Genetic Patterns May Identify Who Is at Risk for Life‑Threatening Dengue Complications
When you have dengue, you typically feel like you’re dying. But with proper care, only 5 to 20 percent of dengue cases develop life-threatening complications. This progression is related to a set of 20 genes that can predict who is at risk for dengue hemorrhagic fever and dengue shock syndrome, according to a recent discovery by scientists at the Stanford University School of Medicine, who hope the finding can be developed into a test that identifies vulnerable patients.
Currently, medical protocol is to monitor for certain symptoms, or for results of lab tests, that signal severe dengue (previously known as
dengue hemorrhagic fever), but these complications only manifest in the late stages of the disease— often after the patient appears to be on the mend.
“These practices are not nearly sensitive or accurate enough, and some patients end up admitted to the hospital unnecessarily, while others are discharged prematurely,” said Dr Shirit Einav, the study’s co-senior author and an associate professor of medicine, and of microbiology and immunology at the University.
Over the past decade, the number of dengue cases have been steadily rising in India, a fact widely credited to rapid urbanization and climate change — which means India is likely to see many more dengue cases in the future, as both trends accelerate. In 2017, of the 1,88,401 dengue cases recorded across the country, 325 were fatal; there is no record of how many progressed to severe dengue and recovered.
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Dengue is endemic to many countries around the world, and its strains vary. Purvesh Khatri, PhD, an associate professor of medicine and of biomedical data science at Stanford and one of the study’s authors, said the team collated data from five previous studies involving at total of 450 patients. “We looked at the data and asked, ‘Irrespective of the patient’s genetic background, age and the genetics of the dengue virus itself — different regions have different forms of dengue — what is the molecular response that always shows up when you have a dengue infection?'” Khatri said. “But we weren’t comparing healthy versus infected patients; we compared those who had an uncomplicated dengue infection with those who developed severe dengue.”
The individuals who developed severe dengue had a particular pattern of expression among 20 genes; 17 of which underexpressed, while three were overactive. But the degrees of under- and over-activity varied, prohibiting the development of a clear-cut pattern.
So, the team developed a score informed by these genes’ patterns of expression; they higher the score, the more risk of severe dengue. “This prediction method is more of a continuum than a binary,” Khatri said.
In two tests, one based on data and the other based on human patients, the expression score was able to predict with 100 percent accuracy the patients who developed severe dengue, though only three-quarters of those predicted ultimately developed the complication.
Their scoring mechanism is a long way from clinical application, but it’s one of the more promising developments in dengue treatment in a long time, if only because it “is already performing better than the current standard of care,” Einav said.