Two down, one to go: After decades-long campaign, type 3 polioviruses are set to be eradicated

After months of bad news, the international army of people who have been working for decades to eradicate polio will likely have something to celebrate this week. A global commission is expected to announce that type 3 polioviruses have been eradicated.

The announcement is expected on Thursday, which is World Polio Day. If it comes, type 3 polio will be the second species of polioviruses to have been vanquished. There were originally three types of polioviruses, named 1 through 3. With the eradication of type 3, only type 1 polioviruses remain.

Having something to cheer is seen as a morale booster for the many people who have been working so long on this elusive project, as well as a way to show weary funders and countries eager to focus on other health priorities that ground is being gained. The formal bid to eradicate all polio began in 1988 and is now nearly 20 years past its original target date.

“It is important to have some good news to show the world that we are making progress, even though it is a challenging situation and we have huge hurdles,” said Michel Zaffran, director of polio eradication for the World Health Organization, one of several partners in the campaign.

Carol Pandak, director of Rotary International’s PolioPlus program, agreed. The idea of an effort to rid the world of polio originally came from the Rotary movement, and Rotarians around the globe have raised over $2 billion for the campaign over the years.

“From a Rotary perspective, we’re pleased to see that this may happen. And it would mark an important milestone in our progress,” Pandak told STAT.

As with all things related to the complicated effort to end polio, however, even a celebration has to strike a careful balance. Too much bad news may discourage funders and partners. But celebration of a job partly done must underscore that there’s much more work to do.

“I think that’s something to celebrate,” said Dr. David Heymann, who for a number of years oversaw the WHO’s polio efforts and who now chairs a committee that advises the eradication campaign. “Of course the risks with that are that people misunderstand and the donor funding base disappears in countries and in the donor community. So it’s a very delicate road to travel.”

Next month will mark seven years since the last type 3 poliovirus was spotted, in Nigeria. The process of declaring a poliovirus species eradicated can begin if it has not been detected for three years. But there has been no rush to declare type 3 viruses gone. Likewise, more than 15 years passed between the last detection of a type 2 poliovirus in 1999 and the 2015 declaration it was eradicated.

Certifying that a species of polioviruses is truly gone is a methodical process that involves collecting and studying data from around the world. It is overseen by the Global Commission for the Certification of the Eradication of Poliomyelitis.

“The level of certainty has to be very high,” Dr. David Salisbury, chair of the panel, told STAT.

The commission met last Thursday and Friday in Geneva. In addition to human data outlining when the last known cases of type 3 paralytic polio occurred, the panel also had information about polioviruses detected by the multiple countries that conduct sewage surveillance for the viruses. By now more than 1.5 million environmental (sewage) or fecal samples have been tested and none has contained type 3 polio, Salisbury said.

On occasion, those same samples test positive for type 1 polioviruses as well as for viruses from the live polio vaccine used in many parts of the developing world. That increases confidence, Salisbury said, “that if there was wild-type 3 [poliovirus], you’d have found it.”

Declaring the virus gone isn’t simply a ceremonial matter, the checking of a box. It comes with new tasks, including work to ensure that any type 3 polio that exists anywhere in the world — in vaccine manufacturing facilities or research laboratories — is catalogued and adequately contained.

The goal is to guarantee that a virus that has been driven from the world isn’t unleashed on it again by accident or human error. Heymann, a professor at the London School of Hygiene and Tropical Medicine who heads a committee working on containment of type 2 viruses, said there will need to be a global action plan to contain type 3 viruses as well.

Were this happening a few years ago, the declaration that type 3 was gone would probably have been followed by a decision to drop the type 3 component from the oral polio vaccine, which currently protects against type 1 and type 3 viruses. But at this point it seems unlikely the polio eradication program would take on that work, given that an earlier move to drop type 2 viruses out of the vaccine isn’t working as planned.

That 2016 effort, known in the polio world as “the switch,’’ saw all countries that use the oral vaccine replace, in a globally synchronized fashion, a 3-in-1 vaccine with a 2-in-1 version that didn’t contain type 2 vaccine viruses. The vaccine viruses are live but have been weakened to make them safe to administer.

(The United States does not use the oral vaccine. It uses an injectable polio vaccine made of killed polioviruses.)

The decision to drop the type 2 component from the vaccine was taken because the viruses in the vaccine can, on occasion, paralyze children. Once there was no further chance of contracting wild type 2 polio, it was thought it would be unethical to continue to subject children to even a small risk from the type 2 vaccine viruses.

Some people argue the same ethical dilemma will be triggered with the declaration that type 3 viruses have been eradicated. But the problems with the type 2 switch will likely dissuade the polio eradication program from attempting another any time soon.

“I don’t think it’s a good idea. I think it’s probably distracting from dealing with type 2 [problems] at this point,” said Nick Grassley, a professor of infectious diseases epidemiology at Imperial College London, who has done work on polio eradication for years. “I don’t think we want to go through that experience with type 3.”

The switch worked well in many countries; the type 2 polio vaccine viruses disappeared after type 2-containing vaccine was no longer used.

But in a number of countries where too few children had been vaccinated against polio, the type 2 vaccine viruses continued to circulate among susceptible children. When polio vaccine viruses cycle through enough children, they can regain the power to paralyze. So far this year nearly 100 children in at least nine countries have been paralyzed by type 2 vaccine-derived viruses.

Most of the outbreaks are happening in sub-Saharan Africa, but China and now Pakistan have reported cases as well.

The way to stop spread of type 2 vaccine viruses is to move in quickly with oral vaccine that targets only type 2 polio. But the stockpile of vaccine made before the switch for these contingencies is running low and the polio eradication program was recently given the go-ahead from the WHO’s expert vaccine committee to use half doses of vaccine if necessary.

The panel, called the Strategic Advisory Group of Experts on Immunization, also told the polio program it could ask manufacturers to restart production of type 2 oral vaccine — a step program organizers are still hoping they can avoid by getting vaccine manufacturers to process leftover bulk vaccine they have in storage.

These problems come at a time when the fight to extinguish type 1 polio appears to be flagging. From a historic low of 22 cases in 2017, the virus has rebounded. This year so far there have been four times that number of children paralyzed by wild type 1 polioviruses.

Type 1 polio circulates now only in Pakistan and Afghanistan, with the former racking up most of the cases, 72, so far this year. Environmental surveillance for polioviruses has shown they are circulating widely in Pakistan, with at least 250 positive environmental samples so far this year.

“The program is not on track in Pakistan,” WHO’s Zaffran said. “That’s a major setback compared to where we were last year and the year before.”

Eradication efforts in Afghanistan are also facing challenges after the Taliban banned polio workers from going house to house to vaccinate children. Vaccination can occur at fixed sites, Zaffran said, but that is a less effective way to reach all children.

Earlier this year type 1 polioviruses were found in sewage surveillance in southern Iran; analysis of the genetic sequences of the three viruses that were discovered showed they were from a chain of transmission from Pakistan.

Iran has a strong immunization program, Zaffran said. But he worries that next time type 1 viruses might spill over from Pakistan to Syria or Yemen or Somalia or other countries where health systems are weak, reigniting local spread in places that have previously eliminated polio transmission, but which aren’t well positioned to fight it now.

These late-stage hurdles and the protracted lengthening of the eradication effort raise concerns funders will tire of the polio goal. Pandak insisted, though, that Rotary is in this battle until the job is done.

“The prospective of Rotary members is that they made a promise to the children of the world,” she said. “And that promise is not yet delivered. I hear it time and again from our leadership to club members that we keep our promises and we will deliver on our promise of a polio-free world.”