Despite an inexpensive and effective cure and a national initiative by the Centers for Disease Control and Prevention (CDC) to eliminate it, syphilis remains a significant public health problem.1 – 3 In fact, during the past decade, the prevalence of syphilis in the United States has increased, with recent estimates of 4.6 cases per 100,000 persons.1
The US Preventive Services Task Force (USPSTF) recommends targeted syphilis screening in patients at increased risk of infection as well as all pregnant women.4 According to the USPSTF, individuals at increased risk for syphilis include men who have sex with men, incarcerated individuals, commercial sex workers, persons who exchange sex for drugs or money, and those diagnosed with other sexually transmitted infections (STI).4
For numerous reasons, however, targeted syphilis screening as recommended by the USPSTF is not routinely performed in emergency departments (ED).5 – 8 Emergency providers (EPs) lack familiarity with these guidelines, and it is not common practice to assess specifically for the risk of syphilis. When syphilis testing is performed in the ED, it is usually performed for diagnostic purposes in patients with signs of syphilis, like a rash or genital ulcer, or at the discretion of the EP when another STI is strongly suspected. Performing targeted syphilis screening in ED patients diagnosed with other STIs (i.e., after a positive test result returns), as the USPSTF recommends, is also impractical. ED patients, in general, cannot be relied on to follow-up, and contacting them by phone is challenging. Normally, when there is any suspicion for a common STI, such as gonorrhea or chlamydia, empirical treatment is provided at the same time as testing; testing is performed primarily for public health–reporting purposes.
Although syphilis screening according to USPSTF guidelines is not well suited to the ED, it may still be possible to develop an ED-specific approach to screening that is both practical and worthwhile. Prior research has demonstrated high rates of syphilis among ED patients evaluated for other STIs.5,7,9,10 It is already routine practice among some EPs at our institution to screen for syphilis whenever testing for gonorrhea and chlamydia (GC/CT). However, this approach to targeted syphilis screening in ED patients has never been directly investigated.
We undertook a pilot study to determine (1) the rate of syphilis screening among ED patients tested for GC/CT; (2) predictors of syphilis screening in this subpopulation; and (3) the prevalence of syphilis among those screened. We hypothesized that, in our urban ED, syphilis screening is performed on a small proportion of patients being tested for GC/CT, and that the prevalence of syphilis among those tested is high. If true, it would signify that there are many missed opportunities for identifying and treating syphilis, and that measures to maximize syphilis screening in ED patients tested for GC/CT are warranted.
MATERIALS AND METHODS
This was a 1-year retrospective cohort study in single, urban ED. This study was approved by the Medical Center's Institutional Review Board with a waiver of consent.
Study Setting and Population
The ED at the Alameda County Medical Center serves as the regional trauma center in Oakland, CA, supports a 4-year accredited residency program in emergency medicine, and has an annual census of approximately 82,000 visits. ED patients are seen either in the higher acuity, main ED (77%) or in the lower acuity, Fast-Track area (23%). During hours when the Fast-Track area is closed (nights), all patients receive care in the main ED, otherwise designation is based on triage acuity.11 EPs include full-time attending physicians (n = 14), resident physicians (n = 40), and physician assistants (n = 10). A 2006 internal review revealed that 47% of patients are black, 32% Hispanic, 44% females, 2% children aged <12 years, and 53% uninsured.
At the time of this study, GC/CT and syphilis testing were at the discretion of the treating physician, and no institutional testing guidelines were in place. Syphilis testing was performed using the rapid plasma reagin (RPR) test (Arlington Scientific, Inc.), and all reactive RPR tests had titers performed and were confirmed using the treponema pallidum particle agglutination assay (TPPA) (Fujirebio Diagnostics, Inc.). In 2010, the Alameda County Department of Public Health estimated the syphilis case rate to be 4.5/100,000 persons with the majority of new infections in men, of which 84% were among men who have sex with other men.12
Study Protocol and Selection of Participants
We analyzed the laboratory and electronic medical records for all ED visits between January 1, 2010 and December 31, 2010 that had GC/CT tests completed.
Data Collection and Processing
A research assistant, trained in data abstraction but not masked to the study purpose, collected and managed the data. During the study period, all GC/CT, complete blood cell count (CBC), RPR, and TPPA tests performed during each ED visit were downloaded from the electronic laboratory record (Siemens, Inc.) and exported to spreadsheets (Microsoft Excel 2003, Microsoft Corporation, Redmond, WA). We included CBC testing as a surrogate marker for whether patients underwent blood testing in addition to GC/CT testing, supposing that not requiring additional blood testing might be a barrier to ordering an RPR. Additional data that were collected as part of the electronic medical record (including patient demographic information, whether empirical GC/CT treatment was performed with ceftriaxone, azithromycin, and/or doxycycline, disposition, homelessness, language spoken, triage acuity level, and ED area of care) were downloaded, exported to the spreadsheets, and linked to the laboratory records by visit-specific patient account numbers. Each patient was then given a unique study number, and patient-identifying information was removed.
The primary outcome measure was the syphilis screening rate among all GC/CT-tested patients, defined as the proportion of patients completing GC/CT testing that had RPR tests performed. The secondary outcome measure was the prevalence of confirmed syphilis among GC/CT-tested patients who also underwent syphilis screening, defined as the proportion of patients completing GC/CT testing that had a TPPA-confirmed reactive RPR test. Confirmed cases of syphilis were further defined as newly diagnosed if the RPR titer was ≥1:16 and previously diagnosed if the RPR titer was ≤1:8.9
Primary Data Analysis
Unless otherwise specified, each patient visit was analyzed as a separate patient encounter. Continuous data are reported as means with standard deviations, and categorical data are reported as percentages with 95% confidence intervals (CIs). We explored bivariate relationships using the chi-square test to identify covariates associated with performing syphilis testing. Covariates included gender, age, race/ethnicity, homelessness, marital status, results of GC/CT testing, whether empirical GC/CT treatment was performed, whether CBC testing was performed, admission status, acuity, and area of care treatment was received. We then performed multivariable logistic regression to identify independent predictors of performing syphilis screening. We analyzed age as a dichotomous variable at ≤25 years consistent with USPSTF recommendations. Our model specified the use of covariates significant at P ≤ 0.10 in bivariable comparisons. We further used Pearson chi-square test to assess for goodness-of-fit. Results are presented as odds ratios (ORs) with 95% CIs. All data were analyzed using Stata version 10.1 (StataCorp LP, College Station, TX).
Figure 1 shows the results of all syphilis testing in the ED during the study period. Gonorrhea/chlamydia tests were performed in 3951 (4.7%) of the 83,988 total ED visits; of which, 332 tests (8.4%) were reactive (chlamydia reactive only, n = 221, gonorrhea reactive only, n = 76, both chlamydia and gonorrhea reactive, n = 35). Syphilis screening was completed in 1218 (31%) of the 3951 GC/CT-tested visits; of which, 21 tests (1.7%; 95% CI: 1.1%–2.6%) were RPR reactive, 17 of which were confirmed TPPA reactive (1.4%; 95% CI: 0.82%–2.2%). These 17 confirmed tests were in 16 unique patients; of which, 8 (50%) had newly diagnosed syphilis (median RPR titer 1:32; range, 1:16–1:256) and 8 had previously diagnosed syphilis (median RPR titer 1:2; range, 1:1–1:4). Of the 8 patients with newly diagnosed syphilis who were also tested for GC/CT, all were black, 6 were males, and the average age was 25 years.
For comparison, in our ED during the same time period, syphilis testing was completed in 580 (0.7%) of 80,037 visits without GC/CT testing; of which, 24 (4.1%; 95% CI: 2.7%–6.1%) were RPR reactive and 20 were confirmed TPPA reactive (3.4%; 95% CI: 2.1%–5.3%). These 20 confirmed tests were performed in 18 unique patients; of which, 10 (56%) had newly diagnosed syphilis (median RPR titer 1:64; range, 1:32–1:256) and 8 (44%) had previously diagnosed syphilis (median RPR titer 1:4; range, 1:1–1:8). Of these 10 patients with newly diagnosed syphilis who were not also tested for GC/CT, 7 were black, 9 were male, and the average age was 36 years.
Characteristics of patients tested for GC/CT are shown in Table 1. The mean age was 22.6 ± 12 years, and most were female (67%), black (47%), and English speaking (74%). Nearly half (44%) had other blood tests performed, and 19% of patients were empirically treated for GC/CT.
The syphilis screening rate among the patients empirically treated for GC/CT was greater than that among the patients not empirically treated (49%, 371/758 vs. 27%, 862/3193; P < 0.001). The prevalence of TPPA-confirmed syphilis, however, was similar between patients empirically treated for GC/CT with those who were not (0.4%, 3/758 vs. 0.4%, 14/3193; P = 0.869).
Among patients tested for GC/CT, the following unadjusted predictor variables were associated with being screened for syphilis: ≤25 years old, male, black, English speaking, single, triage to the Fast-Track, low acuity, discharged, empirical treatment for GC/CT, and testing GC/CT reactive. In regression analysis, the following predictors were independently associated with syphilis screening: empirical treatment for GC/CT (OR: 1.9, 95% CI: 1.6–2.3), triage to the Fast-Track (OR: 1.8, 95% CI: 1.4–2.3), a reactive GC/CT test (OR: 1.3, 95% CI: 1.0–1.6), and being ≤25 years (OR: 1.2, 95% CI: 1.0–1.4) (Table 2). Patients with the following predictors were less likely to undergo syphilis screening: those who had CBC tests performed (OR: 0.33, 95% CI: 0.28–0.41), females (OR: 0.53, 95% CI: 0.45–0.63), high acuity (OR: 0.60, 95% CI: 0.50–0.71), Spanish speaking individuals (OR: 0.62, 95% CI: 0.47–0.82), and married (OR: 0.68, 95% CI: 0.53–0.87).
We believe that implementing the USPSTF guidelines for syphilis screening in the ED setting is impractical and that other approaches to targeted screening better suited to the ED are needed. Syphilis screening in the ED must balance maximizing the yield of new syphilis diagnosis with feasibility, taking into account existing ED processes, episodic patient care, challenges with patient follow-up, and cost.
In this study, we looked at the rate of syphilis screening and the rate of syphilis infection among ED patients tested for GC/CT. In our ED, the majority of patients undergoing GC/CT testing were not screened for syphilis. Among those who were screened for syphilis, however, the prevalence of TPPA-confirmed tests was 1.4%, with 50% estimated to represent new syphilis diagnoses. Our findings confirm that ED patients tested for GC/CT are at high risk for syphilis and are an appropriate population for targeted screening. Missed opportunities for syphilis diagnosis likely occurred among those who were not screened.
Our low syphilis screening rate of 31% is similar to that found in other ED studies reporting syphilis testing among patients evaluated for STIs.5 – 7,10 Merchant et al recently reported that 73% of 968 ED patients with suspected GC/CT urethritis were not screened for syphilis and Guss et al reported that during a 21-month period, 63% of 308 ED patients diagnosed with an STI were not screened for syphilis.5,7 Among ED patients diagnosed and treated for STIs in a Philadelphia teaching hospital, syphilis screening rates as low as 16% were reported.6 Lastly, a 3-month, prospective study of syphilis screening all ED patients aged 15 to 44 years was only able to achieve a screening rate of 25%.10
The most likely explanation for our relatively low syphilis screening rate is that GC/CT testing is performed in patients with a wide range of actual clinical suspicion for infection. Emergency physicians recognize that the syphilis prevalence is significantly lower than GC/CT prevalence and probably, informally risk-stratify patients who they test for GC/CT, and test for syphilis only selectively. We do not know how well our EPs understand the epidemiology of syphilis, but they may base their decision to test for syphilis on risk factors for syphilis coinfection, such as men reporting having sex with men, suggestive physical findings, such as rash or genital ulcerations, and on the perceived likelihood of GC/CT infection. This is supported by our findings that EPs seemed to reserve syphilis testing for a higher risk cohort of patients, namely those who were younger, male, single, minority, and who they treated empirically for GC/CT.
In our study, the rate of newly diagnosed syphilis among the 1218 patients who were tested for both GC/CT and syphilis was 0.7%. Prior ED research has reported rates of syphilis among patients evaluated for other STIs, ranging from 3% to 6%.5,7,9,10 A retrospective chart review of all ED patients diagnosed and treated with an STI reported a syphilis prevalence of 3% among the 113 patients tested.7 Merchant et al retrospectively reviewed the medical records of nearly 1000 ED patients with suspected GC/CT urethritis (based on relevant International Classification of Diseases-9 codes) and found a syphilis prevalence of 3% among the 258 patients tested for it.5 Ernst et al screened 260 ED patients with clinical symptoms consistent with a variety of STIs and found 16 (6%) to be positive.9 The results of a 2-month screening program in a Philadelphia ED reported a similarly high prevalence of new syphilis diagnoses among patients with other STIs.10
Rates of syphilis in these studies are higher than what we report, probably because of differences in the study populations. The inclusion criteria of STI patients were more strictly defined than in our study, selecting for higher risk patients who were more likely to actually test positive for an STI, and thus for concurrent syphilis infection. In fact, when reported, the prevalence of gonorrhea and/or chlamydia was several times greater than the 8.4% prevalence among our study population.5,9 In the study by Merchant et al, the rate of reactive GC/CT tests was 29%, and in the study by Ernst et al, the prevalence of gonorrhea was 50% and chlamydia was 12%.5,9 In our study, we analyzed the results of syphilis testing among all ED visits where a GC/CT test was performed. The indications for GC/CT testing in our data set are varied and include patients evaluated for presumed high-risk diagnoses (urethritis, cervicitis, or pelvic inflammatory disease) as well as low-risk complaints, such as voiding symptoms or lower abdominal pain. Unfortunately, our data set does not allow us to stratify patients based on complaint or reasons for testing. Additionally, the availability of urine GC/CT testing at our institution has likely lowered the testing threshold, leading to more testing in low-risk patients and lower diagnostic yield.
Whether the results of this study actually support targeted syphilis screening in all ED patients tested for GC/CT is debatable. A specific population prevalence cutoff that warrants syphilis screening has not been proposed by the CDC or the USPSTF. Although our data show that ED patients tested for GC/CT are at a substantial risk for syphilis coinfection, the prevalence of syphilis that we would find if all GC/CT-tested patients were successfully screened would likely be lower than the 0.7% we found in patients who were selected by EPs for syphilis testing.
Nonetheless, we believe that syphilis screening is warranted in the ED subpopulation tested for GC/CT. In our ED, the relatively modest yield is balanced by the potential simplicity and feasibility of automatically linking syphilis screening with GC/CT testing. This approach would increase targeted syphilis screening and would lead to the diagnosis and treatment of many of the currently untreated syphilis cases in our county whose 4.5/100,000 case rate far exceeds the CDC and the Department of Health and Human Services goal of <0.4/100,000.2,3 Future research should prospectively evaluate the yield of this targeted screening approach, incorporating interventions that maximize syphilis screening in patients tested for GC/CT. These interventions would include automatic physician test prompts, STI electronic order sets which bundle GC/CT and syphilis tests, and the use of opt-out syphilis screening when patients are evaluated for STIs.
If ED syphilis screening is to be expanded, adequate follow-up must be ensured. Mechanisms should be in place to (1) notify providers of reactive RPR and confirmatory test results; (2) notify patients of test results; (3) ensure for appropriate follow-up and treatment; and (4) monitor RPR titers after treatment. It will be a challenge for EDs to provide these functions alone, and partnering with primary care physicians, STI clinics, and the local department of public health will be required.
This study has several limitations. The results of this study from a single center, inner-city population may not be generalizable to other ED settings, especially those where GC/CT-tested patients have a different demographic makeup and disease prevalence.
Because of the retrospective design, our analysis was limited to data available in the electronic medical record. Our data set did not allow determination of whether diagnostic syphilis testing led to screening for GC/CT or whether GC/CT testing led to syphilis screening. Patients tested for syphilis alone, however, were considerably more likely to have reactive tests than patients tested for both syphilis and GC/CT. This suggests that syphilis testing alone was probably done for diagnostic purposes in patients with signs or symptoms of syphilis infection, whereas actual syphilis screening, with a lower yield, was done in patients primarily evaluated for GC/CT.
Because our study sample was limited to patients tested for GC/CT, we may have missed other STI cases where syphilis testing was indicated and/or performed, such as suspected chancroid, HIV, condyloma, or herpes, or cases when GC/CT infection was empirically treated without testing for it.
Central to assessing the potential impact of screening is determining the number of truly new syphilis cases identified. Unfortunately, we do not know with certainty whether the presumably new cases of syphilis in this study were previously reported or treated. We classified cases with an RPR titers ≥1:16 as new. However, classifying a diagnosis of syphilis as new, based solely on serology can be misleading.13 Although RPR screening tests are increasingly being replaced by enzyme immunoassay testing, the CDC continues to recommend that nontreponemal tests be used to screen for syphilis and that treponemal testing be used to confirm syphilis as the cause of nontreponemal reactivity.14 Ongoing studies are expected to provide a better understanding of new serologic tests for syphilis and how best to incorporate them into practice settings such as the ED.
In conclusion, the majority of patients undergoing GC/CT testing in our ED are not screened for syphilis, yet the prevalence of infection in those screened is substantial. This suggests there are many missed opportunities for syphilis diagnosis in this ED subpopulation and that it may be an appropriate target for syphilis screening. Measures to maximize syphilis screening in all GC/CT-tested individuals—and the yield of such an approach—should be studied.