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.

Malawi has declared a polio outbreak after a case was detected in a young child in the capital Lilongwe, the first case of wild poliovirus in Africa in more than five years, the World Health Organization (WHO) said. Africa was declared free of indigenous wild polio in August 2020 after going 4 years without a recorded case. Because testing showed that the new case detected in Malawi is linked to a strain from Pakistan, it does not affect Africa’s polio-free status, WHO noted.  “As long as wild polio exists anywhere in the world, all countries remain at risk of importation of the virus,” Matshidiso Moeti, MD, MPH, WHO’s regional director for Africa, said in a statement. The incidence of wild polio has declined nearly 100% since 1988. It continues to be endemic in only two countries, Afghanistan and Pakistan, although only six total cases have been detected in those two countries since the beginning of 2021, according to the Global Polio Eradication Initiative (GPEI).  The GPEI reported that the child in Malawi is a 3-year-old girl who experienced an onset of paralysis on Nov. 19 last year. It said the virus was genetically linked to a strain detected in Pakistan’s Sindh province in October 2019.

“Detection of [wild poliovirus] outside the world’s two remaining endemic countries, Pakistan and Afghanistan, is a serious concern and underscores the importance of prioritizing polio immunization activities,” the GPEI said in a statement. “Until polio is fully eradicated, all countries remain at risk of importation and must maintain high vaccination coverage to protect all children from polio.” According to WHO, health authorities in Malawi have responded to the case with increased surveillance and supplemental immunizations, supported by WHO. Neighboring countries have also ramped up surveillance. A GREI rapid response team based in WHO’s Africa office is deploying to Malawi to support efforts. “Any case of wild polio virus is a significant event, and we will mobilize all resources to support the country’s response,” Modjirom Ndoutabe, MD, polio coordinator at WHO’s Regional Office for Africa, said in a statement.

Four African countries have reported new cases of polio linked to the oral vaccine, as global health numbers show there are now more children being paralyzed by viruses originating in vaccines than in the wild. In a report late last week, the World Health Organization and partners noted nine new polio cases caused by the vaccine in Nigeria, Congo, Central African Republic and Angola. Seven countries elsewhere in Africa have similar outbreaks and cases have been reported in Asia, including the two countries where polio remains endemic, Afghanistan and Pakistan.

In rare cases, the live virus in oral polio vaccine can mutate into a form capable of sparking new outbreaks. All the current vaccine-derived polio cases have been sparked by a Type 2 virus contained in the vaccine. Type 2 wild virus was eliminated years ago. Polio is a highly infectious disease that spreads in contaminated water or food and usually strikes children under 5. About one in 200 infections results in paralysis. Among those, a small percentage die when their breathing muscles are crippled. Donors last week pledged $2.6 billion to combat polio as part of an eradication initiative that began in 1988 and hoped to wipe out polio by 2000. Since then, numerous such deadlines have been missed.

To eradicate polio, more than 95% of a population needs to be immunized. WHO and partners have long relied on oral polio vaccines because they are cheap and can be easily administered, requiring only two drops per dose. Western countries use a more expensive injectable polio vaccine that contains an inactivated virus incapable of causing polio. The Independent Monitoring Board, a group set up by WHO to assess polio eradication, warned in a report this month that vaccine-derived polio virus is “spreading uncontrolled in West Africa, bursting geographical boundaries and raising fundamental questions and challenges for the whole eradication process.” The group said officials were already “failing badly” to meet a recently approved polio goal of stopping all vaccine-derived outbreaks within 120 days of detection. It described the initial attitude of WHO and its partners to stopping such vaccine-linked polio cases as “relaxed” and said “new thinking” on how to tackle the problem was needed.

W.H.O. Report (November 20, 2019)  available at :

http://polioeradication.org/polio-today/polio-now/this-week/

Health authorities here confirmed that the Davao River had been found positive of the polio virus, prompting them to order a massive polio vaccination drive next month, targeting all children in the city.

Dr. Josephine Villafuerte, City Health Officer, said the water samples earlier submitted to the Research Institute for Tropical Medicine (RITM) confirmed the presence of polio virus in the Davao River, prompting health authorities here to set in motion a massive vaccination drive that would begin next month to stop the spread of the virus.

“In October, there will be an outbreak response vaccination. Every children is targeted to be covered,” she said. Villafuerte, however, gave assurance that there was no confirmed polio case here yet.  She said Davao City, President Rodrigo Duterte’s hometown, would be among areas for a massive vaccination campaign aside from the National Capital Region (NCR), Lanao del Sur province, Central Luzon and Calabarzon (Cavite-Laguna-Batangas-Rizal and Quezon) provinces. Villafuerte said the City Health Office would involve the community in the fight against polio resurgence. All village officials would be gathered on Sept. 24 for a planning session.

Village chiefs, she said, should be at the forefront of the fight against polio resurgence and report cases of paralysis immediately. She added that village officials should also be responsible for proper human waste disposal. There was no need for resorts to shut down swimming pools, though, she added. But she cautioned the public against swimming in the city’s resorts until the waters were declared safe.  She added that swimmers, especially children, “may ingest contaminated water.” She also asked resort owners to make sure their water is clean. “They should disinfect the water,” she added.

Parents should be aware of the symptoms of polio like fever, fatigue, headache, vomiting, stiff neck and sudden floppiness of arms or legs. Villafuerte said if parents see these signs on their children, “please go to the doctor immediately.” Department of Health data showed that coverage of polio immunization in Davao City was only 72 percent from 2016 to 2018. Villafuerte said people who have had complete shots of polio vaccine need not worry.

The following essay is reprinted with permission fromThe Conversation, an online publication covering the latest research. The first case of polio in the U.S. since 2013 was announced by New York state health officials on July 21, 2022. The U.S. resident had not been vaccinated. Polio was a common cause of paralysis in children before safe and effective vaccines were invented in the mid-20th century. Thanks to global vaccination campaigns, polio is now almost eradicated, with only 13 cases of endemic wild poliovirus reported in 2022 to date worldwide.  The New York patient reportedly contracted a form of polio that can be traced back to the live, but weakened, poliovirus used in the oral polio vaccine. This version of the vaccine has not been used in the U.S. since 2000. Health officials said the virus affecting the male patient, who has muscle weakness and paralysis, likely originated somewhere overseas, where oral vaccines are still administered. William Petri is an infectious disease specialist and chair of the World Health Organization’s Polio Research Committee. Here he explains what vaccine-derived poliovirus is and why the inactivated polio vaccine administered in the U.S. today can’t cause it. 

What are the two kinds of polio vaccine?

Vaccines introduce a harmless version of a pathogen to your body. The idea is that they train your immune system to fight off the real germ if you ever encounter it. The oral polio vaccine, originally developed by Albert Sabin, uses a live but weakened poliovirus that one swallows in a sugar cube or droplet. Scientists weaken – or attenuate – the virus so it can no longer cause disease.  The other kind of polio vaccine was originally developed by Jonas Salk. It contains inactivated, dead virus. It is administered by an injection. In the U.S., children receive the inactivated polio vaccine at 2, 4 and 6 months of age. It provides nearly complete protection from paralytic polio.

How can the live vaccine lead to a case of polio?

The weakened form of the live virus in the oral vaccine cannot cause disease. However, because the vaccine is given orally, the weakened virus is excreted in the feces and can spread from someone who is vaccinated to their close contacts. If the weakened virus circulates person to person for long enough, it can mutate and regain its ability to cause paralysis. The mutated virus can then infect people in communities with poor sanitation and low vaccination rates, causing disease and even paralysis.  This is an exceedingly rare occurrence. With more than 10 billion doses of the oral polio vaccine administered since 2000, there have been fewer than 800 cases of vaccine-derived polio reported. Apparently, the current patient in New York was somehow exposed to a mutated poliovirus that had been transmitted after vaccination overseas. Earlier this summer, routine surveillance spotted vaccine-derived poliovirus in London’s sewage system, but no cases have been reported there.

Why use the oral vaccine anywhere if it comes with this risk?

There’s a positive aspect to the fact that the weakened live virus can circulate in the community once oral vaccine recipients shed it in their feces. Traveling a feces-to-oral route, it can help induce immunity even in people who weren’t directly vaccinated. The oral polio vaccine is also cheaper and easier to administer than inactivated polio vaccines. Most importantly, the live-virus vaccine stops transmission of wild poliovirus in a way that the inactivated-virus vaccine does not. The eradication of polio in the Americas, Europe and Africa has been accomplished solely through the use of the live oral vaccine. Once polio has been wiped from a continent, then it is safe to stop using the oral live vaccine and use only the inactivated vaccine, which does prevent disease in recipients and does not pose the rare risk of vaccine-derived paralytic polio.  A new and safer oral polio vaccine that has been engineered not to mutate is now replacing the earlier live-virus vaccine. Thus, even this extremely rare complication of polio vaccination should soon become a thing of the past. 

How close is the world to eradicating polio?

Thanks to tremendous global effort, two of the three viruses that cause polio have been eradicated. The world is now on the verge of eradicating the final one, wild poliovirus 1 (WPV1). Today endemic polio is found only in Pakistan, with 12 cases of paralytic polio so far in 2022, and Afghanistan, with just one case this year. Africa has two cases, imported from overseas, which are being contained by additional vaccination campaigns. Once wild poliovirus has been eradicated from the planet, vaccination efforts may be able to switch to the inactivated polio vaccine, eliminating the risk of any future vaccine-derived cases.

This article was originally published on The Conversation. Read the original article.

Suspension of vaccinations expected to lead to fresh outbreaks in polio-free countries. The COVID-19 pandemic is imperiling the worldwide, 3-decade drive to wipe out polio. In an unprecedented move, the Global Polio Eradication Initiative (GPEI) has recommended suspending polio vaccination campaigns to help stop the spread of the novel coronavirus. On 24 March, GPEI’s leadership called on all countries to postpone until at least the second half of this year both mass campaigns to boost immunity to the polio virus and the targeted campaigns underway in Africa to stop outbreaks sparked by the live virus vaccine itself.

The implications are “huge,” says Kim Thompson of Harvard University, who heads one of three modeling groups GPEI has charged with analyzing the possible impacts of the pause. More children will be paralyzed by both the wild and vaccine-derived viruses, and the virus will likely reinvade countries that are now polio-free, GPEI concedes. And polio is only one of several diseases for which mass vaccination efforts will be suspended. 

“We are caught between two terrible situations,” says GPEI head Michel Zaffran of the World Health Organization (WHO). Going door to door delivering drops of oral polio vaccine (OPV) would put both communities and health workers at risk of infection with the novel coronavirus. Halting polio campaigns will enable GPEI to free up its extensive resources, including surveillance systems and tens of thousands of frontline health workers, to aid in the COVID-19 fight, he says. “We have no choice,” Zaffran says. “We did not want to have the program be responsible for worsening the situation with COVID-19.” 

As the global effort to eradicate polio gets tantalizing close to its goal, the program is running in to new challenges. One of the biggest obstacles this year is the proliferation of so-called "vaccine-derived" polio outbreaks. Conventional polio caused by the traditional form of the disease is now only occurring in two countries in the world — Afghanistan and Pakistan. The World Health Organization calls this form "wild" polio and there've been roughly 100 cases so far this year. This is a tiny number compared to the 350,000 cases that occurred globally before the Global Polio Eradication Initiative was launched in 1988.

But what's troubling now is that there are currently more kids being paralyzed by cases of vaccine-derived polio than by the original "wild" variety. "We have seen a lot more countries impacted this year than last year," says Dr. John Vertefeuille, the head of polio eradication at the U.S. Centers for Disease Control and Prevention. There've been outbreaks this year in the Philippines, China, Myanmar, Pakistan and a half a dozen African countries. "Because of the rising number of individual outbreaks," Vertefeuille says. "The CDC has taken a decision to do a surge staffing effort focusing on Africa." He says the CDC is in the midst of sending up to 100 additional personnel to Africa to help track, manage and wipeout vaccine-derived polio outbreaks over a six-month period.

Currently around the world, all children are supposed to get vaccinated against polio. In the U.S. and other wealthy nations, kids get 4 injections of inactivated polio vaccine spread out over their first 7 years of life. This injectable vaccine does not contain live virus, so it does not and cannot cause vaccine-derived polio. In lower income countries with weaker health systems, an oral vaccine containing a live but weakened version of the polio virus is used. It's cheap and easy to administer through a few drops in a child's mouth. In the early days of polio eradication, this live oral vaccine also had the added benefit that it could circulate in a community just like the real, wild virus. In places with poor sanitation, wild polio and the virus in the oral vaccine can spread from sewage to drinking water. At first this was great. Kids who hadn't been vaccinated by health workers ended up getting exposed to the oral vaccine and protected against wild polio because of their lousy drinking water supplies. But over time the virus from the oral vaccine starts to regain strength and if it's allowed to circulate long enough, it reverts back to the point that it can cause paralysis just like the original virus.

"We actually do genetic analysis so that we can understand the closest relative of each (virus) detection that we see globally," says Vertefeuille at the CDC. And in these vaccine-derived outbreaks, they can see that the virus that's paralyzing kids is directly linked to the vaccine that was distributed earlier. "You have to keep vaccinating all the children so you won't have any paralyzed children," Noymer says, "But the more you vaccinate, the more live virus continues to circulate. And the minute you step off the treadmill, you get some paralyzed kids." One way to get off that treadmill would be to get rid of the live oral vaccine and switch to the not-live, injectable vaccine used in the United States. The Global Polio Eradication Initiative has tried to move in that direction but there are several challenges. First there just isn't enough supply globally of the injectable vaccine to cover the hundreds of millions of kids in low income countries. Training vaccinators to give injections is much harder than training them to give two drops in to a child's mouth. Also the vaccines work slightly differently — with the oral version doing a better job of breaking chains of transmission and stopping outbreaks....

Using two types of polio vaccines seems to provide stronger protection against the disease and may boost efforts to eradicate polio, a new study shows. The research involving nearly 1,000 children in India found that giving the Salk inactivated poliovirus vaccine (IPV) to those who had already been given the Sabin live-attenuated oral poliovirus vaccine (OPV) appeared to improve their immunity to the virus that causes polio. The findings, reported in the Aug. 22 issue of the journal Science, could prove crucial in eliminating the world's remaining pockets of polio in places such as Iraq and Syria.

"This study revolutionized our understanding of IPV and how to use it in the global eradication effort to ensure children receive the best and quickest protection possible from this disease," study senior author Dr. Bruce Aylward, assistant director-general for Polio, Emergencies and Country Collaboration at the World Health Organization, said in a journal news release. "IPV should be used to accelerate the eradication of the virus in populations that have limited access to vaccination," study author Dr. Hamid Jafari, WHO's director for polio operations and research, said in the news release. "The study has also provided the evidence for use of IPV among travelers to limit further international spread of the virus."

Since polio vaccine was developed in the 1950s, efforts to eradicate polio have relied mainly on OPV rather than IPV. However, these findings show that giving both vaccines to patients may be the best approach. "The global eradication effort is at a critical crossroad," Jafari said. "Endemic polio is increasingly geographically restricted to populations in insecure and inaccessible areas. Yet the virus in these areas persists with incredible tenacity and threatens the increasingly vulnerable populations in polio-free countries with weak or conflict-affected health systems."