policy decisions working to improve data on rsv to raise...

542019 RESCEU Newsletter9

httpsmailchimpbf8964e78ae0resceu-newsletter9 116

KEYNOTE WP2 team meeting in Amsterdam to discuss health service data

Get to Know the RESCEU Team Papers of the month

Upcoming major RSVrespiratory meetings List of recent RSV papers

KEYNOTE

Harry Campbell

RESCEU WP2 Principal Investigator and WP Co-Leader

Working to improve data on RSV to raise awareness and informpolicy decisions

I co-lead Work-package 2 in RESCEU together with Chuck Knirsch This aims to assembleevidence on the importance of RSV infection and present this to policymakers so that we canraise awareness and knowledge of RSV and make available information that will be needed forvaccine decisions It is hoped that when an effective vaccine becomes available we will beable to shorten the time that policymakers take to make informed decisions

We are assembling national data of health service use associated with RSV from 6 Europeancountries within RESCEU in a coordinated manner We aim to then present these at a high-levelpolicy summit to European policymakers In parallel we are supporting European Centre forDisease Control (ECDC) in taking actions to promote consensus on surveillance approaches toRSV across Europe Improved surveillance systems would generate data which could monitorRSV healthcare burden and its reduction following the introduction of the vaccine It would



also improve our knowledge of RSV seasonality across Europe and of RSV sequence variationacross Europe and over time We are also studying existing guidelines for the management ofbronchiolitis and the use of preventive treatments (Palivizimab) in preterm and other high-riskinfants across Europe We hope then to hold workshops with paediatricians to discuss thereasons for variation and to try to improve and harmonise practices across Europe

At the same time as working on RESCEU I am helping WHO set up pilot RSV surveillanceprojects in GAVI-eligible countries based on the influenza surveillance platform and am withmy colleague Thomas Williams studying global RSV sequence variation with support from NIHIt is hoped that this will give further information on RSV transmission evolution over time andassociations between sequence and disease severity It is a pleasure to work as one of theteam members of RESCEU and make a contribution to improving our understanding of RSV andto controlling this important disease

The Respiratory Viral Epidemiology Group University of Edinburgh including RESCEU early career researchers

Harry Campbell (in the center) and Harish Nair (the RESCEU Coordinator third from the left)

WP2 team meeting in Amsterdam to discuss health service data WP2 will be holding a face-to-face meeting on the 2nd and 3rd of April 2019 in Amsterdam to discuss

the ongoing analysis for Task 21 ldquoNational and regional routine health service datardquo The meeting

will be attended by around 20 people ranging from RESCEU academic partners EFPIA companies and

Affiliated Partners In this occasion the team will review the preliminary analysis of routinely

collected data to explore the healthcare burden of RSV in seven European countries and discuss the

future work towards this task More information on the outcomes of the meeting will beprovided on the next issue of the RESCEU newsletter

Get to Know the RESCEU Team



A series of interviews to members of the RESCEU team where they are interviewed on their vision of RESCEU theircurrent position and how they contribute to the Project

You Li (UEDIN)

You Li (Leo) is a PhD student and part-time research fellow at The University of Edinburgh Scotland

He has a Master of Science in epidemiology and biostatistics and a Bachelor of Medicine in Peking

University China His research interests include modelling global burden of RSV and other

respiratory viruses their transmission and interaction with bacterial infection

Tell us about your professional career

I received training on epidemiology and quantitative analytic skills and obtained my Master of

Science degree in epidemiology and biostatics in the Institute of Reproductive and Child Health

Peking University China After that I moved to Scotland in 2016 and started doctoral study at the

Centre for Global Health Research The University of Edinburgh My PhD project contains two parts

one is the global seasonality of RSV and other respiratory viruses which includes description and

modelling of the seasonality and the other one is the association between viral respiratory infection

and subsequent pneumococcal diseases using the Scottish data Apart from PhD projects I have

been actively involved in modelling global influenza mortality in young children I was also involved

in projects related to the global distribution of Neisseria meningitidis serotypes among healthy

carriers and those with meningococcal diseases Last year I started my post as a part-time research

fellow at The University of Edinburgh and worked as a co-investigator on the WHO research project

about RSV seasonality for countries planning of introduction of RSV prevention strategies I co-

supervised MPH and medical students on topics related to the coinfections of respiratory pathogens

and I am currently supervising online MPH students

Can you please explain a bit about your role at the University of Edinburgh as part of the

RESCEU project

I have been involved in Work Package 1 and 2 of the RESCEU project For WP1 I am responsible for



the Task 16 global seasonality of RSV This task as part of my PhD project describes and models

the global seasonality of RSV aiming to provide important information for health-care planning and

vaccinemAb strategies I am also leading the update of global paediatric RSV disease burden

estimates (Task 110) My role in this task is mainly about the improvement of modelling for global

regional and national estimates of RSV disease burden especially the overall RSV mortality For

WP2 I am involved in Task 21 which assesses the burden of RSV in European countries using

routine health databases I work with Dr Rachel Reeves and the other WP2 partners on the Task 21

analysis plan and provide general advice related to statistical questions

How do you foresee the future of RSV infection after RESCEU project

RESCEU project has created a multi-disciplinary and multi-stakeholder community and has brought

together a diverse group of collaborators As a researcher I think RESCEU provides good

opportunities for researchers from different parts of EU and beyond to work more closely on

reducing RSV infections I would foresee that after RESCEU project many important gaps in

knowledge related to RSV infection would be addressed and sustainability will be one of the

treasures that RESCEU leaves for us For example a sustainable data platform across EU and beyond

will be developed at regional and national levels and will help better quantify the healthcare and

economic impact of RSV

Sabine Tong (Sanofi Pasteur)

Sabine Tong is a confirmed statisticiandata analyst employed by IviData Stats and working as

contractor for Sanofi Pasteur for 2 years


Holding a master of biostatics biomathematics bioinformatics and health from Claude Bernard

University (Lyon France) I have 5 years of experience with programming and statistics in the

pharmaceutical sector Working in contract research organizations I had the opportunity to carry

out different pharmaceutical industriesrsquo projects in various diseases area such as oncology



neurology or rheumatology and to be involved at different steps of the clinical development Since

January 2017 I have been working as a Real World (RW) analyst consultant for Sanofi Pasteur

providing evidences on disease burden and economic burden using different sources of claims

databases (Marketscan CPRD) to support medical decision-making and prevention strategies in

infectious diseases area such as respiratory syncytial virus (RSV) acute otitis media pneumonia

and meningococcal disease

Can you please explain a bit about your role at Sanofi Pasteur as part of the RESCEU project

I have been involved in the RESCEU Work Package 2 (WP2) which aims to assemble existing routinely

collected health and RSV data across Europe (Denmark Netherlands Finland United Kingdom

Scotland Italy and Norway) to inform economics models for WP3

Sanofi Pasteur is supporting the RESCEU WP2 for data in the United Kingdom (UK) using the

combination of primary care from the Clinical Practice Research Datalink (CPRD) linked to

secondary care Hospital Episode Statistics (HES) and mortality data from the Office for National

Statistics (ONS) Having technical and analytical expertise in RW studies and claims databases I

have supported and adapted the data analysis plan to the UK data identifying their strengths and

limits As a Real world analyst my operational role is to carry out the analyses to provide the

estimates of RSV disease burden including childhood sequelae (asthmawheeze) and the economic

burden in the UK


I think that the RESCEU project is an impressive mobilization of capacity and resources

By gathering clinicians epidemiologists scientists health economists statisticians public

health professionals and industries with a strong history of RSV research allowing a close

interaction and collaboration on the questions of RSV impact on health systems and societies

throughout Europe

By building an expanding data platform gathering sustainable knowledge base on RSV through

existing data integration and analysis and via prospective studies and surveillance systems

Thus I believe that the combination of a multidisciplinary approach the availability of several data

sources and the use of similar methods of analysis across EU countries will provide new and robust

evidences an improved understanding and a wider awareness of RSV-associated burden of disease

that will contribute to improve health and wellbeing

Papers of the month

in collaboration with ReSViNET

February 2019

Respiratory syncytial virus and influenza hospitalisations by HIV status in SouthAfrican children



Meredith L McMorrow Stefano Tempia Sibongile Walaza Florette K Treurnicht Jocelyn Moyes

Adam L Cohen Marthi Pretorius Orienka Hellferscee Nicole Wolter Anne von Gottberg Arthemon

Nguweneza Johanna M McAnerney Fathima Naby Omphile MekgoeMarietjie Venter Shabir A

Madhi and Cheryl Cohen The Role of Human Immunodeficiency Virus in Influenza- and Respiratory

Syncytial Virusndashassociated Hospitalizations in South African Children 2011ndash2016 Clin Infect Dis 2019

Feb 1568(5)773-780 doi 101093cidciy532

Summary

McMorrow and colleagues conducted a six-year prospective surveillance for severe respiratory illness

(SRI) in young children under five years old in 3 South African hospitals Both respiratory syncytial

virus (RSV) and influenza associated hospitalisations were laboratory confirmed The median age of

children admitted with RSV and influenza was 44 months vs 139 months with highest annual

hospitalisation rate in infants aged 0-2 months vs 6-11 months respectively This indicates that a

maternal immunisation could serve as an effective strategy for reducing RSV associated

hospitalisations HIV exposure increased both RSV and influenza associated hospitalisation in infants

aged 0-5 months with relative risk (RR) of 14 and 22 while HIV infection was in association with

them in all age group (0-59 months) with RR of 38 and 27 respectively However the impact of the

duration of maternal antiretroviral exposure on RSV or influenza associated hospitalisation was not

measured which could strengthen the study finding

Abstract on Pubmed

February 2019

The endangered future of Syngem a novel bacterium-like particle based needle-freeRSV vaccine

Ascough S Vlachantoni I Kalyan M Haijema BJ Wallin- Weber S Dijkstra-Tiekstra MAhmed MS Roosmalen M van Grimaldi R Zhang Q Leenhouts K Openshaw PJ and ChiuC

Summary

Despite numerous years of research we are still lacking a safe and effective RSVvaccine This process is hindered by numerous problems the lack of a correlate ofprotection being one of themThat this has major consequences for vaccinedevelopment is illustrated by the study performed by Stephanie Ascough PeterOpenshaw and colleagues In their paper they describe the results of a randomizedcontrolled phase 1 trial of a novel needle-free RSV vaccine SynGEM The vaccine isbased on a stable pre-fusion F antigen of the virus and uses a bacterium-like-particle(BLP) as an immune-enhancing carrier The study confirms that the vaccine is safe andthat it is capable of inducing a mild (about 2 to 3-fold) but prolonged increase in RSV-specific antibodies However the study didnrsquot reach the endpoint threshold and fornow SynGEM is withheld from proceeding to next phase trials



This study illustrates that the lack of a correlate of protection brings an uncertainty tothe table which could lead to the premature termination of a potentially effective RSVvaccine The use of a human challenge model (HCM) in RSV vaccine development wouldoffer the possibility to circumvent this insecurity Furthermore it might accelerate RSV-vaccine development

January 2019

Sample size required to detect the effect of RSV vaccination on recurrent wheezing

Riddell CA Bhat N Bont LJ Dupont WD Feikin DR Fell DB Gebretsadik T Hartert TV Hutcheon

JA Karron RA Nair H Reiner RC Jr Shi T Sly PD Stein RT Wu P Zar HJ Ortiz JR WHO Technical

Working Group on Respiratory Syncytial Virus Vaccination During Pregnancy to Prevent Recurrent

Childhood Wheezing Informing randomized clinical trials of respiratory syncytial virus vacciantion

during pregnancy to prevent recurrent childhood wheezing A sample size analysis Vaccine 2018

Dec 1836(52)8100-8109 doi 101016jvaccine201810041 Epub 2018 Nov 22

Summary

Riddell and colleagues investigated the feasibility of utilizing maternal RSV vaccine trials to detect

the effect of RSV vaccine on childhood recurrent wheezing The model inputs came from systematic

reviews and meta-analyses including the following parameters vaccine efficacy allocation ratio

rate of early severe RSV illness risk of recurrent wheezing at age 3 and increased risk of RSV

infection on recurrent wheezing The result showed that among the plausible scenarios the lowest

sample size required was 6196 mother-infant pairs per trial arm and 75 and 47 of plausible

scenarios required more (gt31060 and gt100000) Unfortunately all these scenarios exceed the size

of the only current phase III trial of RSV vaccination in pregnant women which indicated the

impossibility of demonstrating an effect on recurrent wheezing Further efforts are needed to plan

for post-licensure studies to inform the impact of RSV vaccines given during pregnancy on long term

respiratory illness

Abstract on PubMed

January 2019

Miniature lungs the road towards a better model to study RSV disease

Sachs N Papaspyropoulos A Zomer-van Ommen DD Heo I Boumlttinger L Klay D Weeber F Huelsz-

Prince G Iakobachvili N Amatngalim GD de Ligt J van Hoeck A Proost N Viveen MC Lyubimova

A Teeven L Derakhshan S Korving J Begthel H Dekkers JF Kumawat K Ramos E van Oosterhout

MF Offerhaus GJ Wiener DJ Olimpio EP Dijkstra KK Smit EF van der Linden M Jaksani S van de

Ven M Jonkers J Rios AC Voest EE van Moorsel CH van der Ent CK Cuppen E van Oudenaarden

A Coenjaerts FE Meyaard L Bont LJ Peters PJ Tans SJ van Zon JS Boj SF Vries RG Beekman

JM Clevers H



Long-term expanding human airway organoids for disease modeling EMBO J 2019 Jan 14 pii

e100300 doi 1015252embj2018100300 [Epub ahead of print]

Summary

Sachs from UMC Utrecht developed human airway organoids (miniature lungs) that offer the

possibility to study RSV in an human in vitro model The authors show that RSV replicates well in

human airway organoids and that infection can be inhibited after pre-treatment with palivizumab

Furthermore RSV caused epithelial changes that mimic disease characteristics such as epithelial

shedding syncytia formation and alterations of the cytoskeleton Also there was an upregulation

of antiviral genes and an enhanced secretion of cytokines such as IP-10 Both of these findings

reflect the immune responses following RSV infection in infants Lastly human airway organoids

offer the possibility to study the interaction between immune cells and the RSV infected epithelium

The latter is of major importance to increase the knowledge on RSV immune signalling

Altogether RSV ndash infected airway organoids offer the possibility to study numerous aspects of RSV

disease including airway remodelling immune cell interaction and treatment possibilities

Written by Sjanna Besteman

Abstract on PubMed

December 2018

Severy Morbidity and Mortality Associated with Respiratory Syncytial Vires versus Influenza

Infection in Hospitalized Older Adults

Bradley Ackerson Hung Fu Tseng Lina S Sy Zendi Solano Jeff Slezak Yi Luo Christine A Fischetti

Vivek Shinde in Clin Infect Dis 2018 Nov 19 doi 101093cidciy991 [Epub ahead of print]

Summary

A large cohort of adults gt=60 years hospitalised with laboratory confirmed RSV or influenza infection

during 5 consecutive seasons were investigated The study showed that older adults hospitalised

with RSV were slightly older and more likely to have baseline co-morbidity conditions than those

with influenza Regarding hospitalisation outcome they had longer length of hospital stay greater

odds of pneumonia ICU admission COPD exacerbation chronic bronchiolitis emphysema and one-

year mortality than those with influenza even after adjustment for baseline comorbidities This

might reflect the increased use of antiviral therapies for influenza in recent years and differences of

clinical severity in RSV and influenza infection The findings highlight the substantial morbidity and

mortality associated with RSV infection in hospital settings in the expanding population of older

adults who could benefit from RSV vaccines and antivirals

Abstract on PubMed



December 2018

Proinflammatory Effects of Respiratory Syncytial VirusndashInduced Epithelial HMGB1 on Human

Innate Immune Cell Activation

Kempaiah Rayavara Alexander Kurosky dagger Susan J Stafford dagger Nisha J GargAllan R Brasier Dagger x

Roberto P Garofalo and Yashoda M HosakoteJ Immunol 2018 2012753-2766 Prepublished online

1 October 2018 httpwwwjimmunolorgcontent20192753

doi 104049jimmunol1800558

Summary

The first epithelial molecular events upon infection define the size and direction of the

inflammatory response which ultimately defines disease in RSV infected patients Rayavara and

colleagues shed a light on this complex process Previously this group showed that RSV promotes the

release of high mobility group box 1 (HMGB1) by airway epithelial cells HMGB1 is a nuclear protein

which becomes an alarmin after secretion to the extracellular space to induce an inflammatory

response

In the current study they show that HMGB1 forms a link between the infected respiratory

epithelium and the response by immune cells After RSV infection HMGB1 is expressed by airway

epithelial cells This process is dependent on TLR4 and is mediated by the MAPK and NF-kB pathway

Blocking of TLR4 or the NF-kB pathway in AECs decreases the expression of HMGB1 Next they show

that HMGB1 stimulates primary immune cells such as monocytes and macrophages to produce

inflammatory cytokines and chemokines

Blocking the HMGB1 pathway under an umbrella of antiviral treatment might limit immune

pathology and thereby ameliorate the course of disease in children with RSV infection

Abstract on PubMed

Upcoming major RSVrespiratory meetings

WP2 RSV SURVEILLANCE MEETING ON THE DEVELOPMENT OF A HARMONIZED RSVSURVEILLANCE SYSTEM IN EUROPE

As previously announced we are on the eve of the Surveillance Meeting where WP2team is gathering experts from Public Health agencies and academic bodies to discussand develop a suggested framework for an RSV surveillance protocol in Europe basingdiscussions on the 2017 ECDC RSV surveillance survey In this occasion RESCEUpartners SSI RIVM UEDIN PENTA and Affiliated Partners NIPH (N) THL (FIN) NIVEL(NL) will meet representatives of ECDC ndash updating on RSV Atlas and ECDC perspectiveon RSV surveillance ndash WHO ndash giving updates on ongoing RSV pilot surveillance project ndashand many more National Health institutes in Europe



Updates on feasibility assessments for various surveillance systems framework designand further strategical content after the meeting

MARCH 20 ndash 21 2019

COPENHAGEN DENMARK

IMMUNOLOGICAL ASSAYS AND CORRELATES OF PROTECTION FOR NEXT GENERATIONINFLUENZA VACCINES

The Conference on Immunological assays and Correlates of Protection for NextGeneration Influenza Vaccines taking place in Siena (IT) in the end of March willgather scientists from academia industry and government public healthstandardisation and regulatory agencies that develop and evaluate seasonal andpandemic influenza vaccines to focus on relevant steps to develop next-generationinfluenza vaccines More information agenda are available on the website andregistration is possible till the 21st of March

MARCH 31 ndash APRIL 2 2019

SIENA ITALY

10TH EDITION OF THE OPTIONS FOR THE CONTROL OF INFLUENZA IRSVCONFERENCE

The 10th edition of the ISRV Conference on Options for the Control of Influenza will beheld between the 28th of August and the 1st of September in Singapore This is thelargest international conference exclusively dedicated to influenza prevention controland treatment including seasonal flu and pandemic preparedness Highlights of themeeting include new tracks on influenza co-infections with other viral pathogens andkey issues for policy making - special sessions to showcase the latest developments inChinese-speaking countries - pre-conference workshops on a wide variety of topicsincluding technology mathematical modelling and bioinformatics Registration areopening soon See website

AUGUST 28 ndash SEPTEMBER 1 2019

SINGAPORE

List of recent RSV papers

February

Cullen LM Schmidt MR Torres GM Capoferri AA Morrison TG Comparison of Immune Responses to DifferentVersions of VLP Associated Stabilized RSV Pre-Fusion F Protein Vaccines (Basel)157(1)

Manley GCA Parker LC Zhang Y Emerging Regulatory Roles of Dual-Specificity Phosphatases in Inflammatory



Airway Disease Int J Mol Sci 520(3)

Soudani N Caniza MA Assaf-Casals A Shaker R Lteif M Su Y Tang L Akel I Muwakkit S Chmaisse A Homsi MDbaibo G Zaraket H Prevalence and characteristics of acute respiratory virus infections in pediatric cancerpatients

J Med Virol in press

Cullen LM Schmidt MR Morrison TG Effect of Previous Respiratory Syncytial Virus Infection on Murine ImmuneResponses to F and G Protein Containing Virus-like Particles J Virol in press

Alansari K Toaimah FH Almatar DH El Tatawy LA Davidson BL Qusad MIM Monoclonal Antibody Treatmentof RSV Bronchiolitis in Young Infants A Randomized Trial Pediatrics in press

Ek P Boumlttiger B Dahlman D Hansen KB Nyman M Nilsson AC A combination of naso- and oropharyngeal swabsimproves the diagnostic yield of respiratory viruses in adult emergency department patients Infect Dis(Lond)141-8

Velaacutezquez-Cervantes MA Martiacutenez-Castillo M Gonzaacutelez-Garciacutea LD Vargas-Paviacutea TA Martiacutenez-Salazar MG Mancilla-Herrera I Leoacuten-Reyes G Garciacutea-Cordero J Helguera-Repetto AC Leoacuten-Juaacuterez M The BeWo cell line derived from ahuman placental choriocarcinoma is permissive for respiratory syncytial virus infection Virus Genes in press

Ascough S Vlachantoni I Kalyan M Haijema BJ Wallin-Weber S Dijkstra-Tiekstra M Ahmed MS van Roosmalen MGrimaldi R Zhang Q Leenhouts K Openshaw PJ Chiu C Local and Systemic Immunity Against RSV Induced by aNovel Intranasal Vaccine A Randomised Double- Blind Placebo-Controlled Trial Am J Respir Crit Care Med inpress

Cheng J Zhao C Lee HJ Does influenza vaccination or RSV prophylaxis impact resource utilization for childrenafter the diagnosis of airway disorders Int J Pediatr Otorhinolaryngol 612020-24

Green CA Sande CJ Scarselli E Capone S Vitelli A Nicosia A Silva-Reyes L Thompson AJ de Lara CM Taylor KSHaworth K Hutchings CL Cargill T Angus B Klenerman P Pollard AJ Novel genetically-modified chimpanzeeadenovirus and MVA-vectored respiratory syncytial virus vaccine safely boosts humoral and cellular immunity inhealthy older adults J Infect in press

Servia-Dopazo M Purrintildeos-Hermida MJ Peacuterez S Garciacutea J Malvar-Pintos A en nombre del Grupo del Sistema deVigilancia Microbioloacutegica de la Gripe en Galicia Los miembros del Grupo del Sistema de Vigilancia Microbioloacutegica dela Gripe en Galicia que han contribuido a redactar este artiacuteculo son Usefulness of the microbiological surveillanceof respiratory syncytial virus in Galicia (Spain) 2008-2017 Gac Sanit in press Spanish

Voelker DR Numata M Phospholipid regulation of innate immunity and respiratory viral infection J Biol Chemin press

Xie Q Wang Z Ni F Chen X Ma J Patel N Lu H Liu Y Tian JH Flyer D Massare MJ Ellingsworth L Glenn G SmithG Wang Q Structure basis of neutralization by a novel site IIIV antibody against respiratory syncytial virusfusion protein PLoS One 714(2)e0210749

Manuel B Hackbusch M Tabatabai J Hoos J Peters R Schnee SV Ihling CM Schnitzler P Pfeil J RSVpredict AnOnline Tool to Calculate the Likelihood of Respiratory Syncytial Virus Infection in Children Hospitalized WithAcute Respiratory Disease Pediatr Infect Dis J in press

Battles MB McLellan JS Respiratory syncytial virus entry and how to block it Nat Rev Microbiol in press

Crim RL Kumari S Jayanti P Audet S Kulkarni A Beeler J Development of Luciferase ImmunoprecipitationSystems (LIPS) Assay to Detect IgG Antibodies against Human Respiratory Syncytial Virus G-GlycoproteinVaccines(Basel) 17(1)

Antalis E Spathis A Kottaridi C Kossyvakis A Pastellas K Tsakalos K Mentis A Kroupis C Tsiodras S Th17 serumcytokines in relation to laboratory-confirmed respiratory viral infection A pilot study J Med Virol in press

Nikonova AA Pichugin AV Chulkina MM Lebedeva ES Gaisina AR Shilovskiy IP Ataullakhanov RI Khaitov MR KhaitovRM The TLR4 Agonist Immunomax Affects the Phenotype of Mouse Lung Macrophages during RespiratorySyncytial Virus Infection Acta Naturae10(4)95-99

Sarkar I Zardini Buzatto A Garg R Li L van Drunen Littel-van den Hurk S Metabolomic and ImmunologicalProfiling of Respiratory Syncytial Virus Infection after Intranasal Immunization with a Subunit Vaccine



CandidateJ Proteome Res in press

Jorquera PA Mathew C Pickens J Williams C Luczo JM Tamir S Ghildyal R Tripp RA Verdinexor (KPT-335) aSelective Inhibitor of Nuclear Export Reduces Respiratory Syncytial Virus Replication In Vitro J Virol 593(4)

January

Do LAH Tse R Nathanielsz J Anderson J Ong DS Chappell K Mulholland K Licciardi PV An Improved and HighThroughput Respiratory Syncytial Virus (RSV) Micro-neutralization Assay J Vis Exp 26(143)

Salinas FM Vaacutezquez L Gentilini MV O Donohoe A Regueira E Nabaes Jodar MS Viegas M Michelini FM Hermida GAlcheacute LE Bueno CA Aesculus hippocastanum L seed extract shows virucidal and antiviral activities againstrespiratory syncytial virus (RSV) and reduces lung inflammation in vivo Antiviral Res 311641-11

High epidemic burden of RSV disease coinciding with genetic alterations causing amino acid substitutions inthe RSV G-protein during the 20162017 season in The Netherlands

Vos LM Oosterheert JJ Kuil SD Viveen M Bont LJ Hoepelman AIM Coenjaerts FEJ J Clin Virol 2019 Jan 2311220-26 doi 101016jjcv201901007 [Epub ahead of print]

Souty C Masse S Valette M Behillil S Bonmarin I Pino C Turbelin C Capai L Vilcu AM Lina B van der Werf SBlanchon T Falchi A Hanslik T Baseline characteristics and clinical symptoms related to respiratory virusesidentified among patients presenting with influenza-like illness in primary care Clin Microbiol Infect 2019 inpress

Price RHM Graham C Ramalingam S Association between viral seasonality and meteorological factors Sci Rep309(1)929

Zhai J Zou Y Liu J Jin X Ma C Li J Guo R Huang B Analysis of the predicting factors of recurrent wheezing ininfants Ital J Pediatr 2945(1)19

Vos LM Bruning AHL Reitsma JB Schuurman R Riezebos-Brilman A Hoepelman AIM Oosterheert JJ Rapidmolecular tests for influenza respiratory syncytial virus and other respiratory viruses a systematic review ofdiagnostic accuracy and clinical impact studies Clin Infect Dis in press

Cody Meissner H Patient equity and respiratory syncytial virus Immunoprophylaxis Isr J Health Policy Res288(1)15

Gentile A Lucion MF Juarez MDV Areso MS Bakir J Viegas M Mistchenko A Burden of Respiratory Syncytial VirusDisease and Mortality Risk Factors in Argentina 18 Years Active Surveillance in a Childrenacutes Hospital PediatrInfect Dis J in press

Kuypers J Impact of rapid molecular detection of respiratory viruses on clinical outcomes and patientmanagement J Clin Microbiol in press

Liang B Kabatova B Kabat J Dorward DW Liu X Surman S Liu X Moseman AP Buchholz UJ Collins PL MunirSEffects of alterations to the CX3C motif and secreted form of human respiratory syncytial virus (RSV) G proteinon immune responses to a parainfluenza virus vector expressing the RSV G protein J Virol in press

Oh DS Kim TH Lee HK Differential Role of Anti-Viral Sensing Pathway for the Production of Type I Interferon βinDendritic Cells and Macrophages Against Respiratory Syncytial Virus A2 Strain Infection Viruses1511(1)

Topoulos S Giesa C Gatermann S Fussen R Lemmen S Ewig S Analysis of acute respiratory infections due toinfluenza virus A B and RSV during an influenza epidemic 2018 Infection in press

Sachs N Papaspyropoulos A Zomer-van Ommen DD Heo I Boumlttinger L Klay D Weeber F Huelsz-Prince GIakobachvili N Amatngalim GD de Ligt J van Hoeck A Proost N Viveen MC Lyubimova A Teeven L Derakhshan SKorving J Begthel H Dekkers JF Kumawat K Ramos E van Oosterhout MF Offerhaus GJ Wiener DJ Olimpio EPDijkstra KK Smit EF van der Linden M Jaksani S van de Ven M Jonkers J Rios AC Voest EE van Moorsel CH vander Ent CK Cuppen E van Oudenaarden A Coenjaerts FE Meyaard L Bont LJ Peters PJ Tans SJ van Zon JS Boj SFVries RG Beekman JM Clevers H Long-term expanding human airway organoids for disease modeling EMBO J1538(4)

Pugh S Heaton MJ Hartman B Berrett C Sloan C Evans AM Gebretsadik T Wu P Hartert TV Lee RL Estimatingseasonal onsets and peaks of bronchiolitis with spatially and temporally uncertain data Stat Med in press

Sonawane AA Shastri J Bavdekar SB Respiratory Pathogens in Infants Diagnosed with Acute Lower Respiratory



Tract Infection in a Tertiary Care Hospital of Western India Using Multiplex Real Time PCR Indian J Pediatr inpress

Korsten K Blanken MO Buiteman BJM Nibbelke EE Naaktgeboren CA Bont LJ Wildenbeest JG RSV hospitalizationin infancy increases the risk of current wheeze at age 6 in late preterm born children without atopicpredisposition Eur J Pediatr in press

Zou X Chang K Wang Y Li M Zhang W Wang C Lu B Xiong Z Han J Zhang Y Zhao J Cao B for CAP-ChinaNetwork Comparison of the Cepheid Xpert Xpress FluRSV assay and commercial real-time PCR for the detectionof influenza A and influenza B in a prospective cohort from China Int J Infect Dis in press

Esneau C Raynal B Roblin P Brucircleacute S Richard CA Fix J Eleacuteoueumlt JF Galloux M Biochemical characterization of therespiratory syncytial virus N0-P complex in solution J Biol Chem in press

Guerra-Maupome M Palmer MV McGill JL Sacco RE Utility of the Neonatal Calf Model for Testing Vaccines andIntervention Strategies for Use against Human RSV Infection Vaccines (Basel) 87(1)

Ayegbusi OT Ajagbe OA Afowowe TO Aransi AT Olusola BA Awogbindin IO Ogunsemowo OO Faneye AO OdaiboGN Olaleye DO Virus genes and host correlates of pathology are markedly reduced during respiratory syncytialand influenza virus co-infection in BALBc mice Heliyon 35(1)e01094

Hardelid P Verfuerden M McMenamin J Smyth RL Gilbert R The contribution of child family and health servicefactors to respiratory syncytial virus (RSV) hospital admissions in the first 3 years of life birth cohort study inScotland 2009 to 2015 Euro Surveill 24(1)

Xing Y Proesmans M New therapies for acute RSV infections where are we

Eur J Pediatr178(2)131-138

Paes B Kim D Saleem M Wong S Mitchell I Lanctot KL and the CARESS investigators Respiratory syncytial virusprophylaxis in infants with congenital airway anomalies compared to standard indications and complex medicaldisorders Eur J Pediatr in press

Tahamtan A Askari FS Bont L Salimi V Disease severity in respiratory syncytial virus infection Role of hostgenetic variation Rev Med Virol 4e2026

Science M Akseer N Asner S Allen U Risk stratification of immunocompromised children including pediatrictransplant recipients at risk of severe respiratory syncytial virus disease Pediatr Transplant 3e13336

Butler J Gunnarsson R Traves A Marshall H Severe Respiratory Syncytial Virus Infection in Hospitalized ChildrenLess Than 3 Years of Age in a Temperate and Tropical Climate Pediatr Infect Dis J38(1)6-11

December

Ko SH Liau YJ Chi YH Lai MJ Chiang YP Lu CY Chang LY Tarn WY Huang LM Interference of DNAJB6MRJ IsoformSwitch by Morpholino Inhibits Replication of HIV-1 and RSV Mol Ther Nucleic Acids1014251-261

Wouters Y Keyaerts E Rector A Van Even E Vissers S Koletzki D Pattery T Rousseau E Van Ranst M LaffutWComparison of the Idyllatrade Respiratory (IFV-RSV) panel with the GeneXpert Xpertreg FluRSV assay aretrospective study with nasopharyngeal and midturbinate samples Diagn Microbiol Infect Dis in press

Korsun N Angelova S Trifonova I Georgieva I Voleva S Tzotcheva I Mileva S Ivanov I Tcherveniakova TPerenovska P Viral pathogens associated with acute lower respiratory tract infections in children younger than 5years of age in Bulgaria Braz J Microbiol50(1)117-125

Turi KN Wu P Escobar GJ Gebretsadik T Ding T Walsh EM Li SX Carroll KN Hartert TV Prevalence of infantbronchiolitis-coded healthcare encounters attributable to RSV Health Sci Rep 121(12)e91

Belongia EA King JP Kieke BA Pluta J Al-Hilli A Meece JK Shinde V Clinical Features Severity and Incidenceof RSV Illness During 12 Consecutive Seasons in a Community Cohort of Adults ge60 Years Old Open Forum InfectDis 275(12)ofy316

Hijano DR Maron G Hayden RT Respiratory Viral Infections in Patients With Cancer or Undergoing HematopoieticCell Transplant Front Microbiol 1293097 Review

Hurley LP Allison MA Kim L OLeary ST Crane LA Brtnikova M Beaty BL Allen KE Poser S Lindley MC Kempe



APrimary care physicians perspectives on respiratory syncytial virus (RSV) disease in adults and apotential RSV vaccine for adults Vaccine 2137(4)565-570

Gomi R Sharma A Wu W Worgall S Neonatal Genetic Delivery of Anti-Respiratory Syncytial Virus (RSV) Antibodyby Non-Human Primate-Based Adenoviral Vector to Provide Protection against RSV Vaccines (Basel)297(1)

Kombe IK Munywoki PK Baguelin M Nokes DJ Medley GF Model-based estimates of transmission of respiratorysyncytial virus within households Epidemics in press

Mansbach JM Hasegawa K Piedra PA Avadhanula V Petrosino JF Sullivan AF Espinola JA Camargo CAJrHaemophilus-dominant nasopharyngeal microbiota is associated with delayed clearance of respiratorysyncytial virus in infants hospitalized for bronchiolitis J Infect Dis in press

Schmidt RLJ Simon A Popow-Kraupp T Laggner A Haslacher H Fritzer-Szekeres M Redlberger-Fritz M Mayer FJ Anovel PCR-based point-of-care method facilitates rapid efficient and sensitive diagnosis of influenza virusinfection Clin Microbiol Infect in press

Johnson JK Harris FL Ping XD Gauthier TW Brown LASRole of zinc insufficiency in fetal alveolar macrophagedysfunction and RSV exacerbation associated with fetal ethanol exposure Alcohol in press

Asha K Kumar P Sanicas M Meseko CA Khanna M Kumar B Advancements in Nucleic Acid Based Therapeuticsagainst Respiratory Viral Infections J Clin Med in press Review

Caini S de Mora D Olmedo M Portugal D Becerra MA Mejiacutea M Pacurucu MC Ojeda J Bonaccorsi G Lorini C PagetJ Bruno A The epidemiology and severity of respiratory viral infections in a tropical country Ecuador 2009-2016 J Infect Public Health in press

Gates M Shulhan-Kilroy J Featherstone R MacGregor T Scott SD Hartling L Parent experiences and informationneeds related to bronchiolitis A mixed studies systematic review Patient Educ Couns in press

Tang W Li M Liu Y Liang N Yang Z Zhao Y Wu S Lu S Li Y Liu F Small molecule inhibits respiratory syncytialvirus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane FASEBJ in press

Appak Ouml Duman M Belet N Sayiner AA Viral respiratory infections diagnosed by multiplex polymerase chainreaction in pediatric patients J Med Virol in press

Brini I Bhiri S Ijaz M Bouguila J Nouri-Merchaoui S Boughammoura L Sboui H Hannachi N Boukadida J Temporaland climate characteristics of respiratory syncytial virus bronchiolitis in neonates and children in SousseTunisia during a 13-year surveillance Environ Sci Pollut Res Int in press

Smith SE Busse DC Binter Š Weston S Diaz Soria C Laksono BM Clare S Van Nieuwkoop S Van den Hoogen BGClement M Marsden M Humphreys IR Marsh M de Swart RL Wash RS Tregoning JS Kellam P Interferon-inducedTransmembrane Protein 1 restricts replication of virus that enter cells via the plasma membrane J Virol inpress

Jallow S Agosti Y Kgagudi P Vandecar M Cutland CL Simotildees EAF Nunes MC Suchard MS Madhi SA Impairedtransplacental transfer of respiratory syncytial virus (RSV) neutralizing antibodies in HIV-infected compared toHIV-uninfected pregnant women Clin Infect Dis in press

Ban J Lee NR Lee NJ Lee JK Quan FS Inn KS Human Respiratory Syncytial Virus NS 1 Targets TRIM25 toSuppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling Viruses10(12)

Ginsberg GM Somekh E Schlesinger Y Should we use Palivizumab immunoprophylaxis for infants againstrespiratory syncytial virus - a cost-utility analysis Isr J Health Policy Res7(1)63

Naz R Gul A Javed U Urooj A Amin S Fatima Z Etiology of acute viral respiratory infections common inPakistan A review Rev Med Virol12e2024

Wabe N Li L Lindeman R Yimsung R Dahm MR McLennan S Clezy K Westbrook JI Georgiou A Impact of rapidmolecular diagnostic testing of respiratory viruses on outcomes of adults hospitalised with respiratory illness Amulticentre quasi-experimental study J Clin Microbiol in press

Al Harbi AS War against respiratory syncytial virus An 8-year experience at a tertiary hospital Saudi MedJ39(12)1200-1206



Homaira N Briggs N Oei JL Hilder L Bajuk B Jaffe A Omer SB Association of age at first severe RSV diseasewith subsequent risk of severe asthma a population-based cohort study J Infect Dis in press

Groves HE Shields MD RSV and asthma inception - cause and effect or shared susceptibilityJ Infect Dis in press

Reuter SE Evans AM Ward MB Reducing Palivizumab Dose Requirements Through Rational Dose RegimenDesignCPT Pharmacometrics Syst Pharmacol8(1)26-33

Toizumi M Suzuki M Nguyen HAT Le MN Ariyoshi K Moriuchi H Hashizume M Dang DA Yoshida LM Viral AcuteRespiratory Illnesses in Young Infants Increase the Risk of Respiratory Readmission Pediatr Infect DisJ37(12)1217-1222

For more information visit us at wwwresc-euorg Sign up for RESCEU-Newsletter here Next issue in June

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreementNordm 116019 This Joint Undertaking receives support from the European Unionrsquos Horizon 2020 research and innovation

programme and EFPIA

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Synapse Research Management SL middot Carrer Diputacioacute 237 Atico 3ordm middot Barcelona Barcelona 08007 middot Spain





also improve our knowledge of RSV seasonality across Europe and of RSV sequence variationacross Europe and over time We are also studying existing guidelines for the management ofbronchiolitis and the use of preventive treatments (Palivizimab) in preterm and other high-riskinfants across Europe We hope then to hold workshops with paediatricians to discuss thereasons for variation and to try to improve and harmonise practices across Europe

At the same time as working on RESCEU I am helping WHO set up pilot RSV surveillanceprojects in GAVI-eligible countries based on the influenza surveillance platform and am withmy colleague Thomas Williams studying global RSV sequence variation with support from NIHIt is hoped that this will give further information on RSV transmission evolution over time andassociations between sequence and disease severity It is a pleasure to work as one of theteam members of RESCEU and make a contribution to improving our understanding of RSV andto controlling this important disease

The Respiratory Viral Epidemiology Group University of Edinburgh including RESCEU early career researchers

Harry Campbell (in the center) and Harish Nair (the RESCEU Coordinator third from the left)

WP2 team meeting in Amsterdam to discuss health service data WP2 will be holding a face-to-face meeting on the 2nd and 3rd of April 2019 in Amsterdam to discuss

the ongoing analysis for Task 21 ldquoNational and regional routine health service datardquo The meeting

will be attended by around 20 people ranging from RESCEU academic partners EFPIA companies and

Affiliated Partners In this occasion the team will review the preliminary analysis of routinely

collected data to explore the healthcare burden of RSV in seven European countries and discuss the

future work towards this task More information on the outcomes of the meeting will beprovided on the next issue of the RESCEU newsletter

Get to Know the RESCEU Team




You Li (UEDIN)





















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respiratory illness

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SINGAPORE


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policy decisions working to improve data on rsv to raise...

Documents