Evaluation of Outcomes and Quality of Care in Children with Sickle Cell Disease Diagnosed by Newborn Screening: A Real-World Nation-Wide Study in France.

This study's objective was to assess, on a national scale, residual risks of death, major disease-related events, and quality of care during the first five years in children diagnosed at birth with sickle cell disease (SCD). Data were retrospectively collected from medical files of all children with SCD born between 2006-2010 in France. Out of 1792 eligible subjects, 1620 patients (71.8% SS or S/beta°-thalassemia -SB°-) had available follow-up data, across 69 centers. Overall probability of survival by five years was 98.9%, with 12/18 deaths related to SCD. Probability of overt stroke by five years in SS/SB° patients was 1.1%, while transcranial Doppler (TCD) was performed in 81% before three years of age. A total of 26 patients had meningitis/septicemia (pneumococcal in eight cases). Prophylactic penicillin was started at a median age of 2.2 months and 87% of children had received appropriate conjugate pneumococcal vaccination at one year. By five years, the probability of survival without SCD-related events was 10.7% for SS/SB° patients. In contrast, hydroxyurea was prescribed in 13.7% and bone marrow transplant performed in nine patients only. In this study, residual risks of severe complications were low, probably resulting from a good national TCD, vaccination, and healthcare system coverage. Nonetheless, burden of disease remained high, stressing the need for disease-modifying or curative therapy.

Pneumococcal conjugate vaccine-elicited antibody persistence and immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in children previously vaccinated with 4 doses of either 7-valent or 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) antibody persistence and immunologic memory responses may be indicative of protection in previously vaccinated children. In children vaccinated in a previous study with an infant/toddler regimen of 4 doses of PCV7, 4 doses of PCV13, or 3 doses of PCV7 (infant series) and a dose of PCV13 (toddler dose), this follow-on study evaluated antibody persistence ≥24 months after the toddler dose, and immunogenicity and safety of a follow-on dose of PCV13. METHODS: Children ≥3 years of age who had completed the initial study received 1 dose of PCV13 in this phase 3, open-label follow-on study in France. Serotype-specific anticapsular immunoglobulin G (IgG) and functional opsonophagocytic activity (OPA) were compared across the previous study vaccination groups, before, 4-7 days (IgG only), and 1 month after follow-on vaccination. Safety was assessed. RESULTS: Before follow-on vaccination, IgG and OPA levels for the PCV7 serotypes were comparable across vaccination groups, but were generally higher for the 6 additional serotypes in children who received PCV13 in the previous study. At both time points after the follow-on vaccination, IgG and OPA values for all 13 serotypes increased, those for the PCV7 serotypes were similar across vaccination groups, but concentrations for the additional serotypes were higher in children who had received PCV13 in the previous study. PCV13 was well-tolerated. CONCLUSIONS: Antibody persistence and rapid responses after a follow-on dose of PCV13 suggest that even a single toddler dose of PCV13 is likely to provide protection against the 6 additional PCV13 serotypes.

Rapid molecular diagnosis of measles virus infection in an epidemic setting.

During the 2011 measles outbreak in Paris (France), patients with clinical suspicion of measles were tested for virological confirmation of measles virus (MV) infection. To assess the practical value of molecular diagnosis in an epidemic setting, 171 oral fluid samples and 235 serum samples collected from 270 patients were tested prospectively for MV-RNA using a novel one-step real-time RT-PCR assay including an internal control. Serum samples were also tested for MV-specific IgG and IgM antibodies. MV infection was confirmed by detection of MV-RNA and/or MV-IgM for 229 of the 270 patients. The results for the 102 cases with both serum and oral fluid samples available were used to compare the techniques. The detection rate of MV-RNA by RT-PCR was 98% (100/102) for oral fluid and 95% (97/102) for serum samples. The detection rate of MV-IgM was 85% (87/102). Negative MV-IgM results were observed mostly for serum samples collected early after the onset of the rash. A MV-RNA standard of known concentration obtained by in vitro transcription was used to quantify MV-RNA in samples. MV-RNA copy numbers were significantly higher in oral fluid than in serum samples, but did not correlate with time of sampling (within 1 week after the onset of the rash), patient age, or vaccination status. During the early stage of infection, the MV-RNA viral load in serum was lower in patients positive than in those negative for MV-IgG. In conclusion, the one-step real-time RT-PCR assay is a simple and sensitive tool suitable for MV diagnosis within hours.

Acute splenic sequestration crisis in sickle cell disease: cohort study of 190 paediatric patients.

Acute splenic sequestration crisis (ASSC) is an unpredictable life-threatening complication of sickle cell disease (SCD) in infants. Here, our objective was to update available clinical information on ASSC. We retrospectively studied the 190 patients who were diagnosed at birth with SS or Sbeta(0) in the Paris conurbation between 2000 and 2009 and who experienced ASSC. They had 437 ASSC episodes (0.06/patient-year). Median age at the first episode was 1.4 years (0.1-7) and 67% of patients had more than one episode. Age was the only factor predicting recurrence: the risk was lower when the first episode occurred after 2 years versus before 1 year of age (hazard ratio, 0.60; 95% confidence interval, 0.41-0.88; P=0.025). A concomitant clinical event was found in 57% of episodes. The mortality rate was 0.53%. The treatment consisted in watchful waiting without prophylactic blood transfusions or splenectomy in 103 (54%) patients and in a blood transfusion programme in 55 (29%) patients. Overall, splenectomy was performed in 71 (37%) patients, at a median age of 4.5 years (range, 1.9-9.4). In conclusion, aggressive treatment may be warranted in patients experiencing ASSC before 2 years of age. Randomized controlled trials are needed to define the best treatment modalities.

Association of meningococcal phenotypes and genotypes with clinical characteristics and mortality of meningitis in children.

BACKGROUND: Neisseria meningitidis meningitis represents approximately one-half of the meningococcal cases in French children. To explore the contribution of bacterial typing in improving the management of cases, we aimed to describe clinical characteristics and mortality of meningococcal meningitis in children reported to the multicenter survey system, GPIP/ACTIV, in association with phenotypes/genotypes of bacterial isolates. METHODS: From 2001 to 2005, 259 pediatric wards and 168 microbiology laboratories enrolled all children with bacterial meningitis. Risk factors, vaccination status, signs and symptoms, cerebrospinal fluid analysis, treatments and case fatality rate were recorded. RESULTS: A total of 962 cases of Neisseria meningitidis meningitis among a total of 2131 bacterial meningitis (45%) were recorded (mean age, 4.5 +/- 4.7 years). Serogroup distribution of the isolates was 62.3%, 33.7%, 2.9%, 0.6%, and 0.6% for serogroups B, C, W135, A and Y, respectively. The major clonal complexes were ST-41/44 (32.2%), ST-11 (21.9%), ST-32 (20.8%), ST-8 (8.2%), and ST-269 (4.9%). Despite global heterogeneity of the isolates, 2 phenotypes/genotypes were of interest. Isolates of the phenotype/genotype B:14:P1.7,16/ST-32 (56% clustered in the region of Haute Normandie) were observed in older children (8.6 years) and were associated with a higher case fatality rate (12%) than were other phenotypes of serogroup B. The phenotype/genotype C:2a:P1.5/ST-11 was found in 26.3% of serogroup C cases and was possibly associated with a higher mortality among serogroup C (9.9% for C and 5.9% for B, P = 0.04). CONCLUSIONS: This large survey provides data that could be important for implementation of future vaccines. Typing of meningococcal isolates could contribute to an understanding of prognosis in meningococcal meningitis.

Sickle cell children traveling abroad: primary risk is infection.

BACKGROUND: Pediatricians taking care of sickle cell children in France are concerned about giving travel advice. Very few articles are published and no study has been done about it. A lot of pediatricians are using their own experience to decide if sickle cell children can travel abroad. Studying the consequences of such travel for sickle cell children is important to discuss common recommendations. METHODS: We conducted a prospective study from June 2006 to December 2007 on desires to travel expressed during our consultations with sickle cell children. We studied notable events that occurred during travel and at least 2 months after return. RESULTS: Of 52 desires to travel, 10 were cancelled. All of the 42 trips were to Africa. Median duration of travel was 1.29 months (0.5-3). Median age at travel was 7.6 years (0.2-17.7). Events during travel were two hospitalizations (4.8%), a transfusion (2.4%), and four paramedical or medical examinations (9.6%). After return, four events occurred: two SS children had Plasmodium falciparum malaria (4.8%) and two had digestive bacteremia (4.8%) in SC and Sbeta+ children. No event occurred during plane travel. None of our patients died. CONCLUSIONS: The primary risk for sickle cell children traveling to Africa is infection: malaria first and digestive septicemia second. These risks are increased by long travel and poor sanitary conditions. Each travel should be prepared a long time before departure, and each pediatrician should insist on malaria prophylaxis and sanitary conditions, especially for young children. Trips should be shorter than 1 month when possible. A longer prospective study will be done to confirm these results.

[Acute rhinosinusitis in children]. / Infections rhinosinusiennes aiguës de l'enfant.

Rhinosinusitis in children is mainly caused by virus. After medical examination and according to the evolution, two clinical situations are defined: sub acute and persisting rhinosinusitis or acute and severe rhinosinusitis. Due to the development of sinus cavities, location of rhinosinusitis varies with age, ethmoïditis being the first location in young child. Imaging is recommended in cases of severe symptomatology or extra maxillary locations or for complications. Antibiotherapy is recommended in severe cases or complications. The choice of drugs is supported by the bacterial epidemiology of these infections and the level of resistance in France of the different microorganisms involved. In other cases, management includes symptomatic treatment and obvious informations on the different modalities of evolution.