At the end of the decades-long global battle to eradicate polio from the planet, there is what looks like a simple goal: Render every person immune, by vaccination, for long enough that the disease can find no host in which to breed, and thus dies out. That was the strategy behind the eradication of smallpox, and since polio like smallpox affects only humans, it is supposed to work for that disease too.
Of course, it’s a little more complicated, and a paper published last week reveals one of the most challenging complications. It describes a British man of about 30 who, as a toddler, was given the full course of polio vaccines in use at the time—and who, for 28 years, has been harboring mutated, virulent poliovirus in his guts and shedding them in his feces. The researchers who wrote about him call him, and other patients like him, “an obvious risk to the eradication program.”
Long-term shedders of poliovirus have been identified before. It’s a rare phenomenon, and for it to occur, several things have to happen: Someone has to be vaccinated as an infant with the oral polio vaccine, which contains a weakened live virus; has to have an immune-system deficiency that keeps the body from eliminating the vaccine virus after immunity develops; and, usually, has to live in an industrialized country where medical care is good enough to keep children with immune-system deficiencies alive.
That has happened a number of times—more than 70—since polio vaccination began in the 1950s, but only a few people shed virus long enough to make public health planners concerned. This man is the longest-duration shedder known, but he may not be the only one. Sampling programs that look for live poliovirus in sewage have identified mutated vaccine viruses in Finland, Israel and eastern Europe, indicating other, unidentified shedders may be out there too.
A little refresher on polio vaccines: There are two, the original injectable that uses killed virus (Jonas Salk’s original vaccine) and the oral drop version that contains a weakened live virus (Albert Sabin’s formula). The oral vaccine was the first one used in the international eradication campaign, because it is inexpensive to make and can be administered by anyone. It is still used in the developing world, though industrialized countries have gone back to the original injectable.
For all its benefits, the oral version has a known issue, a combination of bug and feature. Once it is given, the vaccine virus replicates in the gut. The feature part is that, when the vaccine virus passes out of the body, it can spread through the environment of places with poor sanitation, conferring a kind of passive secondary immunization on others nearby. The bug part is that, in the few weeks it is replicating, the vaccine virus mutates, and sometimes mutates back past the artificial weakening to the original disease-causing form.
If that reversion happens to someone who lives in an area where vaccination has been patchy, an outbreak of “vaccine-derived” polio can spark—and has, dozens of times since the campaign began. It’s happening right now in Ukraine, in fact, and the World Health Organization is negotiating with the country to begin vaccinations. (There’s an update on the index page of the eradication campaign’s site, but frustratingly it’s part of a slideshow with no static link.)
But those outbreaks have always been easy to detect, and quenched by improved vaccination. However, if the reversion happens in someone who also has an immune disorder, that person becomes a source of infectious virus that mutates continually not for weeks, but for years. And because the person is probably surrounded by other vaccinated individuals, there is no obvious outbreak to help pinpoint the problem—just a slow leak of live virus that could sicken an unvaccinated infant, a vaccine refuser, or a vulnerable immune-compromised adult somewhere else.
The British man’s problem has been known since he was a child—he was first tested in 1995, when one of this paper’s authors was studying the immune condition he suffers from—and numerous attempts have been made to chase polio from his system. None have worked. Extensive analysis of the virus he carries shows that it is virulent, paralyzing lab mice; but also that the vaccines currently in use protect against it.
However. Poliovirus comes in three flavors, strains known for simplicity as type 1, 2 and 3. The vaccines used so far in the campaign have included all three strains, but there are plans to reduce the formula to types 1 and 3 because type 2 has disappeared from the wild. The British man’s strain, however, is type 2, preserved in his system even as it was forced into extinction elsewhere. Could he, or an unlucky person like him, re-ignite an epidemic?
If the world switched from the oral vaccine to the injectable, which the international eradication campaign is planning for, the risk of random outbreaks from mutated virus would go away. The risk of existing shedders continuing to pump out virus would not—not unless vaccination continued indefinitely. The entire goal of the campaign, though, is to vaccinate the world until polio is eradicated, and then stop.
Despite years of fretting, no one has yet proposed a solution to the problem of shedders that accounts for all the complexities: the difficulty of finding them, the necessity of respecting their rights if found, the huge sunk cost of polio eradication that makes it hard to change course, and the difficult sell of achieving novel vaccines that could solve the problem but would be useful only a few years afterward. The authors who wrote up the man’s plight, though, warn that it is definitely time to begin strategizing. “[Vaccine-derived polio] from these patients,” they say, “represent a real risk of polio re-emergence in the post-eradication era.”
Cite: Dunn G, Klapsa D, Wilton T et al. “Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.” PLoS Pathogens, August 27, 2015. DOI: 10.1371/journal.ppat.1005114