Reevaluating immunization delays after red blood cell transfusion.

BACKGROUND: Current American and Canadian guidelines recommend delaying live vaccine immunization by 5 to 6 months after transfusion of red blood cells (RBCs) due to potential interference by serum antibodies. Due to lack of data, the recommendations may be unfounded and prevent valuable vaccination opportunities for children with frequent blood transfusions. The primary aim of this study was to determine measles, mumps, rubella (MMR) vaccine immunogenicity in patients chronically transfused with RBCs. A secondary aim was to quantify vaccine antibodies in RBC donations. STUDY DESIGN AND METHODS: MMR-specific antibodies were quantified in 25 pediatric patients who received both doses of MMR vaccine while on a chronic RBC transfusion program (median, 6.6 years after vaccination). MMR antibodies were also quantified in 30 samples of supernatants from RBC donations. RESULTS: Immunity to each of the MMR components was 68% to 76%. In blood donors born before 1976 (pre-MMR vaccine), 67% of MMR serologies in the supernatants of RBC donations were at the immune level versus 7% in blood donors born after 1976. CONCLUSION: This is the first study of the impact of RBC transfusions on MMR vaccine immunogenicity. Although lower than in the literature (immunity rates, ≥90%), the results show a high rate of immunogenicity of the MMR vaccine in chronically transfused patients. Additionally, results suggest that MMR antibody content in transfusions will continue to decrease with time. Weighing the risks and benefits of disease prevention in a vulnerable population, a reevaluation of immunization delays after RBC transfusions is called for.

Characterization of multiple cytomegalovirus drug resistance mutations detected in a hematopoietic stem cell transplant recipient by recombinant phenotyping.

Cytomegalovirus resistance to antivirals is a major problem in transplant recipients. We evaluated the impact of five mutations (A594V, L595F, and E655K in the UL97 gene and V526L and E756K in the UL54 gene), detected in a blood sample from a stem cell transplant recipient, on drug susceptibilities and replicative capacities of recombinant viruses.

Pediatric RSV-Associated Hospitalizations Before and During the COVID-19 Pandemic.

Importance: Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. Objective: To describe the epidemiology and burden of RSV-associated hospitalizations among children and adolescents in Canadian tertiary pediatric hospitals from 2017 to 2022, including changes during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study was conducted during 5 RSV seasons (2017-2018 to 2021-2022) at 13 pediatric tertiary care centers from the Canadian Immunization Monitoring Program Active (IMPACT) program. Hospitalized children and adolescents aged 0 to 16 years with laboratory-confirmed RSV infection were included. Main Outcomes and Measures: The proportion of all-cause admissions associated with RSV and counts and proportions of RSV hospitalizations with intensive care unit (ICU) admission, prolonged stay (≥7 days), and in-hospital mortality were calculated overall and by season, age group, and region. Seasonality was described using epidemic curves. RSV hospitalizations for 2021-2022 were compared with those in the prepandemic period of 2017-2018 through 2019-2020. Bonferroni corrections were applied to P values to adjust for multiple statistical comparisons. Results: Among 11 014 RSV-associated hospitalizations in children and adolescents (6035 hospitalizations among male patients [54.8%]; 5488 hospitalizations among patients aged <6 months [49.8%]), 2594 hospitalizations (23.6%) had admission to the ICU, of which 1576 hospitalizations (60.8%) were among children aged less than 6 months. The median (IQR) hospital stay was 4 (2-6) days. The mean (SD) number of RSV-associated hospitalizations during prepandemic seasons was 2522 (88.8) hospitalizations. There were 58 hospitalizations reported in 2020-2021, followed by 3170 hospitalizations in 2021-2022. The proportion of all-cause hospitalizations associated with RSV increased from a mean of 3.2% (95% CI, 3.1%-3.3%) before the pandemic to 4.5% (95% CI, 4.3%-4.6%) in 2021-2022 (difference, 1.3 percentage points; 95% CI, 1.1-1.5 percentage points; corrected P < .001). A significant increase in RSV-associated hospitalizations was found in 2021-2022 for 3 provinces (difference range, 2.5 percentage points; 95% CI, 1.4-3.6 percentage points for Quebec to 2.9 percentage points; 95% CI, 1.4-3.5 percentage points for Alberta; all corrected P < .001). Age, sex, ICU admission, prolonged length of stay, and case fatality rate did not change in 2021-2022 compared with the prepandemic period. Interregional differences in RSV seasonality were accentuated in 2021-2022, with peaks for 1 province in October, 4 provinces in December, and 3 provinces in April, or May. Conclusions and Relevance: This study found that the burden of RSV-associated hospitalizations in Canadian pediatric hospitals was substantial, particularly among infants aged less than 6 months, and RSV hospitalizations increased in 2021-2022 compared with the prepandemic period, while severity of illness remained similar. These findings suggest that RSV preventive strategies for infants aged less than 6 months would be associated with decreased RSV disease burden in children.

Impact of the Withdrawal of Palivizumab Immunoprophylaxis on the Incidence of Respiratory Syncytial Virus (RSV) Hospitalizations Among Infants Born at 33 to 35 Weeks' Gestational Age in the Province of Quebec, Canada: The RSV-Quebec Study.

BACKGROUND: Infants born at 33-35 completed weeks' gestational age (wGA) aged <6 months at the start of or born during respiratory syncytial virus (RSV) season and classified as moderate/high risk of severe RSV disease were included in a palivizumab RSV prophylaxis program in the province of Quebec, Canada, until 2014-2015. We assessed the impact of withdrawal of this indication on lower respiratory tract infection (LRTI)/RSV hospitalizations (H) in this population. METHODS: We conducted a 4-year, retrospective, cohort study in 25 Quebec hospitals (2 seasons with and 2 without palivizumab prophylaxis for moderate- to high-risk infants). Our primary outcome was LRTI/RSV-H incidence. We compared LRTI/RSV-H incidence before (2013-2015; seasons 1 + 2 [S1/2]) and after (2015-2017; S3/4) the change in indication. RESULTS: We identified 6457 33-35 wGA births. LRTI/RSV-H occurred in 105/3353 infants (3.13%) in S1/2 and 130/3104 (4.19%) in S3/4. Among LRTI/RSV-H, 86.4% were laboratory-confirmed RSV-H. Adjusting for sex, wGA, and birth month, S3/4 was significantly associated with increased LRTI/RSV-H incidence (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.04-1.76) but not with laboratory-confirmed RSV-H (aOR, 1.19; 95% CI, 0.90-1.58). Mean duration of LRTI/RSV-H was 5.6 days; 22.6% required intensive care unit admission. Comparing S3/4 with S1/2, infant percentage with LRTI/RSV-H classified as moderate/high risk increased from 27.8% to 41.9% (P = .11). CONCLUSIONS: In a province-wide study, we observed a significant increase in LRTI/RSV-H incidence among infants born at 33-35 wGA in the 2 years after withdrawal of RSV prophylaxis.

Antibiotic prophylaxis for childhood urinary tract infection: a national survey.

AIMS: To describe attitudes of paediatricians and paediatric nephrologists regarding antibiotic prophylaxis for urinary tract infection (UTI) and determine the factors associated with its use. METHOD: A self-administered questionnaire was mailed to Canadian paediatricians (1136) and paediatric nephrologists (42). RESULTS: The response rate was 58.1% (684 physicians); 436 who had made a decision about antibiotic prophylaxis for childhood UTI in the previous year were included in the analysis. Of these, 407 (93.3%) were certified in paediatrics and 29 (6.7%) were paediatric nephrologists. Most respondents prescribed prophylaxis for children with grade III-V vesicoureteral reflux (VUR) (96.5%-98%); 69.8 and 92.8% prescribed it for children with grades I and II VUR, respectively. Factors significantly associated with use of prophylaxis for children with grade I VUR were frequency of decision-making about prophylaxis, city size and province. Fifteen percent of physicians felt that their practice regarding antibiotic prophylaxis for children with VUR was evidence based. A hundred one respondents (24.3%) prescribed prophylaxis for infants with a first febrile UTI in the absence of VUR. Nineteen percent felt that their practice regarding antibiotic prophylaxis for these infants was evidence based. Prescription of prophylaxis for children >12 months with recurrent UTI in the absence of VUR was influenced by frequency of pyelonephritis (88.5% of respondents) and presence of voiding dysfunction (53.8%). Nine percent of physicians felt that their practice for these children was evidence based. CONCLUSION: Opinions of Canadian paediatricians and paediatric nephrologists regarding antibiotic prophylaxis for UTI in children vary widely, probably because of the paucity of solid evidence about prophylaxis.

Measuring the Impact of Rotavirus Acute Gastroenteritis Episodes (MIRAGE): A prospective community-based study.

BACKGROUND: Current assessments of the burden of rotavirus (RV)-related gastroenteritis are needed to evaluate the potential benefits of RV immunization interventions. The objective of the present study was to characterize the burden of RV gastroenteritis among children presenting in outpatient settings with gastroenteritis. METHODS: Between January and June 2005, 395 children younger than three years of age presenting with gastroenteritis symptoms (at least three watery or looser-than-normal stools, or forceful vomiting within the previous 24 h period) were recruited from 59 Canadian clinics and followed for two weeks. Stool specimens were tested for the RV antigen. Gastroenteritis-related symptoms, health care utilization, parental work loss and other cases of gastroenteritis in the household were assessed by questionnaires and daily symptom cards that were completed by caregivers. RESULTS: Of 336 conclusive test results, 55.4% were RV positive (RV+). In addition to diarrhea, 67.2% and 89.3% of RV+ children experienced fever or vomiting, respectively. Compared with RV-negative (RV-) children, RV+ children were more likely to experience the three symptoms concurrently (57.0% versus 26.7%; P<0.001), to be hospitalized (12.9% versus 3.9%; P=0.008) and to induce parental work loss (53.8% versus 37.3%; P=0.003). The median duration of gastroenteritis was eight days for RV+ children (nine days for RV- children). Additional cases of gastroenteritis were present in 46.8% of households in the RV+ group (51.3% of households in the RV- group). CONCLUSIONS: RV gastroenteritis cases were more severe than other gastroenteritis cases, were hospitalized more often and were associated with considerably more work loss.

Cardio-respiratory Events and Inflammatory Response After Primary Immunization in Preterm Infants < 32 Weeks Gestational Age: A Randomized Controlled Study.

BACKGROUND: Inflammation may depress respiration in neonates. This study aimed to establish a link between postimmunization inflammation and cardio-respiratory events (CREs). METHODS: Randomized double-blind controlled study of infants born < 32 weeks gestation receiving the 2 months vaccine, which comprised diphtheria and tetanus toxoids and acellular pertussis adsorbed combined with inactivated poliomyelitis vaccines and Haemophilus b conjugate and the pneumococcal conjugate 10-valent vaccines. Infants were randomized to ibuprofen treatment or a placebo group (n = 28/group). C-reactive protein (CRP) and prostaglandins E2 (PgE2) levels were assessed before and after immunization. CREs were recorded for 72 hours. Heart rate variability was assessed by polysomnography. RESULTS: In the placebo group, immunization was associated with significantly increased CRP levels and an increase in CRE (8.6 ± 11.1 before versus 14.0 ± 12.8 after), which did not reach statistical significance (P = 0.08), and no change in PgE2. The increase in CRP was correlated with changes in CRE (r = 0.4: P < 0.05). In the ibuprofen group, immunization significantly increased CRP levels but was not associated with change in CRE (6.7 ± 7.7 before versus 6.8 ± 9.7 after) and PgE2 levels. Comparing the groups, variation in CRE (ΔCRE before versus after immunization) was significantly lower in the ibuprofen group (0.1 ± 7.9 versus 5.4 ± 10.0 ΔCRE; P < 0.05). CONCLUSION: The first immunization of infants born < 32 weeks was associated with an increase in CRP. Ibuprofen treatment significantly attenuated the variation (Δ) in CRE following first immunization in these infants but the current study could not demonstrate an impact on CRP and PgE2 levels. The impact of anti-inflammatory treatment on antigenicity must be evaluated before their clinical use aiming at reducing CRE after immunization in preterm infants.

Palivizumab use among children with congenital heart disease in Quebec: Impact of Canadian guidelines on clinical practice.

BACKGROUND: Palivizumab has been shown to reduce the risk of hospitalization caused by respiratory syncytial virus in children with congenital heart disease (CHD). Guidelines published in 2003 by the Canadian Paediatric Society (CPS) stated that children younger than 24 months with hemodynamically significant CHD should be considered for up to five monthly doses of palivizumab during the winter season. OBJECTIVE: To assess the impact of CPS guidelines on the use of palivizumab in children with CHD. METHODS: Clinical information was reviewed on all patients with CHD who were prescribed palivizumab in 2002-2003 and 2003-2004 and who were followed by one of four paediatric cardiovascular programs in the province of Quebec. RESULTS: Palivizumab was prescribed to 45 children in 2002-2003 and to 146 children in 2003-2004. The number of children receiving more than five doses increased from 10 of 45 (22%) in 2002-2003 to 57 of 128 (45%) in 2003-2004 (P=0.008). One hundred seventeen of 146 children (80%) receiving palivizumab in 2003-2004 met the CPS guidelines versus 38 of 45 children (84%) in 2002-2003 (ie, before the guidelines were published) (P=0.66). Patients not meeting CPS criteria were older than 24 months at the time of the first dose, had hemodynamically insignificant CHD or had lesions adequately corrected by surgery. CONCLUSIONS: The number of children with CHD receiving palivizumab prophylaxis increased significantly following the publication of CPS guidelines. The majority of children were eligible for palivizumab according to the current CPS criteria. More patients received more than five doses in 2003-2004 than in 2002-2003.

A pharmacoeconomic evaluation of 7-valent pneumococcal conjugate vaccine in Canada.

The objective of this study was to evaluate the projected health benefits, costs, and cost-effectiveness of pneumococcal conjugate vaccination for infants and children aged <5 years in Canada. A health state model incorporating incidence, vaccine efficacy, costs, and transitional probabilities for the health states (well, meningitis, bacteremia, otitis media, pneumonia, and death) was constructed for a 10-year time horizon. Implementation of a pneumococcal conjugate vaccine program in Canada for each annual birth cohort of 340,000 persons observed over 10 years would be expected to save approximately 12 lives and 100,000 cases of pneumococcal disease over 10 years, resulting in total savings of $67 million (Canadian dollars [Can$]). Vaccination of healthy infants would result in net savings for society if the vaccine costs less than Can$50 per dose. Moreover, for a vaccine purchase price of Can$67.50, infant vaccination would cost society Can$79,000 per life-year gained. Pneumococcal conjugate vaccination is a potentially cost-effective means of pneumococcal disease prevention.

Outcome of penicillin-nonsusceptible Streptococcus pneumoniae meningitis: a nested case-control study.

BACKGROUND: There are few data comparing the clinical features, management and outcome of penicillin-nonsusceptible (PNSP) meningitis patients with penicillin-susceptible (PSSP) meningitis patients. METHODS: We performed a retrospective, nested case-control study comparing cases with PNSP meningitis with controls with PSSP meningitis obtained from the Immunization Monitoring Program, Active (IMPACT) cross-Canada surveillance study of invasive infections. RESULTS: There were 30 PNSP meningitis cases (10.1% of total) and 45 PSSP meningitis controls from 6 centers obtained from 297 meningitis cases in the IMPACT database from 1991 through 1999. Vancomycin was used for empiric therapy in no cases and controls in 1991 to 1993 and in all cases in 1999. A third generation cephalosporin was used in 93.3% of confirmed PNSP cases, and 70.0% also received vancomycin and/or rifampin. Penicillin was used in 66.7% of confirmed PSSP cases. PNSP cases were more likely than PSSP controls to have a second lumbar puncture (odds ratio, 4.1; P= 0.01). PNSP cases were treated with intravenous antibiotics for an average of 15.6 days compared with 12.3 days for controls ( P= 0.04). Among PNSP cases, those patients who did not receive empiric vancomycin were treated with intravenous antibiotics for an average of 18.5 days compared with 12.0 days for those who did receive empiric vancomycin ( P= 0.04). The overall mortality was 5.3%, and 36.6% of survivors had >or=1 neurologic sequelae, including 19.7% with hearing loss. In multivariate statistical models, PNSP was not a risk factor for intensive care unit admission or neurologic sequelae. CONCLUSIONS: Management of suspected bacterial meningitis and confirmed meningitis in Canadian children changed in the past decade. Treatment of PNSP meningitis is significantly different from that for PSSP meningitis. These changes have occurred in response to the emergence of PNSP in Canada. Neurologic sequelae remain common after meningitis, but there are no differences between PNSP cases and PSSP cases.

The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation.

BACKGROUND: Infants born at 33 through 35 completed weeks of gestation (33-35GA) are at risk for severe respiratory syncytial virus (RSV) infection, and palivizumab prophylaxis lowers hospitalizations for RSV infection by as much as 80%. The 33-35GA cohort comprises 3-5% of annual births; thus expert panels recommend limiting prophylaxis to situations in which frequency or health care impact of RSV infection is high. This study sought to identify independent risk factors for hospitalization for RSV infection. METHODS: This was a multicenter, prospective, observational cohort study of 33-35GA infants followed through their first RSV season (2001/2002 or 2002/2003). Baseline data were collected by interview with parents and review of medical records. Respiratory tract illnesses were identified by monthly phone calls, and medical records were reviewed for emergency room visits or hospitalizations. Risk factors were determined by stepwise logistic regression. RESULTS: Of 1,860 enrolled subjects, 1,832 (98.5%) were followed for at least 1 month, and 1,760 (94.6%) completed all follow-ups. Of 140 (7.6%) subjects hospitalized for respiratory tract illnesses, 66 infants had proven RSV infection. Independent predictors for hospitalization for RSV infection were: day-care attendance (odds ratio, 12.32; 95% confidence interval, 2.56, 59.34); November through January birth (odds ratio, 4.89; 95% confidence interval, 2.57, 9.29); preschool age sibling(s) (odds ratio, 2.76; 95% confidence interval, 1.51, 5.03); birth weight <10th percentile (odds ratio, 2.19; 95% confidence interval, 1.14, 4.22); male gender (odds ratio, 1.91; 95% confidence interval, 1.10, 3.31); > or = 2 smokers in the home (odds ratio, 1.87; 95% confidence interval, 1.07, 3.26); and households with >5 people, counting the subject (odds ratio, 1.79; 95% confidence interval, 1.02, 3.16). Family history of eczema (odds ratio, 0.42; 95% confidence interval, 0.18, 0.996) was protective. CONCLUSIONS: Specific host/environmental factors can be used to identify which 33-35GA infants are at greatest risk of hospitalization for RSV infection and likely to benefit from palivizumab prophylaxis.

Randomized, multicenter trial of a single dose of AS03-adjuvanted or unadjuvanted H1N1 2009 pandemic influenza vaccine in children 6 months to <9 years of age: safety and immunogenicity.

BACKGROUND: During the 2009-2010 influenza pandemic, we evaluated the immunogenicity and safety of different H1N1 2009 pandemic influenza vaccines delivering various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol oil-in-water emulsion-based adjuvant system) in children (NCT00976820). METHODS: Three hundred twenty-two healthy children 6 months to <9 years of age were randomized to receive 2 doses of nonadjuvanted (15 µg or 7.5 µg HA) or adjuvanted vaccine (3.75 µg HA/AS03A or 1.9 µg HA/AS03B), 21 days apart. Blood samples before and after each dose were tested for immune responses using hemagglutination inhibition and microneutralization assays. Safety assessments were done up to day 385. RESULTS: The first dose of both AS03-adjuvanted vaccines elicited strong immune responses (seroprotection rates: 98.3%/99.0%; seroconversion rates: 94.9%/97.0%; geometric mean fold rises: 36.2/33.6), which were higher post-dose 2 (seroprotection rate: 100.0%/100%; seroconversion rate: 100.0%/98.8%; geometric mean fold rise: 157.1/151.6), meeting European regulatory criteria on days 21 and 42. The nonadjuvanted 15 µg HA vaccine also met the regulatory criteria after each dose; the 7.5 µg HA vaccine met them only post-dose 2. Six months post-dose 1, all vaccines except the nonadjuvanted 7.5 µg HA vaccine met European regulatory criteria. Neutralizing antibody response paralleled the hemagglutination inhibition immune response after each dose. Pain at the injection site, lasting 2-3 days, was more common following adjuvanted than nonadjuvanted vaccination. CONCLUSIONS: AS03-adjuvanted H1N1 2009 pandemic influenza vaccine (3.75 µg or 1.9 µg HA), administered as 2 doses, was highly immunogenic, induced long-term immune response to 6 months, with a clinically acceptable safety profile in children aged 6 months to <9 years of age.

The rise of the rats: A growing paediatric issue.

Rat bite fever (RBF), a systemic infection of Streptobacillus moniliformis or Spirillum minus characterized by fever, arthralgias and petechial-purpuric rash on the extremities, carries a mortality rate of 7% to 10% if untreated. In Canada, one adult and two paediatric cases of RBF have been reported since 2000. In recent years, pet rats have become quite popular among children, placing them at an increased risk for RBF. Thus, paediatricians need to be more wary of the potential for RBF in their patients. In the present report, a culture-confirmed case of RBF and two additional cases of suspected infection are described.

Prevalence of positive tuberculin skin tests in foreign-born children.

AIMS: To evaluate the prevalence of positive tuberculin skin tests (TST) in internationally adopted and immigrant children. To identify risk factors for positive TST in these populations. METHODS: The study was a retrospective medical record review in a tertiary care pediatric hospital. All children evaluated at the International Adoption and Immigrant Health Clinic of CHU Sainte-Justine in Montreal, Canada, between 01-01-1998 and 31-12-2001 were included. Demographic and anthropometrical data, BCG vaccination, TST, chest X-ray results and treatment were extracted from the medical records of the patients and analyzed. Positive TST was defined as induration = 10 mm, 48 to 72 hours after injection of five tuberculin units of purified protein derivate. RESULTS: Our population included 670 children: 112 immigrants and 558 adoptees. Median age was 6.9 years for immigrants and 1.1 years for adopted children. Overall incidence of positive TST was 12.2% in our cohort: 31% in the immigrant and 8% in the adopted children groups. There was one case of active tuberculosis. Older age on arrival in Canada and BCG vaccination were identified as risk factors for positive TST in our multivariate model. For each one-year increase in age on arrival in Canada, there was a 1.2 times greater risk for positive TST. CONCLUSIONS: Latent tuberculosis is a frequent problem in foreign-born children. The higher incidence in immigrant children can be explained by older age on arrival.

Hospitalisations for gastroenteritis: the role of rotavirus.

To determine the proportion of hospitalisations for gastroenteritis caused by rotavirus, we tested for rotavirus stool samples of all children under the age of five hospitalised for gastroenteritis between 1 December 1999 and 30 May 2000 in seven community and specialised hospitals in Quebec. Of 944 children hospitalised, 565 (59.9%) were screened for rotavirus and 405 (71.7%) tested positive. From December to April, the proportion of positive results rose from 51.6 to 78.1%. Compared with children whose test results were negative, children who tested positive presented vomiting more frequently upon admission (88.9 versus 60.4%) and needed IV fluids in greater proportion (94.1 versus 78.0%), but spent less time in hospital (2.8 versus 3.3 days). Aside from dehydration, no complications were noted. In Quebec, a large majority of winter and spring hospitalisations for gastroenteritis in children is attributable to rotavirus.