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Successive implementation of seven-valent then 13-valent pneumococcal conjugate vaccines (PCVs) led to a marked decrease in pneumococcal disease burden, including pneumococcal meningitis. We assessed the long-term effect of implementation of PCVs on incidence of pneumococcal meningitis in children in France over a 16-year period.We did a quasi-experimental, population-based interrupted time-series analysis with a nationwide prospective survey over 16 years in France, recruiting children aged younger than 15 years from 227 paediatric wards from January, 2001, to December, 2016. The main outcome by the time-series model was the estimated incidence of pneumococcal meningitis per 100 000 children (of a population of 12·6 million children in 2017) before and after PCV7 and PCV13 implementation. The time-series model was based on segmented regression with autoregressive error.We enrolled 1778 children with pneumococcal meningitis. PCV13 implementation led to a significant reduction in monthly incidence of pneumococcal meningitis from 0·12 per 100 000 children before PCV13 to a nadir of 0·07 in December, 2014 (-38%, 95% CI -56·1 to -20·4; p0·0001). A sharp increase occurred during 2015 and 2016, (+2·3% per month, incidence of 0·13 per 100 000 children at the end of the study period, p=0·0002), mainly related to an increase of serotype 24F, which was frequently penicillin resistant.The early effect of PCV13 implementation greatly reduced the incidence of pneumococcal meningitis in children less than 15 years old. However, a sharp rebound in incidence linked to the emergence of serotype 24F compromised the long-term PCV efficacy. If confirmed in future studies and in other countries, pneumococcal meningitis incidence rebound and 24F emergence should be considered when developing next-generation PCVs.The French Pediatric Infectious Diseases Group, Association Clinique et Thérapeutique Infantile du Val de Marne, Pfizer, and for the National Reference Centre for Pneumococci, the French National Health Agency.

NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease.We evaluated the recently developed Multiplex Ligation-dependent Probe Amplification (MLPA) method to assess the relative copy number of genes. The goal was to determine if MLPA could improve, in addition to direct sequencing, the detection rate of NKX2.1 mutations in a phenotype-selected cohort of 24 patients affected by neurological, thyroid and/or pulmonary disorders.Direct sequencing revealed two heterozygous mutations. Using MLPA, we identified two further heterozygous NKX2.1 gene deletions. MLPA increased the detection rate by 50%. All patients with gene deletions identified were affected by BHC and congenital hypothyroidism.MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. All patients with an NKX2.1 mutation had BHC and congenital hypothyroidism, emphasizing the high prevalence of these signs associated with defective NKX2.1 alleles.

Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). The objectives of the present study were (i) detection of NKX2-1 mutations in patients with CH associated with pneumopathy and/or BHC, (ii) functional analysis of new mutations in vitro and (iii) description of the phenotypic spectrum of brain-lung-thyroid syndrome. We identified three new heterozygous missense mutations (L176V, P202L, Q210P), a splice site mutation (376-2A-->G), and one deletion of NKX2-1 at 14q13. Functional analysis of the three missense mutations revealed loss of transactivation capacity on the human thyroglobulin enhancer/promoter. Interestingly, we showed that deficient transcriptional activity of NKX2-1-P202L was completely rescued by cotransfected PAX8-WT, whereas the synergistic effect was abolished by L176V and Q210P. The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%). Thyroid morphology was normal (55%) and compensated hypothyroidism occurred in 61%. Lung disease occurred in 54% of patients (IRDS at term 76%; recurrent pulmonary infections 24%). On follow-up, 20% developed severe chronic interstitial lung disease, and 16% died. In conclusion, we describe five new NKX2.1 mutations with, for the first time, complete rescue by PAX8 of the deficient transactivating capacity in one case. Additionally, our review shows that the majority of affected patients display neurological and/or thyroidal problems and that, although less frequent, lung disease is responsible for a considerable mortality.

To assess the management of acute otitis media in children by paediatricians and general practitioners in the North of France compared with the AFSSAPS (Agence Française de Sécurité Sanitaire des Produits de Santé) guideline's recommendations of 2005.All eligible family paediatricians (n=68) and a group of general practitioners (n=200) first received a phone call invitation to participate to the study. The volunteers responded to a questionnaire by phone call.The response rates were 67, 6 % for the group of paediatricians and 64, 5 % for the group of general practitioners. The guideline's recommendations were followed by respectively 28, 3 % and 9, 3 % of primary care physicians. The observation option, recommended in children aged more than 2 years, was followed by 46, 5 % of general practitioners and 54, 3 % of paediatricians. The durations of antibiotics were poorly respected by the 2 groups of physicians. In case of allergy to penicillin, the paediatricians followed more the recommendations than the general practitioners.Educational interventions are needed in order to improve the adherence to guidelines of paediatricians and general practitioners for the management of acute otitis media in children.

We report the association of a generalized pustular psoriasis and infection by Staphylococcus aureus which produced Panton-Valentine leukocidin in a 5-year-old child. Another S. aureus strain with the same toxin gene content was also isolated among three family members presenting with cutaneous lesions. Although a methicillin-resistant staphylococcal strain has been reported in association with pustular psoriasis, this is the first report of a Panton-Valentine leukocidin strain associated with generalized pustular psoriasis. The causal relationship between S. aureus produced Panton-Valentine leukocidin and skin lesions is discussed.

Varicella is a common disease characterized by a typical presentation. We report a case of an atypical presentation of varicella with a centrifugal distribution, eruption with many vesicles, no pustular stage in evolution and distal involvement. There were none of the known modifying factors (immunosuppression, skin disease, injury or sun exposure). To explain the distal involvement, we suggest intraepidermic lesions caused by a pre-existing B1 coxsackie infection.