By Professor Lam Sai Kit

KUALA LUMPUR, Malaysia: Virologist Emeritus Professor Datuk Dr. Lam Sai Kit has urged the Malaysian government to look into giving access to a new dengue vaccine that is suitable for individuals who have been previously infected with dengue or not.
Unlike the Dengvaxia vaccine developed by Sanofi Pasteur and cleared for marketing in 2015 (but not in Malaysia), there is no requirement for a pre-vaccination testing as the new Takeda (TAK-003) vaccine, also known as QDENGA, has been approved for use regardless of prior dengue exposure.
Globally, an estimated 3.9 billion people, about half the world population, are at risk of dengue, and it is now endemic in more than 125 countries. According to WHO, there are an estimated 390 million infections and 500,000 hospitalizations each year. 
“Dengue is the fastest spreading mosquito-borne virus and was recognized by WHO in 2019 as one of the ten threats to global health.  
The worldwide incidence of dengue has risen eight-fold in the past 20 years, and is still rising, due to climate change, rapid urbanization, population growth, inadequate waste management and improper water storage which provides breeding grounds for these mosquitoes, facilitating the transmission of the dengue virus.”
Dengue is a viral infection transmitted to humans through the bite of infected mosquitoes. The primary vectors that transmit the disease are Aedes aegypti mosquitoes and, to a lesser extent, Ae. albopictus. 
Dengue can cause a wide range of symptoms, ranging from asymptomatic to mild disease with high fever, severe headache, acute joint and muscle pain. In about 5% of cases, severe internal bleeding, shock and even death can ensue. 
There is no specific treatment for dengue but early detection of disease progression to severe dengue and access to medical care lowers the fatality rates of severe dengue to below 1 percent.
Dengue is an important public health problem in Malaysia. In 2023, the Ministry of Health Malaysia  said that the cumulative number of dengue cases reported up to ME48 increased by 91.3 percent, to 111, 417 cases, compared with 58,239 for the same period in 2022. 
A total of 84 deaths due to dengue fever complications have been reported, compared to 39 deaths for the same period in 2022, said Health D-G, Datuk Dr. Muhammad Radzi Abu Hassan.
“Despite an intensified integrated vector control programme in the country, including the use of Wolbachia-carrying Aedes mosquitoes in hotspots in the Klang Valley, the number of dengue cases has not declined significantly. 
Developing a safe dengue vaccine that will give life-long protection against all four serotypes, and affordable for developing countries where the disease burden is the greatest, has been a priority programme for international agencies, including WHO.”
“Developing a vaccine against all four dengue serotypes has been a challenging task and has been on-going since the 1950s. There are four dengue serotypes (Den 1-4) and infection against one serotype will not protect infection by the other three serotypes. 
As a matter of fact, in some cases, a previous exposure to dengue, through infection or vaccination, can lead to a more serious disease such as dengue hemorrhagic fever and dengue shock syndrome on a second or subsequent infections.”
“Hence, we are looking for a vaccine that will give life-long protection against all four serotypes equally. In addition, the vaccine must be affordable for developing countries where the disease burden is the greatest. Safety is an important issue, and the vaccine should not increase the risk of severe diseases in individuals with pre-existing immunity.” 
The Takeda dengue vaccine, known as QDENGA (TAK-003), is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all four dengue virus serotypes and is designed to protect against any of these serotypes. 
It has been extensively tested across 19 Phase 1, 2 and 3 trials with more than 28,000 participants, ranging in age from 18 months to 60 years, including four and a half years of follow-up data from the global, pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial. 
The pivotal TIDES trial, which is a double-blind, randomized, placebo-controlled trial, assessed a two-dose schedule of the dengue tetravalent vaccine, given three months apart, in more than 20,000 healthy, dengue-naïve children, aged 4 to 16 years, living in dengue-endemic areas, over three years. 
TIDES met its primary and secondary endpoint with 80.2% efficacy at 12- and 18-month follow-up. 
The vaccine efficacy results in preventing hospitalization by 90.4 percent, with sustained overall vaccine efficacy of 61.2 percent and 84.1 percent against disease and hospitalization. 
In terms of safety, Qdenga has been generally well tolerated and no important safety risks have been identified in the TIDES trial.
Based on the data provided by Takeda, the European Union gave approval for the licensing of Qdenga in October 2022.  
It is available for European tourists who travel to Latin America, the Caribbean and Southeast Asia. Qdenga is currently available for children and adults in EU, UK, Indonesia, Thailand and Brazil. 
“As a matter of fact, the city of Dourados in the Brazilian state of Mato Grosso do Sul announced on 3 January 2024 that it has begun the country’s first mass vaccination against dengue using Qdenga. Brazil registered 1.6 million cases of dengue in 2023, and 1,053 deaths, and the country’s health ministry announced it would include Takeda’s shot in the national vaccination program.”
In October 2023, the Qdenga dengue tetravalent live attenuated vaccine has also been recommended for use by the WHO Strategic Advisory Group of Experts (SAGE) in settings with high dengue disease burden and high transmission intensity to maximize the public impact and minimize any potential risk in seronegative persons. 
SAGE recommends the 2-dose vaccine to be introduced to children aged six to 16 years in this setting. WHO will now consider the SAGE recommendation and provide final guidance on the use of Qdenga in public vaccination programs. 
“MoH should look into the licensing of the Qdenga vaccine as soon as possible so that individuals who wish to be vaccinated can have access to it immediately,” said Prof. Lam.
*Emeritus Professor Datuk Dr. Lam Sai Kit is a Research Consultant based at Universiti Malaya and Senior Fellow of the Academy of Sciences Malaysia.*