[The campaign to eradicate polio could succeed in the next few
years. But that’s just the beginning of a new challenge — keeping
it away.]
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SUNDAY SCIENCE: POLIO IS ON THE BRINK OF ERADICATION. HERE’S HOW TO
KEEP IT FROM COMING BACK  
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Aisling Irwin
November 21, 2023
Nature [[link removed]]

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_ The campaign to eradicate polio could succeed in the next few
years. But that’s just the beginning of a new challenge — keeping
it away. _

A child in Tanzania has his finger marked to show that he has
received a polio vaccine during a door-to-door campaign in 2022.,
Ericky Boniphace/AFP via Getty

 

Nobody expected polio to be back.

It’s 2040, a decade since the disease was eradicated. The global
health campaign that vanquished the virus has disbanded; immunization
efforts have slackened. Then, one day, a sick child in a
conflict-wracked country develops paralysis; the cause turns out to be
polio. Scientists trace the origin of the virus to a laboratory on the
other side of the world. A technician at the lab had handled a
forgotten batch of polio-infected material — and then visited their
family abroad.

As cases multiply, the World Health Organization (WHO) appeals for
help to conduct emergency immunization campaigns, but stocks of
vaccines are low and few members of staff have direct experience of
polio outbreaks. Soon there are tens of thousands of cases: millions
more people around the world who haven’t had the vaccine are at
risk.

This is just one of many possible scenarios that could follow polio
eradication. Although the world has not yet eliminated poliovirus,
many observers think it could be gone within three years. The
polio-eradication campaign has increased its intensity and funding in
the past year in the hope of finally meeting a deadline that’s been
postponed many times since efforts were launched in 1988.

The front lines are Afghanistan and Pakistan, where pockets of wild
polio persist but are shrinking
[[link removed]] (see ‘Wild
polio tamed’), and a swathe of Africa, where a polio vaccine that
includes live virus has itself seeded outbreaks
[[link removed]]. There are signs
that health campaigns are now bringing these vaccine-derived episodes
under control.

The final steps towards eradication are formidable, and it’s not
clear when — or whether — nations will reach this goal.
Nonetheless, with the demise of the virus in sight, health authorities
are planning what happens next.

That’s because eradication is not extinction. Polio could lurk in
testing labs and manufacturing facilities — from which it has leaked
in the past — and even in some people. Mistakes years after
eradication could let polio into an unprotected population where it
could “wreak havoc”, says virologist Konstantin Chumakov, former
associate director of vaccine research at the FDA Office of Vaccines
Research and Review in Silver Spring, Maryland.

The end of polio is only the beginning of another effort: developing
the resilience to keep it away, says Liam Donaldson, a public-health
specialist at the London School of Hygiene & Tropical Medicine, UK,
and the lead author of a series of independent reports on the
campaign’s progress (see go.nature.com/49hho4a). “People have
signed up to polio eradication, but they’ve not signed up to the
longer journey.”

STAMPING IT OUT

Only one human disease has so far been declared eradicated: smallpox,
in 1980. Polio has been more complex, says David Heymann, who heads
the WHO’s Containment Advisory Group. That’s because of a key
difference: every smallpox infection produces symptoms, but polio can
silently infect up to 1,000 people before causing a case of paralysis.
The other snag is that polio can be caused not only by the wild virus,
but also, in very rare cases, by the vaccines deployed to prevent it.
Eradication means getting rid of both forms for good.

The main tool is vaccination. Industrialized, polio-free countries use
an inactivated poliovirus vaccine (IPV), which doesn’t prevent the
virus infecting the body and being shed in stools, but does protect
against paralysis. Provided that immunization levels with IPV remain
high and sanitation is good, a rogue poliovirus will probably peter
out, 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,
children in at-risk countries still receive another type: an oral
poliovirus vaccine (OPV) that contains an attenuated form of the live
virus, and can stop polio’s spread — which is crucial for
eradication. It’s also cheaper and easier to deliver than IPV, which
is administered by injection. The oral campaign has been hugely
successful. Since 1988, the Global Polio Eradication Initiative (GPEI)
estimates it has prevented 20 million cases of polio paralysis.

A chemist processes samples at the National Polio and Measles
Laboratory in Bangladesh. Credit: G.M.B. Akash/Panos

But OPV has some important downsides. There is a low risk that the
vaccine itself can cause paralysis. And, on rare occasions, the
weakened virus used in the vaccine can mutate sufficiently to regain
virulence. This can lead to outbreaks of cases known as
vaccine-derived polio among people who have not been vaccinated fully
or at all. “If we continue OPV,” says Estivariz, “we never stop
the circle.” Most countries are now using IPV in their routine
immunization programmes alongside OPV, and the WHO recommends that IPV
administration should continue for a decade after disease transmission
has been stopped, to protect against any accidental releases or hidden
pockets of the virus.

Polio will be certified as eradicated when no case has been observed
for three years, and when there is no sign of it in environmental
surveillance data — that is, in samples of waste water. A year after
that, OPV must be withdrawn to prevent vaccine-derived polio. The
problem, however, is that removing it will be an extraordinarily
delicate manoeuvre. Done messily, this process could trigger the
return of the virus.

In 2016, for instance, the withdrawal of an OPV across 150 countries
went disastrously wrong. “The results were sobering”, says
Kimberly Thompson, an epidemiologist at the research non-profit
organization Kid Risk, in Orlando, Florida.

There are three strains of wild polio — types 1, 2 and 3. Type 2 was
declared eradicated in 2015, and type 3 followed in 2019. The oral
vaccine contained attenuated versions of all three strains, but after
type 2 was eradicated, the aim was to withdraw vaccines containing
that strain to minimize the risk of seeding vaccine-derived type 2
polio. So the GPEI orchestrated a two-week period in April 2016 in
which all three-strain oral vaccines were switched for versions
containing just types 1 and 3.

Swiftly, however, cases of vaccine-derived type 2 polio began to build
— in two countries in 2016, spreading to 24 countries by 2020, with
countries in Africa worst affected. A case popped up in the United
States in 2022, and the United Kingdom found the virus in wastewater
samples. The cumulative number of paralysis cases so far is just over
3,200; the yearly total peaked at more than 1,000 in 2020 and now
seems to be declining, with 238 recorded so far this year (see ‘Rare
and receding: vaccine-derived polio’). African countries are still
running multiple emergency campaigns delivering oral type 2 vaccines
to stamp these outbreaks out.

Why the rebound? First, populations in the regions affected weren’t
sufficiently vaccinated beforehand with IPV, which would have
protected them until any outbreaks could be controlled. This was
partly owing to a gap in vaccine supply, says Ondrej Mach, who
co-chairs a new GPEI group that will oversee future withdrawals of the
oral vaccine.

What’s more, says Mach, just before the switch, vaccine-derived type
2 polio was detected in Nigeria. Transmission was probably already
under way in Nigeria and other countries, adds Mach, and the emergency
type 2 vaccine seeded further outbreaks.

Since 2021, however, this seeding has become much less likely:
vaccination campaigns are controlling the outbreaks using
a genetically engineered oral vaccine
[[link removed]], which has an
even lower chance of becoming virulent than the OPVs used previously.

What risks does the post-polio world face if full oral withdrawal goes
wrong? An analysis by Kid Risk and the CDC gave one answer (D. A.
Kalkowska _et al. Risk Anal. _https://doi.org/k428; 2023). Their
model considers what might happen if all OPV use stopped in 2027 but
vaccine-derived polio was not completely eliminated beforehand and
outbreak responses were weak. In one scenario, the model predicts that
there could be as many as 40,000 cases of paralysis caused by
vaccine-derived polio 8 years after OPV administration is
discontinued. To avoid this, the authors suggest that population
immunity in areas with polio cases today needs to be very high —
about 90% — just before withdrawal. Thompson says that most
countries have achieved this in the past, at least for short periods
of time.

KEEPING A LOOKOUT

Even after OPVs are successfully withdrawn, therefore, countries
can’t let their guard down. They must put in place surveillance
“to detect any poliovirus, no matter where in the world it appears
and however fleetingly”, says a report by the Transition Independent
Monitoring Board, an independent group of scientists that reports
periodically on the polio endgame and is chaired by Donaldson.

Polio surveillance takes two main forms: searching for cases of
paralysis that might be caused by polio; and monitoring waste water
for any virus shed by carriers.

Both will be crucial for years, as an example from Malawi shows. The
country had been free from wild polio for three decades when, in 2021,
a stool sample from a three-year-old with paralysis arrived at the
national laboratory to be sent abroad for testing. The sample sat for
two months before it was shipped with others, says Jamal Ahmed, who
coordinates polio eradication for the WHO in its African region, which
comprises 47 countries. The result came back a month later: it was
wild polio type 1, not seen in the continent since 2016.

Sequencing traced its origin to Pakistan, but also revealed that the
virus had been circulating for two years undetected — possibly in
Malawi, and possibly elsewhere. Because Malawi had no wastewater
surveillance at the time, it was impossible to know.

A health worker gives an oral polio vaccine to a child in Karachi,
Pakistan, in 2022.Credit: Asif Hassan/AFP via Getty

Within 30 days of receiving the result, emergency immunizations began.
Six campaign rounds later, says Ahmed, Malawi has seen no more cases
of wild polio. And, with the WHO’s help, the country swiftly
installed environmental surveillance sites.

The episode also showed that the emergency vaccination programme
wasn’t up to the job, says Jay Wenger, who leads the polio programme
at the Bill & Melinda Gates Foundation in Seattle, Washington. “We
had to rebuild the polio infrastructure we had before” to get rid of
the virus, he says.

Global wastewater surveillance has become a bigger priority since the
COVID-19 pandemic, says Donaldson, because politicians are paying more
attention to trends in disease. Ahmed says that 41 of the 47 member
states of WHO Africa now have environmental polio surveillance, and
that the rest will soon catch up.

Innovations are helping to speed up a process in which timeliness is
crucial. One breakthrough is direct detection, a method that leapfrogs
several of the conventional stages of the testing process; for
example, by extracting RNA directly from samples without the need to
culture them.

THE THREAT OF ESCAPE

No matter how successful the eradication effort is, the virus will
remain in research institutes and vaccine-manufacturing facilities —
and in an unknown number of routine diagnostic labs.

Escapes happen. Last year, a lab worker at a manufacturing facility in
Utrecht, the Netherlands, picked up type 3 virus at the facility, and
this was then detected in wastewater surveillance outside the plant.
No cases of paralysis resulted. Vaccine manufacturing is “a huge
containment nightmare”, says Mach.

The WHO has a plan for poliovirus containment that urges nations to
minimize the number of facilities retaining poliovirus materials and
to destroy any unnecessary stocks. At the moment, the WHO knows of 74
facilities that hold polio, in 22 countries.

The first step was for each country to set up a national authority for
containment by 2018, to ensure that facilities comply with biosafety
requirements. China and Romania have not yet done this, and other
countries have missed subsequent deadlines.

Even for compliant facilities, forgotten samples remain a threat, says
Andy Macadam at the National Institute for Biological Standards and
Control in Potters Bar, UK. “All you have to do is mislabel the
tube.” And polio might lurk in some facilities that are not even
subject to the containment plan, says Heymann. This could include
frozen stool samples taken for other reasons at a time when polio was
circulating.

Since 2000, there have been 21 reported incidents of poliovirus
release from laboratories and vaccine-production facilities in 8
countries, with 16 cases of polio as a result, according to Derek
Ehrhardt, who heads the WHO’s poliovirus containment unit. Most
cases have been in vaccine-manufacturing facilities, but five of them
were in research labs in which workers discovered that vials
containing poliovirus were mislabelled (none of those
cross-contamination incidents led to paralysis). The solution, says
Heymann, is better biosecurity in all labs.

To reduce the need for live virus, scientists are developing ways to
produce the inactivated vaccine without it — for example, by using a
non-infectious, genetically engineered starting material, or by
designing vaccines from virus-like particles or messenger RNA.

A SURPRISING SOURCE

There is yet another source of poliovirus, unforeseen 35 years ago
when eradication efforts began.

In most people who receive the oral vaccine, the immune system
generates antibodies that protect them against the virus. But in a
small number of people born with particular immune deficiency
disorders, the immune system allows the attenuated virus from the
vaccine to live on, evolving as time goes by and emerging in their
stools. No drugs have been proved to cure an ongoing polio infection.

Only some of the several hundred types of immunodeficiency lead to
chronic retention of poliovirus. No one knows how many people are
affected, and no such shedding is known to have triggered a polio
outbreak, although it might have contributed to one in the Philippines
in 2019–21.

But, says Mach, even one person retaining and shedding poliovirus is
incompatible with eradication. “We have to do something.” An
international — if patchy — search for people with these immune
disorders who have chronic polio has produced a register of 200
individuals.

One person with the condition lives in the United Kingdom and was
vaccinated with OPV as a child. For more than 20 years, he
asymptomatically carried — and shed — the attenuated virus, which
evolved to its disease-causing form. His gut was “essentially a
culture vessel”, says David Boyle at PATH, a non-profit
medical-research organization based in Seattle, Washington.

That’s why scientists were surprised to learn that the person’s
infection had gone.

It disappeared after he received the antiviral drug remdesivir for
severe COVID-19 in August 2021. This could be coincidence, says
Macadam, but it bolsters the case that antivirals could be used to
treat polio infection (two such drugs are being explored as polio
treatments). Monoclonal antibodies are also under development.

COMPLACENCY AND RESPONSIBILITY

Keeping vaccination rates high for at least a decade after eradication
will be the best protection — but there are fears that commitment to
IPVs might wane once eradication has been declared. Routine
immunization campaigns struggle to reach every child, especially
during conflict, disasters or pandemics. COVID-19 drove the number of
unvaccinated or undervaccinated children up to 23 million in 2020.

Added to this is the growing problem in some regions of vaccine
scepticism and complacency, which grew worse because of activism
against COVID-19 vaccines, says Peter Hotez, a vaccine specialist and
public advocate at Baylor College of Medicine in Houston, Texas.

With so much to be done to maintain a polio-free world, Donaldson is
asking who will be accountable once the GPEI disbands a year after
eradication, handing its responsibilities to WHO departments, partners
and national health programmes.

A transition has already begun in some countries, but many have
struggled to find their own funding amid changing government
priorities. Slackening efforts now could bring bigger problems in the
future, says Aidan O’Leary, who directs polio eradication at the
WHO. “If we collectively take our eye off the ball and don’t build
the resilience of health systems going forward, then we face further
problems down the line.”

But done well, says O’Leary, the post-polio world could bring wider
health benefits for everyone: better surveillance and immunization
measures, and more joined-up health services. “The last mile of the
polio eradication programme”, he says, “is the first mile for
global public-health security.”

_Nature_ 623, 680-682 (2023)

_doi: [link removed]

_AISLING IRWIN is a freelance journalist writing mostly about science,
the environment and development whose work regularly appears in New
Scientist, Nature, SciDev._

_NATURE is a weekly international journal publishing the finest
peer-reviewed research in all fields of science and technology on the
basis of its originality, importance, interdisciplinary interest,
timeliness, accessibility, elegance and surprising conclusions. Nature
also provides rapid, authoritative, insightful and arresting news and
interpretation of topical and coming trends affecting science,
scientists and the wider public._

_Nature's mission statement_

_First, to serve scientists through prompt publication of significant
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Second, to ensure that the results of science are rapidly disseminated
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_Nature's original mission statement was published for the first time
on 11 November 1869._

__

STUDY: THE INDO-EUROPEAN LANGUAGE FAMILY WAS BORN SOUTH OF THE
CAUCASUS
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By FRANK JACOBS
Though over three billion people speak an Indo-European language,
researchers are not sure where the language family originated.
Strange Maps
September 16, 2023

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