a1723: Polio in Haiti (fwd)

[Bob Corbett <corbetre@webster.edu>]

From: Greg Chamberlain <GregChamberlain@compuserve.com>


(Wall St Journal, 16 April 02)


Polio Cases From Viral Mutation Raise Debate on Ending Vaccine

By GAUTAM NAIK



Olen Kew made an unusual discovery two years ago while testing stool
samples taken from two paralyzed children on the Caribbean island of
Hispaniola. Though pesticide poisoning was the initial suspected cause of
the paralysis, "we found a smoking gun," says Mr. Kew, a virologist at the
U.S. Centers for Disease Control and Prevention in Atlanta. "It was an
outbreak of polio."

This was puzzling because the island, home to Haiti and the Dominican
Republic, had been free of the disease for at least a decade. Mr. Kew
concluded that the virus had re-emerged from a more ominous source: one of
the two polio vaccines in use.

The vaccine in question uses a live form of the virus that is too weak to
cause the disease but is strong enough to stimulate the body's immune
system into building a defense against polio. Scientists have long
speculated that the virus contained in the vaccine might in some rare cases
re-emerge in a virulent form. But this had never been seen. It wasn't until
Mr. Kew and his colleagues analyzed the changes in the genes of the
Hispaniola bug that they saw the alarming manner in which the virus had
"back-mutated."

In a study that appeared on Friday in the journal Science, Mr. Kew and his
colleagues described how the virus, originating in the vaccine, had grabbed
the DNA of other pathogens, or disease-bearing micro-organisms, and then
undergone a series of genetic changes. By studying the pattern of gene
mutations, the scientists could tell how the virus had evolved and become
dangerous again. They learned that it had lurked for about two years,
moving from person to person, and then had reverted to a virulent form and
caused the very disease it was meant to prevent.

After Mr. Kew sounded the warning in 2000, about 2.3 million children were
quickly vaccinated in Haiti and the Dominican Republic. But the rogue virus
eventually killed two children and paralyzed 19 others. Scientists now
believe that vaccine-derived viruses were behind similar outbreaks in the
Philippines in 2001 and in Egypt in 1988.

The mutating vaccine is bad news for the World Health Organization and
other public-health groups, which are tantalizingly close to eradicating
polio. It has awakened them to the risk that polio could come back even
after the disease is deemed to be officially wiped out. And it has added
new fuel to a sensitive debate over whether to end vaccination altogether.
The WHO hopes to eradicate polio by the end of this year and, provided no
new cases emerge over the next three years, certify the world as polio-free
by 2005. Now it may be forced to rethink its strategy for what it calls the
"polio endgame."

"Lots of people were perhaps a little naive about the complexity of how we
get out of this," concedes Bruce Aylward, head of the WHO's global
polio-eradication effort. "A post-Cold War, post-Sept. 11 era has
concentrated the minds of people about how difficult this really is."

On Tuesday, the Geneva-based WHO and other groups plan to hold a series of
news conferences in nine cities, including London, Washington and Geneva.
At these events, officials will outline the progress made in snuffing out
polio last year -- especially in challenging places such as Bangladesh and
Congo -- but also the latest hurdles, including the Hispaniola case.

The WHO estimates that the number of global cases last year was about
1,000, although it expects to revise that number downward to the 600 level.
By comparison, there were 350,000 cases reported in 1988 and half a million
per year in the early 1980s.

Behind this extraordinary progress is a pink liquid known as oral polio
vaccine, or OPV. Health officials have long believed that once the disease
was officially eliminated, they could simply withdraw OPV on the same day
world-wide, saving the world annual immunization costs of about $1.5
billion.

But that reassuring vista has always had clouds hanging over it. Scientists
and health officials have been concerned that even if naturally occurring
polio is eradicated, the disease could return through an accident or
bioterrorism. The back-mutating form found in Hispaniola deepens the
threat.

Thousands of unprotected children could suddenly be at risk. Even today,
between 5% and 10% of children in developed countries aren't immunized,
while in many poor countries half the population of children aren't
protected against the disease. In Hispaniola, for example, polio returned
because a large number of children hadn't been vaccinated. In a recent
article for the journal Clinical Infectious Diseases, D.A. Henderson -- who
led the campaign to eradicate smallpox and now heads the new U.S. Office of
Public Health Preparedness -- warns of a "serious catastrophe" and suggests
that oral vaccination be continued indefinitely.

Many poor countries, where the bulk of polio cases occur today, would
rather stick to the original plan. They argue that once the disease is
gone, it is pointless -- and too expensive -- to keep vaccinating their
huge populations.

"I don't buy it," says Jean-Marie Okwo-Bele, a former WHO official, who led
the polio-vaccination campaign in his native Congo a decade ago and is now
chief of polio immunization for Unicef in New York. "Just because you
anticipate a handful of cases are you going to keep immunizing children
with billions of doses a year?"

Polio mainly affects children. The virus enters through the mouth, often
through food or water contaminated by the fecal matter of an infected
person. After multiplying in the throat and intestines, it can invade the
central nervous system and cause irreversible paralysis of the limbs.
Worse, it can attack parts of the brain and weaken respiratory muscles.
When large polio epidemics swept through the U.S. and Europe in the 1940s
and 1950s, many victims were forced to use "iron lungs" -- huge metal
cylinders that regulated their breathing and kept them alive.

The biggest break against polio came in the 1950s, when Jonas Salk
developed the first effective vaccine. Also known as the inactivated polio
vaccine, or IPV, it is made from a dead virus. So there is no fear that it
will ever back-mutate and become virulent. But IPV is expensive to produce,
making it costly for developing countries, and it must be injected by a
trained person, making it unsuitable for mass vaccinations in many places.

In the early 1960s, another American scientist, Albert Sabin, came up with
an easy-to-administer oral form of the vaccine -- OPV -- which is made by
deactivitating the infectious parts of the virus. OPV costs just nine cents
a dose in developing countries. Not only does it provide long-lasting
immunity to the vaccinated person, its effects also spread -- via fecal
contact -- to others who aren't themselves vaccinated. Today, much of the
industrialized world uses IPV, while poorer countries prefer OPV.

Even before the Hispaniola case emerged, some virologists warned about
exactly such a scenario. In May 1988, about 50 health specialists met at
the Geneva offices of the WHO and debated the conclusions of a 100-page
report written by Paul Fine, an expert in communicable disease at the
London School of Hygiene and Tropical Medicine.

"Some people thought that the disease would just go away," recalls Mr.
Fine, who was present at the meeting. But his research, he says, "concluded
that the transmissibility of polio might persist in countries with poor
hygiene."

Some based their assumptions on the approach taken once smallpox was
stamped out. Soon after that disease was officially eradicated in 1980,
vaccine manufacturing facilities were dismantled and stocks of the virus
were destroyed in all but two facilities, one in the U.S. and one in
Russia. Smallpox vaccines can last for decades when stored properly, and
many developed countries have maintained millions of doses in case the
disease returns. Terrorism fears after Sept. 11 prompted the U.S. to
recently order millions of additional doses.

_______________

Countries where polio still exists:

Areas of High Infection Rates:
India
Pakistan
Afghanistan
Nigeria
Niger

Areas of Low Infection Rates:
Ethiopia
Somalia
Sudan
Angola
Egypt

Source: World Health Organization
______________


Polio presents thornier problems. OPV vaccines cannot be stored beyond a
few years, which means that manufacturing facilities might have to be
maintained at huge expense even after polio is wiped out. Nor is it easy to
spot an outbreak. While a smallpox victim is readily identified because of
a distinctive rash, only one in about 200 polio carriers shows signs of
paralysis, even though all 200 may continue to infect others. The only way
to tell is by examining stool specimens.

There are also concerns about whether the virus might somehow escape from
laboratories. Unlike smallpox, stockpiles of the polio virus exist in
hundreds of medical facilities around the world, where it is used as a tool
for research and education. Polio is not nearly as infectious or as lethal
as smallpox. But it may still be a tempting addition to the arsenal of a
bioterrorist, once the disease is gone and populations are again
vulnerable.

"It's the morning after," notes Mr. Aylward of the WHO. "We've got to be
ready for this."

The widespread existence of polio-virus stocks also means that the risks of
an accidental escape from a lab are significantly higher. Two years ago, a
group of scientists identified 12 instances of such potentially dangerous
substances escaping from labs between 1941 and 1976. Indeed, the last
smallpox case actually occurred when the virus escaped from a lab in
Birmingham, England, in 1978.

The WHO has a plan by which it hopes to locate labs around the world that
store polio virus and ensure that the stockpiles are destroyed or
adequately contained. The agency says that the task is formidable but
manageable. Others are more skeptical, noting that the WHO has no
enforcement authority and cannot guarantee that secret stockpiles of polio
virus won't be stashed somewhere.

Other scientists worry that polio might re-emerge from an even more
unlikely source: People who suffer from certain rare immune-deficiency
disorders that are usually genetic in origin. A normal person, immunized
with OPV, will naturally excrete the virus for five to six weeks after
being given the vaccine. Then, an antibody response in the person's body
stops that process. But people with immune-deficiency disorders can't
produce the necessary antibodies and go on excreting the virus for months
or years. Could such excreted viruses silently circulate and, years later,
when mass immunizations are halted, mutate into a virulent form?

"We don't know. But I don't think it's something we can afford to ignore,"
says Philip Minor, head of virology at Britain's National Institute of
Biological Standards and Control, which tests vaccines for the government.

Mr. Minor says that so far, a dozen patients with rare immune disorders
have been identified who excrete the virus for years after being given OPV.
He cites the case of an otherwise healthy man in Birmingham, England, who
has excreted the virus since 1995.

Mr. Minor notes that people infected with HIV also have compromised immune
systems. While there's no proof so far, and HIV isn't a genetic disease,
"the question of whether AIDS patients fall into this category is a huge
one," he adds.

Such risks have prompted scientists such as Mr. Henderson of the U.S. to
suggest that polio vaccinations should be continued indefinitely. One
approach would be to discard OPV and use only the injectible version of the
vaccine, IPV. Because it's made from a dead virus, it can't revert to a
virulent form. But this, too, is fraught with political complications.

In the latest issue of Science, Mr. Fine and Neal Nathanson of the
University of Pennsylvania write: "Unfortunately, this strategy could be
perceived as offering a double standard of public-health prevention,
because developing countries would be exposed to a risk that the
industrialized nations -- those that can afford IPV -- could avoid."

Dissension has already sprung up. "You use IPV, fine. But who is going to
procure it for poorer countries?" says Mr. Okwo-Bele of Unicef. He suggests
that a better approach might be to stop all vaccinations once polio is
eradicated, and then use intense surveillance to ensure that no new cases
of the disease crop up. "It's cheap and effective," he says.

Some of these problems might have been averted if scientists had worked on
inventing an inexpensive oral vaccine that didn't have the potential to
back-mutate. But it isn't cheap or easy to develop such vaccines and so, in
the 1980s, the WHO opted not to do so. "It would be a great thing to have,
but to divert resources at that time wouldn't have been appropriate," says
the WHO's Mr. Aylward. Mr. Henderson, writing in the journal Vaccine in
1999, described that decision as "an extraordinary act of ignorance." (Mr.
Henderson wasn't available to be interviewed for this article.)

Now it may be too late to come up with a new and improved polio vaccine. So
the WHO and other health groups are left to tussle with the global
implications of the Hispaniola case even as they savor the opportunity to
declare victory over a disease that once killed and maimed thousands.

Says Mr. Aylward of the WHO: "After eradication, it would be unfortunate if
the only polio left in the world was caused by man."