The outbreak of SARS at Tan Tock Seng Hospital--relating epidemiology to control.

Abstract

The outbreak of severe acute respiratory syndrome (SARS) began after the index case was admitted on 1 March 2003. We profile the cases suspected to have acquired the infection in Tan Tock Seng Hospital (TTSH), focussing on major transmission foci, and also describe and discuss the impact of our outbreak control measures.
Using the World Health Organization (WHO) case definitions for probable SARS adapted to the local context, we studied all cases documented to have passed through TTSH less than 10 days prior to the onset of fever. Key data were collected in liaison with clinicians and through a team of onsite epidemiologists.
There were 105 secondary cases in TTSH. Healthcare staff (57.1%) formed the majority, followed by visitors (30.5%) and inpatients (12.4%). The earliest case had onset of fever on 4 March 2003, and the last case, on 5 April 2003. Eighty-nine per cent had exposures to 7 wards which had cases of SARS that were not isolated on admission. In 3 of these wards, major outbreaks resulted, each with more than 20 secondary cases. Attack rates amongst ward-based staff ranged from 0% to 32.5%. Of 13 inpatients infected, only 4 (30.8%) had been in the same room or cubicle as the index case for the ward.
The outbreak of SARS at TTSH showed the challenges of dealing with an emerging infectious disease with efficient nosocomial spread. Super-spreading events and initial delays in outbreak response led to widespread dissemination of the outbreak to multiple wards.

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May 2006, Vol. 35 No. 5
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The Tan Tock Seng Hospital SARS Outbreak—Mark IC Chen et al
The Outbreak of SARS at Tan Tock Seng Hospital – Relating Epidemiology
to Control
Mark IC Chen,1MBBS, MMed (PH), MSc, Yee-Sin Leo,1MBBS, MMed, FRCP, Brenda SP Ang,2MBBS, Mmed, Bee-Hoon Heng,3MBBS, MSc (PH),
Philip Choo,4MBBS, FRCP, FAMS
Introduction
Severe acute respiratory syndrome (SARS) is an emerging
infectious disease caused by a novel coronavirus.1-3
Worldwide, the virus caused a total of 8098 reported
infections and 774 deaths4 before it was brought under
control. Several publications have commented on the risk
of transmission within hospitals.5-9
The epidemic in Singapore began after a 23-year-old
female returned from a visit to Hong Kong and was
admitted on 1 March 2003 to Tan Tock Seng Hospital
(TTSH), a 1400-bed acute care hospital.10 Primary,
secondary and tertiary transmission of infection ensued
shortly after her admission,11 before infection control
measures were instituted.
By the end of the outbreak on 31 May 2003, 206 cases
had been diagnosed.12 An additional 32 cases were identified
following a review of laboratory and clinical information in
July 2003.13 The TTSH index is thought to have initiated
the chain of transmission which infected all cases in
Singapore, except for 6 other imported infections.
This paper reviews the outbreak at TTSH. It describes the
profile of cases suspected to have acquired the infection in
TTSH, focussing on the major areas where transmission
occurred, and the epidemiological control measures
implemented. It also discusses how those control measures
contributed to the eventual control of the outbreak.
Materials and Methods
This study focuses on all cases of probable SARS who
may have acquired the infection within TTSH. This was
operationally defined as persons documented to have passed
through TTSH less than 10 days prior to the onset of fever;
1Communicable Diseases Centre, Tan Tock Seng Hospital
2Infection Control, Tan Tock Seng Hospital
3Health Services and Outcomes Research, National Healthcare Group
4Chairman Medical Board, Tan Tock Seng Hospital
Address for Reprints: Dr Mark Chen I-Cheng, Clinical Epidemiology, 38 Snowdon Drive, Colindale, London, United Kingdom NW97RE.
Email: Mark_Chen@pacific.net.sg
Abstract
Introduction: The outbreak of severe acute respiratory syndrome (SARS) began after the
index case was admitted on 1 March 2003. We profile the cases suspected to have acquired the
infection in Tan Tock Seng Hospital (TTSH), focussing on major transmission foci, and also
describe and discuss the impact of our outbreak control measures. Materials and Methods: Using
the World Health Organization (WHO) case definitions for probable SARS adapted to the local
context, we studied all cases documented to have passed through TTSH less than 10 days prior
to the onset of fever. Key data were collected in liaison with clinicians and through a team of on-
site epidemiologists. Results: There were 105 secondary cases in TTSH. Healthcare staff (57.1%)
formed the majority, followed by visitors (30.5%) and inpatients (12.4%). The earliest case had
onset of fever on 4 March 2003, and the last case, on 5 April 2003. Eighty-nine per cent had
exposures to 7 wards which had cases of SARS that were not isolated on admission. In 3 of these
wards, major outbreaks resulted, each with more than 20 secondary cases. Attack rates amongst
ward-based staff ranged from 0% to 32.5%. Of 13 inpatients infected, only 4 (30.8%) had been
in the same room or cubicle as the index case for the ward. Conclusions: The outbreak of SARS
at TTSH showed the challenges of dealing with an emerging infectious disease with efficient
nosocomial spread. Super-spreading events and initial delays in outbreak response led to
widespread dissemination of the outbreak to multiple wards.
Ann Acad Med Singapore 2006;35:317-25
Key words: Communicable diseases, Emerging; Cross infection; Patient isolation
Original Article

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Annals Academy of Medicine
The Tan Tock Seng Hospital SARS Outbreak—Mark IC Chen et al
the resulting number of cases based on this definition hence
differ slightly from those reported elsewhere.14 The case
definitions for suspected and probable SARS were adapted
from those issued by the World Health Organization
(WHO),15 and are given below.
Suspect Case
FEVER plus one of the following:
1. CLOSE CONTACT with a known case of SARS, OR
2. VISITED at-risk locations, in this case TTSH, OR
3. History of travel, to countries other than Singapore in
which there were reported foci of transmission of SARS,
the above exposures having occurred less than 10 days
prior to the onset of fever.
Probable Case
A SUSPECT case with:
1. radiographic findings of pneumonia or respiratory
distress syndrome, OR
2. pathological features at autopsy that were consistent
with SARS, OR
3. positive SARS coronavirus (SARS-CoV) on PCR
testing on 2 specimens taken from 2 different sites, OR
4. positive serology for SARS-CoV.
Epidemiologic investigations at TTSH began on the
evening of 14 March 2003, 13 days after the index case was
admitted. All suspected and probable cases admitted to
TTSH were notified to the team of on-site epidemiologists
through a case-reporting form, who then collected the
relevant epidemiological data and investigated possible
epidemiological linkages. Data on cases not admitted to
TTSH were obtained from the respective treating institutions
and other previously published data.6,16,17
Data items included demographics, administrative data
on dates of admission and isolation, and epidemiological
information on dates of fever onset, possible dates and
locations of exposure, type and degree of contact, and the
suspected source of infection where ascertainable. Cases
were considered infective from the day of onset of symptoms.
Isolation was defined as being nursed in a special facility
for SARS, where health staff worked under the protection
of N95 masks, gowns and gloves, which were the standard
for personal protective equipment (PPE) for staff.
Attack rates were computed for staff, using denominator
information obtained from the TTSH human resource staff
database; this analysis was attempted only for ward-based
staff, as the requisite data for computing attack rates for
non-ward-based staff (e.g., physiotherapists, radiographers)
were not available. We also computed attack rates for
exposed inpatients where possible. For wards with inpatient
infections, cubicle attack rate was the number of secondary
infections in patients divided by the number of patients
whose stay in that cubicle overlapped with the index; an
attack rate for all patients passing through the exposed
ward up till the removal of the last infective case was also
computed from contact tracing data.
All statistical analyses were performed using the software
SPSS for Windows version 11.5.
Results
Start of the Outbreak
The outbreak began after the TTSH index case was
admitted on 1 March 2003 to Ward X, a 38-bed facility with
an isolation room (equipped to hold up to 2 beds) and six
6-bed cubicles separated by a low wall, and common bath
areas. Clinical features of the index have been described in
a previous publication.10 She stayed in Ward X till 6 March
2003, when her clinical deterioration warranted transfer to
the intensive care unit (ICU). There, she was nursed with
respiratory precautions, on suspicion of possible “avian
flu” following reports from Hong Kong,18 which she had
recently visited.
Descriptive Profile of Cases
In all, 105 cases fulfilled our criteria as possibly having
acquired the infection in TTSH (Table 1). This included 91
cases diagnosed during the outbreak, and a further 14 cases
retrospectively reclassified as probable SARS in July 2003,
on the basis of positive serological results that only became
available after the outbreak.
The majority of the secondary cases were healthcare staff
(57.1%). Earlier cases (onset before 16 March 2003)
consisted mostly of staff and visitors, whereas cases who
acquired the disease as inpatients made up a sizeable
proportion (29%) of the cases infected after 22 March
2003. While the average time from onset to isolation was
longest amongst visitors, the highest proportion of those
admitted to non-isolation facilities comprised cases
acquiring the infection as patients, suggesting that these
cases were the most likely to be missed at presentation. Of
the patients infected, 10/13 (76.9%) developed symptoms
from the disease only after being discharged from hospital
(following recovery from the original reason for their
admission).
Progression of the Outbreak
Figure 1a gives the time-profile of the entire outbreak.
While the earliest secondary cases had begun to present by
4 March 2003, the outbreak was only detected on 13 March
2003 following the WHO global alert issued on 12 March
2003. By the time outbreak investigations were initiated,
the first wave of infections had already occurred. The
infection subsequently spread to other areas in the hospital
(Fig. 2). Ninety-three cases (88.6%) had documented
exposures in 7 wards where outbreaks were suspected to

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The Tan Tock Seng Hospital SARS Outbreak—Mark IC Chen et al
Table 1. Key Features of Cases Infected in the TTSH Outbreak
Features *Healthcare staff (n = 60)Visitors (n = 32)Patients (n = 13) Total (n = 105)
†From retrospective reclassification – %9 (15.0) 1 (3.1)4 (30.8)14 (13.3)
Median age (range) – y 29 (19-71)38 (14-73) 59 (25-90)31 (14-90)
Males – No. (%)5 (8.3)12 (37.5)6 (46.2)23 (21.9)
Ethnicity – No. (%)
Chinese28 (46.7)24 (75.0)10 (76.9)62 (59.0)
Malay7 (11.7)6 (18.8) 1 (7.7)14 (13.3)
Indian10 (16.7) 0 (0.0)2 (15.4)12 (11.4)
Other15 (25.0) 2 (6.3)0 (0.0)17 (16.2)
Date of onset – No. (%)
Before 16/3/0317 (28.3)18 (56.3)4 (30.8)39 (37.1)
16/3/03 to 21/3/0332 (53.3)10 (31.3)3 (23.1)45 (42.9)
22/3/03 and later11 (18.3)4 (12.5)6 (46.2)21 (20.0)
Presence of comorbid disease – No. (%) 3 (5.0)3 (9.4)‡10 (76.9)16 (15.2)
Admission to non-isolation facility
after illness onset – No. (%)
2 (3.3)4 (12.5)8 (61.5)14 (13.3)
Average time in days from onset
to isolation – Median (Range)
3.8 (3.0, 0-12) 4.9 (5.5, 1-11)§3.9 (3.0, 1-8)4.2 (4.0, 0-12)
* Three (5.0%) allied health staff, 2 cleaners (3.3%), 10 doctors (16.7%), 4 health attendants/healthcare assistants (6.7%), 32 nurses (53.3%), 5 (8.3%)
student nurses and 4 (6.7%) ward clerks.
† Reclassified as probable cases when serological results which only became available after the end of the outbreak were reviewed between June and July
2003. Twelve cases (9 healthcare staff, 1 visitor and 2 of the inpatients) had already been previously diagnosed as suspected cases; the remaining 2
inpatient cases were detected during a retrospective screening programme involving combined serological and PCR screening of 70+ long-staying
patients of TTSH.
‡ Comorbid disease considered were those which could compromise immune function (e.g., diabetes mellitus, malignancies, autoimmune disease) or cause
respiratory insufficiency (e.g., chronic obstructive lung disease, congestive cardiac failure).
§ Excludes 2 patients who were part of a ward quarantine cohort and not isolated.
PCR: polymerase chain reaction; TTSH: Tan Tock Seng Hospital
have occurred, including 3 major outbreaks in 2 general
wards (X and Y) and in the Coronary Care Unit (CCU;
henceforth referred to as Ward Z), as well as 4 minor
outbreaks in the ward designated P, Q, R and S. We
describe the various ward-based outbreaks below.
Ward X outbreak: The time-course of the Ward X
outbreak is given in Figure 1b. The initial wave of infections
(onset up to 11 March 2003) consisted largely of staff and
visitors, all of whom reported direct contact with the
original index case who was admitted to the ward on 1
March 2003 and was subsequently transferred out on 6
March 2003. Later cases involved mainly staff and
inpatients, and may have been due to transmission by
secondary cases remaining in the ward. Ward X produced
the index cases that seeded Wards Y, P, Q, R and S, as well
as the index case for the major outbreak in Singapore
General Hospital (SGH; see Figure 2).19
Ward Y outbreak: The outbreak in Ward Y began when
a nurse working in Ward X was admitted on 10 March 2003
with a febrile illness, which was initially suspected to be
dengue fever. By the time she was isolated on 13 March
2003, she was suspected to have infected multiple secondary
cases, including 12 staff, 8 visitors and 3 patients (Fig. 1c),
although in retrospect, some of these cases could have also
have been infected by the index case for Ward Z, who was
an adjacent inpatient in the same room, and who developed
symptoms on 12 March 2003 and then was transferred out
on the same day to the CCU (Ward Z). The events in Ward
Z will be described in greater detail below. Two visitors to
Ward Y also subsequently caused minor incidents of
transmission when admitted to National University Hospital
(NUH) and Changi General Hospital (CGH).
Investigators only became aware of the outbreak in Ward
Y after 15 March 2003, when staff from the ward began to
present as cases of suspected and probable SARS.
CCU outbreak (Ward Z): The inpatient from Ward Y,
who had shared the same room as the index case for that
ward, had been admitted for an unrelated febrile illness on
10 March 2003. This patient, who had pre-existing ischaemic
heart disease and diabetes, developed progressive shortness

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Fig. 1a. Overview of epidemic curve TTSH.
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Fig. 1b. Epidemic curve in ward X.
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Fig. 1c. Epidemic curve in ward Y.
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Fig. 1d. Epidemic curve in ward Z.

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of breath on 12 March 2003. There was no contact or travel
history of relevance to SARS prior to hospitalisation, and
blood cultures drawn on admission grew gram-negative
bacilli. Due to her pre-existing ischaemic heart disease, the
presumptive diagnosis was that of worsening cardiac failure
secondary to sepsis, and she was transferred to the coronary
care unit (Ward Z). In the CCU, she rapidly deteriorated,
and had to be intubated on 13 March 2003.
The CCU outbreak (Fig. 1d) was discovered when a staff
member was admitted with a pneumonia-like illness on the
evening on 19 March 2003. Case-finding initiated that
night eventually identified infections in a total of 20 nursing,
medical and allied health staff working in the CCU. Five
visitors to the index case of the CCU also contracted SARS.
No other inpatients of the CCU were clinically diagnosed
to have SARS, although we did not recall these patients for
serological testing when these tests became available later
in the outbreak. A healthcare worker (HCW) seeking
obstetric care would subsequently cause 1 secondary case
at Kandang Kerbau Women’s and Children’s Hospital.
Outbreaks in Wards P, Q, R and S: A staff member in
Ward P, who had no other contact history of note, was
suspected to be infected when the mother of the TTSH
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Fig. 2. Transmission of SARS within TTSH and seeding of other institutions.
Dates of key events
index case was admitted briefly to the ward for a period of
less than 1 day. There were no subsequent incidents of
transmission in that ward.
In Ward Q, a student nurse who had been infected in
Ward X was admitted without precautions for 3 days.
During this time, she was suspected to have infected 2
HCWs; however, no subsequent spread was traced to
patients or staff from this ward.
The index cases for Wards R and S were 2 ex-patients of
Ward X, both of whom had pre-existing end-stage renal
failure. Both patients presented with pneumonia-like illness
on 16 March 2003. While they were quickly isolated
1 day later on 17 March 2003, secondary spread had
already occurred. In Ward R, there was a chain of
transmission involving 3 HCWs, 1 patient, and 1 visitor,
but again no subsequent spread to other wards or hospitals
was traced to this ward. In Ward S, however, an elderly
patient with multiple comorbid conditions was infected
prior to her discharge. This patient would go on to infect a
nurse aide in a nursing home, as well as cause a cluster of
infections in CGH.17
Table 2 summarises the features of the 7 ward-based
outbreaks in TTSH. Of note, super-spreading events,
arbitrarily defined as an outbreak involving 10 or more
secondary infections, occurred in 3 of the wards. The key
difference between the major and minor ward outbreaks
was the time the index case spent in those wards (median
of 5 days versus 1 day respectively, P = 0.042, Mann-
Whitney U test). HCWs were the first to fall ill in 5 out of
7 wards, and were affected in all but Ward S, where