WEDNESDAY, March 20, 2002 (HealthDayNews) -- Although it's long been acknowledged that the only practical way to fight smallpox is with a vaccination, new research has raised hopes the disease can actually be treated.
Scientists say they've found a compound that may offer an effective oral treatment for smallpox, which was once the scourge of the Western world. This revelation is being taken very seriously, given an increased public concern over bioterrorism after last year's anthrax episodes.
Two new studies presented today at the International Conference on Antiviral Research in Prague report that an experimental compound appears to stop the growth of the virus in both tissue cultures and in mice.
Smallpox is an infectious virus that spreads from person to person or through contaminated bed linen or clothing. After an incubation period of roughly two weeks, the disease first causes high fever, headache and malaise. Later, it gives way to a scar-forming rash. The rash can cause severe disfiguration, and the disease has a 30 percent mortality rate in developing countries. As yet, there is no effective treatment.
Vaccination against smallpox stopped 25 years ago in the United States. There is currently a shortage of stored vaccine around the world, but the Centers for Disease Control and Prevention (CDC) has recently taken steps to resume vaccine production.
However, the new studies show it may be possible to treat smallpox. Researchers at USAMRIID and the University of California, San Diego, in collaboration with the National Institutes of Health (NIH) and the CDC, have been screening antiviral compounds in hopes of finding a potential therapy.
One compound the researchers have identified is called cidofovir, which interferes with the virus' ability to reproduce. However, cidofovir must be given intravenously, a potential drawback if a large number of people were exposed to smallpox as in a bioterrorist attack.
So, according to study co-author Dr. Karl Y. Hostetler, the team found a way to change cidofovir into a compound that could be taken orally, and this became hexacyloxypropyl-cidofovir (HDP-CDV).
"The really surprising thing was that the activity of the drug itself, after the modification was made, went up by a very large multiple," Hostetler says. "It was over 100 times more active than the unmodified CDV drug. We not only made it orally available, but it became more active as an antiviral."
The researchers found that mice infected with cowpox, a close cousin to smallpox, could be completely protected by five daily oral doses of HDP-CDV. In a second study on tissue culture infected with smallpox itself, researchers found similarly encouraging results.
"After it's activated in the cell, it blocks the virus from copying itself," Hostetler says. "The virus can't keep on replicating and dividing and making more and more copies."
"It's not a vaccine, but it provides a second line of defense," he adds.
Although the research is still preliminary, toxicology tests of single doses at up to 30 times the strength of those used in this study have shown that HDP-CDV didn't appear to cause any side effects.
"Of course, it's hard to translate these findings from this little animal model into people," says Hostetler.
Infectious disease expert Dr. Gregory J. Moran, an associate professor of medicine at the University of California at Los Angeles, was part of a national symposium that discussed the scenario of a smallpox outbreak in a medium-size American city. He says that ideally, such a scenario would never happen.
"But if there were to be an outbreak, and presumably any outbreak now would be due to some intentional exposure, then it would be helpful to have something that could mitigate the symptoms without using a lot of medical resources," Moran says.
"The more important thing would be to have a vaccine, because that's what's going to really be able to contain it," he says. "But in terms of reducing the mortality from an outbreak, then some treatment may be helpful," especially in a large-scale outbreak.
Still, says Moran, if a small-scale outbreak occurred in the United States, modern medical care and quarantine procedures would make a 30 percent mortality rate unlikely.
However, Hostetler says an oral therapy could be crucial: "After September 11, and followed by the anthrax releases, now it looks like we need to look harder than ever [for a therapy], because anything is possible now."
The anthrax bacterium, which was sent through the mail last fall, infected 22 people in the United States, killing seven. Eleven of those victims -- including all who died -- contracted the inhalation form of the disease, while the rest were infected through the skin.
What To Do: Find out more about smallpox from the Centers for Disease Control and Prevention, the World Health Organization or the Johns Hopkins Center for Civilian Biodefense Strategies.
