Hotton, Anna L. MPH*†; Gratzer, Beau MPP*‡; Pohl, Daniel BA/BS*; Mehta, Supriya D. PhD, MHS†
Men who have sex with men (MSM) are disproportionately affected by STDs and HIV in the United States.1 Since the late 1990s, increases in risk taking and outbreaks of syphilis and gonorrhea have been documented among MSM in the United States,2–10 an alarming reversal of the downward trends that occurred during the height of the AIDS epidemic.
Rates of syphilis began to increase in the United States around 2000 after reaching an all-time low. This trend was largely driven by increases among MSM,11 marking a shift in the epidemiology of syphilis and raising concerns about increases in risk behaviors and the potential for concomitant increases in new HIV infections. The rate of primary and secondary (P&S) syphilis in men increased by 54% between 2002 and 2006; in 2008, MSM accounted for 63% of all P&S syphilis diagnoses.11 These trends highlight the need for enhanced screening and interventions that address the unique prevention needs of MSM.
Syphilis facilitates HIV transmission and acquisition and represents risk behaviors that may increase the risk of HIV transmission.10,12 HIV coinfection of 50% to 70% has been reported among patients diagnosed with early syphilis.3,7,13–16 HIV infection can change the course of syphilis infection and complicate clinical management, particularly among individuals with higher levels of immunosuppression.17,18 Higher RPR titers, multiple primary chancres, more rapid disease progression, slower response to treatment and symptom resolution, and higher risk for relapse and progression to neurosyphilis have been observed among HIV-coinfected syphilis patients compared to their HIV-negative counterparts.17,19,20 Close monitoring of HIV-infected patients diagnosed with syphilis is warranted in order to reduce the potential for development of serious sequelae.
The Centers for Disease Control and Prevention (CDC) recommends clinical and serologic rescreening at 6 and 12 months for all patients diagnosed with early syphilis.21 More frequent screening, at 3-month intervals, is recommended for HIV-coinfected patients and those for whom follow-up is uncertain.21 Serologic monitoring is the only way to determine adequate treatment response, which is typically defined as a four-fold decline in rapid plasma reagin (RPR) titer within 6 months of treatment for patients with primary or secondary syphilis and within 12 months of treatment for patients with early latent syphilis.21 Failure of the RPR titer to decline, or a rise in RPR titer in the absence of reinfection, may be an indication of treatment failure and/or central nervous system invasion and may require additional treatment and/or cerebrospinal fluid evaluation.21
Low follow-up rates have been reported among patients diagnosed with syphilis at sexually transmitted disease (STD) clinics, making it impracticable to monitor these patients for appropriate serologic response following treatment.22 Although patients with a primary care provider may be expected to have more consistent follow-up, few studies have looked at factors affecting follow-up among primary care patients. We examined patient characteristics associated with a return visit to the clinic within 6 months of initial diagnosis, and among patients with a 6-month follow-up visit, patient factors associated with provider testing behavior. The information was used as feedback for medical providers to guide clinical management and in the development of educational messages for patients about the importance of rescreening after a diagnosis of syphilis.
MATERIALS AND METHODS
Subjects and Data Collection
We conducted a historical records-based cohort study, using data collected as part of the MSM Prevalence Monitoring Project. Because the data were collected as part of routine public health surveillance, informed consent was not required. Subjects included MSM age 18 and older who received primary medical care at Howard Brown Health Center, the largest LGBT (Lesbian, Gay, Bisexual, and Transgender) health center in the Midwest. Howard Brown has a primary care facility and also provides STD testing through a separate walk-in clinic. Follow-up among patients at the STD clinic is generally very low, and patients who do return to the clinic often do so for STD-specific symptoms. We limited our analysis to patients in primary care because this is a stable patient population in which we would be able to assess “missed” opportunities.
MSM were defined as men who identified as gay or bisexual and/or reported sex with a man in the previous 60 days. All clients with an initial diagnosis of primary, secondary, or early latent syphilis between January 2002 and December 2008 were included. Subsequent visits were analyzed to determine the proportion who met the CDC criteria for rescreening within 6 months of initial diagnosis. We included all return patient visits that took place through December 2009, to allow for a full year of follow-up of initial diagnoses through December 2008. We excluded 22 visits that took place within 30 days of the initial diagnosis because of limited clinical relevance in terms of rescreening. Demographic information, HIV status, and clinical and diagnostic information were extracted from electronic medical records. Diagnoses of syphilis were made based on CDC staging criteria and compared with Disease Intervention Specialist (DIS) records for accuracy. STD history was defined as a reported history of syphilis, gonorrhea, chlamydia, herpes, genital warts, or other STDs.
The outcomes for analyses were: timely follow-up (defined as having a return visit within 6 months of initial diagnosis), and repeat syphilis testing within 6 months of initial diagnosis (among patients who returned to the clinic). Additionally, we examined how the time from initial syphilis diagnosis to subsequent testing varied by explanatory variables.
We examined associations between syphilis stage at initial diagnosis, year of diagnosis, age, race/ethnicity, HIV status, STD history at the time of diagnosis, and each of the 2 study outcomes: timely follow-up and repeat testing. Period of diagnosis was dichotomized as diagnosis in 2007–2008 versus diagnosis in 2002–2006. This dichotomy was chosen because a new electronic medical record system was implemented in late 2006, and follow-up was thought to have improved after this time. There were no differences in follow-up or repeat testing among patients diagnosed during 2002–2004 and those diagnosed in 2004–2006, so the earlier periods were combined. We initially examined race/ethnicity as a 4-category variable (white, black, Hispanic, other); however, because there were no differences in either outcome variable among the nonwhite racial/ethnic groups, we combined them for subsequent analyses and compared white versus nonwhite race/ethnicity. Age was analyzed as a continuous variable and dichotomized about the median (age >34 vs. ≤34).
We used Pearson χ2 tests to assess differences in independent proportions and Wilcoxon tests to assess differences in distributions of continuous variables between clients with and without adequate follow-up. We compared median time between initial diagnosis and subsequent syphilis testing according to age, race/ethnicity, stage at diagnosis, HIV status, STD history, and year of diagnosis with the Wilcoxon rank sum test. Confidence intervals around median follow-up times were calculated based on the binomial distribution. Similar analyses were conducted to identify factors associated with follow-up, and factors associated with repeat syphilis testing among patients who returned to the clinic. We used Poisson regression with robust error variance to calculate adjusted relative risks (RR) and 95% confidence intervals (CI) for associations between covariates and follow-up and repeat testing. Variables with a P < 0.10 in exploratory analyses were entered into multivariable Poisson regression. Age and race/ethnicity were included in multivariable Poisson regression despite lack of significance in univariate analysis for consistency with other published literature. STD history was removed from multivariable models because of high correlation with HIV status, and because HIV status explained more of the overall variance in follow-up than STD history. Data were analyzed using SAS version 9.2.
From January 2002 through December 2008, 5788 tests for syphilis were performed among MSM in primary care, and 256 (4.4%) cases of early syphilis were detected among 225 men: 46 (20%) primary, 91 (40%) secondary, and 88 (39%) early latent (Table 1). After the initial diagnosis, 134 of 225 (59.6%) had a return visit within 6 months, and cumulatively 161 of 225 (71.6%) had a return visit within 1 year. The median time between initial diagnosis and return visit was 4.0 months (95% CI: 3.7–4.5 months). The cumulative proportion of patients who were rescreened rose with increasing time since the initial diagnosis, from 52% among patients who returned at 1 to 3 months to 70% at 6 months and 86% at 12 months. Patients were primarily white (53%) and HIV-positive (75%), with a previous STD history (71%).
Factors Associated With Timely Follow-up
In univariate analysis, patients who were HIV-positive, diagnosed with secondary or early latent syphilis, and diagnosed with syphilis in 2007–2008 were more likely to return to the clinic within 6 months (Table 1). There were no differences by age or race/ethnicity in the proportion with timely follow-up. In multivariable Poisson regression analysis, HIV status and diagnosis in 2007–2008 were significant predictors of 6-month follow-up after adjustment for other covariates (Table 2). HIV-positive men were more likely to return to the clinic within 6 months (aRR = 1.93; 95% CI: 1.31–2.85); as were those diagnosed in 2007–2008 (aRR = 1.28; 95% CI: 1.04–1.57). When analysis was restricted to HIV-positive men (results not shown; available from authors), those with STD history were less likely to return to the clinic within 6 months (RR = 0.79; 95% CI: 0.64–0.98); there were no other associations with any of the covariates and follow-up.
Factors Associated With Repeat Testing Among Men With 6-Month Follow-up
Among patients with timely follow-up (n = 134, Table 1), diagnosis in 2007–2008 was associated with a greater likelihood that the patient was tested at the return visit (aRR = 1.24; 95% CI: 1.00–1.53). Patients diagnosed with secondary or early latent syphilis were less likely to be screened at the return visit (aRR = 0.80; 95% CI: 0.65–0.99). No other patient characteristics, including age, race/ethnicity, or HIV status, were associated with testing at the return visit (Table 3). When the analysis was restricted to HIV-positive patients (results not shown), diagnosis in 2007–2008 was associated with increased likelihood of repeat testing at 6 months (aRR = 1.30; 95% CI: 1.05–1.61). Those diagnosed with secondary or early latent syphilis were less likely to be retested at 6 months (aRR = 0.81; 95% CI: 0.64–1.01), as were those over the age of 34 (aRR = 0.80; 95% CI: 0.62–1.03).
As a continuous outcome, HIV-positive patients had shorter time from initial diagnosis to subsequent tests compared to those whose HIV status was negative or unknown (5.6 vs. 7.1 months; P = 0.067) (Table 4). Over time, there was a significant decline in time from initial diagnosis to repeat syphilis test, from 6.5 months in 2002–2006 to 4.6 months in 2007–2008 (P = 0.020).
The extent to which CDC recommendations for rescreening are met depends on a combination of patient and provider behaviors, namely that the patient returns to the clinic in a timely manner after diagnosis and then that the provider tests for syphilis at the follow-up visit. Overall, only 60% of clients returned to the clinic within 6 months of initial diagnosis and 30% of those who returned were not retested. HIV-positive patients were more likely to return to the clinic in 6 months, a finding that was expected based on standard clinical recommendations that HIV-positive patients be scheduled for routine laboratory assessments at 3 to 6 month intervals.
Encouragingly, our results demonstrate that both follow-up and rescreening improved during the study period. This likely resulted from increasing utilization of the electronic medical record system that was implemented in late 2006 to generate patient reminders for follow-up, and expanded efforts by DIS to encourage patients to screen regularly in the first year after diagnosis, including offering reminder phone calls to patients. Patients diagnosed in 2007–2008 were more likely to return to the clinic within 6 months of initial diagnosis, increasing from 53% in 2002–2006 to 76% in 2007–2008. While current methods for improving follow-up have been effective, additional methods for motivating patients to take an active role in their follow-up are needed.
In terms of provider testing behaviors, just over half of patients who returned to the clinic within 1 to 3 months of diagnosis were rescreened for syphilis. It is debatable whether rescreening is necessary during this period, but it is clinically prudent to err on the side of caution if future follow-up is uncertain and because 75% of primary care patients were HIV coinfected at the time of syphilis diagnosis. Our clinic serves a high risk population with a relatively high percentage of reinfection. We believe close monitoring is particularly important in this population because there may be greater potential for ongoing transmission compared to a general population cohort. The fact that HIV-positive patients were not more likely to be rescreened at 6 months among patients with timely follow-up suggests that providers may benefit from education as to the importance of more frequent screening among HIV-positive patients. It is possible that failure to screen HIV-positive patients at shorter intervals reflects a lack of concern by providers about loss to follow-up among these patients. In keeping with the improvements in timely follow-up, testing among patients who returned to the clinic within 6 months of initial diagnosis increased from 64% in 2002–2006 to 81% in 2007–2008. However, although timely follow-up and clinician screening increased, even in this later period, the combination of lack of timely follow-up and rescreening resulted in 39% of patients without CDC recommended follow-up. These results highlight a need for provider education, and provide a basis for adjusting clinical practice.
Appropriate follow-up is important for ensuring adequate treatment response, and also offers additional opportunities for HIV testing, education, and preventive counseling. Although it may be difficult to distinguish treatment failure from reinfection among asymptomatic patients, both require prompt clinical attention. Studies have shown high rates of reinfection (of 7%–12%) among MSM diagnosed with syphilis, particularly among HIV-infected MSM.23,24 In our study, 11% of clients were diagnosed with syphilis on more than 1 occasion. Frequent rescreening provides an opportunity to detect new infections early, and to offer treatment to sexual contacts of patients diagnosed with syphilis to interrupt disease transmission; prompt detection and treatment is particularly important for a disease in which symptoms are often unrecognized and which tends to cluster in core high-risk groups.25 Because syphilis increases the risk of HIV transmission and acquisition,12,26 prompt identification and treatment is important for reducing the spread of both infections.
Our results may not be generalizable to other MSM populations or other clinical care settings. Low follow-up rates have been documented among STD clinic patients. In a study of STD clinic patients diagnosed with syphilis in Baltimore, 64% of HIV-positive patients and 77% of HIV negative patients had no documented follow-up syphilis serology.22 In a study in San Francisco, diagnosis at the municipal STD clinic was associated with lower likelihood of having a follow-up test within 6 months of initial diagnosis.27 Compared to those seeking care in STD clinics or other acute care settings, MSM in primary care represent a relatively stable population. As an LGBT-focused health center, medical providers are familiar with issues specific to the MSM community, and as a high morbidity area for syphilis and HIV, providers are accustomed to caring for coinfected patients. The majority of primary care patients diagnosed with syphilis are HIV infected. These patients have routinely scheduled visits as part of their HIV care, so it is particularly easy for providers to request syphilis testing as part of routine HIV laboratory evaluation. Howard Brown has an established DIS program, in which DIS work collaboratively with medical providers on the management and follow-up of patients diagnosed with syphilis. The DIS has a unique opportunity to engage with and encourage patients to take an active role in their medical care. For these reasons, our results may represent an optimistic measure of follow-up. Additional data are needed to explore the barriers to timely follow-up among MSM. It is unclear whether failure to follow-up in a timely manner was due to patients' lack of knowledge about the importance of rescreening, lack of emphasis by the provider, other structural issues like convenience of testing, or a combination of these.
Our study has several limitations. First, it was not possible to determine whether clients were tested at venues other than Howard Brown in Chicago or elsewhere. We were also unable to determine whether clients moved out of the area or changed healthcare providers. We assumed that if clients were retested they would have been tested at our facility because they were in primary care at Howard Brown; however, this likely underestimates rates of follow-up and retesting. During the study period, limited information was available on behavioral risk among MSM in primary care, so the extent to which risk assessment by the provider and/or risk taking by the patient influenced follow-up and rescreening behaviors is unknown and warrants further research. Finally, small sample size may have limited our ability to detect associations between patient characteristics and follow-up screening.
It appears that expanded DIS efforts led to improvements in timely follow-up. Although follow-up and rescreening improved over time, a substantial proportion of patients do not return for follow-up and among those who do, many are not rescreened by providers. Our results highlight a need for developing additional strategies for motivating patients to take an active role in their follow-up, even for patients with a regular source of medical care. Timely rescreening for syphilis should be emphasized for both clinicians and clients. HIV status was the primary patient factor associated with timely follow-up, which reflects the importance of having an established source of care. The observed improvements in rescreening demonstrate the potential for improving clinical care through effective utilization of DIS programs and electronic medical record systems.
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