm3, IQR 71-227, vs 51 cells ×103/mm3, IQR 12-113), than JIA. Apyrexia occurred later in children with JIA (40% after 2 days, 95% CI 17% to 75%) than children with SA (82%, 95% CI 68% to 92%), as did CRP<10 mg/L (18% at 7 days, 95% CI 6.3% to 29.6% vs 82.1%, 95% CI 76.1% to 89.7%, p=0.01). CONCLUSIONS: There were no sufficiently reliable predictors for differentiating between SA and JIA at onset. The outcomes were different; JIA should be considered in cases of poor disease evolution after antibiotic treatment and joint aspiration.

Surgical Site Infections in Pediatric Spine Surgery: Comparative Microbiology of Patients with Idiopathic and Nonidiopathic Etiologies of Spine Deformity.

BACKGROUND: Surgical site infections (SSIs) are a concern in pediatric spine surgery with unusually high rates for a clean surgery and especially for patients with deformity of nonidiopathic etiology. Microbiologic differences between etiologies of spine deformities have been poorly investigated. METHODS: We reviewed all cases of SSI in spinal surgery between 2007 and 2011. Characteristics of cases and of bacteria according to the etiology of the spine disease were investigated. RESULTS: Of 496 surgeries, we identified 51 SSIs (10.3%) in 49 patients. Staphylococcus aureus was the most frequent pathogen whatever the etiology (n = 31, 61% of infection cases). The second most frequent pathogens vary according to the etiology of the spine deformity. It was Gram-negative bacilli (GNB) in nonidiopathic cases (n = 19, 45% of cases) and anaerobe in idiopathic cases (n = 8, 38% of cases), particularly Gram-positive anaerobic cocci (n = 5, 24% of cases). Infection rate was 6.8% in cases with idiopathic spine disease (n = 21) and 15.9% in cases with nonidiopathic spine disease (n = 30). Nonidiopathic cases were more frequently male with lower weight. American Society of Anesthesiologists score was more often greater than 2, they had more frequently sacral implants and postoperative intensive care unit stay. GNB were significantly associated with a nonidiopathic etiology, low weight, younger age and sacral fusion. SSIs were polymicrobial in 31% of cases with a mean of 1.4 species per infection cases. CONCLUSION: S. aureus is the first cause of SSI in pediatric spine surgery. However, Gram-positive anaerobic cocci should be taken into account in idiopathic patients and GNB in nonidiopathic patients when considering antibiotic prophylaxis and curative treatment.

Subperiosteal orbital abscess: volumetric criteria for surgical drainage.

OBJECTIVE: To investigate predictive factors of surgical management of subperiosteal orbital abscess in children. METHODS: A retrospective monocentric study was conducted between 2000 and 2011 with children hospitalized for acute pediatric orbital cellulitis (APOC). Clinical, biological and radiological data as well as medical and surgical management were collected and analyzed. All patients received intravenous antibiotics and underwent a CT-scan. Orbit and subperiosteal intraorbital abscess dimensions were measured on axial and coronal planes and the abscess volume was calculated using a spheroid model. RESULTS: Eighty-three children with APOC (mean age: 4.5 years) were included, 53 were boys (63.9%). Thirty-two children (38.6%) presented with a subperiosteal orbital abscess. Mean abscess volume was 570mm(3) and mean exophthalmos was 4.7mm. Twenty patients were treated surgically, 11 of which by an endoscopic approach. A positive correlation was observed between the volume of the abscess or exophthalmos and surgical drainage: 57.9% of patients underwent surgery when exophthalmos was >4mm, 29.4% between 2 and 4mm, and none when <2mm. All patients with an abscess volume >500mm(3) or >5% of orbital volume were operated on whereas only 30% or 39% of patients, respectively, in case of smaller volumes (P<0.05). CONCLUSION: Surgery for subperiosteal orbital abscess is usually performed in case of visual complications or unfavorable medical outcome. The importance of the exophthalmos and the volume of the abscess measured on the CT-scan are predictive factors of surgery in children with subperiosteal orbital abscess without visual complications.

New real-time PCR-based method for Kingella kingae DNA detection: application to samples collected from 89 children with acute arthritis.

Inoculation of blood culture vials with joint fluid samples has revealed the important pathogenic role of Kingella kingae in pediatric arthritis. However, recent studies based on broad-range 16S ribosomal DNA PCR and real-time PCR without a probe suggest that conventional methods remain suboptimal. We developed a new real-time PCR method with a probe that is highly specific for K. kingae and applied it to joint fluid samples collected from 89 children with suspected arthritis admitted to our institution during a 2-year period. Real-time PCR was also applied to blood samples obtained before surgery and to joint drainage fluid samples obtained during several days after surgery. Thirty-six (40%) of the 89 cases of suspected septic arthritis had positive culture. Staphylococcus aureus was the main isolate (n = 19/36, 53%), followed by K. kingae (n = 7/36, 19%). Specific real-time PCR identified K. kingae in 24 of the 53 culture-negative cases. Thus, K. kingae was present in 31 (52%) of the 60 documented cases, making it the leading pathogen. Real-time PCR on all 15 blood DNA extracts from patients with K. kingae infection was negative, demonstrating that joint fluid positivity did not result from DNA circulating in blood. Real-time PCR amplification of drainage fluid samples showed that the pathogen could be detected for up to 6 days after antibiotic initiation. K. kingae real-time PCR applied to DNA extracted from joint fluid samples, but not from blood samples, markedly improved the etiological diagnosis of septic arthritis in children. Retrospective diagnosis is feasible for up to 6 days after treatment initiation.

Recurrent staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6.

We investigated an otherwise healthy patient presenting two episodes of staphylococcal cellulitis and abscesses, accompanied by high fever and biological signs of inflammation but, paradoxically, with no detectable increase in serum levels of C-reactive protein (CRP), an IL-6-responsive protein synthesized in the liver. Following in vitro activation of whole blood cells from the patient with multiple cytokines, TLR agonists, heat-killed bacteria, and mitogens, we observed a profound and specific impairment of IL-6 secretion. However, the patient's PBMCs, activated in the same conditions but in the absence of the patient's plasma, secreted IL-6 normally. The patient's serum contained high titers of IgG1 autoantibodies against IL-6, which specifically neutralized IL-6 production by control PBMCs as well as IL-6 responses in the human hepatocellular carcinoma cell line Hep3B. These anti-IL-6 autoantibodies were detected over a period of 4 years, in the absence of any other autoantibodies. Our results indicate that these Abs probably prevented an increase in CRP concentration during infection and that impaired IL-6-mediated immunity may have contributed to staphylococcal disease. Patients with severe bacterial infections and low serum CRP concentrations should be tested for anti-IL-6 autoantibodies, especially in the presence of other clinical and biological signs of inflammation.

[Respiratory syncytial virus in hospitalized children. A 3-year study]. / La fréquence du virus respiratoire syncytial et des autres virus respiratoires dans les hospitalisations de l'enfant. Une enquête de 3 ans.

OBJECTIVE: To assess the prevalence of respiratory syncytial virus (RSV) and other important respiratory viruses in children hospitalized in a pediatric hospital in Paris (France) during a 3-year period (2001 to 2004). PATIENTS AND METHODS: The study included all patients aged 8 days to 16 years admitted from the community through emergency department with bronchiolitis, pneumonia, upper respiratory tract infection, asthma or acute isolated fever and who had nasopharyngeal samples taken for viral identification by immunofluorescence (RSV, influenza, para-influenza, and adenoviruses). RESULTS: A virus was found in 464 of 1208 patients with samples taken. RSV was identified in 375 patients, 74% of them younger than 6 months and diagnosed with bronchiolitis. RSV was isolated more often than any other virus, overall and for all diagnoses except "isolated fever," for which influenza was more frequent. In patients aged 24 months or older, influenza and RSV were identified at the same frequency. Overall, influenza virus was found in 53 patients, adenoviruses in 24 and para-influenza viruses in 11. CONCLUSION: RSV was the respiratory virus isolated most often, even in older children, during this 3-year study. The relative rarity of hospitalizations due to para-influenza viruses is characteristic of this area, compared with some other countries.

Rotavirus NSP4 114-135 peptide has no direct, specific effect on chloride transport in rabbit brush-border membrane.

The direct effect of the rotavirus NSP4 114-135 and Norovirus NV464-483 peptides on 36Cl uptake was studied by using villus cell brush border membrane (BBM) isolated from young rabbits. Both peptides inhibited the Cl-/H+ symport activity about equally and partially. The interaction involved one peptide-binding site per carrier unit. Whereas in vitro NSP4 114-135 caused nonspecific inhibition of the Cl-/H+ symporter, the situation in vivo is different. Because rotavirus infection in young rabbits accelerated both Cl- influx and Cl- efflux rates across villi BBM without stimulating Cl- transport in crypt BBM, we conclude that the NSP4 114-135 peptide, which causes diarrhea in young rodents, did not have any direct, specific effect on either intestinal absorption or secretion of chloride. The lack of direct effect of NSP4 on chloride transport strengthens the hypothesis that NSP4 would trigger signal transduction pathways to enhance net chloride secretion at the onset of rotavirus diarrhea.