The Centers for Disease Control and Prevention estimates that there are over 3 million new cases of chlamydia and gonorrhea infections annually in the United States.1 In high-risk obstetric populations, the incidence of sexually transmitted infections (STIs) may exceed 25% in the first trimester and 38% in routine third trimester screening.2 In the first 6 months after treatment of Chlamydia trachomatis infection, 6% of women aged <20 years may be reinfected.3 Given minimal resources and the increasing burden of STIs, partner notification conducted by health care providers or public health field investigators for chlamydia and gonorrhea is generally cost-prohibitive at the local level. As a result, many providers have resorted to patient referral for treatment of sexual partners. However, this is a suboptimal method of ensuring partner therapy, resulting in treatment of only 36% of male partners in heterosexual relationships.4
Expedited partner therapy (EPT) is the delivery of medications or prescriptions to patients diagnosed with an STI intended for use by their sexual partner(s) without clinical assessment of the partner(s). EPT has been associated with a 73% reduction in gonorrhea reinfection in heterosexual partnerships.5 EPT can be delivered in 1 of the 3 ways: the patient delivers the medication to their sexual partner; the patient delivers prescriptions to their sexual partner; or partners receive medication at pharmacies or public health clinics. Although EPT is legally permissible in 30 states, obstetric providers remain reluctant to practice EPT due to concerns regarding liability.6,7
The American College of Obstetrics and Gynecology supports the use of EPT for treatment of STIs and encourages health care providers to advocate for enhanced availability of STI treatment services.8 As many as 60% of infants delivered from mothers with cervical chlamydia infection have immunologic evidence of infection.1 Additionally, there is a 1.53 increased odds of preterm delivery and premature rupture of membranes with an active chlamydia infection.9,10 Because of such significant sequelae, all pregnant women in the United States are screened for infection as part of routine prenatal care and treated expeditiously.11–13
Prenatal care allows obstetric providers to educate both parents-to-be. Given the continuum of contact that women have with health care providers and the father of the baby during pregnancy, concurrent patient-partner treatment (CPPT), also known as bring your own partner or BYOP treatment strategy, appears to be an effective method of preventing repeat positive STIs. CPPT involves the practitioner providing treatment to the index patient, as well as to sexual partner(s), which may be an attractive alternative of preventing STIs. Thus, the objectives of this study were to determine whether CPPT reduces the prevalence of a positive test of cure (TOC) for chlamydia and/or gonorrhea infection in pregnant women.
MATERIALS AND METHODS
An observational study of pregnant women aged 15 to 40 years diagnosed with chlamydia and/or gonorrhea infection was conducted at an urban academic teaching hospital over a 16-month period. A CPPT program was implemented as a service to the community. During the preparation phase of the program, all nursing staff and prenatal care providers underwent an in-service regarding STI counseling, treatment, and CPPT. The standard clinical protocol involved a discussion of the diagnosis, need for treatment of herself and all the sexual partners within the past 30 days (to identify the most recent sexual partner in proximity to STI diagnosis), and methods to prevent reinfection such as abstinence and condom use. CPPT services were first offered in November 2008 and included a brief interview conducted by risk reduction trained study staff, STI counseling, distribution of condoms, and safer-sex materials. Providers were encouraged to offer CPPT services to all eligible pregnant women. To be eligible for CPPT services, women must have had the following: pregnancy diagnosed with urine pregnancy test, β human chorionic gonadotropin >5, or confirmation of intrauterine pregnancy by ultrasound; ability to comply with the study protocol; continued access to medical care; and laboratory-confirmed chlamydia and/or gonorrhea infection in the current pregnancy. Women were ineligible for CPPT if they had any of the following: reported STI treatment before contact by study staff, partner(s) with allergy to antibiotics, suspected case of verbal, physical, or sexual abuse; coinfected with HIV or syphilis, or inability to contact partner or no further contact with partner.
Prenatal providers notified pregnant women of a positive chlamydia and/or gonorrhea test by telephone and as part of the new program were offered CPPT. Women were advised to notify their sexual partner(s) of the infection and the option of concurrent treatment. Couples accepting CPPT were given an appointment to present together at the clinic. If women were informed of the infection during a prenatal visit and their sexual partner was present, then they were offered CPPT at that visit. If she reported >1 sexual partner, the other partner(s) was scheduled for treatment at a separate visit. CPPT consisted of directly observed treatment for chlamydia (1 g oral azithromycin) and/or gonorrhea (400 mg oral cefpodoxime) of both the pregnant woman and her sexual partner(s). Partners were referred to local STI clinics for additional screening and treatment as needed. Because of clinical regulations regarding parenteral administration of ceftriaxone, cefpodoxime was selected instead for the treatment of gonorrhea. Women who declined or were not offered CPPT received a prescription for 1 g oral azithromycin and an intramuscular injection of 125 mg ceftriaxone by a registered nurse or physician for the treatment of chlamydia and gonorrhea, respectively. These women were then advised to notify their sexual partner(s) and recommend that they seek care from their primary medical doctor or local STI clinic for counseling, screening, and treatment.
Assessment of Infection
As a component of routine prenatal care at our clinic, women were screened for chlamydia infection at the initial prenatal visit and during the late third trimester of pregnancy. In addition, testing for STIs occurred at any time patients reported vaginal symptoms suggestive of an STI. A TOC was obtained at least 3 weeks after the treatment to document resolution of infection. Chlamydia and gonorrhea infection were detected using nucleic acid amplification test (NAAT, Gen-Probe, Aptima Inc). Participants with a chlamydia and/or gonorrhea infection after observed or self-reported treatment were retreated until a negative TOC was obtained. Repeat positive chlamydia and/or gonorrhea infection was defined as at least 2 positive tests after a documented treatment.
A log of all chlamydia and/or gonorrhea nucleic acid amplification tests performed on pregnant women during the study timeframe from any location within the University of Pennsylvania Health System was obtained from the central laboratory. Demographic data and clinical management of those women receiving prenatal care at our clinic were abstracted through a chart review.
The Institutional Review Board of the University of Pennsylvania granted approval for the study. Pregnant women and their sexual partners gave written informed consent before enrollment. CPPT participants were each compensated $20.
Demographic data and uptake were analyzed using descriptive statistics. χ2 or Fisher exact tests were used for categorical data, and Student t test was used for continuous variables. We evaluated the effect of CPPT on the odds of a positive TOC and repeat positive test for chlamydia and/or gonorrhea. Inference for odds ratios (ORs) were computed by Cornfield test or Fisher exact test and 95% exact 2-sided confidence intervals (CIs) were reported. These analyses were done for all subjects combined and stratified by infection (chlamydia or gonorrhea). We further evaluated the effect of CPPT on the time of cure. Kaplan-Meier curves were plotted for the CPPT and the standard patient referral group, and the midpoint in time to cure was assessed by log-rank test in days and converted to standard obstetric nomenclature of weeks and days. As these are current status data, the time to cure was estimated using the midpoint between the estimated gestational age (EGA) at diagnosis of chlamydia and/or gonorrhea infection and the EGA of the first negative TOC. It should be noted that the data are right-censored, as some subjects were still positive at the last visit. Study participants that did not receive a TOC or screening test for chlamydia and/or gonorrhea infection in the third trimester were not included in the analyses (cross tabs, logistic regression, and survival curves); they were only included in the descriptive statistics. Secondary infections were excluded from the analysis. For example, if a woman tested positive for chlamydia initially and was later diagnosed with gonorrhea, the gonorrhea infection was excluded from the analysis and vice versa.
It was necessary to assess whether 1 or more of the covariates measured could be a proxy for the apparent effect of CPPT on the odds of a positive TOC. Hence, logistic regression was used to determine whether any of the covariates had an association with a positive TOC. Parity, EGA at initial test, age <20 years, history of substance use, level of education, and prior STI were included in the regression model. CPPT and gonorrhea infection status were not included in the analysis due to sparse cell counts.
To ensure that EGA did not confound the effect of CPPT, the analysis of CPPT was corrected for EGA. EGA at initial test was stratified by trimester into 3 groups (day 1–93 days, 94–186 days, and greater than 186 days) and analyzed by exact Cochran–Mantel–Haenszel test. The exact P value for a treatment effect of CPPT on TOC is reported, as well as the pooled OR estimate and exact 2-sided 95% CI.
STATA (StataCorp 2011; Stata Statistical Software: Release 12. College Station, TX: StatCorp LP) and the statistical programming package R, library function Mantel-Haenszel test were used for all statistical inferences.
During the initial 16 months of CPPT service implementation, 2938 obstetric patients received prenatal care and delivered at the study site teaching hospital. Of these patients, 241 (8.2%) were diagnosed with chlamydia and/or gonorrhea infection and were included in the study cohort (Fig. 1). Of them, 97.1% (234) of the cohort were Black and 96.7% (233) never married. The median age of the cohort was 20 years; 61.4% (81) were high school graduates; 27.8% (67) admitted to some level of substance use (tobacco or illicit drugs) before pregnancy (Table 1).
Use of CPPT Treatment
Of the 241 pregnant women with chlamydia and/or gonorrhea infection, 92 (38.2%) were offered CPPT. Among these women who were offered CPPT, 45 (48.9%) accepted, whereas the remainder declined (Fig. 1). In total, 196 (81.3%) participants were given a prescription for azithromycin and/or ceftriaxone and advised to refer their partner(s) for STI screening and therapy. The CPPT and patient referral groups differed statistically in marital status and history of an STI (chlamydia, gonorrhea, herpes simplex virus, and syphilis) history (Table 1).
Initial TOC and Repeat Infection
Two hundred thirteen (88.4%) of the study cohort had a TOC performed. Twenty-eight women (11.6%) did not have a TOC performed. The prevalence of an initial positive TOC was 11.6% and 1.66% for chlamydia and gonorrhea infection, respectively, in the entire cohort. There were no initial positive TOCs or repeat positive TOCs in the CPPT group for either chlamydia and/or gonorrhea infection.
Either Chlamydia or Gonorrhea
There were 35 initial positive TOCs in the patient referral group (unadjusted OR = 0, 95% CI = 0–0.37, P < 0.0001) for either chlamydia or gonorrhea infection (Table 2). In the patient referral group, there were 19 (18.1%) repeat positive TOCs (unadjusted OR = 0, 95% CI = 0–1.23, P = 0.12) for either chlamydia or gonorrhea infection (Table 2). The 45 subjects who received CPPT for chlamydia and/or gonorrhea had a 100% decreased odds of having a positive TOC and a 100% decreased odds of having a repeat positive test (Table 2).
There were 28 (14.7%) initial positive TOCs in the patient referral group (unadjusted OR = 0, 95% CI = 0–0.49, P = 0.003) and 17 (17.9%) repeat positive TOCs for chlamydia infection (unadjusted OR = 0, 95% CI = 0–1.44, P = 0.20) (Table 2). The 36 subjects who received CPPT for chlamydia infection had a 100% decreased odds of having a positive TOC.
There were 4 (30.8%) initial positive TOCs in the patient referral group (unadjusted OR = 0, 95% CI = 0–1.67, P = 0.23) and 0 repeat positive TOCs for gonorrhea infection (Table 2). The 4 subjects who received CPPT for gonorrhea infection had a 100% decreased odds of having a positive TOC.
There were 3 initial positive TOCs and 5 repeat positive TOCs in the patient referral group for chlamydia and gonorrhea infection. ORs by CPPT status could not be calculated because of insufficient data.
Time to Cure
The median time to cure was 5.1 weeks (standard deviation [SD] = 3.8) in the patient referral group versus 4.4 weeks (SD = 2.3) in the CPPT group (P = 0.001, log-rank test, 2-sided (Fig. 2).
Multiple Regression Analysis
Parity, age <20, history of substance use, level of education, and prior STI did not significantly confound the effects of CPPT. The EGA at initial test was significantly associated with a decreased likelihood of a positive TOC (OR = 0.99, 95% CI = 0.99–1.00) for either chlamydia or gonorrhea infection (Table 3). The combined OR for a positive TOC in the CPPT versus patient referral groups with either chlamydia or gonorrhea (adjusted OR = 0, 95% CI = 0–0.43, P = 0.001) and chlamydia alone (adjusted OR = 0, 95% CI = 0–0.57, P = 0.005) were estimated while controlling for EGA stratum. CPPT status was not included in the analysis due to sparse cell counts.
This is the first study to evaluate an innovative alternative to EPT in pregnancy. In all, 8.2% of our obstetric population was diagnosed with chlamydia and/or gonorrhea, and the results of the CPPT program were very encouraging. CPPT effectively eliminated a positive TOC, reduced the time to cure, and decreased the number of pregnant patients who presented in labor with a positive chlamydia test as the last documented test result.
We removed the perceived barriers to STI treatment such as lack of insurance coverage, a primary care provider or access to clinical services in order to increase partner participation. However, roughly 1 of every 5 couples received CPPT services, which was a surprising finding. We assumed mothers and fathers would be motivated to accept CPPT services to protect the health of the fetus. Explanations for the 48.9% uptake in patients who were offered CPPT include an overwhelming number of pregnant women who were unable or refused to get partner participation. The remaining women who did not participate were largely because of poor efforts on the part of our staff. The nursing staff was keen to treat pregnant women with an STI immediately after diagnosis; therefore, they were not offered CPPT as an alternative treatment strategy. Interestingly, our rate of uptake was slightly higher than that reported for CPPT use in family planning clinics in California.14 Other studies have shown poor acceptability of EPT services in a real-world clinical setting based on provider type. Therefore, regularly scheduled provider training may have improved the acceptance rate, especially among non-nursing staff.15
Despite the observational study design, our study has several strengths. First, it modeled an alternate partner treatment strategy that can be used in obstetric clinics where providers are uncomfortable with EPT or it is illegal. Second, CPPT visits often were incorporated into the regularly scheduled obstetric visits, which enabled easy access to the sexual partner. Third, observed partner therapy confirmed that the couple was indeed treated thereby eliminating the uncertainty associated with EPT or patient referral. Finally, our study required participation of the sexual partner(s) who was also the father of the baby in majority of the cases. Including the sexual partner in discussions regarding abstinence during treatment and STI prevention helped to educate both individuals of the partnership.
However, nonrandomization of study participants is a major limitation in determining the true impact of CPPT on a positive TOC during pregnancy. In our cohort, we show that those opting to receive CPPT were likely to be single or admitted to a prior STI. These women may be more likely to opt for CPPT because of their history of STI and knowledge of associated morbidity of persistent or recurrent infection. Furthermore, unmeasured factors such as relationship and partner characteristics or health-related behaviors may have contributed to improved outcomes in the CPPT group. Indeed, randomization may have reduced potential biases; however, CPPT is inherently biased because it requires the partner's physical presence. Couples who are willing and able to attend prenatal visits together may have different motivational health behaviors than women who attend alone. Our findings are also limited in application to subjects infected with gonorrhea, given the small sample size for analysis and the differing antibiotics administered. In addition, CPPT is useful only in the clinical settings where the health care provider is able to deliver medications to patients and their sexual partner(s). Despite these limitations, our study is of tremendous value to prenatal care providers who are uncomfortable with EPT and may be considering alternative means of partner therapy. The observational design highlights some of the major issues that must be addressed in a CPPT program or a randomized study.
In sum, our findings demonstrate that CPPT is effective in decreasing the prevalence of a positive TOC for chlamydia infection in obstetric patients. As a public health strategy, CPPT ensures STI treatment of sexual partners who may not have access to care while providing immediate treatment, STI prevention counseling, and referral to health care. CPPT may be a useful alternative to prenatal providers who are legally prohibited or reluctant to provide EPT.
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