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Objectives
1) To estimate the age and gender distribution
of serologically confirmed SARS cases in the Beijing population,
2) To estimate the proportion of non or pauci-symptomatic
infections among household members of SARS cases,
3) To study the household attack rate of SARS,
and risk factors for infection among household contacts of serologically
confirmed SARS cases,
4) To study the sensitivity and the specificity
of the WHO case definition of probable cases using serology as the
gold standard,
5) To study genetic factors of host susceptibility.
Description of work
During the 2003 SARS epidemic in Beijing, a total
of 2521 probable and 739 suspect SARS cases were reported All households
of Beijing probable SARS cases will be visited for this study (field
work planned for the summer/fall 2004). After informed consent is
obtained, blood will be drawn for serological testing. For exposure
and clinical symptoms assessment, data from questionnaire administered
during the epidemic episode (March to June 2003) will be used. A
household will be defined as the residency of a SARS case. This
definition means that a household could consist of only the SARS
case. All individuals living in the household of a SARS case are
defined as household members. A probable index case will be defined
as the first individual from a household classified as a probable
SARS case (WHO criteria). A probable secondary case will be defined
as one individual diagnosed as probable SARS case (WHO criteria)
living in a household where an index case has been previously identified.
In addition, familial households will be specifically identified
in this study to prepare the genetic factor of host susceptibility
study. Familial households will be defined as individuals living
together in one residency during the exposition period of the index
case and having biological links (nuclear family= father + mother
+ children whatever the child age). Sera and Buffy Coat / PBMC will
be stored at -80°C. A confirmed SARS case is defined as positive
results to 2 serological tests. When discordant results will be
reported, a western-blot method will be performed.
Different statistical analysis methods will be
used to respond to the objectives:
1) Age and gender distribution of SARS cases
will be estimated using serologically confirmed data.
2) The proportion of non or pauci-symptomatic infections will
be estimated as the proportion of individuals who had positive
serology among subjects who were neither suspect nor probable
SARS cases in 2003.
3) Household attack rate. For this analysis, households consisting
of the index patient only will be excluded. The household attack
rate will be estimated as the number of households with at least
one secondary case divided by the total number of index patient’s
households. The household member attack rate will be defined as
the total number of secondary cases divided by the total number
of household members (excluding the index patient). Risk factors
for infection will be analysed using the epidemiological data
collected during the contact tracing of cases during the 2003
epidemic and during the 2004 study visit. Exposures of secondary
cases to the index case will be compared to those of non-infected
household members to identify risk factors for infection. Multivariate
analysis will be carried out to identify independent risk factors
using logistic regression analysis.
4) The sensitivity and specificity of the WHO case definition
will be estimated using serologically confirmed cases as the gold
standard. The sensitivity will be the proportion of probable cases
among serologically confirmed cases. The specificity will be the
proportion of non-probable cases among serologically negative
cases.
Deliverables
D33 Estimate of the age and gender
distribution of serologically confirmed SARS cases in the Beijing
population
D34 Spectrum of clinical manifestations
in serologically-confirmed SARS CoV infections including children
D35 Sensitivity and specificity
of the WHO case definition.
D36 Family based association study
to investigate the role of common polymorphisms in susceptibility
to SARS disease
Milestones and expected result
M0-M10: Prepare and performed
field work
M10-M24: statistical analysis
on risk factors and sensitivity/specificity of the WHO case definition
M10-M24: analysis for the identification
of genetic factors (family based association study)
M18-M30: synthesis of all the
WP results
M24-M36: Preparation of manuscripts
and report
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