FACULTY OF HEALTH SCIENCES
NATIONAL UNIVERSITY OF MALAYSIA
2010/2011
NNNB
EPIDEMIOLOGY
GROUP 1: SYSTEMIC ACUTE RESPIRATORY
SYNDROME
NAME
MATRIC NUMBER
MOHD SHAFIQ BIN RAHMAT
A 122576
NUR HASNIEZA BINTI MOHD ROSLI
A 126797
KHO JIA HUI
A 126752
KHOR YUN YING
A 126731
SYAFINAZ BINTI CHE OMAR
A 127457
AIDA FARAHIN BINTI ABDULLAH
A 127481
HAZURAIHA BINTI KOSNIN
A 127484
OOR VASI D/O SAMYNAZAN
A 126710
TENG CHOON
A 126721
LEONG QI FANG
A 126803
ANG SHU MIN
A 126786
OOI THENG CHOON
A 126721
1.0 INTRODUCTION
On 12 March 2003, the World Health Organization (WHO) issued a global alert on the outbreak
of a new form of pneumonia-like-disease. The illness, officially known as severe acute
respiratory syndrome (SARS), is potentially fatal and highly contagious, and has spread quickly
to many parts of the world in a matter of a few weeks.
Aided by globalization and the ease of air travel today, the disease has been reported in
many countries such as China, Hong Kong, Vietnam, Singapore, Canada, US, with a large
number of infections and a significant number of deaths. Since SARS is transmitted person-to –
person, extermination of the agents of transmission would not be a plausible solution.
There are three main factors that make SARS a particularly difficult problem to deal with. First,
victims who suffer from the illness display symptoms that are very much similar to those of the
common flu. It usually begins with a high fever (over 38ºC), accompanied by symptoms such as
headache, sore throat, shortness of breath and dry cough.
This makes it difficult to distinguish SARS from the typical cold. Before the alert on the
disease was sounded, many initial cases were wrongly diagnosed as common flu; and general
practitioners
sent
patients
home
prescribing
them
with
regular
antibiotics.
The second worrying characteristic of SARS is that it spreads from person-to person with ease.
Experts have established that the illness is spread by “close contact”. The virus is believed to
have the resilience to survive out of the human body for a few hours. Hence, an infected person
can release droplets of bodily fluids containing the virus into the air when coughs, or when he
rubs his mouth or nose and touches an object.
The virus can be passed on to a second person who breathes in the droplets, or who
touches a contaminated object such as door knob and rubs his face. The ease of infection has led
to a great number of people being infected at the onset of the outbreak. Investigations have
shown that most of the infected are mostly family members and friends of the victim, or health
workers.
Lastly, SARS is dangerous because with an incubation period of less than ten days, it acts
fast-and in some cases, kills fast. Although its fatality rate is not exceptionally high at 4%, its
1
high infection rate can result in a significant number of deaths. SARS is also more dangerous for
older people who have weaker immune systems or are already suffering from health
complications like heart problems, diabetes and high blood pressure. Most of the victims who
killed by SARS were idle-aged or older folks with inherent health problems. For this group of
people, SARS has the capability to rapidly complicate their existing health problems and cause
their physical conditions to deteriorate rapidly. However, there were also a few cases whereby fit
and young adults fell ill quickly and have to breathe with the aid of respirators within a week of
infection.
The new coronavirus was isolated in Vero E6 cells from nasal and throat swab specimens
of two patients in Thailand and Hong Kong with suspected SARS. The isolate was identified
initially as a coronavirus by electron microscope (EM). The little hooks sticking out of the viral
body are the telltale characteristics that help classify the pathogens as members of the
coronavirus family. The identity was corroborated by results of immunostaining, indirect
immunofluorescennce antibody (IFA) assays, and reverse transcriptase-polymerase chain
reaction (RT-PCR) with sequencing of a segment of the polymerase gene. IFA testing of sera and
RT-PCR analysis of clinical specimen from SARS cases were positive for the new coronavirus.
Coronavirs particles were also identified by EM in cells obtained by bronchial lavage from a
patient with SAS. Sequence analysis suggested that this new agent is distinct from other known
coronavirus.
As of today, the spread of SARS has been fully contained, with the last infected human
case seen in June 2003 (disregarding a laboratory induced infection case in 2004). However,
SARS is not claimed to have been eradicated (unlike smallpox), as it may still be present in its
natural host reservoirs (animal populations) and may potentially return into the human
population in the future.
In late May 2003, studies from samples of wild animals sold as food in the local market
in Guangdong, China found that the SARS coronavirus could be isolated from palm
civets(Paguma sp.), but the animals did not always show clinical signs. The preliminary
conclusion was that the SARS virus crossed the xenographic barrier from palm civet to humans,
and more than 10,000 masked palm civets were destroyed in Guangdong Province. Virus was
2
also later found in raccoon dogs (Nyctereuteus sp.), ferret badgers (Melogale spp.) and domestic
cats.
In 2005, two
studies
identified a
number of SARS-like coronaviruses
in
Chinese bats Phylogenetic analysis of these viruses indicated a high probability that SARS
coronavirus originated in bats and spread to humans either directly, or through animals held in
Chinese markets.
2.0 EPIDEMIOLOGY
2.1 Malaysia
In Malaysia, the outbreak resulted is two deaths due to the probability of SARS in
Jerantut, Pahang and Penang. The victim who involved with history has ever visited China or
Singapore. The total number of cases includes those who've recovered or died.This Table shows
the incidence of SARS in Malaysia since WHO records began.
Infection
Mortality
Recovered
Reclassified
8
2
5
2
“Table 1. Showing number of infection, mortality, recovered and reclassified cases of SARS in
Malaysia from 5 April to 24 May 2003.”
2.2 Asia
In 2003, SARS became an outbreak of cases in the hospital systems of Hong Kong, Vietnam,
Singapore and been transmitted to many county in Asia. The infection has possibility start from
Guangdong, China.
2.2.1 Hong Kong
The Hong Kong index patient (the physician from Guangdong, China) infected 12 other persons
who had been staying at the same hotel. Two of these individuals were subsequently responsible
for outbreaks in two local hospitals.
The Hong Kong health authorities immediately
implemented enhanced infection-control procedures in all hospitals in Hong Kong, including
3
stringent barrier and respiratory protection for healthcare workers, daily environmental
disinfection of affected wards, and cohorting of SARS patients. Towards the end of March 2003,
a further SARS outbreak occurred among residents of Amoy Gardens, Hong Kong, with a total
of 320 SARS cases in less than three weeks. The probable index patient was a patient suffering
from chronic renal failure; in addition to person-to-person spread and to the use of communal
facilities such as lifts and staircases, the SARS virus may have been spread through the sewage
systems of the buildings (Government of Hong Kong Special Administrative Region).
“Figure 1.Epidemic curve, Hong Kong.”
After the initial phase of exponential growth, the rate of confirmed SARS cases fell to
less than 20 per day by April 28. The Hong Kong epidemic seems to have been under control
even earlier, by early April 2003, in the sense that each case had, already by then, failed to
replace itself. The main reason for this would have been the reduction in the contact rate between
infectious individuals and the rest of the population.
At the beginning of June, public hospitals attempted to resume normal service, grappling
with a backlog of an estimated 16 000 postponed operations because of the suspension of 30% of
4
the medical services during the SARS crisis. By June 16, 1755 cases of SARS had been
diagnosed in Hong Kong. 295 patients (16.8%) had died. 1386 patients (79.0%) had recovered.
Around 30% of cases occurred in healthcare workers. Among these, nurses were the most
exposed category, accounting for about 55% of all infected healthcare workers. 15% were
doctors, 27% support staff. Eight medical workers had died by June 2.On June 23, the WHO
removed Hong Kong from its list of areas with recent local transmission of SARS.
2.2.2 Vietnam
The outbreak in Vietnam began on February 26, when a 48-year-old Chinese-American
businessman was admitted to the French hospital in Hanoi with a 3-day history of high fever, dry
cough, myalgia and a mild sore throat. He had previously been in Hong Kong, where he visited
an acquaintance staying on the 9th floor of the hotel where the Guangdong physician was a
guest. By March 5, secondary probable SARS cases were identified among health care workers
in Hanoi, and subsequently 63 people were infected. On April 28, the WHO removed Vietnam
from the list of affected areas, making it the first country to successfully contain its SARS
outbreak. The absence of any new cases for a continuous 20-day period (the duration of two
incubation periods) was an encouraging indicator that appropriate detection and protection
measures, as recommended by the WHO, were able to contain outbreaks and prevent their
further spread:

Prompt identification of persons with SARS, their movements and contacts;

Effective isolation of SARS patients in hospitals;

Appropriate protection of medical staff treating these patients;

Comprehensive identification and isolation of suspected SARS cases;

Exit screening of international travelers;

Timely and accurate reporting and sharing of information with other authorities and/or
governments.
5
2.2.3 Singapore
Close contact is usually required for transmission in most cases. The index case of SARS in
Singapore was a previously healthy 23-year-old woman of Chinese ethnicity who had been
staying on the 9th floor of Hotel M during a vacation to Hong Kong from February 20-25, 2003.
She developed fever and a headache on February 25 and a dry cough on February 28. She was
admitted to a hospital in Singapore on March 1. At that time, SARS had not yet been recognized
as a new disease easily spread in hospitals.
As a result, hospital staffs were unaware of the need to isolate patients and protect them.
Over a period of several days, the index patient infected at least 20 other people. No further
transmission from this patient was observed after strict infection control measures were
implemented. The virus initially spread rapidly among hospital staff, patients, visitors, and their
close family contacts. Later on, spread of infection between hospitals occurred when patients
with underlying disease - which masked the symptoms of SARS - were transferred to other
hospitals, placed in rooms with other patients, and managed without adequate protective
equipment (WHO).
The outbreak in Singapore was amplified by several so-called "super spreaders. 144 of
Singapore's 206 probable cases have been linked to contact with only 5 individuals (WHO).
6
“Figure2.Probable cases of severe acute respiratory syndrome, by reported source of infection Singapore, February 25-April 30, 2003.”
On April 20, after the identification of a cluster of illness among employees at a crowded
wholesale market, the market was closed for 15 days and more than 400 persons were placed in
home quarantine. The spread of infection was limited to only 15 other persons.In Singapore,
76% of infections were acquired in a healthcare facility; the remainder either had household,
multiple, or unknown exposures. Due to rigorous contact tracing and isolation procedures, 81%
of probable SARS cases had no evidence of transmission to other persons with a clinically
identifiable illness. Of the 84 (42%) healthcare workers with probable SARS, 49 were nurses;
13, physicians; and 22, persons with other occupations (attendants, radiographers, housekeepers,
a porter, and a cleaning supervisor); no SARS cases have been reported among laboratory
workers or pathologists.238 cases of SARS were diagnosed in Singapore; 33 patients died. On
May 31, Singapore was removed from the list of areas with recent local transmission (WHO).
2.2.4 China
Up until mid-April, the Chinese authorities underestimated the magnitude of the epidemic in
Beijing, with only 37 cases having been reported by April 19. In the following two days, the
Chinese authorities announced more than 400 new SARS cases. Additional reports indicated that
7
SARS had spread to other provinces, including western Guangxi, northern Gansu, and Inner
Mongolia. On April 23, the WHO extended its SARS-related travel advice to Beijing and the
Shanxi Province of China, recommending that persons planning to travel to these destinations
consider postponing all but essential travel. Four days later, the Chinese Authorities closed
theaters, Internet cafes, discos and other recreational activities and suspended the approval of
marriages in an effort to prevent gatherings where SARS could be spread. To date, the epidemic
in China seems to be under control. 5,327 cases of SARS have been diagnosed, 349 patients have
died. On June 24, Beijing was removed from the list of areas with recent local transmission.
2.2.5 Taiwan
The first two suspected SARS cases were diagnosed in a couple on March 14. The man had a
history of travel in February to the Guangdong Province and to Hong Kong. On March 26, a
Taiwanese resident of Hong Kong's Amoy Gardens flew to Taiwan and took a train to Taichung
to celebrate the traditional festival, Qing Ming. The man's brother became Taiwan's first SARS
fatality, and a fellow passenger on the train was also infected. Suddenly, in the last 10 days of
April, the number of cases began to increase steadily, which would have made Taiwan's
epidemic the third-worst in the world after China and Hong Kong. The origin of the outbreak
was a laundry worker aged 42 years with diabetes mellitus and peripheral vascular disease who
was employed at hospital A. On April 12, 14, and 15, he had a fever and diarrhea and was
evaluated in the emergency department. The patient remained on duty and interacted frequently
with patients, staff, and visitors. The patient had sleeping quarters in the hospital's basement and
spent off-duty time socializing in the emergency department. On April 16, because of worsening
symptoms, the patient was admitted to the hospital with a diagnosis of infectious enteritis. On
April 18, the patient became short of breath. A chest radiograph showed bilateral infiltrates, and
the patient was transferred to an isolation room in the intensive care unit with suspected SARS.
Because the index patient had been symptomatic for 6 days before SARS was diagnosed, the
number of potentially exposed persons was estimated at 10,000 patients and visitors and 930
staff. On April 24, hospital A was contained, and all patients, visitors, and staff were quarantined
within the building. Healthcare worker clusters at eight additional hospitals in Taiwan have been
linked to the initial outbreak at hospital A. Preliminary data suggest that many of these clusters
8
occurred when pre-symptomatic patients or patients with SARS symptoms attributed to other
causes were discharged or transferred to other healthcare facilities. SARS later extended to
multiple cities and regions of Taiwan, including several university and private hospitals. Four of
these hospitals, including a 2,300-bed facility in southern Taiwan, discontinued emergency and
routine services. Sporadic community cases also were reported in Taipei and southern Taiwan.
The April outbreak in Taiwan may serve as an example of the far-reaching consequences of one
single unrecognized SARS case. On July 5, Taiwan was removed from the list of areas with
recent local transmission (WHO).
2.3 Worldwide
The disease began spreading around the world along international air travel routes to Canada and
other cities in the world (WHO. SARS: Status of the Outbreak)
2.3.1 Canada
SARS was introduced to Toronto by a woman of Hong Kong descent who had traveled home to
visit relatives from February 13 to February 23, 2003. Whilst visiting their son in Hong Kong,
she and her husband stayed at Hotel M from February 18 until February 21, at the same time and
on the same floor as the Guangdong physician from whom the international outbreak originated.
The woman and her husband only stayed in the hotel at night, and spent the days visiting their
son. They returned to their apartment in Toronto, which they shared with two other sons, a
daughter-in-law and a five-month-old grandson on February 23, 2003. Two days later, the
woman developed fever, anorexia, myalgia, a sore throat, and a mild non-productive cough. She
died nine days after the onset of the illness. On March 8 and 9, five out of the six adult family
members presented with symptoms of SARS.
By mid-May, the Toronto epidemic was thought to be over after the initial outbreak had
mostly come under control. However, an undiagnosed case at North York General Hospital led
to a second outbreak among other patients, family members and healthcare workers.The new
outbreak spread from the SARS ward on the eighth floor of North York General Hospital, where
a 96 year old man undergoing surgery for a fractured pelvis on 19 April is believed to have
9
contracted the disease. The man developed pneumonia-like symptoms after his surgery but was
not suspected of having SARS. He died on 1 May.A woman from the hospital's orthopedic ward,
who was transferred to St John's Rehabilitation Hospital on 28 April, was later recognized as
having a mild case of SARS, and five other SARS cases then appeared at St John's Hospital.
The second Toronto outbreak demonstrates that spread among health care workers can occur
despite knowledge about the epidemiology and transmission of SARS. SARS patients with
chronic illnesses occurring concurrently with fever and/or pneumonia with a plausible diagnosis
are extremely challenging to the public health and healthcare systems. On July 2, the WHO
removed Toronto from its list of areas with recent local transmission. To date, 251 cases of
SARS have been diagnosed in Canada, most of them in the Toronto area. 43 patients have died.
2.3.2 Other country
Country
Cumulative
number
case(s)
of
Number of deaths
Case fatality ratio
(%)
Australia
6
0
0
Canada
251
43
17
China
5327
349
7
France
7
1
14
Germany
9
0
0
Hong Kong
1755
299
17
India
3
0
0
Indonesia
2
0
0
Italy
4
0
0
Kuwait
1
0
0
10
Macao
1
0
0
Malaysia
5
2
40
Mongolia
9
0
0
New Zealand
1
0
0
Philippines
14
2
14
Republic of Ireland
1
0
0
Republic of Korea
3
0
0
Romania
1
0
0
Russian Federation
1
0
0
Singapore
238
33
14
South Africa
1
1
100
Spain
1
0
0
Sweden
5
0
0
Switzerland
1
0
0
Taiwan
346
37
11
Thailand
9
2
22
United Kingdom
4
0
0
United States
29
0
9
Vietnam
63
5
8
Total
8098
774
9.6
11
“Table 2 .The official number of SARS cases reported from countries over the time period
November 1, 2002 to July 31, 2003, is shown in the table. “Notes: The cumulative number of
cases includes the number of deaths.
3.0 SIGN AND SYMPTOMS
SARS or Severe Acute Respiratory Syndrome, is a contagious respiratory infection that presents
a number of symptoms and signs. Signs and symptoms of SARS disease typically develop within
two to 10 days after exposure to the virus. The SARS illness usually begins with a fever
(measured temperature greater than 100.4°F [>38.0°C]). The fever is sometimes associated with
fever, chills or other symptoms, including headache, dry coughing, general feeling of discomfort,
and body aches.
Less common symptoms are also possible and sometimes can be seen such as diarrhea, dizziness,
nausea and vomiting. Some people also experience mild respiratory symptoms at the outset. In
some patients, body aches and headaches may appear 12 to 24 hours before fever. Some people
also have mild respiratory symptoms (sore throat or runny nose) at the outset. About 10 to 20
percent of patients with symptoms of SARS have diarrhea.
After two to seven days, SARS patients may develop a dry cough and shortness of breath. These
SARS symptoms may be accompanied by or progress to a condition in which the oxygen levels
in the blood are low (hypoxia). In 10 to 20 percent of cases, patients require mechanical
ventilation as they develop severe difficulty breathing, the result of insufficient oxygen in blood.
Severe respiratory illness may occur before abnormalities are noted on chest X-ray. There might
be radiographic (X-ray) findings of pneumonia or acute respiratory distress syndrome. Most
people will recover within 1 to 2 weeks.
SARS may be associated with other symptoms such as malaise, loss of appetite, confusion and
sometimes even rash. For children and young infants, they might not follow the exact pattern that
is seen in adults. Doctors should look for atypical symptoms in very young infants.
12
4.0 DIAGNOSIS AND INTERVENTION
4.1 Diagnosis
Before the actual case of SARS can be ascertained, all diagnoses are based primarily on clinical
symptoms and using laboratory test results as a secondary basis. SARS can also be diagnosed
based on the history of recent travel to high risk areas or history of close contacts with person
with SARS and also by chest x-ray. The symptoms of SARS are high fever, shivering, cough,
extreme lethargy, muscle aches, flu symptoms, diarrhea and general malaise.
Table 1 - Clinical symptoms at presentation (in %)
Lee et al. Peiris et
Donnelly et
Booth et
n=138
al.
al.
al.
n=50
n > 1250
n=144
100
94
99
or 73
74
65*
28*
Cough
57
62
50
69
Myalgia
61
54
51
49
Malaise
n.a.
50
64
31
Runny nose
23
24
25
2
Sore throat
23.
20
23
12
Shortness of n.a.
20
31
n.a.
Fever
Chills
100
rigors
breath
Diarrhea
20
10
27
24
Headache
56
20
50
35
13
*chills
Scientists from the Chinese University of Hong Kong and the Prince of Wales Hospital have
pinpointed the cause of this mysterious respiratory illness to that of viral origin. By examining
extracted tissue samples from SARS infected patients and analyzing them, the virus was initially
believed to belong to the paramyxoviridae family. However, further studies showed that it is
more likely to be a type of coronavirus. The researchers estimate the incubation period of the
virus to be between three to seven days. This has prompted authorities to impose “10-day
quarantines” for suspected cases.
During the course of illness, abnormal hematological values are common. Early studies
have shown lymphopenia and thrombocytopenia to be frequent in SARS patients. There is now
one study which analyzed the hematological changes during SARS in more detail. Progressive
lymphopenia was found in the peripheral blood of 153/157 (98 %) patients with SARS, reaching
its lowest point in the second week. Lymphopenia was also shown in hemato-lymphoid organs at
postmortem examination. The lymphocyte count commonly recovered in the third week, but
about 30% of patients were still lymphopenic by the fifth week of SARS. Most patients had
reduced CD4 and CD8 T cell counts during the early phase of illness, with mean CD4 and CD8
T cell counts of 287 cells/µl (normal: 410 to 1590 cells/µl) and 242 cells/µl (normal: 62 to 559
cells/µl), respectively. Low CD4 and CD8 lymphocyte counts at presentation were associated
with an adverse outcome in this study.
Transient leucopenia was found in 64% of patients during their first week of illness.
However, during the second and third week of illness, 61% developed leucocytosis.
Neutrophilia (> 7.500/µl) developed in 82% of patients, possibly reflecting the wide use of
corticosteroids. In total, 55% of patients developed a self-limiting thrombocytopenia, possibly
caused by an immune mechanism. With the exception of 2% of patients, the degree of
thrombocytopenia was mild (platelet counts >50.000/µl), reaching a low point at the end of the
first week. No patient had major bleeding or required platelet transfusion.
For the laboratory findings, common electrolyte and biochemical abnormalities include
elevated levels of lactate dehydrogenase (LDH), aspartate and alanine aminotransferases and
creatine kinase are usually obtained. (Table 2) Since high lactate dehydrogenase levels are often
14
seen in association with tissue damage, some authors propose that this finding indicates
extensive lung injury. However, it seems possible that elevated levels of lactate dehydrogenase
and transaminases may be, at least partially, secondary to the hemolytic effect of ribavirin
treatment. In a multivariate analysis, elevated LDH was an independent predictor for poor
outcome in SARS patients.
A substantial proportion of patients demonstrate low calcium, phosphorus, magnesium,
sodium and potassium levels. These abnormalities tend to worsen during hospitalization. Again,
it remains unclear whether these changes reflect the natural course of the infection or whether
they are secondary to the effects of treatment with ribavirin or other agents that affect renal
tubular function. There is evidence that the clotting profile (prothrombin time, activated partialthromboplastin time, international normalized ratio, and D-dimer) may be deranged in a
substantial number of patients.
Table 2 - Laboratory findings at presentation (in %)
Lee,
n=138
Leukopenia (< 3.5 x 34
et
al. Peiris,
n=50
26
109/l)
Lymphopenia (< 1.0 x 70
68
109/l)
Thrombocytopenia
45
40
Alanine
23
34
32
26
aminotransferase Ý
Creatine kinase Ý
15
et
al.
LDH Ý
71
n.a.
Hyponatremia
20
n.a.
Hypokalemia
25
n.a.
D-dimer levels Ý
45
n.a.
activated 43
n.a.
Prolonged
partial-thromboplastin
time
n.a. = not available.
The new coronavirus was isolated in Vero E6 cells from nasal and throat swab specimens
of two patients in Thailand and Hong Kong with suspected SARS. The isolate was identified by
electron microscopy (EM). The identification was corroborated by results of immunostaining,
indirect immunofluorescence antibody (IFA) assays, and reverse transcriptase-polymerase chain
reaction (RT-PCR) with sequencing of a segment of the polymerase gene. Coronavirus particles
were also identified by EM in cells obtained by bronchial lavage from a patient with SARS.
In order to prove beyond doubt that a candidate virus is causing SARS, “gold-standard”
tests will be needed. One such test is the enzyme-linked immunosorbent assay (ELISA), which
can detect antibodies produced by the patient’s immune system to fight a particular virus. The
diagnosis of SARS can be done by PCR testing, Seroconversion by ELISA or IFA and virus
isolation.
16
4.1.1 PCR testing
For PCR testing, there are at least 2 different clinical specimens needed for example from the
nasopharyngeal and stool. Besides that, there can also be the same clinical specimen collected on
2 or more days during the course of the illness for example 2 or more nasopharyngeal aspirates
are obtained for diagnosis
The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness
onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4
for urine specimens. The latest stool sample that was positive by reverse transcriptionpolymerase chain reaction was collected on day 75 while the patient was receiving intensive
care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average
positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs,
rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a
moderate yield (29.7%-40.0%), whereas throat washing and urine specimens showed a lower
yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab
specimens were the least likely to transmit infection, and the combination gave the highest yield
for coronavirus detection by RT-PCR. . If a positive PCR result has been obtained, it should be
confirmed by repeating the PCR using the original sample or having the same sample tested in a
second laboratory. Amplifying a second genome region could further increase test specificity.
Clinicians should save any available clinical specimens (respiratory, blood, and serum)
for additional testing until a specific diagnosis is made. Acute and convalescent (greater than 21
days after the onset of symptoms) serum samples should be collected from each patient who
meets the definition criteria for SARS. Specific instructions for collecting suspected patients
infected with SARS are needed.
17
4.1.1a Collecting Respiratory Specimens
Eight types of respiratory specimens may be collected for viral and/or bacterial diagnostics:
1) Nasopharyngeal wash or aspirates
2) Nasopharyngeal swabs
3) Oropharyngeal swabs
4) Broncheoalveolar lavage
5) Tracheal aspirate
6) Pleural fluid taps
7) Sputum
8) Post-mortem tissue.
Nasopharyngeal wash/aspirates are the specimen of choice for detection of most respiratory
viruses and are the preferred specimen type for children under age 2 years.
In contrast to most respiratory pathogens for which respiratory specimens are optimally collected
within 72 hours after the onset of symptoms, levels of SARS-CoV may be higher later in the
course of the illness.
i) Collecting specimens from the upper respiratory tract

Nasopharyngeal aspirates or swabs.
Have the patient sit with head tilted slightly backward. Instill 1 ml-1.5 ml of non
bacteriostatic saline (pH 7.0) into one nostril. Flush a plastic catheter or tubing with 2
ml-3 ml of saline. Insert the tubing into the nostril parallel to the palate. Aspirate
nasopharyngeal secretions. Repeat this procedure for the other nostril. Collect the
specimens in sterile vials. Label each specimen container with the patient’s ID number
18
and the date collected. If shipping domestically, use cold packs to keep the sample at
4°C. If shipping internationally, pack in dry ice.

Nasopharyngeal or oropharyngeal swabs
Use only sterile dacron or rayon swabs with plastic shafts. Do not use calcium alginate
swabs or swabs with wooden sticks, as they may contain substances that inactivate some
viruses and inhibit PCR testing.

Nasopharyngeal swabs -- Insert a swab into the nostril parallel to the palate. Leave the
swab in place for a few seconds to absorb secretions.
Swab both nostrils.
Oropharyngeal swabs -- Swab the posterior pharynx and tonsillar areas, avoiding the
tongue.

Place the swabs immediately into sterile vials containing 2 ml of viral transport media.
Break the applicator sticks off near the tip to permit tightening of the cap. Label each
specimen container with the patient’s ID number and the date the sample was collected.
If shipping domestically, use cold packs to keep sample at 4°C.
If shipping
internationally, pack in dry ice.
ii) Collecting specimens from the lower respiratory tract

Broncheoalveolar lavage, tracheal aspirate, pleural fluid tap
Centrifuge half of the specimen, and fix the cell pellet in formalin. Place the remaining
unspun fluid in sterile vials with external caps and internal O-ring seals. If there is no
internal O-ring seal, then seal tightly with the available cap and secure with Parafilm®.
Label each specimen container with the patient’s ID number and the date the sample was
collected. If shipping domestically, use cold packs to keep sample at 4°C. If shipping
internationally, ship fixed cells at room temperature and unfixed cells frozen.

Sputum
19
Educate the patient about the difference between sputum and oral secretions. Have the
patient rinse the mouth with water and then expectorate deep cough sputum directly into
a sterile screw-cap sputum collection cup or sterile dry container.If shipping
domestically, use cold packs to keep sample at 4°C. If shipping internationally, pack in
dry ice.
4.1.1b Collecting Blood Components
Serum and blood (plasma) should be collected early in the illness for RT-PCR testing. The
reliability of RT-PCR testing performed on blood specimens decreases as the illness progresses.
Both acute and convalescent serum specimens should be collected for antibody testing. To
confirm or rule out SARS-CoV infection, it is important to collect convalescent serum specimens
>28 days after the onset of illness.
A. Collecting serum for antibody or RT-PCR testing
Collect 5 ml-10 ml of whole blood in a serum separator tube. Allow the blood to clot, centrifuge
briefly, and collect all resulting sera in vials with external caps and internal O-ring seals. If there
is no internal O-ring seal, then seal tightly with the available cap and secure with Parafilm ®. The
minimum amount of serum preferred for each test is 200 micro liters, which can easily be
obtained from 5 mL of whole blood.
A minimum of 1 cc of whole blood is needed for testing of pediatric patients. If possible, collect
1 cc in an EDTA tube and in a clotting tube. If only 1cc can be obtained, use a clotting tube.
Label each specimen container with the patient’s ID number and the date the specimen was
collected. If unfrozen and transported domestically, ship with cold packs to keep the sample at
4°C. If frozen or transported internationally, ship on dry ice.
B. Collecting EDTA blood (plasma) for RT-PCR
20
Collect 5 ml-10 ml of blood in an EDTA (purple-top) tube. Transfer to vials with external caps
and internal O-ring seals. If there is no internal O-ring seal, then seal tightly with the available
cap and secure with Parafilm®. Label each specimen container with patient’s ID number and
date of collection. Store and ship blood specimens with cold packs to keep the sample at 4°C.
4.1.1c Collecting Stool Specimens for PCR
Begin collecting stool specimens as soon as possible in the course of the illness. Although
collecting earlier specimens is ideal, SARS-CoV has been detected in stool as late as one month
after the onset of symptoms. Place each stool specimen -- as large a quantity as can be obtained
(at least 10 cc) -- in a leak-proof, clean, dry container, and refrigerate at 4°C. Patients may drape
plastic kitchen wrap across the back half of the toilet, under the toilet seat, to facilitate collection
of stool specimens.
IMPORTANT: Refrigerate or freeze tubes after specimens are placed in them. If specimens will
be examined within 48 hours after collection, they can be refrigerated. If specimens must be
held longer than 48 hours, freeze them as soon as possible after collection. Although storage in
an ultra-low freezer (-70°C) is preferable, storage in a home-type freezer (if properly set at 20°C) is acceptable for short periods.
4.1.2 Seroconversion by ELISA or IFA:
ELISA or IFA is a negative antibody test on acute serum followed by positive antibody
test on convalescent serum. Antibodies against SARS-CoV become detectable with high
sensitivity around 10 days after the onset of infection, but they can be undetectable prior to this
by current testing methods.
Positive antibody test results indicate that there has been an infection with SARS-CoV.
Seroconversion from negative to positive, or a four-fold rise in antibody titre in the serum of a
convalescent patient compared with that patient’s serum during acute illness, denotes a recent
infection. A negative serological result 21 days after onset of symptoms indicates absence of
21
SARS-CoV infection. Cross-reactions with antibodies to other agents (including the human
coronaviruses HCoV-229E and HCoV-OC43) are not known.
Several serological studies with SARS patient sera have been reported and these show varying
sensitivities
and
specificities.
Serological
studies
with
SARS
patient
sera
using
immunofluorescence tests (IIFT) or ELISA showed sensitivities between 92 and 99%. The
reference serological method is the neutralization test and this was compared to enzyme linked
immunosorbent assay (ELISA), immunofluorescence assays (IFA) and the immunochromatic
test (ICT). Antibody determination using IFA or ELISA was the most reliable method for
identifying infections with SARS-CoV. The ICT had a poor sensitivity.
4.1.3 Virus isolation
Patient specimens such as respiratory secretions, blood, or stool can be inoculated in suitable cell
lines for growth of the infectious agent. Cell culture requires considerable expertise, is time
consuming and quite demanding.
Vero cells have been used for culture. After isolation, the virus has to be confirmed and this is
usually done with nucleic acid based tests. Positive results indicate presence of viable SARSCoV, whilst negative cell culture results do not exclude SARS. These viruses were originally
isolated in organ cultures of human embryonic trachea and subsequently grown in tissue culture
in fibroblasts.
Although most coronaviruses are highly species specific, under certain experimental conditions
some human strains may infect different species though, for example, intra-cerebral inoculation
of African green monkeys. Serial passaging in heterologous cell lines can extend the host range.
This leads to the virus being able to employ a larger variety of receptors on the cell surface.
Coronaviruses show a marked degree of tissue tropism. Closely related viruses may show
different tropism, some tending towards respiratory infections and others to gastrointestinal
infections.
These tropisms are influenced by both host cell surface characteristics and by viral Sglycoprotein variation. Although coronaviruses replicate in the cytoplasm the role of the nucleus
22
in this respect is unknown. Coronaviruses usually cause lytic infections although persistent
infections are also known to occur depending on the particular virus strain and host cell.
4.1.4 Imaging
Imaging plays an important role in the diagnosis of SARS and monitoring of response to therapy.
A predominant peripheral location, a progression pattern from unilateral focal air-space opacity
to unilateral multifocal or bilateral involvement during treatment, and lack of cavitation,
lymphadenopathy, and pleural effusion are the more distinctive radiographic findings (Wong
2003b).
At the onset of fever, 70-80 % of the patients have abnormal chest radiographs
(Booth, Wong 2003b, Peiris 2003b). It should be noted that, in a substantial proportion of cases,
chest radiographs may be normal during the febrile prodrome, as well as throughout the course
of illness. In other cases, radiological evidence of pneumonic changes may precede the fever
(Rainer), particularly in individuals with co-morbidities who may be impaired in their ability to
mount a fever (Fisher 2003a).
Chest X-ray findings typically begin with a small, unilateral, patchy shadowing, and
progress over 1-2 days to become bilateral and generalized, with interstitial or confluent
infiltrates. Air-space opacities eventually develop during the course of the disease. In patients
who deteriorate clinically, the air-space opacities may increase in size, extent, and severity
(Tsang, Lee).
In the first large cohort from Hong Kong, 55 % of the patients had unilateral focal
involvement and 45 % had either unilateral multi-focal or bilateral involvement at the onset of
fever (Lee). Within a prospective cohort, initial involvement was confined to one lung zone in
49% and was multi-zonal in 21% of the patients (Peiris 2003b).
The initial radiographic changes may be indistinguishable from those associated with
other causes of bronchopneumonia. The research group from Hong Kong suggested that chest
radiographs might offer important diagnostic clues, in particular when, after approximately one
23
week, unilateral, predominantly peripheral areas of consolidation progress to bilateral patchy
consolidation, and when the extent of the lung opacities is correlated with the deterioration in
respiratory function (Lee).
There seems to be a predominant involvement of the peripheral-zone. Pleural effusions,
cavitation, and hilar lymphadenopathy are usually absent. Respiratory symptoms and positive
auscultatory findings are disproportionally mild compared with the chest radiographic findings
(Lee).
One large study focused on radiographic appearances and the pattern of progression
(Wong 2003b). Within this cohort of 138 patients, four patterns of radiographic progression were
recognized: type 1 (initial radiographic deterioration to a peak level, followed by radiographic
improvement) in 70.3%, type 2 (fluctuating radiographic changes) in 17.4%, type 3 (static
radiographic appearance) in 7.3%, and type 4 (progressive radiographic deterioration) in 5.1% of
the patients. Findings during deterioration are compatible with the radiological features of acute
respiratory distress syndrome.
The predominant abnormalities found on initial CT scans are areas of sub-pleural focal
consolidation with air bronchograms and ground-glass opacities (Tsang). The lower lobes are
preferentially affected, especially in the early stages. Patients with more advanced cases show a
more bilateral involvement (Wong 2003a). The lesions tend to be peripheral and smaller in the
less severely affected lungs, also suggesting an earlier stage of the disease. In patients with more
advanced cases, there is involvement of the central, perihilar regions by larger (>3 cm) lesions.
The majority of the lesions contained an area of ground-glass opacification with or without
consolidation. Other findings include intralobular thickening, interlobular septal thickening, a
crazy-paving pattern, and bronchiectasis (Wong 2003a). Obvious bronchial dilatation is
generally not found (Lee).
Radiographically, SARS may be indistinguishable from other severe forms of
pneumonia. It also shares CT features with other conditions that result in subpleural air-space
disease, such as the pneumonia of bronchiolitis obliterans and acute interstitial pneumonia
(Tsang).
24
Radiologists from the Prince of Wales Hospital, Hong Kong, recommend the following protocol
for diagnostic imaging of suspected SARS patients (Wong 2003a):

Patients with symptoms and signs consistent with SARS and with abnormalities on chest
radiographs are followed up with serial radiography. CT scanning is not required for
diagnosis.

Patients with symptoms and signs consistent with SARS and with a normal chest
radiograph undergo thin-section CT to confirm the diagnosis. They subsequently undergo
serial radiography for follow-up.
Identifying hospitalized patients with SARS is difficult, especially when no epidemiological
link has been recognized and the presentation of symptoms is non-specific. Patients with SARS
might develop symptoms common to hospitalized patients (e.g., fever or prodromal symptoms of
headache, malaise, and myalgia), and diagnostic testing to detect cases is limited (MMWR 52:
547-50). Unless specific laboratory tests (PCR, detection of SARS antibodies; see Chapter
7: Diagnostic Tests) confirm the initial suspicion of SARS infection, the diagnosis of SARS is
based on the clinical findings of an atypical pneumonia not attributed to any other cause, as well
as a history of exposure to a suspect or probable case of SARS, or to their respiratory secretions
or other body fluids.
As mentioned above, during the early stages, SARS may be difficult to differentiate from
other viral infections, especially when symptoms are unspecific (Rainer). The initial diagnostic
testing for suspected SARS patients should include chest radiography, pulse oximetry, bacterial
cultures of blood, sputum, and urine, serology for mycoplasma, chlamydia, influenza,
parainfluenza, respiratory syncytial and adenoviruses, nasopharyngeal aspirates for viral cell
cultures, and direct sputum smear for Pneumocystis jiroveci by silver stain. A specimen for
Legionella and pneumococcal urinary antigen testing should also be considered.
The radiographic appearance of peripheral air-space opacities is indistinguishable from other
causes of atypical pneumonia, such as Mycoplasma, Chlamydia, and Legionella, and overlaps
with other types of viral pneumonia. The presence of air-space opacity on chest radiographs has
been helpful in the confirmation of the diagnosis (Wong 2003b).
25
4.2 Intervention
The 2003 outbreak of severe acute respiratory syndrome (SARS) was contained largely through
traditional public health interventions, such as finding and isolating case-patients, quarantining
close contacts, and enhanced infection control. The independent effectiveness of measures to
"increase social distance" and wearing masks in public places requires further evaluation.
Limited data exist on the effectiveness of providing health information to travelers. Entry
screening of travelers through health declarations or thermal scanning at international borders
had little documented effect on detecting SARS cases; exit screening appeared slightly more
effective. The value of border screening in deterring travel by ill persons and in building public
confidence remains unquantified. Interventions to control global epidemics should be based on
expert advice from the World Health Organization and national authorities. In the case of SARS,
interventions at a country's borders should not detract from efforts to identify and isolate infected
persons within the country, monitor or quarantine their contacts, and strengthen infection control
in healthcare settings.
A variety of intervention measures exist to prevent and control diseases with pandemic
potential like SARS or pandemic influenza. They differ in their approach and effectiveness in
reducing the number of cases getting infected. The effects of different intervention measures
were investigated by a mathematical modelling approach, with comparisons based on the
effective reproduction number (Re). The analysis showed that early case detection followed by
strict isolation could control a SARS outbreak. Tracing close contacts of cases and contacts of
exposed health care workers additionally reduces the Re.
Tracing casual contacts and measures aiming to decrease social interaction were less
effective in reducing the number of SARS cases. The study emphasizes the importance of early
identification and isolation of SARS cases to reduce the number of people getting infected.
However, doing so transfers cases to health care facilities, making infection control measures in
hospitals essential to avoid nosocomial spread. The modelling approach applied in this study is
useful for analysing interactions of different intervention measures for reducing the Re of SARS.
5.0 TREATMENT
26
Treatment for SARS is prescribed as the same line as for any other unknown form of atypical
pneumonia and largely involves provision of ventilator support, anti-pyretics, and supplemental
oxygen. The first development treatment strategies for SARS were based on theoretical, from
clinical observations and inferences. Prospective randomized controlled treatment trials were
understandably lacking during the first epidemic of this disease. The mainstream therapeutic
interventions for SARS involve broad-spectrum antibiotics and supportive care, as well as
antiviral agents and immunomodulatory therapy.
5.1 Antibiotic therapy
Rapid laboratory tests that can be used to diagnose the SARS-CoV virus in the first few days of
infection are not yet available. Anti-bacterial agents are routinely prescribed for SARS because it
has non-specific features. Appropriate empirical antibiotics are needed to cover against common
respiratory pathogens as per national or local treatment guidelines for community-acquired or
nosocomial pneumonia. Some antibiotics are known to have immunomodulatory properties, in
addition to their antibacterial effects. For example, quinolones and macrolides. Their effect on is
still undetermined.
5.2 Antiviral therapy
Scientific institutions worldwide have been vigorously identifying or developing an efficacious
antiviral agent with the discovery of the SARS-CoV as the etiologic agent. Intensive in vitro
susceptibility tests are underway.
5.2.1 Ribavirin
Ribavirin is a nucleoside analogue which was widely chosen as an empirical therapy for SARS
because it has broad-spectrum antiviral activity against many DNA and RNA viruses. It has
since become the most frequently administered antiviral agent for SARS and it was commonly
used with corticosteroids. The use of ribavirin has caused a lot of criticism due to its unproven
efficacy and undue of side effect. Ribavirin has no direct in vitro activity against SARS-CoV at
non-toxic concentration. Based on clinical experience, including quantitative reverse
transcriptase polymerase chain reaction (RT-PCR) monitoring the nasopharyngeal viral load, has
also not been able to suggest any substantial in vivo antiviral effect from this drug.
27
The prevalence of side effects from this drug is dose-related. High doses often have more
adverse effects. For example, hemolytic anemia, elevated transaminase levels and bradycardia.
Lower doses of ribavirin did not show clinically significant adverse effects. In elderly, side
effects have also been observed frequently.
5.2.2 Neuraminidase inhibitor
Oseltamivir phosphate, neuraminidase inhibitor used for treatment of both influenza A and B
viruses. There is no evidence that neuraminidase inhibitor has any efficacy against SARS-CoV.
So it is normally not a recommended treatment apart from in its role as an empirical therapy to
cover possible influenza.
5.2.3 Protease inhibitor
Lopinavir-ritonavir co-formulation, a protease inhibitor preparation which is used to treat human
immunodeficiency virus (HIV) infection. Protease inhibitor has been used in combination with
ribavirin in several Hong Kong hospitals, which is hope it can inhibit the coronaviral proteases,
then blocking the processing of the viral replicase polyprotein and preventing the replication of
viral RNA. Preliminary results show that the addition of lopinavir-ritonavir to the contemporary
use of ribavirin and corticosteroids, especially when administered early might reduce intubation
and mortality rates.
5.2.4 Human interferons
Interferons, a family of cytokines which is important in the cellular immune response. They are
classified into two types. Type I (interferon α and β, sharing components of the same receptor)
and type II (interferon γ which binds to a separate receptor system) which have different antiviral
potentials and immunomodulatory activities. As reported from China and Canada, the use of
interferons in the treatment of SARS are limited to interferons α.
In the small Canadian series using interferon alfacon-1, faster recovery was observed. It is also
known as consensus interferon, which shares 88% homology with interferon α -2b and about
30% homology with interferon β . In Germany, In vitro testing of recombinant interferons
against SARS-CoV was recently carried out using interferon α -2b, interferon β -1b and
28
interferon γ -1b. Interferon β was found to be far more potent than interferon α or γ , and it
remained effective even after viral infection. Interferon α selectivity index was 50-90 times
lower than that of interferon β, although it can effectively inhibit SARS-CoV replication in cell
cultures. These in vitro results show that interferon β is promising and can be used in future
treatment trials.
5.2.5 Human immunoglobulin
It was used in some hospitals in China and Hong Kong. An IgM-enriched immunoglobulin
product was tried in selected SARS patients. However, their effectiveness in SARS remains
uncertain as there was often concomitant use of other therapies such as corticosteroids. An
experimental treatment tried in Hong Kong which is convalescent plasma is collected from
recovered patients. Neutralizing immunoglobulins in convalescent plasma were believed can
curb increases in the viral load.
5.2.6 Alternative medicine
Traditional herbal medicine has been frequently used in conjunction with Western medicine to
treat SARS, and is believed to be effective which is used in China. Glycyrrhizin, an active
component derived from liquorice roots, was tested against SARS-CoV in vitro. Before this, it
has been used in the treatment of HIV and hepatitis C virus infections, and was found to be
relatively non-toxic with infrequent side effects, for example, hypertension and hypokalemia. It
can inhibit the adsorption, penetration and replication of SARS-CoV in Vero cell cultures and
was most effective when administered both during and after viral adsorption. But glycyrrhizin
can only act against SARS-CoV at very high concentrations, so its clinical dosing and utility
remain uncertain. Perhaps it can be explored as an adjunct therapy for SARS, or continued as an
ingredient or base in herbal preparations.
5.6 Immunomodulatory therapy
Acute infections in general can stimulate the release of proinflammatory cytokines. There may
be an excessive host response or cytokine dysregulation in SARS. Clinical deterioration can
paradoxically occur despite a fall in the viral load as IgG seroconversion takes place as well as
from autopsy findings which demonstrate a prominent increase in alveolar macrophages with
29
hemophagocytosis. A tri-phasic model of pathogenesis was proposed comprising viral
replicative, immune hyperactive and pulmonary destructive phase. Immunomodulatory is
carefully applied during the hyper-immune phase can be an important treatment component in
SARS.
5.6.1 Corticosteroids
As described in many Chinese and Hong Kong reports, corticosteroids timely used often led to
early improvement in terms of subsidence of fever, radiographic infiltrates resolution and better
oxygenation. However, based on their effectiveness, adverse immunosuppressive effects and
impact on final patient outcomes, there are a lot of skepticism and controversy about the use of
this substance.
Corticosteroids showed no benefits at an early Singaporean report on five patients on
mechanical ventilation. It concluded that two-thirds progressed after early use of ribavirin and
corticosteroids, but only about half of these subsequently responded to pulsed doses of
methylprednisolone from a retrospective series of over 320 patients from a regional hospital in
Hong Kong. 80% of patients had recurrence of fever and radiological worsening in a cohort
study. The inconsistencies of treatment outcomes in SARS (or other illnesses) could be due to
differences in the dosing, timing and duration of corticosteroid use. The following points have
been emphasized :

Use of corticosteroids too early may theoretically prolong the viral replicative phase and
increase the viral burden, whereas delayed administration may not be able to halt the
cytokine storm and can prevent immunopathological lung damage.

It supposed to be adjusted based on individual body weight and disease severity.

Adequate duration of corticosteroids is needed to maintain the optimized immune
balance. Too short may result in a rebound of cytokine storm with lung damage, whereas
protracted usage will cause the patient is at risk of various corticosteroid complications.

Corticosteroids is beneficial but it has its own risk. It is not only facilitates coronaviral
replication in the absence of an effective antiviral agent, but also can invites bacterial
sepsis and opportunistic infections. A SARS patient who died from systemic fungal
infection have been reported.
30
If the patient remains clinically stable, it is likely that an optimal immune balance has been
reached. Moreover, most radiological infiltrates will resolve gradually on a diminishing course of
corticosteroids over 2-3 weeks. Differentiate Radiographic abnormalities
arising
from
a
superimposed bacterial pneumonia from the progressive immunopathological lung damage of
SARS, would result in adding further corticosteroids.
Other immunomodulator that can be use is Thymosin alpha 1.In some Chinese hospitals,
Thymosin alpha 1 is used in the treatment of chronic viral hepatitis B and C, and has also been
administered to SARS patients. It is a safe product and may augment T-cell function. The role
and effectiveness in SARS has not yet been determined.
Tumor necrosis factor blocking agents, namely etanercept and infliximab and some other
compounds like cyclophosphamide, azathioprine, cyclosporin and thalidomide are other
immunomodulatory agents in anecdotal use.
5.6.2 Assisted ventilation
Some SARS patients still develop acute hypoxemic respiratory failure. 20-30% of SARS
warranted admission into intensive care units, and 10-20% eventually required intubation and
mechanical ventilation according to the current literature.
5.6.2a Non invasive ventilation
Non invasive ventilation is a valuable treatment for acute respiratory failure of various causes,
and can avoid complications related to intubation and invasive ventilation. Its application in
SARS may be of particular benefit since patients are normally treated with high dose
corticosteroids, which exposed them to infections including ventilator-associated pneumonia.
It was commonly employed in many Chinese and Hong Kong hospitals. It can improve
oxygenation and tachypnea within an hour, and it can help to prevent adding further
corticosteroids for respiratory failure. Generally, it was found to be able to avoid intubation and
invasive ventilation in up to two-thirds of SARS patients with deterioration.
In contrast, the scenarios for non-SARS-related acute respiratory distress syndrome,
higher pressures were generally not necessary and should be avoided whenever possible, because
31
not only was there usually no additional clinical improvement observed, but it can also add to the
risk of pneumothorax and pneumomediastinum.
Although it can improved patient outcome, the infective risks associated related to aerosol
generation have decreased its use in many hospitals.
5.6.2b Invasive ventilation
SARS-related respiratory failure patients who continue to deteriorate while on non invasive
ventilation, or in whom non invasive ventilation is contraindicated, supposed to be promptly
intubated and mechanically ventilated. The actual endotracheal intubation procedure can cause a
high infective risk and healthcare workers must strictly adhere to all infection control measures.
The procedure is best performed by highly skilled personnel using rapid sequence induction to
minimize the risk. It has been recommended to use other approaches like a "modified awake"
intubation technique and elective intubation upon recognizing signs of imminent need for airway
management.
Ventilation method and settings with reference to the strategies for acute respiratory
distress syndrome (ARDS) are used by most centers. The pressure and volume control
ventilation can be employed. The tidal volume should be maintained low at 5-6 ml per Kg of the
predicted body weight, and plateau pressures are maintained less than 30 cm H2O. Adequate
sedation should be applied to ventilated patients and a short-term neuromuscular blockade might
required for permissive hypercapnia mechanically.
6.0 Control of SARS
Prevention and control measures were initiated by the Ministry Of Health(MOH) SARS Task
Force, which was formed on 15 March 2003 and chaired by the Director of medical
service(DMS). Its members included the chief executive officers of all hospitals, chairmen of
medical boards, infectious disease physicians, epidemiologists and virologists. Strategies to
contain the rapid nosocomial transmission were discussed, formulated and effectively
implemented across all healthcare institutions through the Infectious Diseases Act and Private
Hospitals and Medical Clinics Act.
The Ministerial Committee on SARS (chaired by the Minister for Home Affairs) was
established on 7 April to provide political guidance and quick strategic decisions to minimise the
32
socioeconomic impact of SARS. The Executive Group, comprising permanent secretaries of the
relevant ministries, was responsible for the overall coordination and implementation of multiagency issues outside the healthcare setting, while an Inter-Ministry SARS Operations
Committee ensured that cross-ministry operational issues on SARS were well coordinated. A
Ministerial SARS Combat Unit was also appointed on 20 April; 3 of its members were medical
doctors.
It worked closely with the public and private hospitals and other healthcare institutions to
prevent and control SARS transmission in these facilities. Key measures implemented were
directed at the prevention and control of SARS in the community, healthcare institutions and the
borders. Community In the prevention and control of SARS within the community, the key
strategy was to detect persons with suspected or probable SARS as early as possible and isolate
them in. At the same time, the Infectious Diseases Act was reviewed and amended to ensure that
all necessary public health measures could be taken to control the outbreak; e.g., handling and
disposal of bodies due to SARS within 24 hours of death.
Early identification of SARS cases was done through several ways, including active
contact tracing for all contacts within 24 hours of notification of a case, mandatory home
quarantine enforced through the use of electronic cameras, and intensive education of healthcare
professionals and the public. To allay the concern of parents, all preschools, primary and
secondary schools were closed for 2 to 3 weeks at the end of March to early and mid-April 2003.
Healthcare Institutions The MOH implemented very stringent infection control procedures to
prevent and contain outbreaks in hospitals, nursing homes and other healthcare institutions.
At the first point of contact with healthcare facilities [accident and emergency (A&E)
departments, specialists outpatient clinics], triage was carried out to separate out febrile patients.
To widen the surveillance net, the WHO’s definition for suspected and probable SARS was
expanded to include any HCW with fever and/or respiratory symptoms (particularly in a cluster
of 3 or more febrile cases), inpatients (>16 years old) with atypical pneumonia under
investigation, sudden unexplained deaths with respiratory symptoms, and in patients with fever
(>38 o C) of more than 72 hours and with relevant travel history but without known causes. Case
finding was further intensified with the introduction of thrice-daily temperature surveillance of
all health care worker (HCW)s in every institution and active surveillance for cluster of febrile
33
person especially , among the immunocompromised, who tend to have atypical clinical
presentations, and staff from the same work area. Sick leave of HCWs was centrally monitored.
Audits were periodically conducted to ensure that the directives and guidelines issued by the
MOH were strictly enforced. Strict enforcement of the proper use of personal protective
equipment (PPE) (test-fitted N95 mask, gowns, gloves and goggles/protective eye gear if
managing suspicious cases, and powered air purified respirator for high-risk procedures such as
intubation), control of visitors, restriction of movements of health care workers s (including
confining their practice to one institution) and patients (readmission to the same hospital within
21 days after discharge), and close monitoring of discharged patients from SARS-affected wards.
In addition to issuing a health alert advising travellers to avoid SARS-affected countries, unless
absolutely necessary, MOH took various measures to minimize the risk of imported case.
These measures were implemented in phases. Health alert notices were issued at the
airport to inbound air passengers from SARS-affected countries to highlight the signs and
symptoms of SARS and the need to seek immediate attention if fever developed. Health
screening of all incoming air and sea passengers and crew from affected areas was carried out
through temperature checks using thermal imaging scanners. Travellers picked up by the
scanners had their temperature re-checked by nurses who would refer them for further
examination by doctors at the air and sea terminals if they were confirmed to have a fever. Those
who were suspected of having SARS were sent to hospital for further assessment and admission
for isolation and treatment if necessary. Incoming bus passengers at the land checkpoints were
also screened with the thermal scanners. Screening was progressively extended to travellers
coming in via other vehicles at the land checkpoints. All visitors through air, sea and land
checkpoints were required to complete a SARS health declaration card to facilitate contact
tracing.
However, not a single case of SARS was detected through these measures. Very stringent
steps were taken to minimise the possibility of exporting cases to other countries. These
measures included the rapid containment of outbreaks, and mandatory temperature screening of
all outgoing travellers. In addition, special bilateral arrangements on the exchange of information
necessary to conduct contact tracing and quarantine was set up with Malaysia and Indonesia.
34
7.0 EXAMPLE OF SARS CASES
7.1 SARS OURBREAK IN CHINA
Beijing, China, experienced the largest outbreak of SARS in the world with a total of 2,521
reported probable cases, according to background information in the article.
The outbreak began March 5, 2003, with the importation of several cases among travelers from
other SARS-affected areas and soon accelerated as multiple SARS cases occurred in health care
facilities, peaking in late April when more than 100 new patients with SARS were being
hospitalized daily.
During the first week of May, the number of new cases dropped steeply and then declined
steadily during the next few weeks, with the onset of the last probable case on May 29, 2003.
The onset of the last case occurred only 6 weeks after the peak of the outbreak.
Xinghuo Pang, M.D., of the Beijing Center for Disease Prevention and Control, and colleagues
evaluated the measures taken to rapidly control the SARS outbreak in Beijing and assess the
effectiveness of some of these measures.
The researchers reviewed data from standardized surveillance forms from SARS cases (2,521
probable cases) and their close contacts observed in Beijing between March 5, 2003, and May
29, 2003. Procedures implemented by health authorities were investigated through review of
official documents and discussions with public health officials.
The researchers found that healthcare worker training in use of personal protective equipment
and management of patients with SARS and establishing fever clinics and designated SARS
wards in hospitals predated the steepest decline in cases.
During the outbreak, 30,178 persons were quarantined. Among 2,195 quarantined close contacts
in 5 districts, the attack rate was 6.3 percent, with a range of 15.4 percent among spouses to 0.36
percent among work and school contacts.
The attack rate among quarantined household members increased with age from 5.0 percent in
children younger than 10 years to 27.6 percent in adults aged 60 to 69 years. Among almost 14
35
million people screened for fever at the airport, train stations, and roadside checkpoints, only 12
were found to have probable SARS.
The national and municipal governments held 13 press conferences about SARS. The time lag
between illness onset and hospitalization decreased from a median of 5 to 6 days on or before
April 20, 2003, the day the outbreak was announced to the public, to 2 days after April 20.
7.2 SARS OURBREAK IN SINGAPORE
The SARS outbreak entered Singapore through three young women, who were in Hong Kong
from 20 to 24 February this year. They were infected by a doctor from Guangzhou by a chance
encounter in the lift lobby on the 9th floor of the MetropoleHotel in Mongkok in Hong Kong. In
that chance encounter, the Chinese doctor was also to spread the disease to four other people
besides the three Singaporeans. One was a local Hong Kong resident who visited a friend at the
hotel, another was a 55-year-old Vancouver man, the third was a 78-year-old Toronto woman,
and the fourth was a 48-year-old American businessman.The local Hongkonger became ill, and
for a time was erroneously designated the index case in Hong Kong until the story of the real
index case – the Guangzhou professor – surfaced. The rest returned home to become the index
cases in Toronto and Vancouver, Hanoi, and Singapore. Singapore, as at 30 March 2003, had 91
cases and three deaths. The secondary cases were hospital doctors, nurses, and family members
of the index cases.There are thankfully no cases out in the community, meaning those cases with
no known source. This is a new viral infection and its infective capability is still being inferred
from the cohort of infected cases in Singapore, Hong Kong and elsewhere. From the Singapore
and Hong Kong experiences, the victims shed viruses when they are very ill. This will explain
the secondary cases occurring among the healthcare providers in hospitals. Also, the virus is
spread to those in close contact with the cases. It also appears that some cases are “Super
Infectors”, meaning that these cases are more able to spread the infection to others around them.
It is clear with present day travel that a bug can spread very rapidly across countries. As has
occurred with the SARS Reflections on the outbreak, the spread to Hong Kong, Vietnam,
Canada and Singapore came from one case coming across Guangzhou to Hong Kong. The WHO
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report dated 29 March showed a tally of 37 cases with 470 cases and 10 deaths in Hong Kong, 58
cases and 4 deaths in Vietnam, 3 deaths in Canada, and 89 cases with 2 deaths in Singapore.
An epidemiological network for early reporting remains the best way to limit the global spread.
The doctors in Hanoi were fast to report its index case to WHO as a baffling case. This is a
judgment call that requires clinical acumen to spot the index case to be unusual. Not always easy,
but nevertheless, an important skill. The doctor who did that in Hanoi was Carlo Urbani.
“Because of his early detection of SARS, global surveillance was heightened and many new
cases have been identified and isolated before they infected hospital staff,” said the Genevabased
UN health agency in a statement. Unfortunately, this doctor succumbed to SARS. He was
infected in the process of caring for the index case in Hanoi, and eventually died in Bangkok on
29 March, where he had gone for a meeting.
The present outbreak in Singapore and in the region, demonstrates the importance of a global and
national network of epidemiological collection, investigation, processing, and disseminating
points.The WHO, the CDCs and laboratories are crucial in providing the information and in
advising communities what need to be done. Obviously, the close cooperation between WHO,
countries, centres, and scientists remain paramount. The adequate funding of such a network
both locally and globally is good investment for mankind.
The cooperation of the community in control measures, like the closing of schools and other
activities likely to allow transmission, is crucial. And it is a fine judgment between being too
restrictive and too liberal. Until more is known about the ability of the disease to spread, it is
safer to take more steps that may turn out to be not necessary later.Having adequate operating
information for the public and medical practitioners will help to restore calm and behaviour that
will be productive in bringing the infection under control.
Each emerging infection that tests the defence network of the human race also reminds us of the
great vulnerability of the human race. The possibility of a virulent superbug beyond the grip of
medical science and technology is there. All this underscores the importance of the study and
practice of communicable disease control, including drastic quarantine measures. It is important
not to be lulled into complacency because infectious diseases have receded into the background
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from the top causes of death of many countries. Each of us is a stakeholder, and if each of us
remembers that, the battle is more likely to be won with the least number of victims.
The SARS outbreak is a timely reminder of the importance of being prepared against
communicable diseases, and where the control of a mysterious bug requires the stakeholder
mentality that we are all vulnerable. There is also the confidence that together, we can erect a
strong defence against the onslaught of the invisible invader.
8.0 CONCLUSION
Though scientists and researchers have established the complete genetic code of the Corona
virus, it will be a while before they come up with a suitable treatment option . Currently, the
supportive care given to the patient is proving to be an important factor in patient recuperation.
However, the combined efforts in the various biotech companies and other research institutes
will hopefully shed light on this dreaded disease that has taken a toll on humanity.The SARS
outbreak put a large number of patients in hospital, resulted in the death of many patients,
disrupted the lives of countless people and damaged the economy.On the positive side, however
it highlighted the importance of a cohesive professional and community response in resolving the
crisis rapidly. Moving forward, the lessons learnt from SARS will result in countries having a
much higher level of preparedness for infectious disease outbreaks. However, the model of close
community participation and partnership in tackling public health problems. In this respect, we
can learn much more from SARS than just control of infectious diseases.
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9.0 REFERENCES
19/2/2011

http://www.sarsreference.com/sarsref/treat.htm

http://www.clearleadinc.com/site/sars.html

http://www.medindia.net/patients/patientinfo/SARS_conclusion.htm#ixzz1EPkhBY7a

http://books.google.com.my/books?id=ZGIzRhGo_E0C&pg=PA163&lpg=PA163&dq=c
onclusion+for+severe+acute+respiratory+system&source=bl&ots=XJuakX6MA3&sig=v
fAZrqI4c3Djc0HdqcjMCZQogiM&hl=en&ei=3NBfTerxC8_HrQeXo_CEAg&sa=X&oi
=book_result&ct=result&resnum=10&ved=0CGgQ6AEwCQ#v=onepage&q=conclusion
%20for%20severe%20acute%20respiratory%20system&f=fa
17/2/2011

http://www.sarsreference.com/sarsref/epidem.htm

http://www.epinorth.org/eway/default.
39

http://www.biomedcentral.com/1471-2334/10/50/prepub
18/2/2011

http://www.who.int

http://www.diaspoir.net/health/sars/Malaysia.html.

http://straitstimes. asia1.com.sg/columnist/0,1886,56-178860,00.html

http://www.who.int/ csr/sarscountry/2003_03_29/en/

http://www.channelnewsasia.com/stories/southeastasia/view/36120/1/.html
21/2/2011

http://respiratory-lung.health-cares.net/sars-diagnosis.php

http://www.wrongdiagnosis.com/s/sars/tests.htm

http://health.nytimes.com/health/guides/disease/severe-acute-respiratory-syndromesars/overview.html
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