By Barry C. Fox, M.D., University of Wisconsin
It’s ironic that just when we think we’ve won the battle to conquer smallpox, we have to fear that it still resides in labs around the world and could be used for bioterrorism. You may be surprised to know that the United States government has obtained enough vaccines to treat up to 2 million people in the event of a bioterrorism attack.

Smallpox: A Feared Disease
The government has a priority list of smallpox vaccine candidates and healthcare first responders. The vaccine can prevent disease even if it is administered three days after exposure. Smallpox is feared for several reasons: the lack of an antiviral treatment, the fact that most people are not immune to the virus, and because it is highly contagious by aerosol particles or contact with the pox.
Let’s take a look at an actual case outbreak from 1969 in Meschede, Germany. There were 17 cases of smallpox during this outbreak. The virus particles disseminated through the air at a single hospital. The index or first case was a young man in 1969 who traveled from Pakistan to Dusseldorf and then Meschede. Along the way, he received a dose of live smallpox vaccine. He became ill 10 days later and was hospitalized with a fever.
Originally, physicians thought he had typhoid fever, and isolation was initiated for any direct patient contact with healthcare workers. But the medical personnel failed to take a history that included his recent vaccination. Although he did have a cough, airborne isolation precautions were not initially implemented. A few days later, when he developed a rash, he was diagnosed with smallpox, confirmed by electron microscopy and isolation of the virus.
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Mysterious Smallpox?
Let’s talk about why this case is so interesting. This is the kind of mystery case that infectious disease physicians love. How did 17 more people contract smallpox? All three floors of the hospital had secondarily infected patients. Why? Linens and dishes had been meticulously separated and disinfected, and the index patient never left the first floor.
Investigators looked carefully at where the nurses had gone, if there were patient visitors, and even at the priest who came to visit the patients. No link was found to the spread of smallpox. You are beginning to see how the theory of an airborne transmission seemed more plausible. Consequently, air currents within the building were studied by releasing smoke in the patient’s room and monitoring where it went.
It entered the hallway where visitors were talking with physicians, as well as the rooms next door. The smoke then went up a stairway into the second floor, where it spread to various rooms. Finally, it went out our index patient’s window, right up the building wall to other open windows, into patient rooms on the third floor. The mystery was solved.
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Final Steps to Conquer Smallpox

So, what about the future of smallpox? The last few vials of smallpox are currently being held in high-security labs in the United States and Russia. Approximately every five years, the World Health Organization, or WHO, meets to make an important decision: Should they eliminate the virus or save the remaining vials?
Although destroying the vials would prevent the virus from being used as a terror-related weapon, leading virologists argue that the stock should be kept for research purposes—just in case the virus re-emerges in the future.
But, in 2014, the almost unthinkable happened; two vials of smallpox were found in a storage freezer box at the National Institutes of Health. The box seemed to date to the 1950s but had only been hiding in that location since 1972; not where it was supposed to be. This, of course, resulted in protocols being re-examined and better security enacted.
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Smallpox in Bioterrorism
Out of the different scenarios that pose a threat in the event of a bioterrorist attack, smallpox could be a lethal weapon. But how would we know we are under a bioterrorist attack? It is difficult to identify the early stages of a bioterrorist attack for several reasons.
First, it is not until medical facilities begin to be overwhelmed with large numbers of victims with similar symptoms that epidemiologists begin to suspect either an epidemic or a bioterrorist attack. If the biological agent happens to be spread by human-to-human contact, 10 or 12 other individuals would likely have already been infected. That makes it difficult to trace the source of the attack and try to contain it.
What would be the first signs of a bioterrorist attack? Some epidemiological clues might help us. You might see an unusual pattern of illness cropping up in the wrong season or a non-endemic area. For example, it would be strange to see a large number of tularemia cases in a geographic area without the appropriate animal vectors. Or you might see an illness that is unusual for a particular population. Or you might even see a large number of birds or animals dying, which would act as a sentinel event. Now you can see why individual vigilance and health department surveillance are essential.
Common Questions about the Battle to Conquer Smallpox
It’s hard to conquer smallpox because it is highly contagious, and also there is a lack of antiviral treatment. This is what makes the disease scary.
Some leading virologists argue they can be used for research purposes since conquering smallpox is only a small part of conquering all diseases.
If a disease spreads in an area that is usually unlikely for it to do, or if a population becomes infected with an illness, not at the usual season, then it probably is a bioterrorism attack.