The dengue virus has evolved “dramatically” in India over the past few decades, according to a study led by scientists at the Indian Institute of Science (IISc), highlighting the need to develop a vaccine against the strains found in the country.
The number of dengue fever cases has been steadily increasing over the past 50 years, especially in the districts of Southeast Asia. However, there are no approved vaccines against the mosquito-borne viral disease in India, although some vaccines have been developed in other countries.
“We tried to understand how different the Indian variants were and found that they were very different from the original strains used for vaccine development,” said Rahul Roy, an associate professor in the department of chemical engineering at IISc Bengaluru.
The study, published in the journal PLOS Pathogens, examined all available (408) genetic sequences of Indian dengue strains from infected patients collected between 1956 and 2018 by others and the team itself.
There are four broad categories serotypes of the dengue virus (1, 2, 3, and 4). Using computational analysis, the team examined how much each of these serotypes deviated from its ancestral sequence, from each other, and from other global sequences.
“We found that the sequence changes in a very complex way,” said Roy, corresponding author of the study. Until 2012, dengue 1 and 3 were the dominant strains in India, the researchers said.
But in recent years, dengue 2 has become more dominant across the country, while dengue 4 once considered the least contagious is now carving out a niche in southern India, they found.
The team investigated what factors determine which strain is dominant at any given moment. One possible factor could be Antibody Dependent Enhancement (ADE), said Suraj Jagtap, a PhD student at IISc and first author of the study.
Immune response recognize and bind pathogen
ADE occurs when antibodies produced during an immune response recognize and bind to a pathogen, but are unable to prevent infection. Instead, these antibodies act as a “Trojan horse,” allowing the pathogen to enter cells and impair the immune response.
Jagtap explained that sometimes people can be infected first with one serotype and then develop a secondary infection with another serotype, leading to more severe symptoms.
The researchers believe that if the second serotype is similar to the first, antibodies in the host’s blood made after the first infection bind to the new serotype and to immune cells called macrophages. This proximity allows the newcomer to infect macrophages, making the infection more severe, they said.
The human body after primary infection
“We knew that ADE increases severity, (but) we wanted to know if it could also change the evolution of the dengue virus,” noted Jagtap. The researchers noted that several strains of each serotype exist in the viral population at any given time.
Antibodies created in the human body after primary infection provide complete protection against all serotypes for about 2-3 years. Over time, antibody levels begin to decline and cross-serotype protection is lost, they said.
The researchers suggest that if the body is infected at this time with a similar – not identical – strain of the virus, then ADE is triggered, giving that new strain a huge advantage and causing it to become the dominant strain in the population. Such an advantage lasts for several more years, after which antibody levels are too low to make a difference, they said.
According to researchers, reported dengue cases in 2018 have increased more than 25-fold (three-year average) since 2002 in India. All the four geographical regions namely – North, East, South and West-Central India show regular increases in dengue cases as well as deaths within 2-4 years, they added.
Read Now:After the end of ice age, the ice sheet of West Antarctica retreated far inland and regained from
