Seroconversion to Seasonal Influenza Viruses after A(H1N1)pdm09 Virus Infection, Quebec, Canada

We looked for cross-reactive antibodies in 122 persons with paired serum samples collected during the 2009 pandemic of influenza virus A(H1N1)pdm09. Eight (12%) of 67 persons with A(H1N1)pdm09 infection confirmed by reverse transcription PCR and/or serology also seroconverted to the seasonal A/Brisbane/59/2007 (H1N1) virus, compared with 1 (2%) of 55 A(H1N1)pdm09-negative persons (p<0.05)

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series

Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. Findings We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 years (2·0–10·0) in upper middle-income countries, and 7·0 years (3·6–16·8) in high-income countries. Interpretation This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed

Utility of neuraminidase inhibitor dispensing data as a tool for influenza surveillance

Surveillance performed using routinely collected electronic data offers advantages that include a short reporting delay and a low acquisition cost. Monitoring of neuraminidase inhibitor (NI) dispensing in community pharmacies has emerged as a possible automated information source for influenza surveillance. However, little is known about the utility of these data for monitoring influenza activity. Therefore, we aimed to evaluate the timeliness, correlation, and predictive accuracy of community pharmacy NI dispensing in relation to laboratory-confirmed influenza activity in Quebec, Canada, during 2010-2013. Our secondary objective was to compare the characteristics of NI dispensing to those of visits for influenza-like illness (ILI) in emergency departments (ED), a commonly used source of surveillance data.Provincial weekly counts of positive influenza laboratory tests were used as a reference measure for the level of influenza circulation. We applied ARIMA models to account for seasonality and computed cross-correlation functions to measure the strengths of association and lead-lag-relationships of NI dispensing and ILI ED visits to our reference indicator. Finally, using an ARIMA model, we evaluated the ability of NI dispensing and ILI ED visits to predict laboratory–confirmed influenza. NI dispensing was significantly correlated (R=0.68) with influenza activity with no lag; the earliest statistically significant correlation occurred with a lead-time of 1 week. The maximal correlation of ILI ED visits was not as strong (R=0.50), but occurred with a lead-time of 1 week. Both NI dispensing and ILI ED visits were significant predictors of laboratory-confirmed influenza in a multivariable model; the predictive potential was greatest when NI counts were lagged to precede laboratory surveillance by two weeks.We conclude that NI dispensing data can provide timely and valuable information for the surveillance of influenza at the provincial level.La surveillance qui s'appuie sur des données électroniques recueillies et enregistrées en routine offre des avantages tels qu'un court retard de déclaration ainsi qu'un faible coût d'acquisition. La surveillance des ventes au détail de médicaments sur prescription contre l'influenza, les l'inhibiteurs de la neuraminidase (NI), a émergé comme une source possible d'information automatisée pour la vigie sanitaire de la grippe. Toutefois, les caractéristiques de la performance de ces données comme objet de surveillance ne sont pas bien connues. Dès lors, nous avons cherché à évaluer les données de distribution des NI dans les pharmacies communautaires comme un nouvel outil de surveillance de l'influenza, de par leur relation d'ordre temporelle (décalage), de leur corrélation et de leur capacité prédictive, en comparaison à l'activité grippale confirmée en laboratoire, au Québec, Canada, de 2010 à 2013. Notre objectif secondaire était de comparer ces caractéristiques à celles de la surveillance des visites pour syndrome d'allure grippal (SAG) inscrites aux d'urgences.Les données hebdomadaires provinciaux du nombre de tests de laboratoire positifs pour l'influenza ont été utilisées comme mesure de référence pour le niveau d'activité grippale. Nous avons appliqué la méthodologie de modélisation ARIMA pour tenir compte de la saisonnalité et de l'autocorrélation. Nous avons ensuite calculé les fonctions de contre-corrélation pour mesurer les forces d'association et explorer les relations temporelles entre la distribution des NI et les visites SAG avec notre mesure de référence. Enfin, nous avons évalué la valeur prédictive de la distribution des NI et des visites SAG dans le montage d'un modèle ARIMA pour les comptes d'influenza confirmés en laboratoire.La distribution des NI était significativement corrélée (R = 0,68) avec l'activité grippale au temps de latence zéro; la première corrélation statistiquement significative a eu lieu avec un décalage anticipatoire d'une semaine. La corrélation maximale des visites SAG n'était pas aussi forte (R = 0,50), mais a culminé une semaine plus tôt que les distributions NI. Tant la distribution des NI et les visites SAG à l'urgence étaient des variables prédictives significatives dans un modèle multivarié de cas confirmés en laboratoire; le potentiel prédictif du modèle était maximal lorsque les distributions NI ont été décalées pour précéder la surveillance en laboratoire de deux semaines.Ainsi, nous concluons que les données de distribution NI peuvent fournir des informations utiles et en temps opportun pour la surveillance de la grippe à l'échelle provinciale

A near-fatal infection with oseltamivir-resistant seasonal influenza A in a previously healthy child: Case report

A case of near-fatal oseltamivir-resistant seasonal influenza A infection in a previously healthy four-year-old boy is reported. This case highlights three important points for physicians: oseltamivir-resistant influenza A (H1N1) has recently emerged in North America; contrary to previously held beliefs, such strains are capable of causing severe disease in healthy children; and given this change in epidemiology, clinicians caring for children with severe seasonal influenza A infection should consider empiric dual therapy with oseltamivir and amantadine

The effect of Telehealth Antimicrobial Stewardship Program (Tele-ASP) on antimicrobial use in a pediatric intensive care unit: Pre- and post-implementation single center study

Background: Overuse or misuse of antimicrobials is common in pediatric intensive care units (PICU) and may be associated with poor clinical outcomes. Although an antimicrobial stewardship program (ASP) has been found to improve this practice, the required expertise in infectious diseases may be limited in some centers. We aimed to evaluate the effect of telehealth ASP on the rate of PICU antimicrobial use in a center without a local Infectious Diseases consultation service. Methods: A retrospective cohort study was performed between October 1st, 2018, and October 31st, 2020, in Farwaniya Hospital PICU, a 20-bed unit. All pediatric patients who were admitted to PICU and received systemic antimicrobials during the study period were included and followed until hospital discharge. The ASP team provided weekly prospective audit and feedback on antimicrobial use starting October 8th, 2019. A pediatric infectious diseases specialist joined the ASP rounds remotely. Descriptive analyses and a pre-post intervention comparison of days of therapy (DOT) were used to assess the effectiveness of the ASP intervention. Results: There were 272 and 156 PICU admissions received systemic antimicrobial before and after the initiation of ASP, respectively. Bronchiolitis and pneumonia were the most common admission diagnoses, together compromising 60.7% and 61.2% of cases pre- and post-ASP. The requirement for respiratory support was higher post-ASP (76.5% vs. 91.5%, p < 0.001). Average monthly antimicrobial use decreased from 922 (95%CI 745–1000) to 485 DOT/1000 patient-days (95%CI 246–722, P < 0.05). A decline in DOT was observed across most antibiotic classes, except for ceftriaxone. No effect on the length of PICU stay, length of hospitalization, or mortality was observed. Most (89.7%) ASP recommendations were followed either fully or partially. Conclusion: In settings where Infectious Diseases consultation services are unavailable, PICU telehealth ASP can be effectively implemented and associated with significantly reducing antimicrobial use

Reduced Susceptibility to Neuraminidase Inhibitors in Influenza B Isolate, Canada

We identified an influenza B isolate harboring a Gly407Ser neuraminidase substitution in an immunocompromised patient in Canada before antiviral therapy. This mutation mediated reduced susceptibility to oseltamivir, zanamivir, and peramivir, most likely by preventing interaction with the catalytic Arg374 residue. The potential emergence of such variants emphasizes the need for new antivirals

Panton-Valentine leukocidin in pediatric community-acquired Staphylococcus aureus infections

Purpose: Panton-Valentine Leukocidin (PVL) is an exotoxin produced by strains of Staphylococcus aureus (SA). Its importance as a virulence factor is controversial. We aim to further characterize the role of PVL in pediatric community-acquired SA infections. Methods: In a cohort study conducted from July to November 2006, we prospectively collected all strains of SA isolated at the Montreal Children’s Hospital causing community-acquired infections in children aged 18 years or younger. The strains were analyzed for the presence of the PVL encoding genes by PCR and were phage typed. Strains resistant to methicillin or pvl+ were analyzed by pulsed-field gel electrophoresis. A medical chart review blinded to patient pvl status was performed to retrieve demographic and clinical data. Data were analyzed by logistic regression. Results: We identified 74 pediatric community-acquired SA infections. Nineteen strains (25.7%) were positive for the pvl genes. Four isolates (5.4%) were resistant to methicillin and three of these were pvl+. No predominant clone was identified by phage typing or pulsed field gel electrophoresis. Pvl+ and pvl- infections were statistically similar for patient age, hospital admission, length of hospital stay, invasive disease, intravenous antibiotics and outcomes. Pvl+ strains were more likely to cause abscesses (OR 20.79; 95% CI 4.93 – 87.58), less likely to cause superficial skin infections (OR 0.18; 95% CI 0.05 – 0.64) and less likely to be resistant to erythromycin (OR 0.048; 95% CI 0.004 – 0.52). Conclusions: In a clonally heterogeneous population of pediatric community-acquired SA infections, pvl+ strains were associated with abscess formation and erythromycin susceptibility, but not invasive disease

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis

Background: The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA. Methods: Before the 2013–2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated. Results: Influenza RNA was detected in 16% fewer participants (95% CrI: −7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: −16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: −2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: −0.37, 1.26). Conclusion: The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and −negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference