The SARS crisis of 2003 was an instance when vigorous
international cooperation and intervention may have successfully prevented a
global health crisis. It fully showed the value of the WHO influenza
surveillance network. During the near pandemic between November 2002 and July
2003, with 8,096 known infected cases and 774 deaths (a mortality rate of 9.6%).
Here are the key events of the crisis. Local outbreaks of SARS infections were
reported in China, Hong Kong, Taiwan, Vietnam, Singapore, Philippines, Mongolia,
Canada, and the USA. A number of dead-end sporadic cases were reported in other
countries who received infected visitors from affected countries.
Identification of SARS. In early Feb 2003,
Guandong province in China reported 305 cases and 5 deaths caused by
atypical pneumonia of unknown cause. It later transpired that Guandong
was already having similar cases as early as Nov 2006. On the 19th Feb
2003, the WHO influenza network activated emergency pandemic plans after
receiving a report from Hong Kong confirming a case of Influenza H5N1
infection. This proved to one of the defining events in the control of
the SARS outrbreak. On the 21st Feb, a Chinese medical professor came to
Hong Kong to attend a relatives wedding. He stayed at a room on the 9th
floor of the Metropole Hotel. Six people who stayed on the same floor of
that hotel were infected and they carried the infection to the rest of
Hong Kong, Vietnam and Canada. Therefore all the cases outside China
could be traced to that event. In early March - Carlo Urbani identified
SARS (Severe Acute Respiratory Syndrome) as a unique clinical entity in
patients who had been infected by patient in a Vietnam hospital. That
patient had previously stayed on the 9th floor of the Metropole hotel.
WHO was put on alert. Sadly, Urbani himself later became infected and
died.
Discovery of SARS Virus. Initially, a number
of agents were implicated as the causative agent, including chlamydia,
metapneumoviruses, and influenza H5N1 but it soon became apparent that a
new agent may be involved. The breakthrough came on 21st March when the
Hong Kong university reported the isolation of an unknown virus in FRhk4
cells, and were able to demonstrate a rising antibody response against
this virus by IF in patients with SARS. Furthermore, virus-like
particles were seen in lung biopsies. On 22nd March, CDC reported the
growth of a corona-like virus in Vero E6 cells. This was identified as a
new coronavirus and PCR based diagnostic tests became rapidly available.
Properties or SARS Virus
The SARS virus is a novel coronavirus that did not
belong to the previously known OC43 and 229E serogroups. It had a genome
of 29,000 bases. It had some rather unusual virological aspects.
-
Incubation period:- mean 6.37
(95% CI 5.29-7.75)
-
Risk of transmission is
greatest around day 10 of illness when maximum excretion of the
virus occurs in respiratory secretions and faeces.
-
No evidence that patients can
transmit infection 10 days after fever has resolved.
-
The virus appeared to be
endemic in bats, where they do not cause any disease. The jump to
human appeared to have occurred via Civet cats, which is a delicacy
in Southern China.
Epidemiology
-
Incubation around 6 days.
-
Spread by droplets – there is no evidence it is an
airborne disease. It is not certain whether faecal-oral spread can
occur.
-
Health care workers were at special risk, especially
those involved in procedures that may generate aerosols. In some cases,
transmission to health care workers occurred despite that the staff was
wearing full protection. The fact that medical staff is at special risk
is probably due to the fact that maximum excretion of the virus occurs
more than one week after the onset of symptoms, when the patient is
likely to be in hospital.
-
Risk of transmission is greatest at around day 10 of
illness when maxi
-
No evidence that patients can transmit infection 10
days after fever has resolved.
-
Children are rarely affected
by SARS
-
The implications of the
Metropole Hotel are not yet fully understood.
-
Risk of in-flight transmission
– 5 international flights had been associated with the transmission
of SARS. No evidence of in-flight transmission after the 27 March
2003 WHO advisory on flights.
ˇ@
Super-spreading Events. The SARS virus is not
normally highly infectious but certain individuals have spread the virus to
a large number of individuals. These individuals were already known as
super-spreaders but the WHO now prefer to call them super-spreading events.
In Hong Kong, 3 super-spreading events are known to have occurred.
-
Metropole Hotel - this is not fully understood.
-
Prince of Wales Hospital - the patient was an asthmatic who was put on a
nebulizer. It is that that the nebulizer allowed the virus to travel much
wider and further than it would normally do.
-
Amoy Garden - this is perhaps the most spectacular event of the whole
crisis. 321 persons in the housing estate were infected. Residents of
affected blocks were first quarantined in their homes and then
transferred to internment camps. The clustering of cases suggested that
a defective sewage system was probably responsible.
Diagnosis
The initial diagnosis of SARS was clinical. According to the
guidelines issued by the WHO, SARS may be
suspected
in a patient who has:
- Any of the symptoms including a fever of 38 ˘XC
(100.4 ˘XF) or more AND
- Either a history of Contact (sexual or casual) with
someone with a diagnosis of SARS within the last 10 days
OR Travel to any of the regions identified by the
WHO as areas with recent local transmission of SARS
(affected regions as of 10 May 2003 that were parts of
China, Hong Kong, Singapore and the province of Ontario,
Canada).
A probable case of SARS has the above findings
plus positive chest x-ray findings of atypical pneumonia or
respiratory distress syndrome.
With the advent of diagnostic tests for the
coronavirus probably responsible for SARS,
the WHO has added the category of
"laboratory confirmed SARS" for patients who
would otherwise fit the above "probable"
category who do not (yet) have the chest
x-ray changes but do have positive
laboratory diagnosis of SARS based on one of
the approved tests (ELISA,
immunofluorescence or PCR).
A battery of laboratory tests became rapidly available on
the discovery of the SARS virus.
RT-PCR - This is the mainstay of diagnosis of SARS
infection. A variety of specimens can be used including NPA (preferred),
throat swabs, trachael aspirates, and faeces.
Virus Isolation - Vero E6 and FRhk4 cells may be
used. However, the positivity rate is much lower than PCR and stringent
Biosafety Level III facilities are required. Therefore, this is not
recommended for small routine laboratories.
Serology - SARS virus infection may be confirmed
by seroconversion or rising titres of antibodies. IFT and ELISAs are
available but originally, whole virus antigen was used which required
biosafety level III facilities. Because of the low predictive value of the
first generation PCR assays, a serological diagnosis was often the only
means of confirming a diagnosis of SARS.
Treatment
A number of treatments were tried initially including
ribavirin and steroids. However there is little evidence to suggest that any
therapies used during this period was effective. In 2004, it was reported
that researchers in China had successfully produced a vaccine that induced
antibodies in 24 out of 36 volunteers but more research will be needed to
ascertain whether it would be effective.
Post Epidemic
Since
July 2003, laboratory acquired cases of SARS had been reported in
Singapore, Taiwan and China. These have occurred in Biosafety level III
and IV laboratories. Sloppy practices and procedures were to blame
rather than failings in the containment equipment. In Jan 2004, a 32 old
male with diagnosed with naturally acquired SARS in Guandong, China. He
infection was linked to contact with civet cats and the Chinese
authorities promptly ordered the slaughter of 10,000 civet cats and
related species of animals in the area.