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Sequelae of genital Chlamydia trachomatis infection in women are more strongly linked to repeat infections than to initial ones, and persistent or subsequent infections foster continued transmission.To identify factors associated with persistent and recurrent chlamydial infection in young women that might influence prevention strategies.Teenage and young adult women with uncomplicated C trachomatis infection attending reproductive health, sexually transmitted disease, and adolescent medicine clinics in five US cities were recruited to a cohort study. Persistent or recurrent chlamydial infection was detected by ligase chain reaction (LCR) testing of urine 1 month and 4 months after treatment.Among 1,194 women treated for chlamydial infection, 792 (66.4%) returned for the first follow-up visit , 50 (6.3%) of whom had positive LCR results. At that visit, women who resumed sex since treatment were more likely to have chlamydial infection (relative risk [RR], 2.0; 95% CI, 1.03–3.9), as were those who did not complete treatment (RR, 3.4; 95% CI, 1.6–7.3). Among women who tested negative for C trachomatis at the first follow-up visit, 36 (7.1%) of 505 had positive results by LCR at the second follow-up visit. Reinfection at this visit was not clearly associated with having a new sex partner or other sexual behavior risks; new infection was likely due to resumption of sex with untreated partners. Overall, 13.4% of women had persistent infection or became reinfected after a median of 4.3 months, a rate of 33 infections per 1,000 person months.Persistent or recurrent infection is very common in young women with chlamydial infection. Improved strategies are needed to assure treatment of women’s male sex partners. Rescreening, or retesting of women for chlamydial infection a few months after treatment, also is recommended as a routine chlamydia prevention strategy.