Preliminary data that we and others have collected suggests that diaphragm use may be associated with an increased risk of (1) E. coli vaginal colonization; (2) asymptomatic and symptomatic UTI; and (3) recurrent UTI. The prospective cohort study we propose is designed to confirm these associations in an optimal study design, and to investigate possible biological mechanisms through which diaphragm use predisposes to UTI. In addition, we will determine the interaction of diaphragm use with other factors thought to increase susceptibility to UTI in young women, specifically (i) sexual intercourse; (ii) specific E. coli virulence factors; and (iii) enhanced uroepithelial cell adherence. As diaphragm use may contribute to the causation of 30-40% of UTIs in young women and is a potentially reversible risk factor, these relationships are particularly important to study. We will accomplish the following specific aims: 1. In a prospective cohort study, compare 300 new diaphragm- spermicide users and 300 women initiating the use of spermicide alone with 300 new oral contraceptive users to determine the relative risk of asymptomatic bacteriuria (ASB) and symptomatic UTI in the first two groups. Compare diaphragm users who experience UTI with diaphragm users who do not in order to identify factors predisposing to UTI in this group. 2. Determine whether increased vaginal colonization with E. coli accompanies diaphragm-spermicide use by evaluating women just before first use and throughout the first month of use of each contraceptive method. Simultaneously assess the impact of each contraceptive method on the normal vaginal flora. Correlate changes in vaginal E. coli colonization with subsequent risk of ASB and symptomatic UTI. 3. Determine the presence and degree of urinary obstruction and post-void residual urine in diaphragm users, and the relationship of these variables to risk of ASB and UTI. 4. Determine whether vaginal and uroepithelial cells prospectively collected from women in each of the 3 groups demonstrate an increased ability to bind uropathogenic E. coli in an in vitro bacterial adherence assay as compared with cells collected from the same woman before the initiation of diaphragm, spermicide, or oral contraceptive use. Determine whether periods of increased epithelial cell adherence correlate temporally with vaginal E. coli colonization. 5. Characterize the E. coli strains causing ASB and UTI in diaphragm users, spermicide users and oral contraceptive users as to the presence or absence of bacterial properties associated with uropathogenicity, specifically serotype, hemolysin, aerobactin, type 1 fimbriae, P fimbriae and bacterial adherence. Determine rates of vaginal colonization with uropathogenic and non- uropathogenic E. coli, and the proportion of such colonization episodes that progress to ASB and UTI in each of the groups of women.
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