| Malik Peiris on Containing SARS and Watching for What’s Next |
 Over the years, infectious illnesses from seasonal flu viruses to
deadly pandemics have emerged from the depths of China to spread
throughout the world. In late 1997, it was the avian flu that jumped
from chickens to humans, infecting 18 people, killing 6, and running
through the newspapers for weeks on end. In the spring of 2003, it was
the mutant coronavirus known as SARS—for severe acute respiratory
syndrome—that infected more than 8,000 individuals in 30 countries and
killed over 700 of them. But SARS, despite the nightmares it engendered,
was quickly controlled and then vanquished by a massive public-health
response spearheaded by the World Health Organization (WHO) and
representing an unprecedented collaboration of research laboratories
worldwide.
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"SARS brought home to everybody the dimensions of emerging
infections in the 21st century," says Malik Peiris of the
Department of Microbiology, University of Hong Kong"
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On the front lines of this effort was a collaboration of virus
hunters working out of the University of Hong Kong and Queen Mary’s
Hospital, led by Malik Peiris, who managed within weeks to culture the
SARS virus from victims of the infection and then promptly identify it.
As a result of this team effort, Peiris’s initial report, published on
April 19, 2003 in the Lancet ("Coronavirus as a possible
cause of severe acute respiratory syndrome," 361[9366]:
1319-25, 2003), has racked up more than 300 citations in just a year and
a half, recently ranking among the hottest papers in medicine (at #6 in
the July/August 2004
issue, and, in the current roundup, just out of the
Top Ten at #11). A follow-up report published four weeks later by Peiris
and his collaboration (Lancet, 361[9371]: 1767-72, 2003),
studying the clinical progression of the SARS virus through the
community, has already garnered more than 180 citations as well (see the
table below). In all, according to the latest update of the Hot
Papers database, Peiris and coauthors currently account for seven highly
cited reports published over the last two years. (Visit the ESI Special
Topic: Coronaviruses.)
Peiris, now 55, earned his medical degree, an M.B.B.S, from the
University of Ceylon in 1972 and then his doctorate in virology from
Oxford University, U.K., in 1981. The following year he returned to Sri
Lanka to set up a virology lab in the Department of Microbiology at the
University of Peradeniya, where he stayed until 1988, when England
beckoned again and Peiris spent seven years as a virologist at the Royal
Victoria Infirmary, Newcastle, a WHO Reference Center for Rapid Virus
Diagnosis. In 1995, he moved to the University of Hong Kong, where he is
now Assistant Dean of Research Affairs in the Faculty of Medicine and a
professor in the Department of Microbiology.
Peiris spoke to Science Watch from his office in Hong Kong.
Your first experience with a disease outbreak predates
your Hong Kong years. Tell us about that.
Peiris: In 1982, I went back to Sri Lanka as a lecturer to
set up a virology lab, where we studied insect-borne viruses such as
Japanese encephalitis. That’s when we had to face a major outbreak. In
one hospital alone, there were over 500 cases of Japanese encephalitis.
The initial outbreak was in 1985, and we went on to study exactly what
was going on in the whole ecology of the disease. Not just in humans,
but in pigs, mosquitoes—the whole ecosystem. Subsequently we had
another major outbreak in 1987.
What did pigs have to do with it?
Peiris: The natural reservoir of the virus is wild birds.
But if you have any significant number of pigs, they will pick up the
virus from the wild birds and then serve as a bridge between the
bird-mosquito virus cycle and humans. The chance of a spillover to
humans becomes much greater. The dangerous combination is pigs, the
correct type of mosquito—one that generally breeds in rice fields—and
the virus presence in birds. Presumably, the virus was in Sri Lanka for
years and years. The reason this outbreak occurred at that point in time
is that a few years before, the administration, with all good
intentions, decided to diversify the agricultural base of the farmers by
introducing pig breeding into this intense rice-growing area. They
actually encouraged farmers to do small-scale pig husbandry as a way of
increasing income and protein source. But in terms of disease ecology,
it resulted in this huge outbreak. The episode really illustrates the
problems that can arise by changing agricultural practices.
What brought you to Hong Kong?
Peiris: I came in 1995, and my initial task was to set up a
diagnostic virology laboratory for Queen Mary’s Hospital. Within two
years we had the avian flu outbreak. That was November-December 1997. We
were involved with many other people in tackling that outbreak,
particularly in trying to develop diagnostic methods and other tools.
Subsequent to that outbreak, I got more interested in avian and animal
influenza viruses and their threat to human health. We had a research
program together with one of my predecessors here, Ken Shortridge, and
subsequently we joined with another colleague, Yi Guan, in studying
these viruses—particularly in birds and poultry, but also in pigs.
What made this avian flu virus so interesting?
|
High-Impact Papers by Malik Peiris et al.,
Published Since 1994
(Ranked by total citations)
| Rank |
Paper |
Citations |
| 1 |
J.S.M.
Peiris, et al., "Coronavirus as a possible
cause of severe acute respiratory syndrome," Lancet,
361(9366): 1319-25, 2003. |
309 |
| 2 |
J.S.M.
Peiris, et al., "Clinical progression and
viral load in a community outbreak of
coronavirus-associated SARS pneumonia: a prospective
study," Lancet, 361(9371): 1767-72, 2003. |
187 |
| 3 |
K.Y.
Yuen, et al., "Clinical features and rapid
viral diagnosis of human disease associated with avian
influenza A H5N1 virus," Lancet,
351(9101): 467-71, 1998. |
186 |
| 4 |
R.A.M.
Fouchier, et al., "Aetiology – Koch’s
postulates fulfilled for SARS virus," Nature,
423(6937): 240, 2003. |
111 |
| 5 |
M.
Peiris, et al., "Human infection with
influenza H9N2," Lancet, 354(9182): 916-7,
1999. |
110 |
| 6 |
J.M.
Nicholls, et al., "Lung pathology of fatal
severe acute respiratory syndrome," Lancet,
361(9371): 1773-8, 2003. |
77 |
|
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Peiris: Well, the bird flu incident in 1997 taught us that,
contrary to previous belief, avian viruses can directly infect humans
and cause severe disease and even death. Thus, H5N1 viruses constituted
a killer. It was clearly important to see what that virus was doing in
the environment, following the containment of the bird flu outbreak in
December 1997. In collaboration with Dr. Rob Webster in Memphis and with
funding from the NIAID, we set up systematic surveillance of avian
influenza viruses. The parent H5N1 virus was stable until about the year
2000. Then it started to change quite dramatically by mixing its genes
with other avian influenza viruses. By the end of 2002, we had two
outbreaks of bird flu in two public parks in Hong Kong. Quite a number
of birds, including ducks, swans, geese, and a whole range of ornamental
birds, started dying due to this virus. Together with the department of
agriculture, we detected this virus in wild birds as well. These highly
pathogenic avian influenza viruses are rarely found in wild birds, so
these findings had us increasingly concerned about this virus. In early
February of 2003, when we heard about the outbreak of so-called unusual
pneumonia going on in Guangdong province, it really rang warning bells
for us. We thought that it could be the avian flu virus that had
acquired the ability to transmit from human to human—that we were
looking at the beginning of a new influenza pandemic.
What were the first things you did when you heard about
this outbreak?
Peiris: We did two things. First, along with the Hospital
authority and the Department of Health here in Hong Kong, we set up an
enhanced surveillance of all severe pneumonia cases in Hong Kong. You
have to keep in mind that there was nothing very distinctive about this
new pneumonia. And severe pneumonia is a pretty common disease. There
will be plenty of patients with severe pneumonia in any major city, and
Hong Kong was no different in this respect. The first unusual finding of
that investigation was a family that had been to China and returned, and
who had evidence of H5N1 pneumonia. The daughter had died in China of an
undiagnosed pneumonia-like illness, and the father died back in Hong
Kong. The son was ill but fortunately recovered. From the father and son
we identified this avian flu virus, which was the first time since 1997
that it had been identified in humans. Taking into account our previous
concerns, it seemed to us that maybe avian flu was the culprit, and we
shared this information with the WHO.
But it was not the avian flu?
Peiris: No, it proved to be a red herring in the short term,
because avian flu was not the cause of SARS. However, our suspicions
were not completely unfounded, because H5N1 avian flu exploded across
Asia just a few months later, leading to human cases and deaths. But
coming back to SARS: we were still left trying to find out what was
responsible for the outbreak in Guangdong. When we looked at further
patients, we saw no evidence of influenza or avian flu in these
patients, but we did end up isolating, from two patients, this very
unusual virus that turned out to be the new coronavirus. We were by then
working as part of the WHO network of laboratories searching for the
etiology of SARS. We reported our findings to this network. Two other
labs within the WHO network also came to this same conclusion. So all
this is teamwork—teamwork within the WHO network and within our own
research group, including my colleagues K.H. Chan, Leo Poon, Yi Guan,
and John Nicholls, along with K.Y. Yeun and Wilina Lim from the
Department of Health.
In what ways is SARS different from known coronaviruses?
Peiris: It’s different in many ways, such as the way it
grows and what it grows in. It’s all different. If you look at it
genetically, it certainly falls into the coronavirus family, but it’s
clearly distinct from all the coronaviruses, whether in humans or
animals.
Before the coronavirus was accepted as the etiological
agent of SARS, other candidates were also under consideration. How was
this resolved?
Peiris: Some labs reported seeing a paramyxovirus, and
another lab in Hong Kong reported detecting a human metapneumovirus, as
did some labs in Canada. The consensus in mainland China was that SARS
was due to chlamydia, a type of bacteria. I think the problem was that
some of these SARS patients actually had more than one virus. Because
when scientists went back and looked at these patients with
metapneumovirus, they also invariably had the SARS coronavirus too. Once
you put patients in the hospital together with all the other patients,
they tend to share their viruses. Presumably that’s what was happening
with the metapneumovirus.
Without this WHO-coordinated worldwide network of
laboratories to identify the virus so quickly, could SARs have turned
into the kind of worldwide pandemic of influenza, such as the famous
1917-18 flu epidemic?
Peiris: It’s very useful to find a cause and identify the
actual virus and develop the correct diagnostic tests, but you can’t
neglect the role of conventional, old-fashioned public-health
epidemiology and control measures. At the end of the day that’s really
what controlled the outbreak of SARS: identifying suspected patients
with SARS, getting them out of the communities and into hospitals,
putting them in isolation, and putting other contacts of these people
under observation or, in some cases, in quarantine. Certainly the
identification of the virus was extremely useful in that process, but I
would not want to minimize the role of determined, conventional
public-health measures.
So the virus could have been controlled, even without
knowing exactly what it was?
Peiris: That’s correct. Although knowing what it was
certainly helped—for example, we quickly developed a diagnostic test
so we could now precisely differentiate this disease from other
pneumonias. Once we started using these tests, it became clear that the
virus was also present in feces. That was a surprise. We also found out
that this virus is extremely stable. Most respiratory viruses die quite
rapidly once they leave the body. But this doesn’t. In feces, it
remains stable for days and days. So we learned a huge amount of
important information that helped in control, but the good old-fashioned
techniques were the key. It was the very quick overall response from
many countries, all coordinated through the WHO, that prevented this
outbreak from going on and on.
What lessons did you learn from SARS that will help the
next time a virus like this emerges?
Peiris: SARS brought home to everybody the dimensions of
emerging infections in the 21st century. It really shocked people to
realize how quickly a virus can be all over the world, can spread
worldwide within weeks. It also brought home the importance of
animal-human interface, because as you know, SARS is primarily an animal
infection. It crossed over to humans and then really took off. That
means we need to be alert to similar problems at the animal-human
interface. If you look back at all the major emerging infection problems
over the last few decades—whether West Nile or mad cow disease or the
avian flu or SARS—these were all animal pathogens that jumped to
humans. So it’s crucial that we have good surveillance on this.
What constitutes sufficient surveillance in this case?
Peiris: Veterinarians throughout the world are already
looking at viruses that cause disease in poultry and other livestock,
but there are viruses that can still cause problems in humans that might
not be so easy to notice. The SARS virus was not killing anything in a
visible way in the animal kingdom. So I’m talking about regular
surveillance in apparently healthy populations of poultry and wild
birds. That’s the type of surveillance we need.
Are we going to see another situation like SARS in the
near future? Is it a given?
Peiris: It’s very likely. It seems we’ve been having one
major emerging infection every two or three years in some part of the
world. SARS was unique in that it had learned to jump from human to
human. Most of the others still go from animal to human. In that way,
SARS was all the more dramatic. I certainly hope we do not have another
one like that for some time—at least not in this neck of the woods.
But it’s likely that we will see something, somewhere, in the next few
years. And I think we all need to be prepared for that.
Visit the ESI Special
Topic: Coronaviruses.
Science
Watch®, September/October 2004, Vol. 15, No. 5
Citing URL:
http://www.sciencewatch.com/sept-oct2004/sw_sept-oct2004_page3.htm |
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