Publications by authors named "Ulrich Heininger"

195 Publications

Pertussis-like illness is not the same as pertussis.

Authors:
Ulrich Heininger

J Pediatr (Rio J) 2021 Feb 24. Epub 2021 Feb 24.

University of Basel Children's Hospital, Division of Pediatric Infectious Diseases and Vaccinology, Basel, Switzeland. Electronic address:

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http://dx.doi.org/10.1016/j.jped.2021.02.001DOI Listing
February 2021

Cohort profile: SARS-CoV-2/COVID-19 hospitalised patients in Switzerland.

Swiss Med Wkly 2021 02 15;151:w20475. Epub 2021 Feb 15.

Institut de Santé Globale, Faculté de Médecine de l'Université de Genève, Geneva, Switzerland.

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.
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http://dx.doi.org/10.4414/smw.2021.20475DOI Listing
February 2021

Preventive measures for accompanying caregivers of children in paediatric health care during the COVID-19 pandemic-walking an ethical tightrope.

Clin Microbiol Infect 2021 Feb 2. Epub 2021 Feb 2.

Department of Infectious Diseases and Vaccinology, University of Basel Children's Hospital, Basel, Switzerland; Swissnoso, the National Centre for Infection Control, Bern, Switzerland.

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http://dx.doi.org/10.1016/j.cmi.2021.01.023DOI Listing
February 2021

Acceptance of universal varicella vaccination among Swiss pediatricians and general practitioners who treat pediatric patients.

BMC Infect Dis 2021 Jan 6;21(1):12. Epub 2021 Jan 6.

MSD Merck Sharp & Dohme AG, Lucerne, Switzerland.

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.
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http://dx.doi.org/10.1186/s12879-020-05586-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789518PMC
January 2021

Strikingly Decreased Community-acquired Pneumonia Admissions in Children Despite Open Schools and Day-care Facilities in Switzerland.

Pediatr Infect Dis J 2020 Dec 15;Publish Ahead of Print. Epub 2020 Dec 15.

Department of Paediatric Pharmacology University of Basel Children's Hospital (UKBB) Basel, Switzerland Institute for Medical Microbiology and Hospital Hygiene Heinrich Heine University Düsseldorf Düsseldorf, Germany Division of Infectious Diseases and Hospital Epidemiology University Children's Hospital Zurich Zurich, Switzerland Paediatric Emergency Department University Children's Hospital Inselspital University of Bern Bern, Switzerland Swiss Tropical and Public Health Institute University of Basel Basel, Switzerland Ambulatory Study Centre University of Basel Children's Hospital (UKBB) Basel, Switzerland Department of Infectious Diseases and Vaccinology University of Basel Children's Hospital (UKBB) Basel, Switzerland Department of Paediatric Pharmacology University of Basel Children's Hospital (UKBB) Basel, Switzerland Department of Paediatric Pharmacology and Department of Infectious Diseases and Vaccinology University of Basel Children's Hospital (UKBB) Basel, Switzerland.

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http://dx.doi.org/10.1097/INF.0000000000003026DOI Listing
December 2020

Randomised placebo-controlled multicentre effectiveness trial of adjunct betamethasone therapy in hospitalised children with community-acquired pneumonia: a trial protocol for the KIDS-STEP trial.

BMJ Open 2020 12 29;10(12):e041937. Epub 2020 Dec 29.

Department of Paediatric Pharmacology, University of Basel Children's Hospital (UKBB), Basel, Switzerland.

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.
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http://dx.doi.org/10.1136/bmjopen-2020-041937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778765PMC
December 2020

Long-Term Outcomes of Acute Osteoarticular Infections in Children.

Front Pediatr 2020 25;8:587740. Epub 2020 Nov 25.

Infectious Diseases and Vaccinology Unit, University of Basel Children's Hospital, Basel, Switzerland.

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. 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. 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. 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).
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http://dx.doi.org/10.3389/fped.2020.587740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737431PMC
November 2020

[Pertussis (whooping cough)].

Authors:
Ulrich Heininger

Pneumologe (Berl) 2020 Oct 6:1-12. Epub 2020 Oct 6.

Universitäts-Kinderspital beider Basel, Spitalstr. 33, 4056 Basel, Schweiz.

Pertussis is caused by the gram-negative bacterium . The disease manifestations range from unspecific coughing to life-threatening courses with hyperleukocytosis and respiratory failure, especially in young infants. The diagnosis is based on clinical symptoms and microbiological detection methods. The treatment consists of macrolide antibiotics and caffeine can be used against apnea. The incidence is 10-40 cases/100,000 inhabitants per year and highest in infants (approximately 50), followed by adolescents (30-35). In the first 5 months of life more than 50% of all children with pertussis are hospitalized. Vaccination prevention consists of basic immunization and regular booster doses with acellular component vaccines. Vaccination of pregnant women is the most promising strategy to prevent severe pertussis in young infants. Infants of vaccinated mothers should still be immunized in a timely manner for their own protection from the age of 2 months onwards.
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http://dx.doi.org/10.1007/s10405-020-00345-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537784PMC
October 2020

Diphtheria, Tetanus, and Pertussis: Unequal Vaccine Siblings With Distinct Characteristics.

Authors:
Ulrich Heininger

Clin Infect Dis 2021 Feb;72(3):534

Department of Infectious Diseases and Vaccinology, University of Basel Children's Hospital, Basel, Switzerland.

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http://dx.doi.org/10.1093/cid/ciaa642DOI Listing
February 2021

Clinical and Epidemiologic Characteristics of Pertussis in Hospitalized Children: A Prospective and Standardized Long-term Surveillance Study.

Pediatr Infect Dis J 2021 Jan;40(1):22-25

From the Paediatric Infectious Diseases and Vaccinology Unit, University of Basel Children's Hospital, Basel, Switzerland.

Background: Surveillance of incidence and severity of pertussis is key to control success and shortcomings of vaccination programs followed by adaptations of recommendations if necessary. In Switzerland, nationwide reporting of hospitalizations due to pertussis in children has a long tradition and resumed in 2013 to evaluate the effects of pertussis immunization in pregnancy introduced in 2013.

Methods: Since 2013, all patients <16 years of age hospitalized with suspected or proven pertussis have been reported to the Swiss Pediatric Surveillance Unit. Patient data comprising clinical and epidemiologic characteristics and laboratory confirmation were assessed in a standardized fashion, and case definitions were applied to all cases reported until the end of 2019.

Results: Two hundred thirteen of 294 cases were valid cases of pertussis. Of these, 168 (79%) occurred in <6-month-old infants. Mean duration of hospitalization was 8 days (median 5, range 2-47) overall and highest in neonates (14.2 days); 85% of all patients had ≥1 complication, most commonly cyanosis and dyspnea, especially in infants. Overall, case fatality rate was 1.4% (8.7% in neonates). Only 4 (2%) of 168 mothers of infants <6 months had been vaccinated during pregnancy; 14 (12%) of 112 patients with precise records of immunization had completed their primary series and were up-to-date for age.

Conclusions: Despite a decline of cases associated with the introduction of immunization against pertussis in pregnancy, control of the disease remains challenging, mainly due to failure to vaccinate rather than vaccine failure.
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http://dx.doi.org/10.1097/INF.0000000000002904DOI Listing
January 2021

[Pertussis (whooping cough)].

Authors:
Ulrich Heininger

Monatsschr Kinderheilkd 2020 Jul 7:1-12. Epub 2020 Jul 7.

Universitäts-Kinderspital beider Basel, Spitalstr. 33, 4056 Basel, Schweiz.

Pertussis is caused by the gram-negative bacterium . The disease manifestations range from unspecific coughing to life-threatening courses with hyperleukocytosis and respiratory failure, especially in young infants. The diagnosis is based on clinical symptoms and microbiological detection methods. The treatment consists of macrolide antibiotics and caffeine can be used against apnea. The incidence is 10-40 cases/100,000 inhabitants per year and highest in infants (approximately 50), followed by adolescents (30-35). In the first 5 months of life more than 50% of all children with pertussis are hospitalized. Vaccination prevention consists of basic immunization and regular booster doses with acellular component vaccines. Vaccination of pregnant women is the most promising strategy to prevent severe pertussis in young infants. Infants of vaccinated mothers should still be immunized in a timely manner for their own protection from the age of 2 months onwards.
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http://dx.doi.org/10.1007/s00112-020-00941-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364744PMC
July 2020

Do fathers care about their own immunisation status? The Child-Parent-Immunisation Survey and a review of the literature.

Swiss Med Wkly 2020 Jul 2;150:w20289. Epub 2020 Aug 2.

Department of Infectious Diseases and Vaccinology, University of Basel Children's Hospital, Basel, Switzerland.

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. 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. 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. 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.  .
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http://dx.doi.org/10.4414/smw.2020.20289DOI Listing
July 2020

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement.

Front Immunol 2020 24;11:1282. Epub 2020 Jun 24.

Department of Medicine and Surgery, Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy.

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 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.
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http://dx.doi.org/10.3389/fimmu.2020.01282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326941PMC
June 2020

Swiss consensus recommendations on urinary tract infections in children.

Eur J Pediatr 2021 Mar 3;180(3):663-674. Epub 2020 Jul 3.

Paediatrics, Lucerne Children's Hospital, Cantonal Hospital Lucerne, Spitalstrasse, 6000, Luzern 16, Switzerland.

The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis. What is Known: • Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age. • Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. What is New: • Vesicoureteric reflux (VUR) remains a risk factor for UTI but per se is neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended. • A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.
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http://dx.doi.org/10.1007/s00431-020-03714-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886823PMC
March 2021

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study.

Lancet Child Adolesc Health 2020 09 25;4(9):653-661. Epub 2020 Jun 25.

Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK; Department of Paediatrics, Royal Children's Hospital Melbourne, University of Melbourne, Melbourne, Australia; Department of Paediatric Infectious Diseases & Immunology, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK. Electronic address:

Background: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic.

Methods: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission.

Findings: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support.

Interpretation: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed.

Funding: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.
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http://dx.doi.org/10.1016/S2352-4642(20)30177-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316447PMC
September 2020

Children and adolescents in the CoVid-19 pandemic: Schools and daycare centers are to be opened again without restrictions. The protection of teachers, educators, carers and parents and the general hygiene rules do not conflict with this.

GMS Hyg Infect Control 2020 28;15:Doc11. Epub 2020 May 28.

German Society for Pediatric Infectious Diseases (DGPI), Berlin, Germany.

In the opinion of the medical societies of hygiene and pediatrics undersigning the present statement, the analyses published to date regarding transmission of SARS-CoV-2 and the course of CoVid-19 show that children play a much less significant role in the spread of the virus than do adults. According to the findings available to date, not only do children and adolescents less frequently fall ill with CoVid-19, they also generally become less severely ill than do adults. The vast majority of infections in children and adolescents are asymptomatic or oligosymptomatic. Even the first analyses from China demonstrated that children and adolescents play a subordinate role in the transmission of the virus - not only to other children and adolescents, but also to adults. Taking into account regional infection rates and available resources, daycare centers, kindergartens and elementary schools promptly should be reopened. For children, this should be possible without excessive restrictions, such as clustering into very small groups, implementation of barrier precautions, maintaining appropriate distance from others or wearing masks. A factor more decisive than individual group size is the issue of sustaining the constancy of respective group members and the avoidance of intermixing. Children can be taught basic rules of hygiene such as handwashing and careful hygiene behavior when coming into contact with others during mealtimes and/or when using sanitary facilities. Independent of the prevention measures implemented for children and adolescents, the protection of teachers, educators and caregivers is crucial, (e.g., the maintenance of appropriate distance from others, use of medical masks, situation-dependent hand disinfection, when necessary, supported by regular pool testing). Children over the age of 10 and adolescents up to school graduation age are more capable of actively understanding and conforming to specific hygiene rules. For this group, maintaining appropriate distance from others (1.5 meters), wearing a mouth-and-nose protection (whenever they are not sitting in their assigned classroom seats) and consistent education regarding the basic rules of infection prevention may provide increased options for normalizing teaching activities. Children and adolescents suspected of infection with SARS-CoV-2 should be tested immediately in order to either confirm or rule out such an infection. Evidence of individual infections in children or students must not automatically lead to the closure of the entire daycare center or school. A detailed analysis of the chain of infection is a prerequisite for a balanced approach to infection control. The opening of schools and children's facilities should be accompanied by specifically structured, model surveillance studies that further clarify outstanding questions about infectious disease events and hygiene control. These prospective, concomitant examinations will be essential for the purpose of evaluating and verifying the effectiveness of the required hygiene measures.
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http://dx.doi.org/10.3205/dgkh000346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273848PMC
May 2020

Diphtheria, tetanus and pertussis: unequal vaccine siblings with distinct characteristics.

Authors:
Ulrich Heininger

Clin Infect Dis 2020 Jun 9. Epub 2020 Jun 9.

University of Basel Children's Hospital, Department of Infectious Diseases and Vaccinology, Spitalstrasse, Basel, Switzerland.

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http://dx.doi.org/10.1093/cid/ciaa643DOI Listing
June 2020

Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines: Setting Expectations Appropriately.

Authors:
Ulrich Heininger

Pediatr Infect Dis J 2020 07;39(7):e123-e124

From the Faculty of Medicine, University of Basel, Basel, Switzerland.

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http://dx.doi.org/10.1097/INF.0000000000002741DOI Listing
July 2020

Pertussis vaccination in mixed markets: Recommendations from the Global Pertussis Initiative.

Int J Infect Dis 2020 Jul 12;96:482-488. Epub 2020 May 12.

Krefeld, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ijid.2020.04.081DOI Listing
July 2020

Whole-exome sequencing for the identification of rare variants in primary immunodeficiency genes in children with sepsis - a prospective population-based cohort study.

Clin Infect Dis 2020 Mar 18. Epub 2020 Mar 18.

Department of Paediatrics, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.

Background: The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of underlying PID. We applied whole-exome sequencing (WES) to a national cohort of children with sepsis to identify rare, predicted pathogenic variants in PID genes.

Methods: Multicenter population-based prospective study including previously healthy children ≥28 days and <17 years admitted with blood culture-proven sepsis. Using a stringent variant filtering procedure, analysis of WES data was restricted to rare, predicted pathogenic variants in 240 PID genes for which increased susceptibility to bacterial infection has been reported.

Results: 176 children presenting with 185 sepsis episodes underwent WES (median age 52 months, IQR 15.4-126.4). 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) were found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants which were previously reported to lead to PID. The variants occurred in PID genes across all 8 PID categories as defined by the International Union of Immunological Societies. We did not observe a significant correlation between clinical or laboratory characteristics of patients and the presence or absence of PID variants.

Conclusions: Applying WES to a population-based cohort of previously healthy children with bacterial sepsis detected Variants of Uncertain Significance in PID genes in one out of five children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility.
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http://dx.doi.org/10.1093/cid/ciaa290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744985PMC
March 2020

Immunization stress-related response - Redefining immunization anxiety-related reaction as an adverse event following immunization.

Vaccine 2020 03 2;38(14):3015-3020. Epub 2020 Mar 2.

Department of Essential Medicines and Health Products (EMP), World Health Organization, Genève, Switzerland.

The Council for the International Organizations of Medical Sciences (CIOMS) and WHO working group on pharmacovigilance defines five cause specific AEFI which includes an immunization anxiety-related reaction. Historically this term has been used to describe a range of symptoms and signs that may arise after immunization that are related to "anxiety" about the immunization. However, the term "anxiety" does not adequately capture all the elements of this cause specific AEFI. In 2015, the Global Advisory Committee for Vaccine Safety convened an expert working group with the purpose of redefining, preventing and managing this particular AEFI. The term "Immunization Stress-Related Response" is proposed to replace the former terminology. We present a manual that redefines this AEFI and present a framework for prevention, diagnosis and management in both an individual and also when such events occur as clusters and affect multiple individuals. Since such mass events can result in cessation of immunization programmes and/or a loss of public confidence, a communication response is essential.
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http://dx.doi.org/10.1016/j.vaccine.2020.02.046DOI Listing
March 2020

The Susceptibility to Other Infectious Diseases Following Measles During a Three Year Observation Period in Switzerland.

Pediatr Infect Dis J 2020 06;39(6):478-482

From the Infectious Diseases and Vaccinology, University of Basel Children's Hospital, Basel, Switzerland.

Background: Measles virus infection leads to significant immunosuppression. In developing countries, this translates to an increased nonspecific mortality, whereas its effects in developed countries are less clear.

Methods: We performed a cohort study to investigate whether children hospitalized with measles (cases) between 2000 and 2015 in Switzerland would have a higher frequency of hospital admissions due to other infectious diseases thereafter than children who did not have measles (controls). Cases were identified by ICD-10 discharge diagnoses for measles and/or keyword search and matched to 2 controls by time of hospitalization, age and sex. All hospitalizations ≤3 years after original admission, infectious or noninfectious in origin, were identified in cases and controls.

Results: One hundred thirteen cases (56% males), mean age 9.0 years (range 2 weeks-17.8 years), and 196 controls were identified. Twelve rehospitalizations due to an infectious disease occurred in 11 cases and 6 in 6 controls (episode rates 0.106 versus 0.031 per person; ratio 3.47; 95% CI: 1.20-11.3; P = 0.012) in 3 years of follow-up. Of these, 9 and 3 occurred in cases and controls, respectively, during year 1 [ratio 5.20 (95% CI: 1.30-29.88; P = 0.012)]. Infectious diseases following measles affected various organ systems, were neither particularly severe nor fatal and revealed no specific pattern.

Conclusions: The increased risk for nonspecific infectious disease hospitalizations supports the concept of immunologic amnesia after measles. Universal immunization against measles provides additional benefit beyond protection against measles itself.
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http://dx.doi.org/10.1097/INF.0000000000002599DOI Listing
June 2020

Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review.

BMC Infect Dis 2020 Feb 13;20(1):136. Epub 2020 Feb 13.

Immunization Unit, Robert Koch Institute, Seestrasse 10, 13353, Berlin, Germany.

Background: Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy.

Methods: We searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach.

Results: We identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome.

Conclusion: Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented.

Trial Registration: PROSPERO CRD42018087814, CRD42018090357.
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http://dx.doi.org/10.1186/s12879-020-4824-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020352PMC
February 2020

Endocarditis Associated With Varicella-Case Report and Review of the Literature.

Front Pediatr 2019 4;7:500. Epub 2019 Dec 4.

Paediatric Infectious Diseases, Lucerne Children's Hospital, Cantonal Hospital Lucerne, Lucerne, Switzerland.

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 (or Group A Streptococcus, GAS), which colonizes epithelial surfaces, primarily of the throat and skin. In rare instances, varicella may also be associated with 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 endocarditis in children.
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http://dx.doi.org/10.3389/fped.2019.00500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904297PMC
December 2019

Coverage rates and timeliness of nationally recommended vaccinations in Swiss preschool children: A descriptive analysis using claims data.

Vaccine 2020 02 30;38(6):1551-1558. Epub 2019 Nov 30.

Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Spitalstrasse 26, CH-4031 Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Spitalstrasse 26, CH-4031 Basel, Switzerland; Boston Collaborative Drug Surveillance Program, MA 11 Muzzey St, Lexington, MA 02421, USA. Electronic address:

Background: Low vaccination coverage as well as incomplete and delayed vaccinations pose a risk for the individual and population protection from vaccine-preventable diseases.

Aim: To describe vaccination patterns for nationally recommended basic and supplementary vaccinations in Swiss preschool children.

Methods: We performed a descriptive study based on administrative claims data from a large Swiss health insurer (Helsana), in cohorts of children born between January 2010 and December 2016. We assessed coverage rates of nationally recommended basic vaccinations (i.e., diphtheria, tetanus, acellular pertussis [DTaP], Haemophilus influenzae type b [Hib], poliomyelitis [IPV], measles, mumps, and rubella [MMR]) and supplementary vaccinations (i.e., pneumococcal conjugate vaccine [PCV] and meningococcal group C conjugate vaccine [MCV]) for each birth cohort at the age of 13, 25, and 37 months. Additionally, we analysed timeliness of vaccinations using inverse Kaplan-Meier curves. Results were extrapolated to the Swiss population.

Results: The study population comprised 563,216 children. We observed continuously increasing coverage rates for all vaccinations until the 2015 birth cohort. Overall, up-to-date status for the first dose of studied vaccinations at 37 months was as follows: DTaP: 95.4%; Hib: 94.9%; IPV: 95.5%; MMR: 86.8%; PCV: 83.2%; and MCV: 66.7%. On average, however, only seven out of ten children had an up-to-date status for completed basic vaccinations; even less (six out of ten) were up-to-date for recommended supplementary vaccinations at 37 months of age. Moreover, 4% of all analysed children received none of the recommended vaccinations and there were substantial regional differences. Delays in vaccine administration were common. The most frequently postponed basic vaccination was MMR; 22.6% of children vaccinated with the first dose experienced delays relative to age-appropriate standards.

Conclusion: To avoid future outbreaks and transmission of vaccine-preventable diseases, vaccination coverage in Switzerland must be further improved. In addition, more emphasis should be placed on timely vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2019.11.057DOI Listing
February 2020

What Matters to Parents Regarding Immunization of Their Children: Systematic Analysis of Expert Advice to Parents in an Internet Forum.

Pediatr Infect Dis J 2020 02;39(2):157-163

From the Department of Infectious Diseases and Vaccinology, University of Basel Children's Hospital, Basel, Switzerland.

Background: World Health Organization announced vaccine hesitancy among the top 10 threats to global health in 2019. While the number of persons looking for information on health topics on the internet is increasing, information regarding immunization on the internet is often inaccurate and misleading. We aimed to determine the kind of information parents seek on the internet for decision-making regarding immunizations for their children.

Methods: We investigated threads of an internet vaccine forum, where parents can get personalized advice from a vaccine expert, with regard to the types of vaccines and content of the questions. One thousand six hundred twenty consultations (4896 questions) between September 2001 and December 2018 were examined. Of these, 1386, including 4000 questions, were related to immunizations of the user's child. Date of consultation, user gender and country of residence, age of the child; kind of vaccine(s), and topic of the question according to the following categories were analyzed: Vaccination schedule, safety, effectiveness, necessity, vaccine application, serology, exchangeability of different vaccine types and brands, maternally acquired immunity, reimbursement, and vaccine product related.

Results: Most questions concerned infants (47.7%) and regarded measles-component (28.9%) and diphtheria-tetanus-pertussis combination vaccines (25.3%). Parents were mainly interested in vaccination schedule (33.8%), safety (26.6%), and effectiveness (17.8%) of vaccines. Over time, safety-related questions decreased, and effectiveness related questions increased. Disease outbreaks or newly introduced vaccines and vaccinations temporarily raised interest. From 2011 onwards, most questions regarded measles-component vaccines.

Conclusions: Our findings will assist health care professionals and policy makers in preparing targeted information campaigns to address questions and counteract vaccine hesitancy.
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http://dx.doi.org/10.1097/INF.0000000000002509DOI Listing
February 2020

Advance system testing: Vaccine benefit studies using multi-country electronic health data - The example of pertussis vaccination.

Vaccine 2020 12 31;38 Suppl 2:B31-B37. Epub 2019 Oct 31.

VACCINE.GRID, Spitalstrasse 33, Basel, Switzerland; P95, Epidemiology and Pharmacovigilance, Leuven, Belgium; Julius Global Health, University Medical Center Utrecht, Heidelberglaan 100, the Netherlands. Electronic address:

The Accelerated Development of VAccine benefit-risk Collaboration in Europe (ADVANCE), a public-private consortium, implemented and tested a distributed network system for the generation of evidence on the benefits-risks of marketed vaccines in Europe. We tested the system by estimating the incidence rate (IR) of pertussis and pertussis-related complications in children vaccinated with acellular (aP) and whole-cell (wP) pertussis vaccine. Data from seven electronic databases from four countries (Denmark: AUH and SSI, Spain: SIDIAP and BIFAP, UK: THIN and RCGP RSC and Italy: Pedianet) were included in a retrospective cohort analysis. Exposure was defined as any pertussis vaccination (aP or wP). The follow-up time started 14 days after the first dose. Children who had received any pertussis vaccine from January 1990 to December 2015 were included (those who switched type, or had unknown type were excluded). The outcomes of interest were confirmed or suspected pertussis and pertussis-related pneumonia and generalised convulsions within one month of pertussis diagnosis and death within three months of pertussis diagnosis. The cohort comprised 2,886,367 children ≤5 years of age. Data on wP and aP vaccination were available in three and seven databases, respectively. The IRs (per 100,000 person-years) for pertussis varied largely and ranged between 0.15 (95% CI: 0.12; 0.19) and 1.15 (95% CI: 1.07; 1.23), and the trends over time was consistent with those observed from national surveillance databases for confirmed pertussis. The pertussis IRs decreased as the number of wP and aP vaccine doses increased. Pertussis-related complications were rare (89 pneumonia, 7 generalised convulsions and no deaths) and their relative risk (vs. non-pertussis) could not be reliably estimated. The study demonstrated the feasibility of the ADVANCE system to estimate the change in pertussis IRs following pertussis vaccination. Larger sample sizes would provide additional power to compare the risk for complications between children with and without pertussis. The feasibility of vaccine-type specific effectiveness studies may be considered in the future.
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http://dx.doi.org/10.1016/j.vaccine.2019.08.078DOI Listing
December 2020