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Kingella kingae arthritis in children is now mainly diagnosed by PCR, which has surpassed conventional culture of joint fluid. As oropharynx colonization is the first step of Kingella kingae invasion, we prospectively investigated the possibility of cultivating it from throat swabs, in children hospitalized for K. kingae arthritis. Throat culture was 5.6-fold more sensitive than joint fluid cultures in isolating K. kingae (66.7% vs. 11.9% respectively, p <0.001) and may be used to perform antibiotic susceptibility testing., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Unlabelled: Few data are available on the impact of a tuberculosis exposure on newborns in a maternity ward., Objectives: To describe the screening and clinical course of infants exposed during the neonatal period to a caregiver with bacillary tuberculosis., Patients and Methods: Infants exposed during the postnatal period in a maternity unit in Paris, from March to August 2005, to a caregiver with bacillary tuberculosis were included in a standardized screening protocol. The screening performed at baseline (M0) and at 3 months (M3) included a clinical evaluation, a tuberculin skin test (TST), and a chest X-ray. A preventive treatment for tuberculosis with isoniazid and rifampicin for 3 months was systematically proposed., Results: At M0, 182 of the 217 infants (84%) with significant exposure were evaluated. Data were available for 172 infants. The median age at M0 was 4.9 months (IQR=3.8-6.2). At M0, 4 of 172 infants (2.3%) had latent TB infection. Between M0 and M3, 19 infants (11%) were lost to follow-up and 1 on 153 developed a latent TB infection. No cases of tuberculosis disease were diagnosed. The treatment was administered properly in 83% of cases and side effects were observed in 11% of infants without any serious adverse event. Four infants received no treatment and 11 stopped their treatment prematurely., Conclusion: In the absence of neonatal massive exposure, although low (2.9%), the risk of latent TB infection requires close monitoring of the infants exposed. However, in the context of a mild exposure in the maternity unit, surveillance without systematic initiation of TB preventive treatment could be discussed., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Acute bacterial parotitis is a rare infectious disease in infants under 3 months of age., Objectives: To describe the clinical characteristics and the course of acute bacterial parotitis in infants less than 3 months old., Patients and Methods: Infants under 3 months of age, hospitalized at Robert Debré university hospital, Paris, France, between January 2005 and December 2009 for acute bacterial parotitis, were included in a retrospective study., Results: Five infants less than 3 months of age were included in this study, for a frequency of 2.5/1000 hospitalizations in this age group. All were born at term, 4 of 5 were male. Three of the 5 patients had specific clinical signs of parotitis on admission. One patient had septic shock on admission. The ultrasound confirmed the parotitis in all cases. No parotid abscess was demonstrated on imaging. All patients had at least one abnormal inflammatory biological test (WBC, CRP, PCT). Bacteria were identified in 4 of 5 cases: Staphylococcus aureus was isolated in the pus culture of the Stenon duct in 2 patients and a group B Streptococcus was isolated from blood culture of 2 other patients. The duration of intravenous antibiotic therapy varied from 4 to 13 days, and the total duration of antibiotic therapy was between 10 and 16 days. No surgical procedures were needed., Conclusion: Acute bacterial parotitis in infants under 3 months of age might be associated with localized infections due to S. aureus, but also with a more severe clinical presentation due to group B streptococcus infection. Early diagnosis and appropriate antibiotic therapy might prevent the progression to serious complications., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objectives: Evaluating the frequency and modalities of transmissible infection prevention counseling in children before a stay in tropical or subtropical areas., Methods: Description of the frequency and modalities of transmissible infection prevention counseling (except specific vaccination) given prior to travel in children attending a tertiary care center in Paris, France, for fever occurring within 3 months following a return from Africa. Data were collected retrospectively from medical observations and telephone interviews with parents., Results: A total of 173 children were included; 98 and 75 returned from sub-Saharan Africa and North Africa, respectively. Forty-one percent were less than 2 years old. Eighty-one percent of the children had consulted before leaving. Among children who returned from North Africa, the proportion of children who had a specific preventive consultation before travel was lower than among children who returned from sub-Saharan Africa (respectively, 72.1% versus 94.7%; p<0.001). In children having consulted before traveling, specific hygiene and diet advice had been given in 72% of cases but less frequently in children who traveled in North Africa compared to children who traveled to sub-Saharan Africa (respectively, 57.8% vs. 92.2%; p<0.001). Among children who returned from North Africa, those who had no preventive consultation before travel had febrile gastrointestinal infection more frequently than those who had a consultation before traveling (p=0.003)., Conclusion: Although in this study the majority of children traveling to Africa receive transmissible infection prevention counseling before the travel, prevention could be improved, particularly before a stay in North Africa., (Copyright © 2011. Published by Elsevier SAS.)

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages., (Copyright © 2011. Published by Elsevier SAS.)

We conducted a retrospective study comparing the presenting clinical and biologic features of 64 children who had septic arthritis caused by Kingella kingae with 26 children who had septic arthritis caused by Staphylococcus aureus. Children with K. kingae septic arthritis were significantly younger than those with S. aureus septic arthritis. Otherwise, there were no significant differences between the 2 groups with respect to fever, location, white blood cell count, synovial fluid cell count, C-reactive protein, or serum fibrinogen. However, the clinical course was significantly better for children with septic arthritis caused by K. kingae as evidenced by shorter hospitalization and fewer adverse events. Presumptive antibiotic therapy for septic arthritis in young infants should take into account both of these pathogens, even in case of mild presentation.

Management of bone and joint infections in children associates early appropriate antibiotic therapy against Staphylococcus aureus and Kingella kingae and, if necessary, surgical drainage of abscess or septic arthritis. In 2007, the Paediatric Infectious Diseases Group of the French Society of Paediatrics (GPIP) proposed guidelines for antibiotherapy in acute and non-complicated cases, with an intravenous therapy during 4 to 7 days followed by oral therapy during 3 weeks., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Nonvaccine serotypes are increasingly responsible for pneumococcal empyema. We developed a one-step polymerase chain reaction for identifying all serotypes covered by the 13-valent conjugate vaccine. Over 1 year, we identified serotypes 19A (n = 6), 1 (n = 2), 3 (n = 1) and 7F/A (n = 2), both in culture-positive and culture-negative pleural fluid from 11 children with empyema., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

Background: rotaviruses are the major cause of acute gastroenteritis in young children worldwide, and require careful surveillance, especially in the context of vaccination programs. Prospective surveillance is required to monitor and characterize rotavirus infections, including viral and clinical data, and to detect the emergence of potentially epidemic strains., Methods: between 2006 and 2009, stool samples and clinical records were collected from 2044 children with acute diarrhea admitted to the pediatric emergency units of 13 French university hospitals. Rotaviruses were detected in stools, then genotyped by reverse transcription-polymerase chain reaction with regard to their outer capsid proteins VP4 and VP7., Results: the genotyping of 1947 rotaviruses showed that G1 (61.7%) and G9 (27.4%) strains were predominant and stable, followed by G2 (6.5%), G3 (4.0%), and G4 (2.5%) strains. Most strains were associated with P[8] (92.9%). Overall, 31 uncommon strains and possible zoonotic reassortants were detected including G12 and G8 strains, some being closely related to bovine strains. No difference in clinical presentation and severity was found among genotypes., Conclusions: the relative stability of rotavirus genotypes currently cocirculating in France may ensure vaccine effectiveness in the short and medium term. However, the likely emergence of G12 and G8 strains should be monitored during ongoing and future vaccination programs, especially as all genotypes can cause severe infections. Special attention should be paid to the emergence of new rotavirus reassortants not included in current rotavirus vaccines.

Invasive group A streptococcal (GAS) infections have a broad and evolving clinical spectrum, associated with various GAS genotypes and/or virulence factors that are only poorly described in children. We aimed to assess the clinical and molecular characteristics of invasive GAS infections in 28 children admitted from 2000 to 2007 at a large French pediatric tertiary care center. The GAS isolates were characterized molecularly by emm-typing and by the determination of the main virulence factors: speA, speB, speC, smeZ-1, ssa, sic, and silC. The median age of the children was 2.9 years. Osteoarticular infection (OAI) was the main clinical manifestation (n=15/28, 53%). emm-1 predominated (n=10/28), followed by emm-12, 3, and 4. No significant correlation was found between emm type and clinical manifestations, but emm-1 predominated in cases of OAI (n=7/15) and was associated with speA, speB, smeZ-1, and sic virulence factor genes. In this pediatric study, we describe a predominance of OAI associated with emm-1 GAS. Further larger international pediatric studies, including host immunity evaluation, are needed in order to better assess the pathogenesis of GAS infection in children.

Inoculation of blood culture vials with joint fluid samples has revealed the important pathogenic role of Kingella kingae in pediatric arthritis. However, recent studies based on broad-range 16S ribosomal DNA PCR and real-time PCR without a probe suggest that conventional methods remain suboptimal. We developed a new real-time PCR method with a probe that is highly specific for K. kingae and applied it to joint fluid samples collected from 89 children with suspected arthritis admitted to our institution during a 2-year period. Real-time PCR was also applied to blood samples obtained before surgery and to joint drainage fluid samples obtained during several days after surgery. Thirty-six (40%) of the 89 cases of suspected septic arthritis had positive culture. Staphylococcus aureus was the main isolate (n = 19/36, 53%), followed by K. kingae (n = 7/36, 19%). Specific real-time PCR identified K. kingae in 24 of the 53 culture-negative cases. Thus, K. kingae was present in 31 (52%) of the 60 documented cases, making it the leading pathogen. Real-time PCR on all 15 blood DNA extracts from patients with K. kingae infection was negative, demonstrating that joint fluid positivity did not result from DNA circulating in blood. Real-time PCR amplification of drainage fluid samples showed that the pathogen could be detected for up to 6 days after antibiotic initiation. K. kingae real-time PCR applied to DNA extracted from joint fluid samples, but not from blood samples, markedly improved the etiological diagnosis of septic arthritis in children. Retrospective diagnosis is feasible for up to 6 days after treatment initiation.

An asthmatic girl was first hospitalized at age 2(9/12) years because of dyspnoea, lung consolidations and/or atelectasis, and rattling. Between ages 2(9/12) and 6(2/12) years, she required three hospitalizations in ICU out of nine hospitalizations for the same symptoms. Differential diagnosis of this difficult to treat asthma disclosed severe tracheomalacia and persistent asthma. Treatments given according to the clinical, radiological and functional findings failed to decrease frequency and severity of acute respiratory episodes. Eventually, positive pressure ventilation delivered at airway opening (via a mouthpiece) associated to active respiratory physiotherapy succeeded in removing atelectasis and quickly cured the five following acute episodes without any further hospitalization. This case report is about diagnosis procedure, intricate asthma and tracheomalacia, and open mind to unusual therapeutics that may disclose potential help.

We used real-time PCR to examine the persistence of Bordetella pertussis DNA in serial nasopharyngeal aspirates from 22 children treated for pertussis. After 5 days of treatment, PCR was positive for all 21 assessable patients. After 14 and 21 days, PCR was still positive for 83% (10/12) and 66% (4/6) of assessable patients, respectively. One patient was tested 1 month after treatment initiation, and B. pertussis DNA was still detectable. Quantitative analysis showed that the DNA concentration diminished during treatment in all except one case. The PCR cycle threshold at which B. pertussis DNA became detectable increased by a mean of 1.7 cycles per day (range, 0.86 to 3.68 cycles per day). Real-time PCR can thus be used to diagnose pertussis in young children for up to 3 weeks after treatment initiation. Its potential value for assessing the treatment outcome remains to be determined.

Management of paediatric skeletal infections remains delicate in France due to the absence of general agreement or official recommendations from the French National Societies. However, practices have evolved since 40 years towards simplified and mostly ambulatory treatment modalities. The Paediatric Infectious Diseases Group of the French Society of Paediatrics (GPIP) has elaborated guidelines funded on the joint analysis of bacterial epidemiology, comparison of common antimicrobial spectra, pharmacokinetic and pharmacodynamic parameters and clinical studies. The aim of this article is to review the evolution of therapeutic concepts of treatment of bone and joint infections in paediatrics for 40 years with the aid of main published clinical studies.

Unlabelled: Only few drugs for uncomplicated Plasmodium falciparum malaria are available in children. Atovaquone-proguanil is a recent antimalarial drug licensed in France for the uncomplicated P. falciparum malaria in adults. Few paediatric studies have evaluated atovaquone-proguanil in children for uncomplicated malaria in endemic area, but no study have evaluated this treatment for imported malaria., Objective: To evaluate treatment by atovaquone-proguanil for uncomplicated and imported P. falciparum malaria in children., Methods: We retrospectively evaluated the tolerance and the efficacy of atovaquone-proguanil in the children admitted in Robert-Debré Hospital (Paris) for a P. falciparum malaria. From January 2004 to December 2005, 48 children with a median age of 7,5 years (IQR 4-11) were treated with atovaquone-proguanil for a uncomplicated P. falciparum malaria, except for 5 children who had an isolated hyperparasitemia greater or equal to 5%., Results: Atovaquone-proguanil was stopped for 3/48 children because of vomiting. Fever resolved in all the children between Day 3 and 7, following the beginning of the treatment. One child, with a favourable outcome, had a positive parasitemia at Day 4 equal to the initial parasitemia (0,1%). No late therapeutic failure was observed among the 24 children evaluated up to one month after starting treatment., Conclusion: Atovaquone-proguanil is an efficient and well-tolerated antimalarial treatment for uncomplicated P. falciparum malaria in children. The risk of vomiting should lead to a systematic initial hospitalisation of children treated with atovaquone-proguanil.

We investigated an otherwise healthy patient presenting two episodes of staphylococcal cellulitis and abscesses, accompanied by high fever and biological signs of inflammation but, paradoxically, with no detectable increase in serum levels of C-reactive protein (CRP), an IL-6-responsive protein synthesized in the liver. Following in vitro activation of whole blood cells from the patient with multiple cytokines, TLR agonists, heat-killed bacteria, and mitogens, we observed a profound and specific impairment of IL-6 secretion. However, the patient's PBMCs, activated in the same conditions but in the absence of the patient's plasma, secreted IL-6 normally. The patient's serum contained high titers of IgG1 autoantibodies against IL-6, which specifically neutralized IL-6 production by control PBMCs as well as IL-6 responses in the human hepatocellular carcinoma cell line Hep3B. These anti-IL-6 autoantibodies were detected over a period of 4 years, in the absence of any other autoantibodies. Our results indicate that these Abs probably prevented an increase in CRP concentration during infection and that impaired IL-6-mediated immunity may have contributed to staphylococcal disease. Patients with severe bacterial infections and low serum CRP concentrations should be tested for anti-IL-6 autoantibodies, especially in the presence of other clinical and biological signs of inflammation.

Objective: To assess the prevalence of respiratory syncytial virus (RSV) and other important respiratory viruses in children hospitalized in a pediatric hospital in Paris (France) during a 3-year period (2001 to 2004)., Patients and Methods: The study included all patients aged 8 days to 16 years admitted from the community through emergency department with bronchiolitis, pneumonia, upper respiratory tract infection, asthma or acute isolated fever and who had nasopharyngeal samples taken for viral identification by immunofluorescence (RSV, influenza, para-influenza, and adenoviruses)., Results: A virus was found in 464 of 1208 patients with samples taken. RSV was identified in 375 patients, 74% of them younger than 6 months and diagnosed with bronchiolitis. RSV was isolated more often than any other virus, overall and for all diagnoses except "isolated fever," for which influenza was more frequent. In patients aged 24 months or older, influenza and RSV were identified at the same frequency. Overall, influenza virus was found in 53 patients, adenoviruses in 24 and para-influenza viruses in 11., Conclusion: RSV was the respiratory virus isolated most often, even in older children, during this 3-year study. The relative rarity of hospitalizations due to para-influenza viruses is characteristic of this area, compared with some other countries.

The diagnosis of acute osteomyelitis and septic arthritis is a clinical one. Acute-phase reactants, such as white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are useful to help the clinicians at the time of initial diagnosis. The WBC count may be normal in up to 80 % of cases and it is not a reliable indicator. The ESR is elevated in 80 % of cases. CRP is elevated more than 80 % of cases. CRP rises rapidly within 48 hours of admission and returns to normal within a week after appropriate therapy. Its rapid kinetics is useful for follow-up of the response treatment. Patients who require surgical drainage procedures have prolonged time to normalization of CRP. PCT is a useful specific marker for predicting severe infection but its sensibility to detect bone and joint infections seems to be low.

The rotavirus is the major cause of infantile gastroenteritis. The virus infects the mature enterocytes of the villus tip of the small intestine and induces a watery diarrhea. Diarrhea can occur in the absence of histological changes in the intestine, and, conversely, the histological changes can be asymptomatic. Rotavirus decreases the activities of digestive enzymes at the apical brush border membrane and inhibits Na+ -solute cotransport systems. Accumulation of carbohydrates in the intestinal lumen as well as malabsorption of nutrients and a concomitant inhibition of water absorption can lead to a malabsorptive component of diarrhea. Since the discovery of the NSP4 enterotoxin, several hypotheses have been proposed in favour of an additional secretion component in the pathogenesis of diarrhea. Rotavirus induces a moderate net chloride secretion at the onset of the diarrhea. The mechanisms appear to different from those used by bacterial enterotoxin that cause pure secretory diarrhea. Rotavirus stimulated C1- reabsorption in villi, and failed to stimulate C1- secretion in crypt. Intestinal villi could secrete chloride as a result of rotavirus infection. The chloride secretory response is regulated by a dependant calcium signalling pathway induced by NSP4. The overall response is weak, suggesting that NSP4 may exert both secretory and subsequent antisecretory actions, hence limiting C1- secretion.

Rotavirus is the major cause of infantile gastroenteritis and each year causes 611,000 deaths worldwide. The virus infects the mature enterocytes of the villus tip of the small intestine and induces a watery diarrhea. Diarrhea can occur with no visible tissue damage and, conversely, the histological lesions can be asymptomatic. Rotavirus impairs activities of intestinal disaccharidases and Na+-solute symports coupled with water transport. Maldigestion of carbohydrates and their accumulation in the intestinal lumen as well as malabsorption of nutrients and a concomitant inhibition of water reabsorption can lead to a malabsorption component of diarrhea. Since the discovery of the NSP4 enterotoxin, diverse hypotheses have been proposed in favor of an additional secretion component in the pathogenesis of diarrhea. Rotavirus induces a moderate net chloride secretion at the onset of diarrhea, but the mechanisms appear to be quite different from those used by bacterial enterotoxins that cause pure secretory diarrhea. Rotavirus failed to stimulate Cl- secretion in crypt, whereas it stimulated Cl- reabsorption in villi, questioning, therefore, the origin of net Cl- secretion. A solution to this riddle was that intestinal villi do in fact secrete chloride as a result of rotavirus infection. Also, the overall chloride secretory response is regulated by a phospholipase C-dependent calcium signaling pathway induced by NSP4. However, the overall response is weak, suggesting that NSP4 may exert both secretory and subsequent anti-secretory actions, as did carbachol, hence limiting Cl- secretion. All these characteristics provide the means to make the necessary functional distinction between viral NSP4 and bacterial enterotoxins.

A group of European experts in infectious diseases and vaccinology has met on several occasions to assess the rationale for universal vaccination against rotavirus infection of infants in Europe. On the basis of the available data, we concluded that vaccination was the best approach to prevent severe rotavirus gastroenteritis, and that European countries should consider implementing rotavirus vaccination in their routine immunisation programmes. The main barrier to the implementation of rotavirus vaccination in Europe is a general lack of awareness of stakeholders, policymakers, health-care professionals, and parents about rotavirus disease and the advantages of vaccination. Further studies on the cost of the disease and the benefit of vaccination, together with raising awareness are necessary steps to ensure successful implementation of rotavirus vaccination in Europe.

The direct effect of the rotavirus NSP4 114-135 and Norovirus NV464-483 peptides on 36Cl uptake was studied by using villus cell brush border membrane (BBM) isolated from young rabbits. Both peptides inhibited the Cl-/H+ symport activity about equally and partially. The interaction involved one peptide-binding site per carrier unit. Whereas in vitro NSP4 114-135 caused nonspecific inhibition of the Cl-/H+ symporter, the situation in vivo is different. Because rotavirus infection in young rabbits accelerated both Cl- influx and Cl- efflux rates across villi BBM without stimulating Cl- transport in crypt BBM, we conclude that the NSP4 114-135 peptide, which causes diarrhea in young rodents, did not have any direct, specific effect on either intestinal absorption or secretion of chloride. The lack of direct effect of NSP4 on chloride transport strengthens the hypothesis that NSP4 would trigger signal transduction pathways to enhance net chloride secretion at the onset of rotavirus diarrhea.

We describe two cases of aseptic meningitis occurring some time after pneumococcal meningitis. Both cases may have resulted from an inflammatory response to persistent pneumococcal cell membrane components, as the cerebrospinal fluid samples were positive by the Binax NOW Streptococcus pneumoniae antigen test. Potential mechanisms and diagnostic impact are discussed.

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.

Rotaviral diarrheal illness is one of the most common infectious diseases in children worldwide, but our understanding of its pathophysiology is limited. This study examines whether the enhanced net chloride secretion during rotavirus infection in young rabbits may occur as a result of hypersecretion in crypt cells that would exceed the substantial Cl(-) reabsorption observed in villi. By using a rapid filtration technique, we evaluated transport of (36)Cl and D-(14)C glucose across brush border membrane (BBM) vesicles purified from villus tip and crypt cells isolated in parallel from the entire small intestine. Rotavirus infection impaired SGLT1-mediated Na(+)-D-glucose symport activity in both villus and crypt cell BBM, hence contributing to the massive water loss along the cryptvillus axis. In the same BBM preparations, rotavirus failed to stimulate the Cl(-) transport activities (Cl(-)/H(+) symport, Cl(-)/anion exchange and voltage-activated Cl(-) conductance) at the crypt level, but not at the villus level, questioning, therefore, the origin of net chloride secretion. We propose that the chloride carrier might function in both normal (absorption) and reversed (secretion) modes in villi, depending on the direction of the chloride electrochemical gradient resulting from rotavirus infection, agreeing with our results that rotavirus accelerated both Cl(-) influx and Cl(-) efflux rates across villi BBM.

Pharmacoepidemiological studies are essential in the post-licensing surveillance of vaccines in order to evaluate the potential benefits and risks of vaccines used in common practice. Surveillance is required to detect rare or unanticipated vaccine adverse events and to ensure confidence in vaccination. Epidemiological studies provide data on the long-term protection conferred by vaccination, and the incidence and associated mortality of, and population susceptibility to, diseases preventable by vaccine. These studies also allow verification of the compatibility between strains contained in the vaccine as well as circulating strains.

Rotavirus is responsible for infantile gastroenteritis and each year causes 440 000 deaths worldwide. The virus infects the mature enterocytes of the villus tip of the small intestine and induces a watery diarrhea. Diarrhea can occur with no visible tissue damage and, conversely, the histological lesions can be asymptomatic. Rotavirus infection impairs intestinal disaccharidases and Na+-solute symports coupled to water transport. Maldigestion of carbohydrates and their accumulation in the intestinal lumen as well as malabsorption of nutriments and a concomitant inhibition of water reabsorption would lead to osmotic diarrhea. The hypothesis that the NSP4 viral enterotoxin, by mobilizing intracellular calcium, would be a secretory agonist remains to be demonstrated. In rotavirus diarrhea, Cl- reabsorption in villi is stimulated and secretion in crypt is unaffected, questioning the origin of Cl- secreted into the intestinal lumen, which possibly arises from the villus base cells. These mechanisms appear to be quite different from those used by bacterial enterotoxins that cause "pure" secretory diarrhea. The viral enterotoxin would induce mainly osmotic diarrhea, especially since NSP4 has been shown to be directly responsible for glucosegalactose malabsorption.

Unlabelled: IFN-alpha detection is useful in some clinical circumstances, but its use has never been validated in young infants with viral infections., Objective: The authors wanted to determine it there was any difference in the assessment of IFN-alpha production between infants under or over six months of age., Patients and Method: A series of 233 children with identified common viral infections who had been assessed for IFN-alpha production was retrospectively analyzed. The viral infections were enteroviral meningitis (n =103), respiratory syncytial virus infections (n =60), and rotavirus gastroenteritis (n =70). Data collected from the group of infants under six months of age (n =105) was compared to that of the older children (n =128). Qualitative and quantitative values of interferon-alpha were determined for each group., Results: Interferon-alpha was detected in very young infants (81.9% of cases) as often as in the older age group (80.3% of cases), for any of the three viral infections (P =0.3-0.63). The mean level of interferon-alpha production detected was not lower in the youngest group, and even higher in the group under six months of age with enteroviral meningitis., Conclusion: Interferon-alpha detection in very young infants is efficient and may be useful to differentiate between viral and bacterial infection particularly when the etiological diagnosis appears uncertain.

Rotavirus is a major cause of infantile gastroenteritis worldwide. However, the mechanisms underlying fluid and electrolyte secretion associated with diarrhea remain largely unknown. We investigated the hypothesis that loss of Cl(-) into the luminal contents during rotavirus infection may be caused by a dysfunction in the chloride absorptive capacity across the intestinal brush-border membrane (BBM). The luminal Cl(-) concentrations in the entire small intestine of young rabbits infected with lapine rotavirus decreased at 1 and 2 days postinfection (dpi), indicating net Cl(-) absorption. At 7 dpi, luminal Cl(-) concentrations were slightly increased, indicating a moderate net Cl(-) secretion. By using a rapid filtration technique, (36)Cl uptake across BBM was quantified by modulating the alkali-metal ion, electrical, chloride, and/or proton gradients. Rotavirus infection caused an identical, 127% +/- 24% increase in all Cl(-) uptake activities (Cl(-)/H(+) symport, Cl(-) conductance, and Cl(-)/anion exchange) observed across the intestinal BBM. The rotavirus activating effects on the symporter started at 1 dpi and persisted up to 7 dpi. Kinetic analyses revealed that rotavirus selectively affected the capacity parameter characterizing the symporter. We report the novel observation that rotavirus infection stimulated the Cl(-) reabsorption process across the intestinal BBM. We propose that the massive Cl(-) reabsorption in villi could partly overwhelm chloride secretion in crypt cells, which possibly increases during rotavirus diarrhea, the resulting imbalance leading to a moderate net chloride secretion.

The hydrodynamic diameters of native rotavirus particles, bovine RF and simian SA11 strains, were determined by quasielastic light scattering. By using this method and agarose gel electrophoresis, the Ca(2+) dissociation constant, K(Ca), governing the transition from triple-layer particles (TLPs) to double-layer particles (DLPs), was shown to increase, at constant pH, as the temperature and/or the ionic strength of the incubation medium increased. We report the novel observation that, under physiological conditions, K(Ca) values for both RF and SA11 rotaviruses were well above the intracytoplasmic Ca(2+) concentrations of various cells, which may explain why TLP uncoating takes place within vesicles (possibly endosomes) during the entry process. A correlation between TLP uncoating and cell membrane permeabilization was found, as shown by the release of carboxyfluorescein (CF) from CF-loaded intestinal brush-border membrane vesicles. Conditions stabilizing the virion in the TLP form inhibited CF release, whereas conditions favoring the TLP-to-DLP transformation activated this process. We conclude that membrane permeabilization must be preceded by the loss of the outer-capsid proteins from trypsinized TLP and that physiological ionic strength is required for permeabilization to take place. Finally, the paper develops an alternative explanation for the mechanism of rotavirus entry, compatible with the Ca(2+)-dependent endocytic pathway. We propose that there must be an iterative process involving tight coupling in time between the lowering of endosomal Ca(2+) concentration, virion decapsidation, and membrane permeabilization, which would cause the transcriptionally active DLPs to enter the cytoplasm of cells.

Lysteriolysin O (LLO) induces a microtubule-dependent activation of mucin exocytosis in the human mucin-secreting HT29-MTX. Cholesterol inhibits the LLO-induced mucin exocytosis, whereas the oxidized form of cholesterol had no inhibitory effect. LLO-induced mucin exocytosis inhibited by cholesterol can be restored by enzymatic treatment with cholesterol oxidase. Inhibition of cholesterol synthesis in HT29-MTX cells results in a decrease in the LLO-induced mucin exocytosis. Other lipids such as gangliosides are able to inhibit the LLO-induced mucin exocytosis, suggesting that the binding of the toxin occurs at a multiplicity of membrane-associated lipids acting as receptors. Incubation of the toxin with lipids such as cholesterol or gangliosides does not decrease binding of LLO to target membranes. The present work also provides evidence that the LLO-induced mucin exocytosis develops independently of the pore-forming activity of the toxin. Finally, we demonstrated that the toxin associates with detergent-insoluble glycolipid microdomains (DIGs) containing VIP/21 caveolin, allowing internalization of the toxin and subsequent activation of the mucin exocytosis.

To gain further insight into the mechanism by which lactobacilli develop antimicrobial activity, we have examined how Lactobacillus acidophilus LB inhibits the promoted cellular injuries and intracellular lifestyle of Salmonella enterica serovar Typhimurium SL1344 infecting the cultured, fully differentiated human intestinal cell line Caco-2/TC-7. We showed that the spent culture supernatant of strain LB (LB-SCS) decreases the number of apical serovar Typhimurium-induced F-actin rearrangements in infected cells. LB-SCS treatment efficiently decreased transcellular passage of S. enterica serovar Typhimurium. Moreover, LB-SCS treatment inhibited intracellular growth of serovar Typhimurium, since treated intracellular bacteria displayed a small, rounded morphology resembling that of resting bacteria. We also showed that LB-SCS treatment inhibits adhesion-dependent serovar Typhimurium-induced interleukin-8 production.

Objective: Procalcitonin concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable making it a potentially useful marker for distinguishing between bacterial and viral infections., Patients and Methods: Procalcitonin (PCT) was determined with an immunoluminometric assay on plasma collected at admission in 436 infants and children hospitalized for bacterial or viral infection. It was compared with C reactive protein, interleukin-6 and interferon-alpha measured on the same sample., Results: PCT was 41.3 +/- 77.4 micrograms/l in children with septicemia or bacterial meningitis (n = 53), 0.39 +/- 0.57 microgram/l in children with viral infection (n = 274) and 3.9 +/- 5.9 micrograms/l in children with a localized bacterial infection who had a negative blood culture (n = 109). PCT was > 1 microgram/l in 126 children with a localized or systemic bacterial infection (sensitivity 78%). PCT was < 1 microgram/l in 258 children with a viral infection (specificity 94%). For differenciation between viral and bacterial infections, CRP value > or = 20 mg/l, IL-6 > 100 pg/ml and interferon-alpha > 0 Ul/ml have 85, 48 and 76% sensitivity and 73, 85 and 92% specificity respectively., Conclusions: In this study, a PCT value of 1 microgram/l or greater had better specificity, sensitivity and predictive value than CRP, IL-6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT may be useful in pediatric emergency room for making decision about antibiotic treatments.

Background: Procalcitonin (PCT) concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable, making it a potentially useful marker for distinguishing between bacterial and viral infections., Methods: PCT concentration was determined with an immunoluminometric assay on plasma collected at admission in 360 infants and children hospitalized for bacterial or viral infection. It was compared with C-reactive protein (CRP), interleukin 6 and interferon-alpha measured on the same sample., Results: The mean PCT concentration was 46 microg/l (median, 17.8) in 46 children with septicemia or bacterial meningitis. PCT concentration was > 1 microg/l in 44 of 46 in this group and in 59 of 78 children with a localized bacterial infection who had a negative blood culture (sensitivity, 83%). PCT concentration was > 1 microg/l in 16 of 236 children with a viral infection (specificity, 93%). PCT concentration was low in 9 of 10 patients with inflammatory disease and fever. A CRP value > or =20 mg/l was observed in 61 of 236 patients (26%) with viral infection and in 105 of 124 patients (86%) with bacterial infection. IL-6 was > 100 pg/ml in 14% of patients infected with virus and in 53% with bacteria. A secretion of interferon-alpha was found in serum in 77% of viral infected patients and in 8.6% of bacterial infected patients., Conclusions: In this study a PCT value of 1 microg/l or greater had better specificity, sensitivity and predictive value than CRP, interleukin 6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT values are higher in invasive bacterial infections, but the cutoff value of 1 microg/l indicates the severity of the disease in localized bacterial infection and helps to decide antibiotic treatment in emergency room. PCT may be useful in an emergency room for differentiation of bacterial vs. viral infections in children and for making decisions about antibiotic treatments.

Background: Benign intracranial hypertension is due to an increased intracranial pressure of unknown cause. The initial symptoms, complications and associations with medical conditions are discussed., Case Report: A 6-year-old girl developed symptoms of benign intracranial hypertension following reduction of oral corticosteroid therapy. Laboratory studies and head-computed tomographic scan were normal. Examination of the optic discs showed bilateral papilledema and the cerebrospinal fluid pressure was increased. The patient was given prednisone therapy 1 mg/kg daily initially, associated with acetazolamide, and removal of 25 mL of cerebrospinal fluid. All the symptoms resolved and the treatment was gradually decreased. The child developed no further visual failure., Conclusion: Benign intracranial hypertension with the risk of permanent visual loss is a complication underrecognized in children. All patients receiving large doses of the corticosteroids who complain of headache or blurring vision, particularly following a reduction of corticosteroid dosage, should have an ophtalmoscopic examination to exclude this complication.