Prevalence and Genetic Diversity of Adenovirus 40/41, Astrovirus, and Sapovirus in Children with Acute Gastroenteritis in Kansas City 2011-2016.

BACKGROUND: Most U.S. acute gastroenteritis (AGE) episodes in children are attributed to norovirus, whereas very little information is available on adenovirus 40/41 (AdV40/41), astrovirus or sapovirus. The New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based AGE surveillance in young children. METHODS: We tested and typed stool specimens collected between December 2011 to June 2016 from one NVSN site in Kansas City for the three viruses, and calculated hospitalization and emergency department (ED) detection rate. RESULTS: Of 3,205 collected specimens, 2,453 (76.5%) were from AGE patients (339 inpatients and 2,114 ED patients) and 752 (23.5%) were from healthy controls (HC). In AGE patients, astrovirus was detected in 94 (3.8%), sapovirus in 252 (10.3%) and AdV40/41 in 101 (4.5%) of 2249 patients. In HC, astrovirus was detected in 13 (1.7%) and sapovirus in 15 (2.0%) specimens. Astrovirus type 1 (37.7%) and genogroup I sapoviruses (59.3%) were most prevalent.Hospitalization rates were 5 (AdV40/41), 4 (astrovirus) and 8 (sapovirus) per 100,000 children <11 years old, whereas ED rates were 2.4 (AdV40/41), 1.9 (astrovirus) and 5.3 (sapovirus) per 1000 children <5 years old. CONCLUSIONS: Overall, AdV40/41, astrovirus, and sapovirus were detected in 18.6% of AGE in a large pediatric hospital in Kansas City.

Emergence of Novel Norovirus GII.4 Variant.

We detected a novel GII.4 variant with an amino acid insertion at the start of epitope A in viral protein 1 of noroviruses from the United States, Gabon, South Africa, and the United Kingdom collected during 2017-2022. Early identification of GII.4 variants is crucial for assessing pandemic potential and informing vaccine development.

Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritis.

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.

Measuring Environmental Exposure to Enteric Pathogens in Low-Income Settings: Review and Recommendations of an Interdisciplinary Working Group.

Infections with enteric pathogens impose a heavy disease burden, especially among young children in low-income countries. Recent findings from randomized controlled trials of water, sanitation, and hygiene interventions have raised questions about current methods for assessing environmental exposure to enteric pathogens. Approaches for estimating sources and doses of exposure suffer from a number of shortcomings, including reliance on imperfect indicators of fecal contamination instead of actual pathogens and estimating exposure indirectly from imprecise measurements of pathogens in the environment and human interaction therewith. These shortcomings limit the potential for effective surveillance of exposures, identification of important sources and modes of transmission, and evaluation of the effectiveness of interventions. In this review, we summarize current and emerging approaches used to characterize enteric pathogen hazards in different environmental media as well as human interaction with those media (external measures of exposure), and review methods that measure human infection with enteric pathogens as a proxy for past exposure (internal measures of exposure). We draw from lessons learned in other areas of environmental health to highlight how external and internal measures of exposure can be used to more comprehensively assess exposure. We conclude by recommending strategies for advancing enteric pathogen exposure assessments.

Parathyroid 4D CT: What the Surgeon Wants to Know.

Parathyroid four-dimensional (4D) CT is an increasingly used and powerful tool for preoperative localization of abnormal parathyroid tissue in the setting of primary hyperparathyroidism. Accurate and precise localization of a single adenoma facilitates minimally invasive parathyroidectomy, and localization of multiglandular disease aids bilateral neck exploration. However, many radiologists find the interpretation of these examinations to be an intimidating challenge. The authors review parathyroid 4D CT findings of typical and atypical parathyroid lesions and provide illustrative examples. Relevant anatomy, embryology, and operative considerations with which the radiologist should be familiar to provide clinically useful image interpretations are also discussed. The most important 4D CT information to the surgeon includes the number, size, and specific location of candidate parathyroid lesions with respect to relevant surgical landmarks; the radiologist's opinion and confidence level regarding what each candidate lesion represents; and the presence or absence of ectopic or supernumerary parathyroid tissue, concurrent thyroid pathologic conditions, and arterial anomalies associated with a nonrecurrent laryngeal nerve. The authors provide the radiologist with an accessible and practical approach to performing and interpreting parathyroid 4D CT images, detail what the surgeon really wants to know from the radiologist and why, and provide an accompanying structured report outlining the key information to be addressed. By accurately reporting and concisely addressing the key information the surgeon desires from a parathyroid 4D CT examination, the radiologist substantially impacts patient care by enabling the surgeon to develop and execute the best possible operative plan for each patient. ©RSNA, 2020.

The Norovirus Epidemiologic Triad: Predictors of Severe Outcomes in US Norovirus Outbreaks, 2009-2016.

BACKGROUND: Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. Clarifying the viral, host, and environmental factors (epidemiologic triad) associated with severe outcomes can help target public health interventions. METHODS: Acute norovirus outbreaks reported to the National Outbreak Reporting System (NORS) in 2009-2016 were linked to laboratory-confirmed norovirus outbreaks reported to CaliciNet. Outbreaks were analyzed for differences in genotype (GII.4 vs non-GII.4), hospitalization, and mortality rates by timing, setting, transmission mode, demographics, clinical symptoms, and health outcomes. RESULTS: A total of 3747 norovirus outbreaks were matched from NORS and CaliciNet. Multivariable models showed that GII.4 outbreaks (n = 2353) were associated with healthcare settings (odds ratio [OR], 3.94 [95% confidence interval {CI}, 2.99-5.23]), winter months (November-April; 1.55 [95% CI, 1.24-1.93]), and older age of cases (≥50% aged ≥75 years; 1.37 [95% CI, 1.04-1.79]). Severe outcomes were more likely among GII.4 outbreaks (hospitalization rate ratio [RR], 1.54 [95% CI, 1.23-1.96]; mortality RR, 2.77 [95% CI, 1.04-5.78]). Outbreaks in healthcare settings were also associated with higher hospitalization (RR, 3.22 [95% CI, 2.34-4.44]) and mortality rates (RR, 5.65 [95% CI, 1.92-18.70]). CONCLUSIONS: Severe outcomes more frequently occurred in norovirus outbreaks caused by GII.4 and those in healthcare settings. These results should help guide preventive interventions for targeted populations, including vaccine development.

Birth Cohort Studies Assessing Norovirus Infection and Immunity in Young Children: A Review.

Globally, noroviruses are among the foremost causes of acute diarrheal disease, yet there are many unanswered questions on norovirus immunity, particularly following natural infection in young children during the first 2 years of life when the disease burden is highest. We conducted a literature review on birth cohort studies assessing norovirus infections in children from birth to early childhood. Data on infection, immunity, and risk factors are summarized from 10 community-based birth cohort studies conducted in low- and middle-income countries. Up to 90% of children experienced atleast one norovirus infection and up to 70% experienced norovirus-associated diarrhea, most often affecting children 6 months of age and older. Data from these studies help to fill critical knowledge gaps for vaccine development, yet study design and methodological differences limit comparison between studies, particularly for immunity and risk factors for disease. Considerations for conducting future birth cohort studies on norovirus are discussed.

Molecular epidemiology of noroviruses in children under 5 years of age with acute gastroenteritis in Yaoundé, Cameroon.

Norovirus is a common cause of acute gastroenteritis (AGE) among children in developing countries. Limited data on the prevalence and genetic variability of norovirus are available in Cameroon, where early childhood mortality due to AGE is common. We tested 902 fecal specimens from children younger than 5 years of age hospitalized with AGE between January 2010 and December 2013. Overall, 76 (8.4%) samples tested positive for norovirus, of which 83% (63/76) were among children below 12 months old. Most of the noroviruses detected were in children infected between July and December of each year. All norovirus-positive specimens were genotyped, with 80% (61/76) being GII.4 (three variants detected). Genotypes GI.2, GI.6, GII.1, GII.2, GII.3, GII.6, GII.16, GII.17, and GII.21 were also detected. Interestingly, GII.4 Sydney and GII.17 Kawasaki viruses were found as early as 2010, years before their emergence globally. This study suggests norovirus is a significant cause of moderate to severe gastroenteritis among young children in Cameroon. The results are important to highlight appropriate prevention and control strategies for reducing the burden of norovirus disease.

Inactivation of Escherichia coli O157:H7 and Salmonella during washing of contaminated gloves in levulinic acid and sodium dodecyl sulfate solutions.

Field workers often wear gloves harvesting ready-to-eat produce; however, fields are not sterile environments and gloves may become contaminated numerous times during a working shift. This study explored the potential for inactivation of Escherichia coli O157:H7 and Salmonella when contaminated gloves were washed in levulinic acid (LV) and sodium dodecyl sulfate (SDS) solutions. Washing nitrile gloves with increasing concentrations of LV above 1.0% led to a decreased prevalence of glove contamination by Salmonella (P = 0.0000). A higher level of prevalence occurred for solid agar-cultured pathogens than liquid broth-cultured pathogens after nitrile gloves were washed in LV/SDS (P = 0.0000). Pathogens residing on latex gloves were more likely to be completely inactivated by washing in 0.5% LV/0.1% SDS solutions than nitrile or Canners gloves that exhibited inconsistent responses dependent on the pathogen strain. However, drying after washing nitrile gloves in 0.5% LV/0.1% SDS led to additional pathogen inactivation (P = 0.0394). Pathogen transfer from gloves to produce was implied as the pathogen prevalence on cantaloupe rind handled by LV/SDS-washed gloves was not statistically different from the prevalence on gloves (P = 0.7141). Hence, the risk of produce contamination may still exist but would be reduced by washing gloves in LV/SDS.

Genetic and Epidemiologic Trends of Norovirus Outbreaks in the United States from 2013 to 2016 Demonstrated Emergence of Novel GII.4 Recombinant Viruses.

Noroviruses are the most frequent cause of epidemic acute gastroenteritis in the United States. Between September 2013 and August 2016, 2,715 genotyped norovirus outbreaks were submitted to CaliciNet. GII.4 Sydney viruses caused 58% of the outbreaks during these years. A GII.4 Sydney virus with a novel GII.P16 polymerase emerged in November 2015, causing 60% of all GII.4 outbreaks in the 2015-2016 season. Several genotypes detected were associated with more than one polymerase type, including GI.3, GII.2, GII.3, GII.4 Sydney, GII.13, and GII.17, four of which harbored GII.P16 polymerases. GII.P16 polymerase sequences associated with GII.2 and GII.4 Sydney viruses were nearly identical, suggesting common ancestry. Other common genotypes, each causing 5 to 17% of outbreaks in a season, included GI.3, GI.5, GII.2, GII.3, GII.6, GII.13, and GII.17 Kawasaki 308. Acquisition of alternative RNA polymerases by recombination is an important mechanism for norovirus evolution and a phenomenon that was shown to occur more frequently than previously recognized in the United States. Continued molecular surveillance of noroviruses, including typing of both polymerase and capsid genes, is important for monitoring emerging strains in our continued efforts to reduce the overall burden of norovirus disease.

Risk factors for overnight respiratory events following sedation for magnetic resonance imaging in children with sleep apnea.

PURPOSE: Children with sleep apnea may be at increased risk for overnight respiratory events (ORE) following anesthesia. We sought to identify ORE risk factors in sleep apnea patients sedated for magnetic resonance imaging (MRI). METHODS: One thousand four hundred seven hospitalizations for children with sleep apnea (by ICD-9 code) occurred at our institution from 5/1/2011 to 2/1/2015. One hundred twenty-seven (9 %) encounters were solely for post-MRI observation representing 96 unique patients. The first post-MRI admission for each patient underwent chart review. ORE was defined as sustained oxygen saturation <90 % with need for increased oxygen or adjustment of respiratory support after release from recovery. Characteristics of patients with and without ORE were compared by chi-squared analysis or independent samples t test. Logistic regression identified associations with ORE. RESULTS: Ten out of 96 (10.4 %) patients had ORE. The average time following sedation to ORE was 10.25 h. ORE patients were hospitalized longer (median 2 vs. 1 day, p < 0.001). Overall, patients were 55 % male, 60 % Hispanic, with median age of 5 years [IQR 2-10] and median body mass index (BMI) of 17.9 [IQR 15.2-24]. On logistic regression, apnea-hypopnea index (AHI; OR 1.007 [95 % CI 1.002-1.011]), anesthesia complication (OR 1.13 [95 % CI 1.01-1.28]), and home non-invasive positive pressure ventilation (NIV; OR 6.08 [95 % CI 1.57-26.17]) were associated with ORE. CONCLUSION: Ninety percent of children with sleep apnea admitted for overnight observation following sedated MRI did not have an ORE. AHI, anesthesia complications, and NIV use may help target higher-risk patients and avoid unnecessary hospitalizations.

The food industry's current and future role in preventing microbial foodborne illness within the United States.

During the past century, the microbiological safety of the US food supply has improved; however, many foodborne illnesses and outbreaks occur annually. Hence, opportunities for the food industry to improve the safety of both domestic and imported food exist through the adoption of risk-based preventive measures. Challenging food safety issues that are on the horizon include demographic changes to a population whose immune system is more susceptible to foodborne and opportunistic pathogens, climate changes that will shift where food is produced, and consumers' preferences for raw and minimally processed foods. Increased environmental and product testing and anonymous data sharing by the food industry with the public health community would aid in identifying system weaknesses and enabling more targeted corrective and preventive actions. Clinicians will continue to play a major role in reducing foodborne illnesses by diagnosing and reporting cases and in helping to educate the consumer about food safety practices.

Contamination of knives and graters by bacterial foodborne pathogens during slicing and grating of produce.

Poor hygiene and improper food preparation practices in consumers' homes have previously been demonstrated as contributing to foodborne diseases. To address potential cross-contamination by kitchen utensils in the home, a series of studies was conducted to determine the extent to which the use of a knife or grater on fresh produce would lead to the utensil's contamination with Escherichia coli O157:H7 or Salmonella enterica. When shredding inoculated carrots (ca. 5.3 log CFU/carrot), all graters became contaminated and the number of E. coli O157:H7 present on the utensil was significantly greater than Salmonella (p < 0.05). Contamination of knives after slicing inoculated produce (4.9-5.4 log CFU/produce item) could only be detected by enrichment culture. After slicing tomatoes, honeydew melons, strawberries, cucumbers, and cantaloupes, the average prevalence of knife contamination by the two pathogens was 43%, 17%, 15%, 7%, and 3%, respectively. No significant increase in the incidence or level of contamination occurred on the utensils when residues were present (p > 0.05); however, subsequent contamination of 7 produce items processed with the contaminated utensils did occur. These results highlight the necessity of proper sanitization of these utensils when used in preparation of raw produce.

Sanitizer efficacy against murine norovirus, a surrogate for human norovirus, on stainless steel surfaces when using three application methods.

Human noroviruses are major etiologic agents of epidemic gastroenteritis. Outbreaks are often accompanied by contamination of environmental surfaces, but since these viruses cannot be routinely propagated in laboratory cultures, their response to surface disinfectants is predicted by using surrogates, such as murine norovirus 1 (MNV-1). This study compared the virucidal efficacies of various liquid treatments (three sanitizer liquids, 5% levulinic acid plus 2% SDS [LEV/SDS], 200 ppm chlorine, and an isopropanol-based quaternary ammonium compound [Alpet D2], and two control liquids, sterile tap water and sterile tap water plus 2% SDS) when delivered to MNV-1-inoculated stainless steel surfaces by conventional hydraulic or air-assisted, induction-charged (AAIC) electrostatic spraying or by wiping with impregnated towelettes. For the spray treatments, LEV/SDS proved effective when applied with hydraulic and AAIC electrostatic spraying, providing virus reductions of 2.71 and 1.66 log PFU/ml, respectively. Alpet D2 provided a 2.23-log PFU/ml reduction with hydraulic spraying, outperforming chlorine (1.16-log PFU/ml reduction). Chlorine and LEV/SDS were equally effective as wipes, reducing the viral load by 7.05 log PFU/ml. Controls reduced the viral load by <1 log with spraying applications and by >3 log PFU/ml with wiping. Results indicated that both sanitizer type and application methods should be carefully considered when choosing a surface disinfectant to best prevent and control environmental contamination by noroviruses.

Presence of antibodies against genogroup VI norovirus in humans.

BACKGROUND: Noroviruses are important enteric pathogens in humans and animals. Recently, we reported a novel canine norovirus (CaNoV) in dogs with diarrhea belonging to a new genogroup (GVI). No data are available on exposure of humans to this virus. METHODS: Sera from 373 small animal veterinarians and 120 age-matched population controls were tested for IgG antibodies to CaNoV by a recombinant virus like particle based enzyme-linked immunosorbent assay. RESULTS: Antibodies to CaNoV were found in 22.3% of the veterinarians and 5.8% of the control group (p < 0.001). Mean corrected OD450 values for CaNoV antibodies were significantly higher in small animal veterinarians compared to the control group. CONCLUSIONS: These findings suggest that CaNoV may infect humans and small animal veterinarians are at an increased risk for exposure to this virus. Additional studies are needed to assess if this virus is able to cause disease in humans.

Paediatric acute hepatitis of unknown aetiology: a national surveillance investigation in the USA during 2021 and 2022.

BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None.

Practice Integration as an Effective Educational Strategy.

Bundles are composed of individually established practices supported by research that, when combined, structure patient care. Implementing bundles improves patient outcomes. The ABCDEF initiative is an example of a bundled approach that improves outcomes of critically ill patients that are related to the likelihood of hospital death within 7 days, delirium and coma days, physical restraint use, intensive care unit readmission, and discharge disposition, with outcomes being proportional to the number of appropriate components performed. The purpose of this quality improvement project was to implement practice integration as an educational strategy to increase nursing knowledge of complex topics and, specifically, components of the ABCDEF bundle. Nurses' knowledge of all the BDE components of the ABCDEF bundle increased after implementing practice integration. Findings from this project support the use of resources to implement practice integration as an educational strategy for comprehensive concepts, specifically the BDE components of the ABCDEF bundle.

Hygienic monitoring in long-term care facilities using ATP, crAssphage, and human noroviruses to direct environmental surface cleaning.

BACKGROUND: Norovirus and C. difficile are associated with diarrheal illnesses and deaths in long-term care (LTC) facilities and can be transmitted by contaminated environmental surfaces. Hygienic monitoring tools such as adenosine triphosphate (ATP) bioluminescence and indicators of fecal contamination can help to identify LTC facility surfaces with cleaning deficiencies. METHODS: High-touch surfaces in 11 LTC facilities were swabbed and tested for contamination by norovirus, a fecal indicator virus, crAssphage, and ATP which detects organic debris. High levels of contamination were defined as log ATP relative light unit values or crAssphage log genomic copy values in the 75th percentile of values obtained from each facility. RESULTS: Over 90% of surfaces tested positive for crAssphage or gave failing ATP scores. Norovirus contamination was not detected. Handrails, equipment controls, and patient beds were 4 times more likely than other surfaces or locations to have high levels of crAssphage. Patient bed handrails and tables and chairs in patient lounges had high levels of both ATP and crAssphage. CONCLUSIONS: Surfaces with high levels of ATP and crAssphage were identified. Quantifying levels of contamination longitudinally and before and after cleaning might enhance infection prevention and control procedures for reducing diarrheal illnesses in LTC facilities.