Rescreening for Chlamydial Infection and Gonorrhea

Matthew R. Golden MD, MPH, H. Hunter Handsfield, MD


July 14, 2003


The Centers for Disease Control and Prevention (CDC) 2002 Sexually Transmitted Disease (STD) treatment guidelines recommend that clinicians "...consider advising all women with chlamydial infection to be rescreened 3-4 months after treatment."[1] Rescreening is distinct from test-of-cure in that it occurs later and is prompted by the recognition that persons diagnosed with STDs are at high risk for acquiring STDs in the future. CDC does not recommend test-of-cure for either gonorrhea or chlamydial infection in patients receiving standard treatment regimens, except in the case of women who are pregnant.

This change in the recommended management of chlamydial infection reflects the changing epidemiology of bacterial STD in the United States and several other factors. These factors include: (1) the recognition of the clinical importance of recurrent infection for increasing risk for infertility, ectopic pregnancy, and chronic pelvic pain; (2) renewed appreciation that the occurrence of STD is perhaps the best risk marker for future infection; and (3) an effort to exploit the opportunities afforded by the new nucleic acid based chlamydial diagnostics. Although rescreening is a promising approach to the control of bacterial STD, this is not the first time the idea has been proposed, and past experience suggests that the barriers to implementation may be formidable.

Over the course of the last 15 years, more than 15 different studies have assessed the risk of recurrent chlamdyial infection in women. Although most employed passive surveillance (no active measures were taken to ensure patients returned for repeat testing) and follow-up periods were variable, these studies demonstrated a consistent pattern. Approximately 5% of women treated for chlamydial infection again tested positive in 4 weeks after treatment, and more than 10% were diagnosed with chlamydial infection again within 4 months of treatment. Two prospective, multicenter studies of rescreening of women diagnosed with chlamydial infection in family planning and STD clinics have been published in the last 3 years; they confirmed findings from previous reports.[2,3] These studies, each of which tested women at 1 and approximately 4 months following treatment, reported that 5% to 6% of women tested positive for Chlamydia trachomatis at the 1-month follow-up and an additional 7% to 13% tested positive 4 months following treatment. These rates exceed the prevalence usually thought to be cost-effective for primary screening, as well as the prevalence seen among virtually any other definable candidate population for chlamydial screening. While fewer data are available on rescreening in men, observational and randomized trial data suggest that recurrent/persistent infection is common.[4,5]

The cause of these high rates of infection is uncertain. Possible reasons include treatment failure (persistence), reinfection from untreated sex partners, and new infections from new sex partners. With respect to persistence, Workowski did not observe chlamydial persistence in a study of 20 women followed with serial cultures and polymerase chain reaction (PCR) testing for 20 weeks after treatment.[6] However, data supporting the possibility for persistence include studies demonstrating that nonreplicative persistence can be induced in vitro, the occurrence of persistent/recurrent infection in women who deny resuming sex, nonculture evidence of infection in women seeking evaluation for infertility, and in women with nongenital chlamydial infections (eg, trachoma, Reiter's syndrome), and the large proportion of initial and persistent/recurrent infections that occur with identical chlamydial serovars.[7,8] To date, little evidence supports antimicrobial resistance as a cause of treatment failure, though laboratory methods to test for C trachomatis resistance are not well established.

Evidence supporting reinfection as a consequence of untreated sex partners includes studies demonstrating that many -- perhaps most -- exposed sex partners are not treated, as well as observational studies in which giving patients medication to give to their sex partners decreased the occurrence of persistent/recurrent infection in infected women. However, a recent randomized trial did not show a significant decline in persistent/recurrent infection in women given medication for sex partners, compared with those simply advised that their partners needed treatment (15% vs 12%, P = .01).[3]

Some infections identified through rescreening are certainly from new partners, but having a new partner does not appear to predict persistent/recurrent infection.[2] Indeed, one study observed significantly higher rates of infection during rescreening of women who denied new partners.[9] Whatever the specific origins of persistent or recurrent infections, it is clear that persons with chlamydial infection are at high risk for having a chlamydial infection again.

But it is not just chlamydia that is a specific problem. It has long been established that patients with STD are at high risk for STD.[10] Although there are few contemporary data, the high rate of recurrent gonorrhea has been recognized for decades[11] and prompted a recommendation for routine rescreening made in the 1970s. This effort was largely abandoned due to difficulties associated with implementation, though we are aware of only a single study that actually assessed rescreening during that time.[12]

Over the past decade, changes in the epidemiology of bacterial STD have provided an impetus for reconsidering rescreening in specific groups. Chlamydia and gonorrhea rates have declined substantially since the 1980s and are now relatively stable in heterosexuals. As the prevalence in screened populations has dropped, the cost per case detected has also increased. However, infection has probably become more concentrated within groups of highly sexually active persons and specific sexual networks, a phenomenon that is more pronounced in those developing gonorrhea than in those with chlamydial infection. This concentration of disease should prompt more targeted, intense interventions such as rescreening.

In addition, changes in diagnostic microbiology may make rescreening easier to implement than it was in the 1970s. Nucleic acid amplification tests (eg, PCR, transcription mediated amplification, and strand displacement assay) make it possible to test urine and self-obtained vaginal specimens, thereby decreasing the need for physical exams. Two recent reports have described rescreening using mailed specimens, though 1 of these studies found that only a small proportion of patients (22%) returned specimens after a collection kit was mailed to them.[13,14]

We believe that the epidemiologic and clinical rationale for rescreening all women with gonorrhea and chlamydial infection is very strong. Clinicians should routinely attempt to rescreen all women with these infections in the 10 to 16 weeks following their initial diagnosis. Efforts to ensure rescreening should include routinely making an appointment for women to return for testing and calling or sending reminder letters to women not rescreened within 16 weeks. Although women diagnosed with gonorrhea or chlamydial infections may be at increased risk for other STDs in some settings, the need for examination should not be a barrier to rescreening, and clinicians may elect to simply have patients provide a specimen for testing. We also recommend rescreening men with gonorrhea and chlamydial infection, though the evidence supporting this recommendation is not as strong. Future research should assess means to improve adherence to rescreening recommendations and to better describe the yield of rescreening among men.


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