Suboptimal vaccination coverage of recommended vaccines among French children with recurrent autoinflammatory fever syndromes: a study from the Juvenile Inflammatory Rheumatism cohort.

INTRODUCTION/OBJECTIVES: To determine vaccination coverage among a French cohort of children with recurrent autoinflammatory fever syndromes (RFS). METHOD: All RFS children aged 2 to 19 years from the Juvenile Inflammatory Rheumatism cohort and followed at the French Reference Center for Autoinflammatory Diseases, Versailles Hospital, were included in our observational study. Immunisation status at ages 2, 7 and 15 years and at the last outpatient visit was evaluated according to the standard French vaccine schedule and recommended supplementary vaccines for patients with immunosuppressive therapy. RESULTS: Of 200 patients, 90 (45%) had periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome; 52 (26%) had familial Mediterranean fever and 50 (25%) had undefined recurrent fever. Complete immunisation as per the standard schedule was obtained by 32% of patients at 2 years, 28% at 7 years, 6% at 15 years and 44% at the last outpatient visit. Similar or higher coverage was obtained by the last outpatient visit for most vaccines, compared to immunisation coverage at 2 years: pneumococcus (91% vs 88%), diphtheria tetanus poliomyelitis (82% vs 86%), hepatitis B (79% vs 69%) and measles, mumps, rubella (91% vs 50%). No patients with immunosuppressive therapy (n = 14) were up to date for all supplementary immunisations recommended for them. CONCLUSION: Vaccination coverage for RFS children is suboptimal, especially for infants who present with recurrent febrile episodes. The initial vaccination delay is partially corrected through specialist follow-up in later years. Coverage according to the supplementary vaccine recommendations for immunosuppressed patients is poor. Key Points • Vaccination coverage for RFS children is suboptimal, especially at 2 years of age which is likely due to the prevalence of early recurrent febrile symptoms. • The initial vaccination delay is partially recovered during later follow-up at an expert rheumatology center. • Specific recommendations are particularly difficult to apply to patients on immunosuppressive therapy.

Transcranial Doppler Use in Non-traumatic Critically Ill Children: A Multicentre Descriptive Study.

Background: The use and perceived value of transcranial Doppler (TCD) scope in paediatric critical care medicine has not been extensively documented. Objective: To describe the use of TCD to assess non-traumatic brain injury in patients admitted to four paediatric intensive care units (PICUs) in France. Methods: We prospectively included all children (aged under 18) assessed with inpatient TCD between November 2014 and October 2015 at one of the four PICUs. The physicians completed a questionnaire within 4 h of performing TCD. Results: 152 children were included. The primary diagnosis was neurological disease in 106 patients (70%), including post ischemic-anoxic brain insult (n = 42, 28%), status epilepticus (n = 19, 13%), and central nervous system infection/inflammation (n = 15, 10%). TCD was the first-line neuromonitoring assessment in 110 patients (72%) and was performed within 24 h of admission in 112 patients (74%). The most common indications for TCD were the routine monitoring of neurological disorders (n = 85, 56%) and the detection of asymptomatic neurological disorders (n = 37, 24). Concordance between the operator's interpretation of TCD and the published normative values was observed for 21 of the 75 (28%) TCD abnormal findings according to the published normative values. The physicians considered that TCD was of value for the ongoing clinical management of 131 (86%) of the 152 patients. Conclusion: TCD is commonly used in French PICUs and tends to be performed early after admission on patients with a broad range of diseases. The physicians reported that the TCD findings often helped their clinical decision making. In view of the subjectivity of bedside interpretation, true TCD contribution to clinical care remains to be determined. Objective studies of the impact of TCD on patient management and clinical outcomes are therefore warranted.

Mycobacterium bolletii Lung Disease in Cystic Fibrosis.

BACKGROUND: The cystic fibrosis (CF) pathogen, Mycobacterium abscessus complex, covers three subspecies: M. abscessus, M. massiliense, and M. bolletii. There are no clinical outcome data concerning M. bolletii. Our aim was to characterize M. bolletii lung infections in patients with CF. METHODS: We included patients with M. bolletii lung infection recorded between 1994 and 2012 in France. Data were collected from the CF registry, medical records, and questionnaires submitted to the CF primary physician. Strains were typed by multilocus sequence typing analysis. RESULTS: Fifteen cases were identified in nine CF centers. Nine patients (60%) presented with nontuberculous mycobacterial pulmonary disease. Follow-up of 13 patients showed a trend to more rapid decline in FEV1 in the first year of colonization (-9.4%; SD 19.3) in comparison with noninfected control subjects (-2.3%; SD 12.1) (P = .16). Twelve patients were treated, and 11 received oral macrolides. Treatment-induced eradication occurred in five patients (41.7%). Four patients died (26.7%), including one patient with fatal nontuberculous mycobacterial pulmonary disease. Inducible macrolide resistance was demonstrated in all strains. Patients always harbored unique strains. CONCLUSIONS: Our study reports the largest study cohort of CF patients infected with M. bolletii. M. bolletii infection affects both children and young adults, is most often symptomatic, and may be fatal. Macrolide-based therapies have poor effectiveness. There is no evidence of patient-to-patient transmission.

Comparative proteomics of respiratory exosomes in cystic fibrosis, primary ciliary dyskinesia and asthma.

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are pulmonary genetic disorders associated with inflammation and heterogeneous progression of the lung disease. We hypothesized that respiratory exosomes, nanovesicles circulating in the respiratory tract, may be involved in the progression of inflammation-related lung damage. We compared proteomic content of respiratory exosomes isolated from bronchoalveolar lavage fluid in CF and PCD to asthma (A), a condition also associated with inflammation but with less severe lung damage. BALF were obtained from 3 CF, 3 PCD and 6 A patients. Exosomes were isolated from BALF by ultracentrifugations and characterized using immunoelectron microscopy and western-blot. Exosomal protein analysis was performed by high-resolution mass spectrometry using label-free quantification. Exosome enrichment was validated by electron microscopy and immunodetection of CD9, CD63 and ALIX. Mass spectrometry analysis allowed the quantification of 665 proteins, of which 14 were statistically differential according to the disease. PCD and CF exosomes contained higher levels of antioxidant proteins (Superoxide-dismutase, Glutathione peroxidase-3, Peroxiredoxin-5) and proteins involved in leukocyte chemotaxis. All these proteins are known activators of the NF-KappaB pathway. Our results suggest that respiratory exosomes are involved in the pro-inflammatory propagation during the extension of CF or PCD lung diseases. SIGNIFICANCE: The mechanism of local propagation of lung disease in cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) is not clearly understood. Differential Proteomic profiles of exosomes isolated from BAL from CF, PCD and asthmatic patients suggest that they carry pro-inflammatory proteins that may be involved in the progression of lung damage.