5 th <strong>European</strong> <strong>Congress</strong> <strong>of</strong> <strong>Virology</strong>Saturday 14 th September 2013, 8h30 – 10h30WORKSHOP 26: “VIRAL INFECTIONS IN TRANSPLANTAND IMMUNOCOMPROMISED PATIENTS”Chairpersons: Paulo PAIXAO (Lisbon, PORTUGAL)& Thomas SCHULZ (Hannover, GERMANY)AmphitheaterKEYNOTE: AWARD <strong>of</strong> the Italian Society <strong>of</strong> <strong>Virology</strong>: “Excellence in<strong>Virology</strong>”Virologic and immunologic monitoring <strong>of</strong> human cytomegalovirusinfections in the immunocompetent and immunocompromised host:perspectives for the development <strong>of</strong> a subunit glycoprotein pentamericvaccineGiuseppe GERNALaboratori Sperimentali di Ricerca, Area Trapiantologica, FondazioneIRCCS Policlinico San Matteo, 27100 Pavia, ITALYPCR analysis <strong>of</strong> hundreds <strong>of</strong> immunocompetent healthy subjects with andwithout reactivated HCMV infections never revealed presence in wholeblood <strong>of</strong> HCMV DNA at a measurable level (>100 copies/ml blood). Asimilar approach in the immunocompromised host allowed to define onset<strong>of</strong> clinical symptoms at 1,000,000 DNA copies/ml in SOTR, while inHSCTR caution suggested that severe clinical syndromes, such as pneumonia,could start at a viral load <strong>of</strong> ≤ 100,000 copies/ml. This level <strong>of</strong>VL allowed to fix blood levels for preemptive therapy at 300,000 HCMVDNA copies for SOTR, and 30,000 HCMV DNA copies for HSCTR.Levels <strong>of</strong> HCMV-specific CD4+ and CD8+ T-cell responses showing protectionagainst HCMV reactivation were 0.4 T-cells/l blood for boththe immunocompetent and SOTR patients, and 1.0 CD4+ and 3.0 CD8+T-cells/l for HSCTR. In pregnant women with primary HCMV infectionlevels <strong>of</strong> VL never overcame 1,000 DNA copies/ml blood, due tothe prompt T-cell response. Neutralizing antibody titers, as determinedin ARPE-19 epithelial cells, appeared very early during primary infection,reaching extraordinarily high titers in the immunocompromised host(both primary and reactivated infections). B-T-cells interactions must beinvestigated.On the vaccine side, the gH/gL/pUL128L pentamer complex elicits a verystrong antibody response to its components and to the whole complex,both in natural infection <strong>of</strong> humans and experimentally inoculated mice.The T-cell response to the pentamer is now under study.ORAL COMMUNICATIONSREF O147Hepatitis E virus: an underestimated opportunistic pathogen in recipients<strong>of</strong> allogeneic hematopoietic stem cell transplantationSuzan PAS 1 , Jurjen VERSLUIS 2 , Erik AGTERESCH 2 , Robert DEMAN 3 , Jolanda MAASKANT 1 , Marguerite SCHIPPER 4 , AlbertOSTERHAUS 1 , Jan CORNELISSEN 3 , Annemiek VAN DER EIJK 11 Department <strong>of</strong> Viroscience, ErasmusMC, Rotterdam, THE NETHER-LANDS; 2 Department <strong>of</strong> Hematology, ErasmusMC, Rotterdam, THENETHERLANDS; 3 Department <strong>of</strong> Hepatogastroenterology, ErasmusMC,Rotterdam, THE NETHERLANDS; 4 Department <strong>of</strong> Pathology, ErasmusMC,Rotterdam, THE NETHERLANDSHepatitis E virus (HEV) is an emerging health issue in industrializedcountries, particularly in the immunocompromised. Since littleis known <strong>of</strong> HEV infections in allogeneic hematopoietic stem celltransplantation recipients (alloHSCT), we studied HEV infection inalloHSCT.Patients receiving alloHSCT between January 2006 July 2011 were included.Anti HEV serostatus (Wantai assay) before alloHSCT and presence <strong>of</strong>HEV RNA after alloHSCT and during episodes <strong>of</strong> liver function abnormalitieswere assessed. The course <strong>of</strong> HEV infection and clinical implicationswere studied from confirmed cases.328 Patients were included in the study. In total, eight HEV genotype3 infected cases (2.4%) were identified, <strong>of</strong> which five developed chronicHEV. These were misdiagnosed before as hepatic graft versus host disease(n=5) or drug toxicity (n=3). Seroprevalence prior to alloHSCT was 12.9%,2 patients (0.6%) were anti HEV IgM positive, though HEV RNA was notdetected.Four <strong>of</strong> eight cases died with HEV viremia, signs <strong>of</strong> ongoing hepatitis(n=4)and neurologic disease(n=1). The four living patients cleared HEV supportedby ribavirin treatment (n=1) and reduction <strong>of</strong> immune suppression(n=3). Two <strong>of</strong> four living patients were diagnosed with chronic hepatitisand fibrosis by liver biopsy. One HEV patient presented with viralreactivation.We conclude that a differential diagnosis including HEV is mandatorygiven the clinical impact. Future alloHSCT recipients should be screenedfor HEV RNA prior to transplantation and should be monitored afteralloHSCT, especially if liver abnormalities occur.REF O148Prolonged rhinovirus infection in hematological immunocompromisedpatients with impaired T cell immunityAntonio PIRALLA 1 , Marco ZECCA 2 , Anna Amelia COLOMBO 3 ,Alessia GIRELLO 1 , Patrizia COMOLI 2 , Rita MACCARIO 2 , FaustoBALDANTI 11 Molecular <strong>Virology</strong> Unit, <strong>Virology</strong> and Microbiology Department,Fondazione IRCCS Policlinico San Matteo, Pavia, ITALY; 2 PediatricHematology Oncology and Research Laboratories Fondazione IRCCSPoliclinico San Matteo, Pavia, ITALY; 3 Institute <strong>of</strong> Hematology, FondazionePoliclinico San Matteo IRCCS, University <strong>of</strong> Pavia, Pavia, ITALYRespiratory samples from patients hospitalized with acute respiratory syndromein the period 2006 2012 were tested with a panel <strong>of</strong> respiratoryviruses. In 12 hematopoietic stem cell transplant recipients (HSCTR) and3 patients with hematologic diseases a prolonged rhinovirus (HRV) shedding(>30 days) was observed. In these 15 patients, HRV was quantifiedby real time RT PCR and molecular typing was performed by sequencingthe 5 ′ NCR VP4 region in sequential respiratory samples. In detail:11/15 (73.3%) patients were pediatric (10 HSCTR, and 1 acute myeloidleukemia) and 4/15 (26.7%) were adults (2 HSCTR and 2 acute lymphocyticleukemia). The median duration <strong>of</strong> HRV positivity was 64 days(range 30 174 days). Phylogenetic analysis showed the persistence <strong>of</strong>a single HRV type in all patients except one. In 9/12 (75.0%) HSCTRpatients, HRV infection occurred across the transplant aplastic period(either during induction or prior to engraftment). Low level (
5 th <strong>European</strong> <strong>Congress</strong> <strong>of</strong> <strong>Virology</strong>REF O149Factors for Adenovirus Infection and Disease in Pediatric HematopoieticStem Cell Transplant patientsLinda FEGHOUL 1 , Jean Hugues DALLE 2 , Sylvie CHEVRET 1 , MarieOUACHÉE 2 , André BARUCHEL 2 , Mony FAHD 2 , Valérie GUÉRIN ELKHOUROUJ 2 , Ghislaine STERKERS 2 , François SIMON 1 , JérômeLEGOFF 11 Université Paris Diderot, Hopital Saint Louis, Paris, FRANCE;2 Université Paris Diderot, Hopital Robert Debré, Paris, FRANCEAdenovirus (Adv) infections are critical in hematopoietic stem cells transplantation(HSCT). The aim was to determine risk factors for Adv infectionand disease in pediatric HSCT patients. Between September 2010 andDecember 2011, 73 pediatric HSCT patients were prospectively followedfor 12 months and weekly tested for adenovirus in blood and stool. Sheddingwas defined as a positive detection in stool, systemic infection aspositive detection in blood, and disease as systemic infection with Advsymptoms. Multivariable Cox models were used to define predictive factorsfor shedding in stool, systemic infection and disease with estimatedhazard ratio (HR) <strong>of</strong> event as a measure <strong>of</strong> association. Cumulative incidence<strong>of</strong> shedding, infection and disease at 3 months post HSCT were 40%,23% and 17% respectively. Based on multivariable models, cord bloodtransplant was associated with shedding in stool (HR=4.29) and systemicinfection (HR=3.01). Acute GvHD was predictive <strong>of</strong> systemic infection(HR=1.46) and Adv disease (HR=2.55). For the patients with intestinalshedding, the occurrence <strong>of</strong> systemic infection was increased in case <strong>of</strong>high viral load detected in stool (p=0.02). The sensitivity and specificity tohave a systemic infection were respectively 93.33% and 62.5% for loadsin stool above 5.36 log copies/ml. Conclusions: Cord blood transplant andacute GvHD appear the most appealing risk factors for AdV infection andshould be considered to initiate a molecular screening for Adv. Patientswith high AdV viral load in stool must be considered for early anti Advintervention.REF O150Level and kinetics <strong>of</strong> Plasma Torque Teno Virus DNA after LungTransplantation as a Marker to Guide Immunosuppressive TherapyIrene GOERZER 1 , Mats HALOSCHAN 1 , Peter JAKSCH 2 , IsabellaBEJVL 1 , Robert STRASSL 3 , Walter KLEPETKO 2 , ElisabethPUCHHAMMER STOECKL 11 Department <strong>of</strong> <strong>Virology</strong>, Medical University <strong>of</strong> Vienna, Vienna, AUSTRIA;2 Division <strong>of</strong> Thoracic Surgery, Medical University <strong>of</strong> Vienna, Vienna,AUSTRIA; 3 Clinical Institute <strong>of</strong> <strong>Virology</strong>, Medical University <strong>of</strong> Vienna,Vienna, AUSTRIATorque teno virus (TTV), widely spread among humans, causes persistentviremia in healthy persons probably without clinical disease. Transplantrecipients receive immunosuppressive therapy. Its optimization is criticalto avoid rejection or infection, but it is still a challenge as appropriate markersreflecting the state <strong>of</strong> immunosuppression are lacking. In this study,we investigated whether level and kinetics <strong>of</strong> TTV DNAemia could reflectthe patient’s immunosuppression after lung transplantation. Plasma TTVDNA kinetics was analyzed by quantitative PCR in 31 lung transplant recipients(LTRs) over 2 years posttransplantation. Its relation to tacrolimus(Tac) versus cyclosporine (CsA), to infection events and to development<strong>of</strong> bronchiolitis obliterans syndrome (BOS) was assessed. In all LTRs,TTV DNA significantly increased up to day 90 posttransplantation andsustained high TTV levels thereafter. The extent <strong>of</strong> TTV increase wasassociated with mean drug concentrations (p=0.012) and mean TTV levelsthereafter were lower in CsA treated than in Tac treated patients (p