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Repeat Infection With Chlamydia and Gonorrhea Among Females: A Systematic Review of the Literature

Hosenfeld, Christina B. MPH*; Workowski, Kimberly A. MD†‡; Berman, Stuart MD, SCM; Zaidi, Akbar PHD; Dyson, Jeri MD§; Mosure, Debra PHD; Bolan, Gail MD*; Bauer, Heidi M. MD, MPH*

Author Information
Sexually Transmitted Diseases: August 2009 - Volume 36 - Issue 8 - p 478-489
doi: 10.1097/OLQ.0b013e3181a2a933
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Women are disproportionately affected by chlamydial and gonococcal infection in the United States, and account for over 50% of gonorrhea and 75% of reported chlamydia cases.1 Both chlamydia and gonorrhea are associated with a variety of adverse reproductive health outcomes, including pelvic inflammatory disease (PID), ectopic pregnancy, tubal infertility, and perinatal infections.2–4

Reinfection with chlamydia or gonorrhea is associated with an increased risk of reproductive complications. Studies have shown that the ascension of chlamydia or gonorrhea into the upper genital tract is more common for reinfected women than for women experiencing their first infection.2,4–7 Hillis et al found a 2-fold increased risk of ectopic pregnancy among women who had 2 chlamydial infections and 4.5-fold increased risk among women with 3 or more infections.2 In this study, the risk of PID was similarly increased: 4-fold with 2 infections and 6.4-fold for 3 or more infections. Because most of the infections are asymptomatic in females, follow-up testing after treatment is paramount to detecting infection and preventing adverse reproductive health outcomes.

Because having a recent history of chlamydia or gonorrhea infection has been identified as a risk factor for infection, published guidelines suggest retesting after appropriate treatment.8,9 The optimal interval between initial infection and a subsequent test, as well as whether retesting should be gender-specific, has not been well evaluated. In 2006, the Centers for Disease Control and Prevention recommended that clinicians consider advising all women with chlamydial or gonococcal infection to be retested approximately 3 months after treatment.8 Although there is limited information on the benefit of retesting in men, the Centers for Disease Control and Prevention STD Treatment Guidelines and a recent review suggests such testing approximately 3 months after treatment.8,10

Our review of the literature examining chlamydia and gonorrhea reinfection was undertaken to provide the best estimate of reinfection rates in females and to inform evidence-based patient management recommendations for improving the quality of patient care to preserve reproductive health.


We conducted a PubMed search for studies before April 2008 that estimated the rate of reinfection with gonorrhea or chlamydia among females. Queries included “repeat (gonorrhea or chlamydia),” “recurrent (gonorrhea or chlamydia),” “reinfection (gonorrhea or chlamydia),” “reinfection (gonorrhea or chlamydia),” and “rescreening (chlamydia or gonorrhea).” Searches were limited to articles published in English over the past 30 years. A total of 794 unduplicated publications were identified. Of the 794 publications, abstracts were reviewed by the authors for relevance to the topic; and 66 publications were selected for detailed review. Further examination of bibliographies revealed 4 additional publications.

Included in this analysis were original studies conducted in the United States and other industrialized nations that reported a reinfection rate for chlamydia or gonorrhea in human females or provided sufficient data to calculate reinfection rates. Because the focus of the analysis was repeat infection rather than treatment failure, antibiotic efficacy studies, which generally have short-term follow-up, were not included in our analysis. Twenty-three studies were excluded because reinfection rates were not stratified by sex11–21 or specific etiology (chlamydia or gonorrhea),13,14,21–24 the publication was a nonpeer-reviewed letter,25 data were duplicative of already published material,26–28 reinfection rates could not be calculated using the data provided,29–32 or initial infection was not laboratory-confirmed.33 Specific study design, proportion of females retested, diagnostic test type used, length of follow-up, geographic region, and population demographics were not considered in the inclusion and exclusion criteria. To ensure high quality data, only peer-reviewed publications were included; conference abstracts and unpublished data were excluded. A total of 47 studies were included in the final analysis.

We categorized studies into “tiers” based on the research design and follow-up methods. “Active cohorts,” or Tier 1 studies, were those that involved patient enrollment: randomized controlled trials and prospective cohort studies with active follow-up. Tier 2 studies were comprised of “passive cohorts,” prospective or retrospective cohort studies with passive follow-up that did not require patient enrollment, did not have specific retesting intervals, but which collected data on the timing and results of subsequent tests. When reinfection rates were not provided by the original investigators, we calculated these rates for both active and passive cohort studies by dividing the number of females reinfected by the number of females retested after treatment for the initial infection. “Disease registry,” or Tier 3 studies, included those that reported reinfection rates using case-based surveillance systems or clinic-based registries that did not contain information on patients who tested negative. For these studies, reinfection proportions were calculated by dividing the number of patients with a subsequent infection by the number of patients initially infected. At least 2 authors reviewed data from each study and verified reinfection rates.

Summary estimates of the median and range of reinfection rates were determined separately for chlamydia and gonorrhea. For studies that reported reinfection rates for sequential testing within the same study population at different time intervals, the reinfection rate based on the longest timeframe up to 12 month was included in the data analysis. For randomized trials in which reinfection was the outcome of interest and data were stratified by study arm, the reinfection rate based on the control conditions was included in the analysis. The Kruskal-Wallis and Mann-Whitney statistical tests were used to compare median reinfection rates among study tiers. To estimate the optimal timing for retesting patients treated for chlamydia or gonorrhea, we fitted a second degree (quadratic) regression model to the data with rate of reinfection as the dependent variable and time as the independent variable. This model was chosen because it provided the best fit based on standard model selection criteria. Model analyses were performed using SAS 9.1 software (SAS Institute, Cary, NC); PROC REG was used to calculate regression coefficients, and PROC GPLOT was used to plot the data.

To examine which factors were associated with reinfection, summary rates were stratified by study tier, length of follow-up, proportion of females retested (Tiers 1 and 2 only), sample size, diagnostic test used, treatment regimen, and clinical setting. In addition, differential rates were examined among studies that included sufficient data on age, race or ethnicity, coinfection status, symptom status, partner management strategies, and sexual risk behavior.


A total of 47 studies were included in our analysis: 30 studies reported only chlamydia reinfection rates, 9 reported only gonorrhea reinfection rates, and 8 reported both chlamydia and gonorrhea reinfection rates. Of the 16 active cohort Tier 1 studies, 11 examined reinfection rates for chlamydia only and 5 examined reinfection for both chlamydia and gonorrhea (Table 1). Of 15 passive cohort Tier 2 studies, 13 examined reinfection rates for chlamydia only and 2 examined gonorrhea only (Table 2). Of the 16 disease registry Tier 3 studies, 6 measured reinfection rates for chlamydia only, 7 for gonorrhea only, and 3 for both chlamydia and gonorrhea (Table 3).

Chlamydia and Gonorrhea Reinfection in Active Cohort Studies (Tier 1)
Chlamydia and Gonorrhea Reinfection in Passive Cohort Studies (Tier 2)
Chlamydia and Gonorrhea Reinfection in Disease Registry Studies (Tier 3)

Overall, 37 studies took place in the United States and 10 studies were based in non-US populations. US-based studies included populations from at least 20 different states and 17 cities. The length of follow-up ranged from 2 months to 13 years. Although there was variability in the minimum time required for a second infection to be defined as a repeat infection, of those studies that specifically defined this timeframe, all but 234,35 defined reinfection as greater than 2 weeks after an initial positive.

Of the 38 studies reporting chlamydia reinfection rates, the proportion of females reinfected ranged from 0% to 32%, with a median proportion of 13.9%. Median rates of chlamydia reinfection varied somewhat by study design. Among Tier 1 studies, the median reinfection rate was 13.0%; Tiers 2 and 3 had median reinfection rates of 18.0% and 9.4%, respectively (P = 0.19). Rates of chlamydia reinfection were stratified by tier and modeled over time up to 36 months (Fig. 1). Modeled data from Tier 1 studies demonstrated a peak at 13 months with a reinfection rate of 20.9%; the rate at 3 months was 8.4% and the rate at 6 months was 14.7%. This peak was earlier and of similar magnitude to peaks associated with the Tier 2 or Tier 3 models; peak reinfection in Tier 2 studies (24.0%) occurred at 25 months, and reinfection for Tier 3 studies (16.2%) peaked at 36 months. Among Tier 1 and 2 studies, the length of follow-up ranged from 2 to 60 months after the initial chlamydial infection. Modeling chlamydia reinfection within 12 months demonstrated similar peak rates for Tier 1 and Tier 2 studies (18.6% at 10 months and 19.5% at 8 months, respectively). Although the proportion of those retested for chlamydia ranged from 23% to 100%, reinfection rates did not vary with the proportion retested.

Figure 1.:
Observed and modeled chlamydia reinfection rates in females over 36 months, by study tier. Diamond (♦): active cohort studies (Tier 1) observed reinfection rates. Square (▪): passive cohort studies (Tier 2) observed reinfection rates. Triangle (▴): disease registry studies (Tier 3) observed reinfection rates. Solid line: tier 1 modeled reinfection rates. Dashed line: tier 2 modeled reinfection rates. Dotted line: tier 3 modeled reinfection rates.

Of the 17 studies reporting gonorrhea reinfection rates, the proportion of females reinfected ranged from 2.6% to 40%, with a median proportion of 11.7%. The median reinfection rate was 23.6% for Tier 1 studies, 15.8% for Tiers 2 studies, and 9.1% for Tier 3 studies (P = 0.63 for Tiers 1 and 2 compared with Tier 3). Given the relatively fewer data on gonorrhea reinfection, modeling gonorrhea reinfection by tier over a 36-month follow-up period did not result in reliable estimates of reinfection proportions (data not shown). Among Tier 1 and 2 studies, the length of follow-up ranged from 3 to 20 months after the initial positive. The proportion of females retested ranged from 38% to 77%; however, the reinfection rates did not vary by the proportion retested.

Patient demographics were associated with chlamydia and gonorrhea reinfection rates in several studies. Younger age was consistently statistically associated with a higher risk for reinfection. Because of variations in the populations studied, these higher risk groups were identified as “younger” women,34,36–38 women under 20 years of age,39–42 and women under 26 years.2,43–46 Several studies that did not identify statistical significance still noted a trend of increased reinfection in younger participants.47–55 The relationship between race or ethnicity and reinfection varied by study. Non-Hispanic blacks had a significantly higher risk of chlamydia reinfection in some studies;2,37,39,42,44,46,56 however, other studies found no association with reinfection,35,38,41,45,57–59 despite a high proportion of black participants in several of these studies.35,41,57–58 Among the 10 gonorrhea studies that assessed the correlation of non-Hispanic black race with reinfection, blacks were found to be at increased risk for reinfection in 7 studies.37,40,42,44,50,56,60 Of the studies that did not find a statistically significant relationship between race and gonorrhea reinfection, 2 of 3 study populations were over 80% black.36,47

Of the 8 studies that examined the role of coinfection on reinfection estimates, 6 identified a statistically significant association. Five studies demonstrated that coinfection with gonorrhea increased reinfection with chlamydia,2,38–39,46,61 and 3 studies demonstrated that coinfection with chlamydia increased the risk of gonorrhea reinfection.38,40,61 The reason for initial testing and the presence of symptoms were not consistently associated with higher rates of reinfection. In all studies, routine screening in the absence of symptoms identified the majority of infections. Of the 7 studies that provided data on the reasons that females returned for a subsequent test,39,43,46,51,62–64 only 1 study distinguished between the initial and subsequent visit.64

Innovative and effective partner treatment strategies were generally associated with lower rates of reinfection. Expedited partner therapy (EPT) significantly decreased chlamydia reinfection estimates in 1 randomized control trial58 and gonococcal reinfection estimates in another randomized control trial.38 In 2 randomized trials, EPT was associated with lower rates of chlamydia reinfection, however, the results were not statistically significant.38,53

Study characteristics that were not associated with chlamydia or gonorrhea reinfection rates included study sample size, diagnostic test type, treatment regimen, geographic area, timeframe, and clinic type. Clinic type was examined for studies conducted within a single type of venue; however, this comparison among STD,38,42,44,47,52,65 family planning,58–59 and private or managed care clinics49 demonstrated no appreciable differences in reinfection rates. In addition, studies that presented information about the behavioral factors of the study populations, including new or multiple partners30,35,38–40,43–45,47,50–52,55–56,59,61,68 and history of STD,39–40,43,45,47,52 showed no consistent relationship between these factors and risk of reinfection. Of note, several studies did not stratify risk factor analyses by sex36,38,44–45,47,49–50,54,60 or by organism.38,42,56


Our synthesis of studies of chlamydia or gonorrhea reinfection in females demonstrated consistently high rates of repeat chlamydia or gonorrhea infection and provided direct evidence to support clinical guidelines. Combined with the recent review demonstrating high reinfection rates in men,10 our analysis of reinfection rates in females provides substantial evidence to support retesting for chlamydia and gonorrhea among both women and men 3 to 6 months after treatment. Although peak rates for data censored at 12 months follow-up occurred after 6 months, retesting before 6 months may prevent the development of complications. Despite some variability in reinfection rates, retesting would likely benefit all patients irrespective of age, race or ethnicity, symptom status, partner treatment, and sexual risk behavior. It is also important to note that retesting is distinct from a test of cure, which is not recommended unless compliance is in question, symptoms persist, reinfection is suspected, or the patient has chlamydia and is pregnant.8

Establishing the ideal timeframe for retesting is challenging. Currently, retesting of women with chlamydia or gonorrhea is recommended 3 months after completion of treatment.8 Early testing allows prompt identification and treatment of infections acquired shortly after treatment, but fails to identify infections acquired later. Although a more extended timeframe may maximize the number of infections identified, this delay may allow infection to persist and compromise subsequent reproductive health. Another consideration is the practicality of retesting, as several studies demonstrated that less than 30% of initially infected females were retested.48,64 Retesting at 3 to 6 months was supported by tier 1 modeling data that estimated the rate of reinfection at 6 months to be 14.7%, which exceeded the median for tier 1 studies (13.0%) and approached the higher median observed for tier 2 studies (18.0%).

Although the optimal timeframe for retesting may be influenced by whether reinfections are persistent or recurrent, distinguishing between these possibilities has been challenging. Using chlamydia genotyping methods, Blythe et al found a high rate of discordance between the initial and repeat infections among females studied.35 Although useful in distinguishing new infections, genotyping is less useful in identifying persistent infection, since the genotype of the organism acquired from an untreated partner is likely to be the same as the initial infection. A few studies have found evidence that treatment failure may play an important role in persistent chlamydial infection.38,55,69 Further adding to the challenge of establishing the optimal retesting timeframe is the relative lack of data on the rate of or time until the development of complications.

Although several studies demonstrated higher reinfection rates among younger women, the reinfection rate among women over age 25 years exceeded 10% in several studies.34,41,53 Further, our assessment demonstrated similarly high rates of reinfection for a variety of clinical settings including STD clinics, family planning clinics, and managed care organizations. While there is evidence that some approaches to partner treatment, including EPT, reduce reinfection, risk of such reinfection is still substantial.38,53,58 Ensuring that women of all ages return for a subsequent test 3 to 6 months after treatment will likely prevent adverse reproductive health outcomes. Studies in prenatal settings, which found chlamydia reinfection rates of 13% to 32%, support current recommendations that pregnant women at increased risk, including those recently treated for chlamydia or gonorrhea, should be retested during the third trimester to prevent maternal postnatal complications and infection in the infant.8 Effective strategies for improving retesting rates may include patient counseling, flagging medical charts, making advance appointments, and/or retesting reminders by telephone, mail, text messaging, or email.

Surprisingly, reinfection rates observed for active (Tier 1) and passive (Tier 2) cohort studies did not vary by the proportion of females retested. One might expect higher rates of reinfection among women who return to clinic without prompting, especially if they have symptoms, are nonadherent to treatment, or have known re-exposure to an untreated partner. If this was the case, reinfection rates would be expected to decline as a greater proportion of women are retested. Instead, observed findings support interventions to maximize the number of patients retested, since this strategy is likely to identify the largest number of infections.

There were a number of limitations to the summary estimates and analysis of predictors of reinfection. Differences in study design, length of follow-up, and definition of outcome presented challenges in assessing chlamydia and gonorrhea reinfection in females. Compared to Tier 1 studies with active follow-up, reinfection rates identified in Tier 2 and 3 studies would be expected to be less valid estimates of the true incidence in the populations assessed. In particular, Tier 3 studies undoubtedly underestimate true reinfection rates; since data on the proportion of females retested were not reported, the denominator was the number of infected individuals initially reported. To compensate for the effects that study design may have had on reinfection rates, studies were grouped into tiers for a stratified analysis. Increasing the study duration would be expected to be associated with increasing reinfection proportions. In addition, it is not known when the reinfection was actually acquired, only when the test was performed and infection identified. We attempted to minimize the effects of varying follow-up lengths on rates of reinfection by analyzing reinfection within a 12-month timeframe. The bias associated with incomplete retesting is difficult to predict since women with infection may have sought care elsewhere, decreasing observed rates of reinfection, or women may have been retested because they suspected they might be infected, leading to an overestimate of reinfection. Finally, in evaluating factors associated with reinfection, reports may have been biased in favor of statistical associations and several studies did not provide stratified estimates by sex or organism.

Our systematic review has provided substantial evidence for high chlamydia and gonorrhea reinfection rates among females across a variety of study populations and clinic settings. Because repeat infections confer an elevated risk for PID and other complications, retesting women treated for chlamydia or gonorrhea should be a priority. If a patient does not return for retesting, providers should retest at the next clinical visit, regardless of whether the patient believes that her sex partners were treated. Further, given the consistent and substantial rate of reinfection in the 47 studies reviewed, the value of continued documentation of high reinfection rates is questionable. Rather, investigators should focus on developing and evaluating interventions to prevent reinfection and to increase retesting. While several studies have demonstrated effective behavioral interventions to prevent incident infection,70–71 few studies of innovative methods for retesting have been published72 and few studies examined interventions to prevent reinfection.38,53,58 If effective, such clinical interventions may well reduce the risk of PID, ectopic pregnancy, and other adverse reproductive health outcomes.


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