Will an ancient crippler find new legs through bioterror?

As global eradication nears, questions arise about polio

Disease eradication in the current age of bioterrorism inevitably raises the possibility of a defeated pathogen being weaponized. Thus, though smallpox has been eradicated in nature, it lives on as a potential bioweapon. Indeed, smallpox literally remains alive in the known world repositories to enable research that could limit its effectiveness in a bioterrorism attack.

Now comes a similar scenario with polio. Some 125 countries had endemic polio cases in 1988, but now that number has been winnowed down to only six nations. The number of cases of paralytic polio — which was 1,000 per day in 1988 — occurred less than 800 times all of last year, according to David Heymann, MD, executive director for communicable diseases at the World Health Organization (WHO) in Geneva.

"Today in the world, there are actually more [countries] that were polio-free and had polio importations than there are countries with endemic polio," he says. "It is the first time that has occurred."

There are six countries that have continuing polio transmission that has never been interrupted: India, Pakistan, Afghanistan, Egypt, Nigeria, and Niger.

"The epidemiology of polio in all of these countries is changing," Heymann says. "If they have effective campaigns to raise immunization coverage in susceptible children — children under 5 — we believe they will be able to interrupt transmission."

Unfortunately, Nigeria stopped immunizing in some of its northern states last year due to unfounded rumors that the polio vaccine could cause infertility in females. "Those rumors have continued to circulate, and as a result, Nigeria had over half of the 800 cases of polio that occurred last year in the world," he adds. "In addition, Nigeria has exported polio to eight neighboring countries. Those countries had interrupted transmissions in about the year 2000, but they didn’t keep their immunization coverage levels high with polio vaccine. So we see a phenomenon where an endemic country has exported polio to neighboring countries."

The eradication campaign continues in the key regions with immunization plans for vaccinating 63 million children younger than 5. Polio, the ancient crippler, seems to be finally losing its legs. With global eradication now on the horizon, is it foreseeable that vaccinations will end and — as occurred with smallpox — herd immunity will gradually become herd susceptibility? More to the point, could polio possibly become a bioterrorism weapon of the future?

Little attraction or the ideal weapon?

"No self-respecting terrorist is ever going to use the polio virus," says William Sergeant, chairman of the International Poliplus Committee of Rotary International in Oakridge, IL. "Do you realize that of every 200 people who are infected, [only] one of them is paralyzed? I don’t know that any terrorist wants to use a bullet that 199 times [does not do] any good. As a terrorist weapon, it has little attraction."

One could argue that a one in 200 risk of being paralyzed would be sufficient to terrorize people, but it certainly is true that polio is not at the top of the bioterrorist’s weapons wish list. However, that could change as vaccination ends and global immunity wanes.

One article notes that "in a city of 10 million unvaccinated individuals, a rough estimate would be that a single release of virus could result in 7,000 paralytic cases."1 Indeed, Alan Dove, PhD, the co-author of that paper, argues further on his web site [Polio Information Center Online (PICO)] that "as a terrorist weapon, poliovirus is nearly ideal: It is highly contagious, easily released into food or water supplies, and virtually impossible to detect until the damage has already been done."

In any case, both the theoretical threat of bioterrorism and the possibility of reintroduction of wild poliovirus will mean continuing vaccination in some countries for many years.

Inactivated (Salk) poliovirus vaccine (IPV) was licensed in 1955 and was used extensively from that time until the early 1960s. In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent oral poliovirus vaccine (OPV) was licensed and largely replaced IPV use. OPV has been the vaccine of choice in the United States and most other countries of the world since 1963. OPV contains live attenuated strains of all three serotypes of poliovirus.

Live attenuated polioviruses replicate in the intestinal mucosa and lymphoid cells, and in lymph nodes that drain the intestine, according to the Centers for Disease Control and Prevention (CDC). When OPV is used, vaccine viruses are excreted in the stool of the vaccinated person for up to six weeks after a dose. Maximum viral shedding occurs in the first one to two weeks after vaccination. Vaccine viruses may spread from the recipient to contacts. People coming in contact with fecal material of a vaccinated person may be exposed and infected with vaccine virus. For these reasons, the OPV vaccine will no longer be used once polio eradication is declared.

"If a country decides to use vaccine after eradication, it will have to use inactivated polio vaccine," Heymann says. "Countries will make that decision [to continue vaccinating] based on the information that they have. That information will include whether or not they consider polio an agent that could be used in bioterrorism. It has never been used in the past. It has never been placed on the list of pathogens that may be used in bioterrorism by the international group in Geneva. But there will be countries, I am sure, that will consider that it might be a risk; and they will want to consider continuing vaccination."

There is a problem, however, that differentiates poliovirus from smallpox virus. With the latter, researchers do not need the virus to make the vaccine, which is comprised of vaccinia (cowpox). Thus debate has continued about destroying the remaining stocks of smallpox virus. In contrast, stocks of live poliovirus must be available to create the inactivated polio vaccine.

"That is a major difficulty. There are two things that are being done. One is that the companies that produce inactivated vaccine are developing maximum-security areas where they can grow the virus and produce the vaccine," Heymann says. "The second thing is to see if it is possible to produce inactivated polio vaccines from the Sabin [attenuated] virus. There has been vaccine produced from that that is effective, but the question remains whether this can become the procedure which industry will use. We know that some companies don’t want to change their procedures because then there is a whole new licensing [requirement]. So there [probably] will be wild polio virus that is used in vaccine production."

Biosecurity on the front burner

Thus biosecurity at vaccine production and storage facilities will be a major concern as immunizations halt after eradication is achieved.

"One of the things that has been done is inventorying laboratories in anticipation of us getting to the end on polio eradication," explains James Hughes, MD, director of the CDC center for infectious diseases.

"We’ve been involved in helping inventory labs in the United States so that we know, first, where polio virus is. We will be in a position to take whatever action the global community decides is appropriate when the time comes," he adds. "Polio is a disease where the infection is usually asymptomatic, so it is possible that in addition to polio stocks that might be around in laboratories, there might be stool specimens harboring poliovirus. All of that inventorying has to be done as we begin preparing to — at a minimum — consolidate the residual [live virus] stocks in a few places."

Even then there is some question whether the disease will truly be eradicated, particularly since researchers have shown that poliovirus can be genetically created in the lab.2 Regardless of origin, the WHO has contingency plans for the reappearance of polio.

"As we finish the job of interrupting polio transmission, we are also developing mechanisms, which can be used after polio eradication to intervene should there be polio," Heymann says. "Those mechanisms will include a stockpile of oral polio vaccine. It will probably be a monovalent vaccine, but that has to be licensed. There will be a response mechanism that is based at WHO — a global alert and response network that will respond to polio should it occur."

Ultimately, it appears — just as with smallpox — poliovirus will be defeated in the wild but live on under lock and key in designated laboratories.

"Most countries are now doing their inventories — that’s the first phase," he explains. "The second phase is consolidating the specimens, and the third is putting them under maximum security. So it will be treated just as the smallpox virus."

References

1. Dove AW, Racaniello VR, The polio eradication effort: should vaccine eradication be next? Science 1997; 277:779-780.

2. Cello J, Paul AV, Wimmer E. Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template. Science 2002; 297:1,016-1,018.