THE GROWING THREAT OF DENGUE: SHIFTING EPIDEMIOLOGY

Current Endemic Landscape of Dengue

The threat of dengue has expanded beyond traditional areas of endemicity, with over half the world's population now estimated to live in areas at risk of dengue virus transmission.^[1] Multiple factors have contributed to the recent spread of dengue, including globalization, climate change, and increasing urbanization.^[2,3] Identified in 2019 by the World Health Organization as one of the top 10 threats to global health,^[4] dengue remains a significant international public health problem, causing 24 million to 130 million symptomatic cases and 10,000 to 50,000 deaths annually.^{[1, 5,6]} As with many other neglected tropical diseases, dengue has significant economic and social effects, focused mainly in low- and middle-income countries endemic for the disease, with associated costs estimated at $9 billion US annually.^[7] Decision-makers around the world need to adequately plan and respond to the increasing global threat of dengue.^[3]

Dengue Transmission

Dengue virus is a flavivirus transmitted primarily by Aedes aegypti and less commonly by Aedes albopictus mosquito vectors.^[8] The virus is maintained in endemic/epidemic cycles primarily in subtropical and tropical urban areas, with Ae. aegypti populations living and breeding in close contact with humans.^[2] Transmission of the virus primarily occurs through bites to humans by infected mosquitoes and subsequent infection of mosquitoes from biting viremic humans (horizontal transmission) (Figure 1), although some vertical transmission (directly from adults to offspring) and venereal transmissions (from infected males to uninfected females) occur within mosquito populations.^[9] Female mosquitoes become infected with dengue virus if they ingest blood from an infected human during the acute febrile and viremic phase of the illness.^[2] Initially, the virus infects the midgut cells, followed by other tissues and ultimately the salivary glands approximately 8 to 10 days after infection. At this point, the mosquito can pass the virus to a human during feeding, with symptomatic disease occurring approximately 4 to 7 days later. Mosquitoes remain infected and can therefore infect multiple humans during their life span (approximately 1 to 2 weeks).^[2]

Figure 1. Transmission Cycle of Dengue in Humans and Mosquitoes^[2]

 

There are 4 dengue virus serotypes (DENV-1, -2, -3, and -4), which co-circulate in many endemic areas and, while infection with 1 serotype is thought to provide lifelong protection against that serotype, together with transient cross-protection against other serotypes, an individual can have more than 1 infection during their lifetime. Subsequent infection with a different serotype leads to increased risk of hospitalization and more severe disease, at least in part due to antibody-dependent enhancement.^[10-12] Additionally, as mosquito vectors can be infected with multiple arboviruses within endemic regions, there is the potential for co-infection with other potentially serious infections, including Zika and chikungunya.^[13,14]