McLean, Catherine A. MD*; Kohl, Katrin MD, MPH†; Baker, Meghan A. MD‡; Sinclair, Maureen F. MPH§; Ciesielski, Carol A. MD*∥; Markowitz, Lauri E. MD*
IN THE EARLY TWENTIETH CENTURY, syphilis was one of the leading causes of mental illness, blindness, and cardiovascular disease in the United States. 1,2 Following the discovery of penicillin and the implementation of widespread syphilis serologic screening programs, syphilis declined sharply. 3 In 2001, the rate of primary and secondary syphilis increased for the first time since 1990, threatening recent gains in the efforts to eliminate syphilis in the United States 4–6 and highlighting the importance of identifying all cases of infectious syphilis to facilitate prompt control of transmission.
Syphilis surveillance, based upon laboratory reporting of serologic tests for syphilis (STSs), provider clinical reporting, and follow-up investigations by the health department, was established in the United States in 1941 and is critical for syphilis control. The primary objectives of syphilis surveillance are (1) to limit syphilis transmission by rapidly identifying and treating persons with infectious syphilis and (2) to monitor epidemiologic trends in syphilis to inform prevention efforts.
Most new syphilis cases are identified through laboratory reporting of reactive STSs to local health departments, as mandated by state laws. 7 However, STSs are not specific for untreated syphilis. Nontreponemal STSs, such as the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR), are highly sensitive tests that are used for screening and result in occasional false-positives. 8,9 Nontreponemal STS titers vary with the stage of syphilis and are typically higher with active infection, declining in response to therapy. While STS titers usually become undetectable after treatment, in some persons nontreponemal STSs may remain reactive despite effective therapy. 10
For these reasons, reactive nontreponemal tests are confirmed with treponemal tests, such as the fluorescent treponemal antibody absorbed test (FTA-ABS) or the Treponema pallidum particle agglutination test (TP-PA). 8,9 However, treponemal tests can be expected to remain reactive despite effective therapy; a reactive treponemal test may represent past or active infection. Therefore, persons may have a reactive STS with new, untreated infections as well as with prior, effectively treated or prior, untreated syphilis.
Because of test limitations, diagnosis of a new syphilis infection requires interpretation of a STS within the context of a person's symptoms, prior STS results, and history of syphilis infection and treatment. 11,12 Typically, health department personnel review medical records and may conduct field investigations to collect additional historical and clinical information. The objectives of the field investigation are to identify persons with active syphilis infection who have not been adequately treated and to treat sex partners at risk of infection. The evaluation of persons with reactive STS can be time-consuming and costly, especially in areas where many STSs are reported. 13
Because of limited resources, many health department sexually transmitted disease (STD) programs use “reactor grids” to determine which persons with reactive STSs will be evaluated as described above. Reactor grids are sex, age group, and STS titer criteria, arranged on a table layout, used to categorize persons with reactive STS. 14 Reactor grid criteria are determined by local health departments and are typically used to select for further evaluation persons who are younger, have higher titers, and are at greatest risk of transmitting syphilis to a newborn in the form of congenital syphilis (women of child-bearing age).
The Chicago Department of Public Health (CDPH) uses a reactor grid to identify which persons with a reported STS should be evaluated for untreated syphilis, except at the CDPH STD clinics and Cook County Jail, where all reactive STSs are evaluated. The CDPH reactor grid has separate criteria for men and women (Figure 1).
In 1999, Cook County, which includes Chicago, reported the second largest number of primary and secondary syphilis cases in the United States, and beginning in 1998, increases in syphilis among men who have sex with men (MSM) were identified in Chicago, 15 consistent with syphilis outbreaks occurring among MSM in other major United States cities. 16–18
In light of high syphilis morbidity and the increase in syphilis among MSM, we evaluated reactor grid performance and potential implications of its use in Chicago, and we assessed reactor grid use nationally.
Reactor Grid Performance in Chicago
To evaluate reactor grid criteria used by CDPH, we (1) determined whether persons with a reactive STS met reactor grid criteria and were identified as having untreated syphilis and described characteristics of persons not meeting reactor grid criteria and (2) determined how many previously reported, early syphilis cases from sources not using the reactor grid would have been excluded from evaluation and ultimately not reported if reactor grid criteria had been used.
We reviewed all reactive STSs reported to CDPH from (1) Cook County Hospital during a 3-month period in 1999 and (2) all other Chicago providers during a 9-month period in 1999 to 2000, using CDPH records. The number of persons with a reactive STS who did and did not meet reactor grid evaluation criteria, the number who had a medical record review, the number who were referred for a field investigation, and the number who were reported to the Centers for Disease Control and Prevention (CDC) was recorded. Characteristics of persons with a reactive STS who did not meet reactor grid criteria and were therefore not evaluated by the health department were analyzed.
To determine cases of previously reported early syphilis that would have been excluded from evaluation if reactor grid criteria had been used, data from early syphilis cases diagnosed at six CDPH STD clinics and Cook County Jail in 1998 were abstracted from CDPH files. Using syphilis case age, sex, and STS titer, we applied Chicago reactor grid evaluation criteria and determined the characteristics of persons with syphilis who did not meet the evaluation criteria.
National Health Department Survey of Syphilis Surveillance and Reactor Grid Use
We surveyed the 60 health department STD programs in the United States to collect information regarding reactor grid use in 2000. Questions regarding syphilis reactor grid use and case reporting were asked, and reactor grids were reviewed. The survey was distributed by e-mail to the STD Program Managers and returned by e-mail and fax. A follow-up e-mail was sent to nonresponders.
Reactor Grid Performance in Chicago
Among persons with reactive STS, 46% (165/356) did not meet the reactor grid criteria (Figure 2); 62% of men (115/185) and 29% of women (50/171; P < 0.001) with a reactive STS received no further evaluation by the health department. Most persons excluded had titers <1:8. Of persons with titers ≥1:8, 21% (19/91) were not evaluated. Of the individuals who met reactor grid evaluation criteria, 61% (117/191) were subsequently excluded from further investigation following medical record review, and 39% (74/191) were referred for field investigation. Of those referred for field investigation, 19% (14/74), or 4% of the total 356 persons with a reactive STS, were newly identified cases of syphilis and were reported to the CDC. Overall, 140 of the 191 who met reactor grid criteria were determined to have had a history of treated syphilis or had a reactive STS due to another cause (e.g., false positives), and 37 were lost to follow-up.
Of the 669 early syphilis cases reported from CDPH STD clinics and Cook County Jail in Chicago in 1998, 71 (11%) did not meet reactor grid evaluation criteria and may have been excluded from further evaluation if the reactor grid had been used (Table 1). Overall, 17% of men (69/403) and 1% of women (2/265) with early syphilis, including 17% of persons with primary syphilis (9/54), would have been excluded from evaluation and ultimately not reported by use of reactor grid criteria.
National Health Department Survey of Syphilis Surveillance and Reactor Grid Use
A total of 45 (75%) of 60 health department STD programs responded to the survey. Overall, 82% of health departments (37/45) completing the survey reported using reactor grids. A wide range of reactor grids were used, none of which was identical. Most STD programs using reactor grids had different reactor grid criteria for men and women; 76% selected pregnant women and 32% had female sex as an additional criterion for selecting persons for evaluation. Overall, 16% of STD programs conduct no evaluation of a reactive STS for persons ≥60 years of age, regardless of titer. Most reactor grids include a combination of age and titer criteria to indicate who should be evaluated. Of the reactor grids reviewed, 78% did not evaluate some persons with syphilis titers ≥1:8, including nine programs that did not evaluate some persons aged ≤50 years with a syphilis titer ≥1:8.
Variations in syphilis case reporting were also found. Overall, 48% of STD programs (20/42) reported new syphilis cases to the CDC only if adequate treatment was documented.
In Chicago, newly identified cases of syphilis represented only a small proportion of those with a reactive STS reported to the health department. In our investigation, a large number of persons with a reactive STS did not meet reactor grid criteria and therefore were not referred for further evaluation by the health department, including some persons with syphilis titers ≥1:8. Men were more likely than women to be excluded from further investigation because of different evaluation criteria by sex. Data were not available to determine if any individuals excluded from investigation had untreated syphilis, because follow-up of all persons with a reactive STS was not done.
However, our data show that in populations with a high prevalence of syphilis, such as STD clinic and jail populations, the use of reactor grids may result in failure to identify and treat a substantial number of persons with infectious syphilis, including primary syphilis, particularly among men. Of the diagnosed syphilis cases we studied, 11% would have been missed if the reactor grid had been used. While clinical reporting of syphilis cases would lower the number of cases missed (because they are not subject to the reactor grid), most syphilis test reports come from laboratories. 14
In the absence of a specific test for untreated syphilis, reactor grids may focus disease control efforts on persons most likely to have infectious disease. In cities where large numbers of reactive STSs are reported, reactor grids may also help allocate limited health department resources to the most highly infectious syphilis cases and those most likely to lead to congenital syphilis. However, data from our investigation in Chicago indicate that some persons with relatively high titers (≥1:8) were excluded from evaluation by reactor grid criteria.
Further complicating STS interpretation is the clinical use of syphilis titers to follow response to therapy; persons with syphilis will frequently have several STSs performed in the months following initiation of treatment. Even after use of the reactor grid, medical record review found that 73% of persons meeting reactor grid evaluation criteria had a history of treated syphilis or a false-positive test.
Reactor grids may have a substantial impact on syphilis diagnosis, surveillance, and control. Our survey found that reactor grids are used by most STD programs and that criteria vary considerably between STD programs. In cities like Chicago, where there is a resurgence of syphilis among MSM, reactor grid use may limit the timely detection and control of syphilis outbreaks. With the epidemiology of syphilis evolving, local reactor grid criteria must be regularly evaluated in areas where reactor grids are used. 14,19
The increase in syphilis among MSM and the results of this investigation led CDPH to revise Chicago's reactor grid evaluation criteria to initiate follow-up evaluations on more men, especially those with high titers.
The results of our investigation highlight not only the role of the reactor grid but also other aspects of syphilis surveillance, including difficulties in conducting field investigations. Of the 74 persons referred for field investigation, 50% were lost to follow-up. Syphilis patients may be difficult to locate for several reasons, including social problems and distrust of health departments, 20 making it difficult to complete investigations. Other practices detected by our survey, such as the reporting of cases only if adequate treatment is documented, will also impact surveillance data and could result in underreporting of syphilis cases.
With the increase in primary and secondary syphilis in 2001 and the resurgence of syphilis among MSM in the United States, multiple aspects of syphilis surveillance are being reexamined, and the use of reactor grids should be one of these. The availability of a specific serologic test for untreated syphilis would ease diagnosis and surveillance of syphilis, possibly eliminating the need for reactor grids. Because the MSM involved in recent syphilis outbreaks across the country have a median age of 35 years, 15–18 reactor grids that select men for evaluation only at younger ages may limit health departments’ ability to promptly detect and control outbreaks among this population. For syphilis elimination to succeed in the context of evolving syphilis epidemiology, it is critical to evaluate the impact of reactor grid use on achievement of this national goal.
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