New Form of Polio Could Emerge, Say Experts

by Debora MacKenzie

But some polio experts, while paying lip service to this goal, privately doubt it will be that easy. The reason for this doubt is the very weapon that defeated polio. The main vaccine being used to eradicate polio consists of a live, weakened form of the virus. This vaccine virus could persist after the disease-causing polio virus is gone -- and occasionally revert to the dangerous type.

If that happens after vaccination stops, unvaccinated children will be defenseless. Once the disease has gone, "we should not simply stop vaccinating," says Tjeerd Kimman of the National Institute of Public Health and the Environment in the Netherlands. Polio experts raised these concerns at a meeting in Geneva last month.

There is good reason to fear polio. The virus, which is spread by food and water contaminated with feces, doesn't cause serious symptoms in most people. But if it spreads to the nervous system, it can be deadly -- and children are especially vulnerable. In 1955, it killed 2000 people, and paralyzed 16000 in the U.S. alone. By 1963, however, the U.S. had fewer than 100 cases a year, and by 1994 polio had been banished from the Americas.

In 1988, when the WHO launched its global eradication campaign, there were 35000 cases of polio worldwide. In 1998, with 82 percent of the world's children vaccinated, there were just 3200.

So in theory, eradication should be possible. Only humans carry the virus, so if enough people are immunized, the virus will no longer be able to find new victims and will die out, as smallpox did. Then we can stop immunizing people, saving $1.5 billion a year worldwide.

But OPV viruses differ from their nastier relatives by only a few mutations. Paul Fine of the London School of Hygiene and Tropical Medicine says conditions in the gut favour their reversion to pathogenic forms. OPV viruses shed in feces are genetically closer to the dangerous forms, and it is well documented that viruses shed in this way can cause disease.

Usually such reversion happens after the vaccine has induced immunity, so it's very unusual for vaccinated children to become ill. Occasionally, however, they do -- in around one in a million cases. Because of this, and because the likelihood of encountering polio is now low, several European countries and the U.S. now recommend only the inactivated vaccine.

But OPV remains the predominant polio vaccine in the developing world. This is partly because the killed vaccines now available are not as effective as OPV. Don Henderson of Johns Hopkins University, who in the 1970s led the WHO's drive to eradicate smallpox, says the organisation mistakenly believed it had all it needed to banish polio. Writing in Vaccine last year, he said the miscalculation threatened polio eradication. The WHO "in an extraordinary act of ignorance, deliberately scrapped promising efforts to develop an improved vaccine." New vaccine development effectively stopped in the 1960s after the OPV became available.

So for the immediate future we're stuck with large amounts of OPV viruses in the world. Do they pose a threat? That, says Fine, depends on how long they persist after vaccination stops -- and a new generation of susceptible babies emerges.

Reassuringly, he says, the viruses do not seem to survive long in the environment or in most people, and seem not to spread "silently" among immunized people. But they do spread among non-immunised people, such as religious groups in North America and the Netherlands who reject vaccination. There have been no epidemics of paralysis in unvaccinated communities, suggesting that viruses spread in this way are not mutating into the deadly form.

But, Fine cautions, they may simply not have had the chance. Existing non-vaccinated communities are probably not big enough to maintain reservoirs of OPV viruses indefinitely. But the longer the viruses persist, and the more people they infect, the more chance they will have to change.

Ominously, it is also known that OPV viruses can persist for years in people with impaired immune systems, where they also mutate faster than in normal populations -- so the millions of HIV-infected people worldwide might provide a haven for these viruses. Once vaccination stopped, Fine estimates OPV viruses might have to persist only for three to ten years before a large enough population of non-immunised people accumulated to start spreading them. Fine published his calculations at the end of last year in the American Journal of Epidemiology.

Besides the threat of reverting into a deadly form, OPV makes it harder to determine when wild polio virus has been eradicated, Kimman says. The WHO now tests for polio in two ways. One is by watching for cases of paralysis. But only one infection in a hundred or even a thousand causes paralysis. The other test is to look for polio virus excreted into sewage by infected people. But the large amounts of OPV virus excreted by vaccinated people interfere with the tests, and make it hard to detect the wild virus.

At the Geneva meeting, experts debated the merits of continuing vaccination with inactivated viruses for a few years after the last case to eradicate the OPV viruses. Besides giving OPV viruses more time to die out before there are large numbers of non-vaccinated people, the use of inactivated vaccine after OPV vaccination stops would also make monitoring for polio virus easier.

But the cost could be prohibitive. As Kimmans point out, the inactivated vaccine is made from virulent polio virus. If any escaped the vaccine factories, it could be spread by babies too young for vaccination or even by people who've been immunized.

So factories would have to use high levels of containment, making the vaccine very expensive, says Kimman. It is unlikely governments will pay for this, just to prevent possible problems left behind by OPV. As the spectre of polio fades, the WHO already has trouble getting governments to cough up for the existing vaccination programme.

Harry Hull, head of the WHO's polio programme, says that the disease will be eradicated using OPV, but concedes there is no agreement on whether vaccination should completely stop when there are no more cases of polio.

One solution, he says, might be to use an inactivated vaccine made from the weakened viruses now used for OPV. These would do less damage than virulent polio if they escaped the vaccine plant. But that could mean pushing the deadline for eradication back again. "It takes five years to build a vaccine plant," says Hull, "and we're still at the research stage."

And another nagging concern is emerging that could make some afraid to stop vaccinating: bioterrorism. Laboratories all over the world have samples of polio virus. They are supposed to destroy them one year after the disease is eradicated. But prospective terrorists need only hide some now and wait for a generation of unvaccinated children to emerge before they strike. "The horror of polio would make it a good weapon," says Roy Widdus of the WHO. "I would not want to be the one to stop vaccination, given that risk."

So it seems that reports of polio's imminent demise are premature. The current verdict on polio should actually be: down, but not out.