Last week, the Global Polio Eradication Initiative (GPEI) reported seven children, six in the Democratic Republic of the Congo (DRC) and one in neighboring Burundi, had recently been paralyzed by poliovirus strains derived from a vaccine meant to prevent the disease. Unfortunately, such cases are so common—786 were reported last year in Africa, Yemen, and elsewhere—that these seven might not have stood out against the noise. But there was a key difference, GPEI said in a 16 March statement: These are the first cases linked to a new polio vaccine that was painstakingly designed to avoid just this problem.

Known as novel oral polio vaccine type 2 (nOPV2), it was rolled out 2 years ago this month, and public health experts have been closely monitoring whether its use could also spark outbreaks on rare occasions. “It’s disappointing but not entirely unexpected,” says Aidan O’Leary, who heads GPEI. To Simona Zipursky of the World Health Organization, who co-chairs GPEI’s nOPV2 working group, the question for the past 2 years has been when, not whether, such cases would occur. “But you always hope you are wrong,” she says.

Although the novel vaccine is not a magic bullet, the data from the initial rollout show it’s far better than the one it has largely replaced, monovalent OPV2 (mOPV2), Zipursky and others say. The risk of sparking outbreaks with nOPV2 is “much, much lower,” says Ananda Bandyopadhyay, deputy director of technology, research, and policy for polio at the Bill & Melinda Gates Foundation and the other co-chair of the GPEI working group.

Cheap and easy to use, Albert Sabin’s OPV is hands down the best vaccine for eliminating polio in poor settings where clean water and sanitation are lacking. Children shed the weakened virus from the vaccine in their stool for a short time after they receive the oral drops, conferring immunity even on those who are not vaccinated. The problem is that in areas where polio vaccination rates are low, in rare cases the vaccine virus can continue to spread among un- or underimmunized people for months, accumulating enough mutations to revert to its paralytic form. This happens most often with poliovirus type 2, one of three serotypes. For years now, GPEI has been chasing its tail, quashing one type 2 outbreak with mOPV2 only to seed new outbreaks.

In 2011, an international team of researchers, funded by the Gates foundation, began working on a technical fix. Starting with the same type 2 Sabin vaccine virus, they tweaked its genome in several places to make it less likely to revert. The hope was that nOPV2 would not seed new outbreaks—or at least do so much less frequently than mOPV2. Clinical and preclinical data looked good—the vaccine was just as safe and effective as mOPV2 and much more genetically stable, Bandyopadhyay says. But because these reversions are rare events, the new vaccine’s true worth could not be known until it was used widely under close scrutiny.

Since March 2021, GPEI and its country partners have administered almost 600 million doses of the new vaccine to respond to outbreaks in 28 countries—until now, without a hitch. The seven cases of paralysis arose from two separate “emergences”—in other words, two vaccine viruses reverted independently, in South Kivu and Tanganyika provinces in the DRC, and then began to spread. The one case in Burundi, in Bujumbura Rural province, is linked to the South Kivu strain; that virus has also been detected in five sewage samples in a neighboring province.

“This is clearly an extremely rare event,” O’Leary says. Going forward, the job is to figure out just how rare, Zipursky says. “We will continue to gather data to get a true sense of [nOPV2’s] genetic stability.” A preliminary analysis suggests that if mOPV2 had been used instead at this broad scale, an estimated 30 to 40 emergences would have occurred as opposed to two, Bandyopadhyay says.

Vaccine experts are now weighing the relative merits of the two oral options, and that’s important, O’Leary says. But he stresses that the problem of low vaccination coverage should get equal or greater attention. Bandyopadhyay agrees. “If there is persistently poor immunization coverage in a community, there is always a risk that a live, attenuated vaccine virus will revert.”

Both mOPV2 and nOPV2 have stopped many outbreaks where the vaccination campaigns are of high quality. But those can be hard to pull off in parts of the DRC and Burundi. Indeed, GPEI has identified eastern DRC, where these paralytic viral variants arose, as one of seven places globally at highest risk for polio outbreaks—and where once they start, they can be extremely hard to stop. The DRC is rocked by conflict and political instability, which makes it difficult to reach many children with vaccines. It has also been battling simultaneous disease outbreaks, all vying for priority. Routine vaccination rates are low.

“GPEI needs to dig deep and work through all the surveillance data in both countries to understand what is happening with the [nOPV2] vaccine,” O’Leary says. At the same time, he says, the program needs to intensify its efforts to reach all the children being missed by that vaccine.