New Dengue Naming System to Aid Variant Tracking

Genomic surveillance of the evolving SARS-CoV-2 virus has been essential for managing the COVID-19 pandemic, helping researchers identify new variants, track their circulation, and create new vaccines that target the most common emerging variants. The same approach is applied when developing annual flu shots.

This work, however, requires a structured naming system for new variants so that everyone studying and tracking viruses can be on the same page, speaking the same language. To date, dengue virus - the most common mosquito-borne disease worldwide, with more than 12 million cases reported this year already - has lacked an effective naming system.

But Yale researchers and scientists in 14 other countries have established a new system of dengue lineages which, they say, will allow better tracking and improve vaccine development. They recently described the new system in a study published in the journal PLOS Biology.

Dengue virus is spread by mosquitoes and can cause high fever, head and body aches, nausea, and rash in infected individuals. It can also be fatal in severe cases.

While dengue is most common in tropical and subtropical climates, outbreaks in those regions have increased in recent years and dengue has now spread outside of those regions. In 2023, the World Health Organization (WHO) documented nearly 4.6 million cases of dengue infection in the Americas - the region most affected by the virus. So far this year, WHO has documented over 11.7 million. Countries that haven't typically seen cases of dengue, such as the United States and Italy, now are.

"From a public health perspective and from a vaccine development perspective, dengue virus genomic surveillance data is critically needed," said Nathan Grubaugh, associate professor of epidemiology (microbial diseases) at Yale School of Public Health (YSPH) and senior author of the study. "But so far, the way we've organized dengue virus genomic data has been too broad to offer useful information."

To make available data more useful, researchers have typically divided it into smaller categories. But different countries and research groups have developed separate systems, meaning researchers might use different names for the same variant, complicating tracking efforts.

Getting on the same page was important, says Grubaugh, especially with increasing numbers of dengue infections globally and new vaccines rolling out.

Grubaugh and Verity Hill, an associate research scientist in the Department of Epidemiology at YSPH and lead author of the study, reached out to colleagues around the world to create a working group to design a new naming system. They then proposed the design at several international conferences and found universal support.

Essentially, Hill took all of the world's dengue virus genomic sequencing data, updated the standard definitions of what qualified as a separate genotype, then added two new sub-genotype categories - major and minor lineages. Moving from broad categories to narrower ones means new potentially harmful variants will be easier to study.

"With broad categories it can look like regions are affecting by just one or two versions of the virus," said Hill. "But with this increased resolution, we start to see a number of lineages that are circulating around regions."

International colleagues agree this new system will be essential for effectively tracking this growing viral threat.

"The new lineage system we developed provides a crucial tool for understanding the genetic diversity of the dengue virus and enhances our ability to track viral spread and evolution," said Anderson F. Brito, a virologist at the All for Health Institute in São Paulo, Brazil, co-author of the study, and former postdoctoral researcher at YSPH. "In countries like Brazil, where dengue is a serious public health challenge, this system helps identify emerging lineages and better predict outbreak impacts. Additionally, it allows us to monitor how viral lineages may affect the efficacy of a new dengue vaccine, first deployed months ago in Brazil."

The researchers have also launched a website through which others can find information on the new naming system, access research resources, and suggest new lineages based on their own genomic work.

"We'll have a committee that meets yearly to designate new lineages based on submitted data," said Hill.

This research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number DP2AI176740.

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