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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

Routine vaccination against H. influenzae type b (Hib) has dramatically reduced Hib disease burden worldwide. There has been a rise in invasive serotype a (Hia) disease in children, particularly of Indigenous ethnicity. The aim of this study was to describe the age-specific epidemiology of invasive childhood H. influenzae disease in Canada during 2007-2018.

Methods

National data on clinical features and outcomes of children with invasive H. influenzae disease are captured by the Canadian Immunization Monitoring Program, ACTive (IMPACT). Patients aged ≤16 years treated as outpatients or admitted to 12 pediatric tertiary-care hospitals across Canada between 2007-2018 with laboratory-confirmed invasive H. influenzae disease were included. Data were collected using standardized case report forms and isolates were tested at the national referral laboratory.

Results

Overall 528 children were identified and 504 (96%) were hospitalized. Median age was 1.2 years (interquartile range [IQR],0.6-4.0); 236 children (45%) were <1 year old. Overall, meningitis was the most common disease manifestation (n=183, 35%), followed by pneumonia (n=167, 32%) and bacteremia (n=95, 18%). Median length-of-stay amongst hospitalized children was 14 days (IQR,6-17). ICU admission was required for 184 children (35%); median ICU length-of-stay was 5 days (IQR,2-11). Death occurred in 25 children (5%). Among those with known ethnicity, 150/326 (46%) were Indigenous; of whom 85/150 (57%) had Hia disease.

Conclusions

Invasive H. influenzae disease continues to cause significant morbidity and mortality, particularly among Indigenous populations across Canada. Strategies to improve prevention and treatment of these infections are required.

Background

In children, Streptococcus pneumoniae causes up to 78% of bacterial lobar pneumonia, which may be further complicated by pleural effusion or empyema. We aimed to 1) characterize pediatric pneumonia-causing S. pneumoniae over 25 years in Canada before and after use of pneumococcal conjugate vaccines and 2) correlate bacterial genomic data with clinical features in cases.

Methods

Whole genome sequencing was performed on 297 S. pneumoniae isolates from pneumonia cases in 12 pediatric tertiary care hospitals in Canada between 1991 and 2016 from the pre-vaccine, PCV7/10 and PCV13 eras. Isolates and clinical data were obtained from the Canadian Immunization Monitoring Program ACTive (IMPACT). Genome wide associations were assessed using TreeWAS, incorporating phylogenetic data (i.e., evolutionary history) to identify associations between bacterial genomes and outcomes.

Results

Pan-genome analysis identified 4,305 genes including 1,324 which were shared by all isolates. We detected 37 Global Pneumococcal Sequence Clusters (GPSCs) including GPSCs which increased (4 and 119) and decreased (3 and 19) across vaccine eras. Genome wide association studies revealed several non-synonymous nucleotide polymorphisms or gene associations that were statistically significant in association with empyema (3 polymorphisms and 1 gene) and ICU admission >2 days (6 polymorphisms and 1 gene). One complex polymorphism (translating to a 3 amino acid change at position 207) in the gene cbpD, encoding the major pneumococcal virulence factor choline binding protein D, was significantly associated with both empyema and prolonged ICU admission.

Conclusions

The molecular epidemiology of S. pneumoniae has changed in the conjugate vaccine era in terms of GPSCs causing pediatric pneumonia. We have identified both genes and non-synonymous polymorphisms that are associated with empyema and ICU admission providing a starting point for validation studies of their role in pneumococcal pneumonia.

Clinical Trial Registration

This study does not report on the results of a controlled clinical trial

Background

Previous studies showed that comprehensive investigation of children with invasive pneumococcal disease (IPD), revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children presenting with IPD, to assess the proportion with an immunodeficiency in our setting.

Methods

We retrospectively identified patients with IPD by searching the microbiological and immunological databases of the Oxford Children’s Hospital, UK, from January 2015 – November 2020, and collected clinical and laboratory data from the medical records. The following immunological investigations were performed: complement C3 and C4 levels, classical and alternative pathway complement function, IgG, IgA and IgM levels, specific IgG levels (H. influenza B, tetanus, and pneumococcal serotypes), lymphocyte subsets, and CD62L in selected cases. Analysis of vaccine responses is ongoing.

Results

Immunological investigations were performed in 51 children with IPD. Four children (7.8%) had abnormal findings that were deemed of clinical significance; two children were diagnosed with complement deficiencies (Factor I and C2 deficiency), one child had persistently low anti-pneumococcal antibodies, and another child had low IgM, low NK-cells and poor persistence of pneumococcal antibodies. In an additional thirteen children with IPD, no immunological investigations were performed. Of these children, four died and four had possible explanations for the infection (sickle cell disease, tocilizumab treatment, leukaemia treatment and skull base fracture).

Conclusions

We identified clinically relevant abnormal immunological findings in 7.8% of children with IPD. This result might be an underestimation, since children who died were not tested. Our results support the recommendation to perform immunological investigations in children with IPD, since this might reveal underlying immunodeficiencies at an early stage, allowing for necessary preventive measures and close follow-up.

Background

Recurrent respiratory tract infections (rRTI) affect around 10-15% of children aged 0-5 years. Some children with rRTI suffer from an underlying immunological defect, such as a primary antibody deficiency (PAD). We investigated the prevalence of and epidemiological risk factors associated with PAD in children with rRTI and linked this to disease severity.

Methods

Children <7 years of age with rRTI undergoing immunological screening in a secondary and tertiary hospital in The Netherlands were included in a prospective cohort study. In a subgroup of children, parent-reported RTI symptoms were monitored during the winter season with a daily diary mobile phone application. Patient characteristics associated with PAD were identified using multivariable logistic regression analysis with model selection.

Results

Between 2016 and 2019 we included 147 children with rRTI with a median age of 3.4 years (interquartile range 2.1-5.2 years). Although major immune deficiencies were rarely observed, a high percentage of children (55%) showed mild antibody deficiencies. Most prevalent were complete/partial IgA deficiency (23%), IgG4-subclass deficiency (12%) and combined IgA and total IgG deficiency (9%). Prematurity was significantly associated with PAD in multivariate analysis (see Table). In 80 children daily RTI symptoms were monitored during a winter season; the prevalence and duration of RTI symptoms did not differ significantly between children with and without PAD.

Conclusions

The prevalence of PAD in a Dutch cohort of young children with rRTI was remarkably high compared to older pediatric cohorts. Prematurity was associated with PAD, underlining that immune maturation lies at the basis of mild PAD commonly found in the first years of life. Interestingly, RTI symptoms did not differ between children with and without PAD, which suggests that more factors than PAD alone contribute to disease severity.

Clinical Trial Registration

Not applicable

Background

Knowledge of antifungal prescribing in neonatal units is extremely important. However, data on antifungal use in neonatal inpatients across Europe are limited. There is need to collect standardized multi-center data. We organized a European 12-wk modified point-prevalence study (mPPS) to record antifungal consumption in neonates and infants.

Methods

All patients hospitalized in neonatal units (NUs) and receiving systemic antifungals of 17 hospitals across Europe were included. Information about ward demographics was collected once at the beginning; weekly ward and patient data were collected prospectively for the 12-wk study period and entered in REDCap database.

Results: 26 NUs (4 Level 1, 4 Level 2, 18 Level 3) from 17 hospitals, located in 8 European countries with a median capacity of 21 beds participated in the study.

Results

The median percentage of neonates receiving antifungal agents per mPPS week across all NUs Level 3 was 9.6% (range 7.5-11.4). A total of 167 patients were included in the study; 156 patients aged ≤90d (median age=7 days, Q1=3,Q3=20.5d) and 11 aged 3-60 months (median age=4 months, Q1=3,Q3=5.5mo). Prematurity was most common underlying condition among patients ≤90d (86%), whereas chronic respiratory disease (64%) and history of surgery (36%) were among patients 3-60 months.Indication for antifungal prescribing at inclusion was prophylaxis in 77% and treatment in 23%.

Conclusions

Fluconazole was the most frequently prescribed agent both for prophylaxis (98%, N=129) and treatment (39%, N=38). The most common reasons for prophylaxis were prematurity, birth weight <1000g and central venous catheters; whereas for empirical treatment, it was late onset sepsis.

Conclusions: The majority of antifungal prescriptions across European NUs is for prophylaxis. Results from this multicenter study can be a first step to guide a European antifungal stewardship program.

Background

Unaccompanied minors (UM) are a high-risk group for acquiring infectious diseases and data on their vaccination status is scarce. Different approaches are used to screen newly arrived minors in Europe. The aim of this study is to describe their demographic characteristics, as well as their health status and serological protection against different vaccine preventable diseases in order to homogenize screening protocols.

Methods

Retrospective study of all UM that were visited at a reference centre for International Health in Barcelona from January 2017 to February 2020. After ethical approval, data were obtained from electronic medical records and SPSS v20 was used to undertake the statistical analysis. The screening strategy was adjusted by symptoms and area of origin. Chi-square test was used to compare the distribution of categorical variables.

Results

Among 289 minors (89% males, mean age:16) 74% were asymptomatic and 73% completed follow-up. Most of them (60%) were from Sub-Saharian Africa followed by Maghreb and Asia and mean time to first visit since arrival was 5 months (IQR:1-5). At least 1 diagnosis was made in 127 minors. From those, 70% were asymptomatic. We found a high prevalence of latent tuberculosis infection(23%), intestinal parasites(21%) and hepatitis B infection(6%) even in asymptomatic minors, and especially among those from Sub-Saharan Africa. Protection against hepatitis B virus (36%) and measles (80%) were sub-optimal.

Conclusions

These results highlight the importance of screening and immunization programs for UM arriving to Europe, especially in border European countries. The geographic origin determines the prevalence of diseases, thus efforts in elaborating efficient protocols for screening and immunizing newly arrived migrants should be based on this information. These programs are a Public Health priority and should not be forgotten during the current pandemic.