Sadly, it's never the wrong time to blog about polio. There's almost always a news hook. This time, it comes from Papua New Guinea, where a new outbreak of the disease has now reached the capital. As the depressing regularity of these kinds of events suggests, they're not freak accidents. They're predictable - and thoroughly predicted - side-effects of a fundamental tactical blunder by the World Health Organization (WHO).

Begun in 1988, the WHO plan to eradicate polio by the year 2000 2005 2010 2018 sometime in the future relies heavily on the oral polio vaccine (OPV). OPV is a milestone in virological history, and was a huge breakthrough when it was developed. It does, however, have some drawbacks. As I explained in my 2013 post:

The problem is that OPV, originally developed by Albert Sabin, contains live attenuated viruses that routinely revert to wild-type, paralytic strains in vaccinated people. It’s the only vaccine in general use that can cause exactly the disease it’s meant to prevent, and it does so in one of every few million vaccinees. For the eradication effort, a bigger problem is that many, if not all vaccinees secrete the reverted virus for some time. Kids take the vaccine, and a few days later they’re pooping out live, potentially paralytic virus. That’s not a big deal if everyone around them is vaccinated, but in areas where vaccine coverage is spotty it can – and does – lead to outbreaks of polio caused by vaccine-derived strains.

In the eradication program, that has fed a pattern of triumphant declarations followed by major setbacks. A country uses OPV to eliminate wild poliovirus circulation, is declared "polio-free" by the WHO, and then gradually forgets about the disease. Public health budgets get redirected or cut, and vaccination rates decline until the vaccine-derived virus that was waiting in the sewers the whole time re-emerges. Lather, rinse, repeat.

Some of Sabin's vials.

There is another polio vaccine, IPV, made with inactivated virus. Derived from the vaccine Jonas Salk originally developed, IPV has become part of the standard immunization series for children throughout the developed world. Unlike OPV, IPV cannot cause polio and cannot revert, because the virus in it is completely inert. It's dead.

Clearly, the solution to the problem of OPV-derived outbreaks is to have everyone switch to using IPV. Because IPV has to be delivered with a needle, though, it costs a bit more to administer than OPV. The difference is negligible for rich and middle-income countries, but prohibitive in places like Papua New Guinea.

The WHO's latest answer to this is to keep using OPV in poor countries, but to withdraw it more gradually and deliberately, rather than just waiting for immunization rates to tail off. The key to this strategy is that there are three serotypes of poliovirus; immunity to one doesn't protect against the other two. As a result, there are three serotypes in the vaccine. What if we try eliminating them one at a time, instead of all at once? That's exactly the experiment the WHO is doing now.

Type 2 poliovirus was the first to be completely eliminated in the wild, so the WHO switched to using a vaccine that contains only types 1 and 3. As my colleague Vincent Racaniello explains, it's sort of working so far. Like everything else in the polio eradication campaign, though, this success is extremely fragile:

These findings suggest that circulation of type 2 [vaccine-derived poliovirus] can be limited if immunization rates are high in these key regions. Whether or not this goal can be achieved is not known – the areas with low population immunity against poliovirus are typically those with social conditions that prevent adequate vaccination.

Whatever approach they take, the WHO will ultimately have to end all OPV use to eradicate polio. After that, the only vaccine available will be IPV. That will bring the world to the final dilemma of this campaign: vaccine manufacturing.

Making a batch of IPV is conceptually straightforward: grow a huge batch of wild-type poliovirus of all three serotypes, treat it chemically to inactivate it, then fill the vials for shipping. But how will we do the first step safely in a world that's stopped vaccinating?

There are really only two solutions, neither of which is practical. We can either develop an entirely new inactivated polio vaccine that doesn't use the intact virus, or build new vaccine manufacturing plants that use BSL-4 containment, and hope nothing goes wrong. Either would require an immense investment by manufacturers, for a product with vanishingly tiny profit margins. Outside of a few speculative projects by basic research labs, I'm not aware of anyone putting serious effort into this problem.

A more sustainable solution would be to set aside the notion of eradicating one virus, and focus more generally on disease control. This would mean making long-term commitments to building public health infrastructure, providing basic healthcare to everyone, and fixing fundamental sanitation problems such as open defecation. If everyone in the world drank clean water and received the standard immunization series, a whole slew of diseases, including polio, would simply fade away.

The standard rejoinder to that idea is that lofty long-term goals are too hard to sell politically, too hard to fund, and too hard to implement. Eradicating a virus is easier to understand. But we're thirty years into the polio eradication campaign. Does it really still look easier?

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