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Background Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population especially when the population affected is undefined. Methods We evaluated the utility of CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), COVID-19 Case Surveillance System (CCSS), and 2020 U.S. Census data to determine demographic representation in the four stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at U.S. ACTT sites, with the respective 95% confidence intervals, to the reference data in forest plots. Results U.S. ACTT sites enrolled 3,509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic or Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with U.S. Census and CCSS. The proportion of participants ages 65 years was either similar or lower than COVID-NET and higher than CCSS and U.S. Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions While surveillance data of hospitalized cases may not be available early in an outbreak, it is a better comparator than U.S. Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

BackgroundCharacterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making.MethodsWe assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status.ResultsIMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 cases) (rate ratio, 1.48 [95% confidence interval, 1.10–2.00]), largely driven by surveillance IMI cases. Aspergillus was the most common species cultured (33.5% prehurricane and 39.9% posthurricane). About one-quarter (25.8%) of IMI patients lacked classical IMI risk factors such as hematologic malignancy and transplantations. Overall, 45.1% of IMI patients received intensive care, and in-hospital all-cause mortality was 24.2%.ConclusionsIMI incidence likely increased following Hurricane Harvey and outcomes for IMI patients were severe. Patient and clinician education on IMI prevention and identification is warranted, particularly as the frequency of extreme weather events increases due to climate change.

Norovirus infection causing acute gastroenteritis could lead to adverse effects on the gut microbiome. We assessed the association of microbiome diversity with norovirus infection and secretor status in patients from Veterans Affairs medical centers. Alpha diversity metrics were lower among patients with acute gastroenteritis but were similar for other comparisons.

Background The Adaptive COVID Treatment Trial-2 (ACTT-2) found that baricitinib in combination with remdesivir therapy (BCT) sped recovery in hospitalized coronavirus disease 2019 (COVID-19) patients vs remdesivir monotherapy (RMT). We examined how BCT affected progression throughout hospitalization and utilization of intensive respiratory therapies. Methods We characterized the clinical trajectories of 891 ACTT-2 participants requiring supplemental oxygen or higher levels of respiratory support at enrollment. We estimated the effect of BCT on cumulative incidence of clinical improvement and deterioration using competing risks models. We developed multistate models to estimate the effect of BCT on clinical improvement and deterioration and on utilization of respiratory therapies. Results BCT resulted in more linear improvement and lower incidence of clinical deterioration compared with RMT (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95). The benefit was pronounced among participants enrolled on high-flow oxygen or noninvasive positive-pressure ventilation. In this group, BCT sped clinical improvement (HR, 1.21; 95% CI, 0.99 to 1.51) while slowing clinical deterioration (HR, 0.71; 95% CI, 0.48 to 1.02), which reduced the expected days in ordinal score (OS) 6 per 100 patients by 74 days (95% CI, −8 to 154 days) and the expected days in OS 7 per 100 patients by 161 days (95% CI, 46 to 291 days) compared with RMT. BCT did not benefit participants who were mechanically ventilated at enrollment. Conclusions Compared with RMT, BCT reduces the clinical burden and utilization of intensive respiratory therapies for patients requiring low-flow oxygen or noninvasive positive-pressure ventilation compared with RMT and may thereby improve care for this patient population.

Background Norovirus (NoV) is the leading cause of viral diarrhea in patients with cancer. In this study, we describe risk factors associated with acute and chronic NoV infection in this patient population. Methods We identified 132 patients with NoV diarrhea (using stool RT PCR) between 2016-2020 at University of Texas MD Anderson Cancer Center (MDACC). Patient data, including demographics, clinical characteristics, NoV treatments, and complications were retrospectively extracted from charts. Stool samples were analyzed for NoV genogroups and genotypes. We compared characteristics and outcomes of patients with acute diarrhea (< 14day; AD) versus chronic diarrhea ( >14day or recurrences within 12 weeks; CD) and analyzed the data using Pearson Chi square or Fisher’s exact for categorical variables and Wilcoxon rank-sum test for continuous variables. Results Of 132 patients identified, 124 had an underlying cancer (39 solid tumor, 85 hematological malignancies, Table 1). On univariate analysis, CD patients were more likely to have a hematological malignancy (p=0.002), be a hematopoietic stem cell recipient (p= 0.013), have a history of gastrointestinal graft versus host disease (p= 0.011), or have received immunosuppressants or steroids in the 90 days before diarrhea onset (p=0.001, Table 2). CD patients had significantly lower white blood cell counts (p=0.038), absolute neutrophil counts (p=0.049), IgG levels (p= 0.001), and serum albumin levels (p=0.002) at the time of NoV diagnosis (Table 3). Patients with CD more often received symptomatic or NoV targeting treatment, including anti-diarrheal (p=0.005), nitazoxanide (p< 0.001), intravenous immune globulin (p=0.017), and oral IgG (p=0.042). CD patients more often had diarrheal recurrence in the first 4 weeks (p=0.001) or the second month (p< 0.001) after initial diagnosis and needed enteral or parenteral nutrition (p=0.004). We genotyped NoV in 67 patients (Figure 1), resulting in identification of the following genogroups: GI (n=9, 13%), GII.4 (n=23, 34%), and other types of GII (n=35, 52%). Genotype diversity was higher in patients with CD than AD (Figure 1). Conclusion In patients with cancer, CD from NoV is associated with severe immunosuppression, is refractory to therapy and can be caused by a variety of NoV genotypes/genogroups. Disclosures Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support) Pablo C. Okhuysen, MD, FACP, FIDSA, Deinove Pharmaceuticals (Grant/Research Support)Ferring Pharmaceuticals (Consultant)Melinta Therapeutics (Grant/Research Support)Merck & Co. (Grant/Research Support)Napo Pharmaceuticals (Consultant, Scientific Research Study Investigator, Research Grant or Support)Singulex (Consultant)Summit Therapeutics (Grant/Research Support)

Norovirus (NoV) is the leading cause of viral-related diarrhea in cancer patients, in whom it can be chronic, contributing to decreased quality of life, interruption of cancer care, malnutrition, and altered mucosal barrier function. Immunosuppressed cancer patients shed NoV for longer periods of time than immunocompetent hosts, favoring quasispecies development and emergence of novel NoV variants. While nucleic acid amplification tests (NAATs) for NoV diagnosis have revolutionized our understanding of NoV burden of disease, not all NAATs provide information on viral load or infecting genotype. There is currently no effective antiviral or vaccine for chronic NoV infections. Screening for inhibitors of NoV replication in intestinal organoid culture models and creation of NoV-specific adoptive T cells are promising new strategies to develop treatments for chronic NoV in immunosuppressed patients. Herein we summarize data on the epidemiology, clinical manifestations, diagnostic challenges, and treatment of NoV infection in patients with cancer.

As the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines passed UK and US regulatory milestones in late 2020 and early 2021, multiple professional societies offered recommendations to assist pregnant and breastfeeding people as they choose whether to undergo vaccination. Despite such guidance, the lack of data describing vaccine safety, immunogenicity, and efficacy in pregnant and breastfeeding people has made this decision challenging for many. However, even considering the paucity of data, the known risks of coronavirus disease 2019 during pregnancy likely outweigh the not yet fully elucidated risks of SARS-CoV-2 vaccines, which have reassuring safety and efficacy profiles among nonpregnant people.

As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other epidemic coronaviruses and briefly discuss potential mechanisms driving the phenomenon of postacute COVID-19.

Background CAR-T is used to treat certain refractory hematological malignancies. B-cell aplasia and immunosuppression used to treat CAR-T side effects increase infection risk. Little data are available describing Norovirus (NoV) infections in CAR-T recipients. Methods We reviewed the medical records of 134 patients with NoV diarrhea (identified by nucleic acid amplification test) between 2016-2019. Of these patients, nine received CAR-T prior to developing NoV. Here we describe their demographics, clinical characteristics, treatments, and complications. Results The median age was 49 years (Table 1). Patients’ underlying malignancies included Non-Hodgkin’s Lymphoma (4), Acute Lymphoblastic Leukemia (3), Chronic Lymphocytic Leukemia (1) and metastatic Sarcoma (1). Prior to development of NoV, six patients had undergone hematopoietic stem cell transplant, and 1 had received checkpoint inhibitor therapy. Five patients experienced cytokine release syndrome after CAR-T, and 1 experienced CAR-T-related encephalopathy syndrome (Table 2). Two patients received interleukin-6 antagonist therapy, and one received high dose steroids. Time to diarrhea onset post-CAR-T cell infusion was variable(median 256days, IQR 26-523 days).Six had an absolute lymphocyte count< 1000/mm3 at diarrhea onset. Three had diarrhea for >14 days; median diarrhea duration in the other 6 patients was 4 days. Other GI complaints included abdominal pain (3), nausea (4), and vomiting (3). For NoV treatment, three received oral immunoglobulin, and 8 received Nitazoxanide. Complications included development of concomitant GI-GVHD(5), ileus (2), need for TPN (3), renal failure requiring dialysis (2), ICU stay (3), and death (2). Two patients were co-infected with other enteropathogens such as rotavirus, enteropathogenic and enteroaggregative E.Coli and Clostridioides difficile. Three patients with diarrhea lasting >14 days had serial samples collected over time; NoV shedding lasted 81-546 days. NoV was genotyped in 6 patients(Table 3) and included GII.2(2), GII.4(2), GII.6(1) and GII.12(1). Table 1: Patient characteristics (N=9) Table 2: CAR-T related factors Table 3: NoV Genotypes Conclusion NoV belonging to various genotypes is an important cause of acute and chronic diarrhea in patients receiving CAR-T cell therapy. Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary K. Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support)

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

Background Clinical, virologic, and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. Methods US subjects with suspected ZIKV infection were enrolled. Clinical data and specimens were prospectively collected for ZIKV RNA detection and serologic and cellular assays. Confirmed ZIKV infection (cases) and ZIKV-negative (controls) subjects were compared. Dengue-experienced and dengue-naïve cases were also compared. Results We enrolled 45 cases and 14 controls. Commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%), and arthralgia (82.2% and 54.5%), respectively. The sensitivity (94%) and duration of infection detection (80% positivity at 65–79 days after disease onset) by polymerase chain reaction were highest in whole-blood specimens. ZIKV-neutralizing antibodies had a half-life of 105 days and were significantly higher in dengue virus–experienced cases than naïve ones (P = .046). In intracellular cytokine staining assays, the ZIKV proteins targeted most often by peripheral blood mononuclear cells from cases were structural proteins C and E for CD4+ T cells and nonstructural proteins NS3, NS5, and NS4B for CD8+ T cells. Conclusions ZIKV RNA detection was more frequent and prolonged in whole-blood specimens. Immunoglobulin G (IgG) and neutralizing antibodies, but not IgM, were influenced by prior dengue infection. Robust cellular responses to E and nonstructural proteins have potential vaccine development implications.

Background Infection prevention and antibiotic stewardship are critical to the safe and effective delivery of patient care. The primary objective of this fellowship rotation is to train infectious diseases fellows to develop key competencies in the fields of infection prevention and antibiotic stewardship. Methods We implemented an infection prevention and antibiotic stewardship rotation for the first-year infectious disease fellows starting July 2017. This new one-month rotation included several lectures by infectious diseases physicians, infection preventionists and pharmacists. Fellows rounded with infection preventionists (isolation, device, environmental, and endoscopy rounds) and participated in infection control subcommittees (CLABSI, CAUTI, Clostridioides difficile colitis and surgical site infections). Fellows were required to present infection control data and develop a proposal for a quality improvement project using the Define, Measure, Analyze, Improve and Control (DMAIC) method. Knowledge was evaluated through a 25 item questionnaire administered before (pre) and after (post) rotation. Topics included definitions, surveillance, isolation, preventive methods, outbreak investigation, policies, antibiotic stewardship, healthcare economics, and leadership. Results Sixteen fellows have participated in the rotation (2017-2019); all completed the pre- and post- evaluations (same questionnaire). Fellows answered a mean of 11.1/25 questions correctly pre-course (SD 2.3). Scores improved significantly to a mean of 21.2/25 correct answers at the end of the course (SD 2.6, P< 0.001). All fellows presented quality improvement proposals at the end of the rotation, with a mean score of 85.7% (SD 4.6). The fellows were highly satisfied with the course with mean evaluation score 6.2/7 (88.5%). Conclusion The one month duration infection control and antibiotic stewardship rotation that provides basic training in the field at the beginning of the fellowship led to significant improvement in the fellows’ knowledge, and was very well received. An additional track has been implemented during the second year to prepare interested fellows for careers in infection control and/or antibiotic stewardship. Disclosures All Authors: No reported disclosures

Background Norovirus can cause chronic infections with serious morbidity and mortality in immunocompromised patients. While there are no FDA-approved medications for these infections, nitazoxanide, ribavirin, and enterally administered pooled immunoglobulin (IVIG) are used off-label on the basis of expert opinion. Nitazoxanide and ribavirin show antiviral activity in a murine norovirus infection model and an in vitro replicon model of genotype GI.I human norovirus RNA expression, respectively. However, these drugs have not been evaluated in in vitro infections with GII.4 human noroviruses, responsible for most human norovirus disease. We used the stem cell-derived nontransformed human intestinal enteroid (HIE) system, which supports GII.4 human norovirus replication, to evaluate the antiviral activities of nitazoxanide, ribavirin, and IVIG. Methods We inoculated HIEs with GII.4 human norovirus in the presence of half-log dilutions of nitazoxanide (3 µM to 100 µM), ribavirin (10 µM to 10 mM), or IVIG (1:100 to 1:3,000) and a media control. One and 48 hours after inoculation, we extracted and quantified GII.4 norovirus RNA from the HIEs. To demonstrate that replication inhibition was not due to cytotoxicity, we performed quantitative lactate dehydrogenase release assays on the HIEs across the therapeutic range of each compound. Results Nitazoxanide reduced GII.4 replication at 48 hours in a dose-dependent manner, achieving a >90% reduction in viral replication at 10 µM without cytotoxicity. These findings were confirmed in multiple HIE lines representing different intestinal segments and established from different donors. IVIG completely inhibited GII.4 replication at up to a 1:1,000 dilution and was not cytotoxic at therapeutic concentrations. Ribavirin did not reduce GII.4 replication at concentrations up to 10 mMµM, well in excess of levels achieved in human sera with standard doses. Conclusion Nitazoxanide and IVIG, but not ribavirin, potently inhibit GII.4 human norovirus replication in a biologically relevant in vitro model of human norovirus infection. These data highlight the use of HIEs as a new pre-clinical model for developing therapeutics for human norovirus disease. Disclosures All authors: No reported disclosures.

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 Clostridium difficile infection is often considered to result from recent acquisition of a C difficile isolate in a healthcare setting. However, C difficile spores can persist for long periods of time, suggesting a potentially large community environmental reservoir. The objectives of this study were to assess community environmental contamination of toxigenic C difficile and to assess strain distribution in environmental versus clinical isolates. Methods From 2013 to 2015, we collected community environmental swabs from homes and public areas in Houston, Texas to assess C difficile contamination. All positive isolates were tested for C difficile toxins A and B, ribotyped, and compared with clinical C difficile isolates obtained from hospitalized patients in Houston healthcare settings. Results A total of 2538 environmental samples were collected over the study period. These included samples obtained from homes (n = 1079), parks (n = 491), chain stores (n = 225), fast food restaurants (n = 123), other commercial stores (n = 172), and hospitals (n = 448). Overall, 418 environmental isolates grew toxigenic C difficile (16.5%; P < .001) most commonly from parks (24.6%), followed by homes (17.1%), hospitals (16.5%), commercial stores (8.1%), chain stores (7.6%), and fast food restaurants (6.5%). A similar distribution of ribotypes was observed between clinical and environmental isolates with the exception that ribotype 027 was more common in clinical isolates compared with environmental isolates (P < .001). Conclusions We identified a high prevalence of toxigenic C difficile from community environs that were similar ribotypes to clinical isolates. These findings suggest that interventions beyond isolation of symptomatic patients should be targeted for prevention of C difficile infection.

Background. Clostridium difficile infection is often considered to result from recent acquisition of a C difficile isolate in a healthcare setting. However, C difficile spores can persist for long periods of time, suggesting a potentially large community environmental reservoir. The objectives of this study were to assess community environmental contamination of toxigenic C difficile and to assess strain distribution in environmental versus clinical isolates. Methods. From 2013 to 2015, we collected community environmental swabs from homes and public areas in Houston, Texas to assess C difficile contamination. All positive isolates were tested for C difficile toxins A and B, ribotyped, and compared with clinical C difficile isolates obtained from hospitalized patients in Houston healthcare settings. Results. A total of 2538 environmental samples were collected over the study period. These included samples obtained from homes (n = 1079), parks (n = 491), chain stores (n = 225), fast food restaurants (n = 123), other commercial stores (n = 172), and hospitals (n = 448). Overall, 418 environmental isolates grew toxigenic C difficile (16.5%; P < .001) most commonly from parks (24.6%), followed by homes (17.1%), hospitals (16.5%), commercial stores (8.1%), chain stores (7.6%), and fast food restaurants (6.5%). A similar distribution of ribotypes was observed between clinical and environmental isolates with the exception that ribotype 027 was more common in clinical isolates compared with environmental isolates (P < .001). Conclusions. We identified a high prevalence of toxigenic C difficile from community environs that were similar ribotypes to clinical isolates. These findings suggest that interventions beyond isolation of symptomatic patients should be targeted for prevention of C difficile infection.

Background The clinical, virologic and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. Methods US patients with suspected Zika virus (ZIKV) infection were enrolled and clinical data and specimens were prospectively collected. Body fluids were tested for ZIKV RNA by PCR and blood was tested using serologic and cellular immune assays. Findings from those with confirmed ZIKV infections (cases) and ZIKV-negative controls were compared. Results We enrolled 45 cases and 14 controls. The most commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%) and arthralgia (82.2% and 54.5%), respectively. The sensitivity and duration of detection by PCR were highest in whole blood samples (94% of 35 cases who had samples collected up to day 79 post illness onset were positive); strikingly, 84% of those were still positive at 65–79 days post illness onset (Figure 1). ZIKV neutralizing antibodies were detected in all cases and none of the controls, and titers were significantly higher in dengue virus (DENV)-experienced subjects than in DENV-naïve ones (Figure 2). Among cases, anti-ZIKV IgG antibodies were also significantly higher in DENV-experienced patients, while anti-ZIKV IgM antibodies were no higher in DENV-experienced compared with naïve ones. Using intracellular cytokine staining, the highest frequencies of T cells producing IFN-γ, IL-2 and/or TNF-α were against the NS1, NS3, and NS5 proteins for CD4+ T cells, and against the E, NS3, and NS5 proteins for CD8+ T cells (Figure 3). Conclusion Detection of ZIKV RNA was more frequent and much more prolonged in whole blood samples compared with other body fluids. Diagnostic molecular assays on this easily obtained fluid should be prioritized for point-of-care development. Robust cellular responses to E, NS3 and NS5 proteins could have implications for vaccine development. Disclosures R. L. Atmar, Takeda Vaccines, Inc.: Investigator, Research grant.

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.