Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) vs. a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine in meningococcal vaccine-naïve and meningococcal C conjugate vaccine-primed toddlers: a phase III randomised study.

Vaccination remains the best strategy to reduce invasive meningococcal disease. This study evaluated an investigational tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT) vs. a licensed tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MCV4-TT) (NCT02955797). Healthy toddlers aged 12-23 months were included if they were either meningococcal vaccine-naïve or MenC conjugate (MCC) vaccine-primed (≥1 dose of MCC prior to 12 months of age). Vaccine-naïve participants were randomised 1:1 to either MenACYW-TT (n = 306) or MCV4-TT (n = 306). MCC-primed participants were randomised 2:1 to MenACYW-TT (n = 203) or MCV4-TT (n = 103). Antibody titres against each of the four meningococcal serogroups were measured by serum bactericidal antibody assay using the human complement. The co-primary objectives of this study were to demonstrate the non-inferiority of MenACYW-TT to MCV4-TT in terms of seroprotection (titres ≥1:8) at Day 30 in both vaccine-naïve and all participants (vaccine-naïve and MCC-primed groups pooled). The immune response for all four serogroups to MenACYW-TT was non-inferior to MCV4-TT in vaccine-naïve participants (seroprotection: range 83.6-99.3% and 81.4-91.6%, respectively) and all participants (seroprotection: range 83.6-99.3% and 81.4-98.0%, respectively). The safety profiles of both vaccines were comparable. MenACYW-TT was well-tolerated and demonstrated non-inferior immunogenicity when administered to MCC vaccine-primed and vaccine-naïve toddlers.

[Neurologic manifestations of Behcet's disease: analysis of a series of 27 patients]. / Les manifestations neurologiques de la maladie de Behçet: analyse d'une série de 27 patients.

PURPOSE: To describe epidemiological and clinical characteristics of neurological involvement in Behçet's disease (BD) and to determine a subgroup of patients at high risk for this complication. PATIENTS AND METHODS: The medical notes of 105 patients with BD fulfilling the criteria of the international Study Group for Behçet's disease were retrospectively reviewed. Patients were divided into two groups according to the presence (group 1) or not (group 2) of neurological and/or psychiatric involvement attributable to BD. The epidemiological, clinical and genetic (HLA B51 and MICA 6 frequency) features in the two groups were analysed and compared using the Kruskall-Wallis and the chi-square tests. RESULTS: Twenty-seven patients (25.7%) had clinical evidence of neurological involvement. They were 20 men and 7 women. The mean age at neurological onset was 34.26 +/- 8.79 years. Nineteen patients (70.3%) had meningoparenchymal "MP" central nervous system involvement (brainstem: 9, hemispheric involvement: 6, spinal cord: 4, psychiatric involvement: 2, isolated pyramidal signs: 1, aseptic meningitis: 1). Seven patients (25.9%) had cerebral large vessels involvement that is cerebral angio-Behçet "CAB" (intracranial hypertension: 5 cases due to cerebral venous thrombosis: 3 and pseudotumor cerebri: 2, cerebral haemorrhage: 1, cerebral arterial thrombosis: 1). One patient (3.7%) had both "MP" and "CAB" involvement. Headache was significantly more frequent in non-parenchymal patients. In group 1, complete recovery or improvement with mild neurological impairment was seen in 13 cases, improvement with severe disability in 3 cases, worsening in 1 case, the course was stationary in 1 case and 3 patients died (11.2%). Arterial aneurysms were significantly more frequent in "CAB" subgroups than in subgroup 2. CONCLUSION: Frequency of neurological involvements in BD was high in our study. Arterial aneurysms seem to be a risk factor to these complications. Cerebral angio-Behçet appears to be a protector factor against uveitis.

[Circadian rhythm of cortisol and its responsiveness to ACTH during Ramadan]. / Variations de la cortisolémie et de sa réponse à l'ACTH pendant le mois de Ramadan.

UNLABELLED: Changes in the nyctemeral pattern observed during Ramadan include diurnal fasting from sunrise to sunset and delayed and shortened periods of sleep. The purpose of the present study was to investigate the possible effect of these changes on the circadian rhythm of cortisol and its response to exogenous ACTH. SUBJECTS AND METHODS: Eleven healthy male volunteers aged 20 to 35 years were studied for two weeks prior to Ramadan. Two short ACTH stimulation tests (250 microg ACTH 1-24 intravenously) at 8 a.m. and 8 p.m. An average 17 days after the beginning of the month of Ramadan, basal cortisol was measured at 8 a.m. and a short stimulation test was performed at 8 p.m. RESULTS: Before Ramadan, cortisol level was higher at 8 a.m. (749.5 +/- 207 nmol/l) than at 8 p.m. (195.18 +/- 79 nmol/l, p<0.001) and the incremental cortisol response to exo genous ACTH was higher at 8 a.m. (peak at 1.167 +/- 46 nmol/l) than at 8 p.m. (peak at 950 nmol/l) (NS). During Ramadan, morning cortisol level (646.3 81 nmol/l) was lower than before Ramadan (NS). The 8 p.m. cortisol level (319 193 nmol/l) increased slightly during Ramadan (p=0.08) but remained lower than the morning level during Ramadan (p=0.001) and before Ramadan (p<0.001). There was not significant difference between cortisol responsiveness to exogenous ACTH at 8 p.m. during Ramadan (peak at 1.102 51 nmol) and at 8 a.m. and 8 p.m. during Ramadan. DISCUSSION: Changes in eating and sleeping schedule was found to reduce morning cortisol level and raise the evening cortisol level. Adrenal sensitiveness to corticotropin stimulation did not appear to be impaired during Ramadan.

[A disseminated form of Langerhans histiocytosis associated with diabetes insipidus and diabetes mellitus]. / Une forme disséminée d'histiocytose langerhansienne associant un diabète insipide et un diabète sucré.

INTRODUCTION: Langerhans' cell histiocytosis is a rare disorder of unknown etiology characterized by a wide clinical spectrum and varied behavior. Diabetes insipidus is a relatively common feature in Langerhans' cell histiocytosis. The presence of both diabetes insipidus and mellitus associated with histiocytosis in an adult is rare. To our knowledge, only three previous cases have been reported. EXEGESIS: We report the clinical presentation, pathologic findings and clinical progress in an adult female who had disseminated Langerhans' cell histiocytosis (hypothalamic infiltration, multifocal bone involvement) associated with both diabetes insipidus and mellitus. CONCLUSION: The pathogenesis of diabetes mellitus in such an association will be discussed.

[Leukocytoclastic vasculitis, cryoglobulinemia and medullary aplasia associated with hepatitis C]. / Vascularite leucocytoclasique, cryoglobulinemie et aplasie medullaire au cours de l'hépatite C.

Various clinical and immunological extrahepatic manifestations were described during infection by hepatitis C virus (HCV). We reported a rare association, within the same patient, made up with a cutaneous leucytoclastic vasculitis, cryoglobulinemia and aplastic anemia. A 70 years old woman with infection by HCV diagnosed four years ago, was hospitalized due to upper members purpura and six cutaneous ulcerations. Complete blood count revealed a pancytopenia. Prothrombin time was at 65%, AST, ALT an d GT were within normal limits. Test for antibodies to HCV en serum was positive. Bone marrow aspiration showed marked hypocellularity. A skin biopsy showed leucocytoclastic vasculitis of small vessels. Interferon a therapy was not indicated because aplastic anemia. Simultaneous occurrence of cutaneous vasculitis, cryoglobulinemia and aplastic anemia during HCV infection lays the question of their mechanism. Purpura and cutaneous ulcerations can be due to cryoglobulinia.