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Abstract Background Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in school-aged children. Macrolides are the first-line treatment for this infection. However, it is unclear whether macrolides are effective in treating M. pneumoniae CAP, mainly due to limitations in microbiological diagnosis of previous studies. The extensive global use of macrolides has led to increasing antimicrobial resistance. The overall objective of this trial is to produce efficacy data for macrolide treatment in children with M. pneumoniae CAP. Methods The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3–17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and −7.5%. The “at least one” success criterion is used to handle multiplicity with the two co-primary endpoints. With a power of 80% to reject at least one null hypothesis at a one-sided significance level of 1.25%, 376 patients will be required. Discussion This trial will produce efficacy data for macrolide treatment in children with M. pneumoniae CAP that might help to reduce the prescription of antibiotics and therefore contribute to the global efforts toward reducing antimicrobial resistance. Trial registration ClinicalTrials.gov, NCT06325293. Registered on 24 April 2024

Abstract Background In the initial phase of the SARS-CoV-2 pandemic, masking has been widely accepted in healthcare institutions to mitigate the risk of healthcare-associated infection. Evidence, however, is still scant and the role of masks in preventing healthcare-associated SARS-CoV-2 acquisition remains unclear.We investigated the association of variation in institutional mask policies with healthcare-associated SARS-CoV-2 infections in acute care hospitals in Switzerland during the BA.4/5 2022 wave. Methods SARS-CoV-2 infections in hospitalized patients between June 1 and September 5, 2022, were obtained from the “Hospital-based surveillance of COVID-19 in Switzerland”-database and classified as healthcare- or community-associated based on time of disease onset. Institutions provided information regarding institutional masking policies for healthcare workers and other prevention policies. The percentage of healthcare-associated SARS-CoV-2 infections was calculated per institution and per type of mask policy. The association of healthcare-associated SARS-CoV-2 infections with mask policies was tested using a negative binominal mixed-effect model. Results We included 2’980 SARS-CoV-2 infections from 13 institutions, 444 (15%) were classified as healthcare-associated. Between June 20 and June 30, 2022, six (46%) institutions switched to a more stringent mask policy. The percentage of healthcare-associated infections subsequently declined in institutions with policy switch but not in the others. In particular, the switch from situative masking (standard precautions) to general masking of HCW in contact with patients was followed by a strong reduction of healthcare-associated infections (rate ratio 0.39, 95% CI 0.30–0.49). In contrast, when compared across hospitals, the percentage of health-care associated infections was not related to mask policies. Conclusions Our findings suggest switching to a more stringent mask policy may be beneficial during increases of healthcare-associated SARS-CoV-2 infections at an institutional level.

A panel of 24 international experts met in July 2022 to discuss challenges associated with pertussis detection, monitoring, and vaccination in adults; conclusions from this meeting are presented. There has been a shift in the epidemiology of pertussis toward older children and adults. This shift has been attributed to the waning of infection- or vaccine-induced immunity, newer detection techniques causing detection bias, and possibly the replacement of whole-cell pertussis with acellular vaccines in high-income countries, which may lead to immunity waning more quickly. The burden of adult pertussis is still likely under-ascertained due to widespread under-recognition by healthcare professionals (HCPs), under-diagnosis, and under-reporting in this age group. Non-standardized testing guidance and varied case definitions have contributed to under-reporting. Key barriers to HCP engagement with the tetanus, diphtheria, and pertussis (Tdap) vaccine include low awareness, lack of time/funding, and lack of motivation due to low prioritization of Tdap.

ABSTRACTPertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase in pertussis cases affecting older children and adults. To boost immunity, and protect vulnerable populations, an enduring approach to vaccination has been proposed, but gaps remain in the evidence surrounding adult vaccination that are needed to inform such a policy. Gaps include: the true incidence of pertussis and its complications in adults; regional variations in disease recognition and reporting; and incidence of severe disease, hospitalizations, and deaths in older adults. Better data on the efficacy/effectiveness of pertussis vaccination in adults, duration of protection, and factors leading to poor vaccine uptake are needed. Addressing the critical evidence gaps will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to healthcare professionals, policymakers, and payers.

Abstract Background Few methicillin-resistant Staphylococcus aureus (MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes. Methods We accessed 451 historic (1965–1987) MRSA isolates stored in the Culture Collection of Switzerland, mostly collected from the Zurich region. We determined phenotypic antimicrobial resistance (AMR) and performed whole genome sequencing (WGS) using Illumina short-read sequencing on all isolates and long-read sequencing on a selection with Oxford Nanopore Technology. For context, we included 103 publicly available international assemblies from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmec cassette types, AMR, and virulence genes. Results Among the 451 historic Swiss MRSA isolates, we found 17 sequence types (STs) of which 11 have been previously described. Two STs were novel combinations of known loci and six isolates carried previously unsubmitted MLST alleles, representing five new STs (ST7843, ST7844, ST7837, ST7839, and ST7842). Most isolates (83% 376/451) represented ST247-MRSA-I isolated in the 1960s, followed by ST7844 (6% 25/451), a novel single locus variant (SLV) of ST239. Analysis by cgMLST indicated that isolates belonging to ST7844-MRSA-III cluster within the diversity of ST239-MRSA-III. Early MRSA were predominantly from clonal complex (CC)8. From 1980 to the end of the twentieth century, we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally. Conclusions The combined analysis of 1761 historic and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss-German and international MRSA across time.

Abstract Background Reliable species identification of cultured isolates is essential in clinical bacteriology. We established a new study algorithm named NOVA – Novel Organism Verification and Analysis to systematically analyze bacterial isolates that cannot be characterized by conventional identification procedures MALDI-TOF MS and partial 16 S rRNA gene sequencing using Whole Genome Sequencing (WGS). Results We identified a total of 35 bacterial strains that represent potentially novel species. Corynebacterium sp. (n = 6) and Schaalia sp. (n = 5) were the predominant genera. Two strains each were identified within the genera Anaerococcus, Clostridium, Desulfovibrio, and Peptoniphilus, and one new species was detected within Citrobacter, Dermabacter, Helcococcus, Lancefieldella, Neisseria, Ochrobactrum (Brucella), Paenibacillus, Pantoea, Porphyromonas, Pseudoclavibacter, Pseudomonas, Psychrobacter, Pusillimonas, Rothia, Sneathia, and Tessaracoccus. Twenty-seven of 35 strains were isolated from deep tissue specimens or blood cultures. Seven out of 35 isolated strains identified were clinically relevant. In addition, 26 bacterial strains that could only be identified at the species level using WGS analysis, were mainly organisms that have been identified/classified very recently. Conclusion Our new algorithm proved to be a powerful tool for detection and identification of novel bacterial organisms. Publicly available clinical and genomic data may help to better understand their clinical and ecological role. Our identification of 35 novel strains, 7 of which appear to be clinically relevant, shows the wide range of undescribed pathogens yet to define.

Summary: Background: Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome–Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. Methods: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). Findings: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2–12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) −0.05 to 1.0; p = 0.39). Interpretation: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. Funding: NOMIS, Vontobel, and Gaydoul Foundation.

Summary: Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.

AIMS OF THE STUDY: Remdesivir has shown benefits against COVID-19. However, it remains unclear whether, to what extent, and among whom remdesivir can reduce COVID-19-related mortality. We explored whether the treatment response to remdesivir differed by patient characteristics. METHODS: We analysed data collected from a hospital surveillance study conducted in 21 referral hospitals in Switzerland between 2020 and 2022. We applied model-based recursive partitioning to group patients by the association between treatment levels and mortality. We included either treatment (levels: none, remdesivir within 7 days of symptom onset, remdesivir after 7 days, or another treatment), age and sex, or treatment only as regression variables. Candidate partitioning variables included a range of risk factors and comorbidities (and age and sex unless included in regression). We repeated the analyses using local centring to correct the results for the propensity to receive treatment. RESULTS: Overall (n = 21,790 patients), remdesivir within 7 days was associated with increased mortality (adjusted hazard ratios 1.28–1.54 versus no treatment). The CURB-65 score caused the most instability in the regression parameters of the model. When adjusted for age and sex, patients receiving remdesivir within 7 days of onset had higher mortality than those not treated in all identified eight patient groups. When age and sex were included as partitioning variables instead, the number of groups increased to 19–20; in five to six of those branches, mortality was lower among patients who received early remdesivir. Factors determining the groups where remdesivir was potentially beneficial included the presence of oncological comorbidities, male sex, and high age. CONCLUSIONS: Some subgroups of patients, such as individuals with oncological comorbidities or elderly males, may benefit from remdesivir.

Summary: Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.

In light of rising antibiotic resistance, better methods for selection of empiric antibiotic treatment based on clinical and microbiological data are needed. Most guidelines target specific clinical infections, and variably adjust empiric antibiotic selection by certain patient characteristics. Coverage estimates reflect the probability that an antibiotic regimen will be active against the causative pathogen once confirmed and can provide an objective basis for empiric regimen selection. Coverage can be estimated for specific infections using a weighted incidence syndromic combination antibiograms (WISCAs) framework. However, no comprehensive data combining clinical and microbiological data for specific clinical syndromes are available in Switzerland. We therefore describe estimating coverage from semi-deterministically linked routine microbiological and cohort data of hospitalised children with sepsis. Coverage estimates were generated for each hospital and separately pooling data across ten contributing hospitals for five pre-defined patient risk groups. Data from 1,082 patients collected during the Swiss Paediatric Sepsis Study (SPSS) 2011–2015 were included. Preterm neonates were the most commonly represented group, and half of infants and children had a comorbidity. 67% of neonatal sepsis cases were hospital-acquired late-onset whereas in children 76% of infections were community-acquired. Escherichia coli, Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus were the most common pathogens. At all hospitals, ceftazidime plus amikacin regimen had the lowest coverage, and coverage of amoxicillin plus gentamicin and meropenem were generally comparable. Coverage was improved when vancomycin was included in the regimen, reflecting uncertainty about the empirically targeted pathogen spectrum. Children with community-acquired infections had high coverage overall. It is feasible to estimate coverage of common empiric antibiotic regimens from linked data. Pooling data by patient risk groups with similar expected pathogen and susceptibility profiles may improve coverage estimate precision, supporting better differentiation of coverage between regimens. Identification of data sources, selection of regimens and consideration of pathogens to target for improved empiric coverage is important.

AIMS OF THE STUDY: Globally, since the introduction of conjugate-vaccines against encapsulated bacteria, respiratory viruses have caused most hospitalisations for community-acquired pneumonia. The aim of this study was to describe pathogens detected and their association with clinical findings in Switzerland. METHODS: Baseline data were analysed for all trial participants enrolled between September 2018 and September 2020 into the KIDS-STEP Trial, a randomised controlled superiority trial on the effect of betamethasone on clinical stabilisation of children admitted with community-acquired pneumonia. Data included clinical presentation, antibiotic use and results of pathogen detection. In addition to routine sampling, nasopharyngeal specimens were analysed for respiratory pathogens using a panel polymerase chain reaction test covering 18 viral and 4 bacterial pathogens. RESULTS: 138 children with a median age of 3 years were enrolled at the eight trial sites. Fever (obligatory for enrolment) had been present for median 5 days before admission. Most common symptoms were reduced activity (129, 93.5%) and reduced oral intake (108, 78.3%). Oxygen saturation

Abstract Background Though the disease burden of varicella in Europe has been reported previously, the economic burden is still unknown. This study estimated the economic burden of varicella in Europe in the absence of Universal Varicella Vaccination (UVV) in 2018 Euros from both payer (direct costs) and societal (direct and indirect costs) perspectives. Methods We estimated the country specific and overall annual costs of varicella in absence of UVV in 31 European countries (27 EU countries, plus Iceland, Norway, Switzerland and the United Kingdom). To obtain country specific unit costs and associated healthcare utilization, we conducted a systematic literature review, searching in PubMed, EMBASE, NEED, DARE, REPEC, Open Grey, and public heath websites (1/1/1999–10/15/2019). The number of annual varicella cases, deaths, outpatient visits and hospitalizations were calculated (without UVV) based on age-specific incidence rates (Riera-Montes et al. 2017) and 2018 population data by country. Unit cost per varicella case and disease burden data were combined using stochastic modeling to estimate 2018 costs stratified by country, age and healthcare resource. Results Overall annual total costs associated with varicella were estimated to be €662,592,061 (Range: €309,552,363 to €1,015,631,760) in Europe in absence of UVV. Direct and indirect costs were estimated at €229,076,206 (Range €144,809,557 to €313,342,856) and €433,515,855 (Range €164,742,806 to €702,288,904), respectively. Total cost per case was €121.45 (direct: €41.99; indirect: €79.46). Almost half of the costs were attributed to cases in children under 5 years, owing mainly to caregiver work loss. The distribution of costs by healthcare resource was similar across countries. France and Germany accounted for 49.28% of total annual costs, most likely due to a combination of high numbers of cases and unit costs in these countries. Conclusions The economic burden of varicella across Europe in the absence of UVV is substantial (over 600 M€), primarily driven by caregiver burden including work productivity losses.

Abstract Background and purpose Continuous improvement of health and healthcare system is hampered by inefficient processes of generating new evidence, particularly in the case of rare diseases and paediatrics. Currently, most evidence is generated through specific research projects, which typically require extra encounters with patients, are costly and entail long delays between the recognition of specific needs in healthcare and the generation of necessary evidence to address those needs. The Swiss Personalised Health Network (SPHN) aims to improve the use of data obtained during routine healthcare encounters by harmonizing data across Switzerland and facilitating accessibility for research. The project “Harmonising the collection of health-related data and biospecimens in paediatric hospitals throughout Switzerland (SwissPedData)” was an infrastructure development project funded by the SPHN, which aimed to identify and describe available data on child health in Switzerland and to agree on a standardised core dataset for electronic health records across all paediatric teaching hospitals. Here, we describe the results of a two-day symposium that aimed to summarise what had been achieved in the SwissPedData project, to put it in an international context, and to discuss the next steps for a sustainable future. The target audience included clinicians and researchers who produce and use health-related data on children in Switzerland. Key highlights The symposium consisted of state-of-the-art lectures from national and international keynote speakers, workshops and plenary discussions. This manuscript summarises the talks and discussions in four sections: (I) a description of the Swiss Personalized Health Network and the results of the SwissPedData project; (II) examples of similar initiatives from other countries; (III) an overview of existing health-related datasets and projects in Switzerland; and (IV) a summary of the lessons learned and future prospective from workshops and plenary discussions. Implications Streamlined processes linking initial collection of information during routine healthcare encounters, standardised recording of this information in electronic health records and fast accessibility for research are essential to accelerate research in child health and make it affordable. Ongoing projects prove that this is feasible in Switzerland and elsewhere. International collaboration is vital to success. The next steps include the implementation of the SwissPedData core dataset in the clinical information systems of Swiss hospitals, the use of this data to address priority research questions, and the acquisition of sustainable funding to support a slim central infrastructure and local support in each hospital. This will lay the foundation for a national paediatric learning health system in Switzerland.

ObjectivesPost-measles increased susceptibility to subsequent infections seems particularly relevant in low-resource settings. We tested the hypothesis that measles causes a specifically increased rate of infections in children, also in a high-resource setting.MethodsWe conducted a retrospective cohort study on a large measles outbreak in Berlin, Germany. All children with measles who presented to hospitals in Berlin were included as cases, children with non-infectious and children with non-measles infectious diseases as controls. Repeat visits within 3 years after the outbreak were recorded.ResultsWe included 250 cases, 502 non-infectious, and 498 infectious disease controls. The relative risk for cases for the diagnosis of an infectious disease upon a repeat visit was 1.6 (95% CI 1.4–2.0, p < 0.001) vs. non-infectious and 1.3 (95% CI 1.1–1.6, p = 0.002) vs. infectious disease controls. 33 cases (27%), 35 non-infectious (12%) and 57 (18%) infectious disease controls presented more than three times due to an infectious disease (p = 0.01, and p = 0.02, respectively). This results in a relative risk of more than three repeat visits due to an infection for measles cases of 1.8 (95% CI 1.3–2.4, p = 0.01), and 1.4 (95% CI 1.0–1.9, p = 0.04), respectively.ConclusionOur study demonstrates for the first time in a high-resource setting, that increased post-measles susceptibility to subsequent infections in children is measles-specific—even compared to controls with previous non-measles infections.

Abstract Background Over the last two decades, several countries have initiated universal varicella vaccination (UVV) programs in infants. In 2019, the Swiss National Immunization Technical Advisory Group (NITAG) decided to start evaluating the introduction of universal varicella vaccination. There is a theoretical concern that suboptimal vaccination coverage could lead to a shift in the varicella incidence to older age groups, thereby potentially increasing complication rates. To achieve a high vaccination coverage rate, it is important that practicing physicians comply with a potential recommendation for UVV. We studied the perception of varicella and the current vaccination behavior among Swiss pediatricians and general practitioners (GPs) who treat children. We also assessed their intention to advise parents to vaccinate their children against varicella in the event the Swiss NITAG will recommend UVV. Methods Primary data was collected through a structured, 20-min online survey with Swiss pediatricians and GPs who treat children. Results 150 physicians participated in the study: 40 GPs in the German-speaking part, 20 GPs in the French-speaking part, 67 pediatricians in the German-speaking part, and 23 pediatricians in the French-speaking part. The majority (64%) of all participants reported that they currently recommend varicella vaccination for risk groups according to the national immunization plan. About one third of physicians (35%) – predominantly pediatricians – currently already recommend it for all infants. In these situations, a measles, mumps, rubella, varicella combination vaccine is currently used by 58% for the first dose and by 59% for the second dose. 86% of participants stated that they would advise parents to have their children vaccinated against varicella in case of a recommendation for UVV by the Swiss NITAG. 68% responded that they expect many questions from parents and 65% agreed that they have good arguments to convey the importance of varicella vaccination. Conclusions The survey study results show that most participating pediatricians and GPs indicated a favorable attitude towards childhood vaccination against varicella in the setting of a Swiss NITAG recommendation for UVV. This data shows the importance of NITAG recommendations in influencing vaccine education and supporting achievement of high coverage of varicella vaccination.

BACKGROUND: With the invasion of Ukraine by the Russian Army in February 2022, refugees, the majority of whom are women and children, started fleeing the war to neighbouring countries. Even before the current escalation, the conflict in the eastern part of Ukraine has led to the internal displacement of more than 200,000 children, and many others have experienced attacks, e.g. on schools. This inevitably leads to limitations in health care delivery. During transit, overcrowding, poor shelter and vulnerability may further put refugees at increased risk for infectious diseases. This consensus document aims to provide information and guidance regarding health issues that paediatricians and general practitioners may face when caring for Ukrainian children. METHODS: Members of the Migrant Health Reference Group of Paediatrics Switzerland and the Paediatric Infectious Disease Group in Switzerland developed this recommendation between March and April 2022 in a modified Delphi process. RESULTS: A total of 50 recommendations were agreed on with a ≥80% consensus. These include the following topics: i) general aspects, including interpreter services, urgent health needs, personal history and general check-ups; ii) mental health, including how to search for signs of psychological distress without going into traumatic details; iii) vaccinations, including recommendations for evaluation and catch-up; iv) screening for tuberculosis, human immunodeficiency virus, and hepatitis B and C; and v) providing age-appropriate preventive and health service information. CONCLUSION: This document provides current evidence and guidance when caring for paediatric refugees from Ukraine. The recommendations focus on Switzerland but may well be used in other countries. These are based on current evidence and may need to be adapted to individual situations and once further evidence becomes available.

The Global Pertussis Initiative is an expert scientific forum that publishes consensus recommendations concerning pertussis for many regions of the world. Here, we give recommendations for the primary vaccination of infants in those countries where whole-cell pertussis (wP)- and acellular pertussis (aP)-containing combination vaccines are used in parallel. A selective literature review was performed concerning the influence on safety, immunogenicity, and effectiveness of mixing wP- and aP-containing vaccines for primary immunization of infants. In addition, local data were collected from various countries and the results discussed in a face-to-face meeting. Very few data addressing issues of mixing combination vaccines were identified, and no data were available concerning the effectiveness or duration of protection. It was also found that pharmacovigilance data are scarce or lacking in those countries where they would be needed the most. We then identified frequent problems occurring in low- and middle-income countries (LMICs) where both vaccine types are used. Relying on local knowledge, we give practical recommendations for a variety of situations in different settings. Specific needs for additional data addressing these issues were also identified. International bodies, such as the World Health Organization (WHO), as well as vaccine producers should try to find ways to highlight the problems of mixing wP- and aP-containing combination vaccines with robust data. Countries are urged to improve on their pharmacovigilance for vaccines. For practicing physicians, our recommendations offer guidance when wP- and aP-containing vaccines are used in parallel during primary immunization.

Abstract Background Infants

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, pConclusion 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.

BACKGROUND: Improvement of paediatric healthcare is hampered by inefficient processes for generating new evidence. Clinical research often requires extra encounters with patients, is costly, takes place in an artificial situation with a biased selection of patients, and entails long delays until new evidence is implemented into health care. Electronic health records (EHR) contain detailed information on real patients and cover the entirety of patients. However, the use of EHR for research is limited because they are not standardised between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality. AIMS: SwissPedData aims to lay the foundation for a paediatric learning health system in Switzerland by facilitating EHR-based research. In this project, we aimed to assess the way routine clinical data are currently recorded in large paediatric clinics in Switzerland and to develop a national EHR-based set of common data elements (CDEs) that covers all processes of routine paediatric care in hospitals. METHODS: A taskforce of paediatricians from large Swiss children’s hospitals reviewed the current status of routine data documentation in paediatric clinical care and the extent of digitalisation. We then used a modified Delphi method to reach a broad consensus on a national EHR-based set of CDEs. RESULTS: All Swiss children’s hospitals use EHR to document some or all aspects of care. One hundred and nineteen paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national set of CDEs that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 CDEs: 76 in the main module on general paediatrics and between 11 and 59 CDEs per subspecialty module. Among these, 266 were classified as mandatory, 52 as recommended and 18 as optional. CONCLUSION: SwissPedData is a set of CDEs for information to be collected in EHR of Swiss children’s hospitals. It covers all care processes including clinical and paraclinical assessment, diagnosis, treatment, disposition and care site. All participating hospitals agreed to implement SwissPedData in their clinical routine and clinic information systems. This will pave the way for a national paediatric learning health system in Switzerland that enables fast and efficient answers to urgent clinical questions by facilitating high-quality nationwide retrospective and prospective observational studies and recruitment of patients for nested prospective studies and clinical trials.

Summary AIMS OF THE STUDY: Surveillance of pertussis at a national level is important to collect information on the epidemiology of the disease and to design optimal immunisation strategies. After an initial surveillance period for pertussis in hospitalised children in Switzerland from 2006 to 2010, new recommendations (including immunisation in pregnancy) were implemented in the national pertussis immunisation schedule in 2013. To monitor its effects, surveillance was resumed in 2013 and concluded in 2020. METHODS: From 1 January 2013 to 31 December 2020, hospitalised children under the age of 16 years with suspected or proven Bordetella pertussis infection were reported to the Swiss Paediatric Surveillance Unit. We analysed epidemiological and clinical characteristics for all patients who fulfilled the clinical case definition of pertussis (physician diagnosis, cough lasting ≥14 days in combination with at least one of the following symptoms: paroxysmal cough, whooping or post-tussive vomiting, or apnoea not otherwise explained in patients under the age of 12 months) with and without laboratory confirmation (polymerase chain reaction, culture or serology). RESULTS: 220 of the 306 reported cases met the inclusion criteria. Of these, 214 (97%) were laboratory-confirmed B. pertussis infections: 209 by polymerase chain reaction and 5 by culture from nasopharyngeal specimens. 172/220 (78%) patients were infants under six months of age at the day of hospitalisation. The mean annual hospitalisation rate for pertussis was 27.9 per 100,000 children for infants and 2.1 per 100,000 in all children

BACKGROUND: When the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe are compared, the associated COVID-19 mortality seems to have decreased substantially. Various factors could explain this trend, including changes in demographic characteristics of infected persons and the improvement of case management. To date, no study has been performed to investigate the evolution of COVID-19 in-hospital mortality in Switzerland, while also accounting for risk factors. METHODS: We investigated the trends in COVID-19-related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to June 2021, comparing in particular the first and the second wave. We used data from the COVID-19 Hospital-based Surveillance (CH-SUR) database. We performed survival analyses adjusting for well-known risk factors of COVID-19 mortality (age, sex and comorbidities) and accounting for competing risk. RESULTS: Our analysis included 16,984 patients recorded in CH-SUR, with 2201 reported deaths due to COVID-19 (13.0%). We found that overall in-hospital mortality was lower during the second wave of COVID-19 than in the first wave (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.63– 0.78; p

IMPORTANCE:. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES:. To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN:. Data from two prospective cohort studies. SETTING AND PARTICIPANTS:. Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES:. Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS:. In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE:. In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.

Infants are at high risk for severe morbidity and mortality from pertussis disease during early infancy. Vaccination against pertussis in pregnancy has emerged as the ideal strategy to protect infants during these early, vulnerable, first months of life. On 30 November and 1 December 2021, the Global Pertussis Initiative held a meeting that aimed to discuss and review the most up-to-date scientific literature supporting vaccination against pertussis in pregnancy and outstanding scientific questions. Herein, we review the current and historically published literature and summarize the findings as consensus statements on vaccination against pertussis in pregnancy on behalf of the Global Pertussis Initiative.

BACKGROUND SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world with several million victims in 213 countries. Switzerland was severely hit by the virus, with 43,000 confirmed cases as of 1 September 2020. AIM In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19, in addition to their mandatory reporting system. METHODS Patients hospitalised for more than 24 hours with a positive polymerase chain-reaction test, from 20 Swiss hospitals, are included. Data were collected in a customised case report form based on World Health Organisation recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms was more than 5 days after the patient’s admission date. RESULTS As of 1 September 2020, 3645 patients were included. Most patients were male (2168, 59.5%), and aged between 50 and 89 years (2778, 76.2%), with a median age of 68 (interquartile range 54–79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported, with hypertension (1481, 61.7%), cardiovascular diseases (948, 39.5%) and diabetes (660, 27.5%) being the most frequent in adults; respiratory diseases and asthma (4, 21.1%), haematological and oncological diseases (3, 15.8%) were the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly respiratory diseases (2470, 93.2% in adults; 16, 55.2% in children), and renal (681, 25.7%) and cardiac (631, 23.8%) complications for adults. The second and third most frequent complications in children affected the digestive system and the liver (7, 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989, 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. A total of 527 (14.5%) deaths were registered, all among adults. CONCLUSION The surveillance system has been successfully initiated and provides a robust set of data for Switzerland by including about 80% (compared with official statistics) of SARS-CoV-2/COVID-19 hospitalised patients, with similar age and comorbidity distributions. It adds detailed information on the epidemiology, risk factors and clinical course of these cases and, therefore, is a valuable addition to the existing mandatory reporting.

Introduction Community-acquired pneumonia (CAP) causes around 10 hospitalisations per 1000 child-years, each associated with an average 13 non-routine days experienced and more than 4 parent workdays lost. In adults, steroid treatment shortens time to clinical stabilisation without an increase in complications in patients with CAP. However, despite promising data from observational studies, there is a lack of high-quality evidence for the use of steroids.Methods and analysis The KIDS-STEP trial is a multicentre, randomised, double-blind, placebo-controlled superiority trial of betamethasone treatment on outcome of hospitalised children with CAP. Children are enrolled in paediatric emergency departments of hospitals across Switzerland and randomised to adjunct oral betamethasone for 2 days or matching placebo in addition to standard of care treatment. The co-primary outcomes are the proportion of children clinically stable 48 hours after randomisation and the proportion of children with CAP-related readmission within 28 days after randomisation. Secondary outcomes include length of hospital stay, time away from routine childcare and healthcare utilisation and total antibiotic prescriptions within 28 days from randomisation.Each of the co-primary outcomes will be analysed separately. We will test clinical stability rates using a proportion test; to test non-inferiority in readmission rates, we will construct 1−α % CI of the estimated difference and test if it contains the pre-defined margin of 7%. Success is conditional on both tests. A simulation-based sample size estimation determined that recruiting 700 patients will ensure a power of 80% for the study.Ethics and dissemination The trial protocol and materials were approved by ethics committees in Switzerland (lead: Ethikkommission Nordwest und Zentralschweiz) and the regulatory authority Swissmedic. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate.Trial registration number NCT03474991 and SNCTP000002864.

Background: Acute hematogenous osteomyelitis (OM) and septic arthritis require immediate diagnosis and treatment by an interdisciplinary team of pediatric infectious disease specialists and pediatric orthopedic surgeons. Adverse outcomes such as growth disturbance, bone deformity, and chronic infections have been described in older studies. However, there is only little known about long-term follow-up of patients of the last two decades. Therefore, we aimed to evaluate subjective and objective long-term outcomes of these children with osteoarticular infections treated in the millennial years.Methods: Cross-sectional study performed in two pediatric centers including patients admitted for OM and/or SA between 2005 and 2014 and follow-up consultations in 2019. Patients with symptoms of ≤2 weeks duration at initial presentation were contacted. Subjective outcomes were assessed by standardized interview, objective outcomes by clinical examination. Medical charts were used to extract data from the initial presentations. Statistical analysis was performed by non-parametric tests and Fisher's exact test.Results: Of 147 eligible patients 77 (52%) agreed to participate, of which 68 (88%) had an interview and physical examination and 9 (12%) an interview only. Thirty-three (39%) had OM, 26 (34%) SA, and 21 (27%) combined OM/SA. Median (IQR) age at follow-up was 13.3 (10.5–18.0) years with a median (IQR) follow-up of 7.1 (6.1–8.6) years. Persistent complaints including pain, functional differences and scar paresthesia, reported by 21 (28%) patients, were generally mild and only 3 (5%) required ongoing medical care. Objective sequelae including pain, limited range of motion, unilateral axis deformity or asymmetric gait were found in 8 (12%) participants. Older age, female sex, joint involvement, surgical intervention, persistent fever, and C-reactive protein elevation were associated with adverse clinical outcome.Conclusions: Adverse outcomes were observed in a considerable number of patients, most of which were minor, and only few required ongoing medical care. Long-term follow up is advisable for patients with risk factors identified during the initial presentation.This study was registered on ClinicalTrials.gov (NCT03827980).

AIMS We recently conducted a large survey amongst parents of young children exploring attitudes concerning immunisation and the general immunisation status of the children and their parents in Switzerland. Since little is known about the immunisation status of fathers of young children, we present our findings here; data on mothers were previously published elsewhere. METHODS We performed standardised interviews with parents of children born on or after 1 January 2013, and hospitalised at the University of Basel Children’s Hospital, Switzerland, between January and June 2017. If participation was declined, partial consent was sought for four questions regarding age, education level, attitudes towards vaccinations in general and availability of vaccination records of the parents. To compare our study results with other studies focusing on the completeness of the immunisation status of fathers, we conducted a literature search using broad search terms for studies published between 1 April 2009 and 1 December 2019. RESULTS Thirty-nine (20%) fathers of 199 enrolled children participated. The great majority had a positive or mostly positive attitude towards vaccinations, but only 2 (15%) of 13 fathers who participated in immunisation counselling were up-to-date with all generally recommended immunisations. Fifty-two percent of participating fathers reported that the last assessment of their immunisation status by a physician was >5 years ago. After the birth of their child, 56% of fathers had received a recommendation for immunisation against pertussis and 65% of them followed the recommendation. We identified three studies matching our review’s inclusion criteria. None of them reported specific findings for fathers. CONCLUSIONS This is the first study to analyse the complete immunisation status of fathers of young children. It is often incomplete with potentially missed opportunities for updating vaccinations during recent physician consultations. The low participation rate of fathers is a limitation which prohibits generalisation of our findings. However, as healthcare personnel have been shown to have the strongest impact on vaccination uptake, we propose that this group be further sensitised and educated with the goal of improving immunisation rates in fathers of young children.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B Streptococcus vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant.

Infection with varicella zoster virus (VZV) is usually a benign and self-limiting disease. Serious complications by bacterial pathogens do occur, such as necrotising fasciitis (NF). One of the most important is Streptococcus pyogenes (or Group A Streptococcus, GAS), which colonizes epithelial surfaces, primarily of the throat and skin. In rare instances, varicella may also be associated with S. pyogenes endocarditis. Review of the literature reveals only 18 children with infective endocarditis (IE) caused by GAS since 1942. VZV as antecedent illness was found in five (28%). Fourteen (78%) had no pre-existing cardiac abnormalities. Death occurred in three (17%) children. Infective endocarditis with acute deterioration secondary to rupture of mitral valve chordae tendineae necessitating cardiac surgery has not been reported in the literature yet. We present this rare and instructive pediatric case and the results of a literature search on S. pyogenes endocarditis in children.

Introduction: Pertussis is a highly contagious disease of the respiratory tract which is caused by the bacterium Bordetella pertussis and is most severe in those

Abstract Background Varicella is generally considered a mild disease. Disease burden is not well known and country-level estimation is challenging. As varicella disease is not notifiable, notification criteria and rates vary between countries. In general, existing surveillance systems do not capture cases that do not seek medical care, and most are affected by underreporting and underascertainment. We aimed to estimate the overall varicella disease burden in Europe to provide critical information to support decision-making regarding varicella vaccination. Methods We conducted a systematic literature review to identify all available epidemiological data on varicella IgG antibody seroprevalence, primary care and hospitalisation incidence, and mortality. We then developed methods to estimate age-specific varicella incidence and annual number of cases by different levels of severity (cases in the community, health care seekers in primary care and hospitals, and deaths) for all countries belonging to the European Medicines Agency (EMA) region and Switzerland. Results In the absence of universal varicella immunization, the burden of varicella would be substantial with a total of 5.5 million (95% CI: 4.7–6.4) varicella cases occurring annually across Europe. Variation exists between countries but overall the majority of cases (3 million; 95% CI: 2.7–3.3) would occur in children

Background: Interferon-gamma release assays (IGRA) are well-established immunodiagnostic tests for tuberculosis (TB) in adults. In children these tests are associated with higher rates of false-negative and indeterminate results. Age is presumed to be one factor influencing cytokine release and therefore test performance. The aim of this study was to systematically review factors associated with indeterminate IGRA results in pediatric patients.Methods: Systematic literature review guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) searching PubMed, EMBASE, and Web of Science. Studies reporting results of at least one commercially available IGRA (QuantiFERON-TB, T-SPOT.TB) in pediatric patient groups were included. Random effects meta-analysis was used to assess proportions of indeterminate IGRA results. Heterogeneity was assessed using the I2 value. Risk differences were calculated for studies comparing QuantiFERON-TB and T-SPOT.TB in the same study. Meta-regression was used to further explore the influence of study level variables on heterogeneity.Results: Of 1,293 articles screened, 133 studies were included in the final analysis. These assessed QuantiFERON-TB only in 77.4% (103/133), QuantiFERON-TB and T-SPOT.TB in 15.8% (21/133), and T-SPOT.TB only in 6.8% (9/133) resulting in 155 datasets including 107,418 participants. Overall 4% of IGRA results were indeterminate, and T-SPOT.TB (0.03, 95% CI 0.02–0.05) and QuantiFERON-TB assays (0.05, 95% CI 0.04–0.06) showed similar proportions of indeterminate results; pooled risk difference was−0.01 (95% CI −0.03 to 0.00). Significant differences with lower proportions of indeterminate assays with T-SPOT.TB compared to QuantiFERON-TB were only seen in subgroup analyses of studies performed in Africa and in non-HIV-infected immunocompromised patients. Meta-regression confirmed lower proportions of indeterminate results for T-SPOT.TB compared to QuantiFERON-TB only among studies that reported results from non-HIV-infected immunocompromised patients (p < 0.001).Conclusion: On average indeterminate IGRA results occur in 1 in 25 tests performed. Overall, there was no difference in the proportion of indeterminate results between both commercial assays. However, our findings suggest that in patients in Africa and/or patients with immunocompromising conditions other than HIV infection the T-SPOT.TB assay appears to produce fewer indeterminate results.

Background: Blood cultures are essential for the diagnosis and further appropriate treatment in children with suspected sepsis. In most hospitals, children will be empirically treated or closely monitored for at least 48 h awaiting results of blood cultures. Several studies have challenged the optimal duration of empiric treatment in the era of continuously monitored blood culture systems. The aim of our study was to investigate time-to-positivity (TTP) of blood cultures in children with proven sepsis.Methods: The Swiss Pediatric Sepsis Study prospectively enrolled children 0–16 years of age with blood culture positive sepsis between September 2011 and October 2015. TTP was prospectively assessed in six participating academic pediatric hospitals by fully automated blood culture systems.Results: In 521 (93%) of 562 bacteremia episodes (493 children, median age 103 days, range 0 days−16.9 years) a valid TTP was available. Median TTP was 12 h (IQR 8–17 h, range 0–109 h). By 24, 36, and 48 h, 460 (88%), 498 (96%), and 510 (98%) blood cultures, respectively, were positive. TTP was independent of age, sex, presence of comorbidities, site of infection and severity of infection. Median TTP in all age groups combined was shortest for group B streptococcus (8.7 h) and longest for coagulase-negative staphylococci (16.2 h).Conclusion: Growth of bacteria in blood cultures is detectable within 24 h in 9 of 10 children with blood culture-proven sepsis. Therefore, a strict rule to observe or treat all children with suspected sepsis for at least 48 h is not justified.

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.

Cytomegalovirus (CMV) is the most frequent congenital virus infection worldwide. The risk of congenital CMV (cCMV) transmission is highest in seronegative women who acquire primary CMV infection during pregnancy. A growing body of evidence indicates that secondary CMV infections in pregnant women with preconceptual immunity (either through reactivation of latent virus or re-infection with a new strain of CMV) contribute to a much greater proportion of symptomatic cCMV than was previously thought. Here, we describe a case of symptomatic cCMV infection in the newborn of a woman with proven immunity prior to pregnancy. Diagnosis was confirmed by CMV PCR from amniotic fluid and fetal MR imaging. The newborn presented with typical cCMV symptoms including jaundice, hepatosplenomegaly, cholestasis, petechiae, small head circumference, and sensorineural hearing loss, the most common neurologic sequela. CMV was detected in infant blood and urine by PCR, and intravenous ganciclovir was initiated and continued orally for 6 weeks totally. Apart from persisting right-sided deafness, the child exhibited normal neurological development up through the last follow-up at 4.5 years. To date, the most effective strategy to prevent vertical CMV transmission is hygiene counseling for women of childbearing age, which, in our case, and in concordance with recent literature, applies to seronegative, as well as seropositive, women. Once an expecting mother shows seroconversion or signs of an active CMV infection, there are no established procedures to reduce the risk of transmission, or therapeutic options for the fetus with signs of infection. After birth, symptomatic infants can be treated with ganciclovir to inhibit viral replication and improve hearing ability and neurodevelopmental outcome. A comprehensive review of the literature, including our case study, reveals the most current and significant diagnostic and treatment options available. In conclusion, the triad of maternal hygiene counseling, postnatal hearing screening of all newborns, followed by CMV PCR in symptomatic infants, and antiviral therapy of infants with symptomatic cCMV provides an outline of best practice to reduce the burden of CMV transmission sequelae.

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.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.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.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.

Lyme borreliosis is caused by Borrelia burgdorferi sensu lato infection, which responds well to antibiotic therapy in the overwhelming majority of cases. However, despite adequate antibiotic treatment some patients report persisting symptoms which are commonly summarised as post-treatment Lyme disease syndrome (PTLDS). In 2005, the Swiss Society of Infectious Diseases published a case definition for PTLDS. We aimed to review the scientific literature with a special emphasis on the last 10 years, questioning whether the definitions from 2005 are still valid in the light of current knowledge. Furthermore, we describe the clinical history of infection with Borrelia burgdorferi sensu lato, the estimated prevalence of PTLDS, the possible pathogenesis of PTLDS, and treatment options with an emphasis on clinical studies. In summary, we were unable to find a scientific reason for modification of the PTLDS definitions published in 2005. Thus, the diagnostic criteria remain unchanged, namely documented clinical and laboratory evidence of previous infection with B. burgdorferi, a completed course of appropriate antibiotic therapy, symptoms including fatigue, arthralgia, myalgia, cognitive dysfunction or radicular pain persisting for >6 months, a plausible timely association between documented B. burgdorferi infection and onset of symptoms (i.e., persistent or recurrent symptoms that began within 6 months of completion of a recommended antibiotic therapy for early or late Lyme borreliosis), and exclusion of other somatic or psychiatric causes of symptoms. The main therapeutic options remain cognitive behavioural therapy and low-impact aerobic exercise programmes. Growing and unequivocal evidence confirms that prolonged or repeated antibiotic therapy for PTLDS is not beneficial, but potentially harmful and therefore contraindicated. The Guidelines of the Swiss Society of Infectious Diseases offer an evidence based, diagnostic and therapeutic framework for physicians caring for patients suffering from presumptive PTLDS in Switzerland.

We undertook an epidemiological survey of the annual incidence of pertussis reported from 2000 to 2013 in ten Central and Eastern European countries to ascertain whether increased pertussis reports in some countries share common underlying drivers or whether there are specific features in each country. The annual incidence of pertussis in the participating countries was obtained from relevant government institutions and/or national surveillance systems. We reviewed the changes in the pertussis incidence rates in each country to explore differences and/or similarities between countries in relation to pertussis surveillance; case definitions for detection and confirmation of pertussis; incidence and number of cases of pertussis by year, overall and by age group; population by year, overall and by age group; pertussis immunization schedule and coverage, and switch from whole-cell pertussis vaccines (wP) to acellular pertussis vaccines (aP). There was heterogeneity in the reported annual incidence rates and trends observed across countries. Reported pertussis incidence rates varied considerably, ranging from 0.01 to 96 per 100,000 population, with the highest rates generally reported in Estonia and the lowest in Hungary and Serbia. The greatest burden appears for the most part in infants (

OBJECTIVE: To describe all patients admitted to children’s hospitals in Switzerland with a diagnosis of influenza A/H1N1/09 virus infection during the 2009 influenza pandemic, and to analyse their characteristics, predictors of complications, and outcome. METHODS: All patients ≤18-years-old hospitalised in eleven children’s hospitals in Switzerland between June 2009 and January 2010 with a positive influenza A/H1N1/09 reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal specimen were included. RESULTS: There were 326 PCR-confirmed patients of whom 189 (58%) were younger than 5 years of age, and 126 (38.7%) had one or more pre-existing medical condition. Fever (median 39.1 °C) was the most common sign (85.6% of all patients), while feeding problems (p = 0.003) and febrile seizures (p = 0.016) were significantly more frequent in children under 5 years. In 142 (43.6%) patients there was clinical suspicion of a concomitant bacterial infection, which was confirmed in 36 patients (11%). However, severe bacterial infection was observed in 4% of patients. One third (n = 108, 33.1%) of the patients were treated with oseltamivir, 64 (59.3%, or 20% overall) within 48 hours of onset of symptoms. Almost half of the patients (45.1%) received antibiotics for a median of 7 days. Twenty patients (6.1%) required intensive care, mostly for complicated pneumonia (50%) without an underlying medical condition. The median duration of hospitalisation was 2 days (range 0–39) for 304 patients. Two children (

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.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.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

Objective: To review the diagnostic experience with acute haematogenous osteomyelitis (AHOM) and/or septic arthritis at our institution. Methods: Retrospective review of the medical records of those patients with a bacteriologically and/or radiologically confirmed diagnosis, hospitalised in the University Children's Hospital Basel, Switzerland between January 1980 and July 2000. Results: 90 patients (61% males), 4 weeks to 14 years of age, met the inclusion criteria. Median duration of disease prior to hospitalisation was 3 days (range 0-14); 88% were admitted during the first week after onset of complaints. 81 patients received no antimicrobial therapy prior to hospitalisation and are the subject of this presentation. ESR (1st hour in mm; median 36; range 11-124), CRP (mg/l; median 64; range 0-221) and WBC (x 10(9)/l; median 13; range 5-34) were elevated in 100%, 82% and 58% of patients, respectively. Blood cultures (BC) and/or tissue cultures (TC) were performed in 79 (98%) patients. Overall, bacteria were isolated from 53 patients (65%) with Staph. aureus as the most frequent organism (n = 31; 50%). BC were performed in 67 patients and yielded 35 (52%) positive cultures; TC (n = 47) yielded 27 (57%) isolates. In 34 patients with both BC and TC performed, only 12 (35%) were positive in both tests. Diagnostic findings were observed in 23 (59%) of 39 plain radiographs, 31 (56%) of 55 sonograms, 39 (89%) of 44 99mTc-labeled bone scans and 4 (100%) of 4 MRI. 41 patients with diagnostic radiological findings had consecutive TC yielding 30 (73%) bacteriological isolates. Median duration of hospitalisation was 15 days (range 2-66). Conclusion: Our data indicate that the diagnostic procedures of choice should be 1) early bone scan or MRI, 2) BC and 3) TC. Of supportive laboratory parameters, ESR and CRP were most valuable in our hands.