Pelvic Inflammatory Disease (PID), the infection and inflammation of the female upper genital tract, can result in serious sequelae. Markers to predict sequelae following PID are greatly needed. The goal of this research is to explore the role of host genetic factors and delayed care seeking in the development of sequelae following clinically suspected PID. We studied the microbial correlates of delayed care and long-term outcomes among 298 women with histologically confirmed endometritis from the PID Evaluation and Clinical Health (PEACH) study. Mean days of pain prior to care were compared by microbial pathogen, with the longest times among women infected by Chlamydia trachomatis (CT) only (12.3±9.4 days) and Mycoplasma genitalium (MG) only (10.9±8.9 days), and the shortest among women infected by Neisseria gonorrhoeae (NG) only (4.6±5 days) or co-infection (5.6±5.1 days, p<0.001). Infertility, recurrent PID, and chronic pelvic pain were frequent (17%, 20%, and 36%), albeit non-significantly elevated after delayed care. PID patients infected with CT or MG were more likely to delay care, possibly increasing persistent inflammation which may permanently damage the reproductive tract before patients seek care.
Toll-like receptors (TLR) eliminate microbes through inflammatory responses. As genetic variations may increase TLR signaling, we determined if 18 tagging single nucleotide polymorphisms assayed in 4 TLR genes (TLR1, TLR2, TLR4, TLR6) and 2 adaptor molecules (TIRAP, MyD88) were associated with CT, endometritis, or infertility among 205 African Americans with PID from the PEACH study. An empirical p-value <0.004 was significant. Logistic regression revealed that the TLR4 rs1927911 CC genotype was associated with CT (odds ratio (OR) 3.7, 95% confidence interval (CI) 1.6-8.8, p=0.0021). Further, the TLR1 rs4833095 TT genotype displayed trends towards increased CT (OR 2.8, 95% CI 1.3-6.2, p=0.0084). Predicted carriers of the TLR4 GTC haplotype (p=0.006) and the TLR1 TGT haplotype (p=0.04) were more likely to be CT positive. Genetic variations in TLR genes may play a role in CT pathogenesis.
This dissertation yields public health significance by demonstrating the need for increased efforts for early identification and treatment of genital tract infections and providing a novel exploration into the role of genetic variants in CT pathogenesis.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-03302011-134447 |
| Date | 29 June 2011 |
| Creators | Taylor, Brandie DePaoli |
| Contributors | Toni Darville, Catherine Haggerty, Joseph Zmuda, Candace Kammerer, Robert Ferrell |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-03302011-134447/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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