Markers of a recent bocavirus infection in children with Kawasaki disease: "a year prospective study".

BACKGROUND: Retrospective studies and case-reports have suggested the possible role of various viruses in the pathogenesis of the Kawasaki disease. OBJECTIVES: To determine prospectively the incidence of Kawasaki diseases associated with a recent bocavirus infection in the course of a year. STUDY DESIGN: Thirty-two children with Kawasaki disease were enrolled in a 13 months prospective study to assess the frequency of human bocavirus type 1 infections. Seasonal shedding of virus, markers of recent infection such as viraemia, viral load, and serum interferon alpha were analyzed. RESULTS: Three of 32 (9%) children had HBoV-DNA in the serum suggesting a recent infection. HBoV-DNA was detected in naso-pharyngeal aspiration of 7/32 (21.8%) children with Kawasaki Disease and six of them (18%) had an increased viral load. No common respiratory viruses were isolated from the 32 patients with the exception of one adenovirus. The seven bocaviruses were identified during the winter-spring season. In addition, 4 of 7 of Kawasaki disease patients shedding bocavirus had detectable interferon alpha in the blood, indicating a possible active or recent viral infection. CONCLUSIONS: This study shows that a recent bocavirus infection is concomitant with the onset of some cases of Kawasaki disease. Bocavirus may be a cofactor in the pathogenesis of this disease as previously reported for other infectious agents.

Epidemiology and clinical features of gastroenteritis in hospitalised children: prospective survey during a 2-year period in a Parisian hospital, France.

Rotavirus is recognised as the most important agent of severe acute gastroenteritis (AGE) in young children. In a 2-year prospective survey, we investigated the epidemiology and clinical features of the viral and bacterial pathogens in children hospitalised for AGE. The study was performed in a Parisian teaching hospital from November 2001 to May 2004. Clinical data were prospectively collected to assess the gastroenteritis severity (20-point Vesikari severity score, the need for intravenous rehydration, duration of hospitalisation). Stools were systematically tested for group A rotavirus, norovirus, astrovirus and adenovirus 40/41, sapovirus and Aichi virus and enteropathogenic bacteria. A total of 457 children (mean age 15.9 months) were enrolled. Viruses were detected in 305 cases (66.7%) and bacteria in 31 cases (6.8%). Rotaviruses were the most frequent pathogen (48.8%), followed by noroviruses (8.3%) and adenoviruses, astroviruses, Aichi viruses and sapoviruses in 3.5%, 1.5%, 0.9% and 0.4%, respectively. Cases of rotavirus gastroenteritis were significantly more severe than those of norovirus with respect to the Vesikari score, duration of hospitalisation and the need for intravenous rehydration. Rotaviruses were the most frequent and most severe cause in children hospitalised for AGE, and noroviruses also account for a large number of cases in this population.

Unexpected substitution of dominant rotavirus G genotypes in French hospitalized children over five consecutive seasons.

The study was designed to evaluate the circulation of group A rotaviruses in French hospitalized children, and to detect unusual strains. This prospective study was conducted from 2001 to 2006 in children consulting for acute diarrhea at the pediatric emergency department in three French University Hospitals. The rotaviruses were detected by rapid test and genotyped by RT-PCR on the basis of their outer capsid proteins VP4 (P-type) and VP7 (G-type). The stools from 757 children were analyzed. G1P[8] strains were predominant (44.0%), followed by G9P[8] (17.7%), G3P[8] 13.1%, G4P[8] (9.5%), and G2P[4] (1.8%); mixed rotavirus infections occurred in 2.3%. G9 rotaviruses emerged during the 2004-2005 season (73.4%) and remained the second most prevalent strains. Few unusual strains, G6, G8, G12 and P[6]-types, were detected. The monitoring of rotavirus infections should be maintained to document strain distribution and to assess the emergence of new reassortants that may not respond to current rotavirus vaccines.

[Human bocavirus infections]. / Infections à Bocavirus humain.

Human Bocavirus (HboV) was recently cloned by a systematic screening of nasopharyngeal samples from children hospitalized for respiratory tract infections. This virus, genus Bocavirus, family Parvoviridae, was identified by screening for its DNA in 5% of nasopharyngeal aspirates, as reported in several studies. It may be responsible for upper and lower respiratory tract infections of young children under five years with a peak rate in winter. Because of a high rate of viral co-infections, its pathogenic role in these infections should be documented. Further studies are required to determine the role of this possibly systemic virus in other affections.

Prevalence and genetic diversity of Aichi virus strains in stool samples from community and hospitalized patients.

Aichi virus has been proposed as a causative agent of gastroenteritis. A total of 457 stool specimens from children hospitalized with acute diarrhea and 566 stool specimens from adults and children involved in 110 gastroenteritis outbreaks were screened for the presence of Aichi virus by reverse transcription-PCR (RT-PCR) amplification of the genomic region of the 3C and 3D (3CD) nonstructural proteins. Our results show a low incidence of Aichi virus in pediatric samples and the existence of mixed infections with other microbiological agents in some cases. From the outbreak survey, it appears that the presence of Aichi virus is an indicator of mixed infections causing gastroenteritis outbreaks and that it could be involved in half of the oyster-associated outbreaks. A second RT-PCR was developed to amplify a part of the VP1 gene. The phylogenetic analysis showed a good correlation between the two classifications based on 3CD and VP1 gene sequences and revealed the prevalence of genotype A in France. It also allowed us to partially describe an Aichi virus strain that could represent a new genotype, thus suggesting the existence of a certain diversity.

Clinical outcome in children with chronic recurrent multifocal osteomyelitis.

OBJECTIVE: To determine the clinical outcome of children with chronic recurrent multifocal osteomyelitis (CRMO). METHODS: We retrospectively reviewed clinical, biological and radiological data of children with CRMO at five French paediatric centres. Outcome data were obtained through review of hospital charts and questionnaires sent to all patients to assess disease activity and educational and vocational achievement. RESULTS: Forty patients were assessed (34 females and 6 males) with a median age at diagnosis of 11.5 yrs (range 2-17). Median number of initial bony lesions was 2 at onset, and 3.5 over disease course. Median time since diagnosis was 3.5 yrs (range 0.5-15) and median duration of active disease 2.7 yrs (range 0.5-13.5). Nine (22.5%) patients had psychological or physical sequelae. Twenty-nine children (72.5%) responded to the questionnaire. Twenty-six had no physical disability as judged by the HAQ 0-1, two had moderate disability (HAQ: 1-2) and one had severe disability (HAQ: 2-3). Seventeen patients (58.6%) had active disease at follow-up (after 6 months to 15 yrs since diagnosis) and continued to have pain (median value of visual analogue scale: 10/100). CRMO had interfered with patient's education in two cases. CONCLUSIONS: Clinical outcome of children with CRMO is generally good, but a sizeable proportion of patients have active disease at follow-up, and a minority of patients can have a severe and prolonged disease course despite intensive treatments. Further studies are required to determine predictive factors for severe disease.

[Bacterial diarrheas and antibiotics: European recommendations]. / Diarrhées bactériennes et antibiotiques : les recommandations européennes.

The need to limit unnecessary antibiotic treatments and recent studies with unusual antibiotics in pediatrics (fluoroquinolones) or in digestive tract infections (azithromycin) have led to update the treatment of acute gastro-enteritis. In 2007, the European Society for Pediatric Infectious Diseases and the European Society for Gastroenterology Hepatology and Nutrition have issued guidelines. The proven shigellosis as well as the strong suspicion have to be treated promptly with antibiotics, mainly azithromycin. There is no argument to treat moderate salmonella gastroenteritis or carriage. However, the severe cases and those occurring in high risk patient must be treated (ciprofloxacin or ceftriaxone). It is recommended to treat diarrhoea due to Campylobacter jejuni in case of early diagnosis. The presumptive antibiotic treatment should be limited but can not be dismissed, in invasive cases gastro-enteritis, especially in traveller children.

[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.

[Systematic family screening in case of infant pertussis]. / Dépistage familial systématique dans la coqueluche du nourrisson.

The origin of contamination in pertussis of young infants is generally the close relatives. From 2000 to 2004, only serology and culture were available in our hospital. The families of 16 young infants (age below one year) hospitalized for pertussis were screened using serological tests: 21/48 contacts were positive. After 2004, PCR was available for exploration of index cases and families: 35/85 contacts were positive. Of the mothers tested 23/46 were positive compared to 14/41 fathers. Only one parent presented with a typical paroxystic pertussis cough, 60% presented with a nonparoxystic cough having lasted for more than five days and 40% of positive adults did not present with cough. Despite official recommendations, none of these young parents had received an antipertussis booster vaccination. This study shows the high frequency of atypical or nonsymptomatic pertussis in adults in the close family of infected young infants. These adults contribute to spreading the disease.

Detection of human bocavirus in children with Kawasaki disease.

Human bocavirus (HboV) is an emerging virus that has been implicated as a cause of acute upper and lower respiratory tract infection in children. As no serological assay is available, PCR was used to screen nasopharyngeal, serum or stool samples from 16 patients with Kawasaki disease for HBoV nucleic acid. HBoV was identified by PCR in five (31.2%) patients, suggesting that this emerging virus may also play a pathogenic role in some cases of Kawasaki disease.

Pertussis in young infants: apnoea and intra-familial infection.

This study investigated 41 infants, aged <4 months, who were hospitalised with symptoms compatible with pertussis. Of these, 16 had Bordetella pertussis infection confirmed by real-time PCR. For four of these 16 patients, the initial sample was PCR-negative, but samples collected 5-7 days after the onset of infection were PCR-positive. PCR was also positive with samples from 15/16 families and 20/41 household contacts. Nine of the 20 positive household contacts were asymptomatic. Among the 16 infants with proven pertussis, apnoea was more frequent than in a control group for whom PCR was negative with both children and household contacts (69% vs. 28%). It was concluded that real-time PCR performed with samples from household contacts facilitates the diagnosis of infants suspected clinically of having pertussis, thereby enabling earlier treatment.

[Distinction between bacterial and aseptic meningitis in children: refinement of a clinical decision rule]. / Distinction entre les méningites bactériennes et virales chez l'enfant: affinement d'une règle de décision clinique.

OBJECTIVES: To refine and to re-validate the best current tool (the Nigrovic rule: ''outpatient management may be considered for children without seizure, blood neutrophil count>or=10,000/mm(3), positive cerebrospinal fluid -CSF- Gram-staining, CSF protein>or=80 mg/dl, or CSF neutrophil count>or=1,000/mm(3)'') proposed to distinguish between aseptic meningitis (AM) and bacterial meningitis (BM) in the emergency department. METHODS: Children hospitalized for BM between 1995 and 2004, or AM between 2000 and 2004 were included, and randomly divided into derivation (111 children, 14 BM) and internal validation (57 children, 7 BM) sets. The Nigrovic rule was refined on the derivation set, introducing new variables (purpura, toxic appearance and high serum procalcitonin), changing variables thresholds (CSF protein) and withdrawing some variables (blood neutrophil count, CSF neutrophil count), according to previous results, with the aim to obtain 100% sensitivity user friendly tool. The refined rule was then applied on the internal validation set, stayed blinded during the derivation process. RESULTS: The refined rule was: start antibiotics in case of seizure, purpura, toxic appearance, procalcitonin>or=0.5 ng/ml, positive CSF Gram-staining, or CSF protein>or=50 mg/dl. The refined rule had 100% sensitivity on the derivation and the internal validation sets (95% confidence interval 78-100, and 65-100, respectively) with 62 and 51% specificity, respectively. CONCLUSION: The refined rule (called Meningitest) was a highly sensitive, specific and user friendly tool that could allow to safely avoid>50% a posteriori unuseful antibiotic treatments for patients with AM.

[Children arthropod bites protective measures: insecticides and repellents]. / Protection antivectorielle de l'enfant: insecticides et insectifuges.

Vector transmitted diseases are often a serious threat for child health, especially for children traveller in tropical regions. Few arthropod borne diseases are preventable by immunization or chimioprophylaxis. Prevention of most of them is based on personal protection against arthropod bites. The evidence of its efficacy has been established by the use of impregnated bed nets, impregnated clothes with permethrin or mosquito repellent which reduced significantly child malaria morbidity and mortality in endemic countries. These personal protective measures are able to minimize arthropod bites and prevent Chikungunya infection, dengue fever and Lyme disease. The choice of a repellent among the commercialised products need to be efficacy and safety evidence based. This article propose to raise this issue and to give pragmatic recommendations, with a focus to children below 30 months who are at a high toxicological risk. Severity of these diseases allowed to use potentially toxic repellents if misused.

[Vaccinations for traveler child]. / Vaccinations de l'enfant voyageur.

Each year, half a million of children leave France to travel towards countries south or east of the European Union, sometimes in poor sanitary conditions. In order to propose essential or useful immunizations for these trips, the current synthesis will allow the practitioner to insure that the routine French immunization schedule has been followed, and to complete it if needed, to protect the child according to the epidemiological situation in the visited area, to try to reduce the limitations of the immunization of the traveler child. In case of emergency, or close departure, it may be useful to follow an accelerated schedule of the last minute, and, sometimes, to immunize traveler children with a chronic disease. Informations on Internet sites useful for the knowledge of current infectious risks in the destination country are also provided.

[Nosocomial rotavirus infections in a pediatric unit: surveillance during four successive winters]. / Infections nosocomiales à rotavirus dans un service de pédiatrie générale: surveillance au cours de quatre hivers successifs.

UNLABELLED: The incidence of rotavirus and RSV outbreaks during winter seasons leads to overcrowding of pediatric units in the Paris area, and increases the risk of viral nosocomial infections in hospitalized young infants. OBJECTIVE: The aim of this study was to measure the incidence of rotavirus nosocomial infections in children less than 2 years of age during 4 consecutive winters. METHODS: All infants admitted in the pediatric unit during the winter were prospectively screened for rotavirus with a stools exam. All children with negative stools examination on admission but developing diarrhea after 2 days of hospitalization underwent a new screening test for rotavirus in stools. RESULTS: During the 4 consecutive winters, the global incidence of nosocomial rotavirus infection was 13.9% (12.7 to 15.9%). Asymptomatic carriage of rotavirus was detected in 3% of admitted infants. The risk of nosocomial rotavirus infection increases with young age and the length of hospital stay. CONCLUSION: The incidence of nosocomial rotavirus infections was high in this unit. It is related to overcrowding due to coincidence of diarrhea and bronchiolitis outbreaks in the Paris area and to the young age of hospitalized patients.

[Simultaneous outbreaks of rotavirus and respiratory syncytial virus in Paris: a 12-year survey]. / Coïncidence des épidémies de rotavirus et de virus respiratoire syncytial à Paris: 12 ans de surveillance.

OBJECTIVE: The authors had for aim to study the coincidence of RSV and rotavirus epidemic peaks in pediatric patients hospitalized in the Paris area. METHODOLOGY: A retrospective hospital-based monocentric cohort study was made over a 12-year period (1993-2004). Clinical and laboratory findings were prospectively collected on admission. RESULTS: Three thousand and four hundred ninety-six stool samples were positive for rotavirus; 3,507 nasopharyngeal aspirates were positive for RSV. The coincidence of epidemic peaks for both viruses in November, December, and January was observed during the 12 years of the study. CONCLUSION: The exact coincidence of winter outbreaks of RSV and rotavirus is a characteristic of the Paris area. It contributes to increase overcrowding in pediatric units and nosocomial infections.

Antimicrobial treatment of diarrhea/acute gastroenteritis in children.

Acute gastroenteritis (AGE) are usually caused by viruses, especially Rotavirus and Norovirus. Among the bacterial causes, very few warrant antibiotic treatment, mainly Shigella, Vibrio cholerae, Campylobacter (only for severe cases, particularly in the initial phase) and severe cases of Salmonella infection. The antimicrobial treatments proposed in this guide follow the latest guidelines of the European Society of Pediatric Infectious Diseases and the European Society of Pediatric Gastroenterology and Nutrition. Azithromycin is the preferred antibiotic for infections due to Shigella and Campylobacter. Ceftriaxone and ciprofloxacin are recommended for salmonellosis when antibiotic treatment is indicated. In most cases, empirical treatment without bacteriological documentation should be avoided.

[Children tuberculosis after familial contamination: experience in general pediatrics]. / Tuberculose de l'enfant après contage familial: une expérience en pédiatrie générale.

UNLABELLED: The heterogeneity of clinical presentations of children in contact with a tuberculous adult do not allow simple guidelines for treatment and exams. Indications of thoracic computed tomography (CT) in young children and the risk of a follow-up without antituberculous treatment are always discussed. PATIENTS: Sixty-nine children, belonging to 50 families, living in close contact with an adult treated for tuberculosis were explored during 7 years in a General Pediatric Unit. A CT was performed in 51 patients. RESULTS: Mantoux test was negative in 3/17 children with typical tuberculous disease on X-ray. When results of CT were compared with those of standard thoracic X-ray, a difference for the diagnosis of mediastinal adenopathies was found only in children younger than 5 years. Fifty-eight patients were given usual treatment of latent or patent tuberculosis if indicated, or a chemoprophylaxis. All of them had normal clinical and X-ray exam 2 to 4 years later. Eleven children, initially checked in an other unit, were given no treatment, but a follow-up was set up. However, after 6 to 24 months, 4/11 had a patent tuberculosis and 5/11 a latent tuberculosis, 6/9 being aged more than 3 years. CONCLUSION: This study shows that risk of tuberculosis after familial contamination is high, and that the choice of absence of treatment with following re-evaluation, is sometimes questionable because families or doctors do not perform the prescribed follow-up. To perform systematically a thoracic CT, searching for mediastinal adenopathies, is useful only before the age of 5 years.

[Safety of oral ivermectin in children]. / Tolérance de l'ivermectine orale chez l'enfant.

Ivermectin is an antiparasitic drug, a derivate of avermectins, and a product of fermentation of an actinomycete, Streptomyces avermitilis. Its structure associates two avermectins. Ivermectin acts on the chloride-dependent channels of both glutamate and γ-aminobutyric acid, interrupting neurotransmission in invertebrates. In humans, several mechanisms of brain protection exist, including P-glycoprotein, present on the apical face of endothelial cells of the blood-brain barrier and coded by the MDR1 gene. Ivermectin is presently used in mass treatment of onchocerciasis, other filariasis, some intestinal nematode infections, but also in scabies, and more rarely in resistant head lice. The side effects described are related to the release of antigen and cause an inflammatory reaction. Studies conducted in children or infants have shown good tolerance of ivermectin. However, its use in infants who weigh less than 15kg is a problem because of the absence of marketing authorization for this age group. However, the risk of excessive and uncontrolled use in head lice requires close surveillance.

Clinical severity and molecular characteristics of circulating and emerging rotaviruses in young children attending hospital emergency departments in France.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up to investigate the virological and clinical features of RVA infections and to detect the emergence of potentially epidemic strains in France. From 2009 to 2014, RVA-positive stool samples were collected from 4800 children <5 years old attending the paediatric emergency units of 16 large hospitals. Rotaviruses were then genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. Genotyping of 4708 RVA showed that G1P[8] strains (62.2%) were predominant. The incidence of G9P[8] (11.5%), G3P[8] (10.4%) and G2P[4] (6.6%) strains varied considerably, whereas G4P[8] (2.7%) strains were circulating mostly locally. Of note, G12P[8] (1.6%) strains emerged during the seasons 2011-12 and 2012-13 with 4.1% and 3.0% prevalence, respectively. Overall, 40 possible zoonotic reassortants, such as G6 (33.3%) and G8 (15.4%) strains, were detected, and were mostly associated with P[6] (67.5%). Analysis of clinical records of 624 hospitalized children and severity scores from 282 of them showed no difference in clinical manifestations or severity in relation to the genotype. The relative stability of RVA genotypes currently co-circulating and the large predominance of P[8] type strains may ensure vaccine effectiveness in France. The surveillance will continue to monitor the emergence of new reassortants that might not respond to current vaccines, all the more so as all genotypes can cause severe infections in infants.