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SARS molecular epidemiology: a Chinese fairy tale of controlling an emerging zoonotic disease in the genomics era

Identifieur interne : 000C08 ( Pmc/Curation ); précédent : 000C07; suivant : 000C09

SARS molecular epidemiology: a Chinese fairy tale of controlling an emerging zoonotic disease in the genomics era

Auteurs : Guo-Ping Zhao

Source :

RBID : PMC:2435571

Abstract

Severe acute respiratory syndrome (SARS) was the first natural disaster that challenged the Chinese people at the beginning of the twenty-first century. It was caused by a novel animal coronavirus, never recognized or characterized before. This SARS coronavirus (SARS-CoV) exploited opportunities provided by ‘wet markets’ in southern China to adapt to the palm civet and human. Under the positive selection pressure of human host, certain mutated lineages of the virus became readily transmissible between humans and thus caused the epidemic of 2002–2003. This review will provide first-hand information, particularly from Guangdong, China, about the initial epidemiology, the identification of the aetiological agent of the disease, the molecular evolution study of the virus, the finding of SARS-like CoV in horseshoe bats and the mechanistic analysis for the cross-host tropism transition. The substantial scientific contributions made by the Chinese scientists towards understanding the virus and the disease will be emphasized. Along with the description of the scientific discoveries and analyses, the significant impact of these researches upon the public health measurement or regulations will be highlighted. It is aimed to appreciate the concerted and coordinated global response that controlled SARS within a short period of time as well as the research strategy and methodology developed along with this process, which can be applied in response to other public health challenges, particularly the future emerging/re-merging infectious diseases.


Url:
DOI: 10.1098/rstb.2007.2034
PubMed: 17327210
PubMed Central: 2435571

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<title xml:lang="en">SARS molecular epidemiology: a Chinese fairy tale of controlling an emerging zoonotic disease in the genomics era</title>
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<title level="j">Philosophical Transactions of the Royal Society B: Biological Sciences</title>
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<p>Severe acute respiratory syndrome (SARS) was the first natural disaster that challenged the Chinese people at the beginning of the twenty-first century. It was caused by a novel animal coronavirus, never recognized or characterized before. This SARS coronavirus (SARS-CoV) exploited opportunities provided by ‘wet markets’ in southern China to adapt to the palm civet and human. Under the positive selection pressure of human host, certain mutated lineages of the virus became readily transmissible between humans and thus caused the epidemic of 2002–2003. This review will provide first-hand information, particularly from Guangdong, China, about the initial epidemiology, the identification of the aetiological agent of the disease, the molecular evolution study of the virus, the finding of SARS-like CoV in horseshoe bats and the mechanistic analysis for the cross-host tropism transition. The substantial scientific contributions made by the Chinese scientists towards understanding the virus and the disease will be emphasized. Along with the description of the scientific discoveries and analyses, the significant impact of these researches upon the public health measurement or regulations will be highlighted. It is aimed to appreciate the concerted and coordinated global response that controlled SARS within a short period of time as well as the research strategy and methodology developed along with this process, which can be applied in response to other public health challenges, particularly the future emerging/re-merging infectious diseases.</p>
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<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Philos Trans R Soc Lond B Biol Sci</journal-id>
<journal-id journal-id-type="publisher-id">RSTB</journal-id>
<journal-title>Philosophical Transactions of the Royal Society B: Biological Sciences</journal-title>
<issn pub-type="ppub">0962-8436</issn>
<issn pub-type="epub">1471-2970</issn>
<publisher>
<publisher-name>The Royal Society</publisher-name>
<publisher-loc>London</publisher-loc>
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<article-id pub-id-type="pmid">17327210</article-id>
<article-id pub-id-type="pmc">2435571</article-id>
<article-id pub-id-type="publisher-id">rstb20072034</article-id>
<article-id pub-id-type="doi">10.1098/rstb.2007.2034</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>SARS molecular epidemiology: a Chinese fairy tale of controlling an emerging zoonotic disease in the genomics era</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Zhao</surname>
<given-names>Guo-ping</given-names>
</name>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff>
<institution>Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai</institution>
<addr-line>Building 1, 250 Bi-Bo Road, Zhangjiang HiTech Park, Pudong, Shanghai 201203, People's Republic of China</addr-line>
</aff>
<author-notes>
<corresp id="cor1">
<label>*</label>
(
<email>gpzhao@sibs.ac.cn</email>
)</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>27</day>
<month>2</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="ppub">
<day>29</day>
<month>6</month>
<year>2007</year>
</pub-date>
<volume>362</volume>
<issue>1482</issue>
<fpage>1063</fpage>
<lpage>1081</lpage>
<permissions>
<copyright-statement>© 2007 The Royal Society</copyright-statement>
<copyright-year>2007</copyright-year>
</permissions>
<abstract xml:lang="EN">
<p>Severe acute respiratory syndrome (SARS) was the first natural disaster that challenged the Chinese people at the beginning of the twenty-first century. It was caused by a novel animal coronavirus, never recognized or characterized before. This SARS coronavirus (SARS-CoV) exploited opportunities provided by ‘wet markets’ in southern China to adapt to the palm civet and human. Under the positive selection pressure of human host, certain mutated lineages of the virus became readily transmissible between humans and thus caused the epidemic of 2002–2003. This review will provide first-hand information, particularly from Guangdong, China, about the initial epidemiology, the identification of the aetiological agent of the disease, the molecular evolution study of the virus, the finding of SARS-like CoV in horseshoe bats and the mechanistic analysis for the cross-host tropism transition. The substantial scientific contributions made by the Chinese scientists towards understanding the virus and the disease will be emphasized. Along with the description of the scientific discoveries and analyses, the significant impact of these researches upon the public health measurement or regulations will be highlighted. It is aimed to appreciate the concerted and coordinated global response that controlled SARS within a short period of time as well as the research strategy and methodology developed along with this process, which can be applied in response to other public health challenges, particularly the future emerging/re-merging infectious diseases.</p>
</abstract>
<kwd-group>
<kwd>severe acute respiratory syndrome</kwd>
<kwd>SARS coronavirus</kwd>
<kwd>epidemiology</kwd>
<kwd>evolution</kwd>
<kwd>zoonotic disease</kwd>
<kwd>genomics</kwd>
</kwd-group>
</article-meta>
</front>
<floats-wrap>
<fig id="fig1" position="float">
<label>Figure 1</label>
<caption>
<p>The triphasic SARS epidemic in Guangdong Province, China. Shown are the number of daily documented SARS cases reported from individual cities of the Guangdong Province, China, up to February 2003. The early, middle and late phases of the epidemic are defined in the text. The map shows the geographical distribution of cases belonging to the early phase by administrative districts of Guangdong Province. Original epidemiological data were collected and analysed by the Guangdong Center for Disease Control and Prevention. The cases reported from the cities of Heyuan and Shenzhen were combined and treated as Shenzhen cases, because the Heyuan index case was infected in Shenzhen, and after this nosocomial infection no additional infections were reported in Heyuan. The order of the cities is arranged from top to bottom based on the disease onset date of their respective index cases, starting from the earliest to the latest dates of onset. Adapted from
<xref ref-type="bibr" rid="bib13">Chinese (2004)</xref>
.</p>
</caption>
<graphic xlink:href="rstb20072034f01"></graphic>
</fig>
<fig id="fig2" position="float">
<label>Figure 2</label>
<caption>
<p>The time distribution of the onsets of SARS cases as well as the implementation dates for the corresponding public health control measures in Guangdong Province during the 2002–2003 epidemic.</p>
</caption>
<graphic xlink:href="rstb20072034f02"></graphic>
</fig>
<fig id="fig3" position="float">
<label>Figure 3</label>
<caption>
<p>Chest radiographs (the middle panel) of a SARS patient obtained with clinical presentations (the upper panel) during treatment (the lower panel) (
<xref ref-type="bibr" rid="bib106">Zhong & Zeng 2003</xref>
). Indices reflecting the patient's respiratory function status: oxygenation index (OI), arterial oxygen pressure (PO
<sub>2</sub>
), oxygen saturation (SpO
<sub>2</sub>
), fraction of inspired oxygen (FiO
<sub>2</sub>
), respiratory rate (RR). Indices reflecting mechanical ventilation mode: pressure regulated volume control ventilation (PRVC), positive end-expiratory pressure (PEEP).</p>
</caption>
<graphic xlink:href="rstb20072034f03"></graphic>
</fig>
<fig id="fig4" position="float">
<label>Figure 4</label>
<caption>
<p>The profile of N protein detection in blood and antibody response to SARS-CoV from the onset of symptoms to the convalescent phase (
<xref ref-type="bibr" rid="bib11">Che
<italic>et al.</italic>
2004</xref>
).</p>
</caption>
<graphic xlink:href="rstb20072034f04"></graphic>
</fig>
<fig id="fig5" position="float">
<label>Figure 5</label>
<caption>
<p>Strategic design for molecular epidemiology study of SARS. The unrooted phylogenetic tree for SARS-CoV isolates available by April 2003 (the left panel) and the corresponding SARS transmission epidemiology information (the middle panel) were adapted from
<xref ref-type="bibr" rid="bib80">Ruan
<italic>et al.</italic>
(2003)</xref>
. This slide was presented to the CDCP Guangdong Province on 20 May 2003 for the first time.</p>
</caption>
<graphic xlink:href="rstb20072034f05"></graphic>
</fig>
<fig id="fig6" position="float">
<label>Figure 6</label>
<caption>
<p>GZ02-rooted neighbour-joining phylogenetic tree for SARS-CoV genomic sequences of the 2002–2003 epidemic. Colours of strain designations correspond to the epidemiological phases. In general, three colours are used for the three epidemic phases: green for the early, red for the middle and blue for the late. In detail, purple represents strains of the middle phase with a characteristic SNP switch reflecting the genotypic transition of SARS-CoV between the middle and late phases (from the
<bold>G</bold>
:A:
<bold>C</bold>
:T:
<bold>C</bold>
[red] for majority isolates of the middle phase to the
<bold>T</bold>
:G:
<bold>T</bold>
:T:
<bold>T</bold>
[blue] for majority isolates connected with the Hotel M outbreak,
<italic>via</italic>
this rare
<bold>G</bold>
:G:
<bold>C</bold>
:T:
<bold>C</bold>
[purple] isolate of the HZS-2 Hospital); dark blue represents the strains of a cluster of very late cases in Hong Kong with significant deletions in the orf8 region of the SARS-CoV genome. The map distance between individual sequences represents the extent of genotypic difference. This figure indicates the strong correlation between the molecular phylogeny of the viral strains and the epidemiological phases of their corresponding transmission paths. Adapted from
<xref ref-type="bibr" rid="bib13">Chinese (2004)</xref>
.</p>
</caption>
<graphic xlink:href="rstb20072034f06"></graphic>
</fig>
<fig id="fig7" position="float">
<label>Figure 7</label>
<caption>
<p>A rooted phylogenetic tree for SARS-CoV based on MRCA estimations. The virus isolates are from the palm civets of the 2002–2003 epidemic (PC03) and the 2003–2004 outbreak (PC04), as well as from human patients of the early phase of the 2002–2003 epidemic (HP03E) and the 2003–2004 outbreak (HP04). The branch length is proportional to the time-interval. Adapted from
<xref ref-type="bibr" rid="bib84">Song
<italic>et al.</italic>
(2005)</xref>
.</p>
</caption>
<graphic xlink:href="rstb20072034f07"></graphic>
</fig>
<fig id="fig8" position="float">
<label>Figure 8</label>
<caption>
<p>The binding affinity curves of selected mutants of human SARS-CoV S proteins (BJ01) to human ACE2-expressed Hela cells (Hela F5). These mutated S fragments (13-510) were constructed based on the S gene of strain BJ01. They were fused with human Fc. Hela cells expressing human ACE2 were incubated with 100 nM S fragments and the binding affinity of S proteins was detected through FACS analysis using FITC-conjugated anti-human IgG-Fc antibody. The mean fluorescence intensity (MFI) in the
<italic>y</italic>
-axis was determined by a series of FACS analysis in which Hela F5 cells were incubated with serially diluted S fragments from 1 μM to 2 nM. Adapted from
<xref ref-type="bibr" rid="bib73">Qu
<italic>et al.</italic>
(2005)</xref>
.</p>
</caption>
<graphic xlink:href="rstb20072034f08"></graphic>
</fig>
<table-wrap id="tbl1" position="float">
<label>Table 1</label>
<caption>
<p>SARS case comparison of the early-phase patients versus the Super-Spreader Event index patient of the middle phase from the HZS-2 Hospital. (
<italic>R</italic>
, relatives and friends infected;
<italic>H</italic>
, hospital infection;
<italic>T</italic>
, total number of people infected and
<italic>D</italic>
, number of deaths.)</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="bottom" rowspan="3" align="left" colspan="1">cases by cities</th>
<th valign="bottom" align="left" rowspan="1" colspan="1">onset date</th>
<th valign="bottom" colspan="4" align="left" rowspan="1">no. of secondary infections</th>
<th valign="bottom" colspan="4" align="left" rowspan="1">no. of tertiary infections</th>
</tr>
<tr>
<th valign="bottom" rowspan="1" colspan="1"></th>
<th valign="bottom" colspan="4" rowspan="1">
<hr></hr>
</th>
<th valign="bottom" colspan="4" rowspan="1">
<hr></hr>
</th>
</tr>
<tr>
<th valign="bottom" align="left" rowspan="1" colspan="1">dd mm yy</th>
<th valign="bottom" rowspan="1" colspan="1">
<italic>R</italic>
</th>
<th valign="bottom" rowspan="1" colspan="1">
<italic>H</italic>
</th>
<th valign="bottom" rowspan="1" colspan="1">
<italic>T</italic>
</th>
<th valign="bottom" rowspan="1" colspan="1">
<italic>D</italic>
<xref ref-type="table-fn" rid="tblfn1">a</xref>
</th>
<th valign="bottom" rowspan="1" colspan="1">
<italic>R</italic>
</th>
<th valign="bottom" rowspan="1" colspan="1">
<italic>H</italic>
</th>
<th valign="bottom" rowspan="1" colspan="1">
<italic>T</italic>
</th>
<th valign="bottom" rowspan="1" colspan="1">
<italic>D</italic>
</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="1" colspan="1">Foshan index</td>
<td align="left" rowspan="1" colspan="1">16 Nov 2002</td>
<td align="char" char="." rowspan="1" colspan="1">2</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">2</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">2</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">2</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">Heyuan index</td>
<td align="left" rowspan="1" colspan="1">10 Dec 2002</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">8</td>
<td align="char" char="." rowspan="1" colspan="1">8</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">Jiangmen index</td>
<td align="left" rowspan="1" colspan="1">21 Dec 2002</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">Zhongshan index</td>
<td align="left" rowspan="1" colspan="1">26 Dec 2002</td>
<td align="char" char="." rowspan="1" colspan="1">2</td>
<td rowspan="1" colspan="1">6
<xref ref-type="table-fn" rid="tblfn2">b</xref>
</td>
<td rowspan="1" colspan="1">8
<xref ref-type="table-fn" rid="tblfn2">b</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1">3</td>
<td align="char" char="." rowspan="1" colspan="1">4</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">Zhongshan 2nd</td>
<td align="left" rowspan="1" colspan="1">1 Jan 2003</td>
<td align="char" char="." rowspan="1" colspan="1">2</td>
<td rowspan="1" colspan="1">6
<xref ref-type="table-fn" rid="tblfn2">b</xref>
</td>
<td rowspan="1" colspan="1">8
<xref ref-type="table-fn" rid="tblfn2">b</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1"></td>
</tr>
<tr>
<td rowspan="1" colspan="1">Shunde index</td>
<td align="left" rowspan="1" colspan="1">2 Jan 2003</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1">2</td>
<td align="char" char="." rowspan="1" colspan="1">3</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">Shunde SGQ</td>
<td align="left" rowspan="1" colspan="1">8 Jan 2003</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td rowspan="1" colspan="1">5
<xref ref-type="table-fn" rid="tblfn3">c</xref>
</td>
<td rowspan="1" colspan="1">6
<xref ref-type="table-fn" rid="tblfn3">c</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1"></td>
</tr>
<tr>
<td rowspan="1" colspan="1">Guangzhou index</td>
<td align="left" rowspan="1" colspan="1">2 Jan 2003</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">7</td>
<td align="char" char="." rowspan="1" colspan="1">7</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0.5
<xref ref-type="table-fn" rid="tblfn4">d</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1">0.5
<xref ref-type="table-fn" rid="tblfn4">d</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">Shenzhen index</td>
<td align="left" rowspan="1" colspan="1">15 Jan 2003</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">Zhaoqing index</td>
<td align="left" rowspan="1" colspan="1">17 Jan 2003</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
<td align="char" char="." rowspan="1" colspan="1">2</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">Dongguan index</td>
<td align="left" rowspan="1" colspan="1">10 Mar 2003</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">sum (early phase): 11</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1">10</td>
<td align="char" char="." rowspan="1" colspan="1">35</td>
<td align="char" char="." rowspan="1" colspan="1">45</td>
<td align="char" char="." rowspan="1" colspan="1">3</td>
<td align="char" char="." rowspan="1" colspan="1">3</td>
<td align="char" char="." rowspan="1" colspan="1">3.5</td>
<td align="char" char="." rowspan="1" colspan="1">6.5</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td rowspan="1" colspan="1">SQS (Shunde to Guangzhou)</td>
<td align="left" rowspan="1" colspan="1">18 Jan 2003</td>
<td align="char" char="." rowspan="1" colspan="1">0</td>
<td rowspan="1" colspan="1">7
<xref ref-type="table-fn" rid="tblfn5">e</xref>
</td>
<td rowspan="1" colspan="1">7
<xref ref-type="table-fn" rid="tblfn5">e</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">5
<xref ref-type="table-fn" rid="tblfn5">e</xref>
</td>
<td rowspan="1" colspan="1">5
<xref ref-type="table-fn" rid="tblfn5">e</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1"></td>
</tr>
<tr>
<td rowspan="1" colspan="1">ZZF (Guangzhou)</td>
<td align="left" rowspan="1" colspan="1">22 Jan 2003</td>
<td align="char" char="." rowspan="1" colspan="1">23</td>
<td rowspan="1" colspan="1">55
<xref ref-type="table-fn" rid="tblfn5">e</xref>
</td>
<td rowspan="1" colspan="1">78
<xref ref-type="table-fn" rid="tblfn5">e</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1">4</td>
<td align="char" char="." rowspan="1" colspan="1">5</td>
<td rowspan="1" colspan="1">35
<xref ref-type="table-fn" rid="tblfn5">e</xref>
</td>
<td rowspan="1" colspan="1">40
<xref ref-type="table-fn" rid="tblfn5">e</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
</tr>
<tr>
<td rowspan="1" colspan="1">sum (Hospital HZS-2): 2</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="char" char="." rowspan="1" colspan="1">23</td>
<td align="char" char="." rowspan="1" colspan="1">62</td>
<td align="char" char="." rowspan="1" colspan="1">85</td>
<td align="char" char="." rowspan="1" colspan="1">4</td>
<td align="char" char="." rowspan="1" colspan="1">5</td>
<td align="char" char="." rowspan="1" colspan="1">44</td>
<td align="char" char="." rowspan="1" colspan="1">45</td>
<td align="char" char="." rowspan="1" colspan="1">1</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tblfn1">
<label>a</label>
<p>The hospital infection of the Zhongshan City was caused by both the index case and the second case. Therefore, secondary infections in the hospital are shown as the average contribution of these two patients.</p>
</fn>
</table-wrap-foot>
<table-wrap-foot>
<fn id="tblfn2">
<label>b</label>
<p>The hospital infection of Shunde City was believed to be contributed by SGQ and another patient. Therefore, the secondary infections in the hospital are shown as the average contribution of these two patients, except for one member of the medical staff who was known to have had only direct contact with SGQ. SGQ also probably infected two people in the HZS-2 Hospital of Guangzhou.</p>
</fn>
</table-wrap-foot>
<table-wrap-foot>
<fn id="tblfn3">
<label>c</label>
<p>The tertiary infection of the Guangzhou index case involved only one person, but was likely to have two hospital infection origins. Therefore, only the average number (0.5) was used as the contribution made by the secondary cases.</p>
</fn>
</table-wrap-foot>
<table-wrap-foot>
<fn id="tblfn4">
<label>d</label>
<p>Because SQS and ZZF were together in Hospital HZS-2 for a few days, it is difficult to clearly identify the transmission path. Therefore, estimates were made by the staff of HZS-2 Hospital according to the contact history and the onset dates of the patients for the secondary, tertiary and quaternary infections. The secondary infection by ZZF includes numbers of Hospital HZS-3 and Hospital GZS-8. The same principle was applied for the tertiary and the quaternary infections. It was estimated that the quaternary infections originated from ZZF included one friend and 13 hospital-infected patients.</p>
</fn>
</table-wrap-foot>
<table-wrap-foot>
<fn id="tblfn5">
<label>e</label>
<p>The index patient is included.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-wrap>
</pmc>
</record>

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