IISc study shows how dengue evolved in India over last 50 years

“There are no approved vaccines against dengue in India, although some vaccines have been developed in other countries. We were trying to understand how different the Indian variants are, and we found that they are very different from the original strains used to develop the vaccines,” said Rahul Roy, Associate Professor at the Department of Chemical Engineering (CE), IISc, and corresponding author of the study published in the journal PLoS Pathogens.

He and the other collaborators examined all available 408 genetic sequences of the Indian dengue strains from infected patients collected between the years 1956 and 2018 by others as well as the team themselves.

There are four broad categories – serotypes – of the dengue virus (Dengue 1, 2, 3 and 4). Using computational analysis, the team examined how much each of these serotypes deviated from their ancestral sequence, from each other, and from other global sequences. “We found that the sequences are changing in a very complex fashion,” said Roy.

Until 2012, the dominant strains in India were Dengue 1 and 3. But in recent years, Dengue 2 has become more dominant across the country, while Dengue 4 – once considered the least infectious – is now making a niche for itself in South India, the researchers found.

“The team sought to investigate what factors decide which strain is the dominant one at any given time. One possible factor could be Antibody Dependent Enhancement (ADE). Sometimes, people might be infected first with one serotype and then develop a secondary infection with a different serotype, leading to more severe symptoms,” said Suraj Jagtap, a PhD student at CE and the first author of the study.

“We knew that ADE enhances severity but we wanted to know if that can also change the evolution of dengue virus,” he added.

At any given time, several strains of each serotype exist in the viral population. The antibodies generated in the human body after a primary infection provide complete protection from all serotypes for about two-three years, the study claimed.

Over time, the antibody levels begin to drop and cross-serotype protection is lost. The researchers said that if the body is infected around this time by a similar, not identical, viral strain, then the ADE kicks in, giving a huge advantage to this new strain, causing it to become the dominant strain in the population. Such an advantage lasts for a few more years, after which the antibody levels become too low to make a difference.

“Nobody has shown such interdependence between the dengue virus and the immunity of the human population before. Such insights are possible only from studying the disease in countries like India with genomic surveillance because the infection rates here have been historically high and a huge population carries antibodies from a previous infection,” Roy said.