[Acute otitis media in ambulatory practice: epidemiological and clinical characteristics after 7 valent pneumococcal conjugate vaccine (PCV7) implementation]. / Otite moyenne aiguë en pédiatrie ambulatoire : caractéristiques épidémiologiques et cliniques après l'introduction du vaccin antipneumococcique conjugué 7 valent (PCV7).

BACKGROUND: In US, pneumococcal conjugate vaccine (PCV7) had reduced the burden of AOM and changed the profile of the disease. Prior to PCV7 implementation in France, AOM represented 8% of pediatricians visits and failure rate was 12%. The aim of this study is to describe the epidemiologic characteristics of AOM after PCV7 implementation. METHODS: From 2007 to 2008, 30 pediatricians enrolled 3141 patients 3 to 36 months old with AOM. Standardized history and physical examination findings were recorded. Factors related to AOM failures were identified by multivariate logistic regression. RESULTS: AOM accounted for 5.8% of the 43 433 visits or 6.2 cases/week per pediatrician. Among 3141 evaluable AOM cases (mean age 16.7±8 months, peak incidence at 10 months), 99% had been vaccinated with PCV7 and 42.1% attended day care (DCC). Recurrent AOM comprised 24.5% of cases and 51% of children had received ATB in the last 3 months. At the time of diagnosis, 47.1% had fever≥38,5°C, 74.5% otalgia and 4.7% otorrhea. Febrile and painful AOM accounted for 29.5% of cases and cunjunctivitis-otitis syndrome for 18.2%. ATB was prescribed in 98.7% of cases (cefpodoxime proxetil, 59% and amoxicillin/clavulanate, 37%). The failure rate was 6.4% and failure risk was greater in children in DCC (OR=1.50, [1.10;2.05]), young age<18 months (OR=1.47, [1.06;2.04]) and history of recurrent AOM (OR=1.45, [1.02;2.06]). CONCLUSION: Despite PCV7 implementation, AOM remains a very frequent childhood infection and a major reason for ATB prescriptions.

[Acceptability, compliance and schedule of administration of oral antibiotics in outpatient children]. / Acceptabilité, compliance et rythme d'administration des antibiotiques oraux chez l'enfant, en ambulatoire.

BACKGROUND: Compliance with antibiotics is essential to ensure treatment efficacy and to prevent the emergence of bacterial resistant stains. In children who take oral form, the palatability and the frequency of administration seem to be factors important to good compliance. PATIENTS AND METHODS: This observational study was designed to assess the acceptability of oral antibiotics (including generics) commonly prescribed to children by primary care physicians in France. It was given to 50 pediatricians and 50 GPs in private practice. For each patient, the physician and parents completed a questionnaire, and parents filled out a log for each drug intake. RESULTS: Between September 2006 and September 2007, 91 physicians enrolled 2400 children and 1482 patient records are fully assessable. The two factors that improve significantly compliance are administration in two doses by day (OR 2.2 [95% CI 1 6-3]) and acceptability ≥80% (OR 2.6, [95% CI 1.9-3.7]). The acceptability was better for amoxicillin-clavulanic acid 65.4% (95% CI [57.6 to 72.4]) than for cefpodoxime 47.1% (95% CI [43.8-50.4]) or cefuroxime axetil 26% (95% [CI 15.9-39.6]). Conversely, cefpodoxime proxetil obtained a better score for compliance 91.8% (95% CI [89.8 to 93.4) as amoxicillin-clavulanic acid 84.6% (95%CI 80.8 to 87.8) because of its mode of administration in two doses per day. There is no difference between the amoxicillin clavulanic acid reference product and its generics as a whole, however a large variability exists between generics. If, for antibiotics prescribed in two doses per day, the two administrations by day are roughly equidistant, it is not the same for those prescribed three times a day: indeed, while the doses taken are identical, only four hours separate the first intake of the morning from the second intake in mid-day and more than 12 hours between the evening dose from the next morning intake. CONCLUSIONS: This study confirms the disparity in terms of acceptability among the different antibiotics prescribed for children even for the same drug, warranting evaluation for marketing of future generic drugs pediatric oral suspension. The disparity ranges for drugs three times daily asking consequences pharmacokinetics and dosage adjustment for a transition to two doses per day.

A 20-year experience of electron microscopy in the diagnosis of primary ciliary dyskinesia.

Transmission electron microscopy (TEM) analysis of ciliary ultrastructure is classically used for the diagnosis of primary ciliary dyskinesia (PCD). We report our extensive experience of TEM analysis in a large series of patients in order to evaluate its feasibility and results. TEM analysis performed in 1,149 patients with suspected PCD was retrospectively reviewed. Biopsies (1,450) were obtained from nasal (44%) or bronchial (56%) mucosa in children (66.5%) and adults (33.5%). TEM analysis was feasible in 71.4% of patients and showed a main defect suggestive of PCD in 29.9%. TEM was more feasible in adults than in children, regardless of the biopsy site. Main defects suggestive of PCD were found in 76.9% of patients with sinopulmonary symptoms and in only 0.4% of patients with isolated upper and 0.4% with isolated lower respiratory tract infections. The defect pattern was similar in children and adults, involving dynein arms (81.2%) or central complex (CC) (18.8%). Situs inversus was never observed in PCD patients with CC defect. Kartagener syndrome with normal ciliary ultrastructure was not an exceptional condition (10.2% of PCD). In conclusion, TEM analysis is feasible in most patients and is particularly useful for PCD diagnosis in cases of sinopulmonary syndrome of unknown origin.

Local and regional adverse reactions to BCG-SSI vaccination: a 12-month cohort follow-up study.

In a 12-month cohort follow-up study of 2435 children vaccinated in 2007 by Statens Serum Institute BCG strain (BCG SSI, 17.8% had an adverse event (AE): erythema 12.4%, induration 12.2%, abscesses 2.5%, ulceration 0.9%, lymphadenitis 0.1%. The factors associated with a lower risk of AE were: age at vaccination <1 year compared to age >1 year (OR=0.35 [0.2-0.6] for age <28 days, 0.29 [0.2-0.42] for age 29 days to 2 months, and 0.53 [0.37-0.74] for age 3-11 months), a visible papule (OR=0.48 [0.36-0.63]), and a low vaccine dose (OR=0.42 [0.31-0.58]). AE to BCG SSI vaccination were frequent but rarely severe.

[BCG vaccine coverage in private medical practice: First data in children below two years old, seven months after the end of compulsory vaccination in France]. / Couverture vaccinale BCG en médecine libérale : premières données chez le nourrisson, sept mois après la levée de l'obligation vaccinale en France.

OBJECTIVES: In July 2007, compulsory BCG vaccination for all children was replaced by a strong recommendation to vaccinate children at high risk of tuberculosis (children who live in Ile-de-France [IDF] or Guyana regions, who were born or whose parents were born in tuberculosis endemic countries, with a family history of tuberculosis or living in conditions defined as at risk by the doctor). In the absence of tools to detect an early decrease in vaccine coverage (VC) in this specific group, we conducted a survey with the main objective of measuring BCG VC in high risk children for which BCG is now recommended and who were born after the change in BCG vaccine policy. METHODS: Cross-sectional survey performed amongst physicians registered at "Infovac-France", a network of general practitioners and paediatricians particularly aware of recent changes in the field of vaccinations. Each doctor was asked to recruit, during his medical consultation, between six and 12 children aged 2-7 months (born after the end of compulsory BCG vaccination in July 2007) and 8-23 months (born after the withdrawal from the market of the multipuncture form of BCG [Monovax] in January 2006 and before the end of compulsory BCG vaccination in July 2007). Doctors were asked to fill in a structured online questionnaire. Data were standardized and analysed with Stata 9.2. RESULTS: A total of 2536 children, recruited by 279 general practitioners and paediatricians (6.5% of all contacted doctors), were included. VC in the target group of high risk children for who BCG is still recommended and who were seen by doctors working in a private medical practice was: overall 68%; 58% in children born after the end of compulsory BCG vaccination (68% in IDF, 48% outside IDF); 77% in those born after the withdrawal of Monovax from the market and before the end of compulsory BCG vaccination; 90% in children living in IDF born after the end of compulsory vaccination and considered as particularly at risk of tuberculosis (presence of vaccination criteria other than residing in IDF) and 60% in the same category of children whose sole criteria for vaccination was residing in IDF. Of doctors who worked in a private medical practice: 75% used to perform the BCG vaccination themselves and 58% had recommended or suggested vaccination to children at risk who were not yet vaccinated. Seventy-six percent of parents of children at risk of tuberculosis not yet vaccinated accepted BCG vaccination when recommended by their doctor. CONCLUSION: Our survey showed, on the one hand, insufficient VC in children seen in a private medical practice and born after the end of compulsory vaccination for whom BCG is still recommended. This should encourage the Ministry of Health to reinforce its communication concerning this new policy. On the other hand, the survey showed encouraging results concerning both the coverage of children at particularly high risk in IDF and the adherence of doctors and families to the new vaccine policy. These results should be interpreted with caution, taking into account the methodological limitations of this survey.

[Surveillance network of bacterial meningitis in children, 7 years of survey in France]. / Observatoire national des méningites bactériennes de l'enfant en France : résultats de 7 années d'étude.

OBJECTIVES: Consequence of the introduction of vaccines against bacteria involved in meningitis in children and various recommendations concerning antibiotics, the epidemiology of bacterial meningitis has changed during the last fifteen years. The GPIP/ACTIV (Groupe de Pathologie Infectieuse Pédiatrique and Association Clinique et Thérapeutique Infantile du Val de Marne) set up an active surveillance network to analyze the clinical and biological features of bacterial meningitis. METHODS: From 2001 to 2007, 252 French pediatric wards working with 168 microbiology laboratories enrolled all children (0-18 years old) with bacterial meningitis. Risk factors, vaccination status, signs and symptoms, cerebrospinal fluid analysis, treatments and case fatality rate were recorded. RESULTS: 2951 cases of bacterial menigitis were recorded by 237 pediatric wards. Geographical distribution covered a large part of the national territory. Overall, the annual number of cases varied from 452 (in 2001 and 2003) to 378 (in 2004). Meningococcal and pneumococcal meningitis respectively represented about the half (46 %) and the third (28 %) of cases. Few cases of Haemophilus influenzae meningitis were reported (3 %). For the neonatal period, group B Streptococcus and E. coli were the most frequently identified pathogens. In children less than one year old, pneumococcus was the first one, and after 1 year, meningococcus was predominant. The mortality rate varied according to bacteria, 6.6 % for the meningococcus, 11.6 % for pneumococcus, 14.1 % for group B streptococcus and 16.7 % for Listeria meningitis. It varied also with age, 14.9 % among infants 1 to 2 months old and 6.3 % in children over 5 years. CONCLUSION: Closed to 3000 meningitis were recorded during seven years in children, which underlines the interest of the survey. This network is principally supported by the goodwill and availability of pediatricians and microbiologists who participate in the study. This special supplement issue of Archive de Pédiatrie allows a complete presentation of our results. In next following years, any amendment to the immunization schedule, any perspective of implementation of new vaccines will transform the epidemiology and clinical caracteristics of bacterial menigitis. Therefore, continued surveillance appears necessary.

Pneumococcal meningitis in the era of pneumococcal conjugate vaccine implementation.

The French Pediatric Infectious Diseases Group set up an active surveillance network to analyze the clinical and biological features of pneumococcal meningitis and the impact of the seven-valent pneumococcal conjugate vaccine (PCV7). From 2001 to 2005, 234 pediatric wards working with 166 microbiology laboratories enrolled all children with pneumococcal meningitis. Risk factors, signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments and case fatality rates were recorded. One hundred and sixty-nine centers (169/234) reported 616 cases, median age was 0.9 years and 67.2% of children were < or =2 years old. Underlying conditions were present in 13.1% of cases. The proportion of penicillin non-susceptible strains was 48.7%. Vancomycin plus a third-generation cephalosporin was prescribed in 92.7% of cases, and steroids were given before antibiotic treatment in 16.5% of cases. The case fatality rate was 10.8% overall and was not related to age, antibiotic susceptibility or steroid use. In children 2 to 24 months old compared to the prevaccinal period (2001-2002) a decrease of 28.4% of the number of cases was observed in 2005 (P < 0.05). Among children 2 to 24 months old, the proportion of serotypes covered by the PCV7 fell from 39/57 (68.4%) in 2001-2002 to 19/45 (42.2%) in 2005, while the proportion of non-vaccine serotypes and related serotypes increased respectively from 9/57 (15.8%) and 9/57 (15.8%) in 2001-2002 to 14/45 (31.1%) and 12/45 (26.7%) in 2005. Among 52 cases of pneumococcal meningitis that have occurred in vaccinated children (> or =1 dose) with PCV7, 7 were due by vaccine serotypes. This study provides data on underlying conditions, penicillin susceptibility, serotype evolution according to vaccination status and risk factors for mortality for pneumococcal meningitis in children from 2001-2005 in France.

[Impact of the rapid diagnosis downtown in the assumption of responsibility of the children in period of influenza]. / Impact des tests de diagnostic rapide en ville dans la prise en charge des enfants en période de grippe.

Several studies in children showed at the paediatric emergency hospital the interest of influenza rapid diagnostic tests (IRDT) in this disease for which the clinical diagnosis is difficult in children. The purpose of this prospective study carried out in ambulatory paediatric setting was to evaluate impact of the IRDT in the assumption of responsibility of children suspected of Influenza infection. Thirty paediatricians (14 without IRDT, 16 with IRDT) included 602 children between 2004 and 2005. The influenza was confirmed by IRDT in 54% of the cases. Among the 13 symptoms or signs recorded, only 4 - chills (61.6 vs 48.4%), cough (89.8 vs 71.1%), rhinorrhea (97.9 vs 86.2%), and anorexia (50.3 vs 34.8%) - were significantly more frequent (P

Relationship between clinical signs and symptoms and nasopharyngeal flora in acute otitis media.

Possible links between the clinical signs and symptoms of acute otitis media and the composition of the nasopharyngeal flora were investigated by reviewing the files of 1807 children enrolled in four randomised, multicentre trials. A standard protocol was used, nasopharyngeal samples were cultured, and signs and symptoms were recorded. Carriage of Haemophilus influenzae was associated positively with conjunctivitis (OR 4.83, 95% CI 3.76-6.20) and negatively with fever (OR 0.69, 95% CI 0.56-0.86). Carriage of pneumococci was associated positively with fever (OR 1.32, 95% CI 1.08-1.63) and negatively with conjunctivitis (OR 0.50, 95% CI 0.40-0.63).

[French paediatrician and general practitioner's survey about actual and future BCG use]. / Enquête sur les pratiques actuelles et futures du vaccin contre la tuberculose auprès des pédiatres et généralistes en France.

Within the context of future multipuncture withdrawal, we managed, in April 2005, a survey on BCG vaccine habits. During April 2005, 636 paediatricians and 192 GP took part in a survey about BCG, practices managed by InfoVac-France, InVS and AFPA. Most of physicians (73.6%) don't use Mantoux test before BCG vaccination in children less than 6 months old, and the Monovax is the most frequent vaccine used (93.7%). Less than 30% physicians are thinking to be ready to systematically vaccine children after prospected withdrawal of multipuncture vaccination, and almost 1 pediatrician of 5 and one GP of 7 don't want to vaccine anymore. In future, preferred option after Monovax withdrawal is to vaccinate with BCG only the high risk population for tuberculosis (59%). About 60% physicians think that parents could be opposed to intradermal immunization. More than 2/3 of physicians have not an assistant (except the parents) to contain the children during the intradermal injection (71.6%). It seems not acceptable for 2/3 of physicians to address their patients to colleagues or to specialized structures.

[Pneumococcal meningitis in France: age and medical risk factors in children]. / Méningites à pneumocoque de l'enfant en France: âge de survenue et facteurs de risques médicaux.

Streptococcus pneumoniae (Sp) is an important cause of morbidity and mortality among paediatric infectious diseases. The aim of this study is to analyse specific data on Sp meningitis out of the Bacterial Meningitis (BM) French Surveillance Network about mean age of BM cases and clinical features. Overall 367 Sp BM were reported between January 2001 to January 2004 (sex ratio M/F: 1.3), 69.7% were < 2 years old, median age 0.8 year (minmax 0-16.8 years). Before two years old children, 94.1% had no medical risk factor and no underlying conditions: on the other hand, after two years old, these factors were reported in 27% cases (P < 0.001). Mortality rate was 10.9%. On account of a Sp BM's pic at five months, data of the BM French Surveillance Network confirm the necessity of an early vaccination. The vaccine administration at two, three, four months with a booster during the second year, recommended in the vaccinal french calendar, seems particularly adapted to the Sp BM in France.

[Recurrent respiratory tract infections: how should we investigate and treat?]. / Infections respiratoires récidivantes: quels bilans, quels traitements ?

Recurrent respiratory tract infections are a common reason for visits to primary care practitioners or hospital physicians. They are placed at the junction of several medical specialities: paediatrics, ENT, pneumology, allergology, immunology, infectiology. The great diversity of the laboratory tests requested and on the other hand the proposed treatments, are the consequences of the diversity of the patients encountered and the paucity of the evidence based-medicine studies in this setting. The dilemma is how to identify the child for which recurrent respiratory tract infections are the witness of underlying condition, without performing repeated medical examinations, laboratory tests and treatments for normal children for which immunologic development occurs normally. The essential tools are the history analysis, physical examination and few laboratory tests. The other questions are how to include, for these patients, influenza and pneumococcal vaccines in the immunization program and how to assess the benefit/risk ratio and the cost of surgical treatments. This paper presents the thought of an expert group trying to define the situations where biological tests or treatments are useful.

Polymorphic short tandem repeats for diagnosis of the Charcot-Marie-Tooth 1A duplication.

BACKGROUND: A 1.5-Mb microduplication containing the gene for peripheral myelin protein 22 (PMP22) on chromosome 17p11.2-12 is responsible for 75% of cases of the demyelinating form of Charcot-Marie-Tooth disease (CMT1A). Methods for molecular diagnosis of CMT1A use Southern blot and/or amplification by PCR of polymorphic poly(AC) repeats (microsatellites) located within the duplicated region, or the detection of junction fragments specific for the duplication. Difficulties with both strategies have led us to develop a new diagnostic strategy with highly polymorphic short tandem repeats (STRs) located inside the CMT1A duplicated region. METHODS: We tested 10 STRs located within the duplication for polymorphic behavior. Three STRs were selected and used to test a set of 130 unrelated CMT1A patients and were compared with nonduplicated controls. The study was then extended to a larger population of patients. Alleles of interest were sequenced. A manual protocol using polyacrylamide electrophoresis and silver staining and an automated capillary electrophoresis protocol to separate fluorescently labeled alleles were validated. RESULTS: We identified three new STRs covering 0.55 Mb in the center of the CMT1A duplication. One marker, 4A, is located inside the PMP22 gene. The two others, 9A and 9B, more telomerically positioned, have the highest observed heterozygosity reported to date for CMT1A markers: 0.80 for 9A, and 0.79 for 9B. Tetra- and pentanucleotide repeats offered clear amplification, accurate sizing, and easy quantification of intensities. CONCLUSIONS: Combined use of the three STRs allows robust diagnosis with almost complete informativeness. In our routine diagnosis for CMT1A, they have replaced the use of other polymorphic markers, either in a manual adaptation or combined with fluorescence labeling and allele sizing on a DNA sequencer.

Impact of antimicrobial therapy on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis in children with respiratory tract infections.

We conducted a multicenter prospective study to document changes in nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis during antibiotic therapy. A cohort of 629 children with respiratory tract infections underwent nasopharyngeal sampling before and after antibiotic treatment. Susceptibility testing, serotyping, arbitrarily primed polymerase chain reaction, and pulsed-field gel electrophoresis were used to compare pretreatment and posttreatment strains of S. pneumoniae. A significant decrease in carriage of all 3 species (especially S. pneumoniae and B. catarrhalis) was recorded. The increase in the proportion of penicillin-resistant pneumococci (PRP; 66% vs. 44%) was due to the decreased carriage of penicillin-susceptible pneumococci (71 of 629 vs. 176 of 629). The risk of PRP carriage in a given child did not increase. None of the children was found to harbor genetically related strains with increased minimum inhibitory concentrations. Given the multiple resistance of PRP, beta-lactam antibiotic therapy also increased the incidence of macrolide-resistant strains, whereas macrolides selected both macrolide- and penicillin-resistant strains.

Five vs. ten days of antibiotic therapy for acute otitis media in young children.

BACKGROUND: Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years. METHODS: In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period. RESULTS: Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68). CONCLUSIONS: The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol.

One dose ceftriaxone vs. ten days of amoxicillin/clavulanate therapy for acute otitis media: clinical efficacy and change in nasopharyngeal flora.

OBJECTIVE: To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone, 50 mg/kg, vs. a 10-day course of amoxicillin/clavulanate (amox/clav) therapy, 80 mg/kg/day of amoxicillin: 10 mg/kg/day of clavulanate in three divided doses, in children with acute otitis media (AOM) and to evaluate the changes in nasopharyngeal flora after treatment. METHODS: In a prospective, comparative, open randomized, multicenter trial, children were scheduled to return for visits on Days 12 to 14 (main end point) and Days 28 to 42 after the beginning of treatment for AOM. A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14. RESULTS: Between February, 1995, and May, 1996, 513 children with a mean age of 14.2 +/- 6.7 months were enrolled. All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy. At Days 12 to 14 clinical success was obtained in 186 of the 235 children (79%) given ceftriaxone and in 188 of the 228 children (82.5%) treated with amox/clav. Among the patients with clinical success on Days 12 to 14, the success was maintained at Days 28 to 42 for 108 of 183 (59%) patients in the ceftriaxone group and 103 of 187 (55%) patients in the amox/clav group. Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae (59.1%), Haemophilus influenzae (39.4%), Moraxella catarrhalis (55.7%) and the rate of penicillin-resistant S. pneumoniae (52.2%) were comparable between the 2 groups. At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone, 43.9 and 42.2, respectively, and the patients treated with amox/clav, 17.4 and 11.1%, respectively. Among the children carrying S. pneumoniae at Days 12 to 14, the percentage of penicillin-resistant strains reached 63.4% in the ceftriaxone treatment group and 83.0% in the amox/clav treatment group, (P = 0.02). Adverse events (mainly diarrhea) related to the study medication were reported more frequently (P < 0.0001) in the amox/clav treatment group. CONCLUSIONS: In an area with a high rate of penicillin-resistant S. pneumoniae, a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children. There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried, whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment.