Population density profiles of nasopharyngeal carriage of 5 bacterial species in pre-school children measured using quantitative PCR offer potential insights into the dynamics of transmission.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBacterial vaccines can reduce carriage rates. Colonization is usually a binary endpoint. Real time quantitative PCR (qPCR) can quantify bacterial DNA in mucosal samples over a wide range. Using culture and single-gene species-specific qPCRs for Streptococcus pneumoniae (lytA), Streptococcus pyogenes (ntpC), Moraxella catarrhalis (ompJ), Haemophilus influenzae (hdp) and Staphylococcus aureus (nuc) and standard curves against log-phase reference strain broth cultures we described frequency and peak density distributions of carriage in nasopharyngeal swabs from 161 healthy 2-4 y old children collected into STGG broth. In general, detection by qPCR and culture was consistent. Discordance mostly occurred at lower detection thresholds of both methods, although PCR assays for S. pyogenes and S. aureus were less sensitive. Density varied across 5-7 orders of magnitude for the 5 species with the abundant species skewed toward high values (modes: S. pneumoniae log3-4, M. catarrhalis & H. influenzae log4-5 CFU/ml broth). Wide ranges of bacterial DNA concentrations in healthy children carrying these bacteria could mean that different individuals at different times vary greatly in infectiousness. Understanding the host, microbial and environmental determinants of colonization density will permit more accurate prediction of vaccine effectiveness.ESPID research fellowshi

The Effects of LAIV on Nasopharyngeal Bacteria in Healthy 2-4 Year Olds:a Randomized Controlled Trial

Rationale: Viral infections of the upper respiratory tract may influence the commensal nasopharyngeal bacteria. Changes in the bacterial niche could affect transmission dynamics. Attenuated vaccine viruses can be used to investigate this empirically in humans. Objectives: To study the effects of mild viral upper respiratory infections on nasopharyngeal bacterial colonization using live attenuated influenza vaccine (LAIV) as a surrogate. Methods: We used trivalent LAIV to evaluate the effects of viral infection on bacterial carriage and density of Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Staphylococcus aureus. A total of 151 healthy children were randomized 1:1 to receive the vaccine starting either at recruitment (n = 74) or 28 days later (n = 77) in a stepped wedge fashion, allowing comparisons between recipients and nonrecipients as well as whole-group comparisons pre- and postvaccination. Bacterial carriage and density were determined using quantitative polymerase chain reaction assays. Measurements and Main Results: A total of 151 children were recruited, 77 in the LAIV group and 74 in the control group. LAIV recipients (n = 63 analyzed) showed an apparent transient increase in H. influenzae carriage but no further significant differences in carriage prevalence of the four bacterial species compared with controls (n = 72 analyzed). S. pneumoniae density was substantially higher in vaccine recipients (16,687 vs. 1935 gene copies per milliliter) 28 days after the first dose (P < 0.001). Whole-group multivariable analysis (prevaccine, after one dose, and after two doses) also showed increases in density of other species and H. influenzae carriage prevalence. Conclusions: In the absence of any safety signals despite widespread use of the vaccine, these findings suggest that bacterial density, and thus transmission rates among children and to people in other age groups, may rise following attenuated influenza infections without associated clinical disease. LAIV could therefore be used as an experimental tool to elucidate the dynamics of transmission of nasopharyngeal bacteria

High Density Bacterial Nasal Carriage in Children is Transient and Associated With Respiratory Viral Infections - Implications for Transmission Dynamics

To access publisher's full text version of this article click on the hyperlink belowBACKGROUND: This longitudinal study describes the associations between respiratory viral infections, rhinitis and the prevalence and density of the common nasopharyngeal bacterial colonizers, Streptococcus pneumoniae (Sp), Moraxella catarrhalis (Mc), Haemophilus influenzae (Hi) and Staphylococcus aureus. METHODS: In an observational cohort study, 161 children attending day care centers in Bristol, United Kingdom, were recruited. Monthly nasopharyngeal swabs were taken and stored frozen in Skim-milk, tryptone, glucose and glycerin broth (STGG) broth. Quantitative polymerase chain reaction was used for detection of respiratory viruses and 4 bacterial species. t tests and logistic regression models were used for analysis. RESULTS: The frequent colonisers, Sp, Mc and Hi were more frequently found at high density in contrast to Staphylococcus aureus although temporally, high-density carriage was short lived. Respiratory viral infections and symptoms of rhinitis were both independently and consistently associated with higher bacterial density with an observed 2-fold increase in density for Sp, Mc and Hi (P = 0.004-0.017). CONCLUSIONS: For Sp and Hi, the association between young age and higher bacterial DNA density was explained by more frequent viral infection and increased nasal discharge, while the associations between some viral specie's and some bacterial species' density appear to be stronger than others. Increased colonization density and rhinitis may promote transmission of these commonly carried organisms

Decreasing death rates and causes of death in Icelandic children-A longitudinal analysis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Global death rate in children has been declining during the last decades worldwide, especially in high income countries. This has been attributed to several factors, including improved prenatal and perinatal care, immunisations, infection management as well as progress in diagnosis and treatment of most diseases. However, there is certainly room for further progress. The aim of the current study was to describe the changes in death rates and causes of death in Iceland, a high-income country during almost half a century. Methods: The Causes of Death Register at The Directorate of Health was used to identify all children under the age of 18 years in Iceland that died during the study period from January 1st, 1971 until December 31st, 2018. Using Icelandic national identification numbers, individuals could be identified for further information. Hospital records, laboratory results and post-mortem diagnosis could be accessed if cause of death was unclear. Findings: Results showed a distinct decrease in death rates in children during the study period that was continuous over the whole period. This was established for almost all causes of death and in all age groups. This reduction was primarily attributed to a decrease in fatal accidents and fewer deaths due to infections, perinatal or congenital disease as well as malignancies, the reduction in death rates from other causes was less distinct. Childhood suicide rates remained constant. Interpretation: Our results are encouraging for further prevention of childhood deaths. In addition, our results emphasise the need to improve measures to detect and treat mental and behavioural disorders leading to childhood suicide

Periodic fever in MVK deficiency: a patient initially diagnosed with incomplete Kawasaki disease.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Mevalonate kinase deficiency (MKD) is a rare autosomal recessive disorder causing 1 of 2 phenotypes, hyperimmunoglobulin D syndrome and mevalonic aciduria, presenting with recurrent fever episodes, often starting in infancy, and sometimes evoked by stress or vaccinations. This autoinflammatory disease is caused by mutations encoding the mevalonate kinase (MVK) gene and is classified in the group of periodic fever syndromes. There is often a considerable delay in the diagnosis among pediatric patients with recurrent episodes of fever. We present a case of an 8-week-old girl with fever of unknown origin and a marked systemic inflammatory response. After excluding infections, a tentative diagnosis of incomplete Kawasaki syndrome was made, based on the finding of dilated coronary arteries on cardiac ultrasound and fever, and she was treated accordingly. However, the episodes of fever recurred, and alternative diagnoses were considered, which eventually led to the finding of increased excretion of mevalonic acid in urine. The diagnosis of MKD was confirmed by mutation analysis of the MVK gene. This case shows that the initial presentation of MKD can be indistinguishable from incomplete Kawasaki syndrome. When fever recurs in Kawasaki syndrome, other (auto-)inflammatory diseases must be ruled out to avoid inappropriate diagnostic procedures, ineffective interventions, and treatment delay

Pneumococcal Serotypes Colonise the Nasopharynx in Children at Different Densities.

Prevalence of pneumococcal serotypes in carriage and disease has been described but absolute serotype colonisation densities have not been reported. 515 paediatric nasal swab DNA extracts were subjected to lytA qPCR and molecular serotyping by microarray. Absolute serotype densities were derived from total pneumococcal density (qPCR cycle threshold and standard curve) and relative abundance (microarray) and varied widely. Compared to all serotype densities observed, the strongest evidence of differences was seen for serotypes 21 and 35B (higher) and 3, 38 and non-typeables (lower) (p<0.05) with a similar hierarchy when only a single serotype carriage was assessed. There was no evidence of any overall density differences between children with single or multiple serotypes detected but serotypes with mid-range densities were more prevalent. The hierarchy of distinct pneumococcal serotype carriage densities described here for the first time, may help explain the dynamics of transmission between children

Parental views on childhood influenza vaccination.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pag

No One Will be Safe Until Our Children are Safe: Parent's Attitude Towards COVID-19 Childhood Immunization.

To access publisher's full text version of this article click on the hyperlink belo

Low Risk of Central Line-associated Bloodstream Infections in Pediatric Hematology/Oncology Patients.

Icelandic Cancer Society, Reykjavik, IcelandBackground: Central venous lines (CVLs) are essential for standard care of pediatric hematology/oncology patients providing safe administration of cytotoxic drugs and pain-free blood sampling. Central line-associated bloodstream infections (CLABSIs) cause significant morbidity. This study describes the epidemiology, microbiology, and risk factors for CLABSI in all children with malignancies in Iceland. Methods: All children that were diagnosed with malignancy in Iceland and received a CVL during 2008-2017 were included in the study. Characteristics of CVLs and patients were registered, information on risk factors, and microbiology was collected. International standards were used for CLABSI definition. Results: One hundred forty-three CVLs were placed in 94 children. Acute lymphoblastic leukemia was the most common underlying disease (31/94). Median age was 7 years. Implantable ports were the most commonly placed CVLs (82/143, 57%), tunneled lines were 39 (27%). Overall CLABSI rate was 0.24 infections/1000 line-days (14 episodes in 58,830 line-days), with little fluctuations. No CLABSI episodes occurred for 4 consecutive years (2012-2015). Staphylococci (of which 7 Staphylococcus aureus) were the cause of 10/14 episodes. Nine CLABSI episodes led to line removal, but no deaths were linked to CLABSIs. Conclusion: We report very low CLABSI rates over a 9-year period at our hospital, with 4 consecutive CLABSI-free years. Even with the addition of episodes of possible CLABSI, rates were still very low and lower than most published reports