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Commentary
Wresting SARS from Uncertainty
Jairam R. Lingappa,* L.
Clifford McDonald,* Patricia Simone,* and Umesh
D. Parashar*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Suggested citation
for this article:
Lingappa JR, McDonald LC, Simone P, Parashar UD. Wresting SARS from
uncertainty. Emerg Infect Dis [serial online] 2004 Feb [date cited].
Available from: URL: http://www.cdc.gov/ncidod/EID/vol10no2/03-1032.htm
In early March 2003, Carlo Urbani, a World Health Organization (WHO)
epidemiologist stationed in Vietnam, alerted the global health community
to the high transmissibility and lethality associated with an apparently
new respiratory disease. This disease, now called severe acute respiratory
syndrome (SARS), is believed to have emerged in China in November 2002
and progressed to a global health threat by the spring of 2003 (1–3).
On March 15, 2003, with clusters of SARS cases being reported from China,
Hong Kong, Vietnam, Singapore, and Canada, WHO issued a global travel
alert. At that point, the international health community faced a potential
pandemic for which there were no identified causal agent, no diagnostic
laboratory assays, no defined properties or risk factors for transmission,
no infection-control practices of proven efficacy, and no known treatment
or prevention measures. Given that setting, the declaration on July 5
that SARS had been contained (in less than 4 months after its initial
recognition), represented a remarkable achievement for a truly extraordinary
international public health effort.
However, the SARS outbreak was not contained before it had had a substantial
impact: 8,098 cases involving 774 deaths were attributed to SARS (4)
(the original WHO case definitions [5] were revised during
the outbreak to those shown in the Table); fear of
contagion was rife in many communities, especially among healthcare workers;
and billions of dollars had been lost in the airline and tourism industries,
resulting in bankruptcies of airlines and other businesses. However, the
SARS public health response effort was equally important: the world’s
scientific, clinical, and public health communities had successfully instituted
sensitive surveillance for the disease; isolation and infection-control
practices—with intensive contact tracing and community containment, including
quarantine—were effective in limiting continued spread in most cases;
and the causative agent and diagnostic assays for detecting the disease
were identified.
Now, nearly 1 year after the world first faced this infectious disease
challenge, the public health community is equipped with a broader understanding
of the agent, its pathophysiology, clinical signs and symptoms, risk factors
for transmission, and public health measures that can successfully contain
the disease. The breadth of this understanding and international scope
of the outbreak response are reflected in the range of manuscript topics
in this issue of Emerging Infectious Diseases. Herein we review some of
the salient features of the biology and epidemiology of SARS while underscoring
some of the remaining unanswered questions.
The origins of the SARS-associated coronavirus (SARS-CoV) remain unclear;
however, data suggest that the outbreak may have been preceded by transmission
of this or a related virus from animals to humans. SARS-CoV has now been
shown to infect (although not necessarily be transmissible through) other
animals, including macaques (7), ferrets and cats (8),
and pigs and chickens (9), although none of these animals
are known to act as natural amplifying hosts for the virus. Antibodies
to SARS-CoV have been identified in animal handlers (10),
and a SARS-like coronavirus has been identified in palm civets and other
animals indigenous to Guangdong Province, where SARS likely originated
(11). Furthermore, serologic studies in Hong Kong suggest
that SARS-like viruses may have circulated in human populations before
the 2002–2003 outbreak (12).
As the SARS outbreak unfolded in Vietnam, Singapore, and Hong Kong, hospital
workers stood out as a critical high-risk group. We now know that in many
locations the SARS outbreak began with ill travelers coming from other
SARS-affected areas (13). For many affected areas with
low case numbers, such as the United States (where only eight cases were
laboratory-confirmed [14–16]), SARS remained a travel-associated
illness only, with no hospital or community transmission (14,17,18).
However, healthcare settings played a key role in amplifying disease outbreaks
(19). In locations such as Singapore, Canada, and Vietnam,
disease was transmitted to many hospital workers by ill travelers or contacts
of ill travelers, but in these locations, disease was successfully contained
within hospitals. If the disease was not rapidly controlled in healthcare
settings, as occurred in China, Taiwan, and Hong Kong, spread into the
community occurred, resulting in extensive disease transmission (20,21)
(Figure).
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Figure |
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Click to view
enlarged image
Figure. Cumulative
cases of severe acute respiratory syndrome and proportion among
healthcare workers by geographic region, November 1, 2002–July 31,
2003.
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Most SARS patients had a clear history of exposure to other SARS patients
or SARS-affected areas. Even in China, despite its extensive community
transmission, intensive investigation successfully linked many cases previously
classified as “unlinked” to high-risk exposures to SARS patients in fever
clinics and other locations (20). Older persons were
at greatest risk for severe disease, with fatality rates of nearly 50%
in persons >60 years of age, whereas, for unclear reasons, fewer children
were affected; those that were had lower morbidity and mortality (22–24).
A critical question has been whether SARS-CoV is transmitted through
large droplets or on fomites, as occurs with respiratory syncytial virus,
variola, and mycoplasma, or through aerosols, as occurs with measles and
varicella. We now know that large droplets are likely the primary mode
of transmission; however, in some circumstances, clusters suggestive of
aerosol transmission have been described (19,25,26).
Transmission appears to be heterogeneous. Most probable SARS cases were
associated with little or no transmission. Although low transmission most
commonly occurs in association with appropriate infection-control practices
(27), cases have also been documented with no transmission
despite ample exposure opportunities (17,18,28–30).
Transmission in hospital settings has been clearly documented (25,31–33).
Hospital transmission, along with infrequent “superspreading events,”
involving transmission from one case to many secondary cases, was critical
to propagating the outbreak (19,25,26,34).
Limited risk factors for superspreading events have been identified, including
more severe illness, slightly older age, and an increased number of secondary
contacts (34); however, further epidemiologic, virologic,
and host-factor studies are needed to fully elucidate the risk factors
that underlie SARS-CoV transmission.
Fortunately, the outbreak demonstrated that SARS-CoV transmission can
be effectively contained by strict adherence to infection-control practices.
The use of N95 respirators or surgical masks was found to effectively
reduce transmission in hospitals (31,33); this protective
capacity of masks also has been shown for community transmission (20).
Premature relaxation of infection-control measures in some SARS-affected
areas had profound implications (35). Studies have demonstrated
the importance of preexposure infection-control training and consistent
use of masks, gowns, gloves, and eye protection (36).
Serologic and nucleic acid assays to detect SARS-CoV infection and virus,
respectively, were developed early in the outbreak investigation (37–39).
Comparative studies have now confirmed the sensitivity and specificity
of enzyme-linked immunosorbent assays for detecting SARS antibodies (40)
and of multitargeted real-time reverse transcription–polymerase chain
reaction (RT-PCR) assays for detecting SARS-CoV infection (41,42).
Although these assays are sensitive for detecting antibody and viral RNA,
they have provided limited help in diagnosing SARS early in the course
of disease (15,16,43,44). However,
since the SARS clinical case definition is nonspecific, capturing respiratory
illness caused by other pathogens (e.g., Mycoplasma pneumoniae
and influenza) (14), laboratory confirmation of SARS-CoV
infection is of particular importance for focusing control efforts during
an outbreak and for refining SARS clinical studies. Such studies have
shown that less than one third of patients initially have respiratory
symptoms and, although abnormal findings on chest radiographs are universal
for SARS patients, radiographic changes may not be discerned until 7 to
10 days after illness onset (45,46).
Diagnostic assays have also been important in describing the natural
history of SARS infection and the associated immune response (29,43,47).
Seroconversion within 28 days after symptom onset has been documented
in 92% to 100% of probable SARS cases. Furthermore, during the first 4
days of illness, SARS-CoV is detectable by RT-PCR in respiratory secretions
from less than half of the case-patients. Virus is subsequently detected
in stool, and peak levels in both respiratory and stool specimens are
found by day 11–12 of illness; virus can persist in stool for weeks thereafter
(29,42,43,47). These studies underscore
the continued need for SARS-CoV laboratory assays that are sensitive early
in the disease course to support rapid clinical and infection-control
decision-making.
The possibility remains that SARS may reemerge from unidentified animal
reservoirs or from persistently infected humans. Current planning efforts
for response to a future SARS resurgence rely upon vigilant application
of clinical and epidemiologic criteria to evaluate cases of febrile illness
(48). A bold and swift public health response to this
disease must be applied with fairness and in a manner that preserves dignity
for all. Response to any future resurgence of SARS will be aided by the
body of knowledge about the infection that now exists and by the international
experience in successfully containing the first SARS outbreak.
References
- World Health Organization. Acute respiratory syndrome,
China. Wkly Epidemiol Rec 2003;78:41–8.
- World Health Organization. Acute
respiratory syndrome, China, Hong Kong Special Administrative Region
of China, and Viet Nam. Wkly Epidemiol Rec 2003;78:73–4.
- Centers for Disease Control and Prevention. Outbreak
of severe acute respiratory syndrome—worldwide, 2003. MMWR Morb
Mortal Wkly Rep 2003;52:226–8.
- World Health Organization. Summary of probable SARS cases with onset
of illness from 1 Nov 2002 to 31 July 2003. (Accessed Dec 6, 2003).
Available from: URL: http://www.who.int/csr/sars/country/table2003_09_23/en/
- World Health Organization. Severe
acute respiratory syndrome (SARS). Wkly Epidemiol Rec 2003;78:81–3.
- World Health Organization. Case definitions for surveillance of severe
acute respiratory syndrome (SARS). (Accessed Dec 6, 2003), Available
from: URL: http://www.who.int/csr/sars/casedefinition/en/
- Fouchier RA, Kuiken T, Schutten M, van Amerongen G, van Doornum GJ,
van den Hoogen BG, et al. Aetiology:
Koch’s postulates fulfilled for SARS virus. Nature 2003;423:240.
- Martina BE, Haagmans BL, Kuiken T, Fouchier RA, Rimmelzwaan GF, Van
Amerongen G, et al. Virology:
SARS virus infection of cats and ferrets. Nature 2003;425:915.
- Weingartl HM, Copps J, Drebot MA, Marszal PS, Smith G, Gren J, Andonova
M, et al. Susceptibility of pigs and chickens to SARS coronavirus. Emerg
Infect Dis 2004;10: 179–84.
- Centers for Disease Control and Prevention. Prevalence
of IgG antibody to SARS-associated coronavirus in animal traders—Guangdong
Province, China, 2003. MMWR Morb Mortal Wkly Rep 2003;52:986–7.
- Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung
CL, et al. Isolation
and characterization of viruses related to the SARS coronavirus from
animals in southern China. Science 2003;302:276–8.
- Zheng BJ, Guan Y, Wong KH, Zhou J, Wong KL, Young BWF, et al. SARS-related
virus predating SARS outbreak, Hong Kong. Emerg Infect Dis 2004;10:
176–8.
- Centers for Disease Control and Prevention. Update:
outbreak of severe acute respiratory syndrome—worldwide, 2003. MMWR
Morb Mortal Wkly Rep 2003;52:241–8.
- Schrag J, Brooks JT, Van Beneden C, Parashar UD, Griffin PM, Anderson
LF, et al. SARS surveillance during emergency public health response,
United States, March–July, 2003. Emerg Infect Dis 2004;10: 185–95.
- Centers for Disease Control and Prevention. Update:
severe acute respiratory syndrome—worldwide and United States, 2003.
MMWR Morb Mortal Wkly Rep 2003;52:664–5.
- Centers for Disease Control and Prevention. Updated
interim surveillance case definition for severe acute respiratory syndrome
(SARS)—United States, April 29, 2003. MMWR Morb Mortal Wkly Rep
2003;52:391–3.
- Park BJ, Peck AJ, Kuehnert M, Newbern C, Smelsey, McDonald LC. Lack
of SARS transmission among healthcare workers, United States. Emerg
Infect Dis 2004;10: 244–8.
- Peck AJ, Newbern EC, Feikin DR, Isakbaeva ET, Park BJ, Fehr JT, et
al. Lack of SARS transmission and U.S. SARS case-patient. Emerg Infect
Dis 2004: 217–24.
- Wong RSM, Hui DS. Index patient and SARS outbreak in Hong Kong. Emerg
Infect Dis 2004;10: 339–41.
- Wu J, Xu F, Zhou W, Feikin DR, Lin C-Y, He X, et al. Risk factors
for SARS among persons without known contact with SARS patients, Beijing,
China. Emerg Infect Dis 2004;10: 210–6.
- Liang W, Zhu Z, Guo J, Liu Z, He X, Zhou W, et al.
Severe acute respiratory syndrome, Beijing, 2003. Emerg Infect Dis [serial
online] 2004 Jan [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol10no1/03-0553.htm
- Bitnun A, Allen U, Heurter H, King SM, Opavsky MA, Ford-Jones EL,
et al. Children
hospitalized with severe acute respiratory syndrome-related illness
in Toronto. Pediatrics 2003;112:e261.
- Hon KL, Leung CW, Cheng WT, Chan PK, Chu WC, Kwan YW, et al. Clinical
presentations and outcome of severe acute respiratory syndrome in children
[comment]. Lancet 2003;361:1701–3.
- Yang G-G, Lin S-Z, Liao K-W, Lee J-J, Wang L-S. SARS-associated coronavirus
infection in teenagers. Emerg Infect Dis 2004;10: 382–3.
- Christian MD, Loutfy M, McDonald LC, Martinez KF, Ofner M,Wong T,
et al. al. Possible SARS coronavirus transmission during cardiopulmonary
resuscitation. Emerg Infect Dis 2004;10: 287–93.
- Wong T-W, Lee C-K, Tam W, Lau JT-F, Yu T-S, Lui S-F, et al. Cluster
of SARS among medical students exposed to single patient, Hong Kong.
Emerg Infect Dis 2004;10: 269–76.
- Centers for Disease Control and Prevention. Severe
acute respiratory syndrome—Singapore, 2003. MMWR Morb Mortal Wkly
Rep 2003;52:405–11.
- Ha LD, Bloom S, Nguyen QH, Maloney SA, Le MQ, Leitmeyer KC, et al.
Lack of SARS transmission among public hospital workers, Vietnam. Emerg
Infect Dis 2004;10: 265–8.
- Isakbaeva ET, Khetsuriani N, Beard RS, Peck A, Erdman D, Monroe SS,
et al. SARS-associated coronavirus transmission, United States. Emerg
Infect Dis 2004;10: 225–31.
- Goh DL-M, Lee BW, Chia KS, Heng BH, Chen M, Ma S, et al. Secondary
household transmission of SARS, Singapore. Emerg Infect Dis 2004;10:
232–4.
- Seto WH, Tsang D, Yung RW, Ching TY, Ng TK, Ho M,
et al. Effectiveness
of precautions against droplets and contact in prevention of nosocomial
transmission of severe acute respiratory syndrome (SARS) [comment].
Lancet 2003;361:1519–20.
- Ofner M, Lem M, Sarwal S, Vearncombe M, Simor A. Cluster
of severe acute respiratory syndrome cases among protected health care
workers—Toronto, April 2003. Can Commun Dis Rep 2003;29:93–7.
- Loeb M, McGeer A, Henry B, Ofner M, Rose D, Hlywka T, et al. SARS
among critical care nurses, Toronto. Emerg Infect Dis 2004;10: 251–5.
- Shen Z, Ning F, Zhou W, He X, Lin C, Chin DP, et al. Superspreading
SARS events, Beijing. Emerg Infect Dis 2004;10: 256–60.
- Centers for Disease Control and Prevention. Update:
severe acute respiratory syndrome—Toronto, Canada, 2003. MMWR Morb
Mortal Wkly Rep 2003;52:547–50.
- Lau JTF, Fung KS, Wong TW, Kim JH, Wong E, Chung S, et al. SARS transmission
among hospital workers, Hong Kong. Emerg Infect Dis 2004;10: 280–6.
- Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, et
al. A
novel coronavirus associated with severe acute respiratory syndrome
[comment]. N Engl J Med 2003;348:1953–66.
- Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, et al. Coronavirus
as a possible cause of severe acute respiratory syndrome [comment].
Lancet 2003;361:1319–25.
- Drosten C, Gunther S, Preiser W, van der Werf S, Brodt HR, Becker
S, et al. Identification
of a novel coronavirus in patients with severe acute respiratory syndrome
[comment]. N Engl J Med 2003;348:1967–76.
- Wu H-S, Chiu S-C, Tseng T-C, Lin S-F, Lin J-H, Hsu Y-F, et al. Serologic
and molecular biologic methods for SARS-associated coronavirus infection,
Taiwan. Emerg Infect Dis 2004;10: 304–10.
- Emery SL, Erdman DD, Meyer RF, Bowen MD, Newton BR,
Winchell JM, et al. Real-time reverse transcriptase–polymerase chain
reaction assay for SARS-associated coronavirus. Emerg Infect Dis 2004;10:
311–6.
- Zhai J, Briese T, Dai E, Wang X, Pang X, Du Z, et al. Real-time polymerase
chain reaction for detecting SARS coronavirus, Beijing, 2003. Emerg
Infect Dis 2004;10: 300–3.
- Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, et al. Clinical
progression and viral load in a community outbreak of coronavirus-associated
SARS pneumonia: a prospective study. Lancet 2003;361:1767–72.
- Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA,
et al. Clinical
features and short-term outcomes of 144 patients with SARS in the greater
Toronto area [comment]. JAMA 2003;289:2801–9; erratum appears in
JAMA 2003;290:334.
- Choi KW, Chau TN, Tsang O, Tso E, Chiu MC, Tong WL, et al. Outcomes
and prognostic factors in 267 patients with severe acute respiratory
syndrome in Hong Kong. Ann Intern Med 2003;139:715–23.
- Vu HT, Leitmeyer KC, Le DH, Miller MJ, Nguyen QH, Uyeki TM, et al.
SARS in Vietnam, February–May, 2003. Emerg Infect Dis 2004;10: 334–8.
- Chan KH, Poon LLLM, Cheng VCC, Guan Y, Hung IFN, Kong J, et al. Detection
of SARS coronavirus in patients with suspected SARS. Emerg Infect Dis
2004;10: 294–9.
- Jernigan JA, Low DE, Helfand RF. Combining clinical and epidemiologic
features for early recognition of SARS. Emerg Infect Dis 2004;10: 327–33.
Table.
World Health Organization SARS case definitionsa |
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Suspected case-patient: a person presenting
after November 1, 2002,b with a history of (ALL THREE):
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1. High fever (>38°C) AND
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2. Cough or breathing difficulty, AND
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3. One or more of the following exposures during
the 10 days before onset of symptoms:
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close contactc with a person
who is a suspected or probable SARS case-patient
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history of travel to an area with recent
local transmission of SARS
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residing in an area with recent local
transmission of SARS
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Probable case-patient: a suspected case-patient
with:
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1. Radiographic evidence of infiltrates consistent
with pneumonia or respiratory distress syndrome (RDS) on chest x-ray
OR
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2. Consistent respiratory illness that is positive
for SARS coronavirus by one or more assays, OR
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3. Autopsy findings consistent with the pathology
of RDS without an identifiable cause
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aRevised
May 1, 2003 (6). SARS, severe acute respiratory
syndrome. |
bThe surveillance
period begins on November 1, 2002, to capture cases of atypical pneumonia
in China now recognized as SARS. International transmission of SARS
was first reported in March 2003 for cases with onset in February
2003. |
cA close contact
is someone who cared for, lived with, or had direct contact with respiratory
secretions or body fluids of a suspected or probable SARS case-patient. |
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Jairam
R. Lingappa
Dr.
Lingappa worked for the Centers for Disease Control and Prevention
(CDC) from 1998 through 2003, most recently as the medical epidemiologist
for respiratory viral infections with the Respiratory and Enteric
Virus Branch, Division of Viral and Rickettsial Diseases. In that
capacity, he had the responsibility for developing epidemiologic evaluation
of respiratory viral infections in outbreak settings and research
studies. During the 2002–2003 outbreak of severe acute respiratory
syndrome (SARS), Dr. Lingappa led the Special Investigations Team
coordinating CDC’s SARS transmission and natural history investigations.
His research interests include immunologic and genomic aspects of
host response to infectious pathogens and vaccines, as well as pathogen
detection and discovery technologies and emerging infectious diseases.
In January 2004, Dr. Lingappa joined the faculty of the Department
of Medicine at the University of Washington. |
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L.
Clifford McDonald
Dr. McDonald is a medical epidemiologist in the Epidemiology and Laboratory
Branch, Division of Healthcare Quality Promotion, CDC, which has primary
responsibility for public health response activities in healthcare
settings. Dr. McDonald has training in adult infectious diseases,
clinical microbiology, and epidemiology and is an experienced hospital
epidemiologist. During the past outbreak, he was a member of the Clinical
and Infection Control Team, working in the Emergency Operations Center
activated for SARS; he also led the CDC SARS Investigation Team to
Toronto during both phases of the outbreak there. His interests include
antimicrobial resistance and outbreak investigations in hospitals,
and he has performed both domestic and international research in these
areas. |
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Patricia
Simone
Dr. Simone is the associate director for science in the Division of
Global Migration and Quarantine, National Center for Infectious Diseases,
CDC. She is responsible for the scientific activities of that division,
whose missions are to decrease illness and death from infectious diseases
among mobile populations (immigrants, refugees, migrant workers, and
international travelers) crossing international borders destined for
the United States and to decrease the risk for importation and spread
of infectious diseases via humans, animals, and cargo. She is an expert
on tuberculosis and serves as the SARS team leader for travel-related
issues. |
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Dr.
Parashar is the lead medical epidemiologist for the CDC's SARS Task
Force, which has overall responsibility to develop, oversee, coordinate,
and implement CDC's SARS program activities. Dr. Parashar was a member
of the World Health Organization team that investigated the SARS epidemic
in Hong Kong and later led the surveillance team at CDC during the
response to the SARS outbreak in the United States. His other research
interests include the epidemiology of viral gastroenteritis and methods
for its prevention and control, including vaccination strategies. |
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