Welcome to the ESPID 2021 Meeting Calendar

Background

It is not known whether very young children contribute to the transmission of COVID-19. Determining the seroprevalence of antibodies against SARS-CoV-2 in daycare centres that remained open for key workers’ children during a period of lockdown might provide data in this respect.

Methods

Between June 4^th and July 3^rd, 2020, children and staff having attended one of 22 daycare centres during France’s nationwide lockdown (from March 15^th to May 9^th, 2020) were prospectively included. Hospital staff not occupationallyexposed to patients and/or children were enrolled in a comparator group. The presence of anti-SARS-CoV-2 antibodies in capillary whole blood was determined using a rapid chromatographic immunoassay. We computed the raw prevalence as the percentage of individuals with a positive IgG or IgM test, and used Bayesian smoothing to account for imperfect assay sensitivity and specificity.

Results

We enrolled 327 children (mean ± standard deviation age: 1.9 ± 0.9 years), 197 daycare staff, and 164 adults in the comparator group. Positive serological tests were observed for 14 children (raw prevalence [95% confidence interval] = 4.3% [2.6, 7.1]) and 14 daycare staff (7.7% [4.2, 11.6]). After accounting for imperfect assay sensitivity and specificity, we estimated that 3.7% (95% credible interval [1.3, 6.8]) of the children and 6.8% [3.2, 11.6] of the staff had been infected with SARS-CoV-2. The comparator group fared similarly to the daycare staff with 5.5% [2.9, 10.1] testing positive leading to 5.0% [1.6, 9.8] infection rate after accounting for assay characteristics (p=0,53). An exploratory analysis suggested that seropositive children were more likely than seronegative children to have been exposed to an adult household member with confirmed COVID-19 infection (43% vs. 6%, respectively, RR=7.1 [2.2, 22.4]).

Conclusions

According to serological test results, the proportion of infected children was low. Intrafamily transmission seemed more plausible than transmission within daycare centres.

Clinical Trial Registration

ClinicalTrials.gov 04413968

Background

Limited evidence suggests that scar formation after bacille Calmette-Guérin (BCG) immunisation is associated with lower all-cause mortality but does not correlate with protection against tuberculosis. The aim of this post-hoc analysis was to evaluate the association between BCG scar characteristics and the mycobacterial-specific immune response.

Methods

208 infants in Australia were randomised to receive one of three BCG vaccine strains at birth (BCG-Denmark, n=53; BCG-Japan, n=55; or BCG-Russia, n=56) or at 2 months of age (BCG-Denmark, n=44). The size and characteristics of BCG scars were assessed 10 weeks after immunisation. At the same time point, intracellular cytokine secretion (IFNg, IL-2 and TNF) in whole blood assays following in-vitro stimulation with M. tuberculosis, M. ulcerans, PPD and BCG was determined using multi-colour flow cytometry. The relationship between BCG scar characteristics and immunological responses was analysed.

Results

Proportions of single, double, and triple antigen-specific cytokine-producing CD4⁺ T-cells were significantly higher in children who developed a BCG scar compared to those without a scar. The magnitude of the immune response correlated with the size and characteristic of the BCG scar (Figure), even after adjusting for BCG vaccine strain and timing of immunisation in a mixed model analysis.

Conclusions

BCG scar formation is associated with higher mycobacteria-specific T-cell responses. As T-cell responses are important in the immune response against TB, the relationship between BCG scar formation and protection against TB should be explored further.

Clinical Trial Registration

Australian clinical trials registration number: ACTRN12608000227392

Background

Hemolytic uremic syndrome (HUS) is typically a complication of enterocolitis from Shiga toxin-producing Escherichia coli. Streptococcus pneumoniae-associated HUS (SP-HUS) is less frequent, accounting for ~5% of HUS cases in children. This study describes the epidemiology of pediatric SP-HUS in Canada.

Methods

The Canadian Immunization Monitoring Program, ACTive (IMPACT) is a national, sentinel surveillance network for vaccine-preventable diseases. It includes 12 pediatric hospitals and ~90% of tertiary care pediatric beds across Canada. All IMPACT invasive pneumococcal disease (IPD) cases from 1991-2019 were retrospectively analyzed to describe SP-HUS occurrence according to pneumococcal conjugate vaccine (PCV13) history and SP serotype. Fisher’s Exact Test compared serotype prevalence among SP-HUS and non-HUS IPD cases.

Results

From total 6,757 IPD cases, 30 SP-HUS cases (0.44%) were identified. Among SP-HUS patients with known serotypes (25/30), serotypes 3 (9/25, 36%) and 19A (32%) were more prevalent in SP-HUS cases than in non-HUS IPD cases (p<0.01).

PCV13 serotypes occurred in 88% (22/25) of SP-HUS cases, of which 77% (17/22) occurred pre-PCV13 availability. Among the 5 SP-HUS cases occurring post-PCV13, 1 was not immunized and became ill with a vaccine preventable serotype, 1 had unknown vaccine history, and 3 were vaccine failures including serotypes 3 (n=2) and 19A (n=1).

Conclusions

Two PCV13 serotypes (3, 19A) were significantly more prevalent in SP-HUS cases compared to non-HUS IPD and were identified in all vaccine failure SP-HUS cases. Future study will examine if serotypes 3 and 19A are also more prevalent among SP-HUS cases in other geographic regions and if PCV13 is less effective against these serotypes. Further research will also identify vaccine failures in non-HUS IPD cases and compare them to those of SP-HUS.

Background

Mycoplasma pneumoniae (Mp) is a frequent cause of community-acquired pneumonia (CAP) in children. In addition, Mp can cause extrapulmonary disease, including mucocutaneous manifestations, or can be carried in the respiratory tract without causing any symptoms. Factors leading to the wide range of clinical outcomes associated with Mp infection are unclear. We investigated whether a specific genotype is associated with Mp virulence.

Methods

This is a prospective cohort study of Mp polymerase chain reaction-positive children, 3–18 years of age, with CAP (n=25), Mp-induced mucocutaneous disease (n=8), and without symptoms (carriers, n=6) from 2016–2017, from which respiratory specimens and/or Mp DNA extracts were available for extensive molecular characterization. In addition, Mp strains of their family members with respiratory tract infection (n=8) from 2016–2017, and children with Mp-induced mucocutaneous disease (n=7) during 2017–2020 were analyzed. Genotyping was performed using macrolide resistance determination, P1 subtyping, multilocus variable-number tandem-repeat analysis (MLVA), and multilocus sequence typing (MLST). Categorical and continuous variables were compared with the Fisher exact test and Mann-Whitney U test or pairwise Wilcoxon rank sum test with corrections for multiple testing, as appropriate.

Results

During the 2016–2017 study period, P1 subtype 1 (ST1) and 2 (ST2) were equally detected, but ST2 dominated in the first 6 months (n=20/26, 76.9%) and ST1 in the second 6 months (n=16/18, 88.9%) (P=0.00003). DNA levels did not differ between patients with specific outcomes. Macrolide resistance was detected in 1 (1.9%) strain (A2058G mutation). MLVA types included 3–5–6–2 (n=21/45, 46.7%), 3–6–6–2 (n=2/45, 4.4%), 4–5–7–2 (n=14/45, 31.1%), and 4–5–7–3 (n=8/45, 17.8%), and they correlated with P1 subtypes and MLST types. Mp strains were almost identical within families, but varied over geographic location. MLVA types were not associated with specific clinical outcomes, and differed in patients withmucocutaneous disease between 2016–2017 (3–5–6–2, n=5/8, 62.5%) and 2017–2020 (4–5–7–2, n=5/7, 71.4%) (P=0.02).

Conclusions

Our results show that Mp genotypes may not determine specific clinical outcomes, such as pneumonia, extrapulmonary manifestations, or carriage.

Clinical Trial Registration

NCT03613636

Background

Outpatient medical facilities tend to have high antimicrobial prescription rates, and are therefore major targets for antimicrobial stewardship programs. Previous studies have shown high rates of unnecessary antimicrobial prescriptions in outpatient settings (e.g., emergency departments, urgent care clinics, retail clinics, and medical centers). Pediatric primary emergency medical centers in Japan have difficulties in implementing conventional antimicrobial stewardship programs due to the low continuity of stewardship. Accordingly, there is a need to develop effective antimicrobial stewardship program models for these facilities.

Methods

We conducted a single-center, quasi-experimental study to evaluate the effects of a nudge-based antimicrobial stewardship program in reducing unnecessary third-generation cephalosporin prescriptions in a pediatric primary emergency care center. The implemented antimicrobial stewardship program utilizes monthly newsletters that report current antimicrobial use patterns and prescribing targets. We compared the monthly third-generation cephalosporin prescription numbers and proportions of unnecessary prescriptions before and after the program was implemented. The trends in third-generation cephalosporin prescriptions were examined using an interrupted time-series analysis.

Results

The numbers of patients before and after program implementation were 129,156 and 28,834, respectively. The number of unnecessary third-generation cephalosporin prescriptions decreased by 67.2% in the year after program implementation. The interrupted time-series analysis showed that the program was significantly associated with a reduction in third-generation cephalosporin prescriptions (regression coefficient: -0.58, P< 0.001).

Conclusions

The nudge-based antimicrobial stewardship program was effective in reducing third-generation cephalosporin use in a Japanese pediatric primary emergency care center. This simple and inexpensive approach may have applications in other outpatient facilities.

Background

Cryptosporidiosis is an acute gastro-intestinal disease leading to acute dehydration and death in severe cases, particularly among immuno-compromised individuals, including children ≤5 years. Ireland reports the highest Crude Incidence Rates in the EU, with approximately 60% of annual cases attributed to children, however, the spatiotemporal patterns of domestically acquired (sporadic and outbreak-related) cases have not been fully elucidated.

Methods

SaTScan v9.6 was used to undertake space-time scanning of confirmed cases of paediatric cryptosporidiosis notified in Ireland from January 1^st 2008 to December 31^st 2017 (2,672 cases). Cases were geo-coded to one of ~19,000 Census Small Areas (SAs), with discrete Poisson modelling employed for scanning at high spatial resolution. All significant space-time clusters (p < 0.05) were mapped, with binary cluster location summed at SA scale. Final maps provide a “cluster recurrence” index (0 to 10) for the study period.

Results

Three high recurrence “hotspots” were identified, including a large area north-east of Galway City, and two areas south-west and south-east of Limerick City (Figure 1). Identified clusters largely mirrored annual peaks of infection (late spring/early summer). Notably, no space-time clusters were found in major urban conurbations over the study period (i.e., “cold-spots”).

Conclusions

The space-time recurrence index offers a simple approach to identify spatiotemporal patterns of infection, with presented analyses detecting three spatial clusters omitted from routine surveillance. The spatiotemporal epidemiology of cryptosporidiosis reflects the diverse population and geography of the country, with a markedly higher rate of occurrence in rural areas, likely due to the ubiquity of Cryptosporidium spp. sources (e.g., cattle) and pathways (e.g., karstic limestone bedrocks). The elevated burden among children ≤5-years is likely related to immunological status and specific routes of exposure, warranting further study.

Background

Group B Streptococcus (GBS) is a common intestinal coloniser during the neonatal period but also may cause late-onset sepsis or meningitis in up to 0.5% of otherwise healthy colonised infants after day 3 of life. Transmission routes and risk factors of this late-onset form of GBS disease are not fully understood.

Methods

Cases of invasive GBS disease (iGBS) with recurrence (n = 25) and those occurring in parallel in twins/triplets (n = 32) from the UK and Ireland (national surveillance study 2014/15) and from Germany and Switzerland (retrospective case collection) were analysed to unravel shared (in affected multiples) or fixed (in recurrent disease) risk factors for GBS disease.

Results

The risk of iGBS among infants from multiple births was high (17%) if one infant had already developed GBS disease. The interval of onset of iGBS between siblings was significantly shorter compared to recurrent cases (4.5 vs 12.5 days, P = 0.01) indicating differences in mode of infection and pathogenesis. Disturbances of the individual microbiome, including the persistence of infectious foci, are suggested, e.g. by high usage of perinatal antibiotics in mothers of affected multiples, and by the association of an increased risk of recurrence with a short term of antibiotics (OR 4.2 (1.3-14.2), P = 0.02). Identical GBS strains in both recurrent infections and concurrently infected multiples might indicate a failed microbiome integration of GBS strains that are generally regarded as commensals in healthy infants.

Conclusions

The dynamics of recurrent GBS infections or concurrent infections in multiples suggest individual patterns of exposure and fluctuations in host immunity, causing failure of natural niche occupation.

Clinical Trial Registration

Not applicable

Background

Antimicrobial stewardship programs (ASPs) aim to improve antibiotic utilization. Intensive care unit (ICU) setting encountered a high volume of broad-spectrum antibiotic consumption, particularly carbapenems. The computer-assisted post-prescription authorization has been used to authorize carbapenem prescription in Ramathibodi Hospital, Thailand, since 2011, without systematic evaluation. Handshake stewardship is a distinctive approach, focusing on direct communication and a follow-up review of prescribed antibiotics without antibiotic restriction. We aimed to evaluate the impact and acceptability of center-specific ASP, which integrated handshake stewardship to the current computer-assisted post-prescription authorization, in pediatric critically ill patients.

Methods

We performed a pre-and post-implementation study of center-specific ASP, from July 2017 to December 2018, and April 2019 to September 2020, respectively. The primary outcome was the carbapenem consumption rate, measured by days of therapy (DOT) per 1000 patients-ICU days (DOT/1000-ICU days). Secondary outcomes included length of critical care stay (LOCS), 30-day infection-related mortality, carbapenem resistance rate, and acceptability of ASP recommendations.

Results

Two-hundreds and twelve events (163 patients) and 174 events (110 patients) of carbapenem prescription were enrolled in the pre-and post-implementation group, respectively. Carbapenem consumption rate significantly decreased by 45.4% (p < 0.005) (from 667 to 364 DOT/1000-ICU days) (-303 days, 95% Confidence Interval -201.9, -72.6). LOCS, 30-day infection-related mortality, and carbapenem-resistance rate were not significantly different after implementation of ASP. The acceptability of ASP recommendations was 95.4%. Scheduled duration (55.2%) and de-escalation (31.6%) were the two most common ASP recommendations.

Conclusions

Our center-specific ASP, which integrated handshake stewardship and the current computer-assisted post-prescription authorization, significantly reduced carbapenem consumption in pediatric critically ill patients with a high acceptability rate without a negative impact on patients’ clinical outcomes.

Background

In April 2020 some children presented with signs of multisystem inflammation with clinical signs overlapping with Kawasaki disease (KD), most of them requiring admission to the pediatric intensive care unit (PICU).

Methods

Medical data of KD patients from 1st January 2018 until 30th May 2020 was collected from the KAWA-RACE study group. We compared the KD cases diagnosed during the COVID-19 period (1st March-30th May 2020) that were either SARS-CoV-2 confirmed (CoV+) or negative (CoV-) to those from the same period during 2018 and 2019 (PreCoV).

Results

One hundred and twenty-four cases were collected. There was a significant increase in cases and PICU admissions in 2020 (P-trend = 0.001 and 0.0004 respectively).

We found that 56% of KD patients presenting during the pandemic had confirmed SARS-COV-2 infection. Twenty-three (88.5%) of the CoV+ patients fulfilled both PIMS-TC and MIS-C criteria; from CoV- cohort, 45% of patients fulfilled the criteria for MIS-C, and 40% for PIMS-TS.

CoV+ patients were significantly older (7.5 vs 2.5yr), mainly non-Caucasian (64 vs 29%), had incomplete KD presentation (73 vs 32%), lower leucocyte (9.5 vs 15.5x109) and platelet count (174 vs 423x109/L), higher inflammatory markers (C-Reactive Protein 18.5 vs 10.9 mg/dl) and terminal segment of the natriuretic atrial peptide (4766 vs 505 pg/ml), less aneurysm development (3.8 vs 11.1%) and more myocardial dysfunction (30.8 vs 1.6%) than PreCoV patients. Respiratory symptoms were not increased during the COVID-19 period (Table 1).

Conclusions

The KD CoV+ patients mostly meet PIMS-TC and MIS-C criteria. Around half of the KD patients presenting during the pandemic had confirmed SARS-COV-2 infection. Whether this is a novel entity or the same disease on different ends of the spectrum is yet to be clarified.

Clinical Trial Registration

Clinical trial registration: N/A

Background

Neonatal Herpes Simplex Virus (HSV) infection may cause severe morbidity and mortality. With cases increasing, optimising short and long-term management for infants is important to minimise complications.

Aciclovir prophylaxis reduces recurrence of central nervous system (CNS) disease, which may occur in up to 8% of cases. Daily prophylaxis over a 6-month period has been shown to improve neurodevelopmental outcomes. We present outcomes and recurrence rates for this treatment course.

Methods

We reviewed neonates under the care of three tertiary centres with HSV disease, who presented at less than 90 days of age. Demographics, including neonatal history, clinical presentation, initial investigations and treatment were reviewed (Table 1). Follow-up, including recurrence rate on and after prophylactic aciclovir or valaciclovir and management were recorded.

Results

Of 21 patients, six (28%) had HSV-1, 14 (66%) HSV-2 and one unknown. 13 infants were born at term, eight preterm (<37 weeks). 57% presented with central nervous system (CNS) disease. Seven (33%) had recurrences on prophylaxis, despite good adherence to treatment, and 13 (61%) after stopping prophylaxis. All recurrences were skin eruptions. Premature babies were more likely to have recurrences than term babies. 50% of preterms versus 23% of term babies had recurrences on prophylaxis. After discontinuing prophylaxis, 75% of preterms versus 53% term babies had recurrences.

Conclusions

In this small cohort of infants with neonatal HSV disease, after a course of prophylaxis there was still frequent recurrence of skin lesions, but reassuringly there was no CNS recurrence. Of note, recurrence appeared more common in babies born prematurely, implying a less effective immune response to HSV. Further research is needed to investigate the ontogeny of the immune response to HSV in infants of different gestations.

Background

Understanding community SARS-CoV-2 seroprevalence in children is vital in helping understand the epidemiology of the virus and informing COVID-19 public health policy.

Methods

An ongoing community-based repeat cross-sectional seroprevalence study recruited participants aged 0-24 year between October 2019 and August 2020 across 8 regions in England. Participants were predominantly recruited by mail-out to postcodes with Index of Material Deprivation (IMD) distribution representative of the region. Serum samples, demographics and symptom data were obtained, and samples processed analysed by Abbott nucleocapsid and a Public Health England in-house Receptor Binding Domain (RBD) assays to determine the presence of antibodies against SARS-CoV-2. Combined adjusted seroprevalence estimates were calculated incorporating both RBD or Abbott (sensitivity 96.9%, specificity 96.9%).

Results

Of the 1145 participants recruited, 54 (4.7%) were seropositive by Abbott and 56 (4.9%) by RBD. Between June and August 2020 adjusted seroprevalence in 0-4 year olds was 1% (N= 54, CI 0-8) compared with 12.6% (N=114, CI 6.3-20.4) in 20-24 year olds. A logistic regression analysis demonstrated Black and Minority Ethnic (BAME) participants had higher risk of SARS-CoV-2 infection than white participants (multivariate analysis OR 2.9, CI 1.28-6.57, p = 0.011). Risk was inversely related to deprivation (p = 0.003 across IMD quintiles, OR 0.16 for lowest compared to the highest IMD quintile). 16/34 antibody positive participants reported no flu-like symptoms.

Conclusions

A small but significant minority of children had evidence of infection, and this was higher in BAME participants, although co-morbid risk factors such as obesity and type 2 diabetes are less likely in this paediatric population compared with adult cohorts. Ongoing sampling through the second wave of COVID-19 in England, with enhanced BAME recruitment, will further interrogate this association.

Funded by National Institute for Health Research (NIHR)

Clinical Trial Registration

ClinicalTrials.gov Identifier: NCT04061382

Background

The influence of the neonatal intensive care unit (NICU) design on the acquisition of multidrug resistant organisms (MDRO) has not been well-documented. The aim of this study was to examine the effect of open bay unit (OBU) versus single room unit (SRU) design on the incidence of colonization and infection with MDRO and third generation cephalosporin resistant bacteria (3G-CRB) as well as the number of possible transmission events in infants admitted to the NICU.

Methods

All infants admitted to the NICU two years prior to and two years following transition from OBU to SRU were identified. Incidence of colonization, infection and possible transmission events of MDRO were compared between OBU and SRU periods.

Results

Analysis was performed in 1293 NICU infants, which identified 3.2% MDRO carriers including 2.3% extended-spectrum β-lactamase producing Enterobacterales carriers and 18.6% 3G-CRB carriers.

No difference was found in the incidence density per 1,000 patient-days (1.56 OBU, 2.63 SRU, n.s.) between the historic open ward and the new single room units. The MDRO infection rate was low (0.12%) and not found to be different between OBU and SRU infants. We did not find a decrease in possible transmission events per 1,000 patient-days after transition (0.62 OBU, 0.81 SRU, n.s.).

Conclusions

Transition from an open bay to a single room unit NICU was not associated with a reduction in colonization and infection rates or possible transmission events with MDRO in our hospital.