Dengue: A cause for anxiety in endemic regions, a Thai experience

A decade ago, the author of this commentary was a visiting professor at the School of Public Health of Surindra Rajabhat University in Surin, Thailand. He got regular invitations to their Academic Conference during the annual Surin International Folklore Festival. His last visit to this event, in January 2016, gave him sleepless nights. The reason was anxiety triggered by a high-profile dengue death. He had landed a day earlier in Bangkok and took the night train from the capital to Surin, a Thai town near Cambodia. He reached the Hotel in Surin early morning and was sitting in the lounge waiting for the formalities to be completed. The TV in the lounge was showing a large number of mourners in a funeral procession. He guessed that this was no ordinary funeral. He asked at the reception what are they showing in the TV. He was told that popular Thai actor Tridsadee “Por” Sahawong died that morning, five days short of his 36th birthday, after 10 weeks in coma due to dengue hemorrhagic fever.[1] After hearing this, he suddenly started noticing that he was getting mosquito bites on his exposed arms. Aggravating his anxiety was the vexing issue that the sturdy aedes mosquito known as the “tiger mosquito” was a day biter. This makes it difficult to ward off its attack throughout the day when one is exposed. The anxiety and fear of contracting dengue started building up during his 10 days stay in Thailand. He had sleepless nights conjuring up different contingencies, calculating the incubation period to predict whether in case he gets infected, would he be able to return to India or will he get admitted to a hospital in an alien land among people speaking a different tongue? Dengue anxiety is real and high-profile deaths aggravate it. Measuring its intensity with a validated scale is the first step in managing it. Dengue presents challenges in management and vaccine developments, leading to anxious moments for researchers as well. The dengue virus has four serotypes. However, these are like siblings with rivalries instead of similarities. Lifelong immunity develops after recovery from an infection against the infecting serotype only. Cross-protection against other serotypes is short-lived and can instead become a handicap, as a subsequent infection with another serotype increases the risk of severe dengue.[2] This is due to the phenomenon of antibody-dependent enhancement (ADE), in heterogeneous infections by Immunoglobulin G, which when unable to attack the virus join hands with it and facilitates viral entry into the host immune cells via their Fragment, Crystallin, Gamma receptors. This promotes viral replication leading to increased viraemia, increasing the chances of vascular hyperpermeability and severe dengue. However, the exact molecular mechanisms are still not well understood.[2] Early studies in Thailand recognized that dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) peaked in two populations: first-time infected infants born to dengue-immune mothers and children who had experienced a mild or asymptomatic dengue infection and became secondarily infected by a different dengue serotype.[3] The phenomenon of ADE has implications for vaccine development as well. Considering the challenges posed by disease-enhancing cross-reactive antibodies, the objective of vaccine developers was to develop a vaccine with protective antibodies against all Dengue virus (DENV) serotypes.[4] Two such vaccines Dengvaxia and Qdenga are presently available, with different indications. The former is a live attenuated vaccine approved for those with a prior dengue infection. The latter is also a live attenuated vaccine approved for children in endemic areas. While ADE has not been observed with Qdenga, most European countries are cautious and recommend the vaccine only for those with a previously confirmed infection.[4] To conclude, the four strains of the dengue virus pose a public health hazard when infections occur due to different strains at longer intervals. The resultant ADE poses a clinical challenge in the form of severe dengue, DHF and DSS. ADE also poses a challenge in vaccine development. Enough cause for anxiety among dengue researchers. Authors’ contributions AB was responsible for all stages of the manuscript such as concept, drafting, revising and final approval. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Data availability statement Not applicable.