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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.

OBJECTIVE Transient neonatal diabetes mellitus (TNDM) occurs during the 1st year of life and remits during childhood. We investigated glucose metabolism and socioeducational outcomes in adults. RESEARCH DESIGN AND METHODS We included 27 participants with a history of TNDM currently with (n = 24) or without (n = 3) relapse of diabetes and 16 non-TNDM relatives known to be carriers of causal genetic defects and currently with (n = 9) or without (n = 7) diabetes. Insulin sensitivity and secretion were assessed by hyperinsulinemic-euglycemic clamp and arginine-stimulation testing in a subset of 8 TNDM participants and 7 relatives carrying genetic abnormalities, with and without diabetes, compared with 17 unrelated control subjects without diabetes. RESULTS In TNDM participants, age at relapse correlated positively with age at puberty (P = 0.019). The mean insulin secretion rate and acute insulin response to arginine were significantly lower in TNDM participants and relatives of participants with diabetes than in control subjects (median 4.7 [interquartile range 3.7–5.7] vs. 13.4 [11.8–16.1] pmol/kg/min, P < 0.0001; and 84.4 [33.0–178.8] vs. 399.6 [222.9–514.9] µIU/mL, P = 0.0011), but were not different between participants without diabetes (12.7 [10.4–14.3] pmol/kg/min and 396.3 [303.3–559.3] µIU/mL, respectively) and control subjects. Socioeducational attainment was lower in TNDM participants than in the general population, regardless of diabetes duration. CONCLUSIONS Relapse of diabetes occurred earlier in TNDM participants compared with relatives and was associated with puberty. Both groups had decreased educational attainment, and those with diabetes had lower insulin secretion capacity; however, there was no difference in insulin resistance in adulthood. These forms of diabetes should be included in maturity-onset diabetes of the young testing panels, and relatives of TNDM patients should be screened for underlying defects, as they may be treated with drugs other than insulin.

Background: 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. Aims and Methods: 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. Results: 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. Conclusion: 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.

Resume But de l’etude Etudier la conformite des prescriptions medicales des medecins generalistes et pediatres liberaux du departement du Nord de la France, par rapport aux recommandations de l’AFSSAPS de 2005 concernant la prise en charge de l’otite moyenne aigue du nourrisson de plus de 3 mois et de l’enfant. Methode Il s’agissait d’une enquete telephonique avec un questionnaire anonyme en 6 parties, et fonde sur des cas cliniques Des medecins generalistes tires au sort parmi les 2 477 medecins du Nord et de tous les pediatres liberaux du Nord ont ete inclus. Les criteres de jugement ont ete fondes sur les recommandations de l’Agence francaise de securite sanitaire des produits de sante. Resultats Les taux de participation etaient de 64,5 % pour les 200 medecins generalistes et 67,6 % pour les 68 pediatres liberaux. Pour l’indication et le choix d’un antibiotique, les recommandations etaient respectees par 9,3 % des medecins generalistes et 28,3 % des pediatres. La phase d’observation de 48 heures recommandee chez l’enfant de plus de 2 ans etait pratiquee par 46,5 % des medecins generalistes et 54,3 % des pediatres. Les durees d’antibiotherapie recommandees etaient peu respectees par les 2 groupes de praticiens. En cas d’allergie aux betalactamines, les pediatres suivaient plus souvent les recommandations. Conclusion Des efforts d’education et d’information sont necessaires pour ameliorer le suivi des recommandations de l’AFSSAPS concernant la prise en charge de l’otite moyenne aigue du nourrisson et de l’enfant dans le departement du Nord.

Bullous pemphigoid is an autoimmune subepidermal blistering disorder that typically affects elderly adults but can also occur in childhood. We report on a 3-month-old boy who developed bullous pemphigoid 1 week after the second routine administration of a hexavalent vaccine. The disease was resistant to standard therapies (including oral and topical corticosteroids) but was relieved by intravenous immunoglobulin treatment. There was no recurrence of bullous pemphigoid after the next vaccination (3 mos after discontinuation of steroids).

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.

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.

A patient developed agranulocytosis after Epstein-Barr infection. Bone marrow examination revealed normal myelopoiesis with reduced mature neutrophil polymorphonuclear cells. IgG-specific antineutrophil antibodies (anti-HNA-1a) were found in serum and on polymorphonuclear cells, suggesting that the agranulocytosis after infectious mononucleosis was caused by an autoimmune mechanism.

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.

Resume Quarante-six scintigraphies utilisant la [ 123 I] m IBG chez 33 enfants suspects d'etre porteurs d'un neuroblastome en evolutivite mettent en evidence une excellente specificite (96%) et une bonne sensibilite (90%). Des tumeurs peu differenciees et non excretantes peuvent ne pas capter le traceur. Aucune localisation detectable n'a echappea l'identification a la 24 eme heure. L'[ 123 I] m IBG (p, 5n) est recommande pour le diagnostic, le bilan evolutif et le suivi du neuroblastome chez l'enfant.