SARS - A New Disease - Confronting a new disease
by David Bradley
An unusual type of pneumonia emerged in Guangdong in November 2002, said
Professor Malik Peiris of the Department of Microbiology, Faculty of
Medicine, University of Hong Kong. It caused a significant outbreak in the
provincial capital Guangzhou in January 2003 and left the authorities and
hospitals in nearby Hong Kong with a serious cause for concern. After all,
how could any hospital spot a case of this new atypical pneumonia when
around 100 patients each month enter hospital intensive care wards with
severe pneumonia?
Information from clinicians in Guangdong suggested that one unusual feature
of the disease was its propensity to give rise to clusters of cases with
pneumonia, particularly in health care workers. By February and March,
outbreaks of pneumonia were reported from Hanoi and Hong Kong, and medical
scientists recognized they were dealing with an entirely new disease,
subsequently called Severe Acute Respiratory Syndrome, SARS.
The World Health Organization announced that we were facing a major disease
threat and significant numbers of cases were observed in Singapore, Canada
and with individual cases also been reported in Germany. Peiris was among
those who recognized the SARS coronavirus.
The SARS virus was detectable in the respiratory tract, faeces and urine of
sufferers indicating that infection was not confined to the respiratory
tract. In contrast with other respiratory viral infections, SARS CoV was
relatively stable in the environment and in faeces. Respiratory droplets
were likely to be a primary source of transmission, but detection of high
concentrations of virus in faeces and its environmental stability suggested
that faecal contamination may be relevant in explaining large community
outbreaks such as that in Amoy Gardens, Hong Kong.
One question that plagued doctors during the outbreak was how to identify
patients with the new disease. SARS remains an enigmatic disease, said
Peiris. Symptoms look very much like pneumonia. The disease differs in many
respects from other respiratory viral infections. Infection seems to be
associated with the severe pneumonic spectrum of the illness and
asymptomatic infection seems uncommon. In contrast to other respiratory
viral infections, the viral load of SARS CoV in the upper respiratory tract
and faeces is low in the first few days of illness and peaks around day 10
of illness. This may explain why transmission is less common early in the
disease.
A virus similar to SARS CoV has been identified in palm civets, a
tree-dwelling mongoose eaten as a delicacy in China, and other small mammals
in wild game animal markets in Guangdong. These popular markets, Peiris
explained, may be the interfaces where species to species transmission
occurs. People working in these markets and handling these animals often
show antibodies to the virus in their blood.
SARS was a pandemic whose control required a coordinated global response,
said Peiris, the World Health Organization provided leadership in this
regard by coordinating a series of virtual research networks who shared
information on the causes, diagnosis, disease spread, and clinical
management. He pointed out that SARS is but one emerging virus and that
medical science should not focus purely on this disease. At the time of the
meeting, there was already major concern about an outbreak among people in
Vietnam of a strain of bird influenza known as H5N1.
Proof positive
Dutch virologist Professor Albert Osterhaus of Erasmus University,
Rotterdam, The Netherlands outlined the scientific proof that led to a novel
coronavirus being identified as the primary cause of SARS. The laboratory
network for SARS that was established by the World Health Organization was
quite instrumental in allowing scientists to make this discovery, said
Osterhaus.
At first, this unusual pneumonia baffled scientists. The SARS coronavirus
had already been implicated and Osterhaus and his colleagues began
performing clinical and experimental test to determine the virus' precise
role in causing SARS.
As part of the network trying to prove whether SARS-CoV was the primary
cause, they had access to clinical and post-mortem specimens from 436 SARS
patients from six countries. They began testing these samples for infection
with SARS-CoV and also for human Metapneumovirus, a well-known childhood
infection. Its presence in so many of the SARS cases seemed to suggest it
had a primary role in the disease. Indeed, both the newly discovered
coronavirus and the well-known metapneumovirus were common factors in SARS.
To prove one way or another which virus was causing SARS, the researchers
had to prove three things. First, they had to show that the suspect is
present in all known cases. Secondly, they have to isolate it from samples
and grow it in the laboratory. And, finally, isolated cultures must be
capable of causing the disease in newly infected individuals. The first two
are relatively straightforward, it is the latter that involves the most
difficult step.
The researchers had to infect related species with SARS-CoV in an attempt to
replicate the symptoms of SARS. Animals infected animals were found to exude
SARS-CoV from the nose, mouth, and pharynx just two days after infection.
Two of the four animals tested also had the same lung damage seen in SARS
patients. Those infected with just the metapneuomovirus did not display SARS
symptoms. It became clear that the coronavirus was the likely primary cause
of SARS itself.
Indeed, reported Osterhaus, SARS-CoV infection was diagnosed in about three
quarters of patients diagnosed as having SARS, while metapneumovirus was
ultimately diagnosed only in about 12% of patients. This Osterhaus said,
suggested that SARS-CoV was the most likely cause of SARS. Producing the
proof was a tour de force, taking a mere three weeks.
The team demonstrated that three different species other than humans could
be infected with the coronavirus and displayed SARS symptoms. This,
Osterhaus, suggested provides researcher with model systems that will allow
them to study the disease's early stages and to test vaccination and
antiviral therapy.
Spotting SARS
The onset of illness in SARS can take anything up to 12 days after a person
first comes into contact with the SARS coronavirus, explained Dr Maria
Zambon Head of the Respiratory Virus Unit of the UK's Health Protection
Agency. Symptoms can persist for many days with most patients recovering but
it being fatal in a large proportion of elderly people.
Robust tests and confirmatory checks are needed. The SARS virus can be
detected in either the illness phase or by detecting footprints of the virus
(antibodies) in the recovery phase, but ensuring the right test works at the
right time will assist in an emergency by providing an accurate estimate of
how many people have been affected or infected.
When SARS first emerged, medical researchers hunted for the virus in lung
secretions. But it was soon found that the test results depended on the
timing sample collection relative to the onset of illness, and that other
samples including stool and blood samples might also be useful. This
provides doctors with a dilemma - how to tell whether or not a patient
suffering symptoms resembling SARS is infected with that or another virus
with similar symptoms.
A robust test, said Zambon, will not only help doctors bring an epidemic
under control, but would allow them to estimate the disease's true burden.
Albert Osterhaus, Malik Peiris and colleagues in proving SARS coronavirus to
be the primary cause of the disease in April 2003 provided the basis for
diagnostic tests.
Molecular tests have to be able to work fast, finding the telltale genetic
fingerprints of the virus within 12 hours of sample collection to provide
doctors with confirmation of a case. A rapid test is no simple task and
raises quality control issues, such as ensuring good confirmation strategies
and communication so that doctors understand that they have to cope with a
margin of error when a negative result may be falsely negative.
To ensure the most robust and accurate tests are developed, requires a
strong research infrastructure, Zambon emphasized. What you do in normal
conditions determines what you do in an emergency. If you do not have a
strong R&D capability, there will be no capacity to deal with an emergency,
such as having to develop new tests quickly to meet an unanticipated threat,
such as SARS.
Read more about emergent diseases in Session 3:
Understanding
disease transmission and control
