High Incidence of New Sexually Transmitted Infections in the Year following a Sexually Transmitted Infection: A Case for Rescreening

Context The Centers for Disease Control and Prevention recommends that women treated for Chlamydia trachomatis infection return in 3 months for evaluation of reinfection. Contribution When data from the RESPECT-2 trial were used, these investigators found that among patients treated for sexually transmitted infections, 25.8% of women and 14.7% of men acquired 1 or more new infections with Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis during 1 year of follow-up. Approximately 66% of reinfections were asymptomatic. Implications Successful treatment of incident cases of sexually transmitted infections is unlikely to eliminate a reservoir of infection in the community. Physicians need to perform ongoing surveillance on men and women and encourage lifestyle changes in patients with reinfection. The Editors In 1985, the Centers for Disease Control and Prevention (CDC) treatment guidelines recommended that persons infected with Neisseria gonorrhoeae should return for a test of cure to be sure that the antibiotics had cured the infection (1). With new medications, treatment failure became rare, and by 1989, the guidelines suggested testing 1 to 2 months after treatment to detect treatment failure and reinfection (2). By 1993, the guidelines stated only that a test of cure was not recommended for N. gonorrhoeae (3). Test of cure has been unnecessary for Chlamydia trachomatis after treatment with first-line drugs, but infections detected among women several months after treatment have suggested that rescreening might be effective for detecting reinfection (3). Recent studies have found that 11% to 15% of women treated for C. trachomatis were infected when retested 3 to 4 months after treatment, possibly due to treatment failure, reinfection from an untreated partner, or infection from a new partner (46). New infections are often asymptomatic. One study with scheduled follow-up visits found that 62% of new C. trachomatis infections in men and in women were asymptomatic or unrecognized and would therefore probably be missed without rescreening (7). Untreated C. trachomatis infections can persist for years (8) and put infected women at risk for complications of asymptomatic pelvic inflammatory disease (9). In addition, transmission from asymptomatic persons may be responsible for most new infections in a community (10). The CDC has recommended that health care providers consider advising women with diagnoses of C. trachomatis infection to have another C. trachomatis test in 3 monthsnot as a test of cure but as a test for reinfection (11). We wondered whether men might also benefit from retesting, whether retesting should be expanded to include persons with N. gonorrhoeae or Trichomonas vaginalis infections (12), and whether there were other factors that clinicians could use to recommend retesting. We analyzed data from a large prevention counseling trial (13) that included baseline and 4 scheduled follow-up visits of patients in 3 sexually transmitted disease (STD) clinics to determine the incidence of new sexually transmitted infections during the year after a visit to the clinics. Methods A multicenter randomized, controlled trial of HIV prevention counseling with a rapid HIV test or a standard HIV test (RESPECT-2) was conducted in 3 public STD clinics in Denver, Colorado; Long Beach, California; and Newark, New Jersey. Primary analyses and detailed methods are described elsewhere (13). Briefly, eligible clients were those who came to the clinics for a full diagnostic examination for sexually transmitted infections, were HIV-negative at enrollment, reported having vaginal or anal sex in the preceding 3 months, and were 15 to 39 years of age. At the initial visit, participants were counseled, examined, and tested for sexually transmitted infections and HIV infection. Outcomes were measured at 13-week intervals, scheduled 3, 6, 9, and 12 months from the date of enrollment. Before each follow-up visit, study staff mailed a reminder letter to each participant and made a reminder telephone call. When participants did not keep appointments, staff mailed additional reminder letters and made additional telephone calls to reschedule the visit as needed. Participants who were due for a study follow-up visit were screened for sexually transmitted infections and were interviewed if they visited the clinic any time from 1 week before the due date up to 12 weeks after the due date. Participants were given $25 for completing each follow-up visit. This amount was later increased to $50 in an attempt to improve retention rates. Participants were tested for C. trachomatis, N. gonorrhoeae, and T. vaginalis infections at enrollment, at each quarterly follow-up visit, and at other visits not related to the study that occurred during the 12-month follow-up period (interim visits). An incident sexually transmitted infection was defined as a positive laboratory result either preceded by a negative result for the same infection or detected more than 14 days after provision of antibiotics effective against that infection. Testing was done in the local laboratories used by each clinic. Tests for C. trachomatis and N. gonorrhoeae infections were done on urine specimens by using nucleic acid amplification tests. The sensitivity and specificity values from the package inserts for these tests are cited here; the exact values are difficult to establish because there is no gold standard for identifying infected patients (14). The Long Beach and Newark clinics used ligase chain reaction (LCx Uriprobe, Abbott Diagnostics Division, Abbott Park, Illinois); the sensitivity and specificity for C. trachomatis were 93.1% and 97.1%, respectively, and the sensitivity and specificity for N. gonorrhoeae were 97.5% and 98.3%, respectively (15, 16). The Denver clinic used polymerase chain reaction initially (Cobas Amplicor, Roche Diagnostic Systems, Inc., Branchburg, New Jersey); the sensitivity and specificity for C. trachomatis were 93.4% and 96.7%, respectively, and the sensitivity and specificity for N. gonorrhoeae were 97.1% and 98.1%, respectively (17, 18). Eighteen months later, however, this clinic changed to using strand displacement amplification (BDProbeTec ET, BD Diagnostic Systems, Sparks, Maryland); the sensitivity and specificity for C. trachomatis were 90.7% and 96.6%, respectively, and the sensitivity and specificity for N. gonorrhoeae were 96.0% and 98.8%, respectively) (19). Trichomonas vaginalis was cultured by using the InPouch TV test (BioMed Diagnostics Inc., San Jose, California) or modified Diamond medium as the culture medium. The sensitivity has been estimated at 82.4% for the InPouch TV test and 87.8% for Diamond medium; specificity for both culture methods is nearly 100% (20). Cultures were done by using vaginal swab specimens from women. At follow-up visits, vaginal swabs were collected by the participant (Denver and Long Beach) or by a clinician (Newark), depending on local clinic policy. Behavioral data were collected by using Audio Computer-Assisted Self-Interview technology at enrollment and at each scheduled study follow-up visit. For most questions, a uniform 3-month recall period was used, regardless of the time since the most recent study visit. Because previous work has shown that most new infections are asymptomatic, we limited our analysis to participants who returned for testing and therefore could be classified as infected or not infected. Return visits with testing and interviews were scheduled every 3 months, and most participants returned within 2 weeks of their scheduled time. However, some participants also returned before their scheduled visit because of concern about a possible infection. Those who returned early were tested for sexually transmitted infections and were told to return for their scheduled visit for the interview and repeated testing. All test results from interim visits between 2 interviews were associated with behaviors reported during the next scheduled interview after the interim tests. Study interviews were conducted the first time the participant returned during the scheduled follow-up time (visit 1, 84 to 174 days; visit 2, 175 to 265 days; visit 3, 266 to 356 days; and visit 4, 357 to 448 days). Test data from participants who missed interviews were grouped in the analysis with their next interview. We excluded data from visits that occurred after participants missed 2 consecutive follow-up interviews. Men who reported having sex with men in the baseline interview were also excluded because of the small sample size. Person-years at risk were calculated by using the time between interviews. Participants could contribute up to 4 intervals of observation. Those who had multiple infections with the same organism in the same interval were only counted as having 1 infection, but if an infection recurred in a different interval it was counted again. We looked for 2 types of risk factors for infection. First, we looked for characteristics that clinicians could identify during a clinic visit that might predict infection at a subsequent visit. These factors included demographic characteristics, past risk behaviors, and infections detected during that visit. Second, we looked at events that might occur during follow-up that would alert patients to a need to return for testing for sexually transmitted infections. These factors included acquiring a new partner or having sex with more than 1 partner. Multivariate analysis of factors associated with sexually transmitted infection included serial measures for each participant. We performed unconditional logistic regression using generalized estimating equations, which accounted for within-participant correlations of repeated measures (21). Because this method assumes that missing data are missing completely at random, we assessed the relationship between missing visits and response variables for all 2419 participants included in our stu