Genetics and measles, mumps and rubella vaccine response in childhood and adolescence-A systematic review.

Measles, mumps and rubella (MMR) are contagious infectious diseases that can be prevented by immunization. However, MMR infections can occur in previously immunized individuals. The vaccine response is, among other factors, influenced by the combined effects of many genes. This systematic review investigates the genetic influence on measles, mumps and rubella antibody responses after childhood vaccination. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), systematic literature searches were conducted in the medical databases PubMed, EMBASE and PsycINFO. Search strings were adjusted for each database. Citations were included if they measured and compared the immune response with immunogenetics after vaccination with a vaccine containing one or more of the following components: measles, mumps and/or rubella, MMR. The measure of vaccine response studied was antibodies after vaccination. Forty-eight articles were included in the final analysis. The results suggest that genetic determinants, including host genes, and single nucleotide polymorphisms in immune-related genes influence the MMR antibody responses after vaccination. Specifically, replicated associations were found between HLA, CD46, RARB, IRF9, EIF2AK2, cytokine genes and MMR vaccine-induced humoral immune responses. This knowledge can be useful in understanding and predicting immune responses and may have implications for future vaccine strategies.

Surgical procedures in Danish children 1999-2018.

OBJECTIVE: To assess if the overall utilisation of surgery in Danish children 0-5 years of age increased in the period 1999-2018 in line with the development within specialised medical services. The epidemiology on surgical procedures is scarce. METHODS: National register-based cohort study of all Danish children born 1994-2018 (n = 1,599,573) using data on surgery in public and private hospitals from The National Patient Register and data on surgery in private specialist practice from The Health Service Register. Incidence rate ratios were calculated using Poisson regression with 1999 as the reference year. RESULTS: During the study period 115,573 different children (7.2% of the cohort) underwent surgery. The overall incidence of surgical procedures was stable, but the use of surgery increased in neonates mainly due to an increase in frenectomy. Boys underwent more surgery than girls. In children with severe chronic disease the rate of surgery decreased in public hospitals and increased in private specialist practices. CONCLUSION: The utilisation of surgical procedures in Danish children 0-5 years of age did not increase from 1999 to 2018. The use of available register data in the present study may inspire surgeons to conduct further studies to enhance the knowledge within the area of surgical procedures.

Respiratory syncytial virus and influenza hospitalizations in Danish children 2010-2016.

OBJECTIVE: To pave the way for universal or risk factor-based vaccination strategies, the present study aimed to describe the epidemiology and compare risk factors for hospitalization associated with respiratory syncytial virus (RSV) and influenza virus infections in Danish children. METHODS: National register-based cohort study among 403,422 Danish children born 2010-2016. RESULTS: Prior asthma hospitalization, number of children in the household, chronic disease and maternal history of asthma hospitalization were the most important risk factors for both RSV and influenza hospitalization. The incidence of influenza increased at school start. CONCLUSIONS: Our findings enable targeted vaccination programs for high-risk children with asthma-like disease, chronic disease, siblings in the household, or maternal history of asthma hospitalization.

Risk Factors for Hospitalization for Respiratory Syncytial Virus Infection: A Population-based Cohort Study of Danish Children.

BACKGROUND: The aim of this study is to identify the risk factors for hospitalization for respiratory syncytial virus (RSV) infection in Danish children. METHODS: This is a population-based cohort study with follow-up till 24 months of age. A total of 421,943 Danish children were divided into 5 groups based on gestational age (23-32, 33-35, 36, 37-41 and 42-45 weeks). RESULTS: In adjusted Cox regression models, chronic disease, asthma hospitalization before the RSV infection and siblings were associated with an increased risk of hospitalization for RSV infection in all children independent of gestational age. Plurality was associated with a decreased risk in children born between 23 and 36 weeks of gestation, whereas young maternal age, maternal asthma, single parenthood, maternal smoking, being born small for gestational age, Caesarian section, male gender and day care were associated with an increased risk of hospitalization for RSV infection in term children. In postterm children, young maternal age, male sex, being born small for gestational age and maternal smoking were associated with an increased risk of hospitalization for RSV. Asthma hospitalization before the RSV infection and siblings were associated with the highest measures of increased risk of hospitalization for RSV infection independent of gestational age. CONCLUSIONS: By 5 groups of gestational age, we provide estimates of the effects of 12 different factors, which can be regarded as add-on risk factors to those already known to increase the risk of hospitalization for RSV infection. Our study may help clinicians to precisely assess the risk profile in the individual child.

Disappointment and adherence among parents of newborns allocated to the control group: a qualitative study of a randomized clinical trial.

BACKGROUND: When a child participates in a clinical trial, informed consent has to be given by the parents. Parental motives for participation are complex, but the hope of getting a new and better treatment for the child is important. We wondered how parents react when their child is allocated to the control group of a randomized controlled trial, and how it will affect their future engagement in the trial. METHODS: We included parents of newborns randomized to the control arm in the Danish Calmette study at Rigshospitalet in Copenhagen. The Calmette study is a randomized clinical trial investigating the non-specific effects of early BCG-vaccine to healthy neonates. Randomization is performed immediately after birth and parents are not blinded to the allocation. We set up a semi-structured focus group with six parents from four families. Afterwards we telephone-interviewed another 19 mothers to achieve saturation. Thematic analysis was used to identify themes across the data sets. RESULTS: The parents reported good understanding of the randomization process. Their most common reaction to allocation was disappointment, though relief was also seen. A model of reactions to being allocated to the control group was developed based on the participants' different positions along two continuities from 'Our participation in trial is not important' to 'Our participation in trial is important', and 'Vaccine not important to us' to 'Vaccine important to us'. Four very disappointed families had thought of getting the vaccine elsewhere, and one had actually had their child vaccinated. All parents involved in the focus group and the telephone interviews wanted to participate in the follow-ups planned for the Calmette study. CONCLUSIONS: This study identified an almost universal experience of disappointment among parents of newborns who were randomized to the control group, but also a broad expression of understanding and accepting the idea of randomization. The trial staff might use the model of reactions in understanding the parents' disappointment and in this way support their motives for participation. A generalized version might be applicable across randomized controlled trials at large. TRIAL REGISTRATION: The Calmette study is registered in EudraCT (https://eudract.ema.europa.eu/) with trial number 2010-021979-85.

Neonatal bloodstream infections in a pediatric hospital in Vietnam: a cohort study.

Septicemia and bloodstream infections (BSIs) are major causes of neonatal morbidity and mortality in developing countries. We prospectively recorded all positive blood cultures (BSI) among neonates admitted consecutively to a tertiary pediatric hospital in Vietnam during a 12-month period. Among 5763 neonates, 2202 blood cultures were performed, of which 399 were positive in 385 neonates. Among these, 64 died, 62 in relation to septicemia. Of the BSI isolates, 56% was known pathogenic and 48% was gram-negative bacteria, most frequently Klebsiella spp. (n = 78), Acinetobacter spp. (n = 58) and Escherichia coli (n = 21). Only three Streptococcus spp. were identified, none group B. Resistance against antibiotics applied was common. The mortality was highest in neonates with gram-negative BSI compared with no confirmed BSI and gram-positive BSI (P < 0.01). In this setting, the majority of BSI were likely to have been transmitted from the environment. Improvement of hygienic precautions and systematic BSI surveillance are recommended.