No one expected polio to return.
The year is 2040, a decade since the disease was eradicated. The global fitness crusade that defeated the virus has come to a halt; Vaccination efforts have slowed. Then, one day, a physically ill child in a conflict-torn country develops paralysis; The cause, it turns out, is polio. Scientists hint at the origin of the virus in a lab on the other side of the world. A lab technician had treated a forgotten batch of polio-infected devices and then visited their families overseas.
As cases rise, the World Health Organization (WHO) is seeking help to carry out emergency vaccination campaigns, but vaccine materials are scarce and few have direct experience with polio outbreaks. Soon, there will be tens of thousands of cases – millions more. Other people around the world who have not been vaccinated are at risk.
This is just one of many conceivable scenarios that may follow until polio eradication. Although the world has not yet eliminated poliovirus, many observers believe that it could disappear within 3 years. The crusade for polio eradication is more intense. and investment over the next year in hopes of finally meeting a deadline that has been postponed many times since efforts began in 1988.
The front lines are Afghanistan and Pakistan, where cases of wild polio persist but are declining (see “Taming Wild Polio”), and part of Africa, where a polio vaccine that includes a live virus has triggered epidemics. Campaigns are now addressing those vaccine-related episodes.
The final steps towards eradication are formidable and it is unclear when (or if) countries will achieve this goal. However, with the virus in sight, health authorities are making plans for what will happen next.
This is because eradication is extinction. Polio may simply be hiding in testing labs and production facilities (where it has leaked into the afterlife) and even in some people. Mistakes made years after eradication can allow polio to enter an unprotected population where it can “wreak havoc,” says virologist Konstantin Chumakov, former associate director of vaccine studies at the U. S. Vaccine Belt Review and Research Office. the FDA in Silver Spring, Maryland.
Ending polio is just the beginning of an effort: building resilience to keep it away, says Liam Donaldson, a public health specialist at the London School of Hygiene.
So far, only one human disease has been declared eradicated: smallpox, in 1980. Polio is more complex, says David Heymann, who heads the WHO’s containment advisory group. This is due to a key difference: each and every smallpox infection produces symptoms, yet polio can silently infect up to 1,000 people before causing a case of paralysis. The other challenge is that polio can be caused not only by the wild virus, but also, in very rare cases, by the vaccines used to save it. Eradication means getting rid of any of the bureaucracies for good.
The main tool is vaccination. Polio-free industrialized countries use an inactivated polio vaccine (IPV), which does not prevent the virus from infecting the body and being excreted in the feces, but protects against paralysis. As long as IPV vaccination levels are high and sanitation is good, a malicious poliovirus will most likely go away, according to Concepcion Estivariz, a polio researcher at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.
But because the inactivated vaccine can’t block transmission, young people in at-risk countries still get another type: an oral polio vaccine (OPV), which comprises an attenuated form of the live virus and can prevent the spread of polio, which is meant to be eradicated. . . . It is also less expensive and less difficult to administer than IPV, which is given by injection. The oral crusade was a great success. Since 1988, the Global Polio Eradication Initiative (GPEI) estimates that it has prevented 20 million cases of paralysis due to polio.
But the IPO has significant disadvantages. There is a small risk that the vaccine itself will cause paralysis. And, rarely, the weakened virus used in the vaccine can mutate enough to regain its virulence. This can lead to outbreaks of cases known as vaccine-induced polio, among others. who have not been fully vaccinated or have not been vaccinated at all. “If we continue with the IPO,” says Estivariz, “we will never avoid the circle. “Most countries now use IPV in their vaccination regimen systems in conjunction with OPV, and WHO recommends that IPV management continue for a decade after transmission of the disease has been prevented, to oppose any accidental release or concealment of the virus.
Polio will be considered eliminated when no cases have been observed for 3 years and when there is no evidence of the disease in environmental monitoring data, i. e. in wastewater samples. A year later, OPV will need to be withdrawn to save vaccine-induced polio. The problem, however, is that his withdrawal will be an extremely complicated maneuver. If done in a haphazard manner, this procedure can simply lead to the return of the virus.
In 2016, for example, the IPO withdrawal in 150 countries was disastrous. “The effects are sobering,” says Kimberly Thompson, an epidemiologist at the nonprofit research organization Kid Risk in Orlando, Florida.
There are 3 strains of wild polio: types 1, 2, and 3. Type 2 was declared eliminated in 2015 and type 3 followed in 2019. The oral vaccine contained attenuated versions of all 3 strains, but after the eradication of type 2, the goal was to remove vaccines containing this strain to minimize the threat of spread of vaccine-derived polio type 2. That’s why, in April 2016, the GPEI orchestrated a two-week period in which all three-strain oral vaccines were replaced with versions containing only types 1 and 3.
However, cases of vaccine-induced type 2 polio began to multiply rapidly: in two countries in 2016 and in 24 countries in 2020, with African countries being the most affected. A case emerged in the US in 2022 and the UK found detecting the virus in wastewater samples. The cumulative number of paralysis cases so far amounts to just over 3,200; The annual total peaked at more than 1,000 in 2020 and now appears to be declining, with 238 recorded so far this year (see “Rare and declining: vaccine-derived polio”). African countries are still carrying out emergency campaigns distributing type 2 oral vaccines to curb such outbreaks.
What is the reason for this uptick? First, populations in the affected areas were not adequately vaccinated with IPV, which would have them until the outbreak could be controlled. This was partly due to a lack of vaccine supply, says Ondrej Mach, co-chair of a new GPEI organization. in charge of overseeing long-term recalls of the oral vaccine.
What’s more, Mach says, just before the change, vaccine-derived polio type 2 was detected in Nigeria. Transmission is most likely already underway in Nigeria and other countries, Mach adds, and the emergency type 2 vaccine caused new outbreaks.
Since 2021, however, this seeding has become much less likely: outbreaks of vaccination campaigns employing a genetically modified oral vaccine, which is even less likely to become virulent than OPVs used in the past.
What dangers will the post-polio world face if complete oral abstinence fails?An investigation conducted by Kid Risk and the CDC provided an answer (D. A. Kalkowska et al. Risk. https://doi. org/k428; 2023). His style considers what might happen if all use of OPV were stopped in 2027, but vaccine-derived polio was not completely eliminated first and responses to the outbreak were weak. In one scenario, the report predicts there could be as many as 40,000 cases of paralysis caused by vaccine-induced polio eight years after OPV treatment is stopped. To avoid this, the authors recommend that population immunity in areas where polio cases are currently present should be maximized (around 90%) just before withdrawal. Thompson says most countries have achieved this in the past, at least for short periods.
Even after the successful withdrawal of IPOs, countries cannot let their guard down. They will have to establish surveillance “to detect any poliovirus, anywhere in the world and even ephemerally,” says a report on the Transition. Independent Monitoring Board, an independent organization of scientists that regularly reports on polio and is chaired through the Independent Transition Oversight Board, through Donaldson.
Polio surveillance takes two main forms: tracking cases of paralysis that could possibly be caused by polio; and monitor wastewater for any viruses transmitted through carriers.
Both will be very important in the years to come, as the example of Malawi shows. The country had been free of wild polio for three decades when, in 2021, a pattern of stool from a paralyzed 3-year-old boy arrived at the national laboratory for the sample to be stored for two months before being sent with others, says Jamal Ahmed, who coordinates polio eradication for the WHO in the African region. which includes 47 countries. The result came a month later: it was crazy. poliomyelitis type 1, unprecedented on the continent since 2016.
The sequencing traced its origin in Pakistan, but also revealed that the virus had been circulating for two years undetected, most likely in Malawi and most likely elsewhere. Since Malawi did not have a sewage tracking formula at the time, it was necessary to know. .
Within 30 days of receiving the result, emergency vaccinations began. Six seasons later, Ahmed says, Malawi has not had a single case of wild polio. And, with support from WHO, the country temporarily set up environmental monitoring sites.
The episode also showed that the emergency immunization program isn’t up to the task, says Jay Wenger, director of the polio program at the Bill Foundation.
Global wastewater surveillance has been a top priority since the COVID-19 pandemic, Donaldson says, as policymakers pay more attention to disease trends. Ahmed says 41 of the WHO’s 47 member states in Africa now have environmental surveillance for polio, and the rest will soon follow. catch up.
Innovations speed up a procedure where speed is crucial. A major breakthrough is direct detection, an approach that goes beyond several traditional steps in the testing procedure; for example, by extracting RNA directly from samples without the need to culture them.
No matter how successful eradication efforts are, the virus will remain in research institutes and vaccine production facilities, as well as in an unspecified number of regimen diagnostic laboratories.
Leaks happen. Last year, a lab employee at a production plant in Utrecht, the Netherlands, detected a type 3 virus at the plant, which he then detected while tracking tea water out of the plant. No cases of paralysis were observed. Vaccine production is “a massive lockdown nightmare,” Mach says.
WHO has a poliovirus containment plan that calls on countries to minimize the number of facilities containing poliovirus-containing equipment and destroy all stockpiles. Currently, WHO has 74 facilities in 22 countries that are polio-positive.
The first step for each country is to establish a national containment authority until 2018, to ensure that facilities meet biosafety requirements. China and Romania have not yet done so, and other countries have not met upcoming deadlines.
Even for compliant services, forgotten samples remain a threat, says Andy Macadam of the National Institute for Biological Standards and Control in Potters Bar, UK. “All you have to do is mislabel the tube. “And polio may be lurking in some services That’s even subject to the containment plan, Heymann says. This may simply come with frozen stool samples taken for other reasons at a time when polio was circulating.
Since 2000, 21 incidents of poliovirus release have been reported from laboratories and vaccine production facilities in 8 countries, with 16 poliovirus cases resulting, according to Derek Ehrhardt, who heads WHO’s Poliovirus Containment Unit. Most cases occurred in vaccine production. services, however, five of them were in study laboratories where staff discovered that vials containing poliovirus were mislabeled (none of those cross-contamination incidents resulted in paralysis). The solution, Heymann says, lies in greater biosecurity in all laboratories.
To decrease the need for live viruses, scientists are devising tactics to produce inactivated vaccines without them, for example, through a non-infectious, genetically modified raw material or by designing vaccines from virus-like remains or messenger RNA.
There is still a source of poliovirus, unpredictable 35 years ago, when eradication efforts began.
In most people who receive the oral vaccine, the immune formula generates antibodies that oppose them to the virus. But in a small number of people born with specific immune disorders, the immune formula allows the vaccine’s attenuated virus to survive, evolve over time, and emerge in the feces. No medication has been shown to cure persistent polio infection.
Of the many types of immunodeficiency, only a few cause chronic retention of poliovirus. No one knows how many more people are affected, and no such loss has triggered a polio outbreak, although it may have contributed to an outbreak in the Philippines in 2019-2021.
But, Mach says, even a single user who stores and loses poliovirus is incompatible with eradication. “We have to do something. ” A foreign, though irregular, search for people with these immunological disorders and chronic polio yielded a record of another 200 people.
A user with this disease lives in the UK and was vaccinated with OPV as a child. For more than 20 years, it carried and asymptomatically excreted the attenuated virus, which evolved into its pathogenic form. Your gut is “essentially a culture vessel,” says David Boyle of PATH, a nonprofit medical studies organization founded in Seattle, Washington.
That’s why scientists were surprised to learn that the person’s infection was gone.
He disappeared after winning the antiviral drug remdesivir to treat severe COVID-19 in August 2021. That may simply be a coincidence, Macadam says, but it bolsters the argument that antivirals can simply be used to treat polio infection (two of those drugs are being studied as a polio treatment). Monoclonal antibodies are also being developed.
Maintaining peak vaccination rates for at least a decade after eradication will provide the most productive coverage; however, it is considered that commitment to IPV will diminish once eradication is declared. Routine immunization campaigns struggle to succeed in each and every child, especially in times of conflict, crisis, or pandemic. COVID-19 brought the number of unvaccinated or undervaccinated children to 23 million in 2020.
Added to this is the challenge developing in some regions of vaccine skepticism and complacency, which has worsened due to anti-COVID-19 vaccine activism, says Peter Hotez, a vaccine and public specialist at Baylor College of Medicine in Houston, Texas.
With so much to do to achieve a polio-free world, Donaldson wonders who will be up to the task once the GPEI is dissolved a year after eradication, handing over the day-to-day work to WHO departments, partners and national fitness systems.
A transition has already begun in some countries, but many are struggling to place their own investments in the face of governments’ conversion priorities. Declining efforts now may lead to more serious challenges in the future, said Aidan O’Leary, WHO’s polio eradication officer. “If we look away from the challenge and don’t build the resilience of fitness systems in the future, in the long run we will face more challenges. “
But if done right, O’Leary says, global post-polio can bring greater benefits for everyone: increased surveillance and immunization, and more built-in fitness services. “The last mile of the polio eradication program,” he says, “is the first mile for global public safety of fitness. “
Nature 623, 680-682 (2023)
doi: https://doi. org/10. 1038/d41586-023-03602-5
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