Molecular epidemiology of rotavirus among children in Western Canada: Dynamic changes in genotype prevalence in four consecutive seasons.

Rotavirus molecular surveillance remains important in the postvaccine era to monitor the changes in transmission patterns, identify vaccine-induced antigenic changes and discover potentially pathogenic vaccine-related strains. The Canadian province of Alberta introduced rotavirus vaccination into its provincial vaccination schedule in June 2015. To evaluate the impact of this program on stool rotavirus positivity rate, strain diversity, and seasonal trends, we analyzed a prospective cohort of children with acute gastroenteritis recruited between December 2014 and August 2018. We identified dynamic changes in rotavirus positivity and genotype trends during pre- and post-rotavirus vaccine introduction periods. Genotypes G9P[8], G1P[8], G2P[4], and G12P[8] predominated consecutively each season with overall lower rotavirus incidence rates in 2016 and 2017. The demographic and clinical features of rotavirus gastroenteritis were comparable among wild-type rotaviruses; however, children with G12P[8] infections were older (p < 0.001). Continued efforts to monitor changes in the molecular epidemiology of rotavirus using whole genome sequence characterization are needed to further understand the impact of the selection pressure of vaccination on rotavirus evolution.

Clinical Profiles of Childhood Astrovirus-, Sapovirus-, and Norovirus-Associated Acute Gastroenteritis in Pediatric Emergency Departments in Alberta, 2014-2018.

BACKGROUND: Infections by previously underdiagnosed viruses astrovirus and sapovirus are poorly characterized compared with norovirus, the most common cause of acute gastroenteritis. METHODS: Children <18 years old with acute gastroenteritis were recruited from pediatric emergency departments in Alberta, Canada between 2014 and 2018. We described and compared the clinical course of acute gastroenteritis in children with astrovirus, sapovirus, and norovirus. RESULTS: Astrovirus was detected in 56 of 2688 (2.1%) children, sapovirus was detected in 146 of 2688 (5.4%) children, and norovirus was detected in 486 of 2688 (18.1%) children. At illness onset, ~60% of astrovirus cases experienced both diarrhea and vomiting. Among sapovirus and norovirus cases, 35% experienced diarrhea at onset and 80% of 91% (sapovirus/norovirus) vomited; however, diarrhea became more prevalent than vomiting at approximately day 4 of illness. Over the full course of illness, diarrhea was 18% (95% confidence interval [CI], 8%- 29%) more prevalent among children with astrovirus than norovirus infections and had longer duration with greater maximal events; there were a median of 4.0 fewer maximal vomiting events (95% CI, 2.0-5.0). Vomiting continued for a median of 24.8 hours longer (95% CI, 9.6-31.7) among children with sapovirus versus norovirus. Differences between these viruses were otherwise minimal. CONCLUSIONS: Sapovirus infections attended in the emergency department are more similar to norovirus than previously reported, whereas astrovirus infections have several distinguishable characteristics.

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.

Detection and Clinical Implications of Monovalent Rotavirus Vaccine-Derived Virus Strains in Children with Gastroenteritis in Alberta, Canada.

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.

Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments.

OBJECTIVE: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. STUDY DESIGN: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. RESULTS: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%. CONCLUSIONS: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.

Diagnostic Test Accuracy of Commercial Tests for Detection of Shiga Toxin-Producing Escherichia coli: A Systematic Review and Meta-Analysis.

BACKGROUND: Rapid detection of Shiga toxin-producing Escherichia coli (STEC) enables appropriate monitoring and treatment. We synthesized available evidence to compare the performance of enzyme immunoassay (EIA) and PCR tests for the detection of STEC. METHODS: We searched published and gray literature for studies of STEC EIA and/or PCR diagnostic test accuracy relative to reference standards including at least one nucleic acid amplification test. Two reviewers independently screened studies, extracted data, and assessed quality with the second version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Bivariate random effects models were used to meta-analyze the clinical sensitivity and specificity of commercial EIA and PCR STEC diagnostic tests, and summary receiver operator characteristic curves were constructed. We evaluated the certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We identified 43 articles reflecting 25 260 specimens. Meta-analysis of EIA and PCR accuracy included 25 and 22 articles, respectively. STEC EIA pooled sensitivity and specificity were 0.681 (95% CI, 0.571-0.773; very low certainty of evidence) and 1.00 (95% CI, 0.998-1.00; moderate certainty of evidence), respectively. STEC PCR pooled sensitivity and specificity were 1.00 (95% CI, 0.904-1.00; low certainty of evidence) and 0.999 (95% CI, 0.997-0.999; low certainty of evidence), respectively. Certainty of evidence was downgraded because of high risk of bias. CONCLUSIONS: PCR tests to identify the presence of STEC are more sensitive than EIA tests, with no meaningful loss of specificity. However, given the low certainty of evidence, our results may overestimate the difference in performance.

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.

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.

Geogenomic Segregation and Temporal Trends of Human Pathogenic Escherichia coli O157:H7, Washington, USA, 2005-20141.

The often-noted and persistent increased incidence of Escherichia coli O157:H7 infections in rural areas is not well understood. We used a cohort of E. coli O157:H7 cases reported in Washington, USA, during 2005-2014, along with phylogenomic characterization of the infecting isolates, to identify geographic segregation of and temporal trends in specific phylogenetic lineages of E. coli O157:H7. Kernel estimation and generalized additive models demonstrated that pathogen lineages were spatially segregated during the period of analysis and identified a focus of segregation spanning multiple, predominantly rural, counties for each of the main clinical lineages, Ib, IIa, and IIb. These results suggest the existence of local reservoirs from which humans are infected. We also noted a secular increase in the proportion of lineage IIa and IIb isolates. Spatial segregation by phylogenetic lineage offers the potential to identify local reservoirs and intervene to prevent continued transmission.

Strength of the association between antibiotic use and hemolytic uremic syndrome following Escherichia coli O157:H7 infection varies with case definition.

BACKGROUND: The veracity of the association between antibiotic use and hemolytic uremic syndrome (HUS) caused by Escherichia coli O157:H7 has been a topic of debate. We postulated that criteria used to define HUS affect this association. METHODS: We reviewed 471 hospitalized E. coli O157:H7 cases reported in Washington State, 2005-2014, to determine HUS status by various case definitions and antibiotic treatment. We used age-adjusted logistic regression models to estimate the effect of treatment on HUS status according to four common, but heterogeneous, definitions: the Council of State and Territorial Epidemiologists (CSTE) definition, hematology-focused and age-focused definitions from the literature, and hospital diagnosis. RESULTS: Inter-annual variation in antibiotic use was high, but no meaningful change in antibiotic use was observed over this ten-year period. Thirteen percent of cases <18 years-old received antibiotics, compared to 54% of cases ≥18 years-old. The CSTE, hematology-focused, age-focused, and hospital diagnosis definitions identified 149, 57, 74, and 89 cases of HUS, respectively. The association between antibiotic treatment and HUS varied by definition: CSTE odds ratio (OR) 1.57 [95% confidence interval (CI) 0.98, 2.55]; hematology-focused OR 1.73 (95% CI 0.83, 3.54); age-focused OR 2.29 (95% CI 1.20, 4.39); and hospital diagnosis OR 1.94 (95% CI 1.01, 3.72). CONCLUSIONS: Each definition yielded an estimate of the association in the direction of increased risk of HUS with antibiotics. While the range of OR point estimates was relatively small, confidence intervals for two HUS definitions crossed the null and two did not, potentially altering the inference an investigator makes. Discrepant reports of the association between antibiotic use and HUS in the literature might be due in part to the choice of HUS definition, and a consistent definition of HUS should be adopted for research and public health purposes.

Case definitions of hemolytic uremic syndrome following Escherichia coli O157:H7 infection vary in validity.

BACKGROUND: Multiple case definitions for post-diarrheal hemolytic uremic syndrome (D+ HUS) associated with Shiga toxin-producing Escherichia coli (STEC) are used across public health, research, and clinical practice. METHODS: To identify a single definition of D+ HUS for standardized use, we evaluated the comparability and validity of four common, heterogeneous definitions: the Council of State and Territorial Epidemiologists (CSTE) definition, hematology-focused and age-focused definitions from the literature, and hospital diagnosis. We reviewed medical records from 471 hospitalized E. coli O157:H7 cases reported in Washington State, 2005-2014. We assessed 1) reliability across definitions, 2) comparability of temporal trends, and 3) sensitivity and specificity using an omnibus reference standard, developed using a combination of definition agreement and clinical outcomes. With the standard, we classified cases as definite, borderline, or unlikely/not post-diarrheal D+ HUS. RESULTS: Reliability was highest between the age-focused definition and hospital diagnosis (κ = 0.84), and temporal trends were largely comparable across definitions. For definite D+ HUS cases, the age-focused definition had the highest overall validity [100% sensitivity, 95% confidence interval (CI): 94%, 100%; 96% specificity, 95% CI: 94%, 98%]. The CSTE definition had low specificity (75%, 95% CI: 70%, 79%). CONCLUSIONS: In this review, the CSTE definition overestimated the burden of D+ HUS, and the age-focused definition provided the best overall reliability and validity to define post-diarrheal D+ HUS. Disease monitoring and research activities should consider using the age-focused D+ HUS definition.

Heat and Cold Wave-Related Mortality Risk among United States Veterans with Chronic Obstructive Pulmonary Disease: A Case-Crossover Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous pulmonary disease affecting 16 million Americans. Individuals with COPD are susceptible to environmental disturbances including heat and cold waves that can exacerbate disease symptoms. OBJECTIVE: Our objective was to estimate heat and cold wave-associated mortality risks within a population diagnosed with a chronic respiratory disease. METHODS: We collected individual level data with geocoded residential addresses from the Veterans Health Administration on 377,545 deceased patients with COPD (2016 to 2021). A time stratified case-crossover study was designed to estimate the incidence rate ratios (IRR) of heat and cold wave mortality risks using conditional logistic regression models examining lagged effects up to 7 d. Attributable risks (AR) were calculated for the lag day with the strongest association for heat and cold waves, respectively. Effect modification by age, gender, race, and ethnicity was also explored. RESULTS: Heat waves had the strongest effect on all-cause mortality at lag day 0 [IRR: 1.04; 95% confidence interval (CI): 1.02, 1.06] with attenuated effects by lag day 1. The AR at lag day 0 was 651 (95% CI: 326, 975) per 100,000 veterans. The effect of cold waves steadily increased from lag day 2 and plateaued at lag day 4 (IRR: 1.04; 95% CI: 1.02, 1.07) with declining but still elevated effects over the remaining 7-d lag period. The AR at lag day 4 was 687 (95% CI: 344, 1,200) per 100,000 veterans. Differences in risk were also detected upon stratification by gender and race. DISCUSSION: Our study demonstrated harmful associations between heat and cold waves among a high-risk population of veterans with COPD using individual level health data. Future research should emphasize using individual level data to better estimate the associations between extreme weather events and health outcomes for high-risk populations with chronic medical conditions. https://doi.org/10.1289/EHP13176.

Using a bayesian latent class model to evaluate the utility of investigating persons with negative polymerase chain reaction results for pertussis.

Pertussis remains difficult to control. Imperfect sensitivity of diagnostic tests and lack of specific guidance regarding interpretation of negative test results among patients with compatible symptoms may contribute to its spread. In this study, we examined whether additional pertussis cases could be identified if persons with negative pertussis test results were routinely investigated. We conducted interviews among 250 subjects aged ≤18 years with pertussis polymerase chain reaction (PCR) results reported from 2 reference laboratories in Wisconsin during July-September 2010 to determine whether their illnesses met the Centers for Disease Control and Prevention's clinical case definition (CCD) for pertussis. PCR validity measures were calculated using the CCD as the standard for pertussis disease. Two Bayesian latent class models were used to adjust the validity measures for pertussis detectable by 1) culture alone and 2) culture and/or more sensitive measures such as serology. Among 190 PCR-negative subjects, 54 (28%) had illnesses meeting the CCD. In adjusted analyses, PCR sensitivity and the negative predictive value were 1) 94% and 99% and 2) 43% and 87% in the 2 types of models, respectively. The models suggested that public health follow-up of reported pertussis patients with PCR-negative results leads to the detection of more true pertussis cases than follow-up of PCR-positive persons alone. The results also suggest a need for a more specific pertussis CCD.

Differences in risk factors for transmission among Shiga toxin-producing Escherichia coli serogroups and stx profiles.

OBJECTIVES: Trends in the incidence of O157 and non-O157 serogroups of Shiga toxin-producing Escherichia coli (STEC) infections have markedly diverged. Here, we estimate the extent to which STEC serogroups share the same transmission routes and risk factors, potentially explaining these trends. METHODS: With 3048 STEC cases reported in Minnesota from 2010 to 2019, we used lasso penalized regression to estimate pooled odds ratios (pOR) for the association between STEC risk factors and specific STEC serogroups and Shiga toxin gene profiles. We used random forests as a confirmatory analysis. RESULTS: Across an extended period of time, we found evidence for person-to-person transmission associated with the O26 serogroup, relative to other serogroups (pOR = 1.32 for contact with an individual with diarrhea). Rurality was less associated with non-O157 serogroups than O157 (pOR = 1.21 for each increasing level of rurality). We also found an association between unpasteurized juice and strains carrying only stx1 (pOR = 1.41). CONCLUSIONS: Collectively, these results show differences in risk factors across STEC types, which suggest differences in the most effective routes of transmission. Serogroup-specific disease control strategies should be explored. Specifically, preventative measures for non-O157 STEC need to extend beyond those we have employed for O157 STEC.

Enteric Pathogen Testing Importance for Children with Acute Gastroenteritis: a Modified Delphi Study.

The application of clinical diagnostics for gastroenteritis in children has implications for a broad collection of stakeholders, impacting clinical care, communicable disease control, and laboratory utilization. To support diagnostic stewardship as gastroenteritis testing options continue to advance, it is critical to understand which enteropathogens constitute priorities for testing across stakeholder groups. Using a modified Delphi technique, we elicited opinions of subject matter experts to determine clinical and public health testing priorities. There was a high level of overall agreement (≥80%) among stakeholders (final round n = 15) that testing was important for Campylobacter, Escherichia coli O157 and other Shiga toxin-producing E. coli, Salmonella, Shigella, Vibrio, Yersinia, norovirus, and rotavirus. Immunocompromised children were identified as a special population that warranted the additional testing of three to four bacterial and parasitic targets. To support these clinical and public health testing priorities, diagnostic stewardship strategies can be employed, such as educating clinicians, developing new decision support tools, and using multiplex testing in concert with selective result reporting and annotation. IMPORTANCE Children with diarrhea and vomiting who seek care can be infected with a wide variety of infectious agents. This study reports findings from a survey of clinical, public health, and laboratory subject matter experts on the infectious agents that are most important to test for. The majority agreed on the importance of testing children likely infected with several bacterial agents, as well as two common viruses. Although confirming a child is positive for a viral agent is unlikely to change clinical care, participants noted the importance of monitoring these viruses for public health purposes. To avoid over-testing children, however, these results should be used to support diagnostic stewardship strategies and design new decision support tools.

Genomic Analysis of Shiga Toxin-Producing E. coli O157 Cattle and Clinical Isolates from Alberta, Canada.

Shiga toxin (stx) is the principal virulence factor of the foodborne pathogen, Shiga toxin-producing Escherichia coli (STEC) O157:H7 and is associated with various lambdoid bacterio (phages). A comparative genomic analysis was performed on STEC O157 isolates from cattle (n = 125) and clinical (n = 127) samples to characterize virulence genes, stx-phage insertion sites and antimicrobial resistance genes that may segregate strains circulating in the same geographic region. In silico analyses revealed that O157 isolates harboured the toxin subtypes stx1a and stx2a. Most cattle (76.0%) and clinical (76.4%) isolates carried the virulence gene combination of stx1, stx2, eae and hlyA. Characterization of stx1 and stx2-carrying phages in assembled contigs revealed that they were associated with mlrA and wrbA insertion sites, respectively. In cattle isolates, mlrA and wrbA insertion sites were occupied more often (77% and 79% isolates respectively) than in clinical isolates (38% and 1.6% isolates, respectively). Profiling of antimicrobial resistance genes (ARGs) in the assembled contigs revealed that 8.8% of cattle (11/125) and 8.7% of clinical (11/127) isolates harboured ARGs. Eight antimicrobial resistance genes cassettes (ARCs) were identified in 14 isolates (cattle, n = 8 and clinical, n = 6) with streptomycin (aadA1, aadA2, ant(3'')-Ia and aph(3'')-Ib) being the most prevalent gene in ARCs. The profound disparity between the cattle and clinical strains in occupancy of the wrbA locus suggests that this trait may serve to differentiate cattle from human clinical STEC O157:H7. These findings are important for stx screening and stx-phage insertion site genotyping as well as monitoring ARGs in isolates from cattle and clinical samples.

Cognitive factors influenced physical distancing adherence during the COVID-19 pandemic in a population-specific way.

Even early in the COVID-19 pandemic, adherence to physical distancing measures was variable, exposing some communities to elevated risk. While cognitive factors from the Health Belief Model (HBM) and resilience correlate with compliance with physical distancing, external conditions may preclude full compliance with physical distancing guidelines. Our objective was to identify HBM and resilience constructs that could be used to improve adherence to physical distancing even when full compliance is not possible. We examined adherence as expressed through 7-day non-work, non-household contact rates in two cohorts: 1) adults in households with children from Minnesota and Iowa; and 2) adults ≥50 years-old from Minnesota, one-third of whom had Parkinson's disease. We identified multiple cognitive factors associated with physical distancing adherence, specifically perceived severity, benefits, self-efficacy, and barriers. However, the magnitude, and occasionally the direction, of these associations was population-dependent. In Cohort 1, perceived self-efficacy for remaining 6-feet from others was associated with a 29% lower contact rate (RR 0.71; 95% CI 0.65, 0.77). This finding was consistent across all race/ethnicity and income groups we examined. The barriers to adherence of having a child in childcare and having financial concerns had the largest effects among individuals from marginalized racial and ethnic groups and high-income households. In Cohort 2, self-efficacy to quarantine/isolate was associated with a 23% decrease in contacts (RR 0.77; 95% CI 0.66, 0.89), but upon stratification by education level, the association was only present for those with at least a Bachelor's degree. Education also modified the effect of the barrier to adherence leaving home for work, increasing contacts among those with a Bachelor's degree and reducing contacts among those without. Our findings suggest that public health messaging tailored to the identified cognitive factors has the potential to improve physical distancing adherence, but population-specific needs must be considered to maximize effectiveness.

Prevalence of Detection of Clostridioides difficile Among Asymptomatic Children: A Systematic Review and Meta-analysis.

Importance: Detection of Clostridioides difficile has frequently been described in asymptomatic infants and children, but accurate estimates across the age spectrum are unavailable. Objective: To assess the prevalence of C difficile detection among asymptomatic children across the age spectrum. Data Sources: This systematic review and meta-analysis included a search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, Scopus, and Web of Science for articles published from January 1, 1990, to December 31, 2020. Search terms included Clostridium difficile, Peptoclostridium difficile, Clostridioides difficile, CDF OR CDI OR c diff OR c difficile, Clostridium infections OR cd positive diarrhea OR cd positive diarrhea OR Clostridium difficile OR Peptoclostridium difficile OR pseudomembranous colitis OR pseudomembranous enterocolitis, enterocolitis, and pseudomembranous. These were combined with the following terms: bacterial colonization and colonization OR colonized OR colonizing OR epidemiology OR prevalence OR seroprevalence. Study Selection: Studies were screened independently by 2 authors. Studies were included if they reported testing for C difficile among asymptomatic children (ie, children without diarrhea) younger than 18 years. Data Extraction and Synthesis: Data were extracted independently and in duplicate by 2 reviewers. Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was prevalence of C difficile detection among asymptomatic children. Secondary outcomes included prevalence of toxigenic vs nontoxigenic strains of C difficile and prevalence of C difficile detection stratified by geographic region, income status, testing method, and year of testing. Results: A total of 95 studies with 19 186 participants were included. Rates of detection of toxigenic or nontoxigenic C difficile were greatest among infants aged 6 to 12 months (41%; 95% CI, 32%-50%) and decreased to 12% (95% CI, 7%-18%) among children aged 5 to 18 years. The prevalence of toxigenic C difficile colonization was lower, peaking at 14% (95% CI, 8%-21%) among infants aged 6 to 12 months and decreasing to 6% (95% CI, 2%-11%) among children older than 5 years. Although prevalence differed by geographic region (ie, North and South America vs Europe: ß, -0.151, P = .001; North and South America vs Western Pacific: ß, 0.136, P = .007), there was no difference by testing method (ie, culture vs polymerase chain reaction: ß, 0.069, P = .052; culture vs enzyme immunoassay: ß, -0.178, P = .051), income class (low-middle income vs high income: ß, -0.144, P = .23; upper-middle vs high income: ß, -0.020, P = .64), or period (before 1990 vs 2010-2020: ß, -0.125, P = .19; 1990-1999 vs 2010-2020: ß, -0.037, P = .42; 2000-2009 vs 2010-2020: ß, -0.006, P = .86). Conclusions and Relevance: In this systematic review and meta-analysis, C difficile colonization rates among children were greatest at 6 to 12 months of age and decreased thereafter. These estimates may provide context for interpreting C difficile test results among young children.

Farm animal contact is associated with progression to Hemolytic uremic syndrome in patients with Shiga toxin-producing Escherichia coli - Indiana, 2012-2018.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a life-threatening complication of Shiga toxin-producing Escherichia coli (STEC) infection. The relationship between STEC exposure and severity of clinical outcomes is not well documented. We examined whether direct contact with farm animals increased the likelihood of HUS among Indiana residents diagnosed with STEC. METHODS: Exposure data for laboratory-confirmed STEC cases among Indiana residents during 2012-2018 were retrieved. Logistic regression and mediation analysis were performed to determine the extent to which a history of direct contact with farm animals was associated with post-diarrheal HUS independent of age and mediated by stx2 gene presence. RESULTS: A total of 784 STEC cases were retrieved. Of these, 46 (6%) developed HUS. Complete exposure data were available for 600 (77%) cases. A total of 24 (52%) HUS patients reported direct contact with farm animals, while 114 (21%) STEC patients who did not develop HUS reported this exposure. Among all STEC cases, HUS was associated with direct farm animal contact after adjusting for age (OR = 3.40, 95% CI: 1.81, 6.40). Detection of stx2 genes mediated 12% of the association between farm animal contact and HUS. CONCLUSIONS: Direct farm animal contact was a risk factor for development of HUS among laboratory-confirmed STEC cases, independent of stx2 presence. Direct farm animal contact should be considered a potential predictor of progression to HUS when patients present for care and the mechanism for its effect on virulence investigated.