Summary Report

“Revisiting Dengue Research Map for the Future”

Organized by

Thailand Tropical Diseases Research Programme (T-2)

On

Friday, May 2^nd, 2003

At the

Century Park Hotel

INTRODUCTION:

      The T-2 Director, Dr. Somsak Chunharas delivered a brief introduction on the Programme’s status and the main purpose of today’s meeting.  All experts in various fields in relation to Dengue are recruited for discussions in order to generate significant support for Dengue.  Every research interests would be gathered and recorded for any future references. 

      Participants are seated according to their field expertise where each was asked to introduce themselves, along with providing their backgrounds and all past, present, and future works.  In addition, they are requested to address their interests in relation to Dengue.   
 

      Dr. Somsak discussed dengue research in foreign countries before proceeding to its status in Thailand.  The John Hopkins team set in Singapore organizes vaccine development institution that approaches to obtain basic scientists and a new paradigm using Basic Science.  Moreover, Novartis pharmaceuticals have set up an institute as well.  However, despite these organizations of institutions, Taiwan seems to gain most interest from Thailand.   
 
 

DENGUE RESEARCH IN THAILAND (BY DR. POKRATH) 
 

    The content of the presentation is based on information derived from Medline source.  The topics include the following:

• Areas of Dengue Research
• How far is Thailand (by publication)?

A list of publications was presented accordingly to each area of dengue research, ranging from epidemiology, virology of dengue virus, dengue pathogenesis, dengue pathology, immune response to dengue virus, vaccine development, clinical manifestation and management, laboratory diagnosis, dengue vector research, and lastly, socio-economic research. 

      However, it was agreed that Medline is not the most reliable source to search for publications due to 20-30% inaccuracy of listed publications.  Thus, all participants suggested other sources to look into where more publications by Thais are posted. 

      Despite much contribution from Thailand, it is essential to produce publications with assured good literature.  Moreover, there needs to be a well-organized database for Thailand that lists a range of both local and foreign works from the past and present time as a record.  As for now, it was encouraged to conduct a survey on the publications that have been made and for all participants to contribute their publications.  All of these provided information would then be incorporated to a search engine where people may have access to all the listed publications.       
 

A WORD FROM THE T-2 DIRECTOR

      All participants disregarding their histories and backgrounds are invited due to the aim of this meeting, which is to establish collaborations amongst different institutions to work in the dengue field together. 

      Dr. Somsak clarified and emphasized that despite T-2’s role as a granting agency, another aim would be to encourage and help researchers develop and improve their research works.   
 
 

DENGUE RESEARCH: INTERNATIONAL AND THAI SCENES 
 

      Dr. Prida Malasit elaborated on the global activity on dengue research, especially in the US and in Taiwan, upon updating the Thai Dengue map (The PowerPoint slide presentation is attached hereby). 
 

Introduction:

• Vaccine development is the area that receives most grants in America.
• One of the most advanced vaccines is in the hands of the Thais, under Prof. Sutee Yoksan. 
• American teams tend to focus less on genomic approaches and proteomics, which is an area that Thais should turn their attentions to.
• Several attempts have been directed to entomology to accomplish dengue control and determine dengue transmission. 
• Despite the success in producing drugs that are capable in inhibiting the virus, there is a dilemma on the time of drug administration. 
• It is significant to determine the mechanisms in inducing pathogenesis, shock, or death. 
• All immune responses to dengue viruses in humans or mouse models must be studied as well. 
• In regards to virology, the determinants of virulence remained unclear.  Thus, further analysis is continued due to how viruses in SEA and America exhibit different sequences, which cause them to enforce different levels of severity. 
• Core laboratories and research in Thailand are expected to achieve lab of excellence in taking the burden of the processing of specimens and generate specific data to establish a network.  In order to do so, there needs to be strategies where an institution studies patients closely, and maintains a database center for specimen collection.
• The rapid growth in basic research in Taiwan that should be taken into account as a model for Thailand. 
• Concerning Taiwan’s interests in various research areas on dengue and its high investment on epidemiology, there is a high possibility for future cooperation and collaboration between Taiwan and Thailand. 
• Cooperation and working with international partners, especially AFRIMS, are very necessary and essential. 

Vaccine:

   Vaccine is the most efficient strategy in dengue control because other strategies like vector control is difficult.  With the technology we acquire, we have a number of advantages in vaccine development: 

• Infectious clones have been produced and kept at the Center of Vaccine Research (Mahidol). 
• In terms of patients, virus, and epidemiology, Thailand is the most mature on Dengue. 
• Different laboratories follow the same aim, which is to develop as many candidates as possible in five years time.
• Protection, large cohorts, and long-term immunity serve as a ‘window of opportunity’ for Thailand. 
• Conduction of cohorts will ensure the identification on whether the spread of dengue is predictable and will be responsible for vaccine phase III, which will be one of the highest advancements. 
• It would be beneficial to work with vaccine companies and international professionals. 

Diagnostics:

      Clinical research center projects and cohorts will give Thais the opportunity to generate novel approaches. 

• In a community, there should be a good database to assure monitoring and to watch patients closely. 
• The emergence of new technology should be an advantage to the development of diagnostics.  However, support from companies and granting agencies is required. 
• There are several possible developments of diagnostics, although there are certain difficulties presently in developing good kits. 
• The map to develop diagnostics shows the highly possible areas for Thai scientists. 
• Generally speaking, a very strong clinical database center and large cohorts are required in order to make further steps.       

Pathogenesis Studies: Clinical Research:

      Thailand holds good data but lack the mechanism in making use of those data.  These data should be collected altogether in order to determine any possible risk factors. 

• A linkage between different field experts to facilitate discussions would be beneficial.       
• With new technology and existing clinical studies, the definition of protective immunity and inflammation needs to be clarified. 
• Antibody enhancement and epitope mapping may also be elaborated on. 

Virology:

      In developing good proposals, Thailand should look at Taiwan as a model.  “Group granting” may aid in developing proposals by reviewing them until they reach a set standard. This granting mechanism will assure high quality proposals.   

      As for the existing map, researchers are starting to look at non-structural proteins.       
 

Genomic and Proteomic Dengue Research:

      Dr. Prida strongly urges Thai scientists to approach this new conventional research.  However, granting agencies need to make sure that studies will focus on all areas under proteomic, genomics, and post genomic research.   
 
 

GROUP DISCUSSIONS 
 

      All participants are organized into six separate groups to address the status of each field area in Thailand and any possible future progress.  The following issues are discussed and will be recorded as a database:

1. Clinical Research and Management
2. Immunology
3. Research Priorities: Vector Area
4. Virology
5. Diagnostic
6. Epidemiology

   After group discussions were over, a representative from each group presented what has been discussed in the group. 
 

1. Clinical Research and Management

      The target that has been discussed is to decrease the mortality rate and complications.  Research areas include the following:

• Natural history of dengue infection
• Clinical picture of dengue infection
• Clinical predictor score for diagnosis and management for dengue infection
• Fluid therapy and transfusion therapy
• Treatment in unusual manifestation cases
• Factor VII treatment in severe bleeding cases
• Treatment with steroids
• H2 blocker and GI bleeding
• Cardiovascular (CVS) and hemodynamic change

2. Immunology

Direction: 

• Protective immunity: mechanisms
• Mechanisms of pathologic immune activation
  • Role of bystander activation in pathogenesis of DHF
  • Role of heterologous and antigenic sin