Host Factors in Invasive and Recurrent Staphylococcus Aureus Infection
| Status: | Terminated |
|---|---|
| Conditions: | Infectious Disease, Hospital |
| Therapuetic Areas: | Immunology / Infectious Diseases, Other |
| Healthy: | No |
| Age Range: | 2 - Any |
| Updated: | 4/5/2019 |
| Start Date: | May 28, 2009 |
| End Date: | September 17, 2014 |
The incidence of community-associated (CA) staphylococcal infections, especially those caused
by methicillin-resistant Staphylococcus aureus (MRSA), has increased dramatically in recent
years. Although the majority of these infections are limited to the skin and soft tissue and
thus not life threatening, the number of invasive cases in otherwise healthy individuals is
increasing and some are fatal. As a first step toward understanding pathogenesis, there has
been significant focus on elucidating the key CA-MRSA virulence factors. The relative
significance of these factors is still being delineated. By comparison, there has been little
focus on host factors associated with these invasive infections. In this protocol, we will
recruit 100 otherwise healthy subjects with invasive staphylococcal infection, 50 otherwise
healthy subjects with recurrent staphylococcal infections, and obtain samples from 150
unidentified healthy controls from the blood bank to investigate host immunologic factors
predisposing people to staphylococcal infection. Subjects will receive standard of care
treatment for acute or recurrent staphylococcal infections. The primary objective of this
research is to identify host genetic factors that contribute to susceptibility or severity of
community acquired staphylococcal diseases. We will use three experimental approaches to
complete this objective: 1) expression microarray analyses of study population s (subjects
and controls) white cells (neutrophils and peripheral blood mononuclear cells) at rest and
stimulated with staphylococci, 2) evaluation of toll-like receptor (TLR) pathways in the
study population s cells, and 3) evaluation of Th17 cells. The proposed research will address
a key area of staphylococcal pathogenesis for which there is a striking lack of information.
We fully anticipate that the research also will provide critical new information directly
relevant to vaccine, diagnostics, and therapeutics development.
by methicillin-resistant Staphylococcus aureus (MRSA), has increased dramatically in recent
years. Although the majority of these infections are limited to the skin and soft tissue and
thus not life threatening, the number of invasive cases in otherwise healthy individuals is
increasing and some are fatal. As a first step toward understanding pathogenesis, there has
been significant focus on elucidating the key CA-MRSA virulence factors. The relative
significance of these factors is still being delineated. By comparison, there has been little
focus on host factors associated with these invasive infections. In this protocol, we will
recruit 100 otherwise healthy subjects with invasive staphylococcal infection, 50 otherwise
healthy subjects with recurrent staphylococcal infections, and obtain samples from 150
unidentified healthy controls from the blood bank to investigate host immunologic factors
predisposing people to staphylococcal infection. Subjects will receive standard of care
treatment for acute or recurrent staphylococcal infections. The primary objective of this
research is to identify host genetic factors that contribute to susceptibility or severity of
community acquired staphylococcal diseases. We will use three experimental approaches to
complete this objective: 1) expression microarray analyses of study population s (subjects
and controls) white cells (neutrophils and peripheral blood mononuclear cells) at rest and
stimulated with staphylococci, 2) evaluation of toll-like receptor (TLR) pathways in the
study population s cells, and 3) evaluation of Th17 cells. The proposed research will address
a key area of staphylococcal pathogenesis for which there is a striking lack of information.
We fully anticipate that the research also will provide critical new information directly
relevant to vaccine, diagnostics, and therapeutics development.
The incidence of community-associated (CA) staphylococcal infections, especially those caused
by methicillin-resistant Staphylococcus aureus (MRSA), has increased dramatically in recent
years. Although the majority of these infections are limited to the skin and soft tissue and
thus not life threatening, the number of invasive cases in otherwise healthy individuals is
increasing and some are fatal. As a first step toward understanding pathogenesis, there has
been significant focus on elucidating the key CA-MRSA virulence factors. The relative
significance of these factors is still being delineated. By comparison, there has been little
focus on host factors associated with these invasive infections. In this protocol, we will
recruit 100 otherwise healthy subjects with invasive staphylococcal infection, 50 otherwise
healthy subjects with recurrent staphylococcal infections, and obtain samples from 150
unidentified healthy controls from the blood bank to investigate host immunologic factors
predisposing people to staphylococcal infection. Subjects will receive standard of care
treatment for acute or recurrent staphylococcal infections. The primary objective of this
research is to identify host genetic factors that contribute to susceptibility or severity of
community acquired staphylococcal diseases. We will use three experimental approaches to
complete this objective: 1) expression microarray analyses of study population s (subjects
and controls) white cells (neutrophils and peripheral blood mononuclear cells) at rest and
stimulated with staphylococci, 2) evaluation of toll-like receptor (TLR) pathways in the
study population s cells, and 3) evaluation of Th17 cells. The proposed research will address
a key area of staphylococcal pathogenesis for which there is a striking lack of information.
We fully anticipate that the research also will provide critical new information directly
relevant to vaccine, diagnostics, and therapeutics development.
by methicillin-resistant Staphylococcus aureus (MRSA), has increased dramatically in recent
years. Although the majority of these infections are limited to the skin and soft tissue and
thus not life threatening, the number of invasive cases in otherwise healthy individuals is
increasing and some are fatal. As a first step toward understanding pathogenesis, there has
been significant focus on elucidating the key CA-MRSA virulence factors. The relative
significance of these factors is still being delineated. By comparison, there has been little
focus on host factors associated with these invasive infections. In this protocol, we will
recruit 100 otherwise healthy subjects with invasive staphylococcal infection, 50 otherwise
healthy subjects with recurrent staphylococcal infections, and obtain samples from 150
unidentified healthy controls from the blood bank to investigate host immunologic factors
predisposing people to staphylococcal infection. Subjects will receive standard of care
treatment for acute or recurrent staphylococcal infections. The primary objective of this
research is to identify host genetic factors that contribute to susceptibility or severity of
community acquired staphylococcal diseases. We will use three experimental approaches to
complete this objective: 1) expression microarray analyses of study population s (subjects
and controls) white cells (neutrophils and peripheral blood mononuclear cells) at rest and
stimulated with staphylococci, 2) evaluation of toll-like receptor (TLR) pathways in the
study population s cells, and 3) evaluation of Th17 cells. The proposed research will address
a key area of staphylococcal pathogenesis for which there is a striking lack of information.
We fully anticipate that the research also will provide critical new information directly
relevant to vaccine, diagnostics, and therapeutics development.
- INCLUSION CRITERIA:
1. Age greater than or equal to 2 years.
2. Current or past S. aureus infection, either invasive or soft tissue.
3. Willingness to allow storage of blood and tissue samples for future use.
4. Subjects will be eligible without regard to race, gender, or ethnic origin.
EXCLUSION CRITERIA:
1. Infection with known HIV-1, HIV-2 as demonstrated by ELISA and Western blot or viral
load testing.
2. Evidence of intravenous drug abuse in the year prior to the first (or only) S. aureus
infection.
3. Previously known immunodeficiency syndrome.
4. Evidence of active malignancy.
5. Any condition that the investigators judge would compromise the results of the study.
6. Diabetes mellitus.
7. Evidence of healthcare-associated infection invasive device, history of surgery with
implantation of artificial device in previous 12 months, history of surgery without
device implantation in previous 12 month, or dialysis, hospitalization, or residence
in long-term care facility in previous 12 months. An exception to these exclusion
criteria is hospitalization for the acute S. aureus infection at the time of
enrollment.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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