Skip to Content
800-533-8762
  • Careers
  • Newsroom
  • Health Care Professionals
  • About Us
  • Contact Us
UPMC
  • Find a Doctor
  • Services
    • Frequently Searched Services
    • Frequently Searched Services
      Allergy & Immunology Behavioral & Mental Health Cancer Ear, Nose & Throat Endocrinology Gastroenterology Heart & Vascular Imaging Neurosciences Orthopaedics
      Physical Rehabilitation Plastic & Reconstructive Surgery Primary Care Senior Services Sports Medicine Telemedicine Transplant Surgery Walk-In Care Weight Management Women’s Health
      See all Services
    • Services by Region
    • Find a UPMC health care facility close to you quickly by browsing by region.
      UPMC in Western Pa. Western Pa. and New York
      UPMC in Central Pa. Central Pa.
      UPMC in North Central Pa. North Central Pa.
      UPMC in Western Md. Maryland & West Virginia
    • See All Services
  • Locations
    • Locations by Type
    • Locations by Type
      UPMC hospitals
      Hospitals
      Physical Therapy
      Physical Therapy
      Urgent care
      Walk-In Care
      UPMC Outpatient Centers
      Outpatient Centers
      UPMC Imaging Services
      Imaging
      Community Health Centers
      Community Health Centers
      See All Locations
    • Locations by Region
    • Locations by Region
      UPMC in Southwest Pa. Southwest Pa.
      UPMC in North Central Pa. North Central Pa.
      UPMC in Northwest Pa and Ny. Northwest Pa. & Western N.Y.
      UPMC in West Central Pa. West Central Pa.
      UPMC in Central Pa. Central Pa.
      UPMC in Western Md. Maryland & West Virginia
    • See All Locations
  • Patients & Visitors
    • Patient & Visitor Resources
    • Patient & Visitor Resources
      Patients and Visitors Resources Pay a Bill Classes & Events Medical Records Health Library Patient Information
      Patient Portals Privacy Information Shared Decision Making Traveling Patients Visitor Information
      Man uses mobile phone
      Pay a Bill
      Nurse reviews medical chart
      Request Medical Records
  • Patient Portals
  • Find Covid-19 updates
  • Schedule an appointment
  • Request medical records
  • Pay a bill
  • Learn about financial assistance
  • Find classes & events
  • Send a patient an eCard
  • Make a donation
  • Volunteer
  • Read HealthBeat blog
  • Explore UPMC Careers
Skip to Content
UPMC
  • Patient Portals
  • For Patients & Visitors
    • Find a Doctor
    • Locations
    • Patient & Visitor Resources
    • Pay a Bill
    • Services
    • More
      • Medical Records
      • Financial Assistance
      • Classes & Events
      • HealthBeat Blog
      • Health Library
  • About UPMC
    • Why UPMC
    • Facts & Stats
    • Supply Chain Management
    • Community Commitment
    • More
      • Financials
      • Support UPMC
      • UPMC Apps
      • UPMC Enterprises
      • UPMC International
  • For Health Care Professionals
    • Physician Information
    • Resources
    • Education & Training
    • Departments
    • Credentialing
  • Careers
  • Contact Us
  • Newsroom
  • UPMC >
  • Media Relations >
  • News Releases >
  • 063025 genetic ancestry
Media Relations
News Releases
Central Pa. News
North Central Pa. News
Contact Us
Experts
Community-Focused News
Media Kits
Media RSS
Media Relations
News Releases
Central Pa. News
North Central Pa. News
Contact Us
Experts
Community-Focused News
Media Kits
Media RSS

Chat Keywords List

  • cancel or exit: Stops your conversation
  • start over: Restarts your current scenario
  • help: Shows what this bot can do
  • terms: Shows terms of use and privacy statement
  • feedback: Give us feedback
Continue
Chat with UPMC
RESTART
MENU
CLOSE

Genetic Ancestry Linked to Risk of Severe Dengue

For Journalists

Elaine Vitone
Manager
412-925-0320
vitoneeg@upmc.edu

Allison Hydzik
Director, Science and Research
412-647-9975
hydzikam@upmc.edu

Anastasia (Ana) Gorelova
Senior Manager, Science Writing
412-647-9966
gorelovaa@upmc.edu

Want to Make an Appointment or Need Patient Information?
Contact UPMC at

1-800-533-8762.

Go to Find a Doctor to search for a UPMC doctor.

2023 PITT HS

6/30/2025

PITTSBURGH — For the first time, the extreme variability in dengue fever has been linked to a biological mechanism, potentially opening doors to new treatments and vaccines for the most common mosquito-borne disease worldwide. The study was published today in Proceedings of the National Academy of Sciences (PNAS) by researchers from the University of Pittsburgh, UPMC and Instituto Aggeu Magalhães in Brazil.

 

Cases of dengue fever, commonly known as “breakbone fever” for the excruciating joint pain that is the hallmark of the disease, have been rising around the world in recent years. More than half the global population is at risk.

  

“There’s an urgent need for better prevention and treatment for this global threat. Dengue outbreaks can quickly overwhelm local hospitals,” said lead author Priscila Castanha, Ph.D., MPH, assistant professor of infectious diseases and microbiology at Pitt’s School of Public Health. CastanhaPriscila HR

 

The course of the disease varies widely from person to person. Some are asymptomatic; others experience dengue’s painful flu-like symptoms and then recover within days or weeks. “But 5% have serious bleeding, shock and organ failure—they can be critically ill within two days,” said senior author Simon Barratt-Boyes, Ph.D., professor of infectious diseases and microbiology at Pitt Public Health and immunology at Pitt School of Medicine.

 

For decades, epidemiologic studies have documented a puzzling phenomenon: In countries with ethnically diverse populations—like Brazil, Colombia, Haiti and Cuba—people of African ancestry tend to have milder cases of dengue, while people of European ancestry have more severe disease. But no one could explain why.

 

In this study, the team used a model they developed with samples of human skin that had been donated by individuals who had undergone elective skin-reduction surgeries after profound weight loss. The participants consented to contributing their tissues to this study. 

 

“We used skin because it is an immunologic organ and the body’s first line of defense against dengue infection,” said Barratt-Boyes. When maintained in culture under proper conditions, the tissue samples used in this model can survive and carry out their normal immune functions for days, providing a unique opportunity for scientific study, he added, “because the skin is where the story begins with all mosquito-borne diseases.”

 

BarrattBoyesSimonMThe study focused on samples from individuals who had self-identified as having European or African ancestry. First, the researchers objectively measured the ancestral geographic origins written into the skin samples’ DNA by analyzing genetic markers known as single nucleotide polymorphisms. The team then injected each sample with dengue virus, observed the samples’ subsequent immune responses over a 24-hour period and compared them.

 

The team found that the inflammatory response was much greater in skin from people with higher proportions of European ancestry. And unfortunately, in severe dengue, this immune response is prone to “friendly fire.” The virus infects inflammatory cells, actually recruiting them to spread the infection instead of fighting it off. This dynamic is believed to be what is so damaging to blood vessels and organs in severe cases of dengue fever.

 

In the samples from donors of European ancestry, the team saw this friendly fire in action as myeloid cells mobilized to confront the virus, then themselves became infected. The turncoat cells then moved out of the skin and spread out into the dish—similar to how they would spread within the body, traveling through the bloodstream and into lymph nodes.

 

The team further showed that the problem was not the skin itself—it was indeed the inflammatory response. In the samples from individuals with higher proportions of African ancestry, the researchers added inflammatory molecules called cytokines, and the friendly fire ensued. Then, when the team blocked the inflammation within those same samples, the virus’s rate of infection in the cells plummeted.

 

“It makes sense that, in parts of the world where ancient populations were exposed to deadly mosquito-borne viruses—like the one that causes yellow fever, which is related to dengue viruses and has been around for a very long time—those with a limited inflammatory response had an advantage,” said Barratt-Boyes. “They then passed that advantage down to their descendants.” Ancient Europeans’ descendants, however, lack that ancestral exposure and the evolutionary adaptation it made possible.

 

The authors hope that, eventually, the mechanism they’ve identified could be exploited for precision medicine approaches to things like risk assessment, triage in an outbreak, therapies and vaccines. In future studies, they hope to describe this mechanism in further detail, including which specific gene variants contribute to protection from severe dengue. The current study’s broader analysis of geographic ancestry could be an important first step to that end.

 

“Ancestry does affect biology. Evolution has made its mark on everyone’s DNA,” said Castanha.

 

Other authors on the study are Michelle M. Martí, M.S., Parichat Duangkhae, Ph.D., Jocelyn M. Taddonio, M.S., Kristine L. Cooper, M.S., Megan Wallace, M.S., Gwenddolen Kettenburg, M.S., Geza Erdos, Ph.D., Hasitha Chavva, M.S., Aleena Alex, M.S., Pharm. D., J. Peter Rubin, M.D., Simon C. Watkins, Ph.D., Louis D. Falo, Jr., M.D., Ph.D., and Jeremy J. Martinson, Ph.D., all of Pitt; and Ernesto T. A. Marquesa, M.D., Ph.D., of Pitt and Instituto Aggeu Magalhães.

 

This research was supported by Pitt, the Institute for Precision Medicine, the Richard K Mellon Foundation for Pediatric Research and the National Cancer Institute (P30CA047904).


PHOTO DETAILS: click images for high-res versions

 

Right photo:

 

CAPTION: Priscila Castanha, Ph.D., M.P.H., assistant professor of infectious diseases and microbiology at the University of Pittsburgh School of Public Health.
CREDIT: University of Pittsburgh

 

Left photo:

 

CAPTION: Simon Barratt-Boyes, Ph.D., professor of infectious diseases and microbiology at the University of Pittsburgh School of Public Health and of immunology at the University of Pittsburgh School of Medicine.

CREDIT: University of Pittsburgh

  

UPMC
200 Lothrop Street Pittsburgh, PA 15213

412-647-8762 800-533-8762

Patients And Visitors
  • Find a Doctor
  • Locations
  • Pay a Bill
  • Patient & Visitor Resources
  • Disabilities Resource Center
  • Services
  • Medical Records
  • No Surprises Act
  • Price Transparency
  • Financial Assistance
  • Classes & Events
  • Health Library
Health Care Professionals
  • Physician Information
  • Resources
  • Education & Training
  • Departments
  • Credentialing
Newsroom
  • Newsroom Home
  • Inside Life Changing Medicine Blog
  • News Releases
About
  • Why UPMC
  • Facts & Stats
  • Supply Chain Management
  • Community Commitment
  • Financials
  • Supporting UPMC
  • HealthBeat Blog
  • UPMC Apps
  • UPMC Enterprises
  • UPMC Health Plan
  • UPMC International
  • Nondiscrimination Policy
Life changing is...
Follow UPMC
  • Contact Us
  • Website/Email Terms of Use
  • Medical Advice Disclaimer
  • Privacy Information
  • Active Privacy Alerts
  • Sitemap
© 2025 UPMC I Affiliated with the University of Pittsburgh Schools of the Health Sciences Supplemental content provided by Healthwise, Incorporated. To learn more, visit healthwise.org
Find Care
Providers
Video Visit
Portal Login