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Aim: Published studies have suggested that two to five days of intravenous treatment could effectively treat paediatric bone and joint infections (PBJI), allowing a faster discharge. This study analysed the factors associated with PBJI hospital stays lasting longer than five days using the French National Hospital Discharge Database.Methods: We selected children under 15 years hospitalised in 2013 with haematogenous PBJIs using a validated French algorithm based on specific diagnosis and surgical procedure codes. Risk factors for stays of more than five days were analysed using logistic regression.Results: In 2013, 2717 children were hospitalised for PBJI, with 49% staying more than five days. The overall incidence of 22 per 100 000, was highest in males and toddlers. The main causes were septic arthritis (50%) and osteomyelitis (46%) and 50% of the pathogens were Staphylococci. The odd ratios for stays of five days or more were infancy, coded bacteria and sickle cell disease (7.0), having spondylodiscitis rather than septic arthritis (2.2) and being hospitalised in a general hospital rather than a teaching hospital (1.6).Conclusion: Half of the hospital stays exceeded five days, despite scientific evidence supporting a shorter intravenous antibiotherapy regimen. Greater knowledge and widespread use of short treatment regimens are needed. [ABSTRACT FROM AUTHOR]

Aim Little is known about bone and joint infections ( BJIs) in children, despite the risk of growth disturbance. This study examined BJIs epidemiology using the French National Hospital Discharge Database ( HD). Methods Any child <15 years hospitalized with an HD diagnosis of BJI, alone or in combination with sepsis or orthopaedic procedure, was included. The majority of BJIs (96%) were haematogenic infections. We conducted descriptive analyses to evaluate epidemiological and economic outcomes of paediatric haematogenic BJIs. Results There were 2592 paediatric patients with 2911 BJI hospitalizations and an overall incidence of 22 per 100 000. BJIs occurred more frequently in boys than girls (24 vs 19 per 100 000) and in toddlers. Septic arthritis (52%) and osteomyelitis (44%) were the most frequent infections, 16.6% of patients had a micro-organism coded (61% were Staphylococci) and 13% of had comorbidities. The mean hospital stay was 8.6 days, costing approximately €5200 per BJI stay. Conclusion This national study of paediatric BJIs in France showed a higher prevalence in toddlers and boys and demonstrated that the HD database can be used to study BJIs. However, the number of BJI cases was maybe overestimated by coding reactive arthritis as septic arthritis in the absence of bacterial evidence. [ABSTRACT FROM AUTHOR]

Objectives: Virulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates., Methods: Symptomatic infants aged <6 months with a positive B. pertussis culture from 2008-2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 10 9 /L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph., Results: We included 361 infants with pertussis (median age 63 days [interquartile range, 39-86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76-7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06-16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02-19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02-13.83)., Discussion: PRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals., Methods: We included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (<200/mm 3 and ≥200/mm 3 CD4 cell counts) at 1, 6, and 12 months after primary vaccination., Results: A total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm 3 ) and 1092 controls. At 1 month, after adjustment on age, sex, and BMI, PWH had lower seroneutralization titers than controls, and PWH with <200 CD4 cell/mm 3 had lower anti-Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months postprimary vaccination, we did not observe differences between PWH and controls at 12 months., Conclusion: PWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after 6 months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline., Competing Interests: Declarations of competing interest PL has received payment or honoraria for lectures, presentations, speakers bureau, manuscript writing, or educational events from AstraZeneca, GlaxoSmithKline, Janssen, Moderna, Merck Sharp & Dohme, Pfizer, Sanofi Pasteur, Seqirus. KL has received payment or honoraria for lectures, presentations or educational events from GlaxoSmithKline, Moderna, Merck Sharp & Dohme, Gilead. ZM has received payment or honoraria for lectures and presentations from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer. VP has received honoraria for lectures and presentations from Moderna. OL has received payment or honoraria for lectures, presentations, speakers bureau, or educational events from Sanofi Pasteur; Pfizer, Janssen, Moderna, Merck Sharp & Dohme, Seqirus and grants from Sanofi Pasteur; Pfizer, Janssen, GlaxoSmithKline, Moderna. The other authors declare having no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination., Methods: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves., Results: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection., Conclusion: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response., Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection., Design, Setting, and Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023., Main Outcomes and Measures: An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times., Results: A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10-5 vs 37 × 10-5 at day 29; 107 × 10-5 vs 54 × 10-5 at day 57; and 104 × 10-5 vs 70 × 10-5 at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 × 10-5 vs 49 × 10-5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001)., Conclusions and Relevance: The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

Immune response induced by COVID-19 vaccine booster against delta and omicron variants was assessed in 65 adults (65-84 years old) early aftesr a first booster dose. An increase in SARS-CoV-2 neutralizing antibodies was shown in individuals not previously infected without evidence of an age-related effect, with lower increase in those infected before a single dose of primary vaccination. Of note, humoral response was observed only starting from the 5th day after the boost., (© 2022. The Author(s).)

Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination., Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467., Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 ( p  < 0·0001)., Interpretation: The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic., Funding: French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna., Competing Interests: OL reports grant from French ministry of health and grants or contracts from Pfizer, Sanofi-Pasteur, GSK, MSD, AstraZeneca and Janssen. CJ reports fees for boardmembership from AstraZeneca, Pfizer and MSD. TS reports grant from DGOS (French Ministry of health), AstraZeneca, Bayer, Novartis, Sanofi, Boehringer, Daiichi Sankyo, Eli Lilly, GSK and personal fees for boardmembership and consulting from various pharmaceutical companies, including AstraZeneca, Sanofi, Bayer, Ablative Solutions and 4 Living Biotech. KL reports personal fees from Gilead, MSD, Janssen, ViiV, Spikimm and fees for development of educational presentations from Janssen, Gilead, MSD, Sobi, and Chiesi. PL reports personal fees for board membership from Pfizer, Janssen, AstraZeneca, MSD, Viiv, GSK, consultancy and travel accommodation from Pfizer. EBN has received grant pending from Sanofi Pasteur and fees for board membership from Pfizer, and Janssen. MB reports travels grants from various pharmaceutical companies, including Pfizer, Novex, Janssen. XDL reports research grant from INSERM., (© 2022 The Authors.)

Introduction&#160;: Traveling regularly to malaria endemic areas increasingly exposes travelers to various risks which could be mitigated by a pre-travel health consultation. The objective was to study the impact of advice provided during a pre-travel consultation on travelers&#8217; behaviors and practices to identify travelers&#8217; profiles and adapt the prevention recommendations before trave-ling to intertropical zones.Methods&#160;: Two self-assessment questionnaires (Q1-before and Q2-after travelling) were proposed to 271 individuals over 5 months of traveler consultations to assess behaviors (Q1) and practices (Q2). Questionnaires gathered travelers&#8217; profiles, source of information, travel diet and lifestyle, personal vector control, malaria chemoprophylaxis and other frequent risks.Results&#160;: Diet recommendations were the least followed (16&#160;%), especially for people&lt;55 (p&lt;0.03) as well as Visiting Friends and Relatives (VFR) (p&lt;0,001). A correlation between behaviors and practices for personal vector control and immunization and malaria chemoprophylaxis were found (resp.&#160;89% and 78%). Mosquito nets and long sleeve clothes were underused. Changes of opinion resulting from concerns of potential side effects and lack of efficiency (&lt;7%) explained the non-compliance to the pre-travel recommendations. During the stay, although 24% of travelers got sick, medical consultations (&lt;5%) and hospital admissions (&lt;1%) remained low. The General Practitioner remains the main point of contact (41%).Discussion&#160;: Better identifying travelers&#8217; characteristics would allow to improve travel consultation, to refer to their knowledge and focus on preventive measures. It is crucial to highlight the importance of diet measures and insist on the low likelihood of adverse effects in Malaria Chemoprophylaxis.

Aim: To characterize antibiotic (ab) prescriptions in children., Methods: Evaluation of outpatient ab prescriptions in a 3-year cohort of children in primary care using a data warehouse (Massachusetts Health Disparities Repository) by comorbid conditions, demographics, and clinical indication., Results: A total of 15 208 children with nearly 120 000 outpatient visits were included. About one third had a comorbid condition (most commonly asthma). Among the 30 000 ab prescriptions, first-line penicillins and macrolides represented the most frequent ab (70%), followed by cephalosporins (16%). Comorbid children had 54.3 ab prescriptions/100 child-years versus 38.8 in children without comorbidity; ab prescription was higher in urinary tract infections (>60% of episodes), otitis, lower respiratory tract infections (>50%), especially in comorbid children and children under 2 year old. Ab prescriptions were significantly associated with younger age, emergency room visit, comorbid children, and acute infections., Discussion: A clinical data warehouse could help in designing appropriate antimicrobial stewardship programs and represent a potential assessment tool.

Background: Ultra-deep sequencing (UDS) allows detection of minority resistant variants (MRVs) with a threshold of 1% and could be useful to identify variants harbouring single or multiple drug-resistance mutations (DRMs)., Objectives: We analysed the integrase gene region longitudinally using UDS in an HIV-1-infected child rapidly failing a raltegravir-based regimen., Methods: Longitudinal plasma samples at baseline and weeks 4, 8, 13, 17 and 39 were obtained, as well as the mother's baseline plasma sample. Sanger sequencing and UDS were performed on the integrase gene using Roche 454 GS-Junior. A bioinformatic workflow was developed to identify the major DRMs, accessory mutations and the linkage between mutations., Results: In Sanger sequencing and UDS, no MRV in the integrase gene was detected at baseline in either the mother or the child. The major DRM N155H conferring resistance to raltegravir and elvitegravir was detected in 4% of the sequences by week 4 using UDS, whereas it was not detected by Sanger sequencing. The double mutant E92Q + N155H, conferring resistance to the entire integrase inhibitor class, including dolutegravir, emerged at week 8 (16%) and became rapidly dominant (57% by week 13). At the last timepoint under raltegravir (week 17), Y143R emerged, leading to different resistance mutation patterns: single mutants N155H (47%) and Y143R (24%) and double mutants E92Q + N155H (13%), Y143R + N155H (2%) and E92Q + Y143R (2%). The polymorphic substitution M50I was preferentially selected on resistant variants, especially on E92Q + N155H variants., Conclusions: This case study illustrates the usefulness of UDS in detecting early MRVs and determining the dynamics of selected HIV-1 variants in longitudinal analysis., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Intestinal parasitoses are very common infections in tropical areas. By contrast, they are rarely diagnosed in developed countries, and are mostly seen in specific populations., Patients and Methods: This analytical observational study was longitudinally performed in a French university hospital (2007-2011). It dealt with the study of gastrointestinal carriage of parasites in internationally adopted children. A standard stool examination was therefore systematically undertaken for every new immigrant. Association with risk factors was made by uni- and multivariate analysis., Results: Overall, 69 stool samples were analyzed. The proportion of positive samples was 78 %. Protozoans, mainly Giardia duodenalis, were more prevalent than helminths. In univariate analysis, a subject's low weight and height were significantly associated with intestinal parasite carriage. Amoebae were more frequent in older children and in children from Haiti, as confirmed by the trend observed in the multivariate analysis. Flagellates were seen more often in African children. Infections with multiple parasite species were observed in half of the study population, and were inversely correlated to increasing age., Discussion: According to the results of this study, gastrointestinal parasites are still very frequent in stool samples from immigrant children. Since they are easy to transmit, the majority of infections were protozoan. The best antiparasitic strategy lies in: (a) the routine screening of stool from any immigrant child coming from endemic areas and (b) the use of antiparasitic treatment., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

We report the case of a 3-month-old boy hospitalized with acute bronchiolitis. Respiratory distress was associated with cardiogenic shock caused by chaotic atrial tachycardia. The cause of bronchiolitis was a coronavirus NL63 viral infection, confirmed in nasopharyngeal aspirations. The patient required intensive care including diuretics (furosemide), anti-arrhythmic drugs (amiodarone and digoxin), and inotropic drugs (milrinone and levosimendan) associated with mechanical ventilation. The outcome was favorable in 10 days and the sinusal cardiac rhythm was completely restored at discharge., (Copyright © 2013. Published by Elsevier SAS.)

Background: Barth syndrome (BTHS) is an X-linked recessive disorder characterized by cardiomyopathy, skeletal myopathy and cyclic neutropenia in male patients. It is caused by mutations in the TAZ gene coding for the tafazzin, a protein involved in the remodeling of cardiolipin. Loss of cardiolipin in the inner mitochondrial membrane results in respiratory chain dysfunction. No specific symptom has been identified in female carriers., Case Report: We report the first case of BTHS confirmed by TAZ gene analysis in a female patient. This girl experienced severe heart failure at 1-month of age. Echocardiography diagnosed dilated-hypokinetic and hypertrophic cardiomyopathy with noncompaction of the left ventricle. Initial metabolic screening was normal, except for a cyclic neutropenia. Respiratory chain analysis performed on skin fibroblasts revealed a decreased activity of complexes I, III and IV. Screening on a bloodspot showed abnormal monolysocardiolipin:cardiolipin ratio, later confirmed on cultured fibroblasts, indicative of BTHS. Genetic analyses finally confirmed the diagnosis of BTHS, by showing a large intragenic deletion of exons 1 through 5 in the TAZ gene. Cytogenetic analysis showed mosaicism for monosomy X and for a ring X chromosome with a large deletion of the long arm including the Xq28 region. The girl presented recurrent episodes of severe acute heart failure, progressive muscle weakness, and had a fatal septic shock at 3 years., Conclusion: This case highlights that the diagnosis of BTHS should also be suspected in female patients presenting a phenotype similar to affected boys. In these cases, analysis of the monolysocardiolipin:cardiolipin ratio in bloodspots is a rapid and sensitive screening tool for BTHS. However clinical expression in a carrier female requires hemizygosity for the mutated allele of the TAZ gene, which supposes a rearrangement of the TAZ gene region on the other X chromosome., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Danon disease is an X-linked lysosomal disorder, characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation. We report a family with a novel mutation, in which the mother and her three sons were affected with various clinical presentations. A massive hypertrophy of the left ventricle was the predominant feature in the three male patients, with different degrees of severity of cardiac symptoms, from isolated palpitations to cardiac failure and sudden death. Muscle pain and weakness were also variable, but constantly associated with increased plasma CK levels. Finally, the male patients had variable degree of a mental retardation. The mother had an attenuated phenotype, limited to a mild hypertrophic cardiomyopathy with premature ventricular contractions diagnosed during her 40's. Microscopy examination of skeletal muscle biopsy, performed in the youngest patient, demonstrated atrophic myofibers with intracytoplasmic vacuoles suggesting lysosomal glycogen storage disease. Immunohistochemistry analyses in muscle specimen showed no detectable Lysosomal-Associated Membrane Protein-2 (LAMP-2), in keeping with the diagnosis of Danon disease. However, a very low expression of a shortened LAMP-2 protein could be evidenced by Western-blot in the patient's fibroblasts. Molecular investigations identified a novel splicing mutation (IVS6 + 1delG) in the LAMP-2 gene. This case report highlights the intrafamilial variability of Danon disease phenotype. In this case, morphological examination of muscle biopsy, showing lysosomal storage myopathy, and immunohistochemistry analyses can provide key elements for orienting etiologic investigations.