Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.

Resource use and disease severity of children hospitalized for COVID-19 versus multisystem inflammatory syndrome in children (MIS-C) in Canada.

Background: Direct comparisons of paediatric hospitalizations for acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) can inform health system planning. We describe the absolute and relative hospital burden of acute paediatric COVID-19 and MIS-C in Canada. Methods: This national prospective study was conducted via the Canadian Paediatric Surveillance Program from March 2020-May 2021. Children younger than 18 years old and hospitalized for acute COVID-19 or MIS-C were included in the analysis. Outcomes included supplemental oxygen (low-flow oxygen or high-flow nasal cannula), ventilation (non-invasive or conventional mechanical), vasopressors, paediatric intensive care unit (PICU) admission, or death. Adjusted risk differences (aRD) and 95% confidence intervals (CI) were calculated to identify factors associated with each diagnosis. Results: Overall, we identified 330 children hospitalized for acute COVID-19 (including five deaths) and 208 hospitalized for MIS-C (including zero deaths); PICU admission was required for 49.5% of MIS-C hospitalizations versus 18.2% of acute COVID-19 hospitalizations (aRD 20.3; 95% CI, 9.9-30.8). Resource use differed by age, with children younger than one year hospitalized more often for acute COVID-19 (aRD 43.4% versus MIS-C; 95% CI, 37.7-49.1) and more children 5-11 years hospitalized for MIS-C (aRD 38.9% vs. acute COVID-19; 95% CI, 31.0-46.9). Conclusion: While there were more hospitalizations and deaths from acute paediatric COVID-19, MIS-C cases were more severe, requiring more intensive care and vasopressor support. Our findings suggest that both acute COVID-19 and MIS-C should be considered when assessing the overall burden of severe acute respiratory syndrome coronavirus 2 in hospitalized children.

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

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.

C-reactive protein for late-onset sepsis diagnosis in very low birth weight infants.

BACKGROUND: Late-onset sepsis in very low birth weight (VLBW) infants is a diagnostic challenge. We aimed to evaluate the diagnostic utility of the C-Reactive protein (CRP) and the complete blood count (CBC) for late-onset sepsis in VLBW infants. METHODS: In a 5-year retrospective cohort of 416 VLBW infants born at less than 1500 g, there were 590 separate late-onset sepsis evaluations. CRP and CBC were drawn at time of initial blood culture (T0), at 16-24 h (T24) and 40-48 h (T48) after. The positive cut-off values for abnormal values were the following: CRP ≥10 mg/L and CBC with at least one anomaly, including white blood cell count < 5000/mm3, immature neutrophil/total neutrophil ratio > 0.10, or platelet count < 100,000/uL. Sensitivity and specificity for predicting late-onset sepsis were calculated for each laboratory test and their combinations. Receiver operating characteristics curves were obtained for each test and for the absolute change from T0 to T24 in the laboratory value of CRP, white blood cell count and immature neutrophil/total neutrophil. RESULTS: At T0, combining the CBC and the CRP had the highest sensitivity of 66% (95% confidence interval [CI], 58-73) compared to both individual tests for predicting late onset sepsis. At T24, CRP's sensitivity was 84% (95% CI, 78-89) and was statistically higher than the CBC's 59% (95% CI, 51-67). The combination of CBC at T0 and CRP at T24 offered the greatest sensitivity of 88% (95% CI, 82-92) and negative predictive value 93% (95% CI, 89-96), with fewer samples, compared to any other combination of tests. The area under the curve for the change in the white blood cell count from T0 to T24 was 0.82. CONCLUSION: At initial sepsis evaluation (T0), both CBC and CRP should be performed to increase sensitivity. A highly negative predictive value is reachable with only two tests: a CBC at T0 and a CRP a T24.

Thalidomide in Refractory Tuberculomas and Pseudoabscesses.

Paradoxical immune reconstitution inflammatory syndrome is a well-described entity even in immunocompetent children, principally in association with Mycobacterium tuberculosis infections. Central nervous system involvement is a potential life-threatening form, sometimes refractory to standard treatment. We report the case of an HIV-negative refugee teenager, who presented with brain tuberculomas and pseudoabscesses responsive only to thalidomide.

Higher risk of neutropenia associated with piperacillin-tazobactam compared with ticarcillin-clavulanate in children.

BACKGROUND: A series of cases of piperacillin-tazobactam (P/T)-associated neutropenia has been observed recently in children in our center. Because neutropenia was seldom observed in children treated with ticarcillin-clavulanic acid (T/C), we conducted a study to determine if there is an increased risk of neutropenia in children exposed to P/T in comparison with T/C. METHODS: Medical records of subjects aged <18 years who received at least 1 dose of P/T or T/C between 1 January 2008 and 30 June 2011 were reviewed. RESULTS: Two hundred ninety-nine episodes of treatment (65 P/T, 234 T/C) met inclusion criteria. Among those episodes, 213 had data allowing complete white blood cell count analysis and were included in the final analysis. Thirteen cases of neutropenia were observed during the study period. The average time to onset was 17.6 days and all patients were aged <13 years. Seven cases (10.8%) occurred in the P/T group and 6 (2.6%) in the T/C group (unadjusted odds ratio, 4.59; 95% confidence interval, 1.48-14.17). Although a statistically significant correlation was observed between age, treatment duration, and total dose and the development of neutropenia (r = -0.121, P = .037; r = 0.267, P < .001; r = 0.260, P < .001, respectively), this was not the case for sex, indications, neutrophil count at initiation, and concomitant drug treatments. CONCLUSIONS: Although our results need to be confirmed, they suggest that children receiving long courses of therapy (>2 weeks) with P/T may be at increased risk of neutropenia, compared with T/C.

Pediatric Pleural Empyema in the Province of Quebec: Analysis of a 10-Fold Increase Between 1990 and 2007.

BACKGROUND: Although the frequency of pneumonia has decreased over time, an increase in pleural empyema has been observed in different settings worldwide. This study assessed the epidemiology of community-acquired pediatric pleural empyema in the province of Quebec through validation of cases found in a hospitalization discharge database. METHODS: We used the national administrative database of hospitalization to identify children (6 months-14 years) hospitalized for pleural empyema or pleural effusion with drainage from January 1990 until December 2007 and reviewed their medical charts. Patients with pleural effusion secondary to chest trauma, thoracic surgery, malignancies, cardiac failure, or metabolic disorders were excluded. RESULTS: Predictive positive value (PPV) of empyema code in any position among discharge diagnostics in the administrative database was 86.5% (95% confidence interval: 81.9%-90.3%). After chart revision, 292 met the inclusion criteria. Age-adjusted incidence of pleural empyema in the pediatric population increased from 0.23 in 1990 to 4.01/100,000 person-years in 2007. A bacterial pathogen was identified in 46.5%; Streptococcus pneumoniae (Sp) (42%) and S pyogenes (30%) were most frequent. There was no obvious change in the PPV and proportions of children with chronic disease or asthma and in identified pathogens over time, but an increase in pre-admission respiratory symptoms duration (from 3.8 days to 5.7) and nonsteroidal anti-inflammatory drug use (from 0% to 19%) was observed. CONCLUSIONS: From 1990 to 2007, we observed a 10-fold increase in the incidence of pediatric hospitalizations associated with pleural empyema. This increase preceded the introduction of a pneumococcal conjugated vaccine program in Quebec. Sp remained the major pathogen identified.

Modeling the impact of one- and two-dose varicella vaccination on the epidemiology of varicella and zoster.

In many countries, policymakers are being asked to make recommendations regarding the introduction of a 2-dose varicella vaccination program. The objective of this study was to examine the potential impact of 1-dose versus 2-dose varicella vaccination programs on varicella and zoster incidence, using Canada as an example. We developed a deterministic realistic age-structured model that fits 1- and 2-dose vaccine efficacy, varicella force of infection and zoster incidence. Assuming 90% coverage, the base case model (range: min; max) predicts that 1-dose vaccination will reduce varicella and zoster cases by 64% (14%; 96%) and 5% (-2%; 22%), respectively, over 80-years. Adding a second dose is predicted to reduce varicella and zoster by an additional 22% (0%; 82%) and 6% (0%; 14%), respectively. Most varicella cases prevented by the second dose are breakthrough infections. Although the incremental effectiveness of adding the second dose is highly sensitive to vaccine efficacy and mixing, predictions of the overall benefit of a 2-dose program is relatively robust to model assumptions. Adding a 2-dose program may help guarantee high population-level effectiveness against varicella. However, the incremental benefit of a second dose is highly dependant on the effectiveness of the first dose and its impact on zoster.

Pneumonia after implementation of the pneumococcal conjugate vaccine program in the province of Quebec, Canada.

BACKGROUND: In Canada, a pneumococcal conjugate vaccine was licensed in 2001, and in the province of Quebec, a publicly-funded program was implemented for high-risk children in 2002, using a 4-dose schedule, and for all children in 2004, using a 3-dose schedule. OBJECTIVES: To describe the epidemiology of hospitalized pneumonia in the population aged <5 years. METHODOLOGY: Hospital discharge records with a main diagnosis of pneumonia, pleurisy, or empyema were analyzed regarding monthly frequencies by diagnostic categories, duration of stay, proportion of cases admitted to the intensive care unit, and case fatality. RESULTS: Lobar pneumonia represented 32% of 25,319 all-cause pneumonia admissions during the period April 1997 to March 2006. Beginning in the spring of 2004, there was a marked decrease in the frequency of lobar pneumonia, whereas unspecified pneumonia tended to increase to a lesser extent. Compared with the pre-pneumococcal conjugate vaccine period, admissions for all-causes pneumonia decreased by 13% after program implementation and there was no increase in empyema cases. CONCLUSIONS: Results are reassuring as to the effectiveness of the pneumococcal vaccination program in Quebec.

Fatal disseminated Trichosporon asahii infection in a child with acute lymphoblastic leukemia.

Few cases of Trichosporon species infection have been reported in children. The present report describes a case of fatal disseminated Trichosporon asahii infection in a child treated for relapsed leukemia. Voriconazole has previously shown promising activity in vitro, and has been used successfully in the treatment of T asahii infections. The patient died five days after voriconazole treatment was started, and the autopsy revealed widespread systemic dissemination to all organs.

Antibiotic use in children is not influenced by the result of rapid antigen detection test for the respiratory syncytial virus.

BACKGROUND: Rapid antigen detection test (RADT) for respiratory syncytial virus (RSV) is widely used in children hospitalized with acute respiratory tract infection (ARTI), but its influence on antibiotic (AB) use is uncertain. OBJECTIVE: To evaluate if confirmation of RSV infection by RADT modified AB use and elucidate others factors associated with the continuation of antibiotics. STUDY DESIGN: Charts of children hospitalized with viral ARTI aged 0-35 months were reviewed. Modification of antibiotics according to RSV RADT results was compared using Kaplan-Meier estimates and multivariate Cox regression. RESULTS: Of children receiving antibiotics when the RSV RADT result was available, RSV RADT was positive in 144 and negative in 54. Positive RSV RADT results did not lead to modification of antibiotic use. Factors independently associated with cessation of intravenous antibiotics were age > or = 3 months (HR 2.44 [1.41-4.21]) and absence of pneumonia (HR 1.50 [1.03-2.19]). Absence of otitis was associated with cessation of oral antibiotics (HR 9.16 [95% CI, 2.35-35.76]). CONCLUSION: Confirmed presence of RSV by RADT did not influence antibiotic use in young children with ARTI. Except with pneumonia, the risk of bacterial superinfection of RSV infected children is minimal and confirmation of RSV infection should prompt treating physicians to interrupt antibiotics.