Soung Hoon Chang has completed his MD at the age of 25 years from Korea University College of Medicine and has completed PhD at the age of 40 from Korea University College of Medicine. He is the director of Department of Preventive Medicine, Konkuk University School of Medicine. He has published more than 200 papers in reputed journals.

This study aims to describe the epidemiology of influenza-like illness (ILI) and to estimate the incidence rate of ILI in several communities in South Korea, over three influenza seasons. Since 2011, the Community Respiratory Health Survey has been continuously monitoring ILI in 3 community-based cohorts. At the beginning of the season, baseline study took place; Nov. 2011 in Chungju and Ulsan, and in Dec. 2012 in Seoul. For each cohort, approximately 1,000 individuals (age 6 months over) from randomly selected 300 households were recruited. On a weekly basis, participants were asked via telephone interview whether they had ARI (acute respiratory illness) or ILI; from May to October, interview took place every second week. The annual Age-standardized rate (ASR) of ILI per 1,000 populations were 2.3 (95% CI 1.8-2.9) and 3.5 (95% CI 2.7-4.3) in Chungju and Ulsan, 2011/2012 season. In 2012/2013 season, ILI incidence rate were 3.0 (95% CI 2.9-3.1) and 5.5(5.4-5.7) in Chungju and Ulsan. The ASR of ILI per 1,000 populations in Seoul was 12.7 (95% CI 12.5-12.9) per 1,000 populations in 2012/2013. From 44th week 2013 to 29th week 2014, the incidence rates were almost doubled in Seoul and Chungju due to the epidemic of influenza. In Chungju and Ulsan, ILI incidence rates were 4.3(95% CI 4.2-4.5) and 9.0 (95% CI 8.8-9.2) per 1,000 populations. In Seoul, ILI incidence rate of the 2013 season was 21.2 (95% CI 20.9-21.5) per 1,000 populations. The influenza-like illness incidence rate is highest in age 0-6 years and varies by regions. During the 2013/2014 season, the incidence rates of ILI in Chungju, Ulsan, and Seoul were greater than those from other two seasons due to the pandemic of influenza.

Karen Roderick completed her undergraduate studies at Hood College and works as a Research Associate for Lonza BioScience, Walkersville. Her focus is on the development of non-animal origin culture media for vaccine and therapeutic medicine.

Cell-based influenza vaccine production is quickly growing in the vaccine industry to meet the threat of pandemic outbreaks and to eliminate health concerns associated with egg protein allergies. Madin Darby Canine Kidney (MDCK) is a commonly used cell line for production of influenza virus and the cell-based manufacture of inactivated flu vaccines. Expansion of MDCK cells allows for rapid response and quick scale up compared to the traditional egg based vaccine manufacturing process. This study examines the feasibility of using microcarrier-based cell culture for the expansion of MDCK cells in 3D. Several media were compared for their ability to support MDCK cell growth in planar and suspension culture as well as their ability to support flu virus production from MDCK cells. ProMDCK (2D) and ProMDCK (3D) (Lonza) supported excellent cell proliferation and virus production in both planar culture and on multiple types of microcarriers. The preparation and usage of the various microcarriers were based on the manufactures’ recommendations and were evaluated for ease of use, ability to support cell proliferation and virus production, and ability to support MDCK expansion without cell dissociation in disposable culture systems.

LI Can is a PhD candidate in the Dept. of Microbiology, the University of Hong Kong. She mainly researches on vaccine and the pathogenesis of influenza viruses, including pandemic H1N1 virus, H5N1 and H7N9 viruses. She published several papers during her PhD study.

TLR ligands, which can directly stimulate immune responses towards antigens, have shown great promise as novel adjuvants in many vaccine studies. Imiquimod, a synthetic TLR7 agonist, could significantly enhance immune responses together with conventional vaccine strategies. Our previous study showed an inactivated vaccine combined with Imiquimod (VCI) could elicit immediate immune responses against influenza A (H1N1) pdm09 infection in BALB/c mice. Survival rate was significantly improved in VCI group. Neutralizing antibody and virus-specific antibody appeared earlier and with higher titer in VCI group. We further seek the mechanisms overlaying the enhancement of vaccine induced by Imquimod. Our recent study showed 18hrs after intraperitoneal stimulation of VCI, B cells migrated rapidly from peritoneal cavity to spleen. CD86 on lymph node and splenic B cells was up-regulated in VCI group. After infection, B2 cells and T cells increased rapidly in lung of VCI group. Prompt neutrophil infiltration was also detected in lung, together with faster formation of germinal center around infection site. Higher affinity of local virus-specific antibody responses followed afterwards. These results indicated Imiquimod combined with vaccine may stimulate local B cells activation and enhance the proliferation and production of high-affinity antibody. Finally, the fast-acting antibody-based immune responses induced by vaccine combined with Imquimod may provide a new strategy facing immediate unpredicted influenza outbreaks. The mechanisms of early B cell activation deserve further study.

Narasaraju Teluguakula has been working in the field of “Respiratory and infectious diseases” since he joined PhD program in 1995. He obtained Postdoctoral training in Lung Biology at Oklahoma State University, USA from 2001-2004 and in infectious diseases from 2005-2010 at National University of Singapore, Singapore. He has been a ‘mentor’ for many graduate and master students during his Postdoctoral research and also wrote two grants as a co-investigator. He has experience of working with infectious disease models and conceptual knowledge of lung physiology and pathology

Objective: The prime complication characteristic to the influenza virus infection is viral pneumonia, which can then lead to acute respiratory distress syndrome (ARDS). Our previous studies have shown that excessive neutrophils and their generated neutrophil extracellular traps (NETs) contribute to lung tissue injury in severe influenza pneumonia. In the current study, we have evaluated the role of extracellular histones in tissue injury during influenza and tested therapeutic efficacy of anti-histone antibodies alone or in combination with an antiviral agent. Materials and Methods: BALB/c Female mice were challenged with lethal influenza A/PR/8/34 (H1N1), 2500pfu. Lung histopathology was analyzed. Bronchoalveolar lavage (BAL) was analyzed for vascular leakage, alveolar epithelial, endothelial damage and histones release. Histone-mediated cytotoxicity was measured by lactate dehydrogenase (LDH) release assay. Therapeutic efficacy of anti- histone antibodies (100ug/animal, subcutaneous) alone or in combination of oseltamivir (20mg/kg) was evaluated. Results: Influenza infected mice showed increased neutrophil influx, intra-alveolar hemorrhage, edema and macro- and microvascular thrombosis. Infection caused high extracellular histones release into the lung airspace. Released extracellular histones also showed high cytotoxicity in both alveolar epithelial and endothelial cells in vitro. Treatment with anti-histone antibody significantly reduced lung pathology, compared to oseltamivir treatment alone. Further combination of anti-histone antibodies together with oseltamivir resulted in 40% survival after lethal influenza challenge in mice. Conclusions: These results demonstrate that the use of anti- histone antibodies in combination with a classical antiviral therapy can be a novel and effective treatment approach for severe influenza pneumonia.

Janice Koshy, MD completed her medical school at Texas A&M College of Medicine in College Station, TX and her residency in internal medicine at Baylor Scott & White Hospital in Temple, TX. She is currently a second year fellow in Infectious Diseases at Baylor Scott & White and is involved in ongoing research and quality improvement at her institution.

Influenza A is associated with increased mortality making rapid diagnosis and treatment essential. Baylor Scott & White Hospital in Temple, TX employs two PCR tests for the diagnosis of influenza, the Simplexa Flu A/B & RSV (Influenza/RSV PCR) and the xTag Respiratory Viral Panel (RVP PCR). Clinical observation of patients diagnosed with influenza A during the 2013-2014 influenza season has shown that multiple patients with negative RVP PCRs had positive Influenza/RSV PCRs. Due to this observation, we determined if one of the above tests has a higher rate of positivity and which specimen sites have higher rates of positivity for influenza A. A query was run for adult patients from September 2013 through February 2014 that underwent testing for influenza by Influenza/RSV PCR or RVP PCR. The rates of positivity for each test were determined and compared. Then patients who underwent both tests for influenza within seven days with at least one positive test were identified and the rates of positivity between the two tests were determined and compared. The rate of positivity for different specimen sites was determined and within and between each test. 5056 specimens were included. The ratio of positive Influenza/RSV PCRs and RVP PCRs were 0.2970 and 0.1438 respectively (p<0.0001). Forty patients had both tests performed within seven days and the rates of positivity for the Influenza/RSV PCR and RVP PCR were 0.375 and 0.125 respectively (p<0.0035). The rates of positivity were determined for nasal, nasopharyngeal, throat, tracheal aspirate and BAL specimens for the Influenza/RSV PCR and were 0.29, 0.50, 0.36, 1.0, and 0.75 respectively (p<0.0001). The rates of positivity were determined for the same sites for the RVP PCR and were 0.13, 0.29, 0.25, 0.25, and 0.12 respectively (p<0.0001). The Influenza/RSV PCR had significantly higher rates for all specimen sites (nasal p<0.0001, nasopharyngeal p<0.0001, throat p<0.019, tracheal aspirate p<0.0001 and BAL p<0.002). The influenza/RSV PCR has a higher rate of positivity in identifying influenza A. Upper respiratory specimens are easiest for providers to obtain and out of these sites; nasopharyngeal specimens have the highest rate of positivity.

Jennifer Burns is a Pediatric Nurse Practitioner who works in the department of Pediatric Infectious Disease at University of Chicago Comer Children’s Hospital. During the H1N1 pandemic, she established & directed an immunization program for children of medical center employees that grew to include all family members. The program immunized more than 5,000. Since that program was so successful it is done annually at the medical center. Jennifer continues her mission by immunizing students, families, faculty and staff at local schools. She speaks regularly on the behalf of the Illinois Chapter of the AAP on topics related to immunization.

The Pediatric Infectious Diseases created Comer Family Flu Clinic in 2009 during the H1N1 influenza pandemic. It was implemented as an influenza vaccination program to serve family members of medical center and university employees in hopes of reducing workplace absenteeism and lost productivity. It was so successful providing families with flu vaccine, it continued yearly from September to March. In 2013, Pediatrics was concerned ID was taking revenue from them and these patient’s were not going to see their PMD for yearly appointments because they were getting primary care in Flu Clinic. In order for the Flu Clinic to continue we were to assess if the patients were being seen by their PMD. We created a questionnaire to assess why the patients come to family Flu Clinic and to see when they were last seen by their PMD. During the Comer Family flu visit, Health Providers asked 4 questions to obtain information from family regarding when their child’s last appointment was with their Primary Care Provider (PCP). Our second goal was to assess how and why they chose to come to Comer Family Flu Clinic. The questions were: 1) Does your child have a PCP? 2) When was the last time you saw PCP? 3) How did you hear about of the Flu Clinic? 4) What do you like about the Flu Clinic? Results: 95% of patients readily identified a PCP. 60% of patients had seen their PMD within 1 to 6 months of family Flu clinic. 30% reported that they heard about Flu Clinic because they came in previous years, 5% used the website, 20% utilized all methods. 25% of the families liked the hours of Flu Clinic and 55% of the families like both the access hours and the ability of the whole family to get immunized at one time. Patients who had not seen PCP in over a year were sent to schedule an appointment with their PCP. The data showed that 95% of patients had a PCP at UOC and Flu Clinic did not decrease use of PCP’s and those families like the ability to receive flu vaccines together.

Huan-Yuan Chen is associate research scientist in Academia Sinica, Institute of Biomedical Sciences. He completed his Ph.D. from National Tsing Hua University. His laboratory focuses on the study of the roles of galectin-3 in cells involved in skin inflammation.

H5N1 is a highly pathogenic avian influenza virus which causes pneumonia and acute respiratory distress syndrome in human. Virus-induced cytokine dysregulation and excessive inflammatory response contribute to the pathogenesis of human H5N1 disease. Galectin-3 is aβ-galactoside binding animal lectin widely distributed in immune and epithelial cells. Galectin-3 has been reported to regulate various immune functions and shows pro-inflammatory activity. In the present study, we investigated the roles of endogenous galectin-3 in H5N1 virus infection-induced host immune responses. We observed that galectin-3 was up-regulated in the lungs after H5N1 infection in mouse model, and the increased galectin-3 was mainly expressed by the infiltrating cells. Our preliminary data also showed that galectin-3 knockout (Gal-3KO) mice were less susceptible to H5N1 virus infection compared to wild-type (WT) mice, whereas the viral loads in lungs were comparable. Moreover, we found that H5N1-infected Gal-3KO mice exhibited lower degree of lung inflammation, and lower level of neutrophil and macrophage recruitment to lung. In addition, the level of IL-1β in both bronchoalveolar larvage and lung were significantly reduced in H5N1- infected Gal-3KO mice. In the in vitro study, we also showed that bonemarrow-derived macrophages from Gal-3KO mice produced reduced level of proinflammatory cytokinesIL-1β and chemokine MCP-1 compared to those from WT mice in response to H5N1 infection. Combined, our results suggest that galectin-3 may enhance the pathological effects of H5N1 virus infection by promoting inflammatory response and that galectin-3 may be targeted for H5N1 virus-induced severe lung inflammation.