title: Emerging Infectious Literatures and the Zombie Condition

text: The book club format has enabled expert and nonexpert exploration of infection and epidemiology as encountered in popular literature. This exploration reveals that fiction focusing on apocalyptic disease often uses the zombie as embodiment of infection, as well as an exemplar of current knowledge on emerging disease.


Proceedings of the 25th European Paediatric Rheumatology Congress (PReS 2018): Lisbon, Portugal. 5-8 September 2018


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Pneumococcal colonization and carriage


Pneumococcal Pneumonia---Risky Business


title: La prévention et le contrôle des infections au cabinet du pédiatre

text: La transmission d’infections au cabinet du pédiatre est une source de préoccupation croissante. Le présent document traite des voies de transmission des infections et des principes de contrôle des infections actuellement en vigueur. La prévention englobe un aménagement du cabinet et des politiques administratives appropriés, le triage, les pratiques de soins habituelles pour tous les patients (p. ex., hygiène des mains; port de gants, de masques, d’un dispositif de protection oculaire et de blouses pour certaines interventions; nettoyage, désinfection et stérilisation des surfaces et de l’équipement, y compris les jouets; technique d’asepsie pour les interventions invasives), ainsi que les précautions additionnelles en cas d’infections particulières. Les membres du personnel doivent avoir reçu les vaccins nécessaires, et ceux qui sont atteints d’une infection doivent respecter les politiques de restriction au travail.


title: Infection prevention and control in paediatric office settings

text: Transmission of infection in the paediatric office is an issue of increasing concern. This document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (e.g., hand hygiene; use of gloves, masks, eye protection, and gowns for specific procedures; adequate cleaning, disinfection, and sterilization of surfaces and equipment, including toys; and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.


title: 871. Symptomatic Respiratory Syncytial Virus and Adenovirus Upper Respiratory Tract Infections Increase the Risk of Invasive Aspergillosis After Allogeneic Hematopoietic Cell Transplantation

text: BACKGROUND: Invasive aspergillosis (IA) is a serious infectious complication following hematopoietic cell transplantation (HCT). Few studies have reported respiratory viral infections (RVIs) as a risk factor for developing IA, and data regarding specific viruses is sparse. We examined whether specific respiratory viruses were associated with increased risk of developing IA post-HCT. METHODS: In a longitudinal surveillance study of RVIs among allogeneic HCT recipients conducted 2005–2010, weekly post-HCT nasal washes were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1 year post-HCT. Nasal and bronchoalveolar lavage (BAL) samples were tested by multiplex PCR for respiratory syncytial virus (RSV), parainfluenza viruses (PIV)1–4, influenza A/B, human metapneumovirus, adenovirus (ADV), and human rhinoviruses, and coronaviruses. Only respiratory virus detections with symptoms were counted as RVI. Separate Cox proportional hazards models were used to examine adjusted associations between each RVI and the development of first proven/probable IA by 1-year post-HCT. RESULTS: Among 437 patients who survived >28 days following HCT, 39 patients developed IA by 1-year post-HCT (median 87 days, range 5–283). After adjusting for age at HCT, neutropenia, high-grade CMV viremia, and HLA status (matched related vs. others) or severe acute graft-versus-host disease (GVHD Grade 0–2 vs. 3–4), RSV and ADV upper respiratory tract infections (URTI) were associated with increased risk of developing IA (figure). Detection of any respiratory virus in the BAL was associated with IA (P < 0.001). CONCLUSION: RSV and ADV URTI are significant risk factors for development of IA post-HCT; the association between PIV URTI and development of IA approached statistical significance. Viral lower respiratory tract infection was associated with IA. Our data provide a rationale to assess IA as an endpoint in preventive studies of novel agents for respiratory viruses and further emphasize the importance of effective infection prevention practices for RVIs after HCT. [Image: see text] DISCLOSURES: J. Chien, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. A. Waghmare, Ablynx: Investigator, Research support. J. Englund, Gilead: Consultant and Investigator, Consulting fee and Research support. Novavax: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Alios: Investigator, Research support. MedImmune: Investigator, Research support. M. Boeckh, Asun Biopharma: Consultant and Investigator, Consulting fee and Research support. Gilead Sciences: Consultant and Investigator, Consulting fee and Research support. Chimerix Inc.: Consultant and Investigator, Consulting fee and Research support. Humabs: Consultant, Consulting fee. GSK: Investigator, Research support.


title: 1583. The Utility of the Immunodeficiency Scoring Index (ISI) to Predict Outcomes of Coronavirus (HCoV) Infections in Hematopietic Cell Transplant (HCT) Recipients

text: BACKGROUND: Respiratory viral infections in HCT recipients are associated with high morbidity and mortality, especially after progression from upper respiratory tract infection (URI) to lower respiratory tract infections (LRI). Data on risk factors (RF) for LRI and mortality is lacking for HCoV infections after HCT. We aimed to validate our ISI in HCoV infections. METHODS: All adult HCT recipients with HCoV infection from 2015 to 2017 were evaluated. An ISI based on RF was used to classify patients as low (0–2), moderate (3–6), or high (7 or higher) risk for progression to LRI or death. We defined LRI as HCoV detected in nasal wash and/or bronchoalveolar lavage and new lung infiltrates on diagnostic imaging. Clinical parameters were collected and ISI were calculated for comparison. RESULTS: A total of 144 adult HCT recipients with 166 episodes of HCoV infections were analyzed. The most common HCoV serotype for LRI and URI was 229E (42.4%) and OC43 (37.6%), respectively, and most patients were infected between November and March each year (Figures 1 and 2). When compared with URI, patients with LRI were more likely in the pre-engraftment period, had multiple respiratory viruses infections, had nosocomially acquired HCoV, required hospitalization, ICU transfer, and mechanical ventilation (all, P < 0.05). Overall mortality rate was 4% at Day 30 from diagnosis and all patients who died had LRI with an 18% mortality. Among those who died, 33% had nosocomial infection, 67% were co-infected with another respiratory virus and 67% required mechanical ventilation. Using an ISI cut off of <4, the negative predictive value (NPV) for progression to LRI was 86% with a specificity of 76%. CONCLUSION: HCT recipients with HCoV LRI were more likely to have a fatal outcome. The NPV of the ISI for progression to LRI was high and could be used as a prognostic tool for future studies and for therapeutic clinical trials. DISCLOSURES: All authors: No reported disclosures.


title: 2264. The Burden of Respiratory Viral Illness in HIV-Infected Patients

text: BACKGROUND: Among individuals living with human immunodeficiency virus (HIV), pulmonary complications are the most frequent cause of morbidity and mortality. Although bacterial and fungal pathogens are well-described etiologies of lung disease, the role of respiratory viruses remains poorly understood. We sought to describe the burden of respiratory viral illness in HIV-infected inpatients admitted to our tertiary care center. METHODS: All HIV-infected inpatients from August 2015 to March 2018 were approached if they presented with respiratory symptoms, defined as cough, dyspnea, sore throat, rhinorrhea, wheezing, or stridor. Eighty patients were enrolled. After obtaining informed consent, nasopharyngeal swabs and blood were collected. If the subject underwent bronchoscopy per the treating physician, excess bronchoalveolar lavage (BAL) sample was collected. Demographic and clinical data were recorded for each subject. Multiplex PCR testing of all respiratory samples was performed. RESULTS: Of the 70 HIV-infected patients that have undergone complete analysis, 23 (33%) tested positive for respiratory viruses. Of these, 11 (48%) were positive for rhinovirus, 3 were positive for influenza A (13%), 2 for parainfluenza 3 (9%), 2 for coronavirus (9%), and one each tested positive for adenovirus, parainfluenza 4, respiratory syncytial virus and influenza B. One patient had co-infection with rhinovirus and human metapneumovirus. Patients infected with a respiratory virus had severe illness as nearly half (10/23; 48%) required intensive care, 5 (22%) required mechanical ventilation, 4 (17%) were discharged to a higher level of care, and 3 (13%) died. CONCLUSION: The role of respiratory viruses on the lung health of HIV-infected patients is poorly defined. In this study, respiratory viruses were identified in over a third of HIV-infected inpatients, representing a substantial disease burden. Moreover, these patients demonstrated significant disease severity. Given these findings, there is a need for future studies of viral infections in HIV-infected individuals to elucidate mechanisms of susceptibility to reduce the burden of pulmonary morbidity in this vulnerable population. DISCLOSURES: All authors: No reported disclosures.


title: 634. Transcriptional Stimulation of Antiviral Response Components by the Structural and Accessory Human coronavirus OC43 Proteins

text: BACKGROUND: In Kuwait, human coronavirus OC43 (HCoV-OC43) causes 25–30% of common cold, and 8.8% of respiratory infections in hospitalised patients. It is also associated with severe respiratory symptoms in infants, elderly, and immunocompromised patients. Our previous results showed that the expression of antiviral genes in human embryonic kidney (HEK) 293 cells is downregulated in the presence of HCoV-OC43 proteins. To understand the role of HCoV-OC43 proteins in antagonizing antiviral responses of the host, we investigated the effect of HCoV-OC43 structural and accessory proteins on the transcriptional activation of interferon-stimulated response element (ISRE), interferon-β (IFN-β) promoter, and nuclear factor kappa B response element (NF-kappaB-RE). METHODS: HCoV-OC43 ns2a, ns5a, membrane (M), and nucleocapsid (N) mRNA were amplified and cloned into the pAcGFP1-N expression vector, followed by transfection in HEK-293 cells. Two days post-transfection, the cells were co-transfected with a reporter vector containing firefly luciferase under the control of ISRE, IFN-β promoter, or NF-kappaB-RE. Renilla luciferase vector was used as an internal control for transfection efficiency. Following 24 hours of incubation, the cells were treated with either IFN or tumour necrosis factor (TNF) for 6 hours. Thereafter, promoter activity was assayed using the dual-luciferase reporter assay system. Influenza NS1 protein was used as positive control for antagonism. RESULTS: The transcriptional activity of ISRE, IFN-β promoter, and NF-kappaB-RE was downregulated in the presence of ns2a, ns5a, M, or N protein as there was a sharp fall in firefly luciferase levels. Overall, HCoV-OC43 proteins reduced firefly luciferase levels for ISRE and IFN-β promoter by at least ten fold, whereas for NF-kappaB-RE the firefly luciferase levels were reduced by at least fivefold. CONCLUSION: HCoV-OC43 has the ability to block the activation of different antiviral signaling pathways. DISCLOSURES: All authors: No reported disclosures.


title: 2518. The Role of Non-Influenza Viruses in the Seasonal Viral Respiratory Illness: A Epidemiologic Study From October 2016–March 2017

text: BACKGROUND: Influenza virus (IV) is a leading cause of morbidity and mortality worldwide; however, understanding the contribution of non-influenza viruses (NIV) to the annual burden of respiratory illnesses (RI) is evolving. Improvements in diagnostic techniques, including the increasing clinical use of respiratory viral PCR panels (vPCR), have markedly advanced our understanding of the contributions of NIV to the “influenza season.” METHODS: A retrospective analysis of all vPCR results from one hospital system, collected between October 1, 2016 and March 7, 2017, including inpatient and outpatient samples was performed. 2,047 vPCR tests were reviewed; after removing those with undetermined results and internal control samples, 1,924 were analyzed. Data points abstracted included detection and identification of virus, and date of detection. We compared the total and monthly rates of NIV with IV, throughout the study period. RESULTS: Of 1,924 vPCR results, 985 (51%) were positive for a respiratory virus. Of these, 302 (31%) were IV, and 683 (69%) were NIV. For every month studied, the ratio of NIV to IV exceeded 50%, including the height of the season. The most commonly detected viruses were Influenza A (30%), Rhino/Enterovirus (24%), RSV (19%), Coronavirus OC43 (7%) and Metapneumovirus (5%). The peak influenza incidence temporally coincided with the national peak months of January and February. The NIV incidence paralleled the trend in IV incidence, dominated by Rhino/Enterovirus and RSV, but without a specific virus driving the trend. CONCLUSION: Non-influenza respiratory viruses cause substantial viral RI during the winter months. Many viral syndromes during the height of influenza season have traditionally been attributed to IV, including influenza-like-illness (ILI); however, these can now be better characterized using patient-specific vPCR panels, leading to improved understanding of NIV epidemiology. Even during the period of highest IV incidence, NIV infections were more common than IV. Understanding the high prevalence of NIV infections may improve the judicious use of both antibiotics and antivirals. There may also be a role for refinement of ILI, including best practices for diagnosis and treatment. DISCLOSURES: All Authors: No reported disclosures.


title: 1241. Surveillance for Viral Respiratory Infections in Pediatric Chronic Care Facilities

text: BACKGROUND: Residents of pediatric chronic care facilities (PCCFs) are vulnerable to acute respiratory infections (ARIs) due to their underlying medical conditions and infection control challenges in congregate living. METHODS: We conducted active, prospective surveillance for ARIs (defined as ≥2 new signs/symptoms of respiratory illness) among all residents in three PCCFs near New York City from December 7, 2016 to May 7, 2017. The parents/guardians of some residents also provided consent for research specimen collection at the start of the study. In that subset, nasopharyngeal swabs were obtained ≤4 days of ARI symptom onset and weekly for 4 weeks of follow-up to assess viral shedding. Influenza, respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (229E, NL63, OC43, HKU1), parainfluenzavirus (PIV 1–4), metapneumovirus (MPV), adenovirus (AdV), bocavirus (BoV), enterovirus, parechovirus, and M. pneumoniae were tested by the Fast Track Diagnostics Respiratory Pathogens 21 real-time RT-PCR panel. RESULTS: Subset with research specimen collection: Among 79 residents (aged 0–20 years, median = 8), 60 ARIs were reported in 37 (47%) residents. Swabs were obtained at illness onset for 53/60 ARI episodes; among these, there were 25 single-virus detections and five co-detections. An additional 33 single- and five co-detections occurred in 175 follow-up swabs (table). Molecular typing of 32 RV+ specimens identified 13 RV types. All residents: During the 2016–2017 influenza season, 308/322 (96%) age-eligible residents received influenza vaccine and 168/364 (46%) received prophylactic antivirals for influenza exposures. Although influenza was not detected in research swabs, it was detected in 3/200 tests conducted for clinical purposes. CONCLUSION: ARIs were common among residents of three PCCFs, and a variety of respiratory viruses were detected. The rarity of influenza may reflect strong infection control practices in these facilities, including vaccination and prophylactic use of antivirals. DISCLOSURES: All authors: No reported disclosures.


title: 452. Spectrum of Respiratory Pathogens Detected by Multiplex PCR in a Study of Respiratory Tract Infections Among Travelers

text: BACKGROUND: Respiratory tract infections (RTI) are a significant cause of health problems, accounting for about 10% of consultations in returning travelers. Nevertheless, the precise microbial etiology is not identified in many cases. METHODS: Prospectively collected 63 respiratory specimens (sputum or throat swab) from patients presented with respiratory symptoms (cough, sputum, chest pain, dyspnea, tachypnea, or abnormal findings of chest auscultation) after travel were tested using multiplex real-time PCR. The FTD Respiratory pathogens 33 (Fast-track diagnostics, Ltd.) can simultaneously detect 33 different respiratory pathogens directly from respiratory specimens. This test ran in the PCR-Only mode on BD MAX™ (Nippon Becton Dickinson Company, Ltd.) and LightCycler480 System (Roche). RESULTS: Fifty-nine consecutive cases were included in the study. Thirty-nine cases were diagnosed as non-specific upper respiratory tract infections, five cases were influenza, bronchitis, pneumonia, threecases was acute sinusitis, and one case was acute pharyngitis, dengue fever. Twenty-four cases had returned from travel in Southeast Asia, nine from Africa, and 8 from Latin America, seven from South Asia, six from middle east, threefrom North America, threefrom East Asia, 2 from Oceania, and one from Europe. Of the 59 specimens analyzed, 48 (81.4%) tested positive for pathogens whereas 11 tested negative. Commonly detected pathogens were Haemophilus influenzae (14 cases; 23.7%), influenza A (10 cases; 17.0%), rhinovirus (9 cases; 15.2%), Staphylococcus aureus (8 cases; 13.6%), Moraxella catarrhalis (8 cases; 13.6%), Streptococcus pneumonia, coronaviruses OC43, and Mycoplasma pneumoniae (4 cases; 6.8%, respectively). Multiple pathogens were detected in 30.5% of the specimens. In 14 cases (23.7%), both virus and bacteria were detected from one specimen. CONCLUSION: Not only viruses, bacterial pathogens were detected frequently than expected in the patients of RTI. Comprehensive molecular testing such as multiplex real-time PCR would change our understandings of epidemiology of RTI among travelers. [Image: see text] DISCLOSURES: All authors: No reported disclosures.


title: 724. Neurologic Complications in Hospitalized Pediatric Patients with Influenza Infection, A Multicenter Retrospective Study in Korea

text: BACKGROUND: The aim of the study was to evaluate the incidence and characteristics of influenza associated neurologic complications (IANCs) in hospitalized pediatric patients in Korea. METHODS: We performed retrospective review of hospitalized cases of confirmed influenza infection from October 2010 to April 2017. Patient’s data were collected from three referral hospitals in different regions of the country. RESULTS: A total 2,002 laboratory confirmed influenza cases were identified. The median age was 3.3 years old (range 0.0–18.9 years) and 1,003 patients were male (54%). Influenza A was diagnosed in 1,357 cases (68%), influenza B in 624 (31%) and both influenza A and B in 21 (1%). Other combined respiratory virus infection was detected in 104 (5.2%) cases. Out of 2,002 cases, IANCs were identified in 167 cases (8.3%); influenza virus A was detected in 116 (69.4%), B in 50 (29.9%) and both A and B in one case (0.6%). Of 167 cases with IANCs, 25 patients (15%) had underlying neurologic diseases. Eleven patients (11/167, 6.5%) had combined respiratory viral infection (Rhinovirus = 5; respiratory syncytial virus = 3; coronavirus = 2; and bocavirus = 1). The most common diagnosis was a simple febrile seizure (112/167, 67.1%), followed by other seizures (26/167, 15.6%), encephalopathy/encephalitis (17/167, 10.2%), meningitis (7/167, 4.2%), meningism (4/167, 2.4%) and acute ataxia (1/167, 0.6%). In two patients with encephalitis/meningitis, one patient had influenza A and the other patient had influenza B detected by PCR in cerebrospinal fluid. Most of the patients were fully recovered (162/167, 97%) and no neurologic complication occurred in patients who had only initial manifestation of simple febrile seizure. Ten patients (10/167, 6.0%) required hospitalization in intensive care unit. Three patients (3/167, 1.8%) died of encephalopathy (n = 1) and combined encephalopathy/myocarditis (n = 2). Pre-existing neurologic disease was a risk factor of IANCs with an odds ratio of 3.94 (95% confidence interval 2.37 to 6.56, P < 0.0001). CONCLUSION: IANCs is not rare and may cause serious outcome including death. Clinicians should be aware of the increased risk for IANCs in certain patients with neurologic diseases. DISCLOSURES: All authors: No reported disclosures.


title: 677. Using a Multisectoral One Health Approach to Prioritize Zoonotic Diseases in the United States

text: BACKGROUND: Emerging and endemic zoonoses continue to have adverse global impacts. One Health approaches promoting multisectoral, transdisciplinary collaboration are important methods to address zoonoses threats through disease surveillance, prevention, control, and response. We conducted a One Health Zoonotic Disease Prioritization (OHZDP) workshop in the United States (US) to identify zoonotic diseases of greatest national concern that should be jointly addressed by the Centers for Disease Control (CDC), US Department of Agriculture (USDA), Department of the Interior, and partners. METHODS: We used CDC’s OHZDP tool to prioritize zoonoses. Workshop participants selected criteria for prioritization, and developed questions and weights for each criterion. Questions were answered using available literature and expert opinion with subsequent scoring resulting in a ranked zoonotic disease list. After agreeing on a final prioritized disease list, participants used components of the One Health Systems Mapping and Analysis Resource Toolkit, developed by USDA and University of Minnesota, to review multidisciplinary coordination processes for the prioritized zoonotic diseases. RESULTS: Participants selected epidemic or pandemic potential, disease severity, economic impact, introduction or increased transmission potential, and national security as criteria to prioritize 56 zoonoses. The eight prioritized zoonotic diseases for the US were zoonotic influenzas, salmonellosis, West Nile virus, plague, emerging coronaviruses (e.g., SARS, MERS), rabies, brucellosis, and Lyme disease. Agencies then discussed recommendations to enhance One Health approaches to surveillance, response, prevention, and control of the prioritized zoonoses. Key themes and next steps for further implementation of One Health approaches were identified. CONCLUSION: This OHZDP workshop represents the first use of a One Health approach to zoonotic disease prioritization in the United States. It is a critical step forward in US government agency collaboration using One Health approaches. Further, the workshop created a foundation for future US government One Health systems strengthening for the prioritized zoonoses. DISCLOSURES: All authors: No reported disclosures.


title: 739. Middle East Respiratory Syndrome Coronavirus Infection Profile in Qatar: A 7-Year Retrospective Study

text: BACKGROUND: A deadly zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) had emerged over the last 7 years in the Arabian Peninsula. As of February 28, 2018, 2,182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide. The objectives of this study were to identify the clinical and epidemiological characteristics of MERS-CoV infection as well as determine its clinical outcome. METHODS: This was a retrospective-observational study of all laboratory confirmed cases of MERS-CoV infection conducted at the main seven hospitals in the State of Qatar from January, 2012 to April 2018. We used the Fast Track diagnostics real-time reverse-transcription polymerase chain reaction (rRT-PCR), targeting the upE and ORF1a genes respectively. Demographics, clinical information, potential contacts and probable risk factors were collected and analyzed by standard statistical methods. RESULTS: The mean annual incidence was 1.7 per 100,0000 person-years. Among the 24 confirmed cases of of MERS-CoV, males constituted the vast majority of cases (23 males) with a median age of 52 years (range 22–74). Fifty percent of the cases were Qatari and 42% reside in the same region. 67% of the cases had contact with camels, and 21% had contact with MERS-CoV-infected patient. Thirty-eight had travel history within 2 weeks of symptoms onset to the Kingdom of Saudi Arabia. Fifty percent were smokers and 42% had comorbidities. The median symptoms duration was 4.5 days. Most of the patient presented with flu-like symptoms, were fever was the most common presentation, followed by cough, SOB, diarrhea, abdominal pain and headache, 96%, 83%, 33%, 8%, 8% and 4%, respectively. All patients were admitted to a tertiary hospital with a median hospital stay 41 days (8–97). Forty-five percent patients developed severe sepsis with multi-organ failure and needed ICU admission. Fifty percent patients developed acute kidney injury, 29% patients were on hemodialysis and 16% needed extra-corporeal membrane oxygenation. Thirty-three percent patients died. The rest of patients had recovered from the infection and discharged home. Among those who died all had one or more comorbidities. CONCLUSION: MERS-CoV infection is a rare infection in the State of Qatar, seen in both Qataris and expatriates with and without travel history. The infection in patients with comorbidities carries high mortality. DISCLOSURES: All authors: No reported disclosures.


title: 2491. Post-Exposure Prophylaxis With Ribavirin Plus Lopinavir/Ritonavir for Middle East Respiratory Syndrome in Healthcare Workers

text: BACKGROUND: In 2015, an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection occurred in South Korea involving 186 patients, 39 of whom were healthcare workers (HCWs) exposed to the infection. An effective post-exposure prophylaxis (PEP) strategy may limit the spread of infection; however, there is no consensus regarding PEP for MERS-CoV infection. In this study, we assessed (1) the efficacy of oral ribavirin and lopinavir/ritonavir as PEP for HCWs exposed to patients with severe MERS-CoV pre-isolation pneumonia, and (2) safety of the PEP regimen. METHODS: We retrospectively enrolled 43 HCWs with high-risk exposure to MERS-CoV from 5 hospitals affected during this outbreak in South Korea. The rate of MERS-CoV infection was compared between 22 workers at 1 hospital who received PEP consisting of oral ribavirin and lopinavir/ritonavir after exposure to patients with severe MERS-CoV pre-isolation pneumonia and 21 workers at other hospitals who did not receive PEP. RESULTS: Six workers (14%) developed MERS-CoV infection; all of these subjects belonged to the non-PEP group. The attack rate was lower in the PEP group compared with the non-PEP group (0% vs. 28.6%; Odds ratio = 0.405, 95% confidence interval = 0.274–0.599; P = 0.009). The most commonly reported side effects of PEP therapy were nausea and diarrhea, but there were no severe adverse effects associated with PEP therapy. CONCLUSION: PEP with a combination of oral ribavirin and lopinavir/ritonavir appears to be effective and generally safe for preventing MERS-CoV infection after high-risk exposure in healthcare workers. DISCLOSURES: All authors: No reported disclosures.


2018 ACVIM Forum Research Report Program: Seattle, Washington, June 14 ‐ 16, 2018


2018 ACVIM Forum Research Abstract Program: Seattle, Washington, June 14 ‐ 15, 2018


title: PSXIII-19 Swine Health Health and Management Evaluation in American Samoa.

text: American Samoa is working to improve swine production genetics and management. Our objective was to identify health and management factors affecting swine performance. A1998 survey found six leptospirosis serovars and parvovirus and heavy parasites loads, but no brucellosis or pseudorabies. Our 2016 Artificial Insemination Training focused on improving genetics and resulted in 12 sows bred and 103 piglets born. Oour 2017 Swine Farm Evaluation surveyed 26 farms with an average of 9 sows per farm. Serological samples were tested for antibodies against Porcine Circovirus Type 2b (ELISA, 96% positive), Swine Influenza (ELISA, 31%), Senecavirus (IFA, 27%), Mycoplasma hyopneumoniae (ELISA, 15%), Porcine Epidemic Diarrhea (IFA, 15%), and Porcine Reproductive and Respiratory Syndrome (ELISA, 4%, 1 pig). o evidence was seen of Porcine Respiratory Coronavirus (ELISA), Transmissable Gastroenteritis (ELISA) or Pseudorabies (SN). Fecal samples contained Ascaris suum, Oesophagostomum dentatum, Stephanurus dentatus, and, less commonly, Strongyles nodular worm, Stronglyloides, Brachylaemus suis, Necator species, Trichuris suis, and Fasciolopsis buski. Ear scrapings and scratching behavior indicated the presence of sarcoptic mange (31% of farms). Most farms fed a 14% grain feed (88% of farms) and local feeds (coconut, vegetables, fruits, 69%); only one farm fed an 18% starter and one fed milk to young pigs. One or more thin pigs were seen on 46% of farms. Waste is managed either by wash down (85% of farms) or as dry litter (42%); some farms used both. Wastewater concerns led to water restriction on 12% of farms. In conclusion, parasites and suboptimal feeding are constraints on pig growth and performance. Management recommendations to improve production should address these, in addition to improving health and genetics.


title: 474 Productive and reproductive performance of Goat Breeds of Sindh.

text: The study was carried out in Sindh province of Pakistan to investigate productive and reproductive performance of ten local goat breeds. The ten goat breeds included in the study were Kamori, Tapri, Bugi-Turi, Pateri, Kachan, Jattan, Lohri, Chappar, Barri, and Thari. The data were collected using a detailed survey on various productive (birth weight, weaning weight, weaning age, average daily gain, milk yield and lactation length) and reproductive (age at first heat, age at first kidding, kidding interval, service period, number of services per conception and twinning percentage) traits of goats. Up sixteen local farmers of each breed were visited by the investigators and information was recorded/collected on prescribed performas. The highest birth weight was observed in Pateri goat (2.90 ± 0.11kg). In case of weaning weight maximum was observed in Kachan (16.0 ± 0.50kg) and lowest in Thari (11.19 ± 0.40 kg). Moreover weaning age was lowest in Thari (3.0 ± 0.11months) and highest was in Bugi-Turi (8.0 ± 0.14months). The highest milk yield was observed in Tapri and Kamori (~ 3.50 kg) followed by Pateri (~2.90 kg), Bugi Tori, Kacchan, Jattan (~ 2.00 kg) and Lohri, Chapper, Barri and Theri (~1 kg). As far as reproductive traits are concerned; age at first heat was lowest in Pateri (around 7 months) while all other breeds ranged from 11 to 15 months). The maximum twining percentage at first kidding was observed in Chappar (25%). Jattan had lowest kidding interval (5.0 ± 0.16 months). On the basis of overall average pre-weaning growth rate of kids, Tapri and Thari appear to have higher growth potential followed by Kamori and Kachhan. It could be concluded that Tapri, Thari and Kamori may be utilized for meat production under existing circumstances in the order of priority. Similarly, Tapri, Kamori and Pateri may be better utilized as dairy goats as well. [Image: see text]


title: PSXIII-12 Effects of altitudinal floor on nutrient digestibility, energy efficiency, visceral organ mass, and performance by guinea pigs.

text: An experiment was conducted to evaluate the effect of altitude on nutrient digestibility, energy efficiency, performance, and, visceral organ mass by guinea pigs. Twenty male guinea pigs (initial BW 1.011 ± 0.096 kg) were selected in a crossover design experiment, maintained at metabolic cages (2 animals per cage) during a total digestibility period of 25 d (2 periods of 13-d). Animals were randomly assigned at 1 of 2 altitudinal sites, 2986 and 2480 m. above the sea level (masl; 5 cages per altitude). Animals were fed 45 g of alfalfa (DM) to meet energy requirements at maintenance levels. At the end of the digestion phase, an animal from each cage was slaughter to determine body fat content from body specific gravity and visceral organ mass. A subsequent performance phase was evaluated as completely randomized design, and animals were kept at the same altitudinal floor in which they ended period 2 of the crossover period. Animals were fed ad libitum with alfalfa. At the end of the performance phase, all remaining animals were slaughtered and visceral organ mass was measured. Energy intake and Dry matter, were increased by animals at 2986 compared to animals at 2480 masl (P<0.001). Metabolizable energy tended to be lower for animals kept at 2986 masl (P=0.053). Nutrient digestibility was lower for animals kept at 2986 compared to 2480 masl. Liver, kidneys and spleen mass were greater for animals maintained at 2986 masl (P<0.012). Heart mass tended to be greater for animasl kept at 2480 masl (P=0,060). Body fat was not alterd by altitudinal site (P>0.345). Final BW, ADG, and feed conversion rate was decreased by animals fed at 2986 masl (P<0.002). Results from this experiment suggest a novel approach to determine Energy efficiency as affected by altitudinal site. Data from this experiment evidenced a 7% increase on energy requirements on ME for animals kept 516 masl higher. Further research is requiered to apply to other biological models.


In Memoriam: Katrin Susanne Kohl (1964–2018)


RESEARCH COMMUNICATIONS OF THE 28th ECVIM‐CA CONGRESS


Tracking renal injury using multiparametric MRI


title: WACEM 2018 Abstracts

text: The 4(th) Annual World Academic Congress of Emergency Medicine was held in October 2018 in Doha, Qatar. The conference was organized by Trauma Surgeons, Emergency Physicians and Research Team from Qatar. WACEM 2018 was very engaging and informative congress which involved debates, discussion, lectures. competitions and many symposiums. Over 100 International Academic Leaders spoke on cutting-edge research at this congress. The following were the abstracts that were presented at WACEM 2018. There were awards for best papers. A dedicated scientific team worked on selecting and reviewing as well as judging the abstracts.


Abstracts of the papers presented in the international conference of Indian virological society, ‘‘Global viral epidemics: a challenging threat”, during 12–14 November, 2018, at PGIMER, Chandigarh, India


Correction: Vol. 25, No. 5


Surveillance of Respiratory Viruses in Long Term Care Facilities


title: Sequential, within‐season infection with influenza A (H3N2) in a usually healthy vaccinated child

text: Cocirculation of varying influenza types, strains, and lineages allows coinfection and intra‐season sequential infection, although a same‐strain sequential infection has not been previously described. This case report describes the first known case of sequential laboratory‐confirmed influenza A (H3N2) infections in a child within one season.


Abstracts of scientific contributions to GCOM 2019: Berlin, Germany. 27 - 30 March 2019


What's in this issue?


Abstracts from the 35th Annual Meeting of the Society of General Internal Medicine


title: A60 Revealing the evolution of virulence in RNA viruses

text: A combination of high rates of mutation and replication, coupled with strong natural selection, ensures that RNA viruses experience rapid genotypic and phenotypic evolution. Such a ‘fast-forward’ evolution enables viruses to rapidly adapt to new host species, evade host immune responses, and to develop resistance to anti-viral drugs. Similarly, rapid evolution allows viruses to attain new levels of virulence, defined as the ability to cause severe disease in hosts. We hypothesize that distinct viral groups share genetic determinants that modulate virulence that have been acquired through convergent evolution. Thus, common patterns reflecting changing virulence-related specific viral groups could be detected. The main goals for this project are (1) to understand how genetic and phenotypic diversity can be generated among different viral groups by analyzing the variation patterns and determining the selective forces behind them (impact in viral fitness) and (2) to understand how fixed mutations can modulate virulence within different viral groups by performing comparison of strains with differing virulence within a longitudinal timescale. The subject of the study is key emerging and re-emerging virus families of medical importance. Such groups include: Coronaviridae (severe acute respiratory syndrome and Middle East respiratory syndrome-associated coronaviruses), Picornaviridae (Hepatitis A virus), Flaviviridae (Yellow fever, West Nile, Hepatitis C, Dengue, and Zika viruses), Togaviridae (Rubella and Chikungunya virus), Bornaviridae (Borna-disease virus), Filoviridae (Ebola and Marburg viruses), Paramyxoviridae (Measles, Nipah, and Hendra viruses), Rhabdoviridae (Lyssaviruses), Arenaviridae (Lassa virus), Bunyaviridae (Hanta- and Crimean-Congo hemorrhagic fever viruses), and Orthomyxoviridae (Influenza A viruses). Viral genomes collected at different time points, different hosts (human and their most closely related animal reservoirs) and different locations will be compiled. Extensive molecular evolutionary analyses will be carried out to infer gene expansion/contraction within groups, rates of evolution, and changes in selection pressure, including the detection of positive selected genes and sites (adaptive evolution). Positively selected sites will be mapped onto the viral protein structures to reveal their impact on function, and hence the location of potential virulence determinants. Virulence changes among particular viral strains and types will be defined and measured according to definitions based on an increase in: (1) transmissibility, (2) host tropism, (3) immune evasion, (4) morbidity and mortality, (5) drug resistance, and by the incorporation of epidemiological data to determine whether high or low virulence strains within different hosts and localities are spreading most efficiently in nature.


title: A48 Identification and full-genome characterization of Alpha- and Beta-Coronaviruses viruses from bats in Italy

text: Bats are the natural reservoir of Coronaviruses (CoVs). Human CoVs cause mild respiratory diseases worldwide, but, in the last decade, two Beta-CoVs [Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome] caused thousands of deaths and cases worldwide. Phylogenetic analysis suggested the evolutionary origin of mammalian CoVs is derived from bats. In this study, we characterized three Alpha-CoVs and two Beta-CoVs demonstrating the circulation of bat strains in Italy. Isolates were sequenced using a next-generation sequencing approach and genomes reconstructed using the online tool Galaxy Aries. Phylogenetic analyses were conducted using MEGA7 and MrBayes. Similarity plots were generated using SSE v1.2. The structure of the receptor binding domain (RBD) in the S protein was predicted by sequence-homology method using the protein data bank. Bioinformatics analysis permitted the identification of 2 Beta-CoV complete genomes of 30 kb and three Alpha-CoV of 28 kb (named BatCoV-ITA1-5). BatCoV-ITA1 and 2 formed a monophyletic group with MERS-CoV sequences. The comparison of the concatenated domains within ORF1ab confirmed their classification into the MERS-CoV species. The 3D structure of RBD of Italian strains showed two amino acid deletions located in a region corresponding to the external subdomain of MERS-RBD. BatCoV-Ita3 and BatCoV-Ita4/5 were classified into two novel Alpha-CoV species by comparison of concatenated domains within ORF1ab. Due to the high divergence with the Alpha human spike protein strains, it was impossible to establish the protein structure and the potential affinity to human receptor. The Italian strains showed the typical organization of Alpha and Beta-CoVs. We reported two Beta-CoVs closely related to MERS-CoVs from bats belonging to common Italian species (Pipistrellus kuhlii and Hypsugo savii). The analysis of the RBD in the spike protein indicates significant differences from human RBD known to date. The three Alpha-CoV strains were classified into two novel species, confirming the high heterogeneity of CoV strains in bats. Although the studies conducted cannot confirm a risk for humans, surveillance studies are needed to investigate the genetic diversity of CoVs in bats. Because this exceeds what is known for other hosts, it is compatible with bats being the major reservoir of mammalian CoVs.


title: A52 MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of this zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa and the Arabian Peninsula, the continuous appearance of zoonotic MERS cases in humans is confined to the Arabian Peninsula. MERS-CoV from Africa has hitherto been poorly studied. Here, we report the genetic and phenotypic characterization of MERS-CoV from dromedaries in African countries. Phylogenetically, viruses from dromedaries in Africa formed a monophyletic clade, which we have provisionally designated as virus clade C. Molecular dating analyses of MERS-CoV, including clade C viruses, suggests that the ancestral MERS-CoV in dromedaries could have spread to the two continents within a short timeframe. Camel MERS-CoVs from west and north African countries form a subclade (C1) that shares genetic signatures of a major deletion in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung, and BF785 replicated to lower titer in lungs of human DPP4-transduced mice. However, it is still inconclusive whether ORF4b deletions may lead to the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to the zoonotic potential of MERS-CoV.


title: A61 Large RNA genomes: Is RNA polymerase fidelity enough?

text: Large-genome Nidoviruses and Nidovirus-like viruses reside at the current boundary of largest RNA genome sizes. They code for an unusually large number of gene products matching that of small DNA viruses (e.g. DNA bacteriophages). The order of appearance and distribution of enzyme genes along various virus families (e.g. helicase and ExoN) may be seen as an evolutionary marker in these large RNA genomes lying at the genome size boundary. A positive correlation exists between (+)RNA virus genome sizes and the presence of the RNA helicase and the ExoN domains. Although the mechanistic basis of the presence of the helicase is still unclear, the role of the ExoN activity has been linked to the existence of an RNA synthesis proofreading system. In large Nidovirales, ExoN is bound to a processive replicative RNA-dependent RNA polymerase (RdRp) and corrects mismatched bases during viral RNA synthesis. Over the last decade, a view of the overall process has been refined in Coronaviruses, and in particular in our lab (Ferron et al., PNAS, 2018). We have identified genetic markers of large RNA genomes that we wish to use to data-mine currently existing metagenomic datasets. We have also initiated a collaboration to sequence and explore new viromes that will be searched according to these criteria. Likewise, we have a collection of purified viral RdRps that are currently being used to generate RNA synthesis products that will be compared to existing NGS datasets of cognate viruses. We will be able to have an idea about how much genetic diversity is possibly achievable by viral RdRp (‘tunable fidelity’) versus the detectable diversity (i.e. after selection in the infected cell) that is actually produced.


title: A53 MERS-CoV in East African dromedary camels

text: Human Middle East respiratory syndrome is a zoonotic respiratory disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) originating from camels in the Arabian Peninsula. While there are a large number of camels in East Africa, often traded to the Arabian Peninsula, no autochthonous human MERS-CoV case is reported in East Africa. Furthermore, there is limited information of MERS-CoV in East Africa. In this study, MERS-CoV in dromedary camels from Ethiopia was detected using RT-qPCR. Next-generation sequencing was used to obtain the full genome of MERS-CoV. MERS-CoV antibodies were also detected through MERS-spike pseudoparticle neutralization assay. Phylogenetic analysis of full-genome sequences and spike-genome antibodies indicates that MERS-CoV in East Africa is genetically distinct from those in the Arabian Peninsula. The results from this study show that MERS-CoV circulating in dromedary camels in East Africa are genetically distinct from those in the Arabian Peninsula. Further studies are needed to evaluate the risk of zoonotic transmission in East Africa.


title: A54 Genomic analysis of camel-HKU23 in Nigeria dromedary camels reveals strain-specific cross-species recombination

text: Coronaviruses (CoVs) are enveloped, single stranded, positive-sense RNA viruses with a large genomic size of 26–32 kilobases. The first human CoV identified in the 1960s was isolated from patients presenting with common cold symptoms. Subsequent epidemic outbreaks of novel zoonotic CoV transmission were reported, examples including HCoV-229E (229E), HCoV-OC43 (OC43), severe acute respiratory syndrome, and Middle East respiratory syndrome (MERS). The ongoing outbreak of MERS in the Middle East is originating from a zoonotic source of dromedary camels. Surveillance later revealed that three CoV species—HCoV-229E (229E), camel-HKU23, and MERS-CoV—were co-circulating in Saudi Arabia dromedary camels. Camel-HKU23 belongs to Group 2a CoV, which also includes human coronavirus OC43, bovine coronavirus, and porcine hemagglutinating encephalomyelitis virus. Recombination, resulting in the generation of different novel genotypes, has been reported previously among these CoVs. Our surveillance of dromedary camels slaughtered in a major abattoir in Nigeria identified camel-HKU23 from nasal swab samples with a prevalence of 2.2 per cent. Phylogenetic analysis showed Nigeria camel-HKU23 is distinct from those previously identified in Saudi Arabia, while still genetically similar, as they share a monophyletic origin. Recombination analysis of Nigeria camel-HKU23 revealed two recombination breakpoints at positions of 22774–24100 base pairs (bp) and 28224–29362 bp. Recombination breakpoint at position 22774, encoding the Group 2a CoV-specific hemagglutinin esterase gene, exhibited high bootstrap support for clustering with RbCoV HKU14, which was previously detected in domestic rabbits in China. The recombination signal is only observed in Nigeria camel-HKU23, suggesting a regional varied evolutionary history of camel-HKU23. Our findings extended the knowledge of the evolutionary relationship among Group 2a CoVs. Further surveillance in other African camels will be important to elucidate the evolution of camel-HKU23.


Abstracts from the 5th International Conference on Prevention & Infection Control (ICPIC 2019): Geneva, Switzerland. 10-13 September 2019


2019 ACVIM Forum Research Report Program


title: Acceptability of community quarantine in contexts of communicable disease epidemics: perspectives of literate lay people living in Conakry, Guinea

text: During the 2014–2016 Ebola epidemic in West Africa, some communities reacted hostilely to the implementation of quarantine measures. This study's aim was to examine the views of lay people in Guinea on the acceptability of community quarantine. From June to August 2016, 302 adults indicated the acceptability of quarantine in 36 scenarios varying as a function of four factors: the infectious disease's level of contagiousness, its level of lethality, the number of cases in the community and whether persons in quarantine are provided with support services. Five clusters were identified: (1) for 18% of the participants, quarantine is never acceptable; (2) 16% considered, in contrast, that quarantine is always acceptable; (3) for 14%, it depends on the disease's level of contagiousness and lethality; (4) 36% based their judgement not only on the levels of contagiousness and lethality, but also on whether those in quarantine are provided with support services; and (5) 16% had no opinion. Interventions to increase voluntary compliance with community quarantine in Guinea must not be ‘one size fits all’, but must be multifaceted and tailored in design and implementation to match the diversity of people's concerns and needs.


title: 2002. BioFire® Filmarray® Pneumonia Panel: A Powerful Rapid Diagnostic Test for Antimicrobial Stewardship

text: BACKGROUND: BioFire® Filmarray® Pneumonia Panel (BFPP) is a multiplex PCR panel that identifies 33 common bacterial and viral pathogens seen in community- and hospital-acquired pneumonias. It rapidly identifies these pathogens in addition to 7 antibiotic resistance genes on sputum and bronchioalveolar lavage samples in 1 hour. As one of the test centers for this panel, our institution utilized this panel for clinical and laboratory use. We reviewed the impact of BFPP on antimicrobial stewardship, particularly its role in early discontinuation of empiric antibiotics and prompt initiation of optimized targeted therapy. METHODS: We retrospectively reviewed all cases by which BFPP was ordered. We reviewed medical records of each case to identify the results of the panel, culture data, antibiotics used, and subsequent clinical intervention. RESULTS: 43 tests were ordered in total. 17 were for clinical use by an infectious disease specialist and 26 were randomly obtained by the microbiology lab. All 17 clinical cases were intervened upon with the following interventions: discontinuation of anti-pseudomonal antibiotics (8 cases), discontinuation of anti-MRSA antibiotics (5 cases), discontinuation of azithromycin (4 cases), discontinuation of carbapenem (1 case), prevention of inappropriate antibiotic escalation or initiation of inappropriate antibiotics (2 cases), and early IV to PO transition (3 cases). Of the random 26 samples ordered by lab, 13 had opportunities for antibiotic de-escalation if a physician were notified of the results. Viruses were identified in 15 samples with coronavirus being the most common. Virus was the sole pathogen in 9 of the 15 samples. Bacterial pathogens were identified in 20 samples that were reported as normal flora by conventional culture; none of these cases led to or potentially could have led to antibiotic escalation as the sole intervention. CONCLUSION: Clinical use of BFPP had 100% intervention rate with all interventions leading to de-escalation of antibiotics or prevention of inappropriate antibiotics use. Though over-identification of colonizers is a potential limitation, BFPP is a powerful tool for antibiotic stewardship that results in rapid interventions to achieve optimal targeted therapy. DISCLOSURES: All authors: No reported disclosures.


title: 1756. Role of Human bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients

text: BACKGROUND: Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. We examined incidence and disease spectrum of BoV respiratory tract infection (RTI) in HCT recipients. METHODS: In a longitudinal surveillance study of viral RTIs among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1-year post-HCT. Samples were tested by multiplex semi-quantitative PCR for RSV, parainfluenza virus 1–4, influenza A/B, adenovirus, human metapneumovirus, rhinovirus, coronavirus, and BoV. Plasma samples from BoV+ subjects were analyzed by PCR. In addition, we conducted a retrospective review of HCT recipients with BoV detected in bronchoalveolar lavage or lung biopsy. RESULTS: Among 469 patients in the prospective cohort, 21 distinct BoV RTIs (3 pre-HCT and 18 post-HCT) were observed by 1-year post-HCT in 19 patients (median 42 years old, range 0–67) without apparent seasonality. BoV was more frequently detected in the latter half of the first 100 days post-HCT (Figure 1). The frequencies of respiratory symptoms in patients with BoV detected did not appear to be higher than those without any virus detected, with the exception of watery eyes (P < 0.01) (Figure 2). Univariable models among patients with BoV RTI post-HCT showed higher peak viral load in nasal samples (P = 0.04) and presence of respiratory copathogens (P = 0.03) were associated with presence of respiratory symptoms; however, BoV detection in plasma was not (P = 0.8). Retrospective review identified 6 allogeneic HCT recipients (range 1–64 years old) with BoV detected in lower respiratory tract specimens [incidence rate of 0.4% (9/2,385) per sample tested]. Although all 6 cases presented with hypoxemia, 4 had significant respiratory copathogens or concomitant conditions that contributed to respiratory compromise. No death was attributed mainly to BoV lower RTI. CONCLUSION: BoV is infrequently detected in respiratory tract in HCT recipients. Our studies did not demonstrate convincing evidence that BoV is a significant pathogen in either upper or lower respiratory tracts. Watery eyes were associated with BoV detection. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.


title: 1791. Novel Metabolomics Approach for the Diagnosis of Respiratory Viruses Directly from Nasopharyngeal Specimens

text: BACKGROUND: Respiratory virus infections are important causes of morbidity and mortality among pediatric and adult patients. These viruses infect respiratory epithelial cells, where they may induce specific metabolite alterations. As a proof-of-concept, we investigate the novel use of liquid chromatography (LC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF) for the study of host cell metabolite alterations to diagnose and differentiate respiratory viruses. METHODS: We studied nasopharyngeal swab samples positive for respiratory viruses by the eSensor Respiratory Viral Panel (GenMark Diagnostics, Carlsbad, CA). Banked, frozen samples (−80°C) stored in viral transport media were retrieved and thawed. Aliquots of 100 μL were centrifuged at 13.3 × g for 15 minutes, and the filtrate was analyzed by Agilent 6545 Quadrupole LC/Q-TOF (Agilent Technologies, Santa Clara, CA). Compounds were separated using a novel column arrangement based on hydrophobicity and charge using a quaternary solvent manager, followed by accurate mass analysis by LC/Q-TOF. Agilent Mass Profiler 3D principal component analysis was performed, and compound identification was completed using the METLIN metabolite database. RESULTS: A total of 235 specimens were tested by LC/Q-TOF, including 195 positive specimens [including adenovirus, coronavirus, influenza A H1N1 and H3N2, influenza B, human metapneumovirus, parainfluenza viruses 1, 2, 3, and 4, respiratory syncytial virus (RSV), and rhinovirus] as well as 40 negative clinical specimens. LC/Q-TOF primary component analysis (PCA) allowed preliminary identification of key metabolites that distinguished all virus-positive specimens compared with the negative group, and differentiated respiratory viruses from one another including between influenza A 2009 H1N1 and H3N2 subtypes (Figure 1). CONCLUSION: Preliminary data from our LC/Q-TOF analysis show that respiratory viruses exhibit different host cell metabolomic profiles that allow viral differentiation to the species level, and for influenza A virus, the subtype level. This metabolomic approach has substantial potential for diagnostic applications in infectious diseases directly from patient samples, and may be eventually adapted for point-of-care testing. [Image: see text] DISCLOSURES: All authors: No reported disclosures.


title: 2786. The Role of Respiratory Panel PCR in Decreasing Antibiotic Exposure in Patients Diagnosed With a Respiratory Viral Infection

text: BACKGROUND: Respiratory viral infections (RVI) are becoming increasingly recognized as an important cause of pneumonia. There is limited data regarding the role of rapid PCR testing for RVI and its effect on antibiotic duration and length of stay (LOS). METHODS: We performed a single-center, retrospective chart review in adult patients who were admitted and underwent evaluation with the FilmArray Multiplex Respiratory Panel (RP) (Biomerieux™) using a random sample from July 1, 2016 through April 1, 2018. Patient clinical and virologic characteristics, LOS, antibiotic use, and duration of treatment were collected. A Student’s t-test was performed for all comparisons. RESULTS: We identified 540 patients who were admitted and underwent RP testing. The mean age was 57.1 years (range 19–99), 50.2% were immunocompromised, 23.8% were transplant recipients, 70.4% had respiratory symptoms, and 35.7% had an admitting diagnosis of pneumonia. 55.6% required supplemental O(2) and 24.6% had an ICU admission that required either noninvasive or mechanical ventilation. 22.6% (N = 122) of these patients were diagnosed with an RVI, of which 15 were co-infected with two or more respiratory viruses. There were 41 (34%) rhinovirus/enterovirus, 41 (34%) influenza (Types A/H1, A/H3, A/H1-2209, and B), 16 (13%) RSV, 15 (12%) coronavirus (Types NL63, OC43, 229E, and HKU1), 13 (11%) metapneumovirus, and 7 (5%) parainfluenza (Types 2, 3, and 4). 85.2% (104/122) of patients with an RVI received antibiotics. The mean LOS and antibiotic duration were 9.07 days and 7.31 days for patients with an RVI when compared with 11.5 days and 10.4 days for patients without an RVI (P = 0.098; P = 0.032), respectively. In patients with an RVI and negative bacterial cultures, the mean LOS was 8.4 days and mean antibiotic duration was 5.9 days when compared with 16.4 days and 15.5 days for all patients with positive bacterial cultures (P = 0.003; P < 0.0001), respectively. The mean time from available results of + RP to antibiotic discontinuation was 5.1 days in the setting of negative bacterial cultures. CONCLUSION: Although antibiotic exposure and time to discontinuation still remained significant in patients diagnosed with an RVI, there was a marked reduction in LOS and antibiotic duration in the subset of patients with an RVI and negative bacterial cultures. DISCLOSURES: All authors: No reported disclosures.


title: 2792. Association of Body Mass Index with Rates of Hospitalization in Patients with Respiratory Viral Infections—Puerto Rico, 2012–2018

text: BACKGROUND: Obesity is a serious public health problem in Puerto Rico, where 31% of the population is obese. Multiple studies have suggested that adults with influenza who are underweight, overweight, or obese have increased risk of hospitalization compared with those of normal weight. We sought to determine whether risk of hospitalization among patients infected with influenza or other respiratory viruses differs by BMI among patients in Puerto Rico. METHODS: We analyzed data from patients enrolled in the Sentinel Enhanced Dengue Surveillance System (SEDSS), a prospective study of patients with acute febrile illness (AFI), from May 2012 to September 2018. We evaluated those older than 24 months, who had height, weight, and clinical disposition recorded, and tested positive by RT–PCR for infection with influenza A (n = 1253), influenza B (n = 844), adenovirus (n = 435), respiratory syncytial virus (n = 289), parainfluenza virus (n = 361), metapneumovirus (n = 247), or coronavirus (n = 15). BMI categories were determined using standard cutoffs in adults and BMI-for-age percentiles for children and adolescents. Risk of hospitalization by BMI category was calculated using multivariate Poisson regression. RESULTS: Among the 3,388 patients included, 675 (20%) were overweight, 926 (27%) were obese, 405 (12%) were underweight, and 1382 (41%) were normal weight. Median age was 13.4 (range: 2–100 years), and 50% were male. Risk of hospitalization was not significantly different in children and adult patients infected with a respiratory virus who were overweight relative to those that had normal BMI; however, once hospitalized, obese individuals of any age had a mean length of hospital stay 1.7 days longer than normal weight persons (95% CI: 0.27–3.17 days). Among adult patients, underweight patients were nearly 3 times more likely to be hospitalized compared with normal weight patients (relative risk 2.8, 95% CI: 1.4–5.9). Underweight children were not at increased risk of hospitalization. CONCLUSION: Among patients infected with a respiratory virus, risk of hospitalization was higher among underweight adult patients, and obese patients had a longer mean length of stay once hospitalized. Body mass index should be considered when evaluating risk and managing these patients. DISCLOSURES: All authors: No reported disclosures.


title: 1675. Implementation of Electronic Travel History Screening at an Urban Medical Center

text: BACKGROUND: Middle East Respiratory Syndrome (MERS), caused by a novel coronavirus, can lead to severe respiratory failure and death. CDC recommends screening patients who traveled to endemic countries for fever, respiratory symptoms, and exposure to MERS-positive contacts and healthcare facilities. UCLA is a large, academic, medical center located in a diverse city with frequent international travel. We implemented a travel screening (TS) questionnaire in our electronic medical record (EMR) (Figure 1) to identify high-risk patients in order to implement early isolation practices and testing. This study describes the use and performance of our TS for identifying suspect MERS cases. METHODS: An EMR-based tool prompts nurses to ask patients at triage or admission whether they have traveled out of the country in the past 30 days (Figure 1). If patients answer affirmatively, the EMR prompts nurses to inquire about travel to specific high-risk countries and to review symptoms and exposure risks. Upon notification of a potential MERS case, the EID physician on-call reviews the TS, clinical history, epidemiologic risks, and makes a determination whether further evaluation and/or isolation for suspect MERS is necessary. We reviewed travel history, demographics, and symptoms of patients who triggered a positive TS from April 2017 to September 2018. RESULTS: The ED completed 115,815 distinct TS on 81,197 individuals during this time period. The median time from ED arrival to TS completion was 6.4 minutes. 308 ED encounters triggered a positive TS; an additional 257 encounters in other units triggered a positive TS, resulting in 565 positive TS (Table 1). 122 (22%) expressed ≥1 MERS symptom and 29 (24%) expressed both fever and respiratory symptoms. Of these symptomatic patients, 0 had a history of contact with a MERS case; 3 had a history of contact with a healthcare facility while traveling; and 4 had a history of contact with camels. No patients were diagnosed with MERS (Table 2). CONCLUSION: A history of travel to the MERS endemic countries is relatively common at a large urban hospital. Routine electronic screening of patients is an efficient way to identify high-risk travelers. This EMR tool could be modified for other emerging pathogens, such as measles or Ebola, to identify high-risk patients. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.


title: 2324. Respiratory Viral Coinfection in a Birth Cohort of Infants in Rural Nepal

text: BACKGROUND: Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the effects of coinfection on disease severity or healthcare seeking are less well-understood. METHODS: A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in rural southern Nepal. Prospective weekly active household-based surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT–PCR. Coinfection was defined as the presence of two or more respiratory viruses simultaneously detected as part of the same illness episode. Maternal vaccination status, infant age, prematurity, and number of children under 5 in the household were adjusted for with multivariate logistic regression. RESULTS: Of 1,730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected on their primary illness episode. Coinfection status did not differ by maternal vaccination status, infant age, premature birth, and number of children under 5 in the household. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. Overall, infants with coinfection had increased occurrence of fever lasting 4 or more days overall (OR 1.4, 95% CI: 1.1, 2.0), and in the subset of infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 1.0, 1.6). CONCLUSION: A high proportion of infants experiencing their first respiratory illness had multiple viruses detected. Coinfection with influenza was associated with longer duration of fever compared with children with influenza alone, but was not associated with increased illness severity by other measures. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.


title: 2626. Rhinovirus in Children Presenting to the Emergency Department: Role of Viral Load in Disease Severity and Co-Infections

text: BACKGROUND: Rhinovirus (RV) quantitation by reverse transcription-quantitative PCR is limited by variable amplification efficiency across genotypes. We used a precise viral quantitation method, reverse transcription-digital PCR (RT-dPCR), to characterize the role of viral load in clinical outcomes and in viral co-infections in children presenting to a tertiary hospital emergency department (ED). METHODS: Children < 18 years with respiratory symptoms for ≤ 14 days were enrolled from December 1, 2016 to December 31, 2018. Participants had nasal and throat specimens obtained and multiplex PCR testing with a commercial assay (FilmArray; bioMerieux). RV positive samples were quantified using RT-dPCR. Samples with sufficient viral load were sequenced at a 543 bp fragment of the RV VP4/VP2 region. RV species were assigned by comparison to RV sequences in GenBank using BLAST. Clinical data were collected into REDCap. T-tests were used to compare mean viral loads between groups. RESULTS: Of 1703 children enrolled in the ED, 697 were RV/enterovirus positive by FilmArray [median age 18 months (interquartile range 9–39 months)]. Of 590 subjects with viral load available, 276 (47%) were admitted to the hospital. Among RV mono-infections (N = 434), mean viral load did not differ between subjects admitted vs. discharged from the ED (7.03 log copies/mL for both, P = 0.97). Among admitted subjects with RV mono-infection, viral load also did not differ between subjects requiring supplemental oxygen vs. not (7.01 vs. 7.10 log copies/mL, P = 0.6). Subjects with viral co-infections had lower mean RV viral loads (6.31 log copies/mL) compared with those with RV only (7.03 log copies/mL; P < 0.001) (figure). Significantly different RV viral loads were seen with co-infections with respiratory syncytial virus (RSV), metapneumovirus (MPV) and parainfluenza (PIV), but not with influenza, adenovirus or coronavirus. In 525 sequenced samples (46% RV-A, 4% RV-B, 50% RV-C), viral load did not vary between RV viral species (P = 0.09). CONCLUSION: Precise viral quantitation demonstrates children co-infected with RV and RSV, MPV or PIV have lower nasal viral loads than those with RV alone. Among RV mono-infections, RV viral load was not associated with admission or need for supplemental oxygen. [Image: see text] DISCLOSURES: All authors: No reported disclosures.


Practical Healthcare Epidemiology, 4th Edition


title: 1642. Comparing Viral Respiratory Infections Between Children Who Do and Do Not Attend Child Care

text: BACKGROUND: Out-of-home child care (CC) is a risk factor for viral acute respiratory infection (ARI) in young children. Little is known, however, about differences in frequencies of viral infection between CC children and those cared for exclusively at home. METHODS: Using surveillance data from the HIVE household cohort in southeast Michigan from 2014–2018 (4 seasons), we analyzed 1022 illness cases from 354 children aged 0–6 years. Age groups were dichotomized as infants (aged <2 years) and toddlers/preschoolers (aged 2–6 years). Households were prospectively enrolled and nasal respiratory swabs were collected from children upon report of acute illness symptoms. We used real-time RT–PCR to test for 18 respiratory viruses. RESULTS: We detected at least one virus in 855 illness cases (83% of all illnesses reported). Age at first illness onset in all four seasons was significantly younger among CC children than homecare children (P < 0.001) across all 4 years (average difference = 1.25 years). CC children <2 years had slightly lower odds of viral detection during illness (OR = 0.89, 95% CI [0.49, 1.61]) but higher odds at ages 2–6y (1.07 [0.65, 1.76]); neither was statistically significant. Neither CC nor homecare children were significantly more or less at risk for any particular pathogen—expect for rhinovirus in the <2-year group, where odds of rhinovirus infection were 58% lower (OR = 0.42) in CC children compared with homecare counterparts (95% CI, 0.21–0.83). Conversely, CC attendees under 3 more frequently had influenza, RSV, hMPV, parainfluenza, and coronavirus; however, none of these associations were significant. Odds of coinfection (> 1 virus detected) were higher among CC children, but not significant (OR = 1.4 [0.63, 2.96] and 1.2 [0.77, 1.88] in <2 year and 2–6 year age groups, respectively). Among all children <7 year, the mean number of pathogens detected was not different between CC and homecare individuals (1.20 vs. 1.23, P = 0.16). CONCLUSION: As expected, results indicated that CC attendees aged 0–6y experienced illness episodes earlier in life compared with homecare children. Our analysis also indicated that, compared with children cared for at home, CC children were less at risk for rhinovirus infection when young but could potentially be at higher risk for viruses of greater clinical concern. DISCLOSURES: All authors: No reported disclosures.


title: Optimal fluid management in sepsis

text: Sepsis clinically manifests as life-threatening organ dysfunction due to a dysregulated host response to infection.(1) Optimal fluid resuscitation is relevant for all sepsis patients, and perhaps it is most important for those with septic shock. Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greatest risk of mortality, and septic shock is clinically identified as sepsis patients with serum lactate level >2 mmol/L and who require vasopressor infusion to maintain a mean arterial pressure ≥ 65 mm Hg in the absence of hypovolemia. Sepsis is among the most common conditions in the intensive care unit (ICU), accounting for up to half of all hospital deaths and being the third leading cause of death overall in the United States.(2) Sepsis and septic shock are medical emergencies for which treatment and resuscitation should begin immediately. The goals of fluid resuscitation for these patients are: a) to rapidly replace intravascular volume and restore tissue perfusion, and b) to minimize organ dysfunction through timely interventions that either halt or reverse the physiologic derangements. If hypoperfusion is present, at least 30 mL/kg of IV crystalloid fluid should be given rapidly, and additional fluids should be guided by frequent reassessment of hemodynamic status, preferably using dynamic indices to indicate the likelihood of a beneficial response to fluid administration. Fluid administration should be targeted to achieve a MAP of at least 65 mm Hg, and to normalize lactate in patients with elevated lactate due to hypoperfusion.(3) Balanced crystalloids are the fluid of first choice for sepsis resuscitation based on ready availability and taking medication costs into account. Use of 0.9% saline compared to a balanced crystalloid, such as lactated Ringer's or PlasmaLyte, produces more kidney dysfunction and with a greater risk of dying.(4) The individual side effect profiles may best differentiate the natural and synthetic colloids. Albumin may be considered for administration to sepsis patients with refractory shock or who have received substantial amounts of crystalloid fluids, but should not be administered to patients with severe traumatic brain injury.(5) Hydroxyethyl starch (HES) products should not be administered to patients with sepsis because of increased risk of acute kidney injury and death. Gelatin solutions are not recommended in sepsis. Norepinephrine is the vasopressor of first choice for patients with septic shock, and should be administered to achieve a mean arterial pressure of at least 65 mm Hg after excluding hypovolemia as a cause for hypotension. The selection of a second line vasopressor, such as vasopressin, dopamine, phenylephrine, epinephrine or angiotensin-2, depends on patient factors such as underlying cardiac dysfunction, presence of arrhythmias, and current response to vasoconstrictor or inotropic agents. Dopamine should not be used for renal perfusion or protection and it should be avoided in patients with tachyarrhythmias.


In Memoriam: Jay Stephen Keystone (1943–2019)


Hunters Searching among Starry Nights and at the Edges of Life


title: Critical physiological and pathological functions of Forkhead Box O tumor suppressors

text: The Forkhead box, subclass O (FOXO) proteins are critical transcription factors, ubiquitously expressed in the human body. These proteins are characterized by a remarkable functional diversity, being involved in cell cycle arrest, apoptosis, oxidative detoxification, DNA damage repair, stem cell maintenance, cell differentiation, cell metabolism, angiogenesis, cardiac development, aging and others. In addition, FOXO have critical implications in both normal and cancer stem cell biology. New strategies to modulate FOXO expression and activity may now be developed since the discovery of novel FOXO regulators and non-coding RNAs (such as microRNAs) targeting FOXO transcription factors. This review focuses on physiological and pathological functions of FOXO proteins and on their action as fine regulators of cell fate and context-dependent cell decisions. A better understanding of the structure and critical functions of FOXO transcription factors and tumor suppressors may contribute to the development of novel therapies for cancer and other diseases.


title: Needs, Gaps and Opportunities for Infectious Disease Research in British Columbia: A Perspective from Population and Public Health

text: BACKGROUND: A review of infectious disease research activity and capacity was performed in British Columbia and linked to a process for identifying needs, gaps and opportunities from a public health perspective. METHODS: The study was organized in three phases: an environmental scan to describe current research activity in BC; a consultation to identify needs, gaps and opportunities with those conducting research (key informants) and the end users of research results (stakeholders); and a prioritization of the research needs emerging from the consultation. RESULTS: Analysis and synthesis of the consultation data resulted in the identification of nine research themes, which were prioritized in the following order: efficacy and cost-benefit, disease patterns, emerging infectious disease, immunology and vaccines, disease-specific research, health promotion and communications, safe food and water, knowledge translation research and genomics. Six capacity-building themes were also identified: attraction and retention, education and training, collaboration and networks, funding, dissemination of findings, and public health input, surveillance, informatics and databases. INTERPRETATION: The findings were helpful in developing a multi-disciplinary, multi-level infectious disease research agenda linking researchers in universities, hospitals and public health institutions with practitioners and policy-makers in British Columbia’s public health system. The approach is both feasible and important to undertake at the national level. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/BF03405394 and is accessible for authorized users.


title: Développer la capacité d’application des connaissances en santé publique: Le rôle des centres nationaux de collaboration

text: Ce document dresse l’historique et la justification du programme des Centres nationaux de collaboration en santé publique, établi par l’Agence de santé publique du Canada en 2004. Les centres ne sont pas axés sur la recherche primaire, mais plutôt sur la synthèse des preuves scientifiques mondiales qui sont pertinentes pour les politiques, les programmes et les pratiques de santé publique–et leur conversion en « produits du savoir » pour les professionnels de la santé publique, les responsables des politiques et les groupes communautaires afin de guider la prise de décision en santé publique. Les grands principes de la synthèse et de l’application/échange des connaissances (SAEC) aux fins de la santé publique sont passés en revue, de même que de récents sites Web et publications décrivant des projets internationaux dans ce domaine en plein essor. Enfin, certaines pratiques exemplaires pour la SAEC en santé publique provenant d’expériences au Canada et ailleurs dans le monde sont décrites.


title: Safety of prone positioning in critically ill patients

text: Background: During the past two years, 5% of patients admitted to the Medical Intensive Care Unit (MICU) of Hamad General Hospital (HGH) had severe acute respiratory distress syndrome (ARDS) with a PaO(2)/FiO(2) ratio less than 100 mmHg. The risks associated with this condition include ventilator associated lung injury, over distension of lungs, and poor gas exchange which results in increased morbidity and mortality. With quality improvement initiatives like prone positioning, the mortality and morbidity associated with severe acute respiratory syndrome(1) can be reduced by improving hypoxemia(2) with a significant enhancement in PaO(2)/FiO(2) ratios while reducing injurious ventilation. Also, prone positioning can help prevent invasive interventions such as placing patients on extracorporeal membrane oxygenation (ECMO) therapy.(3) Methods: We evaluated the safety of prone positioning for improving hypoxemia in critically ill patients with PaO(2)/FiO(2) ratio < 100 mmHg to PaO(2)/FiO(2) ratio < 200 mmHg from 1(st) January 2017 to 31(st) December 2018, without major complications. Data collected included the PaO(2)/FiO(2) ratios based on arterial blood gases of mechanically ventilated patients before and after prone positioning. We were able to facilitate prone positioning in 72 out of 110 patients with severe ARDS having a total average PaO(2)/FiO(2) ratio of 84.4 ± 30 mmHg. The patients were proned for a maximum of 16 hours in each session where up to three sessions were incorporated. No major complications were encountered during the proning sessions. This was thought to be accomplished through the coordination of a dedicated multidisciplinary team, education and simulation classes for physicians, nurses, and respiratory therapists, following appropriate inclusion and exclusion criteria for prone positioning, and implementing quality measures through Plan-Do-Study-Act (PDSA) cycles as represented in Figure 1. Results: The total average PaO(2)/FiO(2) ratio before proning for 65% of patients (n = 72) with severe acute respiratory distress syndrome(4) was 84.4 ± 30 mmHg and after one hour of 16 hours proning, it improved to 180.3 ± 78 mmHg. The remaining 35% of patients either had traumatic fractures, unstable spinal injury, severe hemodynamic instability, or morbid obesity together with ARDS which made them unfavorable for prone positioning. Out of those who were proned, 11 (12.5%) patients did not have improvement in oxygenation after proning due to non-recruitable lungs and were put on ECMO. The PaO(2)/FiO(2) ratios before and after one hour of implementing the prone position technique in each quarter of 2017 and 2018 are represented in Figure 2. Conclusion: • Sustaining and standardizing the accomplished work of data collection. • Implementing the prone positioning technique across other critical care units of Hamad Medical Corporation. • Keeping a record of minor complications associated with prone positioning and resolving them in further sessions. • Documenting cases with contraindications to prone positioning.


Veiled Dangers in an Idyllic Setting


title: Social Responses to Epidemics Depicted by Cinema

text: Films illustrate 2 ways that epidemics can affect societies: fear leading to a breakdown in sociability and fear stimulating preservation of tightly held social norms. The first response is often informed by concern over perceived moral failings within society, the second response by the application of arbitrary or excessive controls from outside the community.


title: EGFR-vIII downregulated H2AZK4/7AC though the PI3K/AKT-HDAC2 axis to regulate cell cycle progression

text: BACKGROUND: The EGFR-vIII mutation is the most common malignant event in GBM. Epigenetic reprogramming in EGFR-activated GBM has recently been suggested to downregulate the expression of tumour suppressor genes. Histone acetylation is important for chromatin structure and function. However, the role and biological function of H2AZK4/7AC in tumours have not yet been clarified. RESULTS: In our study, we found that EGFR-vIII negatively regulated H2AZK4/7AC expression though the PI3K/AKT-HDAC2 axis. Because HDAC1 and HDAC2 are highly homologous enzymes that usually form multi-protein complexes for transcriptional regulation and epigenetic landscaping, we simultaneously knocked out HDAC1 and HDAC2 and found that H2AZK4/7AC and H3K27AC were upregulated, which partially released EGFR-vIII-mediated inhibition of USP11, negative regulator of cell cycle. In addition, we demonstrated in vitro and in vivo that FK228 induced G1/S transition arrest in GBM with EGFR-vIII mutation. FK228 could enhance anti-tumour activity by upregulating expression of the tumour suppressor USP11 in GBM cells. CONCLUSIONS: EGFR-vIII mutation downregulates H2AZK4/7AC and H3K27AC, inhibiting USP11 expression though the PI3K/AKT-HDAC1/2 axis. FK228 is an effective and promising treatment for GBM with EGFR-vIII mutation.


title: Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): bovine viral diarrhoea (BVD)

text: Bovine viral diarrhoea (BVD) has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on the eligibility of BVD to be listed, Article 9 for the categorisation of BVD according to disease prevention and control rules as in Annex IV and Article 8 on the list of animal species related to BVD. The assessment has been performed following a methodology composed of information collection and compilation, expert judgement on each criterion at individual and, if no consensus was reached before, also at collective level. The output is composed of the categorical answer, and for the questions where no consensus was reached, the different supporting views are reported. Details on the methodology used for this assessment are explained in a separate opinion. According to the assessment performed, BVD can be considered eligible to be listed for Union intervention as laid down in Article 5(3) of the AHL. The disease would comply with the criteria as in Sections 4 and 5 of Annex IV of the AHL, for the application of the disease prevention and control rules referred to in points (d) and (e) of Article 9(1). The assessment here performed on compliance with the criteria as in Section 3 of Annex IV referred to in point (c) of Article 9(1) is inconclusive. The animal species to be listed for BVD according to Article 8(3) criteria are mainly species of the families Bovidae, Cervidae and Camelidae as susceptible species and several mammalian species as reservoirs.


title: iCa(2+) Flux, ROS and IL-10 Determines Cytotoxic, and Suppressor T Cell Functions in Chronic Human Viral Infections

text: Exhaustion of CD8(+) T cells and increased IL-10 production is well-known in chronic viral infections but mechanisms leading to loss of their cytotoxic capabilities and consequent exhaustion remain unclear. Exhausted CD8(+)T cells also called T suppressors are highly immune suppressive with altered T cell receptor signaling characteristics that mark it exclusively from their cytotoxic counterparts. Our study found that iCa(2+) flux is reduced following T cell receptor activation in T suppressor cells when compared to their effector counterpart. Importantly chronic activation of murine cytotoxic CD8(+) T cells lead to reduced iCa(2+) influx, decreased IFN-γ and enhanced IL-10 production and this profile is mimicked in Tc1 cells upon reduction of iCa(2+) flux by extracellular calcium channel inhibitors. Further reduced iCa(2+) flux induced ROS which lead to IFN-γ reduction and increased IL-10 producing T suppressors through the STAT3—STAT5 axis. The above findings were substantiated by our human data where reduced iCa(2+) flux in chronic Hepatitis infections displayed CD8(+) T cells with low IFN-γ and increased IL-10 production. Importantly treatment with an antioxidant led to increased IFN-γ and reduced IL-10 production in human chronic Hep-B/C samples suggesting overall a proximal regulatory role for iCa(2+) influx, ROS, and IL-10 in determining the effector/ suppressive axis of CD8(+) T cells.


Poster Sessions 313-503


Abstracts des Kongresses für Kinder- und Jugendmedizin 2017


title: Die Dialektik der Wissenschaftsfreiheit vor dem Hintergrund der Bioterrorismus-Bekämpfung

text: Die mikrobiologische Forschung ist durch die jüngsten Ereignisse in den USA in unerwartet scharfer Form auf den Prüfstein gestellt worden. Nach dem 11. September 2001 und den darauf folgenden Milzbrandanschlägen wurde dem Terrorismus und speziell dem Bioterrorismus in den USA die höchste Priorität eingeräumt. Damit verbunden war auch eine Problematisierung vor allem der mikrobiologische Forschungsfreiheit. Im vorliegenden Artikel wird daher der Versuch unternommen, einen Überblick über den „Dualuse“- Charakter und die möglichen Gefahren der mikrobiologischen Grundlagenforschung zu geben und auf die negativen Auswirkungen von Selbstzensur, einschränkenden Gesetzesbestimmungen und einseitiger Forschungsförderungspolitik aufmerksam zu machen.


Abstracts 2019 der GNPI und DGPI: 45. Jahrestagung der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin gemeinsam mit der 27. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie, 23.–25. Mai 2019, Leipzig


Dreizehnter Bericht nach Inkrafttreten des Gentechnikgesetzes (GenTG) für den Zeitraum vom 1.1.2002 bis 31.12.2002 : Die Arbeit der Zentralen Kommission für die Biologische Sicherheit (ZKBS) im Jahr 2002


Impfungen


Tuberkulose: Damals und heute ein Thema


Pediatric Radiology Continuing Medical Education Activity


Reply to Ñamendys-Silva and Salluh


33rd Annual Meeting of The Japanese Society of Neuroradiology 5-7 February 2004, Osaka, Japan


Abstractband zum 120. Kongress der DGIM 2014


Oral Presentations_Tuesday


Mitteilungen der DGIM 04/2004


title: Synthesis and preliminary in vitro activity of mono- and bis-1H-1,2,3-triazole-tethered β-lactam–isatin conjugates against the human protozoal pathogen Trichomonas vaginalis

text: In this study, we describe the synthesis of mono- and bis-1H-1,2,3-triazole-tethered β-lactam–isatin conjugates using copper-catalysed azide-alkyne cycloaddition reaction between mono- and di-propargylated azetidin-2-ones and N-alkylazido isatins. The synthesized conjugates were evaluated for their preliminary in vitro analysis against Trichomonas vaginalis at 50 μM. The efficacy of synthesized hybrids was observed to depend on the substituent at N-1 position of β-lactam ring, as well as the presence of single/double 1H-1,2,3-triazole linker. Among the synthesized conjugates, the presence of a p-tolyl substituent at N-1 of β-lactam ring was preferred for good activity profiles while the increase in spacer length did not influence the efficacy of the compounds. Compounds with high levels of potency were further analysed to determine their IC(50) values, as well as cytotoxicity profiles against mammalian cells. The most active compound in the synthesized conjugates displayed an IC(50) value of 10.49 μM against cultured G3 strain of T. vaginalis and was non-toxic to cultured mammalian HeLa cells at the same concentration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00044-014-0956-6) contains supplementary material, which is available to authorized users.


Oral Presentations O1 - O184


Posters P788 - P999


Bandinhalt Band 46—2003


SPR 2012


Scientific Program


Ärztliches Berufsrecht. Hat ein Assistenzarzt bei Vertretung eines Chefarztes Anspruch auf Vergütung?


Stellungnahme der ZKBS zur Risikobewertung des SARS-assoziierten Coronavirus


title: Infektionen der oberen Atemwege

text: BACKGROUND: Upper airway infections contribute significantly to paediatric morbidity and hospitalization especially of young children, are often treated polypragmatically, and are one of the main reasons for antibiotic prescriptions. The severity varies between mild, self-limiting and potentially life-threatening airway obstructions. DIAGNOSIS: The physician involved can normally make the right diagnosis based on the patient′s history and physical findings; additional diagnostic procedures (blood tests, imaging) should be restricted to unclear cases. THERAPY: Antibiotic stewardship should be applied. Imminent airway obstruction will require early and competent paediatric intensive care interventions. Since viral and bacterial upper airway infections can present with similar features, it is useful to approach them under topographical aspects. PREVENTION: Following immunization recommendations can prevent an enormous amount of severe potentially life threatening airway infections.


Angemessene Vorbereitung gegen bioterroristische Anschläge


title: Management biologischer Gefahrenlagen: Überlegungen zur notwendigen Infrastruktur in Ländern und Kommunen

text: Management of a terrorist or criminal attack with biological agents depends on the number of primarily contaminated cases, on the numbers of persons who need medical treatment, on the possibility of human-to-human transmission, and on the tenacity of the germs.In the event of a high rate of human-to-human transmission, the strategy of transmission control depends on the kind of transmission and the effectiveness of measurements implemented by public health authorities. In this respect, it does not differ from the management of the natural emergence of an infectious disease (for example SARS). At all times it is necessary to establish precautions for the clinical management of severely ill persons. The possibility of professional clinical management depends on the number of affected people at one time and the necessary precautions for the medical personnel and the community. Kind, time, and region of the deliberate release of new or manipulated microorganisms or the natural emergence of an infectious disease are not predictable—the risk of human transmission is of course higher in regions with high population density. It is recommended that single cases of a highly contagious, lifethreatening disease be treated in central institutions with special technical support and facilities for staff protection (isolation unit). However, in terms of an epidemic situation, every single region must establish precautions for its own management of such cases.


title: A predictive decision-aid methodology for dynamic mitigation of influenza pandemics

text: In a recent report, the Institute of Medicine has stressed the need for dynamic mitigation strategies for pandemic influenza. In response to the need, we have developed a simulation-based optimization methodology for generating dynamic predictive mitigation strategies for pandemic outbreaks affecting several regions. Our methodology can accommodate varying virus and population dynamics. It progressively allocates a limited budget to procure vaccines and antivirals, capacities for their administration, and resources required to enforce social distancing. The methodology uses measures of morbidity, mortality, and social distancing, which are translated into the costs of lost productivity and medical services. The simulation model was calibrated using historic pandemic data. We illustrate the use of our methodology on a mock outbreak involving over four million people residing in four major population centers in Florida, USA. A sensitivity analysis is presented to estimate the impact of changes in the budget availability and variability of some of the critical parameters of mitigation strategies. The methodology is intended to assist public health policy makers.


title: A Novel CDC42 Mutation in an 11-Year Old Child Manifesting as Syndromic Immunodeficiency, Autoinflammation, Hemophagocytic Lymphohistiocytosis, and Malignancy: A Case Report

text: Background: The CDC42 (Cell Division Cycle 42) gene product, CDC42, is a member of the family of small Rho GTPases, which are implicated in a broad spectrum of physiological functions in cell cycle regulation, including establishing and controlling of the cell actin cytoskeleton, vesicle trafficking, cell polarity, proliferation, motility and migration, transcription activation, reactive oxygen species production, and tumorigenesis. The CDC42 gene mutations are associated with distinct clinical phenotypes characterized by neurodevelopmental, growth, hematological, and immunological disturbances. Case presentation: We report the case of an 11-year-old boy with syndromic features, immunodeficiency, and autoinflammation who developed hemophagocytic lymphohistiocytosis and malignant lymphoproliferation. In this patient, a novel heterozygous p.Cys81Tyr mutation in the CDC42 gene was found by whole exome sequencing. Conclusions: The Cdc42 molecule plays a pivotal role in cell cycle regulation and a wide array of tissue-specific functions, and its deregulation may result in a broad spectrum of molecular and cellular dysfunctions, making patients with CDC42 gene mutations susceptible to infections, immune dysregulation, and malignancy. In the patient studied, a syndromic phenotype with facial dysmorphism, neurodevelopmental delay, immunodeficiency, autoinflammation, and hemophagocytic lymphohistiocytosis shares common features with Takenouchi–Kosaki syndrome and with C-terminal variants in CDC42. It is important to emphasize that Hodgkin's lymphoma is described for the first time in the medical literature in a pediatric patient with the novel p.Cys81Tyr mutation in the CDC42 gene. Further studies are required to delineate precisely the CDC42 genotype–phenotype correlations.


title: Virale Atemwegsinfektionen bei Erwachsenen : Eine Übersicht

text: In the course of a lifetime a decrease of the immunofunction occurs in adults, in particular of the adaptive immune system.Therefore, respiratory virus infections are usually mild and uncomplicated in young healthy people while elderly and frail adults more frequently develop serious diseases of the lower respiratory tract.Even “harmless” agents such as rhino- or coronaviruses frequently induce acute disorders or exacerbations in people with chronic cardiopulmonary diseases or asthma.For rapid diagnosis, detection of the viral antigen, viral genome, and infectivity by shell vial culture are suitable because the humoral immune response is delayed.Primarily, a nasopharyngeal sample should be used and in addition a specific local sample depending on the symptoms. The sensitivity of antigen assays is rather low. A combination of PCR and detection of infectivity increase the detection rate.Among the main respiratory viruses only influenza is preventable by vaccination.The annual revaccination of the elderly and patients with risk factors such as chronic cardiopulmonary diseases is important.Improved vaccines can enhance the immunoreaction.For therapy and prophylaxis against influenza A amantadine may be used.The neuraminidase inhibitors zanamivir and oseltamivir represent potent drugs for antiviral therapy against influenza virus A and B infection. Pleconaril, a capsid function inhibitor with effective antiviral activity against rhinovirus infection, awaits approval.