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Background: Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period., Methods: We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome coronavirus, using data from the epidemic in 2003 in Hong Kong., Results: We estimated the incubation period of severe acute respiratory syndrome based on a subset of patients with available data on exposure periods and a separate subset of patients in a putative common source outbreak, and we found associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders., Conclusions: Our findings suggest that patients with a shorter incubation period went on to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association.

CD209 (DC-SIGN) is an important C-type lectin which acts a receptor of many pathogens. The single nucleotide polymorphism (SNP) -336A>G in the CD209 promoter has been demonstrated to regulate promoter activity and to be associated with several important infectious diseases, such as human immunodeficiency virus-1 (HIV-1), Mycobacterium tuberculosis, and Dengue fever. CD209 facilitates severe acute respiratory syndrome (SARS)-coronavirus spike protein-bearing pseudotype driven infection of permissive cells in vitro. In keeping with previously published findings, our in vitro studies confirmed that this SNP modulates gene promoter activity. Genetic association analysis of this SNP with clinico-pathologic outcomes in 824 serologic confirmed SARS patients showed that the -336AG/GG genotype SARS patients was associated with lower standardized lactate-dehydrogenase (LDH) levels compared with the -336AA patients (p = 0.014, odds ratio = 0.40). High LDH levels are known to be an independent predictor for poor clinical outcome, probably related to tissue destruction from immune hyperactivity. Hence, SARS patients with the CD209 -336 AA genotype carry a 60% chance of having a poorer prognosis. This association is in keeping with the role of CD209 in modulating immune response to viral infection. The relevance of these findings for other infectious diseases and inflammatory conditions would be worth investigating., (Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Myxovirus resistance A (MxA) is an antiviral protein induced by interferon alpha and beta (IFN-alpha, IFN-beta) that can inhibit viral replication. The minor alleles of the -88G>T and -123C>A MxA promoter single-nucleotide polymorphisms (SNPs) are associated with increased promoter activity and altered response to IFN-alpha and IFN-beta treatment. Here, we demonstrate that the -123A minor allele provided stronger binding affinity to nuclear proteins extracted from IFN-beta-untreated cells than did the wild-type allele, whereas the -88T allele showed preferential binding after IFN-beta stimulation. Endogenous IFN-alpha and IFN-beta induction can be suppressed in severe acute respiratory syndrome (SARS) coronavirus infection. In support of our in vitro findings, a large case-control genetic-association study for SARS coronavirus infection confirmed that the -123A minor-allele carriers were significantly associated with lower risk of SARS coronavirus infection, whereas the -88T minor-allele carriers were insignificant after adjustment for confounding effects. This suggests that -123C>A plays a more important role in modulating basal MxA expression, thus contributing more significantly to innate immune response against viral infections that suppress endogenous IFN-alpha and IFN-beta induction such as SARS coronavirus.

Background: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs., Methods and Findings: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0-140.1) and 63.5 d (95% CI 18.0-94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0-52.0) and 8 (IQR 3.2-21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5-16.5, p<0.05, and 7, IQR 3.0-12.0, p<0.01, respectively)., Conclusions: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources.

Background: The 2002-2003 Severe Acute Respiratory Syndrome (SARS) outbreak infected 8,422 individuals leading to 916 deaths around the world. However, there have been few epidemiological studies of SARS comparing epidemiologic features across regions. The aim of this study is to identify similarities and differences in SARS epidemiology in three populations with similar host and viral genotype., Methods: We present a comparative epidemiologic analysis of SARS, based on an integrated dataset with 3,336 SARS patients from Hong Kong, Beijing and Taiwan, epidemiological and clinical characteristics such as incubation, onset-to-admission, onset-to-discharge and onset-to-death periods, case fatality ratios (CFRs) and presenting symptoms are described and compared between regions. We further explored the influence of demographic and clinical variables on the apparently large differences in CFRs between the three regions., Results: All three regions showed similar incubation periods and progressive shortening of the onset-to-admission interval through the epidemic. Adjusted for sex, health care worker status and nosocomial setting, older age was associated with a higher fatality, with adjusted odds ratio (AOR): 2.10 (95% confidence interval: 1.45, 3.04) for those aged 51-60; AOR: 4.57 (95% confidence interval: 3.32, 7.30) for those aged above 60 compared to those aged 41-50 years. Presence of pre-existing comorbid conditions was also associated with greater mortality (AOR: 1.74; 95% confidence interval: 1.36, 2.21)., Conclusion: The large discrepancy in crude fatality ratios across the three regions can only be partly explained by epidemiological and clinical heterogeneities. Our findings underline the importance of a common data collection platform, especially in an emerging epidemic, in order to identify and explain consistencies and differences in the eventual clinical and public health outcomes of infectious disease outbreaks, which is becoming increasingly important in our highly interconnected world.

1. The promotion of personal protective health practices must take into account background perceptions of risk and psychological responses in the community-at-large. 2. Population psycho-behavioural factors in Hong Kong and Singapore are shown to be an important potential vector for the transmission of an infectious agent. 3. Comparative psycho-behavioural surveillance and analysis can yield important insights into generic versus population-specific issues that could be used to inform, design and benchmark public health infection control measures.

1. Geographic information system (GIS) can be applied during an acute infectious disease outbreak to reveal new geospatial information in addition to standard field epidemiological analyses. 2. When applied in real time during the onset and evolution of an epidemic, GIS can monitor and enhance understanding of the transmission dynamics of an infectious agent, thereby facilitating the design, implementation and evaluation of potential intervention strategies.

The near absence of transmission (seroprevalence=0.19%) resulting in asymptomatic infection in this representative high-risk group of close contacts indicates that the prevailing SARS-CoV strains in Hong Kong almost always led to clinically apparent disease.

1. The temporal and spatial evolution of the SARS epidemic in Hong Kong is described. 2. Estimates of key epidemiological distributions and their stability over the course of the epidemic are derived. 3. The characteristics of those who contracted the disease are determined including factors associated with the likelihood of mortality as a result of SARS coronavirus infection.

The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002-2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (+/-0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.

1. SARS coronavirus has low transmissibility at the community level. 2. Subclinical SARS coronavirus infection is rare in children.

1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.

One of the areas most affected by SARS was Beijing with 2521 reported cases. We estimate the effective reproductive number Rt for the Beijing SARS epidemic, which represents the average number of secondary cases per primary case on each day of the epidemic and is therefore a measure of the underlying transmission dynamics. Our results provide a quantitative assessment of the effectiveness of public health control measures. More generally, our results illustrate how changes in Rt will reflect changes in the epidemic curve.

The extensive data collection and contact tracing that occurred during the 2003 outbreak of severe acute respiratory syndrome (SARS) in Hong Kong, China, allowed the authors to examine how the probability of transmission varied from the date of symptom onset to the date of hospitalization for household contacts of SARS patients. Using a discrete-time likelihood model, the authors estimated the transmission probability per contact for each day following the onset of symptoms. The results suggested that there may be two peaks in the probability of SARS transmission, the first occurring around day 2 after symptom onset and the second occurring approximately 10 days after symptom onset. Index patients who were aged 60 years or older or whose lactate dehydrogenase level was elevated upon admission to the hospital (indicating higher viral loads) were more likely to transmit SARS to their contacts. There was little variation in the daily transmission probabilities before versus after the introduction of public health interventions on or around March 26, 2003. This study suggests that the probability of transmission of SARS is dependent upon characteristics of the index patients and does not simply reflect temporal variability in the viral load of SARS cases.

Genetic polymorphisms have been demonstrated to be associated with vulnerability to human infection. ICAM3, an intercellular adhesion molecule important for T cell activation, and FCER2 (CD23), an immune response gene, both located on chromosome 19p13.3, were investigated for host genetic susceptibility and association with clinical outcome. A case-control study based on 817 patients with confirmed severe acute respiratory syndrome (SARS), 307 health care worker control subjects, 290 outpatient control subjects, and 309 household control subjects unaffected by SARS from Hong Kong was conducted to test for genetic association. No significant association to susceptibility to SARS infection caused by the novel coronavirus (SARS-CoV) was found for the FCER2 and the ICAM3 single nucleotide polymorphisms. However, patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P=.0067; odds ratio [OR], 4.31 [95% confidence interval {CI}, 1.37-13.56]) and lower total white blood cell counts (P=.022; OR, 0.30 [95% CI, 0.10-0.89]) on admission. These findings support the role of ICAM3 in the immunopathogenesis of SARS.

For diseases with some level of associated mortality, the case fatality ratio measures the proportion of diseased individuals who die from the disease. In principle, it is straightforward to estimate this quantity from individual follow-up data that provides times from onset to death or recovery. In particular, in a competing risks context, the case fatality ratio is defined by the limiting value of the sub-distribution function, F(1)(t) = Pr(T infinity, where T denotes the time from onset to death (J = 1) or recovery (J = 2). When censoring is present, however, estimation of F(1)(infinity) is complicated by the possibility of little information regarding the right tail of F(1), requiring use of estimators of F(1)(t(*)) or F(1)(t(*))/(F(1)(t(*))+F(2)(t(*))) where t(*) is large, with F(2)(t) = Pr(T

Two factors dominated the epidemiology of severe acute respiratory syndrome (SARS) during the 2002-2003 global outbreak, namely super-spreading events (SSE) and hospital infections. Although both factors were important during the first and the largest hospital outbreak in Hong Kong, the relative importance of different routes of infection has not yet been quantified. We estimated the parameters of a novel mathematical model of hospital infection using SARS episode data. These estimates described levels of transmission between the index super-spreader, staff and patients, and were used to compare three plausible hypotheses. The broadest of the supported hypotheses ascribes the initial surge in cases to a single super-spreading individual and suggests that the per capita risk of infection to patients increased approximately one month after the start of the outbreak. Our estimate for the number of cases caused by the SSE is substantially lower than the previously reported values, which were mostly based on self-reported exposure information. This discrepancy suggests that the early identification of the index case as a super-spreader might have led to biased contact tracing, resulting in too few cases being attributed to staff-to-staff transmission. We propose that in future outbreaks of SARS or other directly transmissible respiratory pathogens, simple mathematical models could be used to validate preliminary conclusions concerning the relative importance of different routes of transmission with important implications for infection control.

Background: Accurate and precise estimates of the incubation distribution of novel, emerging infectious diseases are vital to inform public health policy and to parameterize mathematical models., Methods: We discuss and compare different methods of estimating the incubation distribution allowing for interval censoring of exposures, using data from the severe acute respiratory syndrome (SARS) epidemic in 2003 as an example., Results: Combining data on unselected samples of 149 and 168 patients with defined exposure intervals from Toronto and Hong Kong, respectively, we estimated the mean and variance of the incubation period to be 5.1 day and 18.3 days and the 95th percentile to be 12.9 days. We conducted multiple linear regression on the log incubation times and found that incubation was significantly longer in Toronto than in Hong Kong and in older compared with younger patients, while it was significantly shorter in healthcare workers than in other patients., Conclusions: Our findings suggest subtle but important heterogeneities in the incubation period of SARS among different strata of patients. Robust estimation of the incubation period should be independently carried out in different settings and subgroups for novel human pathogens using valid statistical methods.

Background: An accurate prognostic model for patients with severe acute respiratory syndrome (SARS) could provide a practical clinical decision aid. We developed and validated prognostic rules for both high- and low-resource settings based on data available at the time of admission., Methods: We analyzed data on all 1755 and 291 patients with SARS in Hong Kong (derivation cohort) and Toronto (validation cohort), respectively, using a multivariable logistic scoring method with internal and external validation. Scores were assigned on the basis of patient history in a basic model, and a full model additionally incorporated radiological and laboratory results. The main outcome measure was death., Results: Predictors for mortality in the basic model included older age, male sex, and the presence of comorbid conditions. Additional predictors in the full model included haziness or infiltrates on chest radiography, less than 95% oxygen saturation on room air, high lactate dehydrogenase level, and high neutrophil and low platelet counts. The basic model had an area under the receiver operating characteristic (ROC) curve of 0.860 in the derivation cohort, which was maintained on external validation with an area under the ROC curve of 0.882. The full model improved discrimination with areas under the ROC curve of 0.877 and 0.892 in the derivation and validation cohorts, respectively., Conclusion: The model performs well and could be useful in assessing prognosis for patients who are infected with re-emergent SARS.

Background: Severe acute respiratory syndrome was relatively mild in children, and the incidence was significantly lower when compared with adults. Although previous seroepidemiological studies demonstrated that asymptomatic infection was uncommon among health care workers and adult contacts of patients with severe acute respiratory syndrome, it is unclear whether this would extend to the pediatric population., Objective: The purpose of this study was to determine the seroprevalence of severe acute respiratory syndrome coronavirus among asymptomatic children living near Amoy Gardens (site of largest community outbreak of severe acute respiratory syndrome in Hong Kong) compared with a low-risk region where no community transmission occurred., Methods: The study was conducted from September to October 2003. Target subjects living in the defined high-risk and low-risk areas were approached through the schools within the respective localities. We recruited 353 and 361 children, respectively, from the high-risk and low-risk areas and collected 3 to 5 mL of blood for severe acute respiratory syndrome coronavirus IgG antibody testing by immunofluorescence antibody assay and confirmation by neutralization test. Parents of all of the subjects who joined the study were contacted by telephone, and a standardized questionnaire was administered by a research nurse to collect information including sociodemographic data, history of severe acute respiratory syndrome coronavirus infection in the subjects and members of the household, history of contact with known cases of severe acute respiratory syndrome, presence of severe acute respiratory syndrome-like symptoms since onset of the severe acute respiratory syndrome epidemic, travel history of the child and his/her relatives within the 15 days before any such symptom onset, use of health service as a result of such symptoms, and whether there were deaths of relatives as a result of severe acute respiratory syndrome., Results: Two (0.57%) of 353 asymptomatic children from the high-risk area were tested positive for severe acute respiratory syndrome coronavirus antibody compared with 0 of 361 in the low-risk region. None of the 14 children who lived in the high-risk area and had known contacts with severe acute respiratory syndrome patients were seropositive., Conclusions: As in adults, subclinical severe acute respiratory syndrome coronavirus infection was rare in children in the 2003 epidemic. The very low seroprevalence implies little or no population herd immunity to protect against future resurgence of severe acute respiratory syndrome.

We systematically reviewed the current understanding of human population immunity against SARS-CoV in different groups, settings and geography. Our meta-analysis, which included all identified studies except those on wild animal handlers, yielded an overall seroprevalence of 0.10% [95% confidence interval (CI) 0.02-0.18]. Health-care workers and others who had close contact with SARS patients had a slightly higher degree of seroconversion (0.23%, 95% CI 0.02-0.45) compared to healthy blood donors, others from the general community or non-SARS patients recruited from the health-care setting (0.16%, 95% CI 0-0.37). When analysed by the two broad classes of testing procedures, it is clear that serial confirmatory test protocols resulted in a much lower estimate (0.050%, 95% CI 0-0.15) than single test protocols (0.20%, 95% CI 0.06-0.34). Potential epidemiological and laboratory pitfalls are also discussed as they may give rise to false or inconsistent results in measuring the seroprevalence of IgG antibodies to SARS-CoV.

We propose a Bayesian statistical framework for estimating the reproduction number R early in an epidemic. This method allows for the yet-unrecorded secondary cases if the estimate is obtained before the epidemic has ended. We applied our approach to the severe acute respiratory syndrome (SARS) epidemic that started in February 2003 in Hong Kong. Temporal patterns of R estimated after 5, 10, and 20 days were similar. Ninety-five percent credible intervals narrowed when more data were available but stabilized after 10 days. Using simulation studies of SARS-like outbreaks, we have shown that the method may be used for early monitoring of the effect of control measures.

The setting of a quarantine time for an emerging infectious disease will depend on current knowledge concerning incubation times. Methods for the analysis of information on incubation times are investigated with a particular focus on inference regarding a possible maximum incubation time, after which an exposed individual would be known to be disease free. Data from the Hong Kong SARS epidemic are used for illustration. The incorporation of interval-censored data is considered and comparison is made with percentile estimation. Results suggest that a wide class of models for incubation times should be considered because the apparent informativeness of a likelihood depends on the choice and generalizability of a model. There will usually remain a probability of releasing from quarantine some infected individuals and the impact of early release will depend on the size of the epidemic., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital.

Severe acute respiratory syndrome (SARS) is a highly infectious disease, with high potential for transmission to close contacts, particularly among healthcare workers. This is the first systematic study investigating hospital nurses' physical and psychological health status and the kinds of healthcare used-stratified by the level of contact with SARS patients-during the 2003 outbreak in Hong Kong. Nurses in moderate-risk areas appeared to have more stress symptoms than those working in high-risk areas. It is essential to design hospital support systems and occupational health policy to promote the psychological well-being of nurses during future outbreaks of emerging infections.

Background: In previous literature, the stability and temporal evolution of psychobehavioral responses to an outbreak remained undefined, because of the exclusively cross-sectional nature of such study designs., Methods: Using random-digit dialing, we sampled 4481 Hong Kong residents in 6 population-based surveys that were conducted at different times during and after the 2003 outbreak of severe acute respiratory syndrome (SARS)., Results: Respondents' State-Trait Anxiety Inventory score (range, 10-40) showed a decreasing temporal trend, from a high mean value of 24.8 during the peak of the Amoy Gardens outbreak to a postepidemic mean baseline value of 14.5. Those who perceived a higher likelihood of contracting or dying of SARS had significantly higher anxiety scores. Female respondents, individuals aged 30-49 years, and individuals with only a primary education or less were predisposed to greater anxiety. There was a positive dose-response gradient between anxiety level and uptake of personal protective measures. Males respondents, individuals at the extremes of age, and individuals with lower educational levels were less likely to engage in self-protective behavior. The presence of symptoms was the only consistent predictor for greater use of health services. There was remarkable stability in the magnitude and the direction of associations between predictors and outcomes over time., Conclusions: Our findings can assist in modifying public service announcements in the future, which should be tailored to psychobehavioral surveillance intelligence to achieve the desired behavioral outcomes. Future research should explore the use of more-sophisticated techniques, including structural equation modeling and game-theoretical frameworks, to analyze population psychology and behavior, and it should integrate such findings with transmission dynamics modeling.

Objectives: To compare the public's knowledge and perception of SARS and the extent to which various precautionary measures were adopted in Hong Kong and Singapore., Design: Cross-sectional telephone survey of 705 Hong Kong and 1,201 Singapore adults selected by random-digit dialing., Results: Hong Kong respondents had significantly higher anxiety than Singapore respondents (State Trait Anxiety Inventory [STAI] score, 2.06 vs 1.77; P < .001). The former group also reported more frequent headaches, difficulty breathing, dizziness, rhinorrhea, and sore throat. More than 90% in both cities were willing to be quarantined if they had close contact with a SARS case, and 70% or more would be compliant for social contacts. Most respondents (86.7% in Hong Kong vs 71.4% in Singapore; P < .001) knew that SARS could be transmitted via respiratory droplets, although fewer (75.8% in Hong Kong vs 62.1% in Singapore; P < .001) knew that fomites were also a possible transmission source. Twenty-three percent of Hong Kong and 11.9% of Singapore respondents believed that they were "very likely" or "somewhat likely" to contract SARS during the current outbreak (P < .001). There were large differences between Hong Kong and Singapore in the adoption of personal precautionary measures. Respondents with higher levels of anxiety, better knowledge about SARS, and greater risk perceptions were more likely to take comprehensive precautionary measures against the infection, as were older, female, and more educated individuals., Conclusion: Comparative psychobehavioral surveillance and analysis could yield important insights into generic versus population-specific issues that could be used to inform, design, and evaluate public health infection control policy measures.

Background: As yet, no one has written a comprehensive epidemiologic account of a severe acute respiratory syndrome (SARS) outbreak from an affected country., Objective: To provide a comprehensive epidemiologic account of a SARS outbreak from an affected territory., Design: Epidemiologic analysis., Setting: The 2003 Hong Kong SARS outbreak., Participants: All 1755 cases and 302 deaths., Measurements: Sociodemographic characteristics; infection clusters by time, occupation, setting, and workplace; and geospatial relationships were determined. The mean and variance in the time from infection to onset (incubation period) were estimated in a small group of patients with known exposure. The mean and variance in time from onset to admission, from admission to discharge, or from admission to death were calculated. Logistic regression was used to identify important predictors of case fatality., Results: 49.3% of patients were infected in clinics, hospitals, or elderly or nursing homes, and the Amoy Gardens cluster accounted for 18.8% of cases. The ratio of women to men among infected individuals was 5:4. Health care workers accounted for 23.1% of all reported cases. The estimated mean incubation period was 4.6 days (95% CI, 3.8 to 5.8 days). Mean time from symptom onset to hospitalization varied between 2 and 8 days, decreasing over the course of the epidemic. Mean time from onset to death was 23.7 days (CI, 22.0 to 25.3 days), and mean time from onset to discharge was 26.5 days (CI, 25.8 to 27.2 days). Increasing age, male sex, atypical presenting symptoms, presence of comorbid conditions, and high lactate dehydrogenase level on admission were associated with a greater risk for death., Limitations: Estimates of the incubation period relied on statistical assumptions because few patients had known exposure times. Temporal changes in case management as the epidemic progressed, unavailable treatment information, and several potentially important factors that could not be thoroughly analyzed because of the limited sample size complicate interpretation of factors related to case fatality., Conclusions: This analysis of the complete data on the 2003 SARS epidemic in Hong Kong has revealed key epidemiologic features of the epidemic as it evolved.

We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease "hot spots." Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated.

Background: Accurate, objective models of triage for patients with suspected severe acute respiratory syndrome (SARS) could assess risks and improve decisions about isolation and inpatient treatment., Objective: To develop and validate a clinical prediction rule for identifying patients with SARS in an emergency department setting., Design: Retrospective analysis using a 2-step coefficient-based multivariable logistic regression scoring method with internal validation by bootstrapping., Setting: 2 hospitals in Hong Kong., Participants: 1274 consecutive patients from 1 hospital and 1375 consecutive patients from another hospital., Measurements: Points were assigned on the basis of history, physical examination, and simple investigations obtained at presentation. The outcome measure was a final diagnosis of SARS, as confirmed by World Health Organization laboratory criteria., Results: Predictors for SARS on the basis of history (step 1) included previous contact with a patient with SARS and the presence of fever, myalgia, and malaise. Age 65 years and older and younger than 18 years and the presence of sputum, abdominal pain, sore throat, and rhinorrhea were inversely related to having SARS. In step 2, haziness or pneumonic consolidation on chest radiographs and low lymphocyte and platelet counts, in addition to a positive contact history and fever were associated with a higher probability of SARS. A high neutrophil count, the extremes of age, and sputum production were associated with a lower probability of SARS. In the derivation sample, the observed incidence of SARS was 4.4% for those assigned to the low-risk group (in steps 1 or 2); in the high-risk group, incidence of SARS was 21.0% for quartile 1, 39.5% for quartile 2, 61.2% for quartile 3, and 79.7% for quartile 4. This prediction rule achieved an optimism-corrected sensitivity of 0.90, a specificity of 0.62, and an area under the receiver-operating characteristic curve of 0.85., Limitations: The prediction rule may not apply to isolated cases occurring during an interepidemic period. Generalizability of the findings should be confirmed in other SARS-affected countries and should be prospectively validated if SARS returns., Conclusions: Our findings suggest that a simple model that uses clinical data at the time of presentation to an emergency department during an acute outbreak predicted the incidence of SARS and provided good diagnostic utility.

A total of 1,068 asymptomatic close contacts of patients with severe acute respiratory (SARS) from the 2003 epidemic in Hong Kong were serologically tested, and 2 (0.19%) were positive for SARS coronavirus immunoglobulin G antibody. SARS rarely manifests as a subclinical infection, and at present, wild animal species are the only important natural reservoirs of the virus.

This paper reviews current understanding of the epidemiology, transmission dynamics and control of the aetiological agent of severe acute respiratory syndrome (SARS). We present analyses of data on key parameters and distributions and discuss the processes of data capture, analysis and public health policy formulation during the SARS epidemic are discussed. The low transmissibility of the virus, combined with the onset of peak infectiousness following the onset of clinical symptoms of disease, transpired to make simple public health measures, such as isolating patients and quarantining their contacts, very effective in the control of the SARS epidemic. We conclude that we were lucky this time round, but may not be so with the next epidemic outbreak of a novel aetiological agent. We present analyses that help to further understanding of what intervention measures are likely to work best with infectious agents of defined biological and epidemiological properties. These lessons learnt from the SARS experience are presented in an epidemiological and public health context.

Objective: To examine the public's knowledge and perception of SARS and the extent to which various precautionary measures have been adopted., Design: Cross sectional survey., Setting: General population of Hong Kong at the height of the SARS outbreak (29 March to 6 April 2003)., Participants: 1115 ethnic Chinese adults., Main Results: Forty per cent did not recognise fomites as a possible mode of transmission whereas 55.1% believed that the infection could be transmitted airborne. A large proportion (30.1%) believed they were very or somewhat likely to contract SARS while only one quarter believed they were very likely to survive if they contracted the disease, benchmarked against an actual case fatality ratio of 2.8% at the time of the survey and 15%-20% according to current best estimates. Precautionary measures directed against person to person droplet spread were generally adopted by most while the prevention of transmission through fomites was not practised as frequently. Respondents with higher risk perceptions and a moderate level of anxiety were most likely to take comprehensive precautionary measures against the infection, as were older, female, more educated people as well as those with a positive contact history and SARS-like symptoms., Conclusions: The findings demonstrate that the promotion of protective personal health practices to interrupt the self sustaining transmission of the SARS virus in the community must take into account background perceptions of risk and anxiety levels of the public at large. Continuing public education about preventive measures should be targeted at the identified groups with low current uptake of precautions.

We present an analysis of the first 10 weeks of the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. The epidemic to date has been characterized by two large clusters-initiated by two separate "super-spread" events (SSEs)-and by ongoing community transmission. By fitting a stochastic model to data on 1512 cases, including these clusters, we show that the etiological agent of SARS is moderately transmissible. Excluding SSEs, we estimate that 2.7 secondary infections were generated per case on average at the start of the epidemic, with a substantial contribution from hospital transmission. Transmission rates fell during the epidemic, primarily as a result of reductions in population contact rates and improved hospital infection control, but also because of more rapid hospital attendance by symptomatic individuals. As a result, the epidemic is now in decline, although continued vigilance is necessary for this to be maintained. Restrictions on longer range population movement are shown to be a potentially useful additional control measure in some contexts. We estimate that most currently infected persons are now hospitalized, which highlights the importance of control of nosocomial transmission.

Background: Health authorities worldwide, especially in the Asia Pacific region, are seeking effective public-health interventions in the continuing epidemic of severe acute respiratory syndrome (SARS). We assessed the epidemiology of SARS in Hong Kong., Methods: We included 1425 cases reported up to April 28, 2003. An integrated database was constructed from several sources containing information on epidemiological, demographic, and clinical variables. We estimated the key epidemiological distributions: infection to onset, onset to admission, admission to death, and admission to discharge. We measured associations between the estimated case fatality rate and patients' age and the time from onset to admission., Findings: After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6.4 days (95% CI 5.2-7.7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13.2% (9.8-16.8) for patients younger than 60 years and 43.3% (35.2-52.4) for patients aged 60 years or older assuming a parametric gamma distribution. A non-parametric method yielded estimates of 6.8% (4.0-9.6) and 55.0% (45.3-64.7), respectively. Case clusters have played an important part in the course of the epidemic., Interpretation: Patients' age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine.