Project

Back to overview

Respiratory viruses: improving molecular diagnostic tools and assessment of clinical impact in lung transplant recipients

English title Respiratory viruses: improving molecular diagnostic tools and assessment of clinical impact in lung transplant recipients
Applicant Kaiser Laurent
Number 127160
Funding scheme Project funding
Research institution Laboratoire de Virologie Service des Maladies Infectieuses Hôpitaux Universitaires de Genève
Institution of higher education University of Geneva - GE
Main discipline Internal Medicine
Start/End 01.01.2010 - 31.12.2012
Approved amount 468'000.00
Show all

All Disciplines (2)

Discipline
Internal Medicine
Medical Microbiology

Keywords (8)

transplantation; viral infections; graft rejection; Rhinovirus; Respiratory virus; Lung transplant recipients; Tanzania; Cycstic Fibrosis

Lay Summary (English)

Lead
Our reserach focus on the clinical impact of respiratory viruse and particularly rhinovirus in different populations. Beyond clincial investigations we also investigate basic features of rhinovirus genomic adapatation.
Lay summary
Our research focuses on respiratory viruses and human picornaviruses (rhinovirus and enterovirus). Rhinoviruses are the most frequent cause of respiratory infections in humans and enteroviruses the first cause of acute meningitis. Both clinical and basic researches in the field are conducted under the same roof providing the opportunity to generate synergies and translational projects. Most of our initial clinical research in the field was possible thanks to the development of appropriate molecular tools, and the creation of an adapted virology platform. This platform is used for the detection of respiratory viruses in the upper and lower respiratory tract and offers an attractive tool for collaborations. We established prospective cohort studies in different populations at-risk of complications and could thus assess the epidemiology and the clinical impact of these agents. Thanks to these projects we made the following original observations. In lung transplant recipients we estimate the risk of respiratory viral infections, their clinical consequences, and showed that rhinovirus was a cause of chronic infections. We also challenged the frequently accepted notion that these viruses could cause acute graft rejection. In these investigations we could also analyzed carefully rhinovirus genome variation and adaptation in its human host. In two large collaborations investigations in children with colleague in Bern and Basel we not only designed but also conducted the experiments. In the first one we analyzed rhinovirus viral load in lower respiratory specimens of children with Cystic Fibrosis. In the second one we conducted several thousands of virological tests in a large cohort of Tanzanian children with fever and could establish the microbiological cause of their illness.
Direct link to Lay Summary Last update: 11.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Role of rhinovirus load in the upper respiratory tract and severity of symptoms in lung transplant recipients
Ambrosioni J Bridevaux PO Aubert JD Soccal P Wagner G Kaiser L. (2015), Role of rhinovirus load in the upper respiratory tract and severity of symptoms in lung transplant recipients, in Journal of Clinical Virology, 64(March 2015), 1-5.
Epidemiology of viral respiratory infections in a tertiary care centre in the era of molecular diagnosis, Geneva, Switzerland, 2011-2012
Ambrosioni J Bridevaux PO Wagner G Mamin A Kaiser L. (2014), Epidemiology of viral respiratory infections in a tertiary care centre in the era of molecular diagnosis, Geneva, Switzerland, 2011-2012, in Clinical Microbiol. Infect., 9, 0578-0584.
Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study
Pierre-Olivier Bridevaux and all (2014), Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study, in thorax, 69, 32-38.
Critical analysis of rhinovirus RNA load quantification by real-time reverse transcription-PCR.
Schibler Manuel, Yerly Sabine, Vieille Gaël, Docquier Mylène, Turin Lara, Kaiser Laurent, Tapparel Caroline, Zdobnov Evgeny, Kaiser Laurent (2012), Critical analysis of rhinovirus RNA load quantification by real-time reverse transcription-PCR., in Journal of clinical microbiology, 50(9), 2868-72.
High rhinovirus burden in lower airways of children with cystic fibrosis.
Kieninger12 Elisabeth, Singer1 Florian, Tapparel3 Caroline, Alves12 Marco P, Latzin12 Philipp, Tan4 Hui-Leng, Bossley4 Cara, Casaulta1 Carmen, Bush4 Andrew, Davies4 Jane C, Kaiser3 Laurent, Regamey12 Nicolas (2012), High rhinovirus burden in lower airways of children with cystic fibrosis., in Chest, 1-29.
Picornavirus and enterovirus diversity with associated human diseases.
Tapparel Caroline, Siegrist Fredy, Petty Tom J, Kaiser Laurent, Turin Lara, Kaiser Laurent, Tapparel Caroline (2012), Picornavirus and enterovirus diversity with associated human diseases., in Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in i, 14C, 282-293.
Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies.
Vu D-L, Bridevaux P-O, Aubert J-D, Soccal P M, Kaiser L (2011), Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies., in American journal of transplantation : official journal of the American Society of Transplantation an, 11(5), 1071-8.
Rhinovirus genome variation during chronic upper and lower respiratory tract infections.
Tapparel Caroline, Cordey Samuel, Junier Thomas, Farinelli Laurent, Van Belle Sandra, Soccal Paola M, Aubert John-David, Zdobnov Evgeny, Kaiser Laurent (2011), Rhinovirus genome variation during chronic upper and lower respiratory tract infections., in PloS one, 6(6), 21163-21163.
Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients.
Soccal PM Aubert JD Bridevaux PO Garbino J Thomas Y Rochat T Rochat TS Meylan P Tapparel C (2010), Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients., in Clinical Infectious Diseases, 51 (2)(2010 Jul 1), 163-170.

Collaboration

Group / person Country
Types of collaboration
Tropical Institute Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
University of Berne - InselSpital Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
113426 Rhinoviruses associated with lower respiratory diseases: genetic variability and replications site 01.01.2007 Project funding
120651 Clinical impact and pathophysiological mechanisms of rhinovirus infections in cystic fibrosis lung disease 01.01.2009 Project funding

Abstract

Respiratory viruses are the most frequent cause of infections in humans and can promote seriouscomplications in immunocompromised subjects or those with chronic lung diseases. In lung transplantrecipients, the graft itself is directly exposed to these viruses and thus particularly at risk of dysfunctiononce infected. In previous studies, we have described the impact of these viruses in hospitalizedsubjects and identified unexpected complications in lung transplant recipients. These observationsand a recent pilot study have established the basis of the present multidisciplinary collaborationbetween the University Hospitals of Geneva and Lausanne. The goal is to carefully assess symptomsassociated with viral infections and to evaluate whether respiratory viruses can trigger acute rejectionand bronchiolitis obliterans, the main cause of progressive graft dysfunction and death. To achievethis goal, we will use a longitudinal clinical follow-up approach by enrolling all transplant recipients inour network together with a systematic viral screening over four winter seasons. In order to avoid anyselection bias, we have planned prescheduled screening periods that will be conducted in all cohortsubjects three times per year independent of any symptoms or clinical conditions present. In addition,subjects will be screened systematically during the first three months following transplantation andduring each acute respiratory event and bronchoalveolar lavage procedure. The virological screeningwill use an updated panel of RT-PCR assays applied systematically on upper respiratory specimensand bronchoalveolar lavage fluids when available. The diagnostic assays will be redesignedspecifically for the present project using our most recent expertise and an extensive sequencecollection. The goal here is to design assays likely to detect any divergent strains or new viral variants.This project will provide not only the epidemiological pattern of respiratory viral infections, but also adescription of the associated symptoms and lung function abnormalities. In addition, the study isdesigned to specifically assess the potential causal link between viral respiratory infections and acuteor chronic graft rejections. Another major objective will be to analyze the potential pathologicalabnormalities or specific patterns linked to viral respiratory tract infections. In summary, we willaddress the very relevant question of the short- and long-term impact of these viral infections whichhas never been studied so extensively so far. Our position at the interface between molecular virologyand clinical sciences offers the unique opportunity to correlate clinical end-points with solid virologicalfindings. We have benefited from a preliminary funding that has not only allowed us to establish thebasis of this project, but also to launch the investigation. This strategy potentiates and synergizes thepresent funding request.
-