Adverse Events Following Immunization With mRNA and Viral Vector Vaccines in Individuals With Previous Severe Acute Respiratory Syndrome Coronavirus 2 Infection From the Canadian National Vaccine Safety Network.

BACKGROUND: Adults previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop short-term immunity and may have increased reactogenicity to coronavirus disease 2019 (COVID-19) vaccines. This prospective, multicenter, active-surveillance cohort study examined the short-term safety of COVID-19 vaccines in adults with a prior history of SARS-CoV-2. METHODS: Canadian adults vaccinated between 22 December 2020 and 27 November 2021 were sent an electronic questionnaire 7 days post-dose 1, dose 2, and dose 3 vaccination. The main outcome was health events occurring in the first 7 days after each vaccination that prevented daily activities, resulted in work absenteeism, or required a medical consultation, including hospitalization. RESULTS: Among 684 998 vaccinated individuals, 2.6% (18 127/684 998) reported a prior history of SARS-CoV-2 infection a median of 4 (interquartile range: 2-6) months previously. After dose 1, individuals with moderate (bedridden) to severe (hospitalized) COVID-19 who received BNT162b2, mRNA-1273, or ChAdox1-S vaccines had higher odds of a health event preventing daily activities, resulting in work absenteeism or requiring medical consultation (adjusted odds ratio [95% confidence interval]: 3.96 [3.67-4.28] for BNT162b2, 5.01 [4.57-5.50] for mRNA-1273, and 1.84 [1.54-2.20] for ChAdox1-S compared with no infection). Following dose 2 and 3, the greater risk associated with previous infection was also present but was attenuated compared with dose 1. For all doses, the association was lower or absent after mild or asymptomatic infection. CONCLUSIONS: Adults with moderate or severe previous SARS-CoV-2 infection were more likely to have a health event sufficient to impact routine activities or require medical assessment in the week following each vaccine dose.

Characterizing the Pain Experience of Children With Acute Gastroenteritis Based on Identified Pathogens.

OBJECTIVES: Pain is common with acute gastroenteritis (AGE) yet little is known about the severity associated with specific enteropathogens. We sought to explore the correlation of pain severity with specific enteropathogens in children with AGE. METHODS: Participants were prospectively recruited by the Alberta Provincial Pediatric EnTeric Infection TEam at 2 pediatric emergency departments (EDs) (December 2014-August 2018). Pain was measured (by child and/or caregiver) using the 11-point Verbal Numerical Rating Scale. RESULTS: We recruited 2686 participants; 46.8% (n = 1256) females, with median age 20.1 months (interquartile range 10.3, 45.3). The mean highest pain scores were 5.5 [standard deviation (SD) 3.0] and 4.2 (SD 2.9) in the 24 hours preceding the ED visit, and in the ED, respectively. Prior to ED visit, the mean highest pain scores with bacterial detection were 6.6 (SD 2.5), compared to 5.5 (SD 2.9) for single virus and 5.5 (SD 3.1) for negative stool tests. In the ED, the mean highest pain scores with bacterial detection were 5.5 (SD 2.7), compared to 4.1 (SD 2.9) for single virus and 4.2 (SD 3.0) for negative stool tests. Using multivariable modeling, factors associated with greater pain severity prior to ED visit included older age, fever, illness duration, number of diarrheal or vomiting episodes in the preceding 24 hours, and respiratory symptoms, but not enteropathogen type. CONCLUSION: Children with AGE experience significant pain, particularly when the episode is associated with the presence of a bacterial enteric pathogen. However, older age and fever appear to influence children's pain experiences more than etiologic pathogens.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. CONCLUSIONS: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 1: Live Vaccines.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) may be at increased risk of some vaccine-preventable diseases. The effectiveness and safety of vaccinations may be altered by immunosuppressive therapies or IBD itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on live vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative process and voted on by a multidisciplinary panel. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Three good practice statements included reviewing a patient's vaccination status at diagnosis and at regular intervals, giving appropriate vaccinations as soon as possible, and not delaying urgently needed immunosuppressive therapy to provide vaccinations. There are 4 recommendations on the use of live vaccines. Measles, mumps, rubella vaccine is recommended for both adult and pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). Varicella vaccine is recommended for pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). For adults, recommendations are conditionally in favor of varicella vaccine for those not on immunosuppressive therapy, and against for those on therapy. No recommendation was made regarding the use of live vaccines in infants born to mothers using biologics because the desirable and undesirable effects were closely balanced and the evidence was insufficient. CONCLUSIONS: Maintaining appropriate vaccination status in patients with IBD is critical to optimize patient outcomes. In general, live vaccines are recommended in patients not on immunosuppressive therapy, but not for those using immunosuppressive medications. Additional studies are needed to evaluate the safety and efficacy of live vaccines in patients on immunosuppressive therapy.

Attribution of Pediatric Acute Gastroenteritis Episodes and Emergency Department Visits to Norovirus Genogroups I and II.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis. With vaccines in development, population-based estimates of norovirus burden are needed to identify target populations, quantify potential benefits, and understand disease dynamics. METHODS: We estimated the attributable fraction (AF) for norovirus infections in children, defined as the proportion of children testing positive for norovirus whose gastroenteritis was attributable to norovirus. We calculated the standardized incidence and emergency department (ED) visit rates attributable to norovirus using provincial gastroenteritis visit administrative data. RESULTS: From 3731 gastroenteritis case patients and 2135 controls we determined that the AFs were 67.0% (95% confidence interval [CI], 31.5%-100%) and 91.6% (88.8%-94.4%) for norovirus genogroups I (GI) and II (GII), respectively. Norovirus GII AF varied by season but not age. We attributed 116 episodes (95% CI, 103-129) and 59 (51-67) ED visits per 10 000 child-years to norovirus GII across all ages, accounting for 20% and 18% of all medically attended gastroenteritis episodes and ED visits, respectively. CONCLUSIONS: In children, a large proportion of norovirus GII detections reflect causation, demonstrating significant potential for norovirus GII vaccines. Seasonal variation in the norovirus GII AF may have implications for understanding the role asymptomatic carriage plays in disease dynamics.

Microbial Etiologies and Clinical Characteristics of Children Seeking Emergency Department Care Due to Vomiting in the Absence of Diarrhea.

BACKGROUND: As children with isolated vomiting are rarely able to provide a specimen suitable for routine pathogen testing, we have limited knowledge about their infecting pathogens. METHODS: Between December 2014 and August 2018, children <18 years old with presumed acute gastroenteritis who presented to 2 emergency departments (EDs) in Alberta, Canada, were recruited. Eligible participants had ≥3 episodes of vomiting and/or diarrhea in a 24-hour period, <7 days of symptoms, and provided a rectal swab or stool specimen. We quantified the proportion of children with isolated vomiting in whom an enteropathogen was identified, and analyzed clinical characteristics, types of enteropathogens, resources used, and alternative diagnoses. RESULTS: Of the 2695 participants, at the ED visit, 295 (10.9%), 1321 (49.0%), and 1079 (40.0%) reported having isolated diarrhea, vomiting and diarrhea, or isolated vomiting, respectively. An enteropathogen was detected most commonly in those with vomiting and diarrhea (1067/1321; 80.8%); detection did not differ between those with isolated diarrhea (170/295; 57.6%) and isolated vomiting (589/1079; 54.6%) (95% confidence interval of the difference: -3.4%, 9.3%). Children with isolated vomiting most often had a virus (557/1077; 51.7%), most commonly norovirus (321/1077; 29.8%); 5.7% (62/1079) had a bacterial pathogen. X-rays, ultrasounds, and urine tests were most commonly performed in children with isolated vomiting. Alternate etiologies were most common in those with isolated vomiting (5.7%; 61/1079). CONCLUSIONS: The rate of enteropathogen identification in children with isolated vomiting using molecular diagnostic tests and rectal swabs is substantial. Molecular diagnostics offer an emerging diagnostic strategy in children with isolated vomiting.

Whole-Genome Analysis of Streptococcus pneumoniae Serotype 4 Causing Outbreak of Invasive Pneumococcal Disease, Alberta, Canada.

After the introduction of pneumococcal conjugate vaccines for children, invasive pneumococcal disease caused by Streptococcus pneumoniae serotype 4 declined in all ages in Alberta, Canada, but it has reemerged and spread in adults in Calgary, primarily among persons who are experiencing homelessness or who use illicit drugs. We conducted clinical and molecular analyses to examine the cases and isolates. Whole-genome sequencing analysis indicated relatively high genetic variability of serotype 4 isolates. Phylogenetic analysis identified 1 emergent sequence type (ST) 244 lineage primarily associated within Alberta and nationally distributed clades ST205 and ST695. Isolates from 6 subclades of the ST244 lineage clustered regionally, temporally, and by homeless status. In multivariable logistic regression, factors associated with serotype 4 invasive pneumococcal disease were being male, being <65 years of age, experiencing homelessness, having a diagnosis of pneumonia or empyema, or using illicit drugs.

Characterizing Pain in Children with Acute Gastroenteritis Who Present for Emergency Care.

OBJECTIVE: To characterize the pain experienced by children with acute gastroenteritis (AGE) in the 24 hours before emergency department (ED) presentation. Secondary objectives included characterizing ED pain, discharge recommendations, overall analgesic use, and factors that influenced analgesic use and pain severity. STUDY DESIGN: A prospective cohort was recruited from 2 pediatric EDs (December 2014 to September 2017). Eligibility criteria included <18 years of age, AGE (≥3 episodes of diarrhea or vomiting in the previous 24 hours), and symptom duration <7 days at presentation. RESULTS: We recruited 2136 patients, median age 20.8 months (IQR 10.4, 47.4) and 45.8% (979/2136) female. In the 24 hours before enrollment, most caregivers reported moderate (28.6% [610/2136, 95% CI 26.7-30.5]) or severe (46.2% [986/2136, CI 44.0-48.3]) pain for their child. In the ED, they reported moderate (31.1% [664/2136, 95% CI 29.1-33.1]) or severe ([26.7% [571/2136, 95% CI 24.9-28.7]) pain; analgesia was provided to 21.2% (452/2131). The most common analgesics used in the ED were acetaminophen and ibuprofen. At discharge, these were also most commonly recommended. Factors associated with greater analgesia use in the ED were high pain scores during the index visit, having a primary care physician, earlier presentation to emergency care, fewer diarrheal episodes, presence of fever, and hospitalization at index visit. CONCLUSIONS: Most caregivers of children presenting to the ED with AGE reported moderate or severe pain, both before and during their visit. Future research should focus on the development of effective, safe, and timely pain management plans.

A Clinical Epidemiology and Molecular Attribution Evaluation of Adenoviruses in Pediatric Acute Gastroenteritis: a Case-Control Study.

The objective of this study was to characterize the etiological role of human adenovirus (HAdV) serotypes in pediatric gastroenteritis. Using a case-control design, we compared the frequencies of HAdV serotypes between children with ≥3 episodes of vomiting or diarrhea within 24 h and <7 days of symptoms (i.e., cases) and those with no infectious symptoms (i.e., controls). Stool samples and/or rectal swabs underwent molecular serotyping with cycle threshold (Ct) values provided by multiplex real-time reverse transcription-PCR testing. Cases without respiratory symptoms were analyzed to calculate the proportion of disease attributed to individual HAdV serotypes (i.e., attributable fraction). Between December 2014 and August 2018, adenoviruses were detected in 18.8% (629/3,347) of cases and 7.2% (97/1,355) of controls, a difference of 11.6% (95% confidence interval [CI], 9.6%, 13.5%). In 96% (95% CI, 92 to 98%) of HAdV F40/41 detections, the symptoms could be attributed to the identified serotype; when serotypes C1, C2, C5, and C6 were detected, they were responsible for symptoms in 52% (95% CI, 12 to 73%). Ct values were lower among cases than among controls (P < 0.001). HAdV F40/41, C2, and C1 accounted for 59.7% (279/467), 17.6% (82/467), and 12.0% (56/467) of all typed cases, respectively. Among cases, Ct values were lower for F40/41 serotypes than for non-F40/41 serotypes (P < 0.001). HAdV F40/41 serotypes account for the majority of HAdV-positive gastroenteritis cases, and when detected, disease is almost always attributed to infection with these pathogens. Non-F40/41 HAdV species have a higher frequency of asymptomatic infection and may not necessarily explain gastroenteritis symptoms. Real-time quantitative PCR may be useful in differentiating asymptomatic shedding from active infection.

2017/18 and 2018/19 seasonal influenza vaccine safety surveillance, Canadian National Vaccine Safety (CANVAS) Network.

BackgroundThe Canadian National Vaccine Safety (CANVAS) network monitors the safety of seasonal influenza vaccines in Canada.AimTo provide enhanced surveillance for seasonal influenza and pandemic influenza vaccines.MethodsIn 2017/18 and 2018/19 influenza seasons, adults (≥ 15 years of age) and parents of children vaccinated with the seasonal influenza vaccine participated in an observational study using web-based active surveillance. Participants completed an online survey for health events occurring in the first 7 days after vaccination. Participants who received the influenza vaccine in the previous season, but had not yet been vaccinated for the current season, were unvaccinated controls.ResultsIn 2017/18, 43,751 participants and in 2018/19, 47,798 completed the online safety survey. In total, 957 of 30,173 participants vaccinated in 2017/18 (3.2%; 95% confidence interval (CI): 3.0-3.4) and 857 of 25,799 participants vaccinated in 2018/19 (3.3%; 95% CI: 3.1-3.5) reported a health problem of sufficient intensity to prevent their normal daily activities and/or cause them to seek medical care (including hospitalisation). This compared to 323 of 13,578 (2.4%; 95% CI: 2.1-2.6) and 544 of 21,999 (2.5%; 95% CI: 2.3-2.7) controls in each respective season. The event rate in vaccinated adults and children was higher than the background rate and was associated with specific influenza vaccines. The higher rate of events was associated with systemic symptoms and migraines/headaches.ConclusionIn 2017/18 and 2018/19, higher rates of events were reported following seasonal influenza vaccination than in the pre-vaccination period. This signal was associated with several seasonal influenza vaccine products.

Performance of Stool-testing Recommendations for Acute Gastroenteritis When Used to Identify Children With 9 Potential Bacterial Enteropathogens.

BACKGROUND: The ability to identify bacterial pathogens that necessitate specific clinical management or public health action in children with acute gastroenteritis is crucial to patient care and public health. However, existing stool-testing guidelines offer inconsistent recommendations, and their performance characteristics are unknown. We evaluated 6 leading gastroenteritis guidelines (eg, those of the Centers for Disease Control and Prevention and Infectious Disease Society of America) that recommend when to test children's stool for bacterial enteropathogens. METHODS: Via 2 emergency departments in Alberta, Canada, we enrolled 2447 children <18 years old who presented with ≥3 episodes of diarrhea and/or vomiting in a 24-hour period. All participants were tested for 9 bacterial enteropathogens: Aeromonas, Campylobacter, Escherichia coli O157, other Shiga toxin-producing E. coli, enterotoxigenic E. coli, Salmonella, Shigella, Vibrio, and Yersinia. Patient data gathered at the index visit were used to determine whether guidelines would recommend testing. Sensitivity and specificity to recommend testing for children with bacterial enteropathogens were calculated for each guideline. RESULTS: Outcome data were available for 2391 (97.7%) participants, and 6% (144/2391) of participants tested positive for a bacterial enteropathogen. Guideline sensitivity ranged from 25.8% (95% confidence interval [CI] 18.7-33.0%) to 66.9% (95% CI 59.3-74.6%), and varied for individual pathogens. Guideline specificity for all bacterial enteropathogens ranged from 63.6% (95% CI 61.6-65.6%) to 96.5% (95% CI 95.7-97.2%). CONCLUSIONS: No guideline provided optimally balanced performance. The most sensitive guidelines missed one-third of cases and would drastically increase testing volumes. The most specific guidelines missed almost 75% of cases.

Comparative Evaluation of Enteric Bacterial Culture and a Molecular Multiplex Syndromic Panel in Children with Acute Gastroenteritis.

Although enteric multianalyte syndromic panels are increasingly employed, direct comparisons with traditional methods and the inclusion of host phenotype correlations are limited. Luminex xTAG gastrointestinal pathogen panel (GPP) and culture results are highly concordant. However, phenotypic and microbiological confirmatory testing raises concerns regarding the accuracy of the GPP, especially for Salmonella spp. A total of 3,089 children with gastroenteritis submitted stool specimens, rectal swab specimens, and clinical data. The primary outcome was bacterial pathogen detection agreement for shared targets between culture and the Luminex xTAG GPP. Secondary analyses included phenotype assessment, additional testing of GPP-negative/culture-positive isolate suspensions with the GPP, and in-house and commercial confirmatory nucleic acid testing of GPP-positive/culture-negative extracts. The overall percent agreement between technologies was >99% for each pathogen. Salmonella spp. were detected in specimens from 64 participants: 12 (19%) by culture only, 9 (14%) by GPP only, and 43 (67%) by both techniques. Positive percent agreement for Salmonella spp. was 78.2% (95% confidence interval [CI], 64.6%, 87.8%). Isolate suspensions from the 12 participants with specimens GPP negative/culture positive for Salmonella tested positive by GPP. Specimens GPP positive/culture negative for Salmonella originated in younger children with less diarrhea and more vomiting. GPP-positive/culture-negative specimen extracts tested positive using additional assays for 0/2 Campylobacter-positive specimens, 0/4 Escherichia coli O157-positive specimens, 0/9 Salmonella-positive specimens, and 2/3 Shigella-positive specimens. For both rectal swab and stool samples, the median cycle threshold (CT ) values, determined using quantitative PCR, were higher for GPP-negative/culture-positive samples than for GPP-positive/culture-positive samples (for rectal swabs, 36.9 [interquartile range {IQR}, 33.7, 37.1] versus 30.0 [IQR, 26.2, 33.2], respectively [P = 0.002]; for stool samples, 36.9 [IQR, 33.7, 37.1] versus 29.0 [IQR, 24.8, 30.8], respectively [P = 0.001]). GPP and culture have excellent overall agreement; however, for specific pathogens, GPP is less sensitive than culture and, notably, identifies samples false positive for Salmonella spp.

Pigment Visibility on Rectal Swabs Used To Detect Enteropathogens: a Prospective Cohort Study.

Data are lacking regarding the impact of visible pigment on rectal swab diagnostic accuracy. We describe the test characteristics of rectal swabs with and without pigment in children with gastroenteritis. Between December 2014 and September 2017, children (age, <18 years) with ≥3 episodes of vomiting and/or diarrhea in a 24-h period and symptoms for <7 days were enrolled through two pediatric emergency departments and from a province-wide nursing telephone advice line in Alberta, Canada. Specimens were analyzed by employing nucleic acid amplification panels. The primary outcomes were the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the rectal swabs, with stool specimen results being used as the reference standard. An enteropathogen was detected in 76.0% (1,399/1,841) of the paired specimens. A total of 54.4% (1,001/1841) of the swabs had visible pigment. The respective enteropathogen detection characteristics of swabs with and without visible pigment were as follows: 92.2% (95% confidence interval [CI], 90.0%, 94.0%) versus 83.7% (95% CI, 80.5%, 86.4%) for sensitivity, 94.3% (95% CI, 90.5%, 96.6%) versus 91.2% (95% CI, 86.3%, 94.5%) for specificity, 97.9% (95% CI, 96.4%, 98.8%) versus 96.5% (95% CI, 94.5%, 97.8%) for PPV, and 80.9% (95% CI, 76.0%, 85.1%) versus 65.8% (95% CI, 60.0%, 71.1%) for NPV. Processing of swabs without visible pigment would increase the rate of identification of positive swabs from 50.0% (682/1,365) to 88.3% (1,205/1,365). There is a modest decrease in the reliability of a negative test on swabs without evidence of pigment, but the overall yield is significantly greater when they are not excluded from testing. Hence, rectal swabs without visible feces should not be routinely rejected from testing.

A prospective comparative study of children with gastroenteritis: emergency department compared with symptomatic care at home.

Little is known about the epidemiology and severity of gastroenteritis among children treated at home. We sought to compare illness severity and etiology between children brought for emergency department (ED) care to those managed at home (i.e., community). Prospective cohort study of children enrolled between December 2014 and December 2016 in two pediatric EDs in Alberta, Canada along with children treated at home after telephone triage (i.e., community). Primary outcomes were maximal frequency of vomiting and diarrhea in the 24-h pre-enrollment period; secondary outcomes included etiologic pathogens, dehydration severity, future healthcare visits, and treatments provided. A total of 1613 patients (1317 ED, 296 community) were enrolled. Median maximal frequency of vomiting was higher in the ED cohort (5 (3, 10) vs. 5 (2, 8); P < 0.001). Proportion of children with diarrhea and its 24-h median frequency were lower in the ED cohort (61.3 vs. 82.8% and 2 (0, 6) vs. 4 (1, 7); P < 0.001, respectively). In regression analysis, the ED cohort had a higher maximum number of vomiting episodes pre-enrollment (incident rate ratio (IRR) 1.25; 95% CI 1.12, 1.40) while the community cohort had higher maximal 24-h period diarrheal episodes (IRR 1.20; 95% CI 1.01, 1.43). Norovirus was identified more frequently in the community cohort (36.8% vs. 23.6%; P < 0.001). Children treated in the ED have a greater number of vomiting episodes; those treated at home have more diarrheal episodes. Norovirus is more common among children treated symptomatically at home and thus may represent a greater burden of disease than previously thought.

A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization During Pregnancy and Subsequent Infant Immune Response.

Background: Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods: In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results: Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions: This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration: NCT00553228.

Diagnostic Interpretation Guidance for Pediatric Enteric Pathogens: A Modified Delphi Consensus Process.

BACKGROUND: We sought to develop diagnostic test guidance definitions for pediatric enteric infections to facilitate the interpretation of positive test results in the era of multianalyte molecular diagnostic test platforms. METHODS: We employed a systematic, two-phase, modified Delphi consensus process consisting of three web-based surveys and an expert panel face-to-face meeting. In phase 1, we surveyed an advisory panel of North American experts to select pathogens requiring diagnostic test guidance definition development. In phase 2, we convened a 14-member expert panel to develop, refine, and select the final definitions through two web-based questionnaires interspersed with a face-to-face meeting. Both questionnaires asked panelists to rate the degree to which they agreed that if the definition is met the pathogen is likely to be causative of clinical illness. RESULTS: The advisory panel survey identified 19 pathogens requiring definitions. In the expert panel premeeting survey, 13 of the 19 definitions evaluated were rated as being highly likely ("agree" or "strongly agree") to be responsible for acute gastroenteritis symptoms by ≥67% of respondent panel members. The definitions for the remaining six pathogens (Aeromonas, Clostridium difficile, Edwardsiella, nonenteric adenovirus, astrovirus, and Entamoeba histolytica) were indeterminate. After the expert panel meeting, only two of the modified definitions, C. difficile and E. histolytica/dispar, failed to achieve the a priori specified threshold of ≥67% agreement. CONCLUSIONS: We developed diagnostic test guidance definitions to assist healthcare providers for 17 enteric pathogens. We identified two pathogens that require further research and definition development.

The Use of Routine Blood Cultures in Pediatric Appendicitis.

OBJECTIVES: To determine the proportion of true-positive blood culture results in children presenting to the ED with suspected appendicitis. To describe the current practice of obtaining blood cultures in children with suspected appendicitis. METHODS: We performed a 2-year retrospective health record review of all children aged 2 through 17 years investigated for suspected appendicitis at a tertiary Pediatric Emergency Department. Subjects were identified by searching (a) institutional records for ICD-10-CA coding, (b) diagnostic imaging records of ultrasounds for appendicitis, and (c) surgical database records for nonincidental appendectomies. Abstracted demographic and clinical data were matched to regional laboratory services data to describe the performance and result of blood cultures. RESULTS: Overall, 1315 children investigated for appendicitis were reviewed. Seven hundred fifty (57.0%) were girls, the average age was 11.7 years (SD, 4.0). Blood cultures were obtained in 288 (21.9%) of 1315 patients. Of the 11 (3.8%) cultures that were positive, only 1 (0.35%) was a true positive. Young age, high triage acuity, and presence of fever were associated with the acquisition of cultures (P < 0.001 for all). The proportion of children undergoing appendectomy and the negative appendectomy rate was similar between those with and without blood culture (P = 0.10 and P = 0.96, respectively). CONCLUSIONS: True-positive blood cultures are very rare in children presenting to the ED with suspected appendicitis. Given the potential for false-positive cultures and the social/economic implications of initial testing/retesting of false positives, the use of routine blood cultures for children with suspected appendicitis is not supported.

Physician perspectives on vaccination and diagnostic testing in children with gastroenteritis: A primary care physician survey.

OBJECTIVES: Gastroenteritis remains a common paediatric illness. Little is known about physician knowledge of enteric pathogen diagnostic tests. At the time of study conduct, Alberta lacked a publicly funded rotavirus vaccination program and knowledge of primary care physician perspectives was lacking. We sought to ascertain diagnostic testing methods and to understand knowledge and perceptions regarding enteric pathogen vaccination. METHODS: A 30-item electronic survey was distributed across Alberta's five health care zones. The survey was developed by virology, microbiology, paediatrics, family medicine and public health experts. Participants were members of Alberta's Primary Care Networks, the TARRANT network and The Society of General Pediatricians of Greater Edmonton. Study outcomes included: (1) physician knowledge of available diagnostic tests, (2) perspectives regarding stool sample collection and (3) support for an enteric vaccine program. RESULTS: Stool culture was reported as the test to identify parasites (47%), viruses (74%) and Clostridium difficile (67%). Although electron microscopy and enzyme immunoassay were used to identify viruses in Alberta during the study period, only 20% and 48% of respondents respectively identified them as tests employed for such purposes. Stool testing was viewed as being inconvenient (62%; 55/89), whereas rectal swabs were thought to have the potential to significantly improve specimen collection rates (82%; 72/88). Seventy-three per cent (66/90) of the respondent physicians support the adoption of future enteric pathogen vaccines. CONCLUSIONS: Simplification of diagnostic testing and stool sample collection could contribute to improved pathogen identification rates. Implementation of an enteric vaccine into the routine paediatric vaccination schedule is supported by the majority of respondents.

Influence of Childhood Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease in Adults With Underlying Comorbidities in Calgary, Alberta (2000-2013).

BACKGROUND: Pneumococcal conjugate vaccine (PCV) was introduced into Alberta, Canada's routine childhood immunization programs in 2002 (7-valent [PCV7]) and 2010 (13-valent [PCV13]). We assessed the effect of these programs on the epidemiology of invasive pneumococcal disease (IPD) to determine if PCV-associated indirect protection was relatively reduced in adults with underlying comorbidities. METHODS: Demographic and clinical data were collected by a prospective, population-based surveillance system in Calgary, Alberta, Canada, from January 2000 to December 2013. An indirect cohort study design was used to assess for changes in the proportion of IPD cases with underlying comorbidities. RESULTS: There were 1598 overall and 1346 adult IPD cases from 1 January 2000 to 31 December 2013. Overall IPD incidence decreased 33% (age 0-5 months), 86% (6-23 months), 67% (2-4 years), 26% (5-17 years), 22% (18-64 years), 36% (65-84 years), and 42% (≥85 years) from the prevaccine (January 2000-July 2002) to the post-PCV13 (July 2010-December 2013) period. Over the same timeframe, PCV7 serotype disease incidence declined to ≤1 case per 100 000 persons in all age groups. Neither the proportion of adult cases with immunocompetent comorbidities (relative risk ratio [RRR], 0.93; 95% confidence interval [CI], .62-1.40) nor immunocompromising comorbidities (RRR, 0.99; 95% CI, .61-1.61) differed between the pre-PCV period and post-PCV era. CONCLUSIONS: Childhood PCV programs have provided considerable benefit, with substantial declines in overall and vaccine-serotype IPD in vaccinated children and in unvaccinated persons. Conjugate vaccine-associated indirect protection for adults with comorbidities was similar to that for healthy adults.

Shiga Toxin-Producing Escherichia coli Infection, Antibiotics, and Risk of Developing Hemolytic Uremic Syndrome: A Meta-analysis.

BACKGROUND: Antibiotic administration to individuals with Shiga toxin-producing Escherichia coli (STEC) infection remains controversial. We assessed if antibiotic administration to individuals with STEC infection is associated with development of hemolytic uremic syndrome (HUS). METHODS: The analysis included studies published up to 29 April 2015, that provided data from patients (1) with STEC infection, (2) who received antibiotics, (3) who developed HUS, and (4) for whom data reported timing of antibiotic administration in relation to HUS. Risk of bias was assessed; strength of evidence was adjudicated. HUS was the primary outcome. Secondary outcomes restricted the analysis to low-risk-of-bias studies employing commonly used HUS criteria. Pooled estimates of the odds ratio (OR) were obtained using random-effects models. RESULTS: Seventeen reports and 1896 patients met eligibility; 8 (47%) studies were retrospective, 5 (29%) were prospective cohort, 3 (18%) were case-control, and 1 was a trial. The pooled OR, including all studies, associating antibiotic administration and development of HUS was 1.33 (95% confidence interval [CI], .89-1.99; I(2) = 42%). The repeat analysis including only studies with a low risk of bias and those employing an appropriate definition of HUS yielded an OR of 2.24 (95% CI, 1.45-3.46; I(2) = 0%). CONCLUSIONS: Overall, use of antibiotics was not associated with an increased risk of developing HUS; however, after excluding studies at high risk of bias and those that did not employ an acceptable definition of HUS, there was a significant association. Consequently, the use of antibiotics in individuals with STEC infections is not recommended.