Day 3 :
Keynote Forum
Nicolas Noulin
hVIVO, UK
Keynote: Influenza: The same virus but a very different illness if you are young or old
Time : 9:00-9:30
Biography:
Nicolas Noulin has completed his PhD in Immunology and Molecular Biology from Orleans University (France) and Post-doctoral studies from Institut Pasteur in Paris. He is a Principle Virologist at hVIVO, a company pioneering a technology platform which uses human models of disease.
Abstract:
Respiratory viruses are among the most common causes of hospitalisation and are a particular threat to vulnerable populations such as the elderly. In this study the Human Viral Challenge Model of infection was used to investigate the immune response to a GMP produced wild-type A/Perth/16/2009 (H3N2) Influenza virus in healthy adults of different age classes. After completion of the pre-clinical phase, a dose ranging titration clinical study was carried out in young healthy adults to select the most suitable safe titre of virus with a reproducible profile of pathogenicity. In the next phase the chosen dose was used to address the relationship between the age of infected subjects and the profile of influenza illness. Sero-suitable volunteers were inoculated with A/Perth/16/2009 virus in a quarantine facility and divided into two age groups: 18 to 45 and 46 to 64 years old. The development of symptoms and progression of infection were monitored for 8 days to assess parameters such as safety, clinical symptoms and virus shedding. Seroconversion was evaluated during a follow up visit at day 28 post infection. The progression of the influenza disease was found to be different between the younger and older subject groups in terms of the profile of infection and the time of onset, time to peak, intensity and resolution of symptoms either by self-assessment using a standardised diary card (which has been used for over 15 years and in approximately 2000 subjects) or through diagnosis by a study physician, and in terms of virus shedding, measured by cell infectivity and molecular assays. Results from this study will allow better understanding of the influenza virus in the community and will help in the development of new vaccine strategies and therapeutics for populations at risk, such as the elderly.
- Track 4- Evolution and Epidemiological aspects of Influenza, Track 7: Reassortment and Reverse Genetics, Track 14:Animal flu-ecology, Track 16:Influenza Lung Immunology: Major diseases
Chair
Nicolas Noulin
hVIVO, UK
Session Introduction
Nicolas Noulin
hVIVO, UK
Title: Influenza. The same virus but a very different illness if you are young or old
Time : 09:00-09:30
Biography:
Nicolas has completed his PhD in immunology and molecular Biology at the age of 27 years from Orleans University (France) and postdoctoral studies from Institut Pasteur in Paris. He is Principle Virologist at hVIVO, a company pioneering a technology platform which uses human models of disease.
Abstract:
Respiratory viruses are among the most common causes of hospitalisation and are a particular threat to vulnerable populations such as the elderly. In this study the Human Viral Challenge Model of infection was used to investigate the immune response to a GMP produced wild-type A/Perth/16/2009 (H3N2) Influenza virus in healthy adults of different age classes.
After completion of the pre-clinical phase, a dose ranging titration clinical study was carried out in young healthy adults to select the most suitable safe titre of virus with a reproducible profile of pathogenicity. In the next phase the chosen dose was used to address the relationship between the age of infected subjects and the profile of influenza illness. Sero-suitable volunteers were inoculated with A/Perth/16/2009 virus in a quarantine facility and divided into two age groups: 18 to 45 and 46 to 64 years old. The development of symptoms and progression of infection were monitored for 8 days to assess parameters such as safety, clinical symptoms and virus shedding. Seroconversion was evaluated during a follow up visit at day 28 post infection.
The progression of the influenza disease was found to be different between the younger and older subject groups in terms of the profile of infection and the time of onset, time to peak, intensity and resolution of symptoms either by self-assessment using a standardised diary card (which has been used for over 15 years and in approximately 2000 subjects) or through diagnosis by a study physician, and in terms of virus shedding, measured by cell infectivity and molecular assays.
Results from this study will allow better understanding of the influenza virus in the community and will help in the development of new vaccine strategies and therapeutics for populations at risk, such as the elderly.
Yanbo Yin
Qingdao Agricultural University, CHINA
Title: Epidemiological analysis of H9N2 virus in China
Time : 09:30-09:55
Biography:
Yanbo Yin has completed his PhD from China Agricultral University. Member of avian diseases branch, Executive member of veterinary pathology branch, Chinese Association of Animal Science and Veterinary Medicine; The avian diseases prevention duty expert of Shandong Modern Agricultural Technology & Industry System. He is a professor of Qingdao Agricultral University and has trained more than 30 graduate students. He had published more than 200 peer-reviewed papers in English and Chinese.He is the Member of avian diseases branch, Executive member of veterinary pathology branch, Chinese Association of Animal Science and Veterinary Medicine;The avian diseases prevention duty expert of Shandong Modern Agricultural Technology & Industry System
Abstract:
In our lab, systemic surveillance and epidemiological investigation on H9N2 influenza were conducted. From January 2008 to August 2014, 6569 clinical samples had been collected and tested, and the positive rate of H9N2 influenza was 25.12%. More than 1,000 H9N2 virus strains were isolated. The genome sequences of the virus were determined, and the biological characters were tested. The results showed the mutation speed of HA gene became faster, new clade virus were emerging nearly year by year. Different clade virus was circulating at the same time and same location. The H9N2 virus isolated after 2008 displayed higher virulence to embryonated eggs, and the virulence with higher virulence in embryonated eggs also showed higher pathogenicity in chickens, and caused systemic infection. The antigenicity of H9N2 changed quickly, and formed different antigenic groups, some of which showed significant antigenic difference, compared with earlier vaccine strains. Our study also showed when HA amino acid sequence mutations reached a point (more than 7%), the antigenicity change could be significant. The study results emphasized that the vaccine strain should be updated in a timely manner through surveillance and accompanying laboratory evaluation of contemporary viruses for antigenic similarity with existing vaccine strains, and the genetic and pathogenic variation of H9N2 virus should be closely monitored.
Mohammed N. Al-Ahdal
King Faisal Specialist Hospital and Research Center, Saudi Arabia
Title: Characterization of H5N1 influenza A virus that caused the first highly pathogenic avian influenza outbreak in Saudi Arabia
Time : 09:55-10:20
Biography:
Mohammed N. Al-Ahdal (a Bio-Pharmacist) has completed his Ph.D. in Microbiology and Immunology from the State University of New York at Buffalo in 1985. He is the now the Chairman of the Department of Infection and Immunity at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, where he is also a Principal Scientist. He is a Professor of Microbiology and Immunology at the College of Medicine of Alfaisal University in Riyadh, Saudi Arabia and an Adjunct Professor at Sassari University in Italy and at Brunel University in the U.K. He has published more than 105 papers in reputed journals and serving as an editorial board member of some scientific journals.
Abstract:
Saudi Arabia has experienced a highly pathogenic avian influenza (HPAI) H5N1 outbreak in domesticated birds in 2007. From this outbreak, we sequenced forty-three HA and forty-one NA genes of HPAI-H5N1 viruses and performed phylogenetic analyses to compare these sequences with those of other viruses available in the public databases. Molecular characterization of the H5N1 viruses revealed two genetically distinct clades, 2.2.2 and 2.3.1. Amino acid sequence analysis of HA gene indicated that virus from 2.2.2 contained the sequence SPQGERRRK-R/G at the cleavage site, while from 2.3.1 contained the sequence SPQRERRRK-R/G. Additionally, we identified a few mutations with amino acid substitutions, such as M226I mutation at N-link glycosylation site in two of the isolates, which could affect receptor specificity as well as viral pathogenicity. Amino acid sequence of NA gene showed a 20-amino-acid deletion (positions 49–68) in the NA stalk region, required for enhanced virulence of influenza viruses and its adaptation from wild birds to domestic chickens. Relaxed clock and Bayesian Skyline Plot analysis based on HA and NA genes of our isolates and closely related global representatives indicated lower substitution rates (2.036X10-3 and 2.072X10-3 substitutions/nucleotide/year) when compared with earlier reports (4.23X10-3 and 4.27X10-3 substitutions/nucleotide/year). As close contact between humans and birds is unavoidable, there is a need of a thorough understanding of the epidemiology, factors affecting the spread of the virus and of the viral molecular characteristics of H5N1 viruses circulating in the region.
Devanshi Gohil
Haffkine Institute for Training, Research and Testing, India
Title: Genetic Characterization of co-circulating Influenza A Viruses in the Pandemic (2009-2010) and Post Pandemic (2010-2011) periods in Mumbai
Time : 10:35-11:00
Biography:
Devanshi Gohil is a Research Scholar currently pursuing Doctorate of Philosophy in Medical Microbiology on “Molecular characterization of 2009 H1N1 pandemic influenza & seasonal influenza viruses from patients in Mumbai” at Haffkine Institute for Training, Research and Testing, under Maharashtra University of Health Sciences, Nashik, India. She has done her post-graduation studies in Microbiology from University of Mumbai, India. Presently, she is working as Project Coordinator on National Project entitled Laboratory Based Influenza Surveillance Plan India: Under Integrated Disease Surveillance Project (IDSP) Avian Influenza Lab Network, run by National Center for Disease Control, Government of India, New Delhi, India. She has 7 publications to her credit in National and International journals.
Abstract:
Pandemic influenza A (H1N1) 2009 virus was first detected in May 2009 initiating the pandemic in India. Influenza A viruses has the ability to evade the immune response through the acquisition of genetic changes. Understanding the multiple lineages of influenza virus variants is necessary in lieu of co-circulation of influenza A (H1N1) pdm 09 and seasonal influenza A (H3N2) virus in Mumbai, a global transition hub. However, genetic information of circulating influenza strains in Mumbai is limited. In the present study, we performed molecular and evolutionary analysis of these co-circulating viruses isolated from patients with during August 2009 – March 2011. Positive samples were cultured and the viral genomes for HA and NA were analyzed for both seasonal and pandemic isolates. Molecular analysis revealed substantial sequence variations in both pandemic and seasonal influenza A viruses. HA1 sequences of pandemic isolates were conserved at the receptor-binding site, while variations in the amino acid substitutions at the antigenic sites resulted in the changes at the N-linked glycosylation sequon. In pandemic isolates, amino acid substitutions in the NA gene were dissociated with the catalytic or framework sites. Seasonal Influenza A virus exhibited antigenic drift. Phylogenetic analysis of the HA and NA genes of pandemic and seasonal isolates illustrated their evolutionary closeness or drift with their concomitant prototype vaccine strains respectively. Studies like ours aid in identifying the variations in the circulating influenza virus strains, as well as spot emerging variants, thus abetting a vigilant control over the disease.
Tony Velkov
Monash University
Australia
Title: Molecular characterization of the hemagglutinin receptor-binding specificity of avian influenza viruses: predicting the jump across the species barrier
Time : 11:00-11:25
Biography:
Tony Velkov completed PhD in 2000 from Monash University. His anti-infective discovery research is at the leading edge globally. He was awarded a NHMRC Research Fellowships in 2006, 2011 and 2014. The quality and impact of his independent research was recognized by the NHMRC with an Excellence Award in 2011. He has published over 50 papers in high-caliber journals, 3 book chapters and 15 conference presentations. The dynamic team he leads consists of 3 postdocs, 3 RAs and 9 PhD students. Over the last 6 years, he has obtained >$9M funding from the NIH, NHMRC and foundations.
Abstract:
Influenza is a constant global burden to human health. Seasonal influenza results in significant infections and death, cycling through both hemispheres. On occasion, a novel avian influenza virus crosses the species barrier from birds to humans resulting in an influenza pandemic. The threat of pandemic avian influenza continues with H5N1 and H7N9 consistently infecting humans. In order to evolve from its avian form and gain the pandemic potential for increased transmissibility between humans, the Hem-Agglutinin (HA) of avian influenza viruses will need to undergo mutations in its Receptor Binding Site (RBS) that bring about an avian to human receptor preference switch. In order to understand the major determinants of virus transmissibility and the pandemic potential of the novel avian influenza viruses, we have determined the crystallographic structure of the novel avian influenza H10N7 A/Turkey/MN/3/79 to 1.96Å and mapped the RBS. The amino acid residues responsible for conferring receptor selectivity were identified by site-direct mutagenesis of recombinant H10 HA proteins. The receptor-binding selectivity of the HAs was determined using sialyl glycan binding assays. Docking models were constructed of the H10 HA in complex with α2, 6-sialic acid (human) and α2, 3-sialic acid (avian) penta-saccharide receptor analogs to ascertain the correlation between the binding assay data and the interactions within the receptor binding pocket. The present findings provided a structure-recognition perspective for the receptor binding properties of the novel avian H10 influenza HA.
Mpho Seleka
National Institute for Communicable Diseases, South Africa
Title: Circulating patterns of influenza B in South Africa: 2005-2014
Biography:
Mpho Seleka has completed Master’s of Medical Science Virology from Stellenbosch University, Faculty of Health Sciences, Department of Pathology, at a Division of Medical Virology. She is a Medical Scientist conducting influenza research (genome sequencing) and surveillance at National Institute for Communicable Diseases (NICD), a division of National Health Laboratory Services (NHLS).
Abstract:
In this study, we aim to describe the circulation patterns of the influenza B/Victoria and B/Yamagata lineages in South Africa and to determine the factors associated with hospitalization for SARI following infection with influenza B/Victoria or B/Yamagata lineages. Data for influenza B in South Africa are limited and the molecular epidemiology was previously described for the period of 1998-2001. The study enrolled patients from three influenza surveillance programs (Viral Watch, SARI and ILI) running in South Africa between year 2005 and 2014. Initially, starting from 2005 to 2008, influenza was diagnosed through virus isolation and antigenic characterization. From 2009, the technology of use was changed to real-time PCR assays. Influenza B vaccine strains recommended for the Southern Hemisphere were mismatched to the dominant circulating lineage in 2005, 2008, 2009 and 2011. Factors associated with infection with a specific influenza B lineage were assessed using the Fisher’s exact test. P-values <0.05 were considered to be statistically significant. Analysis was performed using STATA 13. In SARI cases, the overall frenquency of B/Victoria lineage (181/286 [63.3%]) was higher than that of B/Yamagata lineage (105/286 [36.7%]) from the year 2005 to 2014. The highest incidence of influenza B associated with severe lower respiratory tract infections was seen in the age group 0 to 4 (199/482 [41%]), followed by the age group 25 to 44 (146/482 [40%]), and the age group +65 has the lowest incidence (22/482 [5%]). The overall HIV incidene in the SARI case with influenza B is 99/235 (42%).
Biography:
Sherwin Morgan completed his respiratory care training from Malcolm X College of Respiratory Care in Chicago, IL. He is an advanced respiratory care practitioner with the National Board for Respiratory Care in the United States. He is Clinical Practice and Development /Educator/Research Coordinator for the Department of Respiratory Care Services, Section of Pulmonary and Critical Care Medicine at the University of Chicago Medicine. He has published more than 25 peer review papers in multiple medical journals. He has designed, engineered, and collaborated with a number of research studies with the pulmonary medicine department.
Abstract:
Heliox, a helium-oxygen gas mixture, has been used for many decades to treat obstructive pulmonary disease. The lower density and higher viscosity of heliox relative to nitrogen-oxygen mixtures can significantly reduce airway resistance when an anatomic or partial air-flow obstruction is present. Respiratory infections caused by coronavirus / rhinovirus-enterovirus range from the common cold to severe acute respiratory distress syndrome (SARS). In infants, respiratory syndromes can cause bronchitis, viral bronchiolitis, and pneumonia in variable combinations and may produce enough air-flow obstruction to cause respiratory failure. These viral strains are now documented to come from multiple viral agents and continue to mutate into new strains. I present the case of a 10-month old Hispanic male treated with high flow nasal cannula and heliox to avoid intubation. Before heliox the patient was tachypnea 60 – 70 breaths/min and would desaturate to 84% as measured by pulse oximetry with suprasternal chest retractions. After heliox 70/30, his respiratory rate fell 31 to 38 breaths/min. Nutritional support was implemented on day 1 of heliox administration. He was maintained on heliox either 60/40 or 70/30 for 48 hours and heliox discontinued on day three. He was discharged from PICU on day 10 and discharged from the hospital 7 days later. The benefit of heliox itself appeared to be immediate and served as a bridge to support the patient while time and pharmacologic measures took effect and an underlying infection abated.
Hongxin Zhao
Influenza Surveillance Section Respiratory Diseases Department Centre for Infectious Disease Surveillance and Control (CIDSC) Public Health England UK
Title: Epidemiological and virological characteristics of acute respiratory outbreaks during 2014/15 influenza season in the UK
Biography:
Hongxin Zhao is a Senior Scientist working in the Influenza Surveillance Section, Respiratory Diseases department, Public Health England, Colindale, London, UK. He has completed his PhD from University of Plymouth, UK.
Abstract:
The UK has an established respiratory outbreak reporting system used to monitor the activity and impact of influenza. The 2014/15 season has been dominated by the early circulation of A(H3N2). Outbreak reporting from week 40/2014 to 05/2015 has shown 444 acute respiratory outbreaks; 73% (324/444) in elderly care homes, 14% (62/444) in schools, 12% (54/444) in hospitals,. This compares to 122 outbreaks over the whole of 2013/14, 478 in 2012/13 and 230 in 2011/12. Reports of respiratory outbreaks started to increase from week 49/2014, and peaked in week 03/2015. Of 193 outbreaks with testing information, 90% (174/193) were due to influenza A, Fifty (11%) outbreaks reported fatal cases all in care homes. Fatal case numbers ranged from 1 to 17 (CFR 2.2% to 66.7%). Influenza vaccine uptake was available for 87 care homes with a median uptake of 95.0%, (range 11.9% to 100%). Of 42 care home outbreaks with complete information, all were laboratory confirmed to be associated with influenza (26 A(H3), 15 A(not-subtyped), 1 A(H1N1)pdm09 and 1 B). Influenza vaccine effectiveness (VE) could be calculated for 23 outbreaks in care homes with an overall estimated crude VE of -67.8% (range -384.6% to 100%). The higher numbers of reported influenza A confirmed outbreaks in care home settings in 2014/15 in often highly vaccinated populations compared to the previous three seasons was consistent with the pattern of influenza activity observed, where a drifted A(H3N2) variant has emerged and become the dominant strain.
Gloria Ramirez-Nieto
Universidad Nacional de Colombia
Colombia
South América
Title: Genetic variability of SIV circulating in commercial farms from Colombia, between 2008-2013
Biography:
Gloria Ramirez-Nieto has a degree on Veterinary Medicine from the National University of Colombia, a MSc on Veterinary Microbiology from the Royal Veterinary College, University of London and a PhD from the University of Maryland, College Park. She is currently Associate Professor at the School of Veterinary Medicine, National University of Colombia.
Abstract:
In Colombia, swine influenza virus has been present for over forty years, but only until recently viral isolation of classic and pandemic H1N1 swine influenza viruses demonstrated co-circulation of these viruses in the swine population from the main swine producing regions of the country. There was a clear predominance of the pandemic H1N1 subtype after the 2009 pandemic, but a lack of knowledge about the molecular changes at the virus level due to the appearance of this novel virus in a naïve non-vaccinated population. In this study an analysis of the variability at the nucleotide and amino acid level of the sequence of the hemagglutinin (HA) and neuraminidase (NA) genes of swine influenza viruses reported in Colombia between 2008-2013, was performed. The main focus was to look for changes of evolutionary significance, and phylogenetic trees were constructed accordingly to establish evolutionary relationships with swine influenza virus reported worldwide. Analysis of the HA and NA genes of the Colombian H1N1 swine influenza viruses showed that these were closely related to American and Asian strains. Molecular analysis revealed changes representing synonymous and non-synonymous mutations, and the changes that were associated with non-synonymous mutations, have not yet been reported as a cause of change in the antigenicity of these proteins so far. The positions in the sequences of HA and NA with evolutionary significance, were related to differences associated with the affinity and avidity for the recognition of different conformation of sialic acid receptors in the host cells.