V. APPLICATION FORM (Attach to each copy of the proposal.)

INVESTIGATOR'S STATEMENT OF ASSURANCE

The attached investigation involves the use of human subjects. I understand the University policy concerning the use of human subjects and I agree:

1.  To obtain informed consent of subjects who are to participate in this project;

2.  To report to the Human Subjects in Research Committee any unanticipated effects on subjects which become apparent during the course, or as a result, of experimentation and the actions taken as the a result;

3.  To cooperate with members of a committee charged with the continuing review of the project;

4.  To obtain prior approval from the Committee before altering or amending the scope of the project or implementing changes in the approved consent form; and

5. To maintain documentation of consent forms and progress reports as requires by institutional policy.

_________________________________________

PRINCIPAL INVESTIGATOR'S SIGNATURE

Fill in all blanks.

Does the subject group include healthy volunteers? ___yes _x__no

Does the subject group include ill persons? __x_yes ___no

Are subject groups excluded for medical reasons? ___yes __x_no

Are there vulnerable subject groups? ___yes _x__no

If yes, is the exclusion criteria for the study specified? ___yes ___no

Are any subjects under the age of 18? _x__yes ___no

Are any subjects under the age of 12? _x__yes ___no

Are any subjects over the age of 70? _x__yes ___no

Scott Wright_________________________________ Clinical Lab Science

PRINCIPAL INVESTIGATOR'S NAME (faculty)        DEPARTMENT

Cassie Whittier, Reza Panahi, Hayden Behling              Clinical Lab Science

STUDENT RESEARCHER'S NAME                         DEPARTMENT

Weber State University 3905                                     Ogden, Utah 84408

MAILING ADDRESS/MAIL CODE                        CITY, STATE, ZIP 

_________________________________________ _________________

PRINCIPAL INVESTIGATOR'S SIGNATURE          TELEPHONE

_________________________________________ _________________

DEPARTMENT CHAIR'S SIGNATURE                 TELEPHONE

 ___________________________________     DATE

 A. APPLICATION FORM

The application form must be filled out completely so that committee members may have a clear understanding of the nature and human subject implications of the research proposal. A summary paragraph for each section is sufficient. A statement referring to attached materials is not sufficient and will not be accepted. Applications submitted with incomplete forms will be returned without consideration of the proposal.

1. TITLE

Virulence Factors in Hospital and Community Acquired Staphylococcus aureus

2. DESCRIPTION OF THE STUDY

This study will be done using Staphylococcus aureus samples that have been isolated in the LDS Hospital microbiology lab over the past several years.  No contact will be made with the patient from whom the organism was isolated. Genetic testing will be conducted on these samples.

3. DURATION OF THE STUDY

The duration of the study will be from November 2004 to April 2005.

4. MULTICENTER STUDY

Yes, it will be conducted by Weber State Clinical Laboratory Science department in conjunction with the Infectious Disease, Microbiology, and Molecular Pathology departments at LDS Hospital.  All of the laboratory work will be conducted in the Microbiology and Molecular Pathology labs at LDS Hospital.  No organisms will be brought into the Microbiology lab at WSU.

5. NUMBER OF SUBJECTS

360 isolates from past patients will be tested.

6. HEALTH STATUS OF THE SUBJECTS

All isolates come from patients that have a staphylococcus infection and have sought treatment from a medical professional. 

7. SUBJECT GROUPS EXCLUDED

Only isolates previously identified as Staphylococcus aureus will be used in the study.

8. AGES OF SUBJECTS

The study will include isolates from patients of all ages.

9. DESIGN OF THE STUDY

The design of the study is a Case Control Study.

10. RISKS TO SUBJECTS

There is no risk to patients from whom the samples were obtained, because samples have already been obtained and we have no contact with the actual patient.

ANY MODERATE OR HIGH RISK STUDY MUST GO THROUGH A SEPARATE REVIEW PROCEDURE WHICH INCLUDES THE APPROPRIATE ADMINISTRATIVE OFFICER AND THE UNIVERSITY ATTORNEY.

11. BENEFITS TO SUBJECTS AND OTHERS

The study will lead to an increased understanding of Antibiotic resistance and virulence in Staphylococci and may lead to better treatment methods.

12. COSTS TO BE BORNE BY SUBJECTS

There will be no cost to subjects.

13. IS CONFIDENTIALITY ASSURED

Patient names have already been removed from samples and replaced by an accession number. Students working on this project will not have access to actual patient information, however, the employees of LDS Hospital will have access.  (Please note that the students and LDS Hospital stall working on the project will receive IRB training through the Hospital.)

14. CONTRACT OR GRANT NUMBER

We have been approved for funding through the University Undergraduate Research Committee (October 25, 2004 – we have not received a grant number at this time) and additional funding will be supplied by LDS Hospital.

15. NAME OF PRINCIPAL INVESTIGATOR AND DEPARTMENT

The investigator is Scott Wright from the Clinical Laboratory Sciences Department at WSU.

B. DESCRIPTION OF THE STUDY

Project description:

Within the last five years, there has been an increase in community acquired Methicillin Resistant Staphylococcus aureus (MRSA). Before this increase, MRSA was predominantly seen in hospital acquired infections (infections acquired after seventy-two hours of hospitalization) and very rarely in healthy individuals in the community (Etienne). However, more recently there have been cases of MRSA showing up in young healthy individuals worldwide. These infections have shown to be very invasive and often lead to the death of the individual. Diagnosis of some of these patients revealed that the cause of death was an invasive infection known as Staphylococcal Necrotizing Pneumonia. The invasiveness of the community acquired MRSA has been linked to a gene known as the Panton-Valentine Leukocidin gene which codes for the production of a toxin known as Panton-Valentine Leukocidin (PVL) (Vandenesch). This increase in virulence of Staphylococcus aureus poses additional health-risks not only to immuno-compromised patients, but also to the general public. These types of infections result in longer hospitalization and increased healthcare costs (Pombo).

For the past several years, LDS hospital has been saving Staphylococcus aureus isolates for use in conducting research to study the prevalence of the PVL and other virulence genes in the intermountain area. Susceptibility panels done on these samples will also show the relationship of virulence factors and antibiotic susceptibility.

Comparison of susceptibility patterns, the prevalence of three virulence genes, and clinical outcomes of infections caused by hospital acquired MRSA (HA-MRSA), community acquired MRSA (CA-MRSA), and Methicillin Susceptible Staphylococcus aureus (MSSA) will show what role the presence of these genes play in the severity of these infections. 

This project will be carried out independently by the students who will report back to the faculty mentor. The LDS Hospital Infectious Disease and Molecular Pathology physicians and staff will be overseeing the work that will be done by the students.

All the students involved in doing research in this project are ASCP certified Medical Laboratory Technicians and are currently employed in laboratories at Ogden Regional Medical Center, LDS Hospital, and McKay Dee Hospital. All three have had experience with PCR, susceptibility panels, and clinical microbiology.

The results of this research project will be presented at the Utah Society for Clinical Laboratory Science (USCLS) Spring Seminar in April and at the Weber State University Undergraduate Research Symposium in March. The findings will also be submitted to the National Undergraduate Research Symposium, as well as submission for publication to at least one microbiology or clinical pathology medical journal.

Project methods and timeline:

120 samples each of HA-MRSA, CA-MRSA, and MSSA will be run on the Dade Behring Microscan Walkaway to obtain anabiograms. A PCR assay will be run for each of three virulence genes (including PVL) on each sample. These will be run using the Tagman assay on the ABI. Clinical outcomes, including details on length of hospitalization and cost of patient stay, will be obtained for use in comparing the three strains. 

All of the hands-on lab work will be completed by February 1, 2005.  February through April 2005 will be spent compiling data and composing a paper describing the findings of the study.  Also during this time, a presentation for USCLS Spring Seminar and undergraduate research symposium at Weber State University will be prepared.  Students involved in this project have completed the IRB training, and will submit their project in October for IRB approval.

C. INFORMED CONSENT

No informed consent is needed because we are not dealing with the patients. We are just dealing with saved samples from the last several years that were obtained by physicians.