The kinetic profiles of copeptin and mid regional proadrenomedullin (MR-proADM) in pediatric lower respiratory tract infections.

BACKGROUND: Kinetics of copeptin and mid regional proadrenomedullin (MR-proADM) during febrile pediatric lower respiratory tract infections (LRTI) are unknown. We aimed to analyze kinetic profiles of copeptin and MR-proADM and the impact of clinical and laboratory factors on those biomarkers. METHODS: This is a retrospective post-hoc analysis of a randomized controlled trial, evaluating procalcitonin guidance for antibiotic treatment of LRTI (ProPAED-study). In 175 pediatric patients presenting to the emergency department plasma copeptin and MR-proADM concentrations were determined on day 1, 3, and 5. Their association with clinical characteristics and other inflammatory biomarkers were tested by non-linear mixed effect modelling. RESULTS: Median copeptin and MR-proADM values were elevated on day 1 and decreased during on day 3 and 5 (-26%; -34%, respectively). The initial concentrations of MR-proADM at inclusion were higher in patients receiving antibiotics intravenously compared to oral administration (difference 0.62 pmol/L, 95%CI 0.44;1.42, p<0.001). Intensive care unit (ICU) admission was associated with a daily increase of MR-proADM (increase/day 1.03 pmol/L, 95%CI 0.43;1.50, p<0.001). Positive blood culture in patients with antibiotic treatment and negative results on nasopharyngeal aspirates, or negative blood culture were associated with a decreasing MR-proADM (decrease/day -0.85 pmol/L, 95%CI -0.45;-1.44), p<0.001). CONCLUSION: Elevated MR-proADM and increases thereof were associated with ICU admission suggesting the potential as a prognostic factor for severe pediatric LRTI. MR-proADM might only bear limited value for decision making on stopping antibiotics due to its slow decrease. Copeptin had no added value in our setting.

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.

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).

Procalcitonin for Diagnostics and Treatment Decisions in Pediatric Lower Respiratory Tract Infections.

Mortality and morbidity remain high in pediatric lower respiratory tract infections (LRTIs) despite progress in research and implementation of global diagnostic and treatment strategies in the last decade. Still, 120 million annual episodes of pneumonia affect children younger than 5 years each year leading to 1.3 million fatalities with the major burden of disease carried by low- and middle-income countries (95%). The definition of pneumonia is still challenging. Traditional diagnostic measures (i.e., chest radiographs, C-reactive protein) are unable to distinguish viral and from bacterial etiology. As a result, common antibiotic overuse contributes to growing antibiotic resistance. We present an overview of current evidence from observational and randomized controlled trials on a procalcitonin (PCT)-based diagnosis of pediatric LRTIs and discuss the need for an adequate PCT threshold for antibiotic treatment decision-making.

Drivers of antibiotic prescribing in children and adolescents with febrile lower respiratory tract infections.

BACKGROUND: Knowledge of key drivers for antibiotic prescribing in pediatric lower respiratory tract infection (LRTI) could support rational antibiotic use. Thus, we aimed to determine the impact of clinical and laboratory factors on antibiotic prescribing in children and adolescents with febrile LRTI. METHODS: Pediatric patients from the standard care control group of a randomized controlled trial (ProPAED) investigating procalcitonin guided antibiotic treatment in febrile LRTI were included in a multivariate logistic regression analysis to evaluate the impact of laboratory and clinical factors on antibiotic prescribing. RESULTS: The standard care control group of the ProPAED study comprised 165 LRTI patients (median age: 2.7 years, range: 0.1-16), out of which 88 (55%) received antibiotic treatment. Factors significantly associated with antibiotic prescribing in patients with complete clinical and laboratory documentation (n = 158) were C-reactive protein (OR 5.8 for a 10-fold increase, 95%CI 2.2-14.9), white blood count beyond age-dependent reference range (OR 3.9, 95%CI 1.4-11.4), body temperature (OR 1.7 for an increase by 1°C, 95%CI 1.02-2.68), and pleuritic pain (OR 2.8, 95%CI 1.1-7.6). Dyspnea (OR 0.3, 95%CI 0.1-0.7) and wheezing (OR 0.3, 95%CI 0.13-0.95) were inversely associated with antibiotic prescribing. CONCLUSION: Laboratory markers were strong drivers of antibiotic prescribing in children with febrile lower respiratory tract infections, in spite of their known poor prediction of antibiotic need. Building on current guidelines for antibiotic treatment in children with febrile LRTI, a reliable decision algorithm for safe antibiotic withholding considering the laboratory and clinical factors evaluated in this study has the potential to further reduce antibiotic prescribing.

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.

Comparative analysis of clinical characteristics of pandemic influenza a/h1n1 and seasonal influenza a infections in hospitalized children.

Pandemic influenza A/H1N1 (piA) caused significant morbidity and mortality worldwide. We compared characteristics of piA (2009/2010) to those of seasonal influenza A (2007/2008/2009) in 134 (piA/seasonal influenza A: N = 55/79) hospitalized patients <18 years of age. Chronic disease was present in 25%/33%. Most common symptoms were fever (87%/94%), cough (78%/86%), rhinitis (76%/76%) and pharyngitis (67%/68%). Croup syndrome (15%/3%), conjunctivitis (31%/10%) and febrile seizures (26%/13%) were more frequent in piA; 64%/53% patients had ≥1 complication, and 5 (3/2) were admitted to intensive care unit. Oseltamivir use was 20%/0%. Severity of pandemic influenza disease was not different compared with seasonal influenza A in preceding years.

Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infection in children and adolescents (ProPAED): a randomized controlled trial.

BACKGROUND: Antibiotics are overused in children and adolescents with lower respiratory tract infection (LRTI). Serum-procalcitonin (PCT) can be used to guide treatment when bacterial infection is suspected. Its role in pediatric LRTI is unclear. METHODS: Between 01/2009 and 02/2010 we randomized previously healthy patients 1 month to 18 years old presenting with LRTI to the emergency departments of two pediatric hospitals in Switzerland to receive antibiotics either according to a PCT guidance algorithm established for adult LRTI or standard care clinical guidelines. In intention-to-treat analyses, antibiotic prescribing rate, duration of antibiotic treatment, and number of days with impairment of daily activities within 14 days of randomization were compared between the two groups. RESULTS: In total 337 children, mean age 3.8 years (range 0.1-18), were included. Antibiotic prescribing rates were not significantly different in PCT guided patients compared to controls (OR 1.26; 95% CI 0.81, 1.95). Mean duration of antibiotic exposure was reduced from 6.3 to 4.5 days under PCT guidance (-1.8 days; 95% CI -3.1, -0.5; P = 0.039) for all LRTI and from 9.1 to 5.7 days for pneumonia (-3.4 days 95% CI -4.9, -1.7; P<0.001). There was no apparent difference in impairment of daily activities between PCT guided and control patients. CONCLUSION: PCT guidance reduced antibiotic exposure by reducing the duration of antibiotic treatment, while not affecting the antibiotic prescribing rate. The latter may be explained by the low baseline prescribing rate in Switzerland for pediatric LRTI and the choice of an inappropriately low PCT cut-off level for this population. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN17057980 http://www.controlled-trials.com/ISRCTN17057980.

Three-year surveillance of intussusception in children in Switzerland.

OBJECTIVE: We attempted to obtain baseline data on the incidence of intussusception and its association with gastroenteritis in a cross-sectional observational study in children. METHODS: Admissions to all 38 pediatric units in Switzerland because of intussusception were reported to the Swiss Pediatric Surveillance Unit from April 2003 to March 2006. Patient and disease characteristics were assessed prospectively with the use of a standardized questionnaire based on the case definition for intussusception developed by the Brighton Collaboration. Completeness of reporting was verified through capture-recapture analysis. RESULTS: There were 294 patients with reported intussusception; 35 cases were excluded for various reasons, and 29 additional patients were identified through International Classification of Diseases, 10th Revision, codes. After capture-recapture analysis, we estimated underreporting to the Swiss Pediatric Surveillance Unit to be 32% and we calculated a true number of 381 intussusception episodes. The highest level of diagnostic certainty was reached by 248 patients, and 20 fulfilled level 2 criteria; for the remaining 20 patients, available information was insufficient. The mean age of the patients was 2.7 years. The yearly mean incidence of intussusception was 38, 31, and 26 cases per 100,000 live births in the first, second, and third year of life, respectively, with no apparent seasonality. Seventy patients had a history of coinciding gastroenteritis, and 5 of 61 tested positive for rotavirus. Spontaneous devagination was observed for 38 patients; enemas reduced intussusception successfully in 183 cases, whereas surgical treatment was required in 67. All patients recovered without sequelae. CONCLUSIONS: This is the first prospective nationwide surveillance of intussusception in childhood using a standardized case definition. Most cases occurred beyond infancy, and association with rotavirus gastroenteritis was rare.

Seroprevalence and immunization history of selected vaccine preventable diseases in medical students.

To evaluate protection against vaccine-preventable diseases in medical students, we obtained data on immunization status and history of diphtheria, tetanus, pertussis, poliomyelitis, measles, mumps, rubella, varicella and hepatitis B from students with elective periods in our institution. Further, serum antibodies against measles, mumps, rubella and varicella-zoster virus (VZV) and hepatitis B surface (HBs) antigen were determined on a voluntary basis. For students with incomplete immunization status or lack of protective antibodies, vaccination was offered for free. Success of catch-up immunizations was serologically confirmed 4 weeks later. From May 1999 to April 2003, 170 students were enrolled; their mean age was 26 years with a median of 25 years (range 22-48 years). Immunization records were complete in 148 (87%), incomplete in 11 (6.5%) and missing in 11 (6.5%) students. Only 26% of the cohort had a complete and up-to-date immunization status. Seroprevalence of IgG antibodies against measles, mumps, rubella, VZV and HBs (> or = 10 IU/l) in 149 students were 85, 85, 92, 97 and 90%, respectively. Indications for > or = 1 catch-up immunization were found in 125 (74%) students and were accepted by 97 of them (78%). Sixty two (99%) of 63 immunized students available for follow-up demonstrated an adequate serological response. In conclusion, the great majority of medical students had immunization gaps. Systematic immunization programmes for medical students should be implemented.

Prospective surveillance of hospitalisations associated with varicella-zoster virus infections in children and adolescents.

UNLABELLED: Our goal was to determine the epidemiology of severe varicella-zoster virus (VZV) infections in hospitalised paediatric patients. Admissions associated with VZV infection of patients aged 0-16 years were reported by all 38 paediatric units in Switzerland to the Swiss Paediatric Surveillance Unit (SPSU) during 3 consecutive years (4/2000-3/2003). We verified completeness of reporting by capture-recapture analysis with patient records identified by ICD-10 codes. Outcome of illness was assessed 6 months after hospitalisation. A total of 335 cases (235 identified by SPSU reports, 100 by ICD-10 code) were included in this study. Mean age of patients was 4.1 years (median 3.5 years, range 0-16 years); 54% were male. Some 293 (87%) patients presented with chickenpox, 42 (13%) with herpes zoster and 291 (87%) patients were not immunocompromised. A total of 319 complications occurred in 237 (71%) patients: secondary bacterial infections (n =109); central nervous system involvement (n =76); VZV pneumonitis (n =7); others (n =127). Eleven (3%) patients required intensive care and three died. On follow-up, 303 (96%) of 315 patients had completely recovered; sequelae were present in 12 (4%) patients. The calculated hospitalisation rate was 13 per 10(4) cases. CONCLUSION: This study describes a sizeable hospitalisation and complication rate of varicella-zoster virus infections and provides a solid basis for future immunisation recommendations in Switzerland.