Countries in the Asia Pacific have witnessed the burden and threat of vector-borne diseases to individuals, families and societies. Singapore, for instance, witnessed a sharp increase in dengue cases this year. In response, countries have recognized the need for an integrated, comprehensive approach to vector control that will enable the setting and achievement of disease-specific national and global goals. This one-day hybrid event will convene thought leaders and experts from the three countries to discuss innovative measures to tackle the spread of dengue in the region, including the potential of the newly approved dengue vaccine to help protect against the disease.

It would be an opportunity for stakeholders to come together to discuss actionable recommendations that could be adopted to further dengue management in Southeast Asia. Drawing from best practices, the experts will put forth recommendations that are actionable and responsive to the unique challenges faced by countries in the Asia Pacific in reducing dengue transmission.

Presentation Abstracts 

Title: What are the ingredients for eliminating the threat of Dengue?

Dr Vernon Lee, Director of Communicable Diseases at the Ministry of Health, Singapore

 Half of the world’s population is at risk of dengue infection, with almost 400m infections annually. While there have been many interventions over the years to attempt to reduce the threat of dengue, it continues to defy global effort. This presentation will discuss the ingredients that could collectively eliminate the threat of dengue. This includes good vector, virus and disease surveillance; prevention of mosquito breeding and reducing the mosquito population; community engagement and personal protection; optimal clinical management of human cases; and an effective vaccine. While it is unlikely that any one of these measures are sufficient to control the transmission of dengue, combined global effort may lead to possible elimination in the future. 

Title: Five decades of Dengue control in Singapore – Can we control it?

Dr Lee Ching Ng, National Environment Agency, Singapore 

Dengue has, for decades, brought a heavy economic and disease burden to populations around the tropical and subtropical. It now threatens temperate countries.  This talk will summarise the lessons learnt in dengue epidemiology, risk factors, and prevention in tropical Singapore over the last half a century, during which Singapore evolved from a city of 1.9 million people to a highly urban globalised city-state with a population of 5.6 million. The current control programme is characterised by four key features: (i) proactive inter-epidemic surveillance and control which is stepped up during outbreaks; (ii) risk-based prevention and intervention strategies based on advanced data analytics; (iii) coordinated inter-sectoral cooperation between the public, private, and people sectors; and (iv) evidence-based adoption of new tools and strategies. As a result, dengue seroprevalence and force of infection among residents have substantially and continuously declined over the five decades. However, low levels of immunity in the population and viral diversity in the community compounds the population’s vulnerability to outbreaks. Changing global and local landscapes, including climate change, increasing urban populations and global physical connectivity are expected to further make dengue control even more challenging. Adoption of new surveillance and control tools, such as the Gravitrap, Wolbachia technology and vaccines, is paramount to impede the growing threat of dengue and other Aedes-borne diseases.

Title: Dengue vaccine – What is good enough?

Dr Ooi Eng Eong, Professor, Programme in Emerging Infectious Diseases, Duke-NUS Medical School

After more than half a century of research, the world is now poised to make dengue a truly vaccine-preventable disease. One vaccine has already been licensed for use, albeit limited to those with prior dengue virus (DENV) infection. A second vaccine has received approval from the European Medicines Agency, whilst a third vaccine has completed phase III clinical trial with favorable efficacy in preventing symptomatic DENV infection. However, none of these vaccines fully protect against all four DENVs. Would such vaccines still be useful in preventing dengue or would vaccination risks of severe dengue? I will argue, based on molecular mechanisms of antibody-enhanced dengue as well as immune response against DENV and other flaviviruses, that imperfect vaccines can still be deployed to maximize public health benefits whilst containing the risks of uncertainties.  

TAK-003 dengue vaccine scientific data: from backbone to efficacy and favorable safety profile

Dr Alberta Di Pasquale, Regional Medical Affairs, Vaccines Head, Growth and Emerging Markets, Takeda

Vaccines save 2 to 3 million deaths each year and have transformed global public health ever since the covid 19 pandemic¹. Despite vector control and diseases management efforts, dengue cases continue to grow across dengue-endemic and non-endemic regions, there is a need of an additional preventative tool, such as an effective vaccine to help control dengue at the population level. Takeda is developing a live-attenuated tetravalent dengue vaccine candidate (TAK-003) to help address unmet needs in dengue prevention, the formulation is based on a live attenuated DENV-2 genome that provides the backbone to the DENV-1,3,4 recombinant viruses. In natural dengue infections it has been observed that both structural and non-structural components of the dengue virus are important to activate innate, humoral and cell mediated immune responses. TAK-003 has been investigated in an extensive clinical development program encompassing more than 28,175 participants, including a wide range of ages, both seropositive and seronegative people, across endemic and non-endemic regions of the world. Data have shown that TAK-003 provides continued protection against dengue fever through 4.5 years (54 months) after vaccination in the pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial. TAK-003 prevented 84% of hospitalized dengue cases and 61% of symptomatic cases in the overall population, including both seropositive and seronegative individuals, through 4.5 years in a long-term exploratory analysis. In regards of immune response, TAK-003 activates several facets of immunity that may contribute to protection against dengue. Broad spectrum of TAK-003 immune responses may contribute to protection against infection, virus clearance and prevention of severe disease. Our trials also demonstrated TAK-003 has been well tolerated with no important safety risk identified to date. In this presentation, we will discuss in details on the efficacy, immunogenicity and safety profile of TAK-003.

Dengue Vaccination: Policy Perspective from Clinical Trial to National Immunization Program

Dr. Nakorn Premsri, Director of National Vaccine Institute (NVI), Thailand

Dengue Fever still be one of the major health problems especially countries among tropical zone, 70% of the actual burden is in Asia. Severe dengue is a leading cause of serious illness and death in some Asian and Latin American countries. It is observed of the increasing trend of the disease burden, probably from more coverage of case report and improve of diagnosis. However, this increasing informed more precise burden and demonstrated the significance of this vector-borne disease burden. There are available of 2 dengue vaccines which revealed the efficacy study results, Dengvaxia (Sanofi Pasteur) and QDENGA (TAK003-Takeda) which are more prominent with humoral immunity. The incoming consideration of cellular immunity vaccine may play the additional role in heterologous prime-boost concept. The next crucial step of implementing dengue vaccination is to inform the relevant policy bodies at national level for policy and budget approval. All required information needs to be put in place for policy endorsement, e.g., Disease burden, Efficacy result, Health-Economic study, Program feasibility, etc. Thailand’s experience of consideration to approve budget for vaccine in National Immunization Program will be shared in this session.

Wolbachia as a complementary strategy for mosquito-borne arbovirus control

Dr Eggi Arguni,  Lecturer, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Indonesia 

Arboviruses are etiological agents of diseases such as dengue, zika, yellow fever, and chikungunya and are transmitted by mosquitoes. These diseases, called arboviruses, are considered a major public health problem because they cause high morbidity and can be life-threatening. The main vector of arboviruses transmission is Aedes aegypti and Aedes albopictus mosquitoes. Currently, there are no specific treatments for arbovirus infections. Mainly depend on supportive care for symptoms and maintaining vital organs. Furthermore, high-efficacy vaccines have been developed to prevent arboviral infections. However, in the major endemic arboviruses country, these vaccines are not included in the national program, thus unlikely to result in universal protection from infection. Due to this condition, disease prevention mainly relies on vector controls, i.e. the elimination of breeding sites, mosquito bite protection, and the use of chemicals and biological approaches. However, historically the sustained control of arboviruses has been generally ineffective.

The novel biological control of mosquito-borne disease by the use of the naturally bacterial endosymbiont Wolbachia has been successfully tested in field trials in several countries, initiated by World Mosquito Program. The field trials demonstrated the feasibility of Wolbachia introduction into native mosquito populations and reducing dengue transmission to humans. Mosquitoes carrying Wolbachia are being released through two main approaches: population suppression and population replacement. The releases of Wolbachia-infected male mosquitoes have achieved very high population suppression by reducing the fertility of wild mosquito populations. Meanwhile, the replacement of populations by the release of Wolbachia-infected females is self-sustaining. This approach also can greatly reduce local dengue transmission by reducing the vector competence of mosquito populations. Wolbachia releases are best used as a complementary strategy with other existing vector control measures and are not intended to take over them. Together with vaccination, all vector control strategies will be effective ways to reduce mosquito-borne arbovirus disease.