Pelvic inflammatory disease (PID) is caused by both sexually transmitted pathogens, including Neiserria gonorrhoeae and Chlamydia trachomatis, and anaerobic and facultative pathogens.The broad, long term goal of this project is to use both culture-based methods and nucleic acid-based technology to characterize the microorganisms recovered from the endometrial tissues of women with suspected pelvic inflammatory disease (PlD).These data will provide novel data on the etiology of PID and will inform appropriate antimicrobic therapy for PID. Our preliminary data suggests that many of the microorganisms recovered from the endometrial biopsy samples of women with suspected PID using culture methodology in our laboratory do not fit any known taxonomic group based on phenotypic characteristics. Specifically, we propose to: 1) describe the microorganisms in 700 endometrial tissue samples obtained from 250 women enrolled in the acute PID cohort and 200 women enrolled in the cervicitis cohort (Core B), 2) apply genetic sequencing methodology to characterize the novel organisms recovered from the endometrial samples in order to place these organisms into taxonomic groups and to assess whether some organisms are more strongly associated with histologic evidence of endometritis and the signs and symptoms of acute PID, 3) perform antimicrobic susceptibility testing of all organisms recovered from the endometrial samples in order to assess current antibiotic treatments for women with acute PID are appropriate, 4) assess the presence of novel endometrial pathogens in the lower reproductive tract using vaginal samples obtained from women at enrollment through specific nucleic acid probes developed from nucleic acid of unique organisms recovered from the endometrial samples and 5) perform full genomic sequencing of some of the novel bacteria recovered from women with acute PID and/or histologic evidence of acute endometritis in order to establish the identity and correct taxonomic placement of these organisms. At the conclusion of the proposed studies, the role and identity of novel organisms associated with PID will be identified and may form the basis for improved treatment strategies. This project will be supported by Core B, Project 1 and Project 4.

Public Health Relevance

Pelvic inflammatory disease (PID) causes infertility and chronic pelvic pain in women woridwide. This project will identify previously underscribed organisms causing PID and will inform improved treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI084024-05
Application #
8529451
Study Section
Special Emphasis Panel (ZAI1-MMT-M)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$255,242
Indirect Cost
$47,518
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Darville, Toni (2013) Recognition and treatment of chlamydial infections from birth to adolescence. Adv Exp Med Biol 764:109-22
Darville, Toni; Pelvic Inflammatory Disease Workshop Proceedings Committee (2013) Pelvic inflammatory disease: identifying research gaps--proceedings of a workshop sponsored by Department of Health and Human Services/National Institutes of Health/National Institute of Allergy and Infectious Diseases, November 3-4, 2011. Sex Transm Dis 40:761-7
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Taylor, Brandie D; Darville, Toni; Ferrell, Robert E et al. (2013) Racial variation in toll-like receptor variants among women with pelvic inflammatory disease. J Infect Dis 207:940-6
Riley, Melissa M; Zurenski, Matthew A; Frazer, Lauren C et al. (2012) The recall response induced by genital challenge with Chlamydia muridarum protects the oviduct from pathology but not from reinfection. Infect Immun 80:2194-203
Taylor, Brandie D; Darville, Toni; Ferrell, Robert E et al. (2012) Variants in toll-like receptor 1 and 4 genes are associated with Chlamydia trachomatis among women with pelvic inflammatory disease. J Infect Dis 205:603-9
Tuttle, Marie S; Mostow, Eliot; Mukherjee, Pranab et al. (2011) Characterization of bacterial communities in venous insufficiency wounds by use of conventional culture and molecular diagnostic methods. J Clin Microbiol 49:3812-9
Chavez, Jean M; Vicetti Miguel, Rodolfo D; Cherpes, Thomas L (2011) Chlamydia trachomatis infection control programs: lessons learned and implications for vaccine development. Infect Dis Obstet Gynecol 2011:754060

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