Dengue Hemorrhagic Fever: A Model for International Collaboration

Transcription

1 Dengue Hemorrhagic Fever: A Model for International Collaboration Prida Malasit, MD., FRCP Medical Molecular Biology Unit Siriraj Hospital, Faculty of Medicine, Mahidol University, Thailand

2 Dengue Hemorrhagic Fever DHF Caused by dengue viruses flavivirus Four serotypes exist in endemic areas Endemicity in SE Asia, starting in 1950 s Aedes aegypti as vector Sudden onset of shock, leakage and hemorrhage (skin and GI tract) mainly in children Association of DHF with secondary infection

3 Problems Public Health SE Asian countries reported 1.2 million cases of DF/DHF Gubler D. Adv Virus Res 1999;(53):35 MOPH Statistics Gubler D Emerging Infectious Diseases

4 Southeast Asia Calculated average annual dengue infection rate 530 m Vaccine most cost effective 26 m/y But will not be available 6.3 m/y within few years 380,

5 Clinical Manifestation Plasma DNA PBMC Temp. Serology PCR Virus isolation HLA C BP 100 mm Hg %Hct Pleural Effusion Ascites Hypoproteinemia Tourniquet +ve. Petichae +ve 240, ,000 platelets HCT 25, Days of illness Narrow pulse pressure or shock

6 Challenge Questions for Research Mechanisms of shock and leakage? What are they? Any pharmacological agent assist the treatment? Preventable any agent to abort? Why hemorrhage? Public health Efficient Surveillance - Prediction of outbreak? Vector control Vaccine Development

7 Dengue Research in Thailand Key Factors Continual research and clinical activities (since 1960): Children hospital Bangkok and AFRIMS Ministry of Public Health country surveillance system and laboratory services Center for vaccine development Mahidol University Continual interest in basic/clinical research: Existing graduate programs, BSc., PhD/MD Internal granting system the T2 Program The Dengue research map commissioned by T2

8 Key Areas from the Research Map Clinical database for bio-medical research Vaccine development; vaccine trial site Diagnostic development Genomic/Genetic research Clinical trials National surveillance system - Cohort

9 High Quality Clinical Database and Specimen Collection for Dengue Bio- Medical Research Network linking two clinical sites with a University Laboratory Linked to International Collaboration Sites

10 Clinical Management Scheme Pyrexia >3 days Admission Criteria Pyrexia <3 days PCR Admission Consent Treatment/Monitor Specimens Database Reference Laboratory Specimen repository Serological & Virological Follow-Up

11 Clinical Study Record and Specimens Plasma DNA PBMC Temp. Serology PCR Virus isolation HLA C BP 100 mm Hg %Hct Pleural Effusion Ascites Hypoproteinemia Tourniquet +ve. Petichae +ve 240, ,000 platelets HCT 25, Days of illness Narrow pulse pressure or shock

12 Overall Structure of the Units Mainz Germany Siriraj Medical Molecular Biology Unit, Office for Research & Development BIOTEC Medical Biotechnology Unit Chiang Mai Dpt. Microbiology, Fac. Of Medicine Dpt. Immunology, Fac. of Assoc. Med. Sciences Dengue Clinical Units Khon Kaen Songkla Paris Pasteur CNG Imperial College London Wash U. U.S.A.

13 Bring Local Problem into International Arena Center of Excellence Collaborations International Environment Cluster Local Environment Group of Excellence

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15 NYA Den-2 specific T cells 19% NYA Den-1/Den-2 specific T cells 52% IFN-γ IFN-γ Den-2 NYA Den-1 specific T cells 29% No-response CD107a + Den-1 IFN-γ IFN-γ + and/or TNF-α + CD107a + (IFN-γ + and/or TNF-α + )

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17 Network with Mainz University Potential diagnostic tool for early diagnosis of dengue hemorrhagic fever using circulating levels of NS1 protein with the host s SC5b-9 complement complex

18 Academic Contributions (2000-3) PhD new recruits 6 RGJ program 2 PhD/MD Mahidol 4 Master Degree 19 Graduated: master 10 Current students: PhD 12 Master 21 Post Doctoral 2

19 Key Local Factors Set of highly-focused basic research targets Establishment of essential technology and reagents shared between partners Competent personnel handling necessary techniques with quality Adequate supports from local grants High quality clinical database and specimens

20 Key International Factors Willingness to share intellectual property rights - TRUST Efficient management communication, progress monitoring Investment in brain storming sessions for project developments (preferably co-funding) Transparency and just sharing of resources, technology, personnel, funding Partnership in research funding Partnership in research personnel development Partnership in infrastructure developments Long-term commitment from both partners