Retrospective validation of a rapid Lyme fluorescent immunoassay in differentiating Lyme arthritis from other musculoskeletal presentations in children in a Lyme-endemic region.

Lyme arthritis can present similarly to other causes of joint pain and swelling including septic arthritis and other acute and chronic arthropathies of childhood. Septic arthritis, although rare, constitutes an orthopedic emergency and requires early surgical intervention to reduce the risk of permanent joint damage. Currently, results of standard serologic tests to diagnose Lyme disease take days to weeks, which is unhelpful in acute clinical decision-making. Thus, some children with Lyme arthritis are treated empirically for septic arthritis undergoing unnecessary invasive procedures and hospital admission while on inappropriate antibiotic therapy. We retrospectively validated the Quidel Sofia Lyme Fluorescent Immunoassay, a rapid serologic assay that can detect IgG and/or IgM antibodies to Borrelia burgdorferi in 10 minutes, in residual serum samples collected from 51 children who had Lyme arthritis and 55 children with musculoskeletal presentations who were Lyme negative. The sensitivity and specificity of the Sofia IgG to identify cases of Lyme arthritis in children were 100% (95% confidence interval [CI] of 93.0%-100%) and 96.4% (95% CI: 87.5%-99.6%), respectively. The positive likelihood ratio (LR) was 27.5 (95% CI 7-107), and the negative LR was 0.00 (95% LR 0.00-0.15). We propose that the Sofia IgG, a rapid method for identifying Lyme arthritis, may be useful in differentiating Lyme arthritis from other forms of arthritis. Used in conjunction with readily available clinical and laboratory variables, it could help to rapidly identify children who are at low risk of septic arthritis in Lyme-endemic regions. IMPORTANCE: Lyme arthritis is a common manifestation of Lyme disease in children, with clinical features overlapping with other causes of acute and chronic joint pain/swelling in children. We have demonstrated that the Sofia IgG is a reliable test to rule in and rule out the diagnosis of Lyme arthritis in children with musculoskeletal presentations in a Lyme-endemic region. When used in conjunction with clinical and laboratory variables routinely considered when differentiating Lyme arthritis from other diagnoses, the Sofia IgG has the potential to fill an important gap in care, especially when acute decision-making is necessary. The Sofia IgG should be included in prospective research studies examining clinical prediction tools to identify children at low risk of septic arthritis.

Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022.

Importance: Trends in COVID-19 severe outcomes have significant implications for the health care system and are key to informing public health measures. However, data summarizing trends in severe outcomes among patients hospitalized with COVID-19 in Canada are not well described. Objective: To describe trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic. Design, Setting, and Participants: Active prospective surveillance in this cohort study was conducted from March 15, 2020, to May 28, 2022, at a sentinel network of 155 acute care hospitals across Canada. Participants included adult (aged ≥18 years) and pediatric (aged 0-17 years) patients hospitalized with laboratory-confirmed COVID-19 at a Canadian Nosocomial Infection Surveillance Program (CNISP)-participating hospital. Exposures: COVID-19 waves, COVID-19 vaccination status, and age group. Main Outcomes and Measures: The CNISP collected weekly aggregate data on the following severe outcomes: hospitalization, admission to an intensive care unit (ICU), receipt of mechanical ventilation, receipt of extracorporeal membrane oxygenation, and all-cause in-hospital death. Results: Among 1 513 065 admissions, the proportion of adult (n = 51 679) and pediatric (n = 4035) patients hospitalized with laboratory-confirmed COVID-19 was highest in waves 5 and 6 of the pandemic compared with waves 1 to 4 (77.3 vs 24.7 per 1000 patient admissions). Despite this, the proportion of patients with positive test results for COVID-19 who were admitted to an ICU, received mechanical ventilation, received extracorporeal membrane oxygenation, and died were each significantly lower in waves 5 and 6 when compared with waves 1 through 4. Admission to the ICU and in-hospital all-cause death rates were significantly higher among those who were unvaccinated against COVID-19 when compared with those who were fully vaccinated (incidence rate ratio, 4.3 and 3.9, respectively) or fully vaccinated with an additional dose (incidence rate ratio, 12.2 and 15.1, respectively). Conclusions and Relevance: The findings of this cohort study of patients hospitalized with laboratory-confirmed COVID-19 suggest that COVID-19 vaccination is important to reduce the burden on the Canadian health care system as well as severe outcomes associated with COVID-19.

Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018.

BACKGROUND: Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals. METHODS: Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd). RESULTS: Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). CONCLUSIONS: This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.

Development of Quality Indicators to Evaluate the Appropriateness of Empiric Antimicrobial Use in Pediatric Patients.

Background: Use of quality indicators is one strategy recommended to assess antimicrobial prescribing for pediatric inpatients. Objective: To achieve consensus from infectious diseases clinicians on quality indicators that characterize appropriate empiric antimicrobial use for the management of infectious syndromes in pediatric inpatients. Methods: This study was completed using the Delphi technique. The research team developed an initial list of quality indicators, informed by a literature search. A multidisciplinary group of health care providers with expertise in infectious diseases was invited to participate. The list was disseminated to this panel of experts using Opinio survey software. The experts were asked to rate the indicators on a 9-point Likert scale in relation to the following criterion: "The importance of each item in determining appropriateness considering benefit or harm at the individual or population level". Consensus was defined as at least 75% agreement and a median score of 7 or higher. Results: Twelve of 31 invited experts completed at least 1 round of the survey, and 10 completed all rounds. Consensus was achieved on 28 of 31 proposed indicators after 3 rounds. Indicators with consensus were categorized under "empiric choice" (n = 12 indicators), "dose" (n = 5), "duration" (n = 2), "administration" (n = 4), "diagnosis" (n = 2), and "documentation" (n = 3). Six of the indicators for which consensus was achieved were rephrased by the experts. Conclusions: Consensus was achieved on quality indicators to assess the appropriateness of empiric antimicrobial use in pediatric patients. Clinicians and researchers can use these consensus-based indicators to assess adherence to best practice.

Contexte: L'utilisation d'indicateurs de qualité est l'une des stratégies recommandées pour évaluer la prescription d'antimicrobiens aux patients pédiatriques hospitalisés. Objectif: Parvenir à un consensus, entre les cliniciens des maladies infectieuses, portant sur les indicateurs de qualité qui caractérisent l'utilisation empirique appropriée des antimicrobiens pour la prise en charge des syndromes infectieux chez les patients pédiatriques hospitalisés. Méthodes: Cette étude a été réalisée à l'aide de la technique Delphi. L'équipe de recherche a dressé une liste initiale d'indicateurs de qualité éclairée par une recherche documentaire. Un groupe multidisciplinaire de prestataires de soins de santé ayant une expertise dans le domaine des maladies infectieuses a été invité à participer. La liste a été diffusée à ce panel d'experts à l'aide du logiciel d'enquête Opinio. Les experts ont été invités à noter les indicateurs sur une échelle de Likert de 9 points par rapport au critère suivant : « L'importance de chaque élément pour déterminer la pertinence compte tenu du bienfait ou du dommage à l'échelle individuelle ou de la population ¼. Le consensus était défini comme « Un accord d'au moins 75 % et un score médian d'au moins 7 ¼. Résultats: Douze des 31 experts invités ont terminé au moins 1 cycle de l'enquête et 10 les ont tous terminés. Un consensus a été atteint pour 28 des 31 indicateurs proposés après 3 cycles. Les indicateurs qui ont atteint le consensus ont été classés en « choix empirique ¼ (n = 12 indicateurs), « dose ¼ (n = 5), « durée ¼ (n = 2), « administration ¼ (n = 4), « diagnostic ¼ (n = 2) et « documentation ¼ (n = 3). Six indicateurs faisant consensus ont été reformulés par les experts. Conclusions: Un consensus a été atteint pour les indicateurs de qualité visant à évaluer l'utilisation empirique appropriée des antimicrobiens chez les patients pédiatriques. Les cliniciens et les chercheurs peuvent utiliser ces indicateurs basés sur le consensus pour évaluer le respect des meilleures pratiques.

Evaluating the impact of incorporating clinical practice guidelines for the management of infectious diseases into an electronic application (e-app).

OBJECTIVES: To improve dissemination and accessibility of guidelines to healthcare providers at our institution, guidance for infectious syndromes was incorporated into an electronic application (e-app). The objective of this study was to compare empiric antimicrobial prescribing before and after implementation of the e-app. DESIGN: This study was a before-and-after trial. SETTING: A tertiary-care, public hospital in Halifax, Canada. PARTICIPANTS: This study included pediatric patients admitted to hospital who were empirically prescribed an antibiotic for an infectious syndrome listed in the e-app. METHODS: Data were collected from medical records. Prescribing was independently assessed considering patient-specific characteristics using a standardized checklist by 2 members of the research team. Assessments of antimicrobial prescribing were compared, and discrepancies were resolved through discussion. Empiric antimicrobial prescribing before and after implementation of the e-app was compared using interrupted time-series analysis. RESULTS: In total, 237 patients were included in the preimplementation arm and 243 patients were included in the postimplementation arm. Pneumonia (23.8%), appendicitis (19.2%), and sepsis (15.2%) were the most common indications for antimicrobial use. Empiric antimicrobial use was considered optimal in 195 (81.9%) of 238 patients before implementation compared to 226 (93.0%) 243 patients after implementation. An immediate 15.5% improvement (P = .019) in optimal antimicrobial prescribing was observed following the implementation of the e-app. CONCLUSIONS: Empiric antimicrobial prescribing for pediatric patients with infectious syndromes improved after implementation of an e-app for dissemination of clinical practice guidelines. The use of e-apps may also be an effective strategy to improve antimicrobial use in other patient populations.

Epidemiology of Primary and Recurrent Healthcare-Associated and Community-Associated Pediatric Clostridioides difficile Infection in Canada, 2015-2020.

Clostridioides difficile infection (CDI) among children remains a concerning cause of morbidity in hospital settings. We present epidemiological and molecular trends in healthcare- and community-associated CDI among children in Canadian inpatient and outpatient settings, including those who experienced recurrent infections.

Cerebrospinal fluid shunt-associated surgical site infection with three-month versus twelve-month surveillance periods in Canadian hospitals.

Cerebrospinal fluid shunt-associated surgical site infection surveillance for 3 months compared to 12 months after surgery captures 83% of cases with no significant differences in patient characteristics, surgery types, or pathogens. A shorter 3-month follow-up can reduce resource use and allow for more timely reporting of healthcare-associated infection rates for hospitals.

Trends in Clostridioides difficile infection rates in Canadian hospitals during the coronavirus disease 2019 (COVID-19) pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults, Canada, 2015-2019.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015-2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015-2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Pertussis Disease and Antenatal Vaccine Effectiveness in Australian Children.

BACKGROUND: Population-level studies of severe pertussis extending beyond infancy are sparse, and none in the context of antenatal vaccination. We compared hospitalized pertussis cases from birth to 15 years of age before and after introduction of antenatal immunization. METHODS: Active surveillance of laboratory-confirmed pertussis hospitalizations in a national network of pediatric hospitals in Australia January 2012 to June 2019. Impact of maternal vaccination was assessed by vaccine effectiveness (VE) in cases and test-negative controls with <2 months of age and by before-after comparison of age distribution of cases. Among cases eligible for one or more vaccine doses, we examined proportions age-appropriately immunized and with comorbidities by age group. RESULTS: Among 419 eligible cases, the proportion <2 months of age significantly decreased from 33.1% in 2012 to 2014 compared with 19.6% in 2016 to 2019 when mothers of only 4 of 17 (23.5%) cases <2 months of age had received antenatal vaccination. VE was estimated to be 84.3% (95% CI, 26.1-96.7). Across all years (2012-2019), of 55 cases 4-11 months of age, 21 (38%) had ≥2 vaccine doses, whereas among 155 cases ≥12 months of age, 122 (85.2%) had ≥3 vaccine doses. Prevalence of comorbidities (primarily cardiorespiratory) increased from 5 (2.1%) <6 months of age to 36 (24.2%) ≥12 months of age (P < 0.001), with 6/16 (38%) cases ≥12 months of age who required intensive care having comorbidities. CONCLUSIONS: Below the age of 12 months, prevention of severe pertussis will be maximized by high maternal antenatal vaccine uptake and timeliness of infant vaccine doses. Despite full immunization, we found children ≥12 months of age accounted for 27% of hospitalizations <15 years, with 24% having comorbities, suggesting new vaccine strategies, such as additional doses or more immunogenic vaccines, require evaluation.

Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of the current landscape of invasive meningococcal disease in children.

BACKGROUND: Immunizations have led to a decrease in the incidence of invasive meningococcal disease (IMD) in Canada, but this infection still leads to significant morbidity and mortality. OBJECTIVES: The purpose of this study was to determine the burden of illness and management of IMD in paediatric hospitals. METHODS: Data were collected on all cases of IMD in eight paediatric hospitals from 2013 to 2017. RESULTS: There were 17 cases of IMD. Three of eight hospitals had no cases. Just over half of the cases were serogroup B (n=9); a quarter (n=4) were serogroup W; less than a quarter (n=3) were serogroup Y; and one was unknown. Two infected children were not started on antibiotics until day one and day five after the initial blood culture was collected, but had uneventful recoveries. Six cases required admission to intensive care units; two died. Six cases had probable or proven meningitis. Thrombocytopenia was documented in seven cases. All cases had elevated C-reactive protein levels. Seven children received more than seven days of antibiotics; of these seven, only two had complications that justified prolonged therapy (subdural empyema and septic knee). Six cases had a central line placed. CONCLUSION: IMD is now rare in Canadian children, but about one-third of the cases in our study required treatment in the intensive care unit and two died. Clinicians appear to not always be aware that a five to seven-day course is adequate for uncomplicated cases of bacteremia or meningitis.

COVID-19 and missed routine immunizations: designing for effective catch-up in Canada.

COVID-19 has led to disruption in routine immunization programs around the globe and here in Canada. The National Advisory Committee on Immunization (NACI) in Canada has indicated that this sets the stage for serious outbreaks of vaccine-preventable diseases. The World Health Organization has evidence-based guidance on how to address missed opportunities for vaccination, albeit predominately applicable for low- and middle-income countries. In Canada, immunization applies beyond infant and childhood immunization, with immunization across the life course being recommended by NACI. Three components stand out and must be integrated and used concurrently for best effect on catch-up in Canada: (1) Identify who has been missed across the life course; (2) detect delivery gaps, adapt and adjust, and develop multipronged tailored strategies for catch-up; and (3) communicate, document, evaluate and readjust the immunization programs. All must be adapted to the reality of the evolving COVID-19 pandemic. We cannot go back to a pre-COVID-19 world. However, ensuring that routine immunization and catch-up programs are done well during this pandemic strengthens the immunization foundation in Canada for when COVID-19 vaccines become available.

Antimicrobial use among adult inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program: 2009 to 2016.

BACKGROUND: Antimicrobial resistance is a growing threat to the world's ability to prevent and treat infections. Links between quantitative antibiotic use and the emergence of bacterial resistance are well documented. This study presents benchmark antimicrobial use (AMU) rates for inpatient adult populations in acute-care hospitals across Canada. METHODS: In this retrospective surveillance study, acute-care adult hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual AMU data on all systemic antimicrobials from 2009 to 2016. Information specific to intensive care units (ICUs) and non-ICU wards were available for 2014-2016. Data were analyzed using defined daily doses (DDD) per 1000 patient days (DDD/1000pd). RESULTS: Between 2009 and 2016, 16-18 CNISP adult hospitals participated each year and provided their AMU data (22 hospitals participated in ≥1 year of surveillance; 11 in all years). From 2009 to 2016, there was a significant reduction in use (12%) (from 654 to 573 DDD/1000pd, p = 0.03). Fluoroquinolones accounted for the majority of this decrease (47% reduction in combined oral and intravenous use, from 129 to 68 DDD/1000pd, p < 0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1000pd), piperacillin-tazobactam (53 DDD/1000pd), ceftriaxone (49 DDD/1000pd), vancomycin (combined oral and intravenous use was 44 DDD/1000pd; 7% of vancomycin use was oral), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1000pd). Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016 by 46% (p = 0.002) and 26% (p = 0.002) respectively. Ceftriaxone (85% increase, p = 0.0008) and oral amoxicillin-clavulanate (140% increase, p < 0.0001) use increased significantly but contributed only a small component (8.6 and 5.0%, respectively) of overall use. CONCLUSIONS: This study represents the largest collection of dispensed antimicrobial use data among inpatients in Canada to date. Between 2009 and 2016, there was a significant 12% decrease in AMU, driven primarily by a 47% decrease in fluoroquinolone use. Modest absolute increases in parenteral ceftriaxone and oral amoxicillin-clavulanate use were noted but contributed a small amount of total AMU. Ongoing national surveillance is crucial for establishing benchmarks and antimicrobial stewardship guidelines.

Challenges and opportunities of school-based HPV vaccination in Canada.

Primary prevention of human papillomavirus (HPV) through vaccination is a high priority in Canada's cancer prevention efforts. All Canadian provinces and territories have introduced publicly funded, school-based vaccination programs against HPV, but vaccine uptake remains suboptimal in some jurisdictions. We conducted a descriptive qualitative study to better understand the determinants of low HPV vaccine uptake and identify strategies to enhance vaccine acceptance using the socio-ecological model. In Quebec, interviews and focus groups were held in 2015-2016 with 70 key informants including immunization managers, school nurses, school principals, teachers and parents of Grade 4 students (9 years of age). Our findings showed that HPV vaccine uptake was dependent on many interrelated factors at the individual and interpersonal level (e.g. knowledge and attitudes of the different players involved in the vaccination system), at the community level (e.g. social group values and norms, media coverage around the HPV vaccine), at the organizational level (e.g. allocated resources, information provision, consent process, immunization setting and environment) and at the policy level (e.g. changes in provincial HPV vaccine program). We are using the data collection and interpretation tools and approaches developed by our team and used in Quebec to expand our study to four other provinces (British Columbia, Alberta, Ontario and Nova Scotia). We are conducting environmental scans, semi-structured interviews and a survey to better understand the determinants of low HPV vaccine uptake and identify strategies to enhance vaccine acceptance. Having an in-depth understanding of the determinants of HPV vaccination in school settings is critical in order to identify root causes of the suboptimal vaccine uptake and to develop tailored interventions to address these on both supply- and demand-side issues.

Frequency of Adverse Events Following Q Fever Immunisation in Young Adults.

Q fever is a zoonosis of concern in many countries. Vaccination is the most effective means of prevention, and since 1989, Australia has had a licensed Q fever vaccine, Q-VAX®. This vaccine was also used in the Netherlands in 2011 following the largest recorded Q fever outbreak globally. There is a paucity of available data regarding adverse events following immunisation (AEFI) for young adult females. Such data are important for informing future vaccination recommendations both within Australia and internationally. This study collected Q fever vaccine (Q-VAX®) AEFI data in veterinary and animal science students at Australian universities. Students were enrolled at the time of vaccination and were emailed a link to an online AEFI survey one week later. Of the 60% (499/827) that responded, 85% were female and the median age was 18 years. Local injection site reactions (ISRs) occurred in 98% (95%; CI 96⁻99%) of respondents, of which 30% (95% CI 24⁻32%) were severe. Systemic AEFI occurred in 60% (95%; CI 55⁻64%) of respondents within the seven days following immunisation. Medical attention was sought by 19/499 (3.8%) respondents, of whom one sought treatment at a hospital emergency department. Females were more likely than males to experience any local ISR (odds ratio [OR] 9.3; 95% CI 2.5⁻33.8; p < 0.001), ISRs of greater severity (OR 2.5; 95% CI 1.5⁻4.2; p < 0.001), and any systemic AEFI (OR 1.9; 95% CI 1.1⁻3.1; p = 0.016). These safety data suggest that a high frequency of adverse events following immunisation should be expected in young adults, particularly females. However, the consequences of Q fever disease are potentially far more debilitating.

Impact of a publicly funded monovalent rotavirus vaccination program in the Province of Quebec (Canada).

UNLABELLED: In November 2011, the province of Quebec, Canada implemented a publicly funded rotavirus (RV) vaccination program using the monovalent RV vaccine (RV1). To assess its impact, trends in passive RV laboratory detection and Emergency Department (ED) visits for gastroenteritis (GE) at two pediatric centers were evaluated. METHODS: RV tests performed were extracted from the virology laboratory databases and ED visits for GE between July 1, 2006 and June 30, 2013, from the ED databases of The Montreal Children's Hospital (MCH) and Centre Hospitalier Universitaire de Sherbrooke (CHUS). The percent positive RV tests over time and season duration were assessed using 5-week moving averages. We defined season start and end as the first two and the last two consecutive weeks where the percent positive RV tests were ≥ 10%, respectively. RESULTS: Comparing the pre- and post-vaccination program periods, a decrease in the proportion of positive RV tests was seen: 15.9% vs. 5.1% (p<0.001). Pre-vaccination program, RV seasons started between December and February, peaked in March or April and ended in May. In 2011-2012, the season started in March, peaked in April, and ended in May. In 2012-2013, the season lasted 3 weeks in May. ED visits for GE decreased post-introduction of the RV1 program: from 4.8% to 3.4% in 2011-2012, and 4.2% in 2012-13 (p<0.001). In children <2 years of age, ED GE visits decreased from 7.5% to 4.8% in 2011-2012, and 5.2% in 2012-2013 (p<0.001). Admissions for GE also decreased significantly from 0.41% of all ED visits to 0.14% in 2011-2012 and 0.22% in 2012-2013 (p<0.005). CONCLUSION: Implementation of a publicly funded RV vaccination program had a major impact on the epidemiology of RV infections in Quebec: RV seasons have started later and been of shorter duration, peak positives were fewer, and ED visits for GE decreased.

Salmonella enterica serotype Typhi infections in a Canadian pediatric hospital: a retrospective case series.

BACKGROUND: In developed countries, typhoid fever generally occurs in travellers or recent immigrants from endemic areas. Our aim was to describe the epidemiology of Salmonella enterica serotype Typhi infections among children presenting to a pediatric teaching hospital in Montréal, Quebec. METHODS: We included all patients less than 18 years of age who presented to the Montreal Children's Hospital between 1991 and 2011 with a laboratory-confirmed diagnosis of typhoid fever (Salmonella enterica ser. Typhi isolated from blood or stool) in a retrospective case series. RESULTS: During the study period, we identified 39 cases of typhoid fever (mean age of patient 7.5 yr). Four (10.3%) of these cases occurred in newly arrived immigrants shortly after their arrival in Canada (median 15.5 d). Most cases (76.9%) occurred in children who had visited friends and relatives in their home country. None of the travellers had received a vaccination against typhoid fever before their departure. All cases presented with high fever (mean temperature 40.4°C) that lasted for a mean of 15.8 days. Common accompanying symptoms included anorexia, abdominal pain, vomiting and diarrhea. All 39 isolates of S. enterica ser. Typhi were susceptible to third-generation cephalosporins, and 7 were resistant to ciprofloxacin. Ampicillin resistance occurred in 10 (25.6%) of the isolates. No deaths occurred among the study participants. INTERPRETATION: Most cases of typhoid fever occurred in children who had travelled to endemic areas to visit friends and relatives. Thus, there is a role for increased awareness on the part of family physicians and pediatricians caring for these children to discuss travel-related infections during regularly scheduled appointments, because parents might not consult travel clinics or discuss their travel plans before travelling back to their home country.

Direct mitochondrial dysfunction precedes reactive oxygen species production in amiodarone-induced toxicity in human peripheral lung epithelial HPL1A cells.

Amiodarone (AM), a drug used in the treatment of cardiac dysrrhythmias, can produce severe pulmonary adverse effects, including fibrosis. Although the pathogenesis of AM-induced pulmonary toxicity (AIPT) is not clearly understood, several hypotheses have been advanced, including increased inflammatory mediator release, mitochondrial dysfunction, and free-radical formation. The hypothesis that AM induces formation of reactive oxygen species (ROS) was tested in an in vitro model relevant for AIPT. Human peripheral lung epithelial HPL1A cells, as surrogates for target cells in AIPT, were susceptible to the toxicity of AM and N-desethylamiodarone (DEA), a major AM metabolite. Longer incubations (> or =6 h) of HPL1A cells with 100 microM AM significantly increased ROS formation. In contrast, shorter incubations (2 h) of HPL1A cells with AM resulted in mitochondrial dysfunction and cytoplasmic cytochrome c translocation. Preexposure of HPL1A cells to ubiquinone and alpha-tocopherol was more effective than that with Trolox C or 5,5-dimethylpyrolidine N-oxide (DMPO) at preventing AM cytotoxicity. These data suggest that mitochondrial dysfunction, rather than ROS overproduction, represents an early event in AM-induced toxicity in peripheral lung epithelial cells that may be relevant for triggering AIPT, and antioxidants that target mitochondria may potentially have beneficial effects in AIPT.

Staphylococcal pericarditis, and liver and paratracheal abscesses as presentations in two new cases of interleukin-1 receptor associated kinase 4 deficiency.

BACKGROUND: A deficiency in the interleukin-1 receptor activated kinase 4 (IRAK-4) has recently been associated with severe recurrent, predominantly Gram-positive bacterial infections. CLINICAL PRESENTATION: Two unrelated Canadian children with unique presentations of IRAK-4 deficiency are described. Both children had multiple Gram-positive bacterial infections, specifically Staphylococcus aureus and Streptococcus pneumoniae. Although these microorganisms in patients with IRAK-4 deficiency commonly cause invasive infections, such as meningitis, arthritis, and sepsis, the sites of infection in our patients were unique. In the first patient, staphylococcal pericarditis and, on a separate occasion, staphylococcal liver abscesses with generalized peritonitis were presentations. In the second child, S. aureus infection caused submandibular and periauricular lymphadenitis with unsuspected paratracheal abscess as well. These severe infections were not accompanied by the expected constitutional symptoms or hematologic and acute phase responses despite findings of advanced infection on diagnostic imaging. METHODS: Cytokine production [interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha] by whole blood leukocytes and adherent monocytes after stimulation with IL-1beta or various Toll-like receptor agonists [lipopolysaccharide, Poly I:C, S. aureus peptidoglycan (PGN)] was analyzed. IRAK-4 genes were sequenced by standard techniques. RESULTS: Failure by whole blood leukocytes to produce IL-6 or TNF-alpha in response to any of these stimuli was the most consistent finding. In striking contrast, IL-8 production in response to PGN was normal in both cases. Both patients had novel and heterozygous mutations and deletions in the IRAK-4 gene. CONCLUSIONS: Our results indicate that PGN-induced IL-6 production is via IRAK-4 dependent mechanisms, whereas IL-8 response to PGN is via IRAK-4 independent mechanisms. Patients with relatively silent but invasive bacterial infection should raise suspicion of IRAK-4 immunodeficiency.