Updated
November 16th, 2017

Dengue Virus Antibodies May Trigger Severe Infections

Children were 7 times more likely to develop severe cases of dengue

New research is reporting that dengue viruses may modify human immune systems to react in a strange way.

Dengue viral infections can result in a range of symptoms. Some people show no symptoms or only have mild signs of the disease. Other people develop severe complications.

Worldwide, millions of people are infected with dengue each year, with the most severe cases resulting in Hemorrhagic Fever/Dengue Shock Syndrome, which can cause blood vessels to leak and organs to fail.

This study found that a prior dengue infection actually enhances the immune system in a negative way, making the next dengue infection worse.

Known as "breakbone fever" because of the intense joint pain, dengue had been causing problems for decades, maybe even centuries.

In 2009, the World Health Organization revised the classification guidelines for severe dengue to improve clinical management of dengue patients and to capture other complications.

But, dengue rarely caused hemorrhaging or death.

Why had it all of a sudden become so dangerous?

This new study, published in the journal Science, finally appears to answer these questions.

In this study, researchers at the University of California, Berkeley, followed about 6,600 children and studied the relationship between pre-existing anti-DENV binding antibodies (DENV-Abs) and dengue disease severity in a large, well-characterized pediatric cohort study in Managua, Nicaragua. There are 4 species of dengue virus and infection with one does not provide protection from another.  The antibodies from the first infection may cause the second infection to be more serious.

"If a child developed dengue, we could go back to the banked antibody samples and say, 'OK, is there something about the children's antibody levels that are different than that of the healthy kids?” says Dr. Eva Harris, an infectious disease researcher at the University of California, who led the study.

These researchers expected the presence of dengue antibodies in the child's' blood would protect them from new dengue infections.

That's what antibodies are supposed to do.

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If you get infected with a virus, your immune system makes antibodies, which then stays in the blood system to fight off future infections from the same virus.

But, with severe cases of dengue, the exact opposite turns out to be true, Dr. Harris and her research team report.

The antibodies actually backfire. And the effect was significant.

Inside the antibody "danger zone," children were more than 7x more likely to develop severe dengue cases, when compared to children who have never been infected with dengue.

"Actually having higher antibodies wasn't helping either," Dr. Harris said.

"The problem is that you can see antibody-dependent enhancement with many viruses inside test tubes," Harris said. "And it's been unclear how these experiments translate to dengue in humans. That's been the crux of the problem."

"The study answers age-old questions about dengue," Dr. Harris said.

“But raises new questions about Zika."

So the big question Is there a "danger zone" of dengue antibodies that would worsen a Zika infection?

"That's another question that we're working on very actively," Dr. Harris says

Some scientists in the field are still skeptical and want still more proof, as Science's Jon Cohen reported.

But, this study opens up interesting theories about why the Zika virus became such a threat in the tropical regions of South America.

These researchers did not disclose conflicts of interest: Leah C. Katzelnick, Lionel Gresh, M. Elizabeth Halloran, Juan Carlos Mercado, Guillermina Kuan, Aubree Gordon, Angel Balmaseda, Eva Harris.