The Devil's Disease: Dengue Fever

A fascinating summary of the machinations of the Dengue Virus and the difficulties in creating a vaccine for this disease, which is a leading cause of hospitalization in eight tropical Asian countries and which has also been seen recently in the U.S. --from the Johns Hopkins School  of Public Health.
Uvealblues


Spiking fever, searing muscle and joint pain, blood seeping through the skin, shock and possibly death—the severest form of dengue fever can inflict unspeakable misery. Once rare, dengue fever now threatens more than 2.5 billion people. What will it take to stop an old disease spreading with a new vengeance?


Some 2,000 years ago in the Nile region of Egypt, a deadly pathogen confined within a specific species of mosquito found a way to thrive in a new host: human beings. Curiously, a legend among peoples in those ancient times bears striking parallels. In it, Allah punishes a sinful leader called Nimrod by inserting a mosquito into his brain. Driven mad by the insect’s buzzing, Nimrod begs a servant to crack open his skull, allowing the mosquito to fly free.

Ka-dinga pepo, marked by its bright red rash, first appeared in isolated epidemics in tropical and subtropical regions. But as the centuries passed, the mosquito that transmitted the virus stowed away with slave traders and rum-runners, slowly taking hold in new surroundings across the world. By the 17th century, it reached the docks of Boston and Philadelphia.

Everywhere, it infected humans—most frequently children—with spiked fevers, terrible pain in joints, muscles, bones and behind the eyes. It could even cause blood to ooze through the pores. It acquired a variety of graphic names, the best known of them attributed to Dr. Benjamin Rush, a signer of the Declaration of Independence. Rush treated an outbreak in 1780 Philadelphia and, observing the misery afflicting its victims, called it “Break Bone Fever.” In Swahili, however, it was still known as ka-dinga pepo, a disease of the devil. It was but a short linguistic jump for it to become known worldwide as dengue fever.

Whatever its origins, scientists, medical professionals and disease control experts are concerned now with the most recent history of dengue (pronounced DEN-ghee). Before 1950, a typical world map depicting affected regions contained few flecks of color. A dab in Africa, a small glob in Southeast Asia, a sliver of color in South America. Today, it’s as if a can of paint spilled across the bottom half of the map.

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According to the WHO, dengue is the leading cause of hospitalization among children in eight tropical Asian countries. It often overwhelms the national health budgets and fragile health care systems of developing countries. Many scientists refer to it as a disease of poverty.
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With most viruses, a survivor is usually immune to subsequent infections because of antibodies that alert the body to resist new viral invasions. Vaccines—usually weakened forms of a virus—build similar antibodies for resistance. With the eradication of smallpox and near-eradication of polio, vaccine-fostered immunity is a sacred given in public health.

But dengue fever commits sacrilege and it even has its own name: antibody-dependent enhancement. “There’s one thing we are fairly certain of,” says Durbin. “If you have an antibody to a serotype, say Dengue 1, and you are infected with Dengue 2 virus, your Dengue 1 antibody won’t protect you.”

That’s because, says Durbin, the antibody binds itself to the new dengue strain, in effect joining forces with the new virus and helping it gain entry into target cells where it can then replicate. As a result, the bloodstream now contains higher levels of the virus than during the first infection. Often this triggers dengue hemorrhagic fever. Any of the four dengue serotypes can combine with the antibody from any other serotype to cause DHF.

It is, according to Halstead, “a most amazing perversion of the immune response.”

“The cells that are supposed to scout out and kill viruses and the antibodies that are supposed to destroy viruses form an unholy complex to defeat our immune system and promote the life of the dengue virus,” he told a New York Academy of Sciences gathering last year.

The ramifications for dengue fever vaccine development are daunting: A dengue vaccine must be able to combat all four serotypes at the same time. But the hazards only begin there.