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Origin of SARS?


From China's Provinces, a Crafty Germ Spreads

By ELISABETH ROSENTHAL






S HUNDE, China - An
hour south of Guangzhou, the Dongyuan animal market presents endless
opportunities for an emerging germ. In hundreds of cramped stalls that
stink of blood and guts, wholesale food vendors tend to veritable zoos
that will grace Guangdong Province's tables: snakes, chickens, cats,
turtles, badgers, frogs. And, in summer, sometimes rats, too.
They are all stacked in cages one on top of another - which in turn
serve as seats, card tables and dining quarters for the poor migrants
who work there. On a recent morning, near stall 17, there were beheaded
snakes, disemboweled frogs and feathers flying as a half-alive headless
bird was plunked into a basket.
If you were a corona virus, like the one that causes severe acute
respiratory syndrome, known as SARS, it would be easy to move from
animals to humans in the kitchens and food stalls of Guangdong, a
province notorious for exotic cuisine prepared with freshly killed
beasts.
Indeed, preliminary studies of early SARS victims here in Guangdong have
found that an unusually high percentage were in the catering profession
- a tantalizing clue, perhaps, to how a germ that genetically most
resembles chicken and rodent viruses has gained the ability to infect
thousands of humans.
One of the earliest cases, last December, was a seller of snakes and
birds here who died at Shunde's First People's Hospital of severe
pneumonia. His wife and a several members of the hospital staff
contracted it as well, setting off an outbreak that now sounds eerily
familiar.
"Oh yes, I heard that a guy here died of that pneumonia," said Li
Songyu, a 40-year-old wearing a neat tan blouse, as she filleted live
frogs and dumped them into a basket. "But it is very safe and sanitary
now."
Around the same time in December, Huang Xinchu, a chef, was admitted to
the Heyuan People's Hospital, 100 miles to the north, ultimately
infecting eight doctors there. On Jan. 2, another desperately ill chef
was hospitalized in the city of Zhongshan, south of Shunde, setting off
an outbreak.
But if such early outbreaks present scientific hints about the origin of
SARS, they also provide painful political lessons in how a disease that
has spread worldwide could have been prevented.
In early January, alarmed health departments in Shunde, Heyuan and
Zhongshan all reported the strange pneumonia clusters to Guangdong
provincial authorities, who concluded that they were facing a highly
infectious pneumonia caused by a previously unknown agent.
It is unclear whether that conclusion was passed on by provincial
officials to the Ministry of Health in Beijing, or ever reported to
international health agencies that might have conducted an early
investigation into the problem. Instead, it would be another two and a
half months before the strange pneumonia had a name, coined only after
an Italian doctor working in Hanoi, Vietnam, alerted the World Health
Organization about a similar new pneumonia he was seeing there.
And it would be three and a half months before China's leaders would
admit that their country had an epidemic of SARS. From January through
the middle of March, doctors in Asia and Canada were encountering
patients carrying a virulent and highly contagious germ, unaware that
they were facing potentially lethal infection.
During that period, hundreds of health workers fell ill. During that
period, well-meaning doctors were placing SARS patients in ordinary
wards - as they would patients with normal pneumonia - and those
patients were passing the infection on to hundreds of others.
Origins in Food Trade
Scientists have always considered the teeming farms of southern China,
where animals and people crowd together as ideal breeding grounds for
new human viruses, which can jump between species under such conditions.
So it was no surprise in March when the World Health Organization said
it believed that SARS originated in Guangdong.
But when a World Health Organization delegation went to look at data on
the earliest SARS cases, they found few farmers among the victims.
Instead what jumped out was an odd preponderance of food handlers and
chefs - about 5 percent of the first 900 patients, as opposed to less
than 1 percent among patients with normal pneumonia.
So far, studies are in their early stages and have yielded few specific
conclusions. Even if food handlers turn out to be the conduits through
which SARS passed from animals to humans, all evidence points to
human-to-human transmission now.
Still, for much of December and January, several small cities around
Guangzhou were fighting - and often winning - localized battles with the
strange pneumonia that would later be named SARS.
In December, the 32-year-old chef from Heyuan was admitted to the Heyuan
People's Hospital, having fallen sick with pneumonia on his job near the
boom town of Shenzhen. His family had him transferred to Guangzhou when
his condition deteriorated despite medication. But when eight doctors
and nurses fell ill with a similar untreatable pneumonia in Heyuan just
a few days later, hospital officials became alarmed.
On Jan. 1, they told the local health department of the cluster of
cases. "On Jan. 2, we reported a new infectious disease to the
provincial health bureau," said Dr. Ouyang Songhua, deputy chief of the
Heyuan Public Health Department. "They immediately sent out an expert
team to investigate it, deciding it was a pneumonia of previously
unknown cause."
Word of the disease spread among local doctors so that when another chef
with pneumonia arrived at Zhongshan Hospital on Jan. 2, short of breath
and feverish, doctors isolated him in intensive care.
But not soon enough: 13 medical staff members were infected, who in turn
infected 15 others in Zhongshan as well. Outbreaks in Shunde, Heyuan and
Zhongshan peaked in January, and by February the virus was poised to
move on.
By early February, sick and frightened patients from small cities like
these were traveling to more advanced hospitals in the provincial
capital of Guangzhou - and that is when the surge of cases really began.

From Feb. 2 through Feb. 4, a very sick man from Zhongshan made the
rounds of emergency rooms in Guangzhou as treatment failed to improve
his condition, leaving dozens of health workers infected. At the time,
emergency room staff members understood little about the new pneumonia
that had been cropping up around the province. At first, they did not
isolate the man and were wearing no protective gear.
Unfortunately, the man was what is now known as a "super-spreader" - one
of a small group of SARS patients who is highly infectious. Dozens of
doctors and nurses fell sick at the Zhongshan No. 2 Hospital, where he
was finally admitted.
"He was very sick, but who knew there was something so terrible going
around?" said a nurse named Mo at the Zhongshan No. 2 Hospital,
recalling the long, frightening quarantine that followed in February,
when nurses and doctors spent long weeks living in their units waiting
to see if they will start to cough. In China and in much of Asia, more
than 30 percent of SARS victims have been hospital workers.
Hong Kong as a Gateway
On Feb. 21, Dr. Liu Jianlun, a 64-year-old lung specialist from the
Zhongshan hospital, attended his nephew's wedding in Hong Kong, even
though he was running a fever. With what is now known about the disease,
health care providers like Dr. Liu with such extensive exposure to SARS
would be quarantined and forbidden to travel. But no such guidelines
existed then.
At the Metropole Hotel, where he stayed, he passed SARS on to a number
of other guests, including two Canadians, an American businessman en
route to Hanoi, a Hong Kong man, and three young women from Singapore.
SARS, until then confined to the Chinese mainland, was unleashed on the
world.
At the Kwang Wah Hospital in Hong Kong, where Dr. Liu went when his
breathing became labored, he advised shocked doctors and nurses of the
mystery pneumonia that was ravaging his hometown, insisting that they
isolate him behind double panes of glass and don protective gear before
his exam. The doctor died several days later; no one at the hospital was
infected.
But the grisly story was not shared with other doctors in Hong Kong or
the rest of the world. And, with the new corona virus silently breeding
in their bodies, the nine guests at the three-star Metropole Hotel
dispersed on airplanes like bees carrying a deadly pollen, seeding SARS
locally and to far corners of the world.
The woman from Toronto, Kwan Sui-chu, died in a Toronto hospital on
March 5, but not before infecting her son and at least five health
workers. Canada now has identified at least 140 SARS cases, 15 fatal.
Johnny Chen, the American businessman, fell ill at a hospital in Hanoi
in late February, where he ultimately infected 20 health workers,
including Dr. Carlo Urbani, an Italian medical researcher who alerted
the W.H.O. about a new type of pneumonia and who also eventually died of
the disease. The Hong Kong man was admitted to a general ward at the
Prince of Wales Hospital, setting off a huge outbreak.
The three Singapore women fell ill after going home in late February and
were admitted to three hospitals from March 1 to March 3. While two of
the women infected no one else, the third, Esther Mok, another
super-spreader, set off a chain of infection based at the Tan Tock Seng
Hospital, from which over 90 people fell ill, accounting for more than
half Singapore's cases. Ms. Mok has recovered, but many members of her
family became ill, including her mother and father, who both died.
On March 14, the World Health Organization formally issued its worldwide
alert about the new disease, which it called SARS.

A Focus on Prevention
Since then, countries visited by this new plague have taken increasingly
severe steps in order to control further spread of a disease that has
eluded many conventional infection barriers. Because the disease remains
difficult to treat and has a death rate of 5 to 10 percent, by far the
most effective way to deal with it is to stop its spread.
"On an individual level it is relatively low risk, but the proportion of
people who have a severe course appears to be quite high," said Rob
Breiman, a respiratory expert who has worked for the World Health
Organization on the outbreak. "Until we know more about this disease,
protecting against exposure is extremely important."
In Canada, for example, even healthy travelers arriving from affected
areas are advised to go into a 10-day voluntary quarantine, where they
are advised to stay at home, take their temperature frequently and sleep
in a separate room from other family members. Ontario alone now has
7,000 people under various types of quarantine.
But some people have resented the restrictions for what most often
proves to be nothing more than a fever from a common cold. On Easter
Sunday, one health care worker who had been exposed refused to stay at
home, attending church services and a funeral in Toronto. Health
officials are now considering a court order to keep him isolated.
Companies and governments in the West are drastically curtailing travel
to SARS-affected regions. Some are also are requiring employees to stay
at home for 14 days after visiting SARS-infected areas.
"I'm not too worried about the disease," said Jane Cowells, a resident
of New Zealand, as she arrived this week, unmasked, at Beijing Capital
Airport. "But the whole thing is a headache, since when I go home I
can't go back to work for 10 days."
In Vietnam, where the epidemic is now under control, officials said they
were considering sealing off the entire 800-mile border with China to
prevent sick tourists from reintroducing the germ.
In many Asian countries, airports have come to resemble bioterrorism
labs, as nurses in protective gear assess arriving passengers for signs
of disease. No place is more vigilant than Singapore.
Singapore's Drastic Steps
"Welcome to Singapore! Are you feeling well today?" chimes a chorus of
nurses, their faces covered by masks, their eyes by goggles, their
bodies by yellow hospital gowns. Passengers coming from other countries
with SARS are guided to pass through a high-tech thermal scanner that
picks up temperatures over 100. Masked soldiers are there to escort away
those with fever.
Those who pass muster are given a card warning that they might have been
exposed to a deadly disease. Those who are feverish are whisked, without
apology, into a 10-day quarantine, and Singapore means business. Video
cameras will be installed in the home by a security firm, to make sure
patients do not stray. Those few who do are tagged with an electronic
wristband that records their movements.
But even in a small country, placing thousands on quarantine has been a
strain. Last Monday, after a case of SARS was discovered in a vendor at
Singapore's largest vegetable market, the Ministry of Health ordered all
2,400 food sellers to report for quarantine, up from a total of 467
quarantined before. Since 80 percent of the country's vegetables pass
through the Pasir Panjang Market, restaurants were bracing for a
shortage of greens.
"We do what we have to," said Dr. Balaji Sadasivan, a neurosurgeon who
is Singapore's minister of state for health. "I don't think we've seen
anything like this before and it is a global problem. For now this is a
battle that is being fought with the thermometer and quarantine."
Because of elaborate contact tracing, the Singapore outbreak is by far
the best defined in the world. All but 4 of the 188 victims were
infected in the hospital or by a family member at home. The four
exceptions are a child who got the disease from a classmate with an
infected parent, a flight attendant who served an infected doctor from
Singapore on a flight in Europe, a cab driver and a vegetable salesman.
Dr. Sadasivan is unapologetic as he describes the draconian measures his
department has adopted to halt the spread of the germ.
When the three young women from the fateful Hong Kong hotel brought SARS
to three different hospitals in Singapore in early March, Singapore
doctors were unaware of the odd pneumonia that was hospitalizing dozens
of patients each day in Guangdong and so admitted them to ordinary
wards. If the Chinese had publicized their severe pneumonia in
Guangdong, or if the Hong Kong doctors had more aggressively reported
the information about Dr. Liu, their response almost certainly would
have been different.
Two of the women did not pass on the germ, but one infected more than 20
people, both patients and hospital workers. One of the nurses she
infected also proved to be a super-spreader, passing SARS to 26 others.
One of the 26 was a patient in the cardiac intensive care unit whose
SARS was not recognized because of many other medical problems.
Within a month, 90 people at the Tan Tock Seng Hospital had the disease.
The Health Ministry dug up an old law that allowed them to impose
mandatory quarantines, with fines of 5,000 Singapore dollars for those
who disobey. They also essentially closed the 1,000-bed hospital to
other patients - hoping to contain the virus within its walls.
But it escaped all the same. Some patients who had been at Tan Tock Seng
in March contracted the disease and later went to other hospitals when
they developed coughs - setting off secondary outbreaks. One went to
Singapore General for an endoscopy and was screened for SARS, but did
not run the telltale fever because he was on steroids that suppress the
body's response. Ninety people at the hospital were infected.
After this resurgence, the Health Department instituted a policy that
every patient at every hospital be considered a potential SARS patient.
Nurses are always masked when seeing patients, who are allowed only one
visitor a day. Confirmed SARS patients are allowed no visitors at all,
though they can talk to friends and family on their cellphones. Nurses
may not work on more than one unit and patients may not transfer from
hospital to hospital.
"We used to have a health care system organized for efficiency," said
Dr. Sadasivan. "But now our hospitals are organized for SARS
prevention."
Outside of the hospitals, the ministry closed all schools for two weeks
to halt potential transmission of the virus. All cab drivers now take
their temperatures twice a day. Temperature checks and health
questionnaires are standard for those entering buildings.
At Tan Tock Seng Hospital last Monday, an ambulance arrived carrying a
vegetable seller who came under the market quarantine. Although he felt
well, the man said he had a fever, and so the driver told him he might
have to remain in the hospital. Approaching a cordoned-off screening
area, he was resigned, saying, "I don't think I could have the disease,
but I know I have to do it."
China's Slow Response
But Singapore's aggressive, open confrontation with a viral enemy is a
lesson that some other countries have been slow to learn, especially
China, the world's most populous country, where SARS emerged almost half
a year ago.
Although doctors in Guangzhou were well aware of the problem as early as
January, information about an epidemic was suppressed for months, and
only started dribbling out at the beginning of April, under intense
international pressure.
Only in the last week have numbers begun to emerge elsewhere in China,
and the task is still not complete. In Beijing, they already paint an
alarming portrait of an epidemic that is likely to dwarf that in either
Guangdong or Hong Kong.
At a news conference on April 10, He Xiong, the deputy director of the
Beijing Centers for Disease Control, was still delivering a calm
message, endorsing numbers that the government released at the time:
that in Beijing there were only 27 SARS cases, so people should not
worry.
"Of course they can travel, we think it's very safe," he said, referring
to an approaching national vacation when tens of millions of Chinese
would normally be expected to travel.
But that misinformation only fueled the spread of SARS, as people - with
fevers and coughs - continued to go to school and work, passing the
disease on to others. As the number of cases increased well into the
hundreds, the illusion proved hard to maintain in a city with a
world-class gossip network that spread rumors of overflowing SARS wards.

By last weekend, everyone was skeptical, as a smattering of schools and
hospitals mysteriously closed. One People's Armed Police hospital in
Beijing was closed after five patients were infected. The Zhongguancun
No. 1 Primary School closed when a relative of a student got SARS. The
Beijing University Institute of Economics put several dozen people on
quarantine after a secretary's mother got pneumonia.
More than a dozen of Beijing's universities had reported suspected
cases. At the Economics and Finance University alone, more than a dozen
students and faculty members were listed as suspected SARS cases,
resulting in the suspension of classes from April 17.
That day, the main gate of the Northern Construction University was a
panic scene, as masked students made arrangements to flee to their
hometowns in the wake of suspected SARS cases on campus. "I want to get
out of here as soon as possible," said one alarmed student, making calls
on her cellphone to borrow money for the trip home.
Then, last Sunday, the Chinese government fired both the health minister
and the mayor of Beijing, and started releasing alarming data that
confirmed these fears. As of Friday, there were close to 900 confirmed
cases in Beijing, a number that is certain to strain the resources of
city hospitals and will make SARS far difficult to control.
But can the lessons of prevention learned in a tiny, authoritarian
country like Singapore be applied elsewhere, particularly in a vast,
chaotic place like China, with far more cases and a highly mobile
population?
In Singapore, with its aggressive system of identifying and isolating
SARS patients, no health care worker has been infected for over three
weeks. But in Hong Kong, 2 to 10 doctors and nurses are falling ill each
day, in part, health officials there say, because doctors are still not
identifying them as SARS victims early enough and are admitting them to
ordinary wards.
"There is so much we don't know about this virus - how long it will be
with us? Will it mutate and become more easily transmitted?" Dr. Breiman
said. "But it is a little frightening that something which started in
one location could spread so quickly around the world."

 

 
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