A 4-year study on clinical characteristics of children hospitalized with rotavirus gastroenteritis.

Rotavirus (RV) is a frequent cause of severe gastroenteritis (GE) in children. With the licensure of new RV vaccines, data on the burden of disease are important regarding immunization strategies. We reviewed the medical records of children hospitalized with RV infection in our institution between July 2002 and March 2006. Relevant data were extracted in a standardized fashion from records of hospitalized children with a positive RV antigen test in a stool sample. Severity of disease was graded by the 20-point Vesikari score. Population data were obtained from the Federal Office of Statistics. Six hundred eighty-six RVGE were identified and records of 608 hospitalizations (in 607 children) were available. In 539 (89%) cases, RVGE was the primary reason for hospitalization and 69 (11%) were nosocomial infections; yearly peaks occurred between February and May. Cumulative incidence of RVGE was 26.7/1,000 children <3 years of age. Median age of 539 children (55.6% male) with primary RVGE was 1.4 years and median stay in the hospital for both community acquired and nosocomial RVGE was 4 days (interquartile range 3-5). Thirtypercent and 94% of RV hospitalizations were in children <1 and <3 years of age, respectively. Mean Vesikari score was 15 (range 6-20; 96% >11). Intravenous fluids were administered in 378 (70%) patients, 130 (24%) patients were rehydrated via nasogastral tube, and 31 (5.7%) received rehydration by mouth. RVGE causes a substantial burden in children with an estimated risk for hospitalization due to RVGE of one in 37 children <3 years of age.

Human metapneumovirus infections--biannual epidemics and clinical findings in children in the region of Basel, Switzerland.

Human metapneumovirus (hMPV) epidemics vary in time and severity. We report findings for PCR for hMPV and respiratory syncytial virus (RSV) performed on nasopharyngeal aspirates (NPA) of hospitalized and outpatient children with respiratory tract infections between October 2004 and April 2008. A total of 3,934 NPAs were tested for hMPV and 3,859 for RSV. Of these, 198 (5%) were hMPV positive and 869 (23%) were RSV-positive. Median age was 17 months and 9 months for hMPV and RSV, respectively. Fifty-nine percent of hMPV and 58% of RSV patients were hospitalized. Proportions of hMPV positive samples for the four winter seasons were 0.4%, 11%, 0.2%, and 14%. For RSV, they were 28%, 15%, 28%, and 28%. HMPV epidemics follow a biannual variation in our area. Major epidemics were observed in winter seasons starting in odd years (2005/06 and 2007/08), minor epidemics in those starting in even years (2004/05 and 2006/07). RSV epidemics usually follow a reciprocal biannual pattern, leading to annually alternating major RSV and hMPV epidemics.

A multicenter, cross-sectional study on the prevalence and risk factors for nasal colonization with Staphylococcus aureus in patients admitted to children's hospitals in Switzerland.

The rate of nasal carriage of Staphylococcus aureus and associated risk factors were determined in a cross-sectional study involving Swiss children's hospitals. S. aureus was isolated in 562 of 1363 cases. In a stepwise multivariate analysis, the variables age, duration of antibiotic use, and hospitalization of a household member were independently associated with carriage of S. aureus.

Randomized, comparative efficacy trial of oral penicillin versus cefuroxime for perianal streptococcal dermatitis in children.

OBJECTIVE: To investigate the efficacy of penicillin compared with cefuroxime for group A beta-hemolytic Streptococcus pyogenes (GABHS) perianal dermatitis. STUDY DESIGN: Children 1 to 16 years of age with signs and symptoms of perianal dermatitis and a positive anal swab were randomized to penicillin or cefuroxime treatment and were clinically re-evaluated on day 3 and at the end of treatment (cefuroxime, day 7; penicillin, day 10). An anal swab was obtained to document eradication of GABHS at the end of treatment. Severity of disease was assessed with a clinical score (perianal erythema, 5 points; perianal itch, 3 points; painful defecation, 3 points; constipation, 2 points). RESULTS: Patients were enrolled and randomly assigned to penicillin (n = 18) or cefuroxime (n = 17) treatment. Treatment with penicillin was inferior to cefuroxime, which led to premature study termination after consultation with the ethics committee. Clinical improvement was more rapid in the cefuroxime group (P = .028) and GAHBS was not isolated from the anus the last day of therapy in 13 of 14 patients treated with cefuroxime compared with 7 of 15 patients treated with penicillin (P < .01). CONCLUSIONS: Cefuroxime was more effective than penicillin and therefore should be considered as the treatment of choice for perianal dermatitis due to GABHS.

Clinical findings and unusual epidemiologic characteristics of human metapneumovirus infections in children in the region of Basel, Switzerland.

Human metapneumovirus (hMPV) worldwide causes respiratory tract infections with features similar to those of RSV infection. We describe features of hMPV infections in children and compare some of the characteristics with those of RSV infections. From October 2004 to February 2006, 75 patients, 34 hospitalized and 41 outpatients, were diagnosed with hMPV infections by multiplex PCR applied to nasopharyngeal specimens. While hMPV was found rarely in the early phase of the study, a significant increase occurred in the second winter of the study period. Patients with hMPV infections were older than those with RSV infection; clinical characteristics were similar as was the rate of serious disease among hospitalized patients (intensive care treatment: 18% versus 8%). In conclusion, hMPV leads to endemic and epidemic respiratory disease with features similar to those of RSV and should be considered in the differential diagnosis of upper and lower respiratory tract disease.

Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence.

PURPOSE OF REVIEW: To provide an overview of the mechanistic and clinical evidence for the use of nonspecific immunomodulators in paediatric respiratory tract infection (RTI) and wheezing/asthma prophylaxis. RECENT FINDINGS: Nonspecific immunomodulators have a long history of empirical use for the prevention of RTIs in vulnerable populations, such as children. The past decade has seen an increase in both the number and quality of studies providing mechanistic and clinical evidence for the prophylactic potential of nonspecific immunomodulators against both respiratory infections and wheezing/asthma in the paediatric population. Orally administered immunomodulators result in the mounting of innate and adaptive immune responses to infection in the respiratory mucosa and anti-inflammatory effects in proinflammatory environments. Clinical data reflect these mechanistic effects in reductions in the recurrence of respiratory infections and wheezing events in high-risk paediatric populations. A new generation of clinical studies is currently underway with the power to position the nonspecific bacterial lysate immunomodulator OM-85 as a potential antiasthma prophylactic. SUMMARY: An established mechanistic and clinical role for prophylaxis against paediatric respiratory infections by nonspecific immunomodulators exists. Clinical trials underway promise to provide high-quality data to establish whether a similar role exists in wheezing/asthma prevention.

Assessment of immunization status in hospitalized children followed by counseling of parents and primary care physicians improves vaccination coverage: an interventional study.

This prospective, intervention-control study in hospitalized, underimmunized children assessed the effect of vaccination reminders to parents during hospitalization and provides postdischarge rates of catch-up immunizations. One month after hospital discharge, significantly more children in the intervention group (27%) than the controls (8%) had received catch-up immunizations (P < .001).

Prevalence of nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) in children a multicenter cross-sectional study.

In this cross-sectional multicenter study, we determined the rate of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) in children admitted to 9 training hospitals in Switzerland during 1 month. From 1337 patients, 1363 nasal swabs were obtained (mean age 6.1 years, median 4.7 years, interquartile range 1.3-10.4 years) and 562 (41.3%) grew S. aureus. Only one isolate was MRSA (0.18%) which encoded mecA and femA genes as well as SCCmec type IV, whereas Panton-Valentine leukocidin (PVL) was absent.

Antibody responses induced by long-term vaccination with an octovalent conjugate Pseudomonas aeruginosa vaccine in children with cystic fibrosis.

We assessed the serological responses over 10 years to repeated immunization of cystic fibrosis (CF) patients with an O-polysaccharide (OPS)-toxin A conjugate vaccine against Pseudomonas aeruginosa. A retrospective analysis was performed with sera from 25 vaccinated and 25 unvaccinated children treated at the same CF centre and matched for clinical management, age and gender. Yearly immunization led to sustained elevations of serum immunoglobulin G (IgG) antibody levels to all vaccine components. Eighteen unvaccinated patients but only eight vaccinated ones developed chronic pseudomonal lung infections. Infection rapidly caused further marked elevations of polysaccharide- but not toxin A-specific serum IgG in both immunized and nonimmunized patients, indicating that protection did not depend on the quantity of IgG present. However, qualitative analyses revealed that the protective capacity of specific serum IgG antibodies was linked to high affinity and to specificity for OPS serotypes rather than for lipopolysaccharide core epitopes.

Influenza vaccination among healthcare workers in a university children's hospital.

OBJECTIVES: To evaluate the attitudes of pediatric healthcare workers (HCWs) toward influenza vaccination and to increase their rate of immunization. METHODS: A survey was conducted among pediatric HCWs using an anonymous questionnaire. Survey results were used to design an intervention to increase the immunization rate of staff. Immunization rates before (2003-2004) and after (2004-2005) intervention were assessed using immunization clinic records. SETTING: A university children's hospital in Switzerland. INTERVENTIONS: (1) An informational letter based on misconceptions noted in the survey, (2) educational conversations with head nurses, (3) more "walk-in" immunization clinics, and (4) a direct offer of influenza immunization on the wards. RESULTS: Among vaccine nonrecipients, doubts about the efficacy and necessity of influenza immunization were prevalent and more often reported by nurses than physicians (75% vs 41%, P = .002; and 55% vs 23%, P = .001, respectively). Physicians more often than nurses reported lack of time as a reason for not receiving influenza vaccination (23% vs 5%, P = .01). After intervention, the immunization rate of HCWs increased from 19% to 24% (P = .03). The immunization rate of physicians increased from 43% to 64% (P = .004). No change was noted among nurses (13% vs 14%) and other HCWs (16% vs 16%). CONCLUSIONS: Misconceptions about influenza vaccination were prevalent among pediatric staff, particularly nurses. Active promotion and educational efforts were successful in increasing the immunization rate of physicians but not nurses and other HCWs.

Fluoroquinolone antibiotics in infants and children.

The use of fluoroquinolones in children is limited because of the potential of these agents to induce arthropathy in juvenile animals and to potentiate development of bacterial resistance. No quinolone-induced cartilage toxicity as described in animal experiments has been documented unequivocally in patients, but the risk fro rapid emergence of bacterial resistance associated with widespread, uncontrolled fluoroquinolones use in children is a realistic threat. Overall, the fluoroquinolones have been safe and effective in the treatment of selected bacterial infections in pediatric patients. There are clearly defined indications for these compounds in children who are ill.

Predictive value of double tympanocentesis in acute otitis media.

Advances in the understanding of acute otitis media (AOM), lessons learned from antibacterial trials, and the emergence of pathogens with decreased susceptibility to commonly used antibiotics explain the need to redefine the role of tympanocentesis. The diagnostic value of tympanocentesis at baseline to establish the bacterial cause of AOM is well accepted. However, relevant ethical and scientific arguments conclude that repeat (or double) tympanocentesis cannot be recommended as routine procedure, either for the individual patient or for each treatment trial. Relevant aspects on trial design for AOM, with special emphasis on the value of double tympanocentesis, are reviewed.

Reliability of varicella history in children and adolescents.

QUESTION UNDER STUDY: Only limited data are available regarding the reliability of the varicella zoster virus (VZV) history in children and adolescents. Our goal was to determine positive and negative predictive values of varicella history in a prospective cross-sectional study. METHODS: Patients 1-18 years of age who were hospitalised in our institution between 1999 and 2000 were eligible for participation when a blood specimen was taken for any medical reason. Patients with current varicella, immunodeficiency, immunoglobulin treatment in the previous 6 months, or significant language barriers were excluded. After informed consent had been obtained, parents were asked whether their child had a history of varicella (categorized as definite, probable, possible, negative or unknown). Anti-VZV-IgG antibodies were then tested by ELISA (Enzygnost). If the ELISA result was indeterminate, the specimen was analysed by fluorescent-antibody staining of membrane antigen in VZV-infected cells (FAMA), the serological gold standard. RESULTS: 449 patients (mean age 6.4 years, median 5.4 years) were enrolled. History of varicella was definite in 234 (52%), probable in 12 (3%), possible in 1, negative in 196 (44%) and unknown in 6 (1%) patients. Overall, 61% (95% CI: 56-65) of patients were positive for VZV antibodies. Seroprevalence was 25%, 68% and 95% in 1-4 year olds (group 1, n = 167), 5-8 year olds (group 2, n = 136) and 9-18 year olds (group 3, n = 146), respectively. The positive predictive value of a definite history of varicella was 98% (95% CI: 96-100) (93%, 100%, and 98% in groups 1, 2 and 3, respectively). The negative predictive value was 85% (95% CI: 80-90), decreasing with age (group 1: 97%; group 2: 77%; group 3: 26%). CONCLUSIONS: The positive predictive value of a history of varicella is high in children and adolescents. In countries where universal immunization against varicella is not recommended, selectively immunizing adolescents with a negative history can reduce the rate of susceptible individuals efficiently.

The battle against emerging antibiotic resistance: should fluoroquinolones be used to treat children?

Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens. Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information. In some cases, multidrug resistance occurs. Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections. Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation. Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well. We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adults.

Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study.

OBJECTIVE: Recurrent upper respiratory tract infections (URTIs) are common illnesses in young children. As the immunoactive bacterial extract OM-85 has been shown to prevent these infections in both adults and children, the aim of the present trial was to investigate further its efficacy and safety in infection-prone children. METHODS: This is a randomized, double-blind, placebo-controlled, multicenter study with OM-85 in 232 patients aged 36 to 96 months with recurrent URTIs. Treatment was one capsule daily during month 1 and during 10 days in months 3 to 5. URTI was defined by the presence of at least two of the following: rhinitis, pharyngitis, cough, hoarseness, temperature > or = 38.5 degrees C, or URTI-related prescription of an antibiotic. RESULTS: OM-85-treated patients had a lower rate of URTIs (p < 0.05). The cumulated difference in URTIs between the two groups reached - 0.40 URTIs per patient in 6 months, corresponding to a 16% reduction in the active-treatment group with respect to placebo. The largest difference was observed in the patients having had three or more URTIs during the study period; odds ratios for three or more URTIs were 0.51 (95% confidence interval, 0.29 to 0.91) and 0.65 (95% confidence interval, 0.37 to 1.11) after 5 months and 6 months, respectively. The difference between OM-85 and placebo was independent of age but was more important in patients reporting a larger number of URTIs in the previous year. Patients' global assessment showed improvement in comparison to the previous season in the majority of the cases (OM-85, 78.4% of cases; placebo, 75.5%); however, there were more cases reporting worsening with placebo (6.4% vs 0.9%; p = 0.05). CONCLUSIONS: OM-85 treatment significantly reduced the rate of URTIs, particularly in children with a history of frequent URTIs. Safety and tolerance of test medication were good, comparable to placebo.

Potential role of fluoroquinolone therapy in childhood otitis media.

Increased resistance of pneumococci and other pathogens to available antibiotics raises concerns about bacteriologic and clinical failure in children with acute otitis media. Few therapeutic options exist for patients with recurrent infections or recent treatment failure. The limited experience from the compassionate use of fluoroquinolones in pediatrics and pediatric studies has not been linked unequivocally with arthrotoxicity, the primary safety concern in children. Newer 8-methoxyfluoroquinolones may have a role in selected cases associated with multidrug-resistant pathogens.

Attitudes of pediatricians regarding influenza self-immunization: a survey in a Swiss university children's hospital.

OBJECTIVE: To assess the attitude toward influenza immunization of doctors among physicians in our hospital. METHODS: A self-administered questionnaire survey was performed in a voluntary and anonymous manner in early 2002 after influenza immunization for employees with patient contact had been promoted in the fall of 2001. Physicians were asked whether they had been immunized or not and which of the following reason(s) for doing so applied to them: to protect themselves; to protect their patients; to set a positive example. Solicited reasons for decline: not convinced about necessity; not convinced about efficacy; concerns about side effects; negative attitude toward the immunization initiative; fear of injection. RESULTS: Questionnaires were sent to 90 pediatricians and returned by 46 (98%) of 47 immunized and 25 (58%) of 43 unimmunized participants. Self-protection and protection of patients had been equally important reasons for acceptance (87% each); 46% wanted to set a positive example for their patients by being immunized themselves. Unimmunized physicians expressed doubts about necessity (56%), efficacy (32%) and concerns about side effects (24%). Of immunized physicians 98% considered reimmunization for the next season as did 60% of those currently unimmunized. CONCLUSIONS: Prevailing misconceptions indicate that increased educational efforts are necessary to improve acceptance of influenza vaccine in our institution.

Azithromycin versus penicillin V for treatment of acute group A streptococcal pharyngitis.

OBJECTIVE: To compare a 3-day azithromycin vs. a 10-day penicillin V regimen for treatment of acute group A streptococcal (GAS) pharyngitis in children and to determine whether viral infection and/or pharyngeal GAS carriage in patients and adult contacts affect clinical and bacteriologic efficacy. METHODS: This multicenter, randomized, comparative, open label study compared 3-day, once daily 10 mg/kg azithromycin oral suspension with a 10-day regimen of 100,000 IU/kg/day penicillin V oral suspension in three divided doses in children with acute GAS pharyngitis. Clinical and bacteriologic efficacy and tolerability of the antibiotics were evaluated. Recurrence of symptoms and infection was monitored for 6 months. RESULTS: In total, 292 children (age range, 2 to 12 years) received at least one dose of study medication. Clinical success (cure/improvement) with either antibiotic was similar at the end of therapy (Day 14; azithromycin, 95%; penicillin V, 97%) and at Day 28 (azithromycin, 94%; penicillin V, 95%). Bacteriologic eradication was significantly less with azithromycin than with penicillin V at Day 14 (azithromycin, 38%; penicillin V, 81%; P < 0.001) and at Day 28 (azithromycin, 31%; penicillin V, 68%; P < 0.001). There was no associated increase in GAS-related sequelae. The lower incidence of bacteriologic eradication with azithromycin was not the result of possible concomitant viral infections in the patients, GAS carriage in one parent/guardian or any reduced susceptibility in pretreatment GAS isolates. Both antibiotics were equally well-tolerated. CONCLUSIONS: Treatment with 3-day, once daily 10 mg/kg azithromycin for GAS pharyngitis is associated with similar high levels of clinical efficacy, but lower levels of bacteriologic eradication, than with 10-day 100,000 IU/kg/day penicillin V.

Transplacentally acquired immunoglobulin G antibodies against measles, mumps, rubella and varicella-zoster virus in preterm and full term newborns.

IgG antibody values against measles, mumps, rubella and varicella-zoster virus in 71 full term and 101 preterm infants and their 152 mothers and the decay of maternally acquired antibodies during infancy were studied. Both magnitude of transplacental antibody passage and cord blood antibody values correlated with gestational age. After 6 months preterm infants born before 32 weeks of gestation had lost maternal antibodies.

Vaccination of cystic fibrosis patients against Pseudomonas aeruginosa reduces the proportion of patients infected and delays time to infection.

INTRODUCTION: Cystic fibrosis (CF) almost always leads to chronic airway infection with Pseudomonas aeruginosa. Despite advances in antibiotic therapy, after chronic infection rapid deterioration in lung function occurs, increasing morbidity and mortality. Prevention of infection by vaccination is desirable, but earlier trials produced disappointing results. The promising short term immunogenicity and safety of a new P. aeruginosa vaccine prompted us to evaluate its long term efficacy. We conducted a 10-year retrospective analysis of outcomes in a group of vaccinated patients. MATERIALS AND METHODS: In 1989-1990, 30 young children with CF, mean age 7 years, with no prior history of infection with P. aeruginosa, were vaccinated against P. aeruginosa with a polyvalent conjugate vaccine. We report the follow-up of 26 of these patients from 1989 to 2001. The patients were given yearly vaccine boosters. Comparisons were made with a CF patient control group matched for gender, age and, where possible, genetic mutation. Vaccinated patients and controls were attending a single CF clinic and received the same clinical management throughout the study period. Main outcomes were time to infection, proportion of patients infected, development of P. aeruginosa mucoid phenotype, lung function and body weight. RESULTS: The time to infection with P. aeruginosa was longer in the vaccination group than in the control group, and fewer vaccinated patients than controls became chronically infected (32% versus 72%; P < 0.001). The proportion of mucoid infections was higher in the control group (44%) than in the vaccinated group (25%). Patients >/=18 years of age at the end of the study had a lower mean forced expiratory volume at 1 s (FEV1) than did those 13-17 years of age, but this difference was small in the vaccinated group (73.6% versus 83.7%) compared with the controls (48.0% versus 78.7%). In the >/=18 year age category the mean FEV1% at 10 years was 73.6% (vaccinated) and 48.0% (controls) (P < 0.05). In the vaccinated group only 11 (44%) of 25 patients were underweight at the 10-year follow-up compared with 18 (72%) of 25 at the beginning of the study. In the control group 17 (68%) of 25 patients were underweight at 10-year follow-up compared with 16 (64%) of 25 at the beginning of the study. CONCLUSION: Regular vaccination of young CF patients for a period of 10 years with a polyvalent conjugate vaccine reduced the frequency of chronic infection with P. aeruginosa. This was associated with better preservation of lung function. Vaccinated patients gained more weight during the study period, a possible indication of an improved overall health status.