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Dengue Severity Depends on Prior Infection, Genetic Variation

Decoding complex relationship may help vaccine researchers

Scientists have unraveled the mystery of why some cases of dengue are mild while others are severe.
Scientists have unraveled the mystery of why some cases of dengue are mild while others are severe.

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American and Nicaraguan scientists have discovered the reason why a second infection with dengue can often be much more serious, even fatal, than the first.

Dengue is a viral disease spread by mosquitoes. The World Health Organization estimates there may be 50 million infections worldwide every year.

In some cases it causes only a mild fever. In others, the virus can cause a potentially fatal complication called dengue hemorrhagic fever.

Why some cases are mild and others are severe has been something of a mystery that scientists in the U.S. and Nicaragua have now unraveled.

There are four major varieties, or "serotypes" of dengue, and lots of genetic variation within each serotype. Also, in areas where dengue is endemic, people are often infected more than once. The first infection may result in only mild symptoms, and the body produces antibodies that will protect against the particular variety that infected them.

"Those antibodies don't necessarily work against another version of the virus, and those antibodies actually help the other version of the virus to infect the cells that it wants to infect," explained researcher Matthew Henn, of the Broad Institute in Cambridge, Massachusetts.

He said that severe symptoms are more likely when a dengue infection of a particular sub-variety meets a victim whose previous exposure to a different dengue virus has produced a particular set of antibodies.

"And if you have a certain combination of that, you're more prone to get severe forms of the disease."

Henn says the findings of his study have implications for the so-far unsuccessful efforts to develop a dengue vaccine. For example, the vaccine may have to be modified to account for subtypes of the virus that dominate in a particular area.

"There's a good chance that any kind of vaccine that we design for dengue is really going to have to be fine-tuned to the local setting that it may need to be used in."

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