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 (
< 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 (
< 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.
Background. Nasopharyngeal (NP) specimens are commonly used for the detection of respiratory viruses, but throat and saliva specimens are easier to obtain. The objective of this study was to compare ...the viral yield of direct fluorescent antigen detection of NP specimens and nucleic acid amplification tests (NAT) of direct fluorescent antigen-negative NP specimens with the viral yield of NAT of throat swab and saliva specimens. Methods. NP, throat swab, and saliva specimens were obtained from children and adolescents aged ⩽17 years. Direct fluorescent antigen testing of the NP specimen for respiratory syncytial virus, influenza A and B viruses, and parainfluenza virus was performed. If no virus was detected, NAT was performed for these 4 viruses, adenovirus, and human metapneumovirus. If a virus was detected by either method, NAT for the same virus was performed for the corresponding throat swab and saliva specimens. Results. A virus was detected in 105 of the 137 NP specimens. The same virus was detectable by NAT in 87 (83%) of 105 throat swab specimens and 77 (74%) of 104 saliva specimens. The likelihood of viral detection among throat swab and saliva swab specimens was higher when the NP specimen tested positive by direct fluorescent antigen testing, compared with NAT alone, and when the specimens were obtained within 3 days after symptom onset, compared with later in the illness. Conclusions. Throat swab and saliva specimens are inferior to NP specimens for the detection of respiratory viruses but might be acceptable for screening in a setting where it is impractical to obtain an NP specimen.
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.
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.
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%).
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.
Abstract
Background
It is unknown if probiotics exert pathogen-specific effects in children with diarrhea secondary to acute gastroenteritis.
Methods
Analysis of patient-level data from 2 multicenter ...randomized, placebo controlled trials conducted in pediatric emergency departments in Canada and the United States. Participants were 3–48 months with >3 diarrheal episodes in the preceding 24 hours and were symptomatic for <72 hours and <7 days in the Canadian and US studies, respectively. Participants received either placebo or a probiotic preparation (Canada-Lactobacillus rhamnosus R0011/Lactobacillus helveticus R0052; US-L. rhamnosus GG). The primary outcome was post-intervention moderate-to-severe disease (ie, ≥9 on the Modified Vesikari Scale MVS score).
Results
Pathogens were identified in specimens from 59.3% of children (928/1565). No pathogen groups were less likely to experience an MVS score ≥9 based on treatment allocation (test for interaction = 0.35). No differences between groups were identified for adenovirus (adjusted relative risk aRR: 1.42; 95% confidence interval CI: .62, 3.23), norovirus (aRR: 0.98; 95% CI: .56, 1.74), rotavirus (aRR: 0.86; 95% CI: .43, 1.71) or bacteria (aRR: 1.19; 95% CI: .41, 3.43). At pathogen-group and among individual pathogens there were no differences in diarrhea duration or the total number of diarrheal stools between treatment groups, regardless of intervention allocation or among probiotic sub-groups. Among adenovirus-infected children, those administered the L. rhamnosus R0011/L. helveticus R0052 product experienced fewer diarrheal episodes (aRR: 0.65; 95% CI: .47, .90).
Conclusions
Neither probiotic product resulted in less severe disease compared to placebo across a range of the most common etiologic pathogens. The preponderance of evidence does not support the notion that there are pathogen specific benefits associated with probiotic use in children with acute gastroenteritis.
Clinical Trials Registration
NCT01773967 and NCT01853124.
Among children with acute gastroenteritis presenting for emergency department care, neither L. rhamnosusR0011/L. helveticusR0052 nor L. rhamnosusGG treatment results in less severe disease when compared to placebo for the most common etiologic pathogens, including rotavirus.
Objective To identify the gaps in the care of children infected with Shiga toxin-producing Escherichia coli (STEC), we sought to quantitate care received and management timelines. Such knowledge is ...crucial to the design of interventions to prevent the development of hemolytic uremic syndrome (HUS). Study design We conducted a retrospective case-series study of 78 children infected with STEC in Alberta, Canada, through the linkage of microbiology and laboratory results, telephone health advice records, hospital charts, physician billing submissions, and outpatient antimicrobial dispensing databases. Outcomes were the time intervals between initial presentation and reporting of positive culture result and symptom onset to HUS and to describe the proportions that had baseline blood work performed and received antibiotics. Results Seventy-eight children infected with STEC were identified; 13% (10/78) developed HUS. Median time from initial presentation to laboratory stool sample receipt was 33 hours (IQR 18, 42); time to positive culture was 120 hours (IQR 86, 205). Time from symptom onset to HUS diagnosis was 188 ± 37 hours. Baseline blood tests were obtained in 74% (58/78) of infected children. Antibiotics were administered to 50% (5/10) of those who developed HUS and 22% (15/78) of those who did not; P = .11. The provincial telephone advice system received 31 calls regarding 24 children infected with STEC; 23% (7/31) of callers were recommended to seek emergency department care. Conclusions A significant proportion of children developed HUS following multiple interactions with the health care system. Delays in the confirmation of STEC infection occurred. There are numerous opportunities to improve the timing, monitoring, and interventions in children infected with STEC.
The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic ...across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.
While rotavirus vaccine programs effectively protect against severe rotavirus gastroenteritis, rotavirus vaccine strains have been identified in the stool of vaccinated children and their close ...contacts suffering from acute gastroenteritis. The prevalence of vaccine strains, the emergence of vaccine-derived strains, and their role in acute gastroenteritis are not well studied. We developed a locked nucleic acid reverse transcription real-time PCR assay (LNA-RTqPCR) to detect the monovalent rotavirus vaccine (RV1) Rotarix nonstructural protein 2 (NSP2) in children with acute gastroenteritis and healthy controls, and validated it using sequence-confirmed RV1 strains. The association between RV1-derived strains and gastroenteritis was determined using logistic regression. The new assay exhibited 100% (95% CI 91.7%, 100%) diagnostic sensitivity and 99.4% (95% CI 96.2%, 100%) diagnostic specificity, with a detection limit of 9.86 copies/reaction and qPCR efficiency of 99.7%. Using this assay, we identified the presence of RV1-derived NSP2 sequences in 7.7% of rotavirus gastroenteritis cases and 98.6% of rotavirus-positive healthy children (94.4% had previously received the RV1). Among gastroenteritis cases, those whose stool contained RV1-derived strains had milder gastroenteritis symptoms compared to that of natural rotavirus infections. We observed no significant association between RV1-derived strains and gastroenteritis (odds ratio OR 0.98; 95% CI 0.60, 1.72). Our study demonstrated that the new assay is suitable for monitoring RV1-derived rotavirus strain circulation and that the RV1-derived strains are not associated with development of gastroenteritis symptoms.
Norovirus is a major pathogen identified in children with acute gastroenteritis (AGE), little is known about the strain's diversity and their clinical severity. Stool and/or rectal swabs were ...collected from children ≤18 years of age recruited at emergency departments (ED), and a provincial nursing advice phone line due to AGE symptoms in the province of Alberta, Canada between December 2014 and August 2018. Specimens were tested using a reverse transcription real time PCR and genotyped by Sanger sequencing. The Modified Vesikari Scale score (MVS) was used to evaluate the disease severity. The objectives are to identify the Genogroup and Genotype distribution and to compare illness severity between the GI and GII genogroups and to complete further analyses comparing the GII genotypes identified. GII.4 was the genotype most commonly identified. Children with GII.4 had higher MVS scores (12.0 (10.0, 14.0;
= 0.002)) and more prolonged diarrheal (5 days (3.0, 7.8)) and vomiting (3.2 days (1.7, 5.3;
< 0.001)) durations compared to other non GII.4 strains. The predominant strain varied by year with GII.4 SydneyP31 predominant in 2014/15, GII.4 SydneyP16 in 2015/16 and 2017/18, and GII.3P12 in 2016/17. Genogroup II norovirus strains predominated in children with AGE with variance between years; clinical severity associated with different strains varied with episodes being most severe among GII.4 infected children.
Norovirus is an important cause of gastroenteritis outbreaks globally and the most prevalent cause of sporadic gastroenteritis in many regions. Rapid and accurate identification of causative viral ...agents is critical for outbreak investigation, disease surveillance, and management. Because norovirus is not cultivable and has a highly diversified and variable genome, it is difficult to develop diagnostic assays. Detection methods have evolved from electron microscopy to conventional end-point reverse transcription polymerase chain reaction (RT-PCR), immunoassay, real-time RT-PCR, other molecular technologies, and nanotechnology array-based assays. The status and features of various testing methods are summarized in this review.
Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading ...causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus (
< 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus (
< 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children (
< 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.
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