Publications by authors named "Shaun K Morris"

120 Publications

Re-vaccination and adverse event recurrence in patients with adverse events following immunization.

J Pediatr 2022 Aug 7. Epub 2022 Aug 7.

Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada; Canadian Center for Vaccinology, IWK Health, Nova Scotia Health, and Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie University. Electronic address:

Objectives: To estimate the risk of recurrence of adverse events following immunization (AEFIs) upon re-vaccination and to determine among patients with suspected vaccine allergy whether allergy skin test positivity was associated with AEFI recurrence.

Study Design: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019 with AEFIs who required re-vaccination with the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. SIC physicians used guidelines to inform their recommendations. Participants were followed up post-re-vaccination to capture AEFI recurrences. Data were transferred to a central database for descriptive analysis.

Results: Overall, 588 participants were assessed for 627 AEFIs; 570 (91%) AEFIs occurred in children <18 years of age. AEFIs included immediate hypersensitivity (130/627; 21%), large local reactions (110/627; 18%), non-urticarial rash (51/627; 8%), seizures (26/627; 4%), and thrombocytopenia (11/627; 2%). Re-vaccination was recommended to 513/588 (87%) participants. Among participants recommended and due for re-vaccination during the study period, 63% (299/477) were re-vaccinated. AEFI recurrence was 10% (31/299) overall, 31% (15/49) for large local reactions, and 7% (5/66) for immediate hypersensitivity. No recurrence was serious. Among 92 participants with suspected vaccine allergy who underwent skin testing and were re-vaccinated, the negative predictive value of skin testing for AEFI recurrence was 96% (95% CI: 92.5-99.5%).

Conclusion: Most individuals with AEFIs were safely re-vaccinated. Among those with suspected vaccine allergy, skin testing may help determine the safety of re-vaccination.
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http://dx.doi.org/10.1016/j.jpeds.2022.07.019DOI Listing
August 2022

Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020-May 2021.

Lancet Reg Health Am 2022 Nov 1;15:100337. Epub 2022 Aug 1.

Centre for Global Child Health, The Hospital for Sick Children, Toronto, Canada.

Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada.

Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program (CPSP) from April 2020-May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization.

Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1-13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330 including 60 admitted to intensive care), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included pre-existing technology dependence requirements (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), body mass index Z-scores ≥3 (aRR 1·90, 95% CI 1·10-3·28), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39).

Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children.

Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.
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http://dx.doi.org/10.1016/j.lana.2022.100337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342862PMC
November 2022

Travel associated extensively drug resistant typhoid fever: a case series to inform management in non-endemic regions.

J Travel Med 2022 Jul 29. Epub 2022 Jul 29.

Division of Infectious Diseases, Hospital for Sick Children, Toronto, Ontario.

Background: Extensively drug resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem, and encourage preventive interventions as well as appropriate empiric antimicrobial use.

Methods: Cases were extracted from the GeoSentinel database, microbiologic laboratory records of 2 large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella Typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin, and trimethoprim-sulfamethoxazole.

Results: Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1), and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only 1 patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhea. Antimicrobial therapy was started on day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR Salmonella Typhi phenotype, and whole genome sequencing on 3 isolates confirmed their belonging to the XDR variant of the H58 clade.

Conclusions: XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for VFR travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology.
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http://dx.doi.org/10.1093/jtm/taac086DOI Listing
July 2022

Estimating population-based incidence of community-acquired pneumonia and acute otitis media in children and adults in Ontario and British Columbia using health administrative data, 2005-2018: a Canadian Immunisation Research Network (CIRN) study.

BMJ Open Respir Res 2022 06;9(1)

Centre for Vaccine Preventable Diseases, University of Toronto, Toronto, Ontario, Canada

Background: There is a paucity of data on the burden of the full spectrum of community-acquired pneumonia (CAP) and acute otitis media (AOM) from outpatient and inpatient settings across the age spectrum.

Methods: We conducted a population-based retrospective study in Ontario and British Columbia (BC), Canada, to estimate the incidence rate of CAP and AOM in children and adults over a 14-year period using health administrative databases. CAP and AOM cases were identified from outpatient physician consultation and hospitalisation data in both provinces, and from emergency department visit data in Ontario.

Results: During 2005-2018, Ontario had 3 607 124 CAP, 172 290 bacterial CAP, 7814 pneumococcal pneumonia, and 8 026 971 AOM cases. The incidence rate of CAP declined from 3077/100 000 in 2005 to 2604/100 000 in 2010 before increasing to 2843/100 000 in 2018; bacterial CAP incidence rate also declined from 178/100 000 in 2005 to 112/100 000 in 2010 before increasing to 149/100 000 in 2018. The incidence rate of AOM decreased from 4192/100 000 in 2005 to 3178/100 000 in 2018. BC had 970 455 CAP, 317 913 bacterial CAP, 35 287 pneumococcal pneumonia and 2 022 871 AOM cases. The incidence rate of CAP in BC decreased from 2214/100 000 in 2005 to 1964/100 000 in 2010 before increasing to 2176/100 000 in 2018; bacterial CAP incidence rate increased from 442/100 000 in 2005 to 981/100 000 in 2018. The incidence rate of AOM decreased from 3684/100 000 in 2005 to 2398/100 000 in 2018. The incidence rate of bacterial CAP increased with age in older adults (≥65 years) with the highest burden in the oldest cohort aged ≥85 years both before and after 13-valent pneumococcal conjugate vaccine (PCV13) programme in both provinces. Hospitalised pneumococcal pneumonia decreased slightly but non-hospitalised pneumococcal pneumonia increased in BC during PCV13 period. No consistent direct benefit of PCV13 on CAP was observed in the paediatric population.

Conclusions: There is a substantial burden of CAP and AOM in Ontario and BC. Indirect benefits from childhood PCV vaccination and polysaccharide vaccination of older adults have not substantially decreased the burden of pneumococcal pneumonia in older adults.
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http://dx.doi.org/10.1136/bmjresp-2022-001218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240885PMC
June 2022

Seasonality of influenza and coseasonality with avian influenza in Bangladesh, 2010-19: a retrospective, time-series analysis.

Lancet Glob Health 2022 08 13;10(8):e1150-e1158. Epub 2022 Jun 13.

Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Background: Seasonal and avian influenza viruses circulate among human and poultry populations in Bangladesh. However, the epidemiology of influenza is not well defined in this setting. We aimed to characterise influenza seasonality, examine regional heterogeneity in transmission, and evaluate coseasonality between circulating influenza viruses in Bangladesh.

Methods: In this retrospective, time-series study, we used data collected between January, 2010, and December, 2019, from 32 hospital-based influenza surveillance sites across Bangladesh. We estimated influenza peak timing and intensity in ten regions using negative binomial harmonic regression models, and applied meta-analytic methods to determine whether seasonality differed across regions. Using live bird market surveillance data in Dhaka, Bangladesh, we estimated avian influenza seasonality and examined coseasonality between human and avian influenza viruses.

Findings: Over the 10-year study period, we included 8790 human influenza cases and identified a distinct influenza season, with an annual peak in June to July each year (peak calendar week 27·6, 95% CI 26·7-28·6). Epidemic timing varied by region (I=93·9%; p<0·0001), with metropolitan regions peaking earlier and epidemic spread following a spatial diffusion pattern based on geographical proximity. Comparatively, avian influenza displayed weak seasonality, with moderate year-round transmission and a small peak in April (peak calendar week 14·9, 95% CI 13·2-17·0), which was out of phase with influenza peaks in humans.

Interpretation: In Bangladesh, influenza prevention and control activities could be timed with annual seasonality, and regional heterogeneity should be considered in health resource planning. Year-round avian influenza transmission poses a risk for viral spillover, and targeted efforts will be crucial for mitigating potential reassortment and future pandemic threats.

Funding: Canadian Institute of Health Research Vanier Canada Graduate Scholarship.
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http://dx.doi.org/10.1016/S2214-109X(22)00212-1DOI Listing
August 2022

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

Pediatr Blood Cancer 2022 09 11;69(9):e29793. Epub 2022 Jun 11.

Department of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Introduction: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited.

Methods: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes.

Results: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage.

Conclusion: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.
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http://dx.doi.org/10.1002/pbc.29793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350140PMC
September 2022

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

CMAJ 2022 04;194(14):E513-E523

Department of Epidemiology (Merckx), Biostatistics and Occupational Health, McGill University, Montréal, Que.; Department of Pediatrics (Cooke, Dewan, Restivo), University of Calgary, Calgary, Alta.; Department of Pediatrics (El Tal, Bitnun, Morris, Yeh, Yea, Gill), University of Toronto, Toronto, Ont.; Department of Pediatrics (Papenburg, Lefebvre, Scuccimarri), McGill University, Montréal, Que.; Department of Pediatrics (Ulloa-Gutierrez, Brenes-Chacon, Yock-Corrales, Ivankovich-Escoto, Soriano-Fallas, Hernandez-de Mezerville), Hospital Nacional de Niños Dr. Carlos Sáenz Herrera, Caja Costarricense de Seguro Social, San José, Costa Rica; Department of Pediatrics (Nateghian, Haghighi Aski, Manafi), Iran University of Medical Sciences, Tehran, Iran; Department of Pediatrics (Dwilow, Bullard), University of Manitoba, Winnipeg, Man.; Department of Pediatrics (Lopez, Sadarangani, Roberts), University of British Columbia; Vaccine Evaluation Center (Sadarangani), BC Children's Hospital Research Institute, Vancouver, BC; Department of Pediatrics (Barton, Petel), Western University, London, Ont.; Department of Pediatrics (Le Saux, Bowes), University of Ottawa, Ottawa, Ont.; Department of Pediatrics (Purewal, Lautermilch, Tehseen), University of Saskatchewan, Saskatoon, Sask.; Department of Pediatrics (Bayliss), Trillium Health Partners, Mississauga, Ont.; Department of Pediatrics (Wong), McMaster University, Hamilton, Ont.; Department of Pediatrics (Leifso), Queen's University, Kingston, Ont.; Department of Pediatrics (Foo), Memorial University, St John's, NL; Department of Pediatrics (Robinson), University of Alberta, Edmonton, Alta.

Background: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time.

Methods: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement.

Results: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 μg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%).

Interpretation: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.
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http://dx.doi.org/10.1503/cmaj.210873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001008PMC
April 2022

Underestimation of travel-associated risks by adult and paediatric travellers compared to expert assessment: A cross-sectional study at a hospital-based family pre-travel clinic.

Travel Med Infect Dis 2022 May-Jun;47:102315. Epub 2022 Mar 21.

Division of Infectious Diseases, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada; Department of Paediatrics, Faculty of Medicine, University of Toronto, 1 King's College Cir, Toronto, ON, M5S 1A8, Canada; Centre for Global Child Health, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada; Dalla Lana School of Public Health, University of Toronto, 155 College St Room 500, Toronto, ON, M5T 3M7, Canada. Electronic address:

Background: Travellers' perception of their risk for acquiring travel-related conditions is an important contributor to decisions and behaviors during travel. In this study, we aimed to assess the differences between traveller-perceived and expert-assessed risk of travel-related conditions in children and adults travelling internationally and describe factors that influence travellers' perception of risk.

Methods: Children and adults were recruited at the Hospital for Sick Children's Family Travel Clinic between October 2014 and July 2015. A questionnaire was administered to participants to assess their perceived risk of acquiring 32 travel-related conditions using a 7-point Likert scale. Conditions were categorized as vector-borne diseases, vaccine-preventable diseases, food and water borne diseases, sexually transmitted infections and other conditions. Two certified travel medicine experts reviewed each patient's chart and assigned a risk score based on the same 7-point Likert scale. Traveller and expert risk scores were compared using paired t-tests.

Results: In total, 207 participants were enrolled to participate in this study, 97 children (self-reported, n = 8; parent-reported, n = 89), and 110 adults. Travel-related risk for adults and parents answering for their children were significantly underestimated when compared to expert-assessed risk for 26 of the 32 assessed conditions. The underestimated conditions were the same for both adults and parents answering for children. Travel-related risk was not over-estimated for any condition.

Conclusions: Adults underestimated their children's and their own risk for most travel-related conditions. Strategies to improve the accuracy of risk perception of travel-related conditions by travellers are needed to optimize healthy travel for children and their families.
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http://dx.doi.org/10.1016/j.tmaid.2022.102315DOI Listing
May 2022

The effect of the COVID-19 pandemic on influenza-related hospitalization, intensive care admission and mortality in children in Canada: A population-based study.

Lancet Reg Health Am 2022 Mar 5;7:100132. Epub 2021 Dec 5.

Division of Infectious Diseases, The Hospital for Sick Children, Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Background: The COVID-19 pandemic resulted in unprecedented implementation of wide-ranging public health measures globally. During the pandemic, dramatic decreases in seasonal influenza virus detection have been reported worldwide. Information on the impact on paediatric influenza-related hospitalisations is limited. We describe influenza-related hospitalisation in children in Canada following the onset of the COVID-19 pandemic.

Methods: Data on influenza-related hospitalisations, intensive care unit (ICU) admissions and in-hospital deaths in children across Canada were obtained from the Canadian Immunisation Monitoring Program, ACTive (IMPACT). This national active surveillance initiative comprises 90% of all tertiary care paediatric beds in Canada. The study period included eleven influenza seasons, from the 2010/2011 season until the 2020/2021 season inclusive. Time series modelling was used to compare the observed to predicted influenza-related hospitalisations following the COVID-19 pandemic.

Results: Following the COVID-19 pandemic there was a significant decrease in paediatric influenza-related hospitalisations compared to predicted influenza-related hospitalisations for this time period ( < 0•0001). No paediatric influenza-related hospitalisations, ICU admission or deaths were reported for the 2020/2021 influenza season.

Conclusions: We show complete absence of paediatric influenza infection-related hospitalisation in a Canadian National Surveillance Network during the 2020/2021 influenza season. This significant decrease is likely related in large part to non-pharmacological public health interventions implemented during the COVID-19 pandemic, although the potential role of viral interference is unknown.

Funding: The Canadian Immunisation Monitoring Program, Active (IMPACT) influenza surveillance is a national surveillance initiative managed by the Canadian Paediatric Society and conducted by the IMPACT network of paediatric investigators on behalf of the Public Health Agency of Canada's Centre for Immunisation and Respiratory Infectious Diseases.
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http://dx.doi.org/10.1016/j.lana.2021.100132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913102PMC
March 2022

Infants hospitalized for acute COVID-19: disease severity in a multicenter cohort study.

Eur J Pediatr 2022 Jun 25;181(6):2535-2539. Epub 2022 Feb 25.

Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)).    Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.
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http://dx.doi.org/10.1007/s00431-022-04422-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880297PMC
June 2022

Impact of the COVID-19 pandemic on routine immunization coverage in children under 2 years old in Ontario, Canada: A retrospective cohort study.

Vaccine 2022 03 8;40(12):1790-1798. Epub 2022 Feb 8.

Department of Family and Community Medicine, University of Toronto, 500 University Avenue, 5th Floor, Toronto, Ontario M5G 1V7, Canada; Toronto Western Family Health Team, University Health Network, 440 Bathurst Street, 3rd Floor, Toronto, Ontario M5T 2S6, Canada; North York General Hospital, 4001 Leslie Street, Toronto, Ontario M2K 1E1, Canada.

Background: The COVID-19 pandemic has caused a disruption in childhood immunization coverage around the world. This study aimed to determine the change in immunization coverage for children under 2 years old in Ontario, Canada, comparing time periods pre-pandemic to during the first year of the pandemic.

Methods: Observational retrospective open cohort study, using primary care electronic medical record data from the University of Toronto Practice-Based Research Network (UTOPIAN) database, from January 2019 to December 2020. Children under 2 years old who had at least 2 visits recorded in UTOPIAN were included. We measured up-to-date (UTD) immunization coverage rates, overall and by type of vaccine (DTaP-IPV-Hib, PCV13, Rota, Men-C-C, MMR, Var), and on-time immunization coverage rates by age milestone (2, 4, 6, 12, 15, 18 months). We compared average coverage rates over 3 periods of time: January 2019-March 2020 (T1); March-July 2020 (T2); and August-December 2020 (T3).

Results: 12,313 children were included. Overall UTD coverage for all children was 71.0% in T1, dropped by 5.7% (95% CI: -6.2, -5.1) in T2, slightly increased in T3 but remained lower than in T1. MMR vaccine UTD coverage slightly decreased in T2 and T3 by approximately 2%. The largest decreases were seen at ages 15-month and 18-month old, with drops in on-time coverage of 14.7% (95% CI: -18.7, -10.6) and 16.4% (95% CI: -20.0, -12.8) respectively during T2. When stratified by sociodemographic characteristics, no specific subgroup of children was found to have been differentially impacted by the pandemic.

Conclusion: Childhood immunization coverage rates for children under 2 years in Ontario decreased significantly during the early period of the COVID-19 pandemic and only partially recovered during the rest of 2020. Public health and educational interventions for providers and parents are needed to ensure adequate catch-up of delayed/missed immunizations to prevent potential outbreaks of vaccine-preventable diseases.
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http://dx.doi.org/10.1016/j.vaccine.2022.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824235PMC
March 2022

Pretravel plans and discrepant trip experiences among travelers attending a tertiary care centre family travel medicine clinic.

PLoS One 2022 3;17(2):e0262075. Epub 2022 Feb 3.

Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.

Background: International travel can expose travelers to a number of health risks. Pretravel consultation (PC) helps mitigate risk and prepare travelers for health concerns that might arise. The assessment of risk, mitigation strategies, and relevance of pretravel advice is dependent on how closely travelers adhere to their planned travel itinerary and activities. We determined the proportion of returned travelers whose completed travel experiences differed from their stated travel itineraries, and identified discrepancies that significantly altered the traveler's health risk and would have required alternative counseling during their PC.

Methods: We conducted a prospective cohort study at the SickKids' Family Travel Clinic between October 2014 and November 2015. Returned travelers who completed a post-travel survey were included. Pretravel consultation assessments and post-trip surveys were compared to identify discrepant trip experiences.

Results: A total of 389 travelers presented to the clinic for a PC during the study period and 302 (77.6%) were enrolled. Post-travel surveys were received from 119 (39.4%) participants, representing 101 unique itineraries. The median participant age was 36.3 years (IQR 26.6-47.5) and there were 73 female travelers (61%). Most participants (n = 87,73%) were healthy as well as Canadian born (n = 84, 71%). A quarter of travelers were visiting friends and relatives (VFR) (n = 30, 25.2%). The vast majority of returned travelers (n = 109, 92%) reported discrepant trip experiences involving trip duration, countries visited, accommodations, environmental surroundings and/or activities. Almost two thirds of these individuals (n = 68, 62%) would have required alternative pretravel counseling. We did not identify any demographic or planned trip characteristics that predicted discrepant trip experiences requiring alternative pretravel counseling.

Conclusions: The majority of travelers reported discrepant trip experiences and the discrepancies often affected health risk. Therefore, clinicians should consider providing broader counselling during the PC as discrepancies from planned travel are common.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262075PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812894PMC
February 2022

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

Pediatr Infect Dis J 2022 04;41(4):e166-e171

BC Children's Hospital, Vancouver, BC.

Background: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate.

Method: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada.

Results: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers.

Conclusion: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.
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http://dx.doi.org/10.1097/INF.0000000000003454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920017PMC
April 2022

Delay in childhood vaccinations during the COVID-19 pandemic.

Can J Public Health 2022 02 20;113(1):126-134. Epub 2022 Jan 20.

Department of Paediatrics, St. Michael's Hospital, 61 Queen Street East, 2nd Floor, Toronto, ON, M5C 2T2, Canada.

Objectives: In many jurisdictions, routine medical care was reduced in response to the COVID-19 pandemic. The objective of this study was to determine whether the frequency of on-time routine childhood vaccinations among children age 0-2 years was lower following the COVID-19 declaration of emergency in Ontario, Canada, on March 17, 2020, compared to prior to the pandemic.

Methods: We conducted a longitudinal cohort study of healthy children aged 0-2 years participating in the TARGet Kids! primary care research network in Toronto, Canada. A logistic mixed effects regression model was used to determine odds ratios (ORs) for delayed vaccination (> 30 days vs. ≤ 30 days from the recommended date) before and after the COVID-19 declaration of emergency, adjusted for confounding variables. A Cox proportional hazards model was used to explore the relationship between the declaration of emergency and time to vaccination.

Results: Among 1277 children, the proportion of on-time vaccinations was 81.8% prior to the COVID-19 declaration of emergency and 62.1% after (p < 0.001). The odds of delayed vaccination increased (odds ratio = 3.77, 95% CI: 2.86-4.96), and the hazard of administration of recommended vaccinations decreased after the declaration of emergency (hazard ratio = 0.75, 95% CI: 0.60-0.92). The median vaccination delay time was 5 days (95% CI: 4-5 days) prior to the declaration of emergency and 17 days (95% CI: 12-22 days) after.

Conclusion: The frequency of on-time routine childhood vaccinations was lower during the first wave of the COVID-19 pandemic. Sustained delays in routine vaccinations may lead to an increase in rates of vaccine-preventable diseases.
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http://dx.doi.org/10.17269/s41997-021-00601-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773389PMC
February 2022

Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh.

BMC Infect Dis 2022 Jan 13;22(1):52. Epub 2022 Jan 13.

Department of Nutritional Sciences, University of Toronto, Toronto, Canada.

Background: Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known.

Methods: This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling.

Results: Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons).

Conclusion: Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.
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http://dx.doi.org/10.1186/s12879-022-07032-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759256PMC
January 2022

Cost-effectiveness analysis of implementing an integrated neonatal care kit to reduce neonatal infection in rural Pakistan.

BMJ Open 2022 Jan 4;12(1):e047793. Epub 2022 Jan 4.

Dalla Lana School of Public Health, University of Toronto Institute of Health Policy Management and Evaluation, Toronto, Ontario, Canada.

Objective: To evaluate the cost-effectiveness of distribution of the integrated neonatal care kit (iNCK) by community health workers from the healthcare payer perspective in Rahimyar Khan, Pakistan.

Setting: Rahimyar Khan, Pakistan.

Participants: N/A.

Intervention: Cost-utility analysis using a Markov model based on cluster randomised controlled trial (cRCT: NCT02130856) data and a literature review. We compared distribution of the iNCK to pregnant mothers to local standard of care and followed infants over a lifetime horizon.

Primary And Secondary Outcome Measures: The primary outcome was incremental net monetary benefit (INMB, at a cost-effectiveness threshold of US$15.50), discounted at 3%. Secondary outcomes were life years, disability-adjusted life years (DALYs) and costs.

Results: At a cost-effectiveness threshold of US$15.50, distribution of the iNCK resulted in lower expected DALYs (28.7 vs 29.6 years) at lower expected cost (US$52.50 vs 55.20), translating to an INMB of US$10.22 per iNCK distributed. These results were sensitive to the baseline risk of infection, cost of the iNCK and the estimated effect of the iNCK on the relative risk of infection. At relative risks of infection below 0.79 and iNCK costs below US$25.90, the iNCK remained cost-effective compared with current local standard of care.

Conclusion: The distribution of the iNCK dominated the current local standard of care (ie, the iNCK is less costly and more effective than current care standards). Most of the cost-effectiveness of the iNCK was attributable to a reduction in neonatal infection.
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http://dx.doi.org/10.1136/bmjopen-2020-047793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728405PMC
January 2022

Caractéristiques des hospitalisations au Canada d’enfants ayant contracté une infection aiguë par le SRAS-CoV-2 en 2020.

CMAJ 2021 11;193(46):E1774-E1785

Unités de pédiatrie générale (Drouin, Luu) et de soins intensifs pédiatriques (Farrell), Département of pédiatrie, et Service des maladies infectieuses (Kakkar), Centre hospitalier universitaire Sainte-Justine; Département de médecine sociale et préventive (Drouin), École de santé publique de l'Université de Montréal, Montréal, Qc; Division de médecine pédiatrique (Moore Hepburn, Giroux, Orkin), Centre for Global Child Health (Farrar, Morris) et Child Health Evaluative Sciences (Morris, Orkin), Hôpital pour enfants malades; Institut pour les politiques, la gestion et l'évaluation de la santé (Moore Hepburn) et départements de pédiatrie (Chan) et de santé publique clinique (Morris), École Dalla Lana de santé publique, Université de Toronto, Toronto, Ont.; Département de pédiatrie (Baerg, Purewal), Université de la Saskatchewan; Divisions de pédiatrie générale (Baerg) et d'infectiologie pédiatrique (Purewal), Hôpital pour enfants Jim Pattison, Autorité sanitaire de la Saskatchewan, Saskatoon, Sask.; Département de santé infantile et féminine (Chan), Trillium Health Partners, Mississauga, Ont.; Service de soins intensifs pédiatriques (Cyr), Centre hospitalier et Faculté de médecine (Cyr), Université de Sherbrooke, Sherbrooke, Qc.; Départements de pédiatrie et de santé de l'enfant (Embree) et microbiologie médicale et infectiologie (Embree), Universi té du Mani toba, Winnipeg, Man.; Division d'infectiologie (Forgie), Département de pédiatrie, Université de l'Alberta; Hôpital pour enfants Stollery (Forgie), Edmonton, Alb.; Département de pédiatrie (Sadarangani, Tang), Université de la Colombie-Britannique, Vancouver, C.-B.; Programme canadien de surveillance pédiatrique (King, Laffin), Société canadienne de pédiatrie, Ottawa, Ont.; Division d'infectiologie pédiatrique (Papenburg), Département de pédiatrie, Hôpital de Montréal pour enfants; Division de microbiologie (Papenburg), Département clinique de médecine de laboratoire, Centre universitaire de santé McGill, Montréal, Qc; Division de pédiatrie générale (Pound), Département de pédiatrie, Centre hospitalier pour enfants de l'est de l'Ontario, Ottawa, Ont.; Division d'hématologie/oncologie pédiatrique (Price), Département de pédiatrie, Université Dalhousie, Halifax, N.-É.; Vaccine Evaluation Center (Sadarangani), Institut de recherche de l'Hôpital pour enfants de la Colombie-Britannique, Vancouver, C.-B.; Agence de la santé publique du Canada (Salvadori), Ottawa, Ont.; Département de pédiatrie (Top), Université Dalhousie, Halifax, N.-É.; Division d'infectiologie (Viel-Thériault), Département de pédiatrie, CHU de Québec-Université Laval, Québec, Qc; Divisions d'infectiologie (Morris) et de neurologie (Donner), Hôpital pour enfants malades; Université de Toronto, Toronto, Ont.

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http://dx.doi.org/10.1503/cmaj.210053-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608451PMC
November 2021

Population-based incidence of invasive pneumococcal disease in children and adults in Ontario and British Columbia, 2002-2018: A Canadian Immunization Research Network (CIRN) study.

Vaccine 2021 12 19;39(52):7545-7553. Epub 2021 Nov 19.

Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: Invasive pneumococcal disease (IPD) burden, evaluated in Canada using reported confirmed cases in surveillance systems, is likely underestimated due to underreporting. We estimated the burden of IPD in Ontario and British Columbia (BC) by combining surveillance data with health administrative databases.

Methods: We established a cohort of 27,525 individuals in Ontario and BC. Laboratory-confirmed IPD cases were identified from Ontario's integrated Public Health Information System and the BC Centre for Disease Control Public Health Laboratory. Possible IPD cases were identified from hospitalization data in both provinces, and from emergency department visit data in Ontario. We estimated the age and sex adjusted annual incidence of IPD and pneumococcal conjugate/polysaccharide vaccine (PCV/PPV) serotype-specific IPD using Poisson regression models.

Results: In Ontario, 20,205 overall IPD cases, including 15,299 laboratory-confirmed cases, were identified with relatively stable age- and sex-adjusted annual incidence rates ranging from 13.7/100,000 (2005) to 13.6/100,000 (2018). In BC, 7,320 overall IPD cases, including 5,932 laboratory-confirmed cases were identified; annual incidence rates increased from 10.9/100,000 (2002) to 13.2/100,000 (2018). Older adults aged ≥ 85 years had the highest incidence rates. During 2007-2018 the incidence of PCV7 serotypes and additional PCV13 serotypes decreased while the incidence of unique PPV23 and non-vaccine serotypes increased in both provinces.

Conclusions: IPD continues to cause a substantial public health burden in Canada despite publicly funded pneumococcal vaccination programs, resulting in part from an increase in unique PPV23 and non-vaccine serotypes.
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http://dx.doi.org/10.1016/j.vaccine.2021.11.032DOI Listing
December 2021

Therapeutic Drug Monitoring of Moxifloxacin to Guide Treatment of Meningitis in an Extremely Preterm Infant.

J Pediatr Pharmacol Ther 2021 10;26(8):857-862. Epub 2021 Nov 10.

() is a rare cause of neonatal bacterial meningitis. Treatment can be challenging because of ' intrinsic antibiotic resistance and the difficulty in accessing antimicrobial susceptibility testing. In this report, we describe an extremely preterm male infant with seizures who had a subsequent diagnosis of meningitis. Because of severity of illness, doxycycline (4 mg/kg IV every 24 hours) and moxifloxacin (5 mg/kg IV every 24 hours) were started empirically. Repeat cerebrospinal fluid cultures were negative and showed decreasing pleiocytosis. Given the concentration-dependent killing of moxifloxacin and concern for endovascular infection from a concomitant cerebral venous sinus thrombosis, serum concentrations of moxifloxacin were obtained to estimate pharmacokinetic and pharmacodynamic parameters. These were compared to the targets described in other case reports of meningitis. The maximum serum concentration (C) was 2.5 mg/L, volume of distribution was 2.2 L/kg, clearance was 0.18 L/kg/hr, terminal half-life was 8.6 hours, and area-under-the-concentration-time curve (AUC) was 28.1 mg•hr/L. Using the range of minimum inhibitory concentrations (MICs) reported in the literature, the estimated C/MIC for this patient was 21 to 158 (target C/MIC: >10) and AUC/MIC was 234 to 1757 (target AUC/MIC: ≥100). Doxycycline and moxifloxacin were continued for 6 weeks. No adverse events to moxifloxacin or doxycycline were observed in the NICU. This report describes the successful treatment of neonatal meningitis and adds to the knowledge of pharmacokinetic and pharmacodynamic parameters of moxifloxacin in neonates. Additional data will help to confirm the role for routine therapeutic drug monitoring of moxifloxacin in neonates.
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http://dx.doi.org/10.5863/1551-6776-26.8.857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592008PMC
November 2021

Population Health Surveillance Using Mobile Phone Surveys in Low- and Middle-Income Countries: Methodology and Sample Representativeness of a Cross-sectional Survey of Live Poultry Exposure in Bangladesh.

JMIR Public Health Surveill 2021 11 12;7(11):e29020. Epub 2021 Nov 12.

Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh.

Background: Population-based health surveys are typically conducted using face-to-face household interviews in low- and middle-income countries (LMICs). However, telephone-based surveys are cheaper, faster, and can provide greater access to hard-to-reach or remote populations. The rapid growth in mobile phone ownership in LMICs provides a unique opportunity to implement novel data collection methods for population health surveys.

Objective: This study aims to describe the development and population representativeness of a mobile phone survey measuring live poultry exposure in urban Bangladesh.

Methods: A population-based, cross-sectional, mobile phone survey was conducted between September and November 2019 in North and South Dhaka City Corporations (DCC), Bangladesh, to measure live poultry exposure using a stratified probability sampling design. Data were collected using a computer-assisted telephone interview platform. The call operational data were summarized, and the participant data were weighted by age, sex, and education to the 2011 census. The demographic distribution of the weighted sample was compared with external sources to assess population representativeness.

Results: A total of 5486 unique mobile phone numbers were dialed, with 1047 respondents completing the survey. The survey had an overall response rate of 52.2% (1047/2006) and a co-operation rate of 89.0% (1047/1176). Initial results comparing the sociodemographic profile of the survey sample to the census population showed that mobile phone sampling slightly underrepresented older individuals and overrepresented those with higher secondary education. After weighting, the demographic profile of the sample population matched well with the latest DCC census population profile.

Conclusions: Probability-based mobile phone survey sampling and data collection methods produced a population-representative sample with minimal adjustment in DCC, Bangladesh. Mobile phone-based surveys can offer an efficient, economic, and robust way to conduct surveillance for population health outcomes, which has important implications for improving population health surveillance in LMICs.
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http://dx.doi.org/10.2196/29020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663489PMC
November 2021

Frequency and patterns of exposure to live poultry and the potential risk of avian influenza transmission to humans in urban Bangladesh.

Sci Rep 2021 11 8;11(1):21880. Epub 2021 Nov 8.

London School of Hygiene and Tropical Medicine, London, UK.

Avian influenza is endemic in Bangladesh, where greater than 90% of poultry are marketed through live poultry markets (LPMs). We conducted a population-based cross-sectional mobile telephone survey in urban Dhaka, Bangladesh to investigate the frequency and patterns of human exposure to live poultry in LPMs and at home. Among 1047 urban residents surveyed, 74.2% (95% CI 70.9-77.2) reported exposure to live poultry in the past year, with the majority of exposure occurring on a weekly basis. While visiting LPMs was less common amongst females (40.3%, 95% CI 35.0-45.8) than males (58.9%, 95% CI 54.0-63.5), females reported greater poultry exposure through food preparation, including defeathering (13.2%, 95% CI 9.5-17.9) and eviscerating (14.8%, 95% CI 11.2-19.4) (p < 0.001). A large proportion of the urban population is frequently exposed to live poultry in a setting where avian influenza viruses are endemic in LPMs. There is thus not only ample opportunity for spillover of avian influenza infections into humans in Dhaka, Bangladesh, but also greater potential for viral reassortment which could generate novel strains with pandemic potential.
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http://dx.doi.org/10.1038/s41598-021-01327-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575886PMC
November 2021

Impact of intrapartum antibiotics on the infant gastrointestinal microbiome: a narrative review.

Arch Dis Child 2022 07 29;107(7):627-634. Epub 2021 Oct 29.

Division of Infectious Diseases and Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada

Background: The composition of the infant gastrointestinal (GI) microbiome has been linked to adverse long-term health outcomes and neonatal sepsis. Several factors are known to impact the composition of the microbiome, including mode of delivery, gestational age, feeding method and exposure to antibiotics. The impact of intrapartum antibiotics (IPAs) on the infant microbiome requires further research.

Objective: We aimed to evaluate the impact of IPAs on the infant GI microbiome.

Methods: We searched Ovid MEDLINE and Embase Classic+Embase for articles in English reporting on the microbiome of infants exposed to IPAs from the date of inception to 3 January 2021. Primary outcomes included abundance and colonisation of and , as well as alpha and beta diversity.

Results: 30 papers were included in this review. In the first year of life, following exposure to IPAs, 30% (6/20) of infant cohorts displayed significantly reduced , 89% (17/19) did not display any significant differences in colonisation, 21% (7/34) displayed significantly reduced alpha diversity and 35% (12/34) displayed alterations in beta diversity. Results were further stratified by delivery, gestational age (preterm or full term) and feeding method.

Conclusions: IPAs impact the composition of the infant GI microbiome, resulting in possible reductions and alpha diversity, and possible alterations in beta diversity. Our findings may have implications for maternal and neonatal health, including interventions to prevent reductions in health-promoting bacteria (eg, probiotics) and IPA class selection.
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http://dx.doi.org/10.1136/archdischild-2021-322590DOI Listing
July 2022

Characteristics of children admitted to hospital with acute SARS-CoV-2 infection in Canada in 2020.

CMAJ 2021 09;193(38):E1483-E1493

Divisions of General Pediatrics (Drouin, Luu) and Pediatric Intensive Care (Farrell), Department of Pediatrics, and Division of Infectious Diseases (Kakkar), Centre Hospitalier Universitaire Sainte-Justine; Department of Social and Preventive Medicine (Drouin), School of Public Health, Université de Montréal, Montréal, Que.; Division of Paediatric Medicine (Moore Hepburn, Giroux, Orkin), Centre for Global Child Health (Farrar, Morris) and Child Health Evaluative Sciences (Morris, Orkin), The Hospital for Sick Children; Institute of Health Policy, Management and Evaluation (Moore Hepburn), and Departments of Pediatrics (Chan) and Clinical Public Health (Morris), Dalla Lana School of Public Health, University of Toronto, Toronto, Ont.; Department of Pediatrics (Baerg, Purewal), University of Saskatchewan; Divisions of General Paediatrics (Baerg) and Pediatric Infectious Diseases (Purewal), Jim Pattison Children's Hospital, Saskatchewan Health Authority, Saskatoon, Sask.; Department of Children's and Women's Health (Chan), Trillium Health Partners, Mississauga, Ont.; Service de soins intensifs pédiatriques (Cyr), Centre Hospitalier, and Faculté de médecine (Cyr), Université de Sherbrooke, Sherbrooke, Que.; Departments of Paediatrics and Child Health (Embree), and Medical Microbiology and Infectious Diseases (Embree), University of Manitoba, Winnipeg, Man.; Division of Infectious Diseases (Forgie), Department of Pediatrics, University of Alberta; Stollery Children's Hospital (Forgie), Edmonton, Alta.; Department of Pediatrics (Sadarangani, Tang), University of British Columbia, Vancouver, BC; Canadian Paediatric Surveillance Program (King, Laffin), Canadian Paediatric Society, Ottawa, Ottawa, Ont.; Division of Pediatric Infectious Diseases (Papenburg), Department of Pediatrics, Montreal Children's Hospital; Division of Microbiology (Papenburg), Department of Clinical Laboratory Medicine, McGill University Health Centre, Montréal, Que.; Division of General Pediatrics (Pound), Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ont.; Division of Pediatric Hematology/Oncology (Price), Department of Pediatrics, Dalhousie University, Halifax, NS; Vaccine Evaluation Center (Sadarangani), BC Children's Hospital Research Institute, Vancouver, BC; Public Health Agency of Canada (Salvadori), Ottawa, Ont.; Department of Pediatrics (Top), Dalhousie University, Halifax, NS; Division of Infectious Diseases (Viel-Thériault), Department of Pediatrics, CHU de Québec-Université Laval, Québec, Que.; Divisions of Infectious Diseases (Morris) and Neurology (Donner), The Hospital for Sick Children; University of Toronto, Toronto, Ont.

Background: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease.

Methods: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital.

Results: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19.

Interpretation: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.
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http://dx.doi.org/10.1503/cmaj.210053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486480PMC
September 2021

Antiviral Use in Canadian Children Hospitalized for Influenza.

Pediatrics 2021 10 21;148(4). Epub 2021 Sep 21.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.

Objectives: Antivirals are recommended for children hospitalized with influenza but are underutilized. We describe antiviral prescribing during influenza admissions in Canadian pediatric centers and identify factors associated with antiviral use.

Methods: We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from 2010-2011 to 2018-2019. Logistic regression analyses were used to identify factors associated with antiviral use.

Results: Among 7545 patients, 57.4% were male; median age was 3 years (interquartile range: 1.1-6.3). Overall, 41.3% received antiviral agents; 72.8% received antibiotics. Antiviral use varied across sites (range, 10.2% to 81.1%) and influenza season (range, 19.9% to 59.6%) and was more frequent in children with ≥1 chronic health condition (52.7% vs 36.7%; < .001). On multivariable analysis, factors associated with antiviral use included older age (adjusted odds ratio [aOR] 1.04 [95% confidence interval (CI), 1.02-1.05]), more recent season (highest aOR 9.18 [95% CI, 6.70-12.57] for 2018-2019), admission during peak influenza period (aOR 1.37 [95% CI, 1.19-1.58]), availability of local treatment guideline (aOR 1.54 [95% CI, 1.17-2.02]), timing of laboratory confirmation (highest aOR 2.67 [95% CI, 1.97-3.61] for result available before admission), presence of chronic health conditions (highest aOR 4.81 [95% CI, 3.61-6.40] for cancer), radiographically confirmed pneumonia (aOR 1.39 [95% CI, 1.20-1.60]), antibiotic treatment (aOR 1.51 [95% CI, 1.30-1.76]), respiratory support (1.57 [95% CI, 1.19-2.08]), and ICU admission (aOR 3.62 [95% CI, 2.88-4.56]).

Conclusions: Influenza antiviral agents were underused in Canadian pediatric hospitals, including among children with high-risk chronic health conditions. Prescribing varied considerably across sites, increased over time, and was associated with patient and hospital-level characteristics. Multifaceted hospital-based interventions are warranted to strengthen adherence to influenza treatment guidelines and antimicrobial stewardship practices.
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http://dx.doi.org/10.1542/peds.2020-049672DOI Listing
October 2021

Epidemiology, clinical features and outcomes of incident tuberculosis in children in Canada in 2013-2016: results of a national surveillance study.

Arch Dis Child 2021 12 20;106(12):1165-1170. Epub 2021 Aug 20.

Infectious Diseases, The Hospital for Sick Children, Toronto, Ontario, Canada.

Purpose: Childhood tuberculosis disease is difficult to diagnose and manage and is an under-recognised cause of morbidity and mortality. Reported data from Canada do not focus on childhood tuberculosis or capture key epidemiologic, clinical and microbiologic details. The purpose of this study was to assess demographics, presentation and clinical features of childhood tuberculosis in Canada.

Methods: We conducted prospective surveillance from 2013 to 2016 of over 2700 paediatricians plus vertical tuberculosis programmes for incident tuberculosis disease in children younger than 15 years in Canada using the Canadian Paediatric Surveillance Program (CPSP).

Results: In total, 200 cases are included in this study. Tuberculosis was intrathoracic in 183 patients of whom 86% had exclusively intrathoracic involvement. Central nervous system tuberculosis occurred in 16 cases (8%). Fifty-one per cent of cases were hospitalised and 11 (5.5%) admitted to an intensive care unit. Adverse drug reactions were reported in 9% of cases. The source case, most often a first-degree relative, was known in 73% of cases. Fifty-eight per cent of reported cases were Canadian-born Indigenous children. Estimated study rates of reported cases (per 100 000 children per year) were 1.2 overall, 8.6 for all Indigenous children and 54.3 for Inuit children.

Conclusion: Childhood tuberculosis may cause significant morbidity and resource utilisation. Key geographies and groups have very high incidence rates. Elimination of childhood tuberculosis in Canada will require well-resourced community-based efforts that focus on these highest risk groups.
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http://dx.doi.org/10.1136/archdischild-2021-322092DOI Listing
December 2021

The impact of the COVID-19 pandemic on influenza, respiratory syncytial virus, and other seasonal respiratory virus circulation in Canada: A population-based study.

Lancet Reg Health Am 2021 Sep 17;1:100015. Epub 2021 Jul 17.

Division of Infectious Diseases, The Hospital for Sick Children, Toronto, ON M5G 1 × 8, Canada.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in implementation of public health measures worldwide to mitigate disease spread, including; travel restrictions, lockdowns, messaging on handwashing, use of face coverings and physical distancing. As the pandemic progresses, exceptional decreases in seasonal respiratory viruses are increasingly reported. We aimed to evaluate the impact of the pandemic on laboratory confirmed detection of seasonal non-SARS-CoV-2 respiratory viruses in Canada.

Methods: Epidemiologic data were obtained from the Canadian Respiratory Virus Detection Surveillance System. Weekly data from the week ending 30 August 2014 until the week ending the 13 March 2021 were analysed. We compared trends in laboratory detection and test volumes during the 2020/2021 season with pre-pandemic seasons from 2014 to 2019.

Findings: We observed a dramatically lower percentage of tests positive for all seasonal respiratory viruses during 2020-2021 compared to pre-pandemic seasons. For influenza A and B the percent positive decreased to 0•0015 and 0•0028 times that of pre-pandemic levels respectively and for RSV, the percent positive dropped to 0•0169 times that of pre-pandemic levels. Ongoing detection of enterovirus/rhinovirus occurred, with regional variation in the epidemic patterns and intensity.

Interpretation: We report an effective absence of the annual seasonal epidemic of most seasonal respiratory viruses in 2020/2021. This dramatic decrease is likely related to implementation of multi-layered public health measures during the pandemic. The impact of such measures may have relevance for public health practice in mitigating seasonal respiratory virus epidemics and for informing responses to future respiratory virus pandemics.

Funding: No additional funding source was required for this study.
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http://dx.doi.org/10.1016/j.lana.2021.100015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285668PMC
September 2021

Antimicrobial susceptibilities and comparative whole genome analysis of two isolates of the probiotic bacterium Lactiplantibacillus plantarum, strain ATCC 202195.

Sci Rep 2021 08 5;11(1):15893. Epub 2021 Aug 5.

Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

A synbiotic containing Lactiplantibacillus plantarum [American Type Culture Collection (ATCC) strain identifier 202195] and fructooligosaccharide was reported to reduce the risk of sepsis in young infants in rural India. Here, the whole genome of two isolates of L. plantarum ATCC 202195, which were deposited to the ATCC approximately 20 years apart, were sequenced and analyzed to verify their taxonomic and strain-level identities, identify potential antimicrobial resistant genes and virulence factors, and identify genetic characteristics that may explain the observed clinical effects of L. plantarum ATCC 202195. Minimum inhibitory concentrations for selected antimicrobial agents were determined using broth dilution and gradient strip diffusion techniques. The two L. plantarum ATCC 202195 isolates were genetically identical with only three high-quality single nucleotides polymorphisms identified, and with an average nucleotide identity of 99.99%. In contrast to previously published reports, this study determined that each isolate contained two putative plasmids. No concerning acquired or transferable antimicrobial resistance genes or virulence factors were identified. Both isolates were sensitive to several clinically important antibiotics including penicillin, ampicillin and gentamicin, but resistant to vancomycin. Genes involved in stress response, cellular adhesion, carbohydrate metabolism and vitamin biosynthesis are consistent with features of probiotic organisms.
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http://dx.doi.org/10.1038/s41598-021-94997-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342526PMC
August 2021

Clinical manifestations and health outcomes associated with Zika virus infections in adults: A systematic review.

PLoS Negl Trop Dis 2021 07 12;15(7):e0009516. Epub 2021 Jul 12.

University of Toronto, Toronto, Ontario, Canada.

Background: Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally.

Methods: This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools.

Findings: We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS.

Conclusions: The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.
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http://dx.doi.org/10.1371/journal.pntd.0009516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297931PMC
July 2021

Effects of Maternal Vitamin D Supplementation During Pregnancy and Lactation on Infant Acute Respiratory Infections: Follow-up of a Randomized Trial in Bangladesh.

J Pediatric Infect Dis Soc 2021 Oct;10(9):901-909

Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background: We examined the effect of maternal vitamin D supplementation during pregnancy and lactation on risk of acute respiratory infection (ARI) in infants up to 6 months of age in Bangladesh.

Methods: This study was nested in a randomized, double-blind, placebo-controlled, 5-arm dose-ranging trial of prenatal and postpartum vitamin D supplementation. One group of women received 0 IU vitamin D per week during pregnancy and for 26 weeks post delivery ("placebo" group), one group received high-dose prenatal vitamin D supplementation of 28 000 IU per week and 26 weeks post delivery, and there were 3 additional dose-ranging groups receiving vitamin D supplementation during pregnancy only (4200, 16 800, and 28 000 IU per week, respectively). Episodes of ARI were identified by active and passive surveillance. The primary outcome was microbiologically confirmed ARI, and the primary analysis compared the high-dose prenatal plus postpartum vitamin D vs placebo groups.

Results: In total, 1174 mother-infant pairs were included. Among infants born to mothers in the placebo group, 98% had a venous umbilical cord 25(OH)D level below 30 nmol/L compared with none in the high-dose prenatal plus postdelivery vitamin D group. Incidence of microbiologically confirmed ARI in the high-dose prenatal plus postpartum vitamin D (1.21 episodes per 6 person-months; N = 235) and placebo groups (1.07 episodes per 6 person-months; N = 234) was not significantly different (hazard ratio of 1.12 [95% confidence intervals: 0.90-1.40]). There were no differences in the incidence of microbiologically confirmed or clinical ARI, upper, lower, or hospitalized lower respiratory tract infection between high-dose prenatal plus postpartum vitamin D and placebo groups.

Conclusions: Despite a high prevalence of maternal baseline vitamin D deficiency and significant effects of maternal vitamin D supplementation on infant vitamin D status, the intervention did not reduce the risk of microbiologically confirmed ARI in infants up to 6 months of age.
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http://dx.doi.org/10.1093/jpids/piab032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557369PMC
October 2021

Defining Clinical Public Health.

Clin Invest Med 2021 06 14;44(2):E71-76. Epub 2021 Jun 14.

Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, ON, Canada; Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, ON, Canada; Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.

Purpose: To solve complex health issues, an innovative and multidisciplinary framework is necessary. The Clinical Public Health (CPH) Division was established at the University of Toronto (UofT), Canada to foster inte-gration of primary care, preventive medicine and public health in education, practice and research. To better understand how the construct of CPH might be applied, we surveyed clinicians, researchers and public health professionals affiliated with the CPH Division to assess their understanding of the CPH concept and its utility in fostering broad collaboration.

Methods: A two-wave anonymous survey of the active faculty of the CPH Division, UofT was conducted across Canada. Wave 1 participants (n = 187; 2016) were asked to define CPH, while Wave 2 participants (n = 192; 2017) were provided a synthesis of Wave 1 results and asked to rank each definition. Both waves were asked about the need for a common definition, and to comment on CPH.

Results: Response rates for the first and second waves were 25% and 22%, respectively. Of the six definitions of CPH from Wave 1, "the intersection of clinical practice and public health," was most highly ranked by Wave 2 participants. Positive perceptions of CPH included multidisciplinary collaboration, new fields and insights, forward thinking and innovation. Negative perceptions included CPH being a confusing term, too narrow in scope or too clinical.

Conclusion: The concept of Clinical Public Health can foster multidisciplinary collaboration to address com-plex health issues because it provides a useful framework for bringing together key disciplines and diverse professional specialties.
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June 2021
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