Flow-cytometric immune phenotyping is influenced by cryopreservation and inter-laboratory variability limiting comparability in multicenter studies. We assessed a system of optimized, pre-mixed dry-antibody panel tubes requiring small amounts of whole blood for validity, reliability and challenges in a Canadian multicenter study (POSITIVE) with long-distance sample shipping, using standardized protocols. Thirty-seven children awaiting solid-organ transplant were enrolled for parallel immune-phenotyping with both validated, optimized in-house panels and the dry-antibody system. Samples were collected before, 3 and 12 months post-transplant. Quality-assurance measures and congruence of phenotypes were compared using Bland-Altman comparisons, linear regression and group comparisons. Samples showed excellent lymphocyte viability (mean 94.8 %) and recovery when processed within 30 h. Comparing staining methods, significant correlations (Spearman correlation coefficient >0.6, p < 0.05), mean difference <5 % and variation 2SD <25 % were found for natural-killer, T and B cells, including many immunologically important cell subsets (CD8+, naïve, memory CD4+ T; switched-memory, transitional B). Some subgroups (plasmablasts, CD1d+CD5hi B cells) showed weak correlations, limiting interpretation reliability. The dry-antibody system provides a reliable method for standardized analysis of many immune phenotypes after long-distance shipping when processed within 30 h, rendering the system attractive for pediatric studies due to small blood amounts required and highly standardized processing and analysis.

The Department of Health and Aged Care acknowledges the providers of the many sources of data used in this report and greatly appreciates their contribution. KEY MESSAGESIt is important to note that due to the COVID-19 epidemic in Australia, data reported from the various influenza surveillance systems may not represent an accurate reflection of influenza activity.Results should be interpreted with caution, especially where comparisons are made to previous influenza seasons.Interpretation of influenza data from April 2020 onwards should take into account, but are not limited to, the impact of social distancing measures, likely changes in health seeking behaviour of the community including access to alternative streams of acute respiratory infection specific health services, and focussed testing for COVID-19 response activities.For information on COVID-19 incidence, severity, and distribution in Australia, please refer to COVID-19 epidemiology reports. Activity• Influenza-like-illness (ILI) activity in the community is low after activity peaked in June 2022.Nationally, notifications of laboratory-confirmed influenza have continued to decrease in the past fortnight and remain lower than average for this time of year compared to previous years. Severity• Clinical severity for the season to date, as measured through the proportion of patients admitted directly to ICU, and deaths attributed to influenza, is low. Impact• The impact for the season to date, as measured through the rate of FluTracking respondents absent from normal duties and the number of sentinel hospital patients with influenza, is low to moderate. At-risk populations• In 2022 to date, people aged 5-9 years, children aged younger than 5 years, and people aged 10-19 years have the highest notification rates. Virology• To date, 82.7% of notifications of laboratory-confirmed influenza reported to the NNDSS were influenza A, of which 94.4% were influenza A(unsubtyped), 0.9% were influenza A(H1N1), and 4.7% were influenza A(H3N2).Influenza B accounted for 0.2% of notifications, less than 0.1% were A&B co-infections, and 17.1% were untyped. Vaccine match and effectiveness• Of the 2,570 samples referred to the WHOCC to date, 92.4% of influenza A(H1N1), 94.5% of influenza A(H3N2), and the six influenza B/Victoria samples, were characterised as antigenically similar to the corresponding vaccine components.• Vaccine effectiveness is a measure of the protective effect of influenza vaccines against influenza and its complications and is typically around 40-60%.Based on preliminary estimates from sentinel hospitals (FluCAN), vaccine effectiveness appears at the lower end of the moderate range in 2022.

In 2013, the SickKids-Caribbean Initiative (SCI) was formalised among The Hospital for Sick Children in Toronto, Canada, the University of the West Indies, and Ministries of Health in six Caribbean countries (Barbados, The Bahamas, Jamaica, St. Lucia, St. Vincent and the Grenadines, and Trinidad and Tobago). The aim was to improve the outcomes and quality of life of children (<18 years) with cancer and blood disorders in the partner countries. Core activities included filling a human resource gap by training paediatric haematologists/oncologists and specialised registered nurses; improving capacity to diagnose and treat diverse haematology/oncology cases; developing and maintaining paediatric oncology databases; creating ongoing advocacy activities with international agencies, decision makers, and civil society; and establishing an integrated administration, management, and funding structure. We describe core program components, successes, and challenges to inform others seeking to improve health service delivery in a multidisciplinary and complex partnership.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

SARS-CoV-2 infection is typically less severe in children and adolescents compared to adults and the vast majority of pediatric patients do not require any care or will recover with supportive care only. In the absence of adequate pediatric data, most recommendations for children and adolescents are based on efficacy and safety data from adult studies and the optimal approach to the management of pediatric patients with acute COVID-19 is not yet determined. A number of national pediatric guidelines are available, and these continue to evolve rapidly with the emergence of new study information. As of January 2022 data from clinical trials in adult patients suggested a benefit to mortality outcomes with the use of dexamethasone, tocilizumab, and janus kinase inhibitors in certain subgroups of patients, potential benefit from the use of remdesivir, as well as emerging evidence for COVID-19 specific monoclonal antibody use. Given the paucity of pediatric data, the use of specific therapy in the context of acute COVID-19 is not considered routine, and decisions regarding specific therapy use are made on discussion with the multidisciplinary clinical team including infectious diseases experts. Guidelines recommend where possible children should be enrolled in available clinical trials. On a case-by-case basis, guidelines suggest specific therapy may be considered appropriate in children with severe or critical COVID-19 or in cases of mild and moderate disease where risk factors for progression to the severe disease exist. This chapter provides an overview of available evidence as of January 2022 and guidance on supportive care and the use of specific therapies for the management of both hospitalized and nonhospitalized pediatric patients with acute COVID-19. It should be noted that due to the rapid evolution of evidence, regularly updated local, national and regional guidance documents should be consulted when determining treatment of pediatric patients with acute COVID-19.

About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario's response.The Science Advisory Table's mandate is to provide summaries of relevant scientific evidence to public health and health care professionals, as well as the general public, by integrating information from existing scientific tables, Ontario's universities and agencies, and the best global evidence.The Science Advisory Table is hosted by Public Health Ontario (PHO).Aligned with PHO's mandate, the Science Advisory Table provides credible and independent scientific and technical advice to inform government and the broader public about COVID-19 and to help prepare for and respond to future public health emergencies.

We provide an update to the Association of Medical Microbiology and Infectious Disease Canada seasonal influenza foundation guideline on the use of antiviral drugs for influenza for the upcoming 2021-2022 influenza season in Canada. Peramivir and baloxavir marboxil were licensed in Canada in 2017 and 2020, respectively, but neither is currently marketed. Thus, this guidance continues to focus on further optimizing the use of oseltamivir and zanamivir. Important issues for this year include the implications of co-circulation of severe acute respiratory syndrome coronavirus 2 and influenza viruses; the role of diagnostic testing in relation to impact on patient management; and dosing and administration recommendations for neuraminidase inhibitors for various at-risk age groups.

Abstract Background Solid-organ transplant (SOT) patients are more vulnerable to infections by antimicrobial-resistant organisms (AROs) because of their hospital exposure, compromised immune systems, and antimicrobial exposure. Therefore, it may be useful for transplant facilities to create transplant-specific antibiograms to direct empirical antimicrobial regimens and monitor trends in antimicrobial resistance. Methods SOT (i.e., lung, liver, renal, and heart) antibiograms were created using antimicrobial susceptibility data on isolates from 2012 to 2018 at The Hospital for Sick Children, a tertiary pediatric hospital and transplant center in Toronto, Ontario. The Clinical Laboratory Standards Institute (CLSI) guidelines were followed to generate the antibiograms. The first clinical isolate of a species from a patient in each year was included irrespective of body site; duplicates were eliminated and surveillance cultures were excluded. Results from 2 years of data were pooled on a rolling basis to achieve an adequate sample size in both SOT and hospital-wide antibiogram. The SOT antibiogram was then compared with the hospital-wide antibiogram of the compatible 2 pooled years from 2012 to 2018. For subgroup analyses in the SOT population, organ-specific antibiograms and transplant timing-specific antibiograms (pretransplant, post-transplant <1 year, and post-transplant ≥1 year) between transplant and sample collection dates were analyzed. All proportions were compared using the χ 2 test. Results The top 5 organisms in one (2 year) analysis period of the SOT antibiogram were Escherichia coli (n = 29), Staphylococcus aureus (n = 28), Pseudomonas aeruginosa (n = 20), Enterobacter cloacae complex (n = 18), and Klebsiella pneumoniae (n = 17). For E.coli, susceptibility in the SOT antibiogram was significantly lower than those in the hospital-wide antibiogram in 2017/2018 for ampicillin (27% vs. 48%; P = 0.015), piperacillin/tazobactam (55% vs. 87%; P < 0.001), cefotaxime (59% vs. 88%; P < 0.001), ciprofloxacin (71% vs. 87%; P = 0.007) and cotrimoxazole (41% vs. 69%; P < 0.001), but not significantly different for gentamicin (94% vs. 91%; P = 0.490), tobramycin (88% vs. 90%; P = 0.701) and amikacin (100% vs. 99%; P = 0.558). These findings were consistent throughout the study period in E.coli. There was no statistically significant difference between the SOT and hospital-wide antibiograms for other organisms. There were no significant differences in susceptibility between organ-specific antibiograms or transplant timing-specific antibiograms in 2012–2018. Conclusions We found that E.coli from the SOT population had a significantly lower sensitivity to all antimicrobials, except aminoglycosides, compared with those from the hospital-wide population. Other organisms had similar susceptibility to the hospital-wide population. Developing a SOT antibiogram will assist in revising and improving empiric treatment guidelines for this population.

Key Message Early suggestions that children are considerably less important for SARS-CoV-2 transmission than adults are not confirmed by recent research. Children could play a relevant role, and public health interventions could be as relevant and impactful to mitigate transmission in children as in adults. Summary Background Children are underrepresented in COVID-19 case statistics and […]

Most healthy people fully recover from influenza illness without medical intervention or antiviral treatment However, given the potential for suboptimal VE this season, antiviral therapy may be of particular importance in the management of individuals with suspected influenza illness despite documentation of having received the 2019–2020 influenza vaccine

In October 2018, the Infectious Diseases Society of America (IDSA) Board of Directors (BOD) decided to develop a 2019 IDSA Strategic Plan. The IDSA BOD has invested in strategic planning at regular intervals as part of an ongoing process to review and to renew the vision and direction of IDSA. Herein, the 2018-2019 strategic planning process and outcomes are described. The 2019 IDSA Strategic Plan presents 4 key initiatives: (1) optimize the development, dissemination, and adoption of timely and relevant ID guidance and guidelines that improve the outcomes of clinical care; (2) quantify, communicate, and advocate for the value of ID physicians to increase professional fulfillment and compensation; (3) facilitate the growth and development of the ID workforce to meet emerging scientific, clinical, and leadership needs; and (4) develop and position a new tool to serve as the leading US benchmark to measure and drive national progress on antimicrobial resistance. The BOD looks forward to developing, implementing, assessing, and advancing the 2019 IDSA Strategic Plan working with member volunteers, Society partners, and IDSA staff.

The benefits of human immunodeficiency virus (HIV) testing in pregnancy, when combined with appropriate maternal antiretroviral therapy and intrapartum and postnatal prophylaxis, are well established. The vertical rate of transmission of HIV in North America is now well below 2%. Efforts must continue to ensure that these benefits are sustained. Women who have received little or no prenatal care and those who present for delivery with unknown HIV status need immediate testing. As more infants are exposed to antiretroviral agents, strategies need to be implemented to ensure adequate follow-up of these infants. Issues relating to the identification of HIV-exposed infants are highlighted.

Purpose Post-transplant (Tx) immunosuppressive therapy needs to achieve a balance between the risk of rejection and consequences of over-immunosuppression (IS) such as infection and tumors. We aimed to develop a novel flow cytometry (FACS)-based tool to assess immune function in patients with different levels of IS as defined by tacrolimus (Tac) levels. Methods Children listed for solid organ Tx (heart, liver, kidney, n=115) were included within a national multi-center study (CNTRP-POSITIVE). Peripheral blood mononuclear cells (PBMC) were isolated prior to Tx (n=115) and at 3 (n=91) and 12 months (n=63) post-Tx. PBMC were stimulated with Staphylococcal enterotoxin B (SEB), CMV or EBV antigens over 16 hours. Activation of CD4+ cells, reflected in CD69 expression and intracellular cytokine (IFNγ, TNFα, IL2) production, was assessed by flow cytometry relative to values found in unstimulated cells. Results were compared between patients with low versus high Tac levels. Results In each individual SEB-stimulated sample a strong positive correlation was found between the quantities of the 3 intracellular cytokines (r=0.658 to 0.874, p 10 μg/L compared to those Conclusion The strong intra-sample correlations between cytokine levels indicate that the assay accurately identifies activated CD4+ cells. The test reliably differentiates between patients with and without IS and between patients with high and low Tac levels. This assay may be useful as a tool to assess intensity of IS and guide IS dosing in individual patients after Tx, however, longitudinal assessment and correlation to clinical outcomes is needed to confirm its potential utility.

cycles defects and organic academia pts. Clinical and surgical data were recorded. Results: From January 2008 to March 2018, 38 (18.1%) out of 209 children underwent LT for MD: primary hyperoxaluria type1 (PH1) [12, 31.5%], tyrosinemia type 1 [6, 15.7%], maple syrup urine disease [5, 3.2%], argininosuccinic aciduria [4, 10.5%], ornithine transcarbamylase deficiency [3, 7.9%], propionic acidemia (PPA) [2, 5.2%], methylmalonicacidemia (MMA) [3, 7.9%], familial hypercholesterolemia [1, 2.6%], alpha 1antitrypsin deficiency [1, 2.6%], LAL deficiency [1, 2.6%], ethylmalonic acidemia [1, 2.6%]. At LT the median age was 55 months (9225) and median weight 18 Kg (7.760). Deceased donor were used in 28 (73.7%) recipients [5 combined liverkidney transplantation(CLKT)] and living donor in 10 (26.3%) patients [1 simultaneous and 3 sequential CLKT]. In all PH1, hemodialysis was performed during the CLKT to reduce the risk of oxalate deposition in the renal graft. A graft from a LT patient with MSUD was used for domino LT in a child with biliary cirrhosis. Patient and graft survival are 97.4% after a median follow up of 32 months (range 5108). One patient, who was late referred to the center, died from hemorrhage after 8 days from CLKT. All LT recipients alive have normal graft function. 8 (21%) biliary and 4 (10.5%) vascular complications were observed; 8 (21%) recipients presented CMV viremia and 3 (7.9%) EBVDNA viremia, all without infection signs. All children received normal protein intake in 24 weeks and no metabolic decompensation occurred. Except 1 child affected by PPA who faced progressive neurological disorder (drugresistant epilepsy), all patients reported neurological improvement or stability, and a better quality of life. Domino LT recipient maintained normal levels of amino acids, with no detectable alloisoleucine on free diet. Conclusion: LT in children with MD achieve excellent outcomes. The multidisciplinary management and the early referral to specialized transplant centres are essential to offer the best treatment to children with MD, permitting to optimize the timing of LT, prevent metabolic decompensation and neurologic progression. Extensive neonatal screening would lead to an increasing number of early referral of MD children undergoing prompt neurological and metabolic assessment, and identify whose might benefit of LT. References: 1. Mazariegos G, Shneider B, Burton B, Fox IJ, Hadzic N, Kishnani P, Morton DH, McIntire S, Sokol RJ, Summar M, White D, Chavanon V, Vockley J. Liver transplantation for pediatric metabolic disease. Mol Genet Metab 2014; 111(4):418427. 2. Darwish AA, McKiernan P, Chardot C. Paediatric liver transplantation for metabolic disorders. Part 1: Liverbased metabolic disorders without liver lesions. Clin Res Hepatol Gastroenterol. 2011 Mar;35(3):194203. 3. Sze YK, Dhawan A, Taylor RM, et al. Pediatric liver transplantation for metabolic liver disease: experience at King's College Hospital. Transplantation. 2009 Jan 15;87(1):8793 TUESDAY, MAY 7, 2019 FROM 08:00 TO 09:30 ORAL SESSION 402 ON INFECTIOUS DISEASES: INTERFACE OF VIRUSES WITH THE IMMUNE RESPONSE