According to the World Health Organization, there are about 50 million new cases of dengue fever around the world each year and about 2.5 billion people, two-fifths of the world's population, are at risk. The disease is spreading, along with the mosquitoes that carry it, into areas like Texas in the United States that are far from the tropics where dengue has been present for a long time. Scientists at an independent research foundation have developed a new line of study that shows promise in fighting the often deadly disease.

Dengue fever is a threat to people in more than 100 countries. It is a flu-like disease that produces a high fever, pain in the eyes and joint aches that can last a week.

Dr. Renu Daval-Drager of the World Health Organization says some cases of what is sometimes called "break bone fever" can be fatal. "Dengue does cause death. Usually, one to two percent of the dengue cases can progress to a severe disease called dengue hemorrhagic fever. This disease results in leaky capillaries and also then hemorrhage. And this can also be resolved, but some of these cases will go into shock and organ failure and then die."

There is no vaccine to prevent dengue and no specific medicine to treat it, so the only defense is eradication of the mosquitoes that carry it and measures to protect people from mosquito bites.

But hope is offered by research being carried out at the Southwest Foundation for Biomedical Research in San Antonio, which relies on very special mice.

The small white animals with pink eyes are kept in a special isolated room so that they will not be exposed to any bacteria or germs that might infect them. They have been altered to be susceptible to human diseases.

Lead researcher Rebeca Rico-Hesse says the mice have been modified or "humanized" by an infusion of stem cells taken from human umbilical cords that were discarded at local hospitals. "We have basically reconstituted the human immune system in these mice and it is only because they have these immune system cells that they can get infected and show symptoms of dengue fever," she said.

By infecting these humanized mice with strains of the dengue virus, investigators can study how the disease takes hold and what factors might cause the more serious and often deadly dengue hemorrhagic fever.

A recent report co-authored by Rico-Hesse and her colleague Javier Mota shows for the first time why some strains of dengue virus are more severe than others. "In this report, we present results of eight different virus strains and we show that the ones that have been associated with the more severe epidemics and the ones that cause hemorrhagic fever in patients are actually of a specific genetic variant," she said.

Lab workers infect the mice artificially with the virus, keeping precise records of how much virus and what type of virus is used. But natural transmission of dengue by mosquitoes involves certain proteins the insects inject into the skin, something that Rico-Hesse says is missing when mice are artificially infected in the lab.

"If you are just, you know, injecting it in with a syringe, you are missing out on all those salivary gland factors and all the things that happen during a natural infection that might either speed up the infection rate or decrease the infection rate. And we also need to know how many mosquitoes it takes to infect a humanized mouse," she said.

Rico-Hesse and her colleagues are breeding mosquitoes in the laboratory to test various strains of the dengue virus transmitted to the mice by mosquitoes.

Because of her extensive work in Latin America with dengue fever victims, Rebecca Rico-Hesse says she feels compelled to speed research as much as possible. "I have had the opportunity to go to many of the countries and see the patients, even children dying in the hospitals in very remote areas of South America. So it has given me a sense of urgency to work more, to do things, to make things come along quicker," she said.

Although effective vaccines or antiviral drugs for dengue may still be a long way off, researchers here say they are making important steps that they hope will one day minimize the suffering and death caused by the illness.