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The Role of Delayed Care Seeking and Toll-like Receptors in Pelvic Inflammatory Disease and Its Sequelae

Taylor, Brandie DePaoli (2011) The Role of Delayed Care Seeking and Toll-like Receptors in Pelvic Inflammatory Disease and Its Sequelae. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Taylor, Brandie DePaolibrandiedtaylor@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHaggerty, Catherinehaggertyc@edc.pitt.eduHAGGERTY
Committee MemberKammerer, Candacecmk3@pitt.eduCMK3
Committee MemberZmuda, JosephZmudaJ@edc.pitt.eduEPIDJMZ
Committee MemberFerrell, Robertrferrell@pitt.eduRFERRELL
Committee MemberDarville, ToniToni.Darville@chp.edu
Date: 29 June 2011
Date Type: Completion
Defense Date: 11 April 2011
Approval Date: 29 June 2011
Submission Date: 30 March 2011
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: delayed care; infertility; Toll-like receptors; Chlamydia trachomatis; Pelvic inflammatory disease
Other ID: http://etd.library.pitt.edu/ETD/available/etd-03302011-134447/, etd-03302011-134447
Date Deposited: 10 Nov 2011 19:33
Last Modified: 15 Nov 2016 13:37
URI: http://d-scholarship.pitt.edu/id/eprint/6658

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