Welcome to the ESPID 2022 Meeting Calendar

Backgrounds:

Only 10 of the 27 EU countries offer gender-neutral HPV-vaccination. In most of them, uptake is lower in boys than in girls. From the school year 2019-2020 onwards, the Flemish government offers gender-neutral free HPV-vaccination in the first year of secondary education, thereby including adolescent boys in its vaccination strategy. In 2021, a survey was performed using the WHO’s EPI-method to assess (among others) adolescent HPV-vaccination coverage in Flanders, Belgium.

Methods

A total of 955 adolescents (°2007) were recruited in 103 municipalities through a two-stage randomized cluster design. After signing informed consent, a parent/caregiver of the adolescent was interviewed at home or through video call (pandemic-dependent). Available documents on vaccination history of the child were transcribed and later completed with information from the electronic Flemish vaccination registry and medical records. The coverage of recommended vaccines in childhood and adolescence was assessed, including HPV-vaccination in boys and girls.

Results:

Overall, 854 adolescents received a first dose of the HPV vaccine (89.4%), and 771 received a second dose (80.7%). In girls, who have been offered HPV-vaccination since 2010, the coverage reached 92.3% and 84.3% for the first and second dose, respectively. Notably, 88.1% of boys in our cohort, who were the first to be offered HPV-vaccination, had received a first (p=0.05 vs. girls), and 78.4% a second dose (p<0.001 vs. girls).

Conclusions/Learning Points:

The first year after the implementation of HPV-vaccination in boys already spurred an immense uptake. The coverage for the first dose is only marginally below that of girls but comparable to that when girls were first offered the vaccine (87.5%). The planning of the second dose coincided with the first COVID-19 lockdown, which could have impacted its coverage.

Backgrounds:

Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of CNS infection in young infants. They have been implicated in neurodevelopmental delay, limited data are available. The aim of this study is to describe clinical outcome and to assess and compare medium-term neurodevelopment following EV and HPeV-CNS-infections.

Methods

A multicentre observational ambispective study was conducted between May-2013 and March-2018. Children under 3 months with EV or HPeV CNS-infection excluding encephalitis were included. Infants were contacted one year after acute infection. Their neurological development was evaluated using ASQ-3-test. If any area was abnormal during first round, a second round was completed later.

Results:

Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) EV and 15 (31.3%) HPeV. At first assessment 14/29 (48.3%) EV and 3/15 (20%) HPeV positive cases presented some developmental concern in the ASQ-3-test. EV-positive infants showed mild and moderate alteration in all domains analysed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (p=0.016). At second assessment 4/13 (30.8%) EV-positive patients showed mild to moderate concerns in communication and gross motor function and 3/13 (23.1%) showed significant concern in fine motor function.

Conclusions/Learning Points:

Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months, 48.3% of the EV-infected infants and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3-test. We recommend monitor neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation if necessary.

Backgrounds:

Shiga-toxin producing Escherichia coli (STEC) can cause mild to bloody diarrhea and Hemolytic Uremic Syndrome (HUS). The expansion whole-genome sequencing (WGS) allows to determine characteristics such as sequence-type and phylogenetic relationship. The National Children´s Hospital of Costa Rica is a tertiary referral hospital within the socialized medical care system. Here, we provide the results of the first genomic study of STEC in Costa Rica, based on a nationwide surveillance program.

Methods

Health records between 2015 and 2020 were reviewed for each patient using a standardized form to retrieve basic, demographic, microbiologic, molecular and clinical characteristics. All stool samples were analyzed by conventional culture techniques, automated antimicrobial susceptibility tests, end-point PCR and/or Filmarray GI Panel assays targeting STEC. WGS was performed using Illumina plattform. Bioinformatic analyses were performed using BioNumerics v7.6.3 software, SPAdes and BLAST. E. coli functional genotyping plugin v1.2 was used for prediction of virulence factors, antimicrobial resistance and O/H predictions. A dendrogram was constructed using the categorical values similarity coefficient and the unweighted pair group method with arithmetic mean (UPGMA). Geographical versus phylogenetic information was visualized using TreeTom.

Results:

29 out of 3768 (0,8%) diarrheal disease studies found STEC as causative agent. The most common features were: age less than 3 years (n=22;76%), bloody diarrhea (n=19;65%), eaeA gene (n=17;59%) stx1 gene (n=22;76%), sequence type ST17 (n=9;31%), serotype O118/O151:H2 (n=7;24%). Hospitalization was required for 6 patients (20%) and 2 developed SUH (7%).

Conclusions/Learning Points:

The first genomic study of STEC in Costa Rica provides valuable information about clinical, epidemiological and microbiological aspects of this disease in the pediatric population. The circulation of serotype O118/O151:H2 seems to be relatively high in comparison with other serotypes found. The HUS development among pediatric cases remain low.

Backgrounds:

Clinically, metagenomics have been most useful in the context of diseases that have poor diagnoses rates. Encephalitis is a prime example, where even in richly-resourced settings, the causative agent remains elusive in the majority of the cases. Here we present the results from 7 years of clinical metagenomics studies performed at the Great Ormond Street Hospital for Children, with samples obtained from in-patients and patients from around the UK and Europe.

Methods

Untargeted metagenomic DNA and RNA sequencing was performed for brain biopsies (fresh, frozen and FFPE) and CSF samples. Negative and positive sequencing controls were included in each sequencing run from 2017 onwards. Sequencing data preprocessing consisted of bioinformatic removal of low quality, low complexity and human sequences. Protein and nucleotide based similarity search was followed by probabilistic taxonomic classification with metaMix to infer the microorganisms present in the sample.

Results:

82 clinical samples from encephalitis patients were sequenced, consisting of 65 brain biopsies (11 FFPE, 54 fresh or frozen) and 17 CSF samples. Pathogens were detected in 24 samples, with no pathogens found in 48 samples. RNA was degraded in 10 samples. Immune system status was recorded for 49 patients (60% immunocompromised). In this subset of patients, we detected the causative pathogen in 13 cases, all immunocompromised patients. Finally, 18 tissue specimens from patients with other suspected infections were sequenced, resulting in similar rates of pathogen and no pathogen detection (39% each outcome, 12% RNA degraded).

Conclusions/Learning Points:

Metagenomics can play an important role in the management of hard to diagnose clinical syndromes, such as, but not limited to encephalitis. The effect is more striking in immunocompromised patients, as this is the patient population most at risk of infection with unexpected or novel microorganisms.

Backgrounds:

Previous studies applying Sepsis-3 criteria to pediatric sepsis were based on retrospective analyses of pediatric intensive care unit (PICU) cohorts. We aimed to validate organ dysfunction criteria in a population-based cohort of children with blood culture-proven infection, including emergency department, PICU, and ward patients.

Methods

National multi-center prospective cohort study of children <17 years with blood culture-proven sepsis between 1.9.2011 and 31.12.2015. We excluded preterm infants and neonates ≤7 days. We compared the 2005 International Pediatric Sepsis Consensus Conference (IPSCC), Pediatric Logistic Organ Dysfunction (PELOD)-2, pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Organ Dysfunction Information Update Mandate (PODIUM) scores measured on day of blood culture sampling to predict 30-day mortality using area under the receiver-operating characteristic curves (AUC). Conditional random forest analyses and generalized linear mixed model prediction were used.

Results:

We analyzed 877 sepsis episodes in 807 children, with a 30-day mortality of 4.3%. Presence of any organ dysfunction ranged from 32.7% (2005 IPSCC) to 55.3% (pSOFA). In adjusted analyses, the accuracy to predict mortality was highest for 2005 IPSCC (AUC 0.871, 95%CI: 0.819−0.924), followed by pSOFA (0.852; 95%CI: 0.784−0.92), PODIUM (0.852; 95%CI: 0.791−0.912), and PELOD-2 (0.827; 95%CI: 0.761−0.892). Neurologic, respiratory, and cardiovascular dysfunction were most predictive of 30-day mortality. Considering only these three organs adjusted AUC was 0.784 (0.70 - 0.868) for 2005 IPSCC and 0.771 (0.684-0.857) for PODIUM, while pSOFA (0.734; 0.641-0.828) and PELOD-2 (0.724; 0.627-0.822) had lower performances.

Conclusions/Learning Points:

When comparing scores for organ dysfunction, 2005 IPSCC performed best, followed by pSOFA and PODIUM criteria. Although the accuracy between scores was comparable, we observed major differences in terms of classification of individual organ dysfunctions. Our findings confirm the importance of neurologic, respiratory, and cardiovascular dysfunction.

Backgrounds:

Febrile seizures are the most common cause of seizure in childhood.They occur in the presence of a fever (>38 degrees Celsius) in children aged between 6 months and 5 years. Viruses are well-described as the predominant causative agents and specific viruses have previously been implicated, including Human Herpesvirus-6 (HHV-6),Influenza A and B, Respiratory syncytial virus (RSV), Parainfluenza, Adenovirus, Rhinovirus and Enterovirus.

Recent innovations in viral respiratory molecular diagnostics allow multiple viruses to be tested simultaneously using multiplex polymerase chain reaction (PCR). SNOTWATCH is a de-identified ecologic analysis platform capturing population level molecular diagnostic results together with hospital and primary care encounters. This project aims to utilise PCR data to understand the relationship between respiratory virus circulation and febrile seizures at a population level. We have created a novel statistical model for assessing these relationships in both time and space.

Methods

Our ecological study assessed relationships between presentations of febrile seizures and nine respiratory viruses detected at the largest hospital network in Melbourne, Australia, from 2010-2019. Associations were studied temporally and spatiotemporally through mixed-effects Poisson regression analysis, using monthly incidence of febrile seizures and positive PCR tests.

Results:

Febrile seizure incidence peaked in June-September each year. Temporal analysis showed febrile seizures were significantly associated with Human metapneumovirus (1.19 RR), Influenza A (1.49 RR), Influenza B (1.33 RR) and RSV (1.52 RR) (Figure 1). Spatiotemporal analysis supported the association between febrile seizures and Influenza A, Influenza B and RSV (1.25, 1.12 and 1.20 RR respectively, p<0.0

Conclusions/Learning Points:

With over 90,000 PCR results and almost 5,000 febrile seizure presentations, our findings confirm the importance of understanding viral circulation patterns and their implications for paediatric health outcomes. Our statistical method may be used in predictive modelling to inform public health policy.

Backgrounds:

Half of new sexual transmitted infections(STI) occur in adolescents, due to poor sexual education and less awareness of disease, leading to risk behaviours. Our aims were to describe the identified STI and estimate their incidence in patients younger than 18-years attended in our hospital over the last 7 years.

Methods

Retrospective descriptive study, including all STI diagnosed in our tertiary hospital in Madrid between 2015-2021. Two periods were compared: A(2015-2017) and B(2018-2021, excluding 2020 due to COVID-19-lockdown).

Epidemiological-clinical data were collected from medical history. Microbiological tests were performed according to symptoms or medical history and they included: PCR for N.gonorrhoeae(NG) and C.trachomatis(CT) in urethral/urine samples, PCR for herpes-simplex-2(HSV-2) or human papillomavirus(HPV) in scraped samples and serological tests for HIV and syphilis.

Results:

There were 58 STI diagnosed: 33 CT, 20 NG, 2 HSV-2, 2 syphilis(one HIV-infected) and 1 HPV, in 44 adolescents. Median age at diagnosis was 17.0years (IQR16.0-17.6); 25(56%) were female. There were 14 coinfections(CT-NG). CT was isolated more frequently in female(22 vs 11, p:0.02) while NG was in males(12 vs 8, p:0.03).

One third of patients were asymptomatic and diagnosed after reporting sexual risk behaviour. All HSV-2 and HPV were tested due to consistent skin lesions. All infections were treated at the emergency room. Three girls required hospitalization due to pelvic inflammatory disease.

The estimated incidence of STI in patients in period A was 0.51 per 1000-patients-years compared to 0.67 per 1000-patients-years in period B (p:0.36).

Conclusions/Learning Points:

C. trachomatis and N. gonorrhoeae are the main STI diagnosed in adolescents in our setting, but other preventable severe STI occurred. Asymptomatic infections were common as well as co-infections. Paediatricians should be familiar to these infections, which may increase in the following years.

Backgrounds:

Invasive pneumococcal diseases (IPDs) are severe diseases in children. Host genetic factors are implicated in susceptibility and severity of IPDs. Further understanding of the molecular factors involved in the development of these severe infections could lead to better treatment, prevention, and thus better outcome. Previous studies identified several candidate genes for IPDs, however, mostly because of methodological shortcomings, these results are yet to be confirmed. Our study aimed to identify rare coding genetic variants implicated in the development of IPDs using whole-exome sequencing of 32 children admitted in pediatric intensive care unit for IPD.

Methods

Contrary to most previous studies related to IPDs, we chose an untargeted approach to find novel variants. We developed a bioinformatic analysis pipeline to identify rare, non-synonymous and possibly pathogenic variants implicated in IPDs. Furthermore, we compared the number of variants observed in our 32 patients to an unrelated control population (n=69) to validate our pipeline and discoveries.

Results:

We identified 86 rare variants at heterozygous state in 18 different genes. The control population presented significantly fewer variants (p=7.6x10^-16) in fewer genes (p=5.5x10^-16). We could, with variants from 6 of these 18 genes, build a highly predictive model perfectly separating cases and controls.

Conclusions/Learning Points:

Our results revealed multiple heterozygous variants in a restricted set of genes for each patient presenting an extreme phenotype of pneumococcal disease, emphasizing the likely polygenicity of IPD risk. In conclusion, these first results suggest an unprecedented immune deficiency involving the association of several rare mutations in immune-related genes. These results may be used to predict the individual risk of children to present IPDs. We will pursue our efforts in characterizing this risk by reproducing our findings with other populations of children with IPDs.

Backgrounds:

In children with intestinal failure on parenteral nutrition (PN), central-line associated bloodstream infections (CLABSI) are the most common complication. The aims of our study were to evaluate rates of CLABSI in children on long-term PN, to establish predisposing risk factors and the efficacy of taurolidine prophylaxis in reducing CLABSI incidence.

Methods

A 3-years prospective cohort study was performed at the Centre for Pediatrics Artificial Nutrition of University of Naples “Federico II”. The primary outcome was the rate of CLABSI/1000 CL-days. Data of all children on PN in follow up were used to calculate the numerator and adjust infection rates.

Results:

Eighteen children on PN were included in the study (13 male, median age of 91,5 months): 8 (45%) with short bowel syndrome, 6 (33%) with intestinal motility disorders, 4 (22%) with congenital enteropathies. Nine have a gastro/enterostomy. During the period of observation, 28 episodes of CLABSI were reported in 10 patients, 6 of which had more than one CLABSI, resulting in a CLABSI rate of 1.65/1000 CVC days [95%CI 1.13-2.38]. Coagulase Negative Staphylococci were the most isolated pathogens (59%). Four cases of S.Aureus-related CLABSI were successfully treated with antibiotics without CL removal. Gram-negative pathogens were only isolated in patients with enterostomy.The presence of a primary non-surgical enteropathy was associated with a recurrence of CLABSI (p= 0,007).The rate of CLABSI was slightly reduced in children receiving taurolidine (1.51/1000 CL-days [95% CI 0.97-2.34]) compared to those receiving standard care (2.45 [95% CI 1.22-4.89]).

Conclusions/Learning Points:

Infections are a major cause of morbidity in children undergoing PN. Primary gut diseases are associated with CLABSI incidence and recurrence. Larger study is needed to analyze the impact of taurolidine prophylaxis.