|
Summary Report of the First Meeting
(MS Word Format)
"Revisiting Dengue Research Map for the Future"
Organized by Thailand Tropical Diseases Research Programme (T-2)
On Friday, May 2nd, 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
3. Research Priorities: Vector Area
- National Control System ?
- Vector Control Measures
- Community involvement
- Insecticide management/resistance
- Larvicide, adulticide
- Biocontrol/predator
- Medicinal plants
- Personal protection
- Ovitrap (lethal ovitrap)
- New Parameter
- Stegomyia indices, BI, HI, CI
- GIS, remote sensing
- Nature of Mosquito Polymorphism
- Update on Enzyme Assay Screening
- Due to constant evolution of insects (mosquitoes) which leads to isoenzyme/gene grouping
- Update on Biology Vector
- Biting time, biting behavior
- Population density
- Vector Competance
- Genetic manipulation of vector
- Identification of each vector as well as its susceptibility
- Transgenic from Vector to Non-vector
- Immune Response in Mosquitoes
- Study of serine protease mediator
- Analysis of Salivary Enzyme
- Allergies and reactions in man
4. Virology
Strain of Virus and the Severity of Infection
1. In vitro system
- Laboratory mutation
- NS1 mutation
- Glycosylation
- Signal transduction
- Cell death and replication
- Capsid mutation
- Nuclear penetration
- Attenuation of replication
- Block encapsulation
- Role of NS1 on complement (C' ) activation
- Correlation of complement (C' )activation and severity
- 5' Non coding region (NCR) mutation
- Possibilities of vaccine candidates
- Propose new strategies for candidate testing - cytokine array
- Field isolates
- 5' NCR mutation
- Natural attenuation
Pathogenesis
- Genomic and virulence of infection
- Gene profile by micro-array analysis
- Signature of DF and DHF
- Nitric Oxide (NO) in viral replication and pathogenesis
- NO on molecular replication inhibition
- Role of NO in DF and DHF
- T-cell immunity in DF and DHF patients
Future Research Plan
- Virology
- Phylogenic analysis for Thai isolates and its relationship with severity
- Pathogenesis
- Mechanisms of neutralization
- Mechanism of apoptosis
- Destruction or protection
- Viral factors
- Host factor (serum factor)
- Effect of co infection on severity of illness?
5. Diagnostics
- Early
- Surrogate markers for prognosis of severity
The issue of sharing monoclonal was brought up, to which Dr. Prida agreed.
Molecular Tests (NAAT)
1. RT-nested PCR
- RT-single-PCR multiplex
- Microchip detection
- Qualitative
- Viral load (fluorescence & Chemiluminescence-based)
2. Real-time RT-PCR
- Quantitative
- Early diagnosis and surrogate marker of severity
- Costs:1000-1500 Baht
3. Detection of viruses in different compartments
6. Epidemiology
Direction:
- Burden
- Prediction (epidemiology and severity)
- Community database
7. Existing Infrastructure and problems
1. Epidemiology data
- National surveillance form 506
- Serotyping surveillance
2. Problems
- Coverage
- Quality
- Validity
- Accessibility
-
Research Questions:
- Improvements of:
- National Surveillance System
- Serotyping
- Molecular Epidemiology
- Early Warning System
- Forecast
- Warning/Alarming
- Detection
- Incidence include asymptomatic cases?/burden
- Dengue infection/PUO
- Risk factors
- Viral virulence
- Environmental factor
- Morbidity and Mortality
- Severity &. Molecular study
Socio-economic:
MOVING FORWARD
Questions and comments from the floor were brought into discussion as followings:
- The contents of the meeting will be posted in T-2's website for other web-visitors to read.
- Concerning the development of cohorts, the following issues should be considered:
- Criteria for good cohorts
- Accommodate projects
- Recruit researchers
- Dr. Prida's project:
- Set up a committee to oversee the use of specimens and database
- Users can request for use and submit their proposals
- Need cohorts
- This central facility aims to get researchers focused
- Mechanisms in improving proposals
- Trainings/workshops in how to write grants
- Regular meetings should be organized to facilitate the exchange of ideas
- What kind of forum?
- Objectives of these meetings
- AFRIMS can provide advices and guidance
CONCLUSION
Two out of three big projects have been submitted to T-2 on the following field areas:
1. Vaccine development
2. Clinical
3. Community-based cohort (has not been submitted yet)
- These projects are to be discussed so that any interested researchers, clinicians, or virologists may contribute help in improving the proposals. Depending on the circumstances, workshops may be required.
- Consulting with experts may be essential to share and exchange knowledge and ideas.
- A Thai team should be set up to organize a "Dengue package". In order to do so, search for partnerships to sponsor this package is significant. Perhaps T-2 may act as a host.
- Recruitment and joining of young scientists may aid in creating clinical research projects, cohorts, and career paths.
CLOSING REMARKS
It was agreed that the majority of proposal writings do not meet the standards, which may be the reason why there are few manuscript writings produced. It is part of the granting agencies' responsibility to provide thorough reviews to ensure good quality proposals. In fact, what makes a good agency is its duty in reviewing proposals, organize events (such as today's meeting), organize support systems to strengthen proposals, and provide continuous informing and knowledge. With reference to SERC's review process, Prof. Tada is satisfied with its aid in improving and mentoring research projects to reach international standards.
The search for funding for Dengue Thailand will be initiated to accumulate all interested researchers. In addition, conferences should be organized to ensure the accumulation of all knowledge from every direction and field. Prof. Tada strongly emphasized the necessity of all researchers to gain knowledge in other fields other than their own in order to broaden their perspectives in future research studies.
A clinical center should be well developed with high fidelity so that close monitoring on every patient is allowed. However, one should be prepared to accept the policy rights.
In conclusion, for database purposes, anyone with sources is kindly requested to submit them. For future references, the contents of today's meeting will be summarized and sent to all participants. Furthermore, updates and new information will be uploaded into the T-2's website where a search engine will be created to provide visitors the access to publications.
T-2 will attempt to put action into what has been proposed today.
Reported by: Ms. Nisarat Pichayapa
Approved by: Dr. Somsak Chunharas, Dr. Ram Rangsin, Dr. Pokrath Hansasuta
|
