Anne Filleron

Background: Musculoskeletal bacterial infections of the pelvis (M-BIP) in children are rare and hard to manage and diagnose, often causing treatment delays and case underestimation. Magnetic resonance imaging (MRI) is the best diagnostic tool, and prompt treatment is crucial to prevent complications. This study aims to describe the clinical presentation, diagnostic methods, and treatments used in M-BIP to improve diagnosis and management. Methods: This retrospective observational study was conducted in 4 centers, including patients under 16 years with M-BIP between 2014 and 2022. Data on demographics, clinical features, biology, imaging and management were collected. For the highly painful forms called M-BIP hyperalgesic syndrome (M-BIP-HS), we proposed an M-BIP-HS definition and evaluated its relevance. Results: We analyzed 52 patients with M-BIP. Pain, fever and limping were the main clinical signs. The median prehospital delay was 3 days (Q1 = 1.75; Q3 = 5). Inflammatory markers were elevated. Staphylococcus aureus (SA) was the most common pathogen. MRI confirmed the diagnosis and potential complications in all cases. Treatment included appropriate analgesics, prolonged antibiotics and, when necessary, surgical drainage. Fifteen patients developed abscesses, experiencing more severe pain, higher C-reactive protein levels and longer intravenous and total antibiotic therapy than those without complications. M-BIP-HS was observed in 30 patients (60%), and 87% of abscess cases presented M-BIP-HS. Conclusions: M-BIP is a rare musculoskeletal infection, often characterized by delayed diagnosis. It is mainly caused by SA and requires prolonged antibiotic therapy. M-BIP-HS was strongly associated with SA and abscess complications, which may expose the condition. We recommend early MRI when M-BIP-HS is present to optimize management, antibiotic duration and perform surgical drainage if needed.

Background: The natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants is still elusive. We aimed at developing a non-invasive tool for detecting specific IgE (sIgE) and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. The sIgEs were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex and confirmed by a capillary Western blot with a nano-immunoassay. EDN concentration was used to investigate the local eosinophilic component. Results: The multiplexed allergen assay detected sIgE in all of the samples. A Western blot was used to confirm the results. The frequency and levels of sIgE in the neonatal fecal samples differed between the infants who developed IgE-mediated diseases and the controls. Allergen specificity was associated with the development of cow’s milk allergy (CMA) and asthma. The development of CMA was predicted by the sIgE response to milk proteins (sensitivity was 88%; specificity was 78%). The EDN levels predicted the development of IgE-mediated diseases (sensitivity was 100%; specificity was 75%). Conclusion: The non-invasive investigation of neonatal fecal sIgE is a promising tool for predicting the subsequent development of IgE-mediated diseases. Clinical Implications: The non-invasive sIgE and EDN profiling of neonatal fecal samples from preterm infants can predict the development of IgE-mediated diseases.

Background: Little is known about the natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants, further hampered by the lack of noninvasive investigations. We aimed at developing a non-invasive tool for the study of IgE and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases (cow’s milk allergy, asthma, or atopic dermatitis) during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. sIgE responses were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex containing whole and molecular allergens and confirmed by capillary Western blot with nano-immunoassay. The local eosinophilic component was investigated by measuring the concentration of EDN. Results: The multiplexed allergen assay detected sIgE in all samples. Confirmation was obtained with Western blot. Frequency and levels of sIgE in neonatal fecal samples differed between infants who developed IgE-mediated diseases and controls. Neonatal fecal sIgE directed to milk proteins predicted later development of cow’s milk allergy (specificity 88%, sensitivity 78%). Allergen specificity of neonatal fecal sIgE was associated with later development of cow’s milk allergy and asthma. Neonatal fecal EDN levels predicted the development of IgE-mediated diseases (sensitivity 100%, specificity 75%). Conclusion: Non-invasive investigation of neonatal fecal sIgE is a promising tool for the prediction of subsequent development of IgE-mediated diseases.

Infectious diseases can result in unanticipated post-infectious inflammatory reactions (PIIR). Our aim was to explore PIIR in 3 frequent pediatric bacterial invasive infections in France by a retrospective monocentric study. We included children hospitalized between 2003 and 2012 for Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), or Streptococcus pyogenes invasive infections. The PIIR had to have occurred between 3 and 15 days without fever despite an individually tailored antibiotic therapy. A descriptive analysis was carried out to determine PIIR risk factors. We included 189 patients, of whom 72, 79, and 38 exhibited invasive infections caused by S pyogenes, SP, and NM, respectively. The mean age was 44 months. PIIR were observed in 39 cases, occurring after a median of 8 days (5–12), with a median duration of 3 days (2–6). Fever, arthritis, and pleural effusion were observed in 87%, 28.2%, and 25.6%, respectively. In multivariate analysis, PIIR were associated with pleuropneumonia, hospitalization in an intensive care unit (ICU), and elevated C-reactive protein (CRP). PIIR were observed in 20% of children after SP, NM, or S pyogenes invasives infections. Their occurrence was associated with the initial severity but not the etiological microorganism. Further studies are warranted to confirm these findings.

Background: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of one year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age one. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age of one year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β, and IL-6. Conclusions: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of one year.

Background: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of 1 year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age 1. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age 1 year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β and IL-6. Conclusion: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of 1 year