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      Mathematical Modeling of Severe Acute Respiratory Syndrome Nosocomial Transmission in Japan: The Dynamics of Incident Cases and Prevalent Cases

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          Abstract

          An outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Hong Kong in late February 2003, resulting in 8,096 cumulative cases with 774 deaths. The outbreak was amplified by nosocomial transmission in many hospitals. Using mathematical modeling, we simulated the number of new incident and prevalent cases of SARS after one infected person was admitted to a hospital (index case). The simulation was tested stochastically using the SEIR model based on previously reported Gamma distributions. We estimated the duration time until 10 beds in negative pressure rooms in Chiyoda‐ku, one of the 23 wards in Tokyo, were fully occupied with SARS‐infected patients. We determined the impact of an increasing number of days on the number of prevalent cases until the index case was isolated. The prevalent cases increase exponentially along with the increase of the non‐isolation period of the index case, and all the beds were fully occupied if the index case was not isolated until more than 6 days. However even 2 days non‐isolation period of the index case could fill up all the beds when 16% of secondary infections are transmitted outside the hospital. There is a possibility that an epidemic will occur with the isolation of the index case even at early days if the infection is transmitted outside the hospital. The simulation results revealed that it was important to recognize and isolate SARS patients as early as possible and also to prevent the transmission spreading outside the hospital to control an epidemic.

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          Most cited references14

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          Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

          The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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            A novel coronavirus associated with severe acute respiratory syndrome.

            A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population. A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus. Copyright 2003 Massachusetts Medical Society
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              Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong

              Summary 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% Cl 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 γ 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. Published online May 7, 2003 http://image.thelancet.com/extras/03art4453web.pdf
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                Author and article information

                Journal
                Microbiol Immunol
                Microbiol. Immunol
                10.1111/(ISSN)1348-0421
                MIM
                Microbiology and Immunology
                John Wiley and Sons Inc. (Hoboken )
                0385-5600
                1348-0421
                14 November 2013
                September 2007
                : 51
                : 9 ( doiID: 10.1111/mim.2007.51.issue-9 )
                : 823-832
                Affiliations
                [ 1 ] Hygiene and Preventive Medicine, Okayama University Graduate School of Medicine Dentistry & Pharmaceutical Sciences Okayama Okayama 700‐8558 Japan
                [ 2 ] Department of Human Ecology, Graduate School of Environmental Science Okayama University Okayama Okayama 700‐8530 Japan
                [ 3 ] Department of Viral Oncology, Institute for Virus Research Kyoto University Kyoto Kyoto 606‐8507 Japan
                [ 4 ] Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases National Institutes of Health 9000 Rockville Pike, Bldg4, #304 Bethesda MD 20892 U.S.A.
                [ 5 ] Department of Mental Health University of Tokyo Graduate School of Medicine Bunkyo‐ku Tokyo 113‐0033 Japan
                Author notes
                [*] [* ] Address correspondence to Dr. Hirofumi Ishikawa, Department of Human Ecology, Graduate School of Environmental Science, Okayama University, 3‐1‐1, Tsushima‐naka, Okayama, Okayama 700‐8530, Japan. Fax: +81‐86‐251‐8837. E‐mail: ishikawa@ 123456ems.okayama-u.ac.jp
                Article
                MIM03978
                10.1111/j.1348-0421.2007.tb03978.x
                7168393
                17895599
                f09d58a1-6b66-4674-9303-2bd81143c406
                © owned by Center for Academic Publications Japan (Publisher)

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 08 December 2006
                : 18 June 2007
                : 25 June 2007
                Page count
                Figures: 4, Tables: 0, References: 21, Pages: 10
                Funding
                Funded by: Japan Society for the Promotion of Science
                Award ID: 16540105
                Funded by: Ministry of Health, Labour and Welfare, Japan for “Research for Emerging and Re‐emerging Infections”
                Award ID: H17‐Sinkou‐ippan‐019
                Categories
                Article
                Articles
                Custom metadata
                2.0
                September 2007
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                sars,nosocomial transmission,stochastic model,simulation

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