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Background Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California), collectively serving >320 000 patients annually. Methods From 1 July 2016 to 30 June 2018, we actively identified inpatient AGE case patients and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatients with AGE through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens by means of multiplex gastrointestinal polymerase chain reaction panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. Results We enrolled 724 inpatients with AGE, 394 non-AGE inpatient controls, and 506 outpatients with AGE. Clostridioides difficile and norovirus were most frequently detected among inpatients (for AGE case patients vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; P < .01 for both) and outpatients (norovirus, 10.7%; C. difficile, 10.5%). The incidence per 100 000 population was highest among outpatients (AGE, 2715; C. difficile, 285; norovirus, 291) and inpatients ≥65 years old (AGE, 459; C. difficile, 91; norovirus, 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/enteroinvasive Escherichia coli cases. Overall, 12% of inpatients with AGE had intensive care unit stays, and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. Conclusions C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round.

Background Norovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California) and examined trends over 4 surveillance years. Methods From November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus, and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served. Results Of 1603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November–April (9.2%, 376/100 000, and 45/100 000, respectively) compared to May–October (3.0%, 131/100 000, and 13/100 000, respectively). An alternate-year pattern was also detected, with highest peak prevalence and outpatient and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14%–25%, 349–613/100 000, and 43–46/100 000, respectively). Conclusions This multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and interannual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population.

SUMMARYNorovirus is the leading cause of acute gastroenteritis in the USA. Although secondary household transmission of norovirus is frequently reported in outbreaks, little is known about specific risk factors for susceptibility and infectiousness in the household. Three norovirus outbreaks were investigated and data were collected on individuals exposed in the primary outbreak setting and their household members. Potential individual- and household-level risk factors for susceptibility and infectiousness were assessed using univariate and multivariate generalised linear mixed models. In the univariate models, the secondary attack rate (SAR) was significantly higher when living in a household with two or more primary cases (incidence rate ratio (IRR) = 2·1; 95% confidence interval (CI) 1·37–3·29), more than one primary case with vomiting (IRR = 1·9; CI 1·11–3·37), and at least one primary case with diarrhoea (IRR = 3·0; CI 1·46–6·01). After controlling for other risk factors in the multivariate models, the SAR was significantly higher among those living in a household with two or more primary cases (adjusted IRR = 2·0; CI 1·17–3·47) and at least one primary case with diarrhoea (adjusted IRR = 2·8; CI 1·35–5·93). These findings underscore the importance of maintaining proper hygiene and isolating ill household members to prevent norovirus transmission in the household.

International Classification of Diseases diagnostic codes are used to estimate acute gastroenteritis (AGE) disease burden. We validated AGE-related codes in pediatric and adult populations using 2 multiregional active surveillance platforms. The sensitivity of AGE codes was similar (54% and 58%) in both populations and increased with addition of vomiting-specific codes.

Background Norovirus is a leading cause of acute gastroenteritis (AGE); however, few data exist on endemic norovirus disease burden among adults. Candidate norovirus vaccines are currently in development for all ages, and robust estimates of norovirus incidence among adults are needed to provide baseline data. Methods We conducted active surveillance for AGE among inpatients at a Veterans Affairs (VA) hospital in Houston, Texas. Patients with AGE (≥3 loose stools, ≥2 vomiting episodes, or ≥1 episode of both loose stool and vomiting, within 24 hours) within 10 days of enrollment and non-AGE control patients were enrolled. Demographic data and clinical characteristics were collected. Stool samples were tested using the FilmArray gastrointestinal panel; virus-positives were confirmed by real-time reverse transcription polymerase chain reaction and genotyped by sequencing. Results From November 2, 2015 through November 30, 2016, 147 case patients and 19 control patients were enrolled and provided a stool specimen. Among case patients, 139 (95%) were male and 70 (48%) were aged ≥65 years. Norovirus was the leading viral pathogen detected (in 16 of 20 virus-positive case patients) and accounted for 11% of all AGE cases. No viral pathogens were detected among control patients. Incidence of norovirus-associated hospitalization was 20.3 cases/100 000 person-years and was similar among those aged

We examined the uptake of rotavirus vaccine and compared trends in acute gastroenteritis (AGE)-associated hospitalizations and outpatient visits among American Indian and Alaska Native (AI/AN) children aged

The Navajo Nation includes approximately 250,000 American Indians living in a remote high desert environment with limited access to public water systems. We conducted a pilot case-control study to assess associations between acute gastroenteritis (AGE) and water availability, use patterns, and quality. Case patients with AGE and non-AGE controls who presented for care to two Indian Health Service hospitals were recruited. Data on demographics and water use practices were collected using a standard questionnaire. Household drinking water was tested for presence of pathogens, coliforms, and residual chlorine. Sixty-one subjects (32 cases and 29 controls) participated in the study. Cases and controls were not significantly different with respect to water sources, quality, or patterns of use. Twenty-one percent (n = 12) of study participants resided in dwellings not connected to a community water system. Eleven percent (n = 7) of subjects reported drinking hauled water from unregulated sources. Coliform bacteria were present in 44% (n = 27) of household water samples, and 68% (n = 40) of samples contained residual chlorine concentrations of

Background Histo-blood group antigens (HBGAs), whose expression is controlled in part by fucosyltransferase 2 (FUT2) and 3 (FUT3) genes, serve as receptors for norovirus and rotavirus. Individuals without functional FUT2 (nonsecretors) or FUT3 (Lewis-negative) genes may have decreased susceptibility to norovirus and rotavirus infections. As the prevalence of secretor and Lewis status can vary by race and ethnicity, we assessed this association in a US Veteran population. Methods Stool and saliva specimens were collected from acute gastroenteritis (AGE) cases and age- and time-matched controls through a multisite, active surveillance platform at four Veterans Affairs hospitals (Atlanta, Bronx, Houston, Los Angeles). Stool specimens were tested with the FilmArray Gastrointestinal Panel; norovirus and rotavirus positive specimens were genotyped. Saliva specimens were analyzed for HBGA expression by EIA using glycan-specific monoclonal antibodies and lectins. Chi-squared and Fisher’s exact tests were conducted to evaluate associations between secretor and Lewis status and infection with norovirus or rotavirus. Results From November 4, 2015–December 30, 2017, 670 AGE cases and 319 controls provided both stool and saliva specimens. Norovirus (21 GII.4 Sydney, 13 GII non-4, 7 GI, 10 untyped) and rotavirus (13 G12P[8], 1 G2P[4], 1 untyped) positive cases were more likely to be secretor positive (90% and 100%, respectively) compared with controls (76%) (P = 0.03 for both). Infections with GII.4 Sydney norovirus (P < 0.01) and G12P[8] rotavirus (P < 0.05) were significantly associated with secretor status. This association was not observed with other norovirus or rotavirus genotypes. No association was observed between Lewis status, race, or ethnicity and infection with norovirus or rotavirus. Conclusion Norovirus and rotavirus infections among a US Veteran population were associated with secretor status in a genotype-dependent manner, and with GII.4 Sydney norovirus and G12P[8] rotavirus, the most common strains. These associations are consistent with previously reported results, and suggest that the efficacy of interventions, such as vaccines, should include consideration of secretor status and predominantly circulating virus strains. Disclosures R. L. Atmar, Takeda Vaccines, Inc.: Investigator, Research grant. V. C. Marconi, ViiV: Investigator, Research support and Salary. Gilead: Investigator, Research support. Bayer: Investigator, Research support.

Background International Classification of Diseases (ICD) diagnostic codes from acute gastroenteritis (AGE)-associated medical encounters are used for AGE disease burden estimates, yet the validity of AGE-related ICD codes in both pediatric and adult populations is unknown. We estimated the validity of AGE-related diagnostic codes in these populations using two different multi-regional AGE active surveillance platforms. Methods Diagnostic codes, demographic and clinical characteristics, and stool pathogen results from AGE-associated medical encounters were obtained for enrolled children

Background The severity of acute gastroenteritis (AGE) in adult populations and the relative contribution of specific pathogens is not well characterized. In 2016, we implemented a multisite AGE surveillance platform in 4 VA hospitals (Atlanta, Bronx, Houston and Los Angeles), collectively serving > 320,000 patients annually. Methods Inpatient AGE cases and age- and time-matched non-AGE controls were identified through prospective screening of admissions using standardized case definitions. Stool samples were tested for 22 pathogens using the FilmArray® Gastrointestinal Panel. Medical conditions were analyzed as risk factors for AGE by multivariate logistic regression. Results From July 2016 to June 2018, 731 cases and 399 controls were enrolled. Risk factors for AGE cases included HIV-positive status (adjusted odds ratio [aOR] 4.6; 95% confidence interval [CI] 1.6–12.9; P < 0.01), severe kidney disease (aOR 4.5; 95% CI 2.0–9.8; P < 0.01), and immunosuppressive therapy (aOR 4.0; 95% CI 1.2–13.3]; P = 0.02). Clostridioides difficile and norovirus were the most commonly detected pathogens in cases (18% and 5%, respectively); detection of these pathogens in cases was significantly higher than detection in controls (8% and 2%, respectively; P < 0.01 for both). The median duration of hospital stay was longer for C. difficile compared with norovirus cases (5 vs. 3 days; P < 0.01), and cases with both pathogens had intensive care unit (ICU) stays (C. difficile: 18%; norovirus: 8%; P = 0.2). Fourteen deaths occurred among AGE cases; 2 were associated with C. difficile and 1 with norovirus; the remainder did not have a clear etiology or pathogen detected. C. difficile and norovirus were detected year-round with a fall and winter predominance; C. difficile prevalence was highest in October, while norovirus prevalence was six times higher in December than in summer months. Conclusion This surveillance platform captured cases of severe AGE, including ICU stays and deaths, among hospitalized US Veterans. C. difficile and norovirus were leading pathogens in AGE cases. These findings can help guide appropriate clinical management of AGE patients and inform public health efforts to quantify and address the associated burden of disease through targeted interventions. Disclosures All authors: No reported disclosures.

BACKGROUND: Ghana was among the first African nations to introduce monovalent rotavirus vaccine (RV1) into its childhood immunization schedule in April 2012. We aimed to assess the impact of vaccine introduction on rotavirus and acute gastroenteritis (AGE) hospitalizations and to estimate vaccine effectiveness (VE). METHODS: Using data from 2 teaching hospitals monthly AGE and rotavirus admissions by age were examined 40 months before and 31 months after RV1 introduction using interrupted time-series analyses. From January 2013 we enrolled children

Background Viruses are frequently implicated in acute gastroenteritis (AGE) outbreaks, yet the endemic burden of norovirus and rotavirus disease in adult populations is not well characterized. In 2016, we implemented a multisite AGE surveillance platform capturing cases and controls in 4 VA hospitals (Atlanta, Bronx, Houston, and Los Angeles), collectively serving >320,000 patients annually. Methods Inpatient AGE cases and age- and time-matched controls were identified through prospective screening of admissions via standardized case definitions. Outpatient cases were passively identified using stool samples submitted for routine clinical microbiological diagnostics. Samples were tested with the FilmArray Gastrointestinal Panel, followed by genotyping of virus positives. Incidence was estimated using population denominators of unique patients served annually by site. Results From December 1, 2016 to February 28, 2018, 875 cases (496 inpatients, 379 outpatients), and 374 controls were enrolled. Norovirus and rotavirus prevalence was highest among outpatient AGE cases (11.6% and 2.9%, respectively) followed by inpatient cases (3.4% and 1.6%, respectively); few controls were positive (norovirus, 1.3%; rotavirus, 0%). Norovirus-associated inpatient incidence was 15.2 per 100,000 population (range by site: 10.7–19.9/100,000) and rotavirus-associated inpatient incidence was 7.5 per 100,000 population (range by site: 0–12.8/100,000). The predominant norovirus genotype was GII.P16-GII.4 Sydney (50%), and rotavirus genotype was G12P[8] (83%). Norovirus was detected every calendar month and peaked in December–January, while rotavirus peaked in April. Nine deaths were documented among AGE inpatient cases, including one norovirus-associated death. Conclusion Implementation of a multisite AGE surveillance platform captured a wide spectrum of illness for norovirus and rotavirus in US Veterans including outpatient visits, inpatient hospitalizations, and one norovirus-associated death. Norovirus was the leading viral pathogen and was detected year-round. Ongoing surveillance using this platform will allow for further characterization of the pathogen distribution and associated AGE disease burden in adults. Disclosures V. Marconi, ViiV: Investigator, Research support and Salary. Bayer: Investigator, Research support. Gilead: Investigator, Research support.

An outbreak of hepatitis E virus (HEV) began in October 2007 in northern Uganda. To determine risk factors and sources for ongoing transmission, we conducted both a case-control study and an environmental investigation. A case patient was defined as having serologic evidence of HEV infection, whereas controls were seronegative. We identified risk factors for infection by univariable and multivariable analyses using conditional logistic regression. Several water sources were tested for HEV RNA. Among 112 cases and 145 controls, storage of drinking water in large-mouthed vessels (adjusted odds ratios [AOR] = 2.83; 95% confidence interval [CI] = 1.16–6.94) and washing hands in a group basin (AOR = 1.90; 95% CI = 1.07–3.38) were associated with HEV infection. HEV RNA was detected from communal hand-rinse and surface-water samples. The epidemiologic and environmental water-testing results suggest that household-level factors played an important role in the transmission of HEV—modalities that have been previously underappreciated.

Background Outbreaks of infection with hepatitis E virus (HEV) are frequently attributed to contaminated drinking water, even if direct evidence for this is lacking. Methods We conducted several epidemiologic investigations during a large HEV infection outbreak in Uganda. Results Of 10,535 residents, 3218 had HEV infection; of these, 2531 lived in households with >1 case. HEV was not detected in drinking water or zoonotic sources. Twenty-five percent of cases occurred > or = 8 weeks after onset of hepatitis in an index case in the household. Households with > or = 2 cases were more likely to have a member(s) who attended a funeral, had close contact with a jaundiced person, or washed hands in a common basin with others (P Conclusions A high attack rate in households, lack of a common source of infection, and poor hygienic practices in households with > or = 2 cases suggest person-to-person transmission of HEV during this outbreak.

In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of northern Uganda where no previous epidemics had been documented. This outbreak has progressed to become one of the largest hepatitis E outbreaks in the world. By June 2009, the epidemic had caused illness in >10,196 persons and 160 deaths.

Background Norovirus is the leading cause of acute gastroenteritis (AGE) outbreaks in the United States; however, little data exist on the burden of endemic norovirus disease among adults. Robust estimates of the norovirus disease burden among US adults are needed to inform assessment of potential norovirus vaccines, which are currently in development. Methods We conducted active surveillance for AGE at the Michael E. DeBakey Veteran’s Affairs (VA) Medical Center, where approximately 104,000 unique patients were served in 2016. Cases were defined as veterans with symptoms of AGE (≥3 loose stools, ≥2 vomiting episodes, or ≥1 episodes of both loose stool and vomiting, within 24 hours) occurring in the previous 10 days, who presented to the emergency department or outpatient clinics (outpatients), or were admitted to the hospital (inpatients). Patients without AGE symptoms in the prior 14 days were enrolled as controls. Demographic data and illness characteristics were collected from enrolled subjects, and stool samples were collected and tested using the FilmArray gastrointestinal panel. Norovirus positives were confirmed by real-time RT-PCR and genotyped after sequencing of conventional PCR products. Results From November 1, 2015–November 30, 2016, 130 inpatient and 85 outpatient AGE cases, along with 20 inpatient and 37 outpatient controls, were enrolled and provided a stool specimen. Among cases, 201 (93%) were male, and 94 (44%) were ≥65 years; median duration of illness was 3 days (range, 1–10 days). Norovirus was detected in 12 (9%) inpatient and 15 (18%) outpatient cases; norovirus was not detected in any controls. Incidence of norovirus-associated hospitalization was 15/100,000 population, and was similar in hospitalized cases aged Conclusion This robust, active surveillance platform employed screening and enrollment of patients in a VA population meeting a standardized AGE case definition, as well as asymptomatic controls. Data from this study highlight the burden of norovirus in adults and importance of a norovirus vaccine. Disclosures R. L. Atmar, Takeda Vaccines, Inc.: Research Support, Research support. B. Lopman, HHS/NIH/NIAID: Grant Investigator, Grant recipient. Bill & Melinda Gates Foundation: Grant Investigator, Grant recipient.

Background In the USA, norovirus is an important cause of epidemic acute gastroenteritis (AGE) as well as a leading cause of pediatric AGE. However, the burden of sporadic norovirus disease in US adults has not been well-documented. Our objective was to estimate the incidence of outpatient visits and hospitalizations for community-acquired norovirus AGE at four Veterans Affairs Medical Centers (VAMCs) and their associated outpatient clinics in Atlanta, GA; Bronx, New York; Houston, TX; and Los Angeles, CA. Methods From November 2011 to September 2015, stool specimens collected for clinician-requested diagnostic testing within 7 days of AGE symptom onset and with reported vomiting or diarrhea were tested for norovirus by real-time RT-PCR and positive samples were genotyped by Sanger sequencing. Incidence of norovirus-associated outpatient visits and hospitalizations were calculated by multiplying the prevalence of norovirus among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the unique patients served at each VAMC. Results 1,620 stool specimens were tested from all 4 sites. Seven percent of outpatient (n = 795) samples (annual range: 3%–10%; range by site: 3%–10%) and 6% of (n = 825) samples from hospitalized patients tested positive for norovirus (annual range: 3%–8%; range by site: 3%–10%). Forty-four percent of norovirus-positive specimens were typed as GII.4 Sydney. Seventy-four percent of norovirus-positive specimens were collected between November and April. From 2011 to 2015, outpatient norovirus incidence was 250/100,000 population (annual range: 129 to 426/100,000; range by site: 87 to 428/100,000), and the incidence of norovirus hospitalizations was 28/100,000 population (annual range: 19 to 39/100,000; range by site: 14 to 57/100,000). By age group and setting, the highest incidence was observed among 45- to 64-year-old outpatients (370/100,000 population), and 85+-year-old inpatients (63/100,000 population). Conclusion This study provides estimates of the incidence of norovirus AGE outpatient visits and hospitalizations across multiple years among a geographically distributed VA population, highlighting the substantial burden of norovirus in US adults. Disclosures All authors: No reported disclosures.

Varicella (chickenpox) is a highly contagious disease caused by the varicella zoster virus (VZV), which, in the absence of vaccination, is a universal infection acquired mainly in childhood. Prior to introduction of varicella vaccine in 1995, an estimated 4 million varicella cases, 11,000 hospitalizations and 100 deaths occurred each year in the United States.1 Since introduction of 1-dose varicella vaccination in the United States, dramatic declines were documented in the number of varicella cases,2 outbreaks,3 varicella-related hospitalizations and deaths.4,5 However, albeit smaller in size and shorter in duration, varicella outbreaks continued to occur in school and daycare settings with high 1-dose varicella vaccination coverage6-9; therefore, a routine 2-dose varicella vaccination was recommended in 2006 for school-aged children and a catch-up vaccination for children of all ages who lacked evidence of immunity.10 The 2-dose program appears to have been rapidly implemented in the United States in the first 5 years since it was recommended. For the 2012–2013 school-year, median 2-dose varicella vaccination coverage among the 36 states and District of Columbia requiring and reporting 2 doses was 93.8% (range: 84.6% in Colorado to ≥99.9% in Mississippi); 14 reported coverage ≥95%.11,12 There are limited data on the effectiveness of the 2-dose varicella vaccine regimen and very limited numbers of 2-dose breakthrough cases reported, thus more data are needed to describe 2-dose vaccine effectiveness (VE) and rash presentations of 2-dose breakthrough varicella. Therefore, a case control study was conducted in West Virginia public schools during 2010 and 2011 to evaluate 1-dose, 2-dose and incremental varicella VE and characterize 2-dose breakthrough varicella.

Background A second dose of varicella vaccine was recommended for U.S. children in 2006. We investigated a suspected varicella outbreak in School District X, Texas to determine 2-dose varicella vaccine effectiveness (VE). Methods A varicella case was defined as an illness with maculopapulovesicular rash without other explanation with onset during April 1–June 10, 2011, in a School District X student. We conducted a retrospective cohort in the two schools with the majority of cases. Lesion, saliva, and environmental specimens were collected for varicella-zoster virus (VZV) PCR testing. VE was calculated using historic attack rates among unvaccinated. Results In School District X, 82 varicella cases were reported, including 60 from Schools A and B. All cases were mild, with a median of 14 lesions. All 10 clinical specimens and 58 environmental samples tested negative for VZV. Two-dose varicella vaccination coverage was 66.4% in Schools A and B. Varicella VE in affected classrooms was 80.9% (95% CI: 67.2–88.9) among 1-dose vaccinees and 94.7% (95% CI: 89.2–97.4) among 2-dose vaccinees in School A, with a second dose incremental VE of 72.1% (95% CI: 39.0–87.3). Varicella VE among School B students did not differ significantly by dose (80.1% vs. 84.2% among 1-dose and 2-dose vaccinees, respectively). Conclusion Laboratory testing could not confirm varicella as the etiology of this outbreak; clinical and epidemiologic data suggests varicella as the likely cause. Better diagnostics are needed for diagnosis of varicella in vaccinated individuals so that appropriate outbreak control measures can be implemented.