The dengue virus (DENV) belongs to the genus Flavivirus within the family Flaviviridae. Flaviviruses are lipid-enveloped, single-stranded RNA viruses. Dengue is a vector-borne disease transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes and caused by the four dengue virus serotypes (DENV 1-4).

Since 2009, WHO classifies dengue illness as: i) dengue without warning signs for progression towards severe dengue; ii) dengue with warning signs for progression towards severe dengue; and iii) severe dengue. Warning signs of severe dengue include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, liver enlargement of >2 cm, or an increase in haematocrit concurrent with a rapid decrease in platelet count. Criteria for severe dengue include any sign of severe plasma leakage leading to shock or fluid accumulation with respiratory distress, severe bleeding, or severe organ impairment.

DENV is endemic in South and Central America, Southeast Asia, and Sub-Saharan Africa. Approximately half of the world is at risk of dengue, which is estimated to cause 400 million infections and 20,000 deaths globally each year. The majority of people living in high endemic areas have been infected by at least one strain of dengue virus by the time they reach adolescence. About 75% of dengue infections could be asymptomatic. In Malaysia in 2024, the cumulative number of 122,423 dengue cases with 117 deaths was reported. The outbreak of dengue occurred in a 4-to-5-year cyclical pattern, following the shift in circulating dengue virus serotypes.

The prevalence of individual serotypes varies across different regions, countries, seasons and over time. Dengue outbreaks are associated with serotype shifts. Dengue cases and serotypes in Malaysia (2013–2024) are shown in Figure 2. A shift in dominance of DENV1 occurred in 2014–2015, followed by DENV2 dominance in 2017–2018. In year 2021, there was a shift in dominance of DENV4 serotype in the country and DENV2 became dominant again in 2023–2025.

Recovery from infection by one serotype provides prolonged immunity against that serotype only, and subsequent infections by heterologous serotypes give rise to the potential immunopathology of severe dengue due to antibody-dependent enhancement. Patients with a second dengue infection with a different serotype are at increased risk of severe dengue. One of the challenges to the development of a dengue vaccine is that it must induce immunity to all 4 serotypes.

With the increasing disease burden and economic modelling supporting the introduction of dengue vaccination, one model suggests that routine vaccination starting at age 7 could reduce symptomatic cases by 34–42% and hospitalisations by 38–47%, resulting in savings of approximately RM 4 billion over 30 years from 2025.