5 th <strong>European</strong> <strong>Congress</strong> <strong>of</strong> <strong>Virology</strong>13h15 – 14h30 SYMPOSIUM INSTITUTPASTEUR – FONDATION MERIEUXNETWORKS“FROM PUBLIC HEALTH AND SURVEILLANCE TO DRUGDISCOVERY”Chairpersons: Florence PRADEL (Lyon, FRANCE)& Kathleen VICTOR (Paris, FRANCE)Room Gratte-Ciel 1, 2, 3Pilot pneumonia multicentric study in the GABRIEL Network<strong>of</strong> Fondation MÉRIEUX: The relevance <strong>of</strong> the respiratory virusesValentina PICOT 1 ; Melina MESSAOUDI 1 , Jean-Noel TELLES 1 ,Florence KOMURIAN-PRADEL 1 , GABRIEL members 2 , GláuciaPARANHOS-BACCALA 11 Emerging Pathogens Laboratory, Fondation Mérieux, International Centerfor Infectiology Research (CIRI), Lyon, FRANCE; 2 GABRIEL membersThe Pilot Multi-centric Pneumonia Study was launched in 2010 in theframework <strong>of</strong> Fondation Mérieux’s research activities coordinated bythe Emerging Pathogens Laboratory (LPE) and the GABRIEL network*.Designed as a prospective multi-centric case-control study, this researchproject is carried out in 9 countries: Brazil, Cambodia, China, Haiti, India(2 sites), Madagascar, Mali, Mongolia, and Paraguay in close collaborationwith hospitals and partners from local research institutions. Thispilot study follows a harmonized protocol (total sample size: 1000 casesand 1000 controls), ethical approval and is carried out under good clinicalpractices compliance. The final purpose <strong>of</strong> this study is to provide informationon the pneumonia etiology (viruses and bacterial) to improve casemanagement <strong>of</strong> the pneumonia ill child.*www.fondation-merieux.org*www.gabriel-network.orgFactors associated with severity <strong>of</strong> influenza virus infections in Africaand Asia: the Institut Pasteur International Network Research ProjectRichard NJOUOM 1 , Soatiana RAJATONIRINA 2 , ArnaudTARANTOLA 3 , Patrice TCHENDJOU 1 , Jean Michel HERRAUD 2 ,Philippe BUCHY 3 , Magali HERRANT 41 Centre Pasteur Cameroon, Yaounde, CAMEROON; 2 Institut PasteurMadagascar, Antananarivo, MADAGASCAR; 3 Institut Pasteur Cambodia,Phnom Penh, CAMBODIA; 4 Institut Pasteur International Network,Paris, FRANCEWhile some factors have been identified to be potentially associated withsevere forms <strong>of</strong> influenza in the industrialized world, very little informationis available from the developing world. Our hypothesis is that the severity<strong>of</strong> influenza might be higher in developing countries where health caresystems are less performant and co-infections are prominent compared tothe industrialized countries. In order to identify risk factors associated withsevere influenza infections in developing countries, a prospective multicentercase-control study <strong>of</strong> patients with laboratory-confirmed influenzainfection is currently going on in the Institut Pasteur International Networkin Africa (Cameroon and Madagascar) and Asia (Cambodia). Cases(severe forms <strong>of</strong> influenza requiring hospitalisation) are age-matched (± 5years) to controls (patients with mild forms <strong>of</strong> influenza treated as outpatients).The inclusion <strong>of</strong> subjects started in 2011 and will end in December2013. The results <strong>of</strong> this study will help to better understand the burden<strong>of</strong> influenza in developing countries.Identification <strong>of</strong> viral pathogens and host-biomarkers in overlappingfebrile childhood illnesses in a malaria-endemic region <strong>of</strong>MadagascarJonathan HOFFMANN 1,2 ; Muriel MAEDER 1 , HenintsoaRABEZANAHARY 1 , Martin RANDRIAMAROTIA 3 , FlorenceKOMURIAN-PRADEL 2 , Eustache PARAMITHIOTIS 4 , ValentinaPICOT 2 , Bénédicte CONTAMIN 1 and GláuciaPARANHOS-BACCALÀ 21 Centre d’Infectiologie Charles Mérieux (CICM), Faculté de Médecine,Université d’Ankatso, Antananarivo, MADAGASCAR; 2 EmergingPathogens Laboratory, Fondation Mérieux, International Center forInfectiology Research (CIRI), Lyon, FRANCE; 3 Fondation Médicaled’Ampasimanjeva (FMA), MADAGASCAR; 4 Caprion Proteomics, Montréal,Québec, CANADAInstitut Pasteur and Fondation Mérieux in Madagascar are centered theirresearch efforts understanding the respiratory viral diversity. Childrenliving in malaria-endemic regions need access to high-quality diagnosisfitting biomedical treatment for malaria illnesses and acute respiratoryinfections (ARIs). In the absence <strong>of</strong> appropriate diagnostic tools, management<strong>of</strong> children illnesses is presumptive and symptom-based. Malariais essentially defined by fever while cough and/or difficult breathing asARIs. Both Institutions recently described the viral etiology <strong>of</strong> ARIs inchildren under 5 years-old in Madagascar. Another ongoing study aimedto identify candidate biomarkers linked to the well-known viral pathogensand Plasmodium. This is a promising approach to develop accurate andrapid diagnostics tools and overcome anti-malarial drug resistance in thesepediatric febrile illnesses.*www.fondation-merieux.orgEnterovirus 71 Epidemic in CambodiaChanna MEY 1 , Thérèse COUDERC 2 , Francis DELPEYROUX 2 , VeasnaDUONG 1 , Marc ELOIT 2 , Jeremy FARRAR 3 , Zhou GANG 4 , SothyHENG 5 , Denis LAURENT 5 , Marc LECUIT 2 , Jean-ClaudeMANUGUERRA 2 , Peijun REN 4 , Beat RICHNER 5 , Rogier VANDOORN 3 , Huang ZHONG 4 , Huachen ZHU 6 , Arnaud TARANTOLA 1 ,Sok TOUCH 7 , Guan YI 6 , Ralf ALTMEYER 4 , Philippe BUCHY 11 Institut Pasteur Cambodia, Phnom Penh, CAMBODIA; 2 Institut Pasteur,Paris, FRANCE; 3 Oxford University Clinical Research Unit, Ho ChiMinh city, VIETNAM; 4 Institut Pasteur in Shanghai/Chinese Academy<strong>of</strong> Science, Shanghai, CHINA; 5 Kantha Bopha hospital, Phnom Penh,CAMBODIA; 6 State Key Laboratory <strong>of</strong> Emerging Infectious Diseases,The University <strong>of</strong> Hong Kong, SAR CHINA; 7 Communicable DiseaseDepartment, Ministry <strong>of</strong> Health, CAMBODIAFrom April to December 2012, over 100 children, mostly under 3 years,died from acute febrile encephalitis associated with respiratory distress.Human Enterovirus 71 (EV71) was detected in 82% <strong>of</strong> severe cases. SeveralEV71 strains were fully or partially sequenced, demonstrating that theCambodian isolates belonged to the C4 subgenotype with close phylogenicrelationships with strains circulating in China between 2009 and2011 and in Vietnam in 2012. No recombination was observed in the fullgenome sequences analyzed. In less severe cases other human enterovirusesand coxsackie species were detected. Seroepidemiological studiesare currently being conducted to better estimate the burden <strong>of</strong> the diseaseand the history <strong>of</strong> the virus circulation in country.Vi<strong>rologie</strong>, Vol 17, supplément 2, septembre 2013S107
5 th <strong>European</strong> <strong>Congress</strong> <strong>of</strong> <strong>Virology</strong>Suramin inhibits Enterovirus 71 replication in vitro and in vivo by blockingvirus entry into target cells through binding <strong>of</strong> the naphthalenetrisulfonic acid group to the viral capsidREN Peijun 1,2,3 , ZOU Gang 1 , Benjamin BAILLY 1,4 , XU Shanshan 1 ,ZENG Mei 5 , CHEN Xinsheng 6 , Patrice GUILLON 4 , AndreaMAGGIONI 4 , Thomas HASELHORST 4 , FernandoARENZANA-SEISDEDOS 3 , LI Jian 6 , Mark VON ITZSTEIN 4 ,LI Qihan 7 , Ralf ALTMEYER 11 Unit <strong>of</strong> Anti-infection research, Institut Pasteur <strong>of</strong> Shanghai, ChineseAcademy <strong>of</strong> Sciences, No. 411 Hefei Road, 200025, Shanghai, China;2 Doctoral School <strong>of</strong> Biochemistry, Biotherapy, Molecular Biology, Infectiology,the University <strong>of</strong> Paris Diderot-Paris 7, 35 rue Hélène Brion,75013, Paris, France; 3 Viral Pathogenesis Laboratory, Institut Pasteur, 28,Rue Dr.Roux, 75724, Paris, France; 4 Institute for Glycomics, Gold CoastCampus, Griffith University, 4222, Queensland, Australia; 5 Department<strong>of</strong> Infectious Diseases, Children’s Hospital <strong>of</strong> Fudan University, 399Wanyuan Road, 201102, Shanghai, China; 6 WuXi AppTec, Co., Ltd.,200131, Shanghai, China; 7 Institute <strong>of</strong> Medical Biology, Chinese Academy<strong>of</strong> Medicine Science, 650118, Kunming, ChinaEnterovirus 71 (EV71) is the causative <strong>of</strong> severe infections <strong>of</strong> centralnervous system leading to cardiopulmonary complications and death inchildren under the age <strong>of</strong> 5. Using a library <strong>of</strong> FDA-approved drugswe identified that the anti-parasitic pediatric drug Suramin as inhibitor<strong>of</strong> EV71 replication in vitro (IC 50 0.08 M, selectivity index >10,000).Time <strong>of</strong> addition and virus binding assays demonstrated that Suraminblocks virus entry into susceptible target cells. Structure-activity relationshipanalysis and Saturation Transfer Difference Nuclear MagneticResonance identified that Suramin binds to the virus surface capsid proteinsvia the naphthalene tri-sulfonic groups. Suramin reduces mortalityin mice and EV71 peak viral load in adult rhesus monkeys when administerediv at the highest human dose allometrically scaled to the monkey.Our data show that the approved pediatric drug Suramin inhibits EV71replication by neutralizing virus particles prior to virus attachment. Ourdata suggest that Suramin is a candidate for further therapeutic developmentfor a safe and efficacious therapy or prophylaxis <strong>of</strong> severe EV71infections.S108 Vi<strong>rologie</strong>, Vol 17, supplément 2, septembre 2013
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