Virus World

Experts have long understood that a new polio vaccine developed to try to minimize the risks associated with the oral polio vaccine made by Albert Sabin might also cause the problem it was created to sidestep. It’s now clear that theoretical risk is a real one. The Global Polio Eradication Initiative announced Thursday that six children in the Democratic Republic of the Congo and one in Burundi have been paralyzed by viruses from the new vaccine, which is referred to as novel oral polio vaccine, or nOPV2. (The “2” signals the vaccine targets type 2 polioviruses.) In addition, five environmental samples collected from Burundi contained the so-called type 2 circulating vaccine-derived polioviruses, or cVDPV2s. “We are disappointed,” said Ananda Bandyopadhyay, deputy director for technology, research, and analytics on the polio team of the Bill and Melinda Gates Foundation, a partner in the polio eradication effort. “Any such outbreak is disappointing.” The Gates Foundation is one of a half-dozen partners in the Global Polio Eradication Initiative. The others include the World Health Organization; UNICEF, the United Nations Children’s Fund; the Centers for Disease Control and Prevention; Gavi, the vaccine alliance; and the service club Rotary International.

Bandyopadhyay and the polio eradication initiative itself were quick to point out that this turn of events was not unexpected. The live polioviruses used in oral vaccines are manipulated to eliminate their ability to paralyze. Children who receive these vaccines shed live viruses in their stools. In settings where sanitation and hygiene are poor, the viruses can move from child to child, effectively indirectly vaccinating children whom vaccination teams haven’t reached — a feature that has made the Sabin vaccines the workhorse of polio eradication. But if the viruses spread long enough, they can regain the ability to paralyze — a problem that led the polio program to stop using type 2 oral vaccine in 2016, in a bold and ultimately failed effort, known as “the switch,” to stop spread of type 2 viruses from the Sabin vaccines. The injectable polio vaccine, designed by Jonas Salk and used in affluent countries like the United States, does not contain live viruses and therefore doesn’t trigger paralysis. But while it prevents paralysis, it cannot stop transmission of polioviruses — wild type or vaccine derived — which makes it less useful in countries where vaccine-derived viruses are spreading. In recent years, the nearly 35-year-old effort to rid the world of polio has managed to drive numbers of infections with wild viruses down to low levels. Last year, only three countries — Pakistan, Afghanistan, and Mozambique — reported 30 cases. So far this year, there has been only one case detected, in a child in Afghanistan. But as the battle against wild viruses has gained ground, use of the oral vaccine has seeded chains of transmission of the vaccine-derived viruses. In 2022, nearly 800 children or young adults in roughly two dozen countries developed paralytic polio after being infected with one of the vaccine viruses from the Sabin vaccines. Among them was an unvaccinated young man in New York State, this country’s first polio case in nearly a decade.

Of the three original strains of polio — types 2 and 3 have been eradicated, only type 1 remains — the portion of the Sabin vaccines targeting type 2 viruses triggers the vast majority of vaccine-derived polio cases. A few years ago, with support from the Gates Foundation, the novel oral vaccine targeting type 2 viruses was developed. It was put into use in mid-March of 2021 — two years ago. Since then 590 million doses of nOPV2 have been administered in 28 countries. The seven cases of paralytic polio, which stem from two chains of vaccine-derived viruses, are far fewer than would likely have occurred if those hundreds of millions of doses had been the Sabin vaccine, Bandyopadhyay said. An analysis from the Gates Foundation’s polio team suggested that there would have been 30 to 40 new chains of type 2 vaccine viruses over that period, rather than two, he said. Other experts agreed it is important to put the finding in context. “I’m not alarmed. It’s a much better tool than we used to have,” said Walter Orenstein, a polio expert at Emory University. “It’s not perfect,” he said of the new oral vaccine. “But given its rarity, it hopefully will be able to do the job. At least not generate lots of these kinds of outbreaks.” Kim Thompson, president of the nonprofit organization Kid Risk and a mathematical modeler who has worked on polio eradication for decades, said this event is only showing the world that what was assumed about the new oral vaccine is in fact true. “This possibility has always been out there in the cards. And really this is just the proof of concept that the nOPV2 can lose the attenuated mutations and behave like other live polioviruses, and particularly do so in populations where [vaccine] coverage is low,” she said. But Thompson is worried that given the low levels of immunity to type 2 polio, even less frequent outbreaks of vaccine-derived viruses will amplify a problem the polio program is struggling to contain. “The reality is that since we have transmission happening in these areas with low coverage and this immunity gap that exists … there’s more room for these viruses to go. That’s part of the challenge here, is to figure out what to do to stop type 2,” she said.

Helen Branswell

Senior Writer, Infectious Diseases

Helen Branswell covers issues broadly related to infectious diseases, including outbreaks, preparedness, research, and vaccine development. Follow her on Mastodon and Post News.

In past Ebola outbreaks, fatality rates have varied from 25% to 90% - but effective treatments are now available, and patients who receive care early see their chances of survival improve significantly.  An outbreak of Ebola has been declared in the Democratic Republic of the Congo - four months after the last one ended. A case was confirmed in a 31-year-old man on 5 April. He was admitted to an Ebola treatment centre on Thursday, but died hours later. The World Health Organisation's regional director for Africa, Dr Matshidiso Moeti, said: "Time is not on our side. The disease has had a two-week head start and we are now playing catch-up." Overall, this is the 14th Ebola outbreak that the Democratic Republic of the Congo has seen since 1976, which is when the virus was first discovered.

Efforts to stem the current outbreak have already begun, with officials confirming that the patient who died has received a safe and dignified burial.  More than 70 of his contacts are also being traced - and vaccinations in the city of Mbandaka are going to be stepped up. Ebola is transmitted by coming into contact with the bodily fluids of an infected person or contaminated materials.  Early symptoms include muscle aches and a fever, which resemble those seen in other common diseases such as malaria. In past Ebola outbreaks, fatality rates have varied from 25% to 90% - but effective treatments are now available, and patients who receive care early see their chances of survival improve significantly. Dr Moeti added: "The positive news is that health authorities in the Democratic Republic of the Congo have more experience than anyone else in the world at controlling Ebola outbreaks quickly."

A second Ebola patient has died in northwestern Democratic Republic of Congo, the World Health Organization (WHO) said on Tuesday, days into a fresh outbreak of the deadly disease. Genetic testing showed an infection confirmed last week in the city of Mbandaka was a new "spillover event", a transmission from an infected animal, and not linked to any previous outbreaks, said the country's National Institute of Biomedical Research.  The second fatality was a 25-year-old woman who was the sister-in-law of the first case, the WHO said on Twitter. She began experiencing symptoms 12 days earlier, it said. The first patient began showing symptoms on April 5, but did not seek treatment for more than a week. He died in an Ebola treatment centre on April 21. The lag time has health workers rushing to identify contacts who may have been infected, the WHO said.

At least 145 people came into contact with the confirmed cases and their health is being closely monitored, the WHO said, noting later that one of the first cases was a health worker.  Mbandaka, a trading hub on the banks of the Congo River, is a city of over one million where people live in close proximity with road, water and air links to the capital Kinshasa. WHO emergencies director for Africa, Ibrahima Soce Fall, said there was a risk the disease could spread to neighbouring Central African Republic and Congo Brazzaville.  "This is concerning but taking into account the capacity build up and experience in Congo we believe it can be contained," Fall said at a press conference in Geneva. Congo has seen 13 previous outbreaks of Ebola, including one in 2018-2020 in the east that killed nearly 2,300 people, the second highest toll recorded in the history of the hemorrhagic fever. The most recent outbreak ended in December in the east after six deaths. Mbandaka, the capital of Equateur province, has also contended with two previous outbreaks - in 2018 and in 2020. The country's equatorial forests are a natural reservoir for the Ebola virus, which was discovered near the Ebola River in northern Congo in 1976.

Scientists at the Centers from Disease Control and Prevention have created a synthetic version of the Ebola virus circulating in the Democratic Republic of the Congo, part of an effort to determine whether diagnostic tests and experimental treatments being used in the field are effective.

The research, conducted in the agency’s most secure laboratories — BSL4 — showed that even though the tests and two of the treatments being used in the field were developed based on earlier variation of Ebola viruses, they continue to be effective against the virus causing the current outbreak, the second largest on record.

The results, reported Tuesday in the journal Lancet Infectious Diseases, are encouraging, but also raise questions about why outside research groups have not received direct access to viral specimens from the DRC and instead had to create a synthetic version. The paper noted that there have been no Ebola samples available to the scientific community from the past four outbreaks in the DRC. Those outbreaks occurred in 2014, 2017, and 2018.

This work was published in the journal Lancet Infectious Diseases:

https://doi.org/10.1016/S1473-3099(19)30291-9