Parental knowledge and attitudes to infant immunization in the context of RSV: All about confidence?

BACKGROUND: Recently, the first RSV vaccines have been approved, but vaccine hesitancy still poses great challenges to immunization programs. OBJECTIVE: To investigate this phenomenon in the context of the new RSV vaccines and an increased virus activity in 2022/23, we assessed parental knowledge and attitudes towards general childhood and RSV vaccines. METHODS: Parents of infants from 0-36 months completed an online questionnaire on demographics, socio-economic status, mental well-being, knowledge on RSV and perceptions of disease, attitudes to general childhood and RSV vaccines. The survey was conducted from February-June 2023 in the region of Regensburg, Germany. We compared continuous or categorical data with two-sided t-tests or Chi-square tests, respectively. Linear and logistic regression models were used to adjust for confounders. RESULTS: From 191 survey participants, 84 % had never refused any recommended vaccination and 91 % trusted their paediatrician's information. 11 % felt that children should have fewer vaccinations or rather get over the illness. Parents who were supportive or undecided about RSV vaccination were less likely to be vaccine hesitant in general (OR 0.03, p < 0.001; OR 0.13, p = 0.003). 58 % reported to have basic or good knowledge on RSV, correlating with a higher socioeconomic index (p = 0.049). 24 % were undecided about RSV immunization, while all parents rated its benefit high in the child's first year of life. Parents who refused RSV vaccination were less concerned about the infection compared to vaccine supporters (OR 0.44, p < 0.001). Parents with previously hospitalized (OR 3.88, p = 0.017) or preterm born children (OR 5.12, p = 0.026) were generally more concerned. CONCLUSION: Many factors influence parental decision-making leading to three main groups of attitudes: vaccine acceptors, refusers and hesitant but accessible parents. They (24%) represent the "target group" to increase vaccine uptake. Information on the vaccine-preventable disease reduces vaccine hesitancy, underlining the importance of healthcare professionals who remain an important source of trust.

Wearable Technologies for Pediatric Patients with Surgical Infections-More than Counting Steps?

Reliable vital sign assessments are crucial for the management of patients with infectious diseases. Wearable devices enable easy and comfortable continuous monitoring across settings, especially in pediatric patients, but information about their performance in acutely unwell children is scarce. Vital signs were continuously measured with a multi-sensor wearable device (Everion®, Biofourmis, Zurich, Switzerland) in 21 pediatric patients during their hospitalization for appendicitis, osteomyelitis, or septic arthritis to describe acceptance and feasibility and to compare validity and reliability with conventional measurements. Using a wearable device was highly accepted and feasible for health-care workers, parents, and children. There were substantial data gaps in continuous monitoring up to 24 h. The wearable device measured heart rate and oxygen saturation reliably (mean difference, 2.5 bpm and 0.4% SpO2) but underestimated body temperature by 1.7 °C. Data availability was suboptimal during the study period, but a good relationship was determined between wearable device and conventional measurements for heart rate and oxygen saturation. Acceptance and feasibility were high in all study groups. We recommend that wearable devices designed for medical use in children be validated in the targeted population to assure future high-quality continuous vital sign assessments in an easy and non-burdening way.

Insufficient Stability of Clavulanic Acid in Widely Used Child-Appropriate Formulations.

Amoxicillin-clavulanic acid (AMC) belongs to the WHO Essential Medicines List for children, but for optimal antimicrobial effectiveness, reconstituted dry powder suspensions need to be stored in a refrigerated environment. Many patients in low- and middle-income countries who are sold AMC suspensions would be expected not to keep to the specified storage conditions. We aimed to assess the stability of both ingredients in liquid formulations and dispersible tablets, combined with nationally representative data on access to appropriate storage. Degradation of amoxicillin (AMX) and clavulanic-acid (CLA) was measured in suspensions and dispersible tablets commercially available in Switzerland at different ambient temperatures (8 °C vs. 28 °C over 7 days, and 23 °C vs. 28 °C over 24 h, respectively). Data on access to refrigeration and electricity were assessed from the USAID-funded Demographic and Health Survey program. In suspensions, CLA degraded to a maximum of 12.9% (95% CI -55.7%, +29.9%) at 8°C and 72.3% (95% CI -82.8%, -61.8%) at a 28 °C ambient temperature during an observation period of 7 days. Dispersible tablets were observed during 24 h and CLA degraded to 15.4% (95% CI -51.9%, +21.2%) at 23 °C and 21.7% (-28.2%, -15.1%) at a 28 °C ambient temperature. There is relevant degradation of CLA in suspensions during a 7-day course. To overcome the stability challenges for all active components, durable child-appropriate formulations are needed. Until then, prescribers of AMC suspensions or pharmacists who sell the drug need to create awareness for the importance of proper storage conditions regarding effectiveness of both antibiotics and this recommendation should be reflected in the WHO Essential Medicines List for children.

Antimicrobial Resistance Following Azithromycin Mass Drug Administration: Potential Surveillance Strategies to Assess Public Health Impact.

The reduction in childhood mortality noted in trials investigating azithromycin mass drug administration (MDA) for trachoma control has been confirmed by a recent large randomized controlled trial. Population-level implementation of azithromycin MDA may lead to selection of multiresistant pathogens. Evidence suggests that repeated azithromycin MDA may result in a sustained increase in macrolide and other antibiotic resistance in gut and respiratory bacteria. Current evidence comes from standard microbiological techniques in studies focused on a time-limited intervention, while MDA implemented for mortality benefits would likely repeatedly expose the population over a prolonged period and may require a different surveillance approach. Targeted short-term and long-term surveillance of resistance emergence to key antibiotics, especially those from the World Health Organization Access group, is needed throughout any implementation of azithromycin MDA, focusing on a genotypic approach to overcome the limitations of resistance surveillance in indicator bacteria.

What Can We Do About Antimicrobial Resistance?

Antimicrobial resistance is of global concern, and preserving the ability of many antimicrobials to kill disease-causing bacteria is likely to become more challenging over time. However, we are speeding up this process dramatically by using antibiotics too much or in the wrong way. Respecting simple key principles of optimal antibiotic prescribing together with commitment to further research in this area from the pediatric community is essential to extend the lifeline of antibiotics for the most vulnerable patients without limiting access to antibiotics for those children who require treatment.

Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study.

RATIONALE: Acute viral respiratory tract infections in children with cystic fibrosis (CF) are known causes of disease exacerbation. The role of viral infections during infancy is, however, less known, although early infancy is thought to be a crucial period for CF disease development.We prospectively assessed symptomatic and asymptomatic viral detection in the first year of life in infants with CF and healthy controls. METHODS: In a prospective cohort study, we included 31 infants with CF from the Swiss Cystic Fibrosis Infant Lung Development Cohort and 32 unselected, healthy infants from the Basel Bern Infant Lung Development Cohort and followed them throughout the first year of life. Respiratory symptoms were assessed by weekly telephone interviews. Biweekly nasal swabs were analysed for 10 different viruses and two atypical bacteria with real-time seven duplex PCR (CF=561, controls=712). MEASUREMENTS AND RESULTS: Infants with CF and healthy controls showed similar numbers of swabs positive for virus (mean 42% vs 44%; OR 0.91, 95% CI 0.66 to 1.26, p=0.6). Virus-positive swabs were less often accompanied by respiratory symptoms in infants with CF (17% vs 23%; OR 0.64, 95% CI 0.43 to 0.95, p=0.026). This finding was pronounced for symptomatic human rhinovirus detection (7% vs 11%; OR 0.52, 95% CI 0.31 to 0.9, p=0.02). CONCLUSIONS: Viral detection is not more frequent in infants with CF and respiratory symptoms during viral detection occur even less often than in healthy controls. It is likely an interplay of different factors such as local epithelial properties and immunological mechanisms that contribute to our findings.

The spectrum of care for pediatric refugees and asylum seekers at a tertiary health care facility in Switzerland in 2015.

The aim of this retrospective study was to describe the epidemiology and spectrum of infections of admitted pediatric refugees and asylum seekers in a tertiary referral hospital in a high-income country in Europe. We identified recent refugees and asylum seekers < 18 years of age admitted to the University Children's Hospital in Basel, Switzerland, in 2015. A retrospective analysis was performed using electronic patient records. We identified 105 admissions in 93 patients with a median age of 5.7 (IQR 2.6-14.5) years. Eritrea, Syria, and Afghanistan were the most frequent countries of origin. The median duration of admission was 4 (IQR 2-6) days with infections and elective surgical interventions being the most common reason (54.8 and 16.1%, respectively). Most infections were airway, skin, and gastrointestinal in 46.4, 20.2, and 11.9%, respectively. The prevalence of tropical infections was 11.9%. The main pathogens identified were influenza A virus (13.8%), Staphylococcus aureus (10.3%), and rhino/enterovirus (10.3%). Previous medical non-infectious conditions were recorded in 13%. CONCLUSION: The study revealed a high burden of infections in admitted patients mostly caused by well-known pathogens prevalent also in the local population. Both tropical infections and pre-existing non-infectious conditions are also important in admitted patients. Better epidemiological data is required to optimize health care for this medically most vulnerable population in refugee crises. What is Known: • Pediatric refugees and asylum seekers are the most vulnerable population in refugee crises. • Data on health concerns and needs in this population is scarce. What is New: • This is one of the first studies on the epidemiology of pediatric refugees and asylum seekers treated as inpatients in a European high-income country. • The high burden of infections is mostly caused by well-known pathogens prevalent also in the local population.

Symptomatic Congenital Cytomegalovirus Infection in Children of Seropositive Women.

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.

Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants.

Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.

Rhinovirus Infections and Associated Respiratory Morbidity in Infants: A Prospective Cohort Study.

BACKGROUND: Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES: To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS: In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephonic interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS: Twenty-seven percent of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months [odds ratio (OR) = 1.71, P = 0.01, 95% confidence interval (CI): 1.13-2.61], outdoor temperatures between 5 and 10°C (OR = 2.33, P = 0.001, 95% CI: 1.41-3.86), older siblings (OR = 2.60, P = 0.001, 95% CI: 1.50-4.51) and childcare attendance (OR = 1.53, P = 0.07, 95% CI: 0.96-2.44). Fifty-one percent of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first 3 months of life (OR = 0.34, P = 0.003, 95% CI: 0.17-0.69) and in infants with atopic mothers (OR = 0.44, P = 0.008, 95% CI: 0.24-0.80). Increased tidal volume (OR = 1.67, P = 0.03, 95% CI: 1.04-2.68) and outdoor temperatures between 2 and 5°C (OR = 2.79, P = 0.02, 95% CI: 1.17-6.61) were associated with more symptoms. CONCLUSIONS: RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy or premorbid lung function.

CHI3L1 polymorphisms, cord blood YKL-40 levels and later asthma development.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1), the gene encoding YKL-40, and increased serum YKL-40 levels are associated with severe forms of asthma. It has never been addressed whether SNPs in CHI3L1 and cord blood YKL-40 levels could already serve as potential biomarkers for milder forms of asthma. We assessed in an unselected population whether SNPs in CHI3L1 and cord blood YKL-40 levels at birth are associated with respiratory symptoms, lung function changes, asthma, and atopy. METHODS: In a prospective birth cohort of healthy term-born neonates (n = 260), we studied CHI3L1 polymorphisms, and measured cord blood YKL-40 levels by ELISA in (n = 170) infants. Lung function was performed at 5 weeks and 6 years. Respiratory health during the first year of life was assessed weekly by telephone interviews. Diagnosis of asthma and allergic sensitisation was assessed at 6 years (n = 142). RESULTS: The SNP rs10399805 was significantly associated with asthma at 6 years. The odds ratio for asthma was 4.5 (95 % CI 1.59-12.94) per T-allele. This finding was unchanged when adjusting for cord blood YKL-40 levels. There was no significant association for cord blood YKL-40 levels and asthma. SNPs in CHI3L1 and cord blood YKL-40 were not associated with lung function measurements at 5 weeks and 6 years, respiratory symptoms in the first year, and allergic sensitisation at 6 years. CONCLUSION: Genetic variation in CHI3L1 might be related to the development of milder forms of asthma. Larger studies are warranted to establish the role of YKL-40 in that pathway.

Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

BACKGROUND: Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. OBJECTIVE: The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. METHODS: Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. RESULTS: Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. CONCLUSION: Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease.

The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.

Chitin, after cellulose, the second most abundant biopolymer on earth, is a key component of insects, fungi, and house-dust mites. Lower life forms are endowed with chitinases to defend themselves against chitin-bearing pathogens. Unexpectedly, humans were also found to express chitinases as well as chitinase-like proteins that modulate immune responses. Particularly, increased levels of the chitinase-like protein YKL-40 have been associated with severe asthma, cystic fibrosis, and other inflammatory disease conditions. Here, we summarize and discuss the potential role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.

False normal Lung Clearance Index in infants with cystic fibrosis due to software algorithms.

BACKGROUND: Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package. AIM: Our aim was to challenge the validity of these software algorithms. METHODS: We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement. RESULTS: In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P < 0.001). Healthy infants showed normal LCI values using both analysis methods (n = 47, paired t-test, P = 0.79). The most relevant reason for false normal LCI values in infants with CF using the automatic modus was the incorrect recognition of the end-of-test too early during the washout. CONCLUSION: We recommend the use of the manual modus for the analysis of MBW outcomes in infants in order to obtain more accurate results. This will allow appropriate use of infant lung function results for clinical and scientific purposes.

Human Rhinovirus Types and Association with Respiratory Symptoms During the First Year of Life.

Human rhinoviruses (HRV) cause respiratory infections and are associated with asthma development. We assessed HRV prevalence, types and association with respiratory symptoms in the first year of life in 20 unselected infants. HRV was detected in 32% of 825 weekly nasal swabs. Seventy-four different types of all three species were identified. HRV presence and related respiratory symptoms are highly heterogeneous.

Dynamics of the nasal microbiota in infancy: a prospective cohort study.

BACKGROUND: Understanding the composition and dynamics of the upper respiratory tract microbiota in healthy infants is a prerequisite to investigate the role of the microbiota in patients with respiratory diseases. This is especially true in early life, when the immune system is in development. OBJECTIVE: We sought to describe the dynamics of the upper respiratory tract microbiota in healthy infants within the first year of life. METHODS: After exclusion of low-quality samples, microbiota characterization was performed by using 16S rDNA pyrosequencing of 872 nasal swabs collected biweekly from 47 unselected infants. RESULTS: Bacterial density increased and diversity decreased within the first year of life (R(2) = 0.95 and 0.73, respectively). A distinct profile for the first 3 months of life was found with increased relative abundances of Staphlyococcaceae and Corynebacteriaceae (exponential decay: R(2) = 0.94 and 0.96, respectively). In addition, relative bacterial abundance and composition differed significantly from summer to winter months. The individual composition of the microbiota changed with increasing time intervals between samples and was best modeled by an exponential function (R(2) = 0.97). Within-subject dissimilarity in a 2-week time interval was consistently lower than that between subjects, indicating a personalized microbiota. CONCLUSION: This study reveals age and seasonality as major factors driving the composition of the nasal microbiota within the first year of life. A subject's microbiota is personalized but dynamic throughout the first year. These data are indispensable to interpretation of cross-sectional studies and investigation of the role of the microbiota in both healthy subjects and patients with respiratory diseases. They might also serve as a baseline for future intervention studies.

The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease.

The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothesized that YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in human and murine CF lung disease and (ii) to investigate whether YKL-40 single-nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein levels were quantified in serum and sputum supernatants from CF patients and control individuals. Levels of the murine homologue BRP-39 were analyzed in airway fluids from CF-like ßENaC-Tg mice. YKL-40SNPs were analyzed in CF patients. YKL-40 levels were increased in sputum supernatants and in serum from CF patients compared to healthy control individuals. Within CF patients, YKL-40 levels were higher in sputum than in serum. BRP-39 levels were increased in airways fluids from ßENaC-Tg mice compared to wild-type littermates. In both CF patients and ßENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39 levelsare increased in human and murine CF airway fluids, correlate with pulmonary function and modulate CF lung disease severity genetically. These findings suggest YKL-40 as a potential biomarker in CF lung disease.