Sandra A. Larsen

A Randomized Trial of Enhanced Therapy for Early Syphilis in Patients with and without Human Immunodeficiency Virus Infection

BACKGROUND Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus (HIV) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis. METHODS In a multicenter, randomized, double-blind trial, we assessed two treatments for early syphilis: 2.4 million units of penicillin G benzathine and that therapy enhanced with a 10-day course of amoxicillin and probenecid. The serologic and clinical responses of patients with and without HIV infection were studied during one year of follow-up. RESULTS From 1991 through 1994, 541 patients were enrolled, including 101 patients (19 percent) who had HIV infection but differed little from the uninfected patients in their clinical presentations. The rates at which chancres and rashes resolved did not differ significantly according to treatment assignment or HIV status. Serologically defined treatment failures were more common among the HIV-infected patients. The single clinically defined treatment failure was in an HIV-infected patient. Rates of serologically defined treatment failure did not differ according to treatment group (18 percent at six months with usual therapy; 17 percent with enhanced therapy). T. pallidum was found at enrollment in the cerebrospinal fluid of 32 of 131 patients (24 percent) and after therapy in 7 of 35 patients tested. None had clinically evident neurosyphilis, and the rate of detection of T. pallidum did not differ according to HIV status. CONCLUSIONS After treatment for primary or secondary syphilis, the HIV-infected patients responded less well serologically than the patients without HIV infection, but clinically defined failure was uncommon in both groups. Enhanced treatment with amoxicillin and probenecid did not improve the outcomes. Although T. pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested, such a finding did not predict treatment failure. The current recommendations for treating early syphilis appear adequate for most patients, whether or not they have HIV infection.

The Response of Symptomatic Neurosyphilis to High-Dose Intravenous Penicillin G in Patients with Human Immunodeficiency Virus Infection

BACKGROUND Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment. We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis. METHODS Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid. We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine. Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days. Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum. RESULTS In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results. In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations. One patient relapsed with meningovascular syphilis six months after therapy. T. pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens. CONCLUSIONS In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop. The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

Crack cocaine smoking and oral sores in three inner-city neighborhoods

Crack cocaine causes blisters, sores, and cuts on the lips and in the mouths of persons who smoke it, and such sores may facilitate the oral transmission of HIV. We recruited young adults aged 18-29 years, who either were current regular crack smokers, or who had never smoked crack, from inner city neighborhoods in New York, Miami, and San Francisco. Participants were interviewed for HIV risk behaviors and history of recent oral sores and were tested for HIV, syphilis, and herpes simplex virus (HSV) antibodies. Among the 2,323 participants recruited, 1,404 (60%) were crack smokers. Crack smokers (10.0%) were more likely than nonsmokers (4.5%) to report having had oral sores in the past 30 days [prevalence odds ratio (POR) 2.4, 95% confidence interval (CI) 1.7-3.4]. Sores were also more prevalent among those who had ever injected drugs (14.3%) than among those who had not (6.7%; POR 2.3, 95% CI 1.7-3.4), and among those with HIV infection (14.3%) than among those without it (8.0%; POR 1.9, 95% CI 1.3-2.8). Among the 429 participants who reported receptive oral sex, those who reported oral sores were more likely than those who did not to have HIV infection, after other HIV risk factors were controlled for (adjusted POR 1.9, 95% CI 1.0-3.6). Our results confirm that crack smokers have a high prevalence of oral sores and provides evidence that these sores, although infrequently, may facilitate oral transmission of HIV.

Evaluation of sera from patients with Lyme disease in the fluorescent treponemal antibody-absorption test for syphilis

To determine whether the cross-reactivity between Treponema pallidum and Borrelia burgdorferi affects the specificity of the fluorescent treponemal antibody-absorption (FTA-Abs) test for syphilis, sera from patients with Lyme disease or syphilis were examined in a quantitative FTA-Abs test. Sera were diluted serially in phosphate-buffered saline, then in sorbent, and were tested with T. pallidum and B. burgdorferi antigens. Nine of 40 sera from patients with known Lyme disease were reactive at the 1:5 dilution with antigen from T. pallidum; only one serum was reactive at the 1:10 dilution. When both antigens were tested, the titer against B. burgdorferi was always higher than that against T. pallidum. Similarly, sera from patients with syphilis showed cross-reactivity with B. burgdorferi. Although reactivity could be absorbed with Treponemal phagedenis (Reiter strain), simultaneous titration with both antigens was easily performed and designated the etiologic agent.

Sexual Behavior, Sexually Transmitted Diseases, and Risk of Cervical Cancer

To explore sexually transmitted diseases and sexual behavior as risk factors for cervical cancer, we analyzed data from a population-based case-control study of breast and cervical cancer in Costa Rica. Data from 415 cases of cervical carcinoma in situ, 149 cases of invasive cervical cancer, and 764 controls were included in the analysis. Multivariate analysis showed that lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, herpes simplex virus type 2 sero-positivity, and serologic evidence of previous chlamydial infection were predictors of carcinoma in situ. Serologic evidence of previous syphilis was not associated with carcinoma in situ. Predictors for invasive cervical cancer included lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, serologic evidence of previous syphilis, herpes simplex type 2 infection, and chlamydial infection. Cigarette smoking, socioeconomic status, self-reported history of sexually transmitted diseases, and douching were not associated with either carcinoma in situ or invasive cervical cancer.

Pathology of the umbilical cord in congenital syphilis: Analysis of 25 specimens using histochemistry and immunofluorescent antibody to Treponema pallidum

Identification of Treponema pallidum in the placenta is important for diagnosis of congenital syphilis; however, spirochetes are difficult to observe in chorionic villi. To determine the sensitivity of umbilical cord examination for T pallidum, and the association of spirochetes with cord pathology, placentas were prospectively obtained from 25 women with untreated syphilis. The most common finding using hematoxylin-eosin staining was a normal-appearing umbilical cord (48%); necrotizing funisitis was the most frequent pathological lesion (36%). Spirochetes were detected using silver and immunofluorescent staining in 89% of cords, including 92% of histologically normal and 84% of abnormal cords. Three specimens showed subamnionic aggregates of spirochetes, consistent with amniotic fluid infection. Necrotizing funisitis was strongly associated with umbilical artery infection by spirochetes (P = .008). There was a 100% correlation between results of silver and immunofluorescent staining. The umbilical cord is a sensitive site for morphological confirmation of T pallidum; it is significant for the pathologist that spirochetes may often be detected in the absence of overt tissue inflammation or necrosis.

Staining intensities in the fluorescent treponemal antibody-absorption (FTA-Abs) test: association with the diagnosis of syphilis.

In 1984 the reporting system for the fluorescent treponemal antibody-absorption (FTA-Abs) test was changed by the Centers for Disease Control (CDC; Atlanta, GA) to eliminate the borderline report. Factors influencing the reliability of the FTA-Abs test results, i.e., sensitivity, specificity, prevalence of syphilis, prescreening of sera with nontreponemal tests, and reproducibility, were considered before the change in the reporting system was recommended and are reported here. The borderline report, when associated with syphilis, was most frequently also associated with the diagnosis of early primary, dark-field-positive, nontreponemal test-nonreactive syphilis. Whereas elimination of the borderline report decreased the sensitivity of the FTA-Abs test as a confirmatory test from 100% to 99.5%, the specificity increased from 82.5% to 88.7%. The 1+ staining intensity had an association of approximately 5% with the diagnosis of syphilis. The changes in the reporting system were designed to assist the clinician in interpreting the results of the FTA-Abs test in those cases that present diagnostic dilemmas.

Laboratory diagnosis of sexually transmitted diseases in facilities within the United States : Results of a national survey

Background and Objectives: The diagnosis of many sexually transmitted diseases (STD) requires laboratory testing. The authors assessed the effects of the introduction of new tests and regulations on STD testing. Study Design: A questionnaire survey was mailed to a random sample of facilities listed in the STD Referral Database inquiring about tests offered, changes in testing, and reasons for changes. Results: Responses from 405 facilities were analyzed. Most responding facilities collected specimens for nontreponemal tests for syphilis (352 of 405 [86.9%]). Since each facilitys information was last updated, the number reporting testing for Chlamydia trachomatis rose from 160 of 405 (39.5%) to 288 of 405 (71.1%), but testing for gonorrhea and chancroid decreased (365 of 405 [90.1%] to 328 of 405 [81%], and 182 of 405 [44.9%] to 32 of 405 [7.9%], respectively). Of 364 responses to a question on changes in tests performed in the last 2 years, 249 (68.4%) reported no change, 81 (22.3%) reported an increase, and 37 (10.2%) reported a decrease. The most frequently added tests were nonculture tests for C. trachomatis (34 of 81 [42%]), and the most frequent reason for adding tests was targeted funding (25 of 81 [30.9%]). The most frequently discontinued tests were cultures and gram stains for gonorrhea (15 of 37 [40.5%]) and other in‐house tests (9 of 37 [24.3%]). Most facilities that discontinued testing cited the Clinical Laboratory Improvement Act as the reason (34 of 37 [91.9%]; 95% confidence interval = 78.1%, 98.3%). Conclusions: The number of facilities testing for C. trachomatis has increased with funding and with the availability of nonculture tests, but the number of those testing for chancroid and gonorrhea has decreased. Implementation of the Clinical Laboratory Improvement Act may be associated with a decrease in the number of facilities performing tests for STD.

Prevalence, incidence, and correlates of syphilis seroreactivity in multiethnic San Francisco neighborhoods.

To examine the extent of infection with syphilis in an inner-city community, we determined the prevalence, incidence, and correlates of syphilis seroreactivity in a representative sample of unmarried whites, African Americans, and Hispanics living in San Francisco during 1988 to 1989 and again 1 year later in 1989 to 1990. One thousand seven hundred seventy single men and women aged 20 to 44 were surveyed in a random household sample drawn from three neighborhoods of varying geographic and cultural characteristics. Syphilitic infection was determined by testing specimens with the microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP). Of blood samples available from 1262 participants from the initial survey, 32 (2.5%) were MHA-TP reactive. After adjustment for age, a reactive syphilis serology was significantly predicted (P < 0.05) by African American race, homosexual activity (men), and less education. In homosexually active men, lifetime number of male sex partners and the presence of antibody to the human immunodeficiency virus (HIV) significantly predicted syphilis seroreactivity (P < 0.01). One year later, of 841 specimens available for testing, an additional 13 (1.5%) had become MHA-TP reactive. Eleven (85%) of the new cases were in heterosexual men and women. Although San Francisco citywide incidence data indicate that syphilis may be decreasing for the city as a whole, incidence data on a community level suggests that syphilitic infection is increasing in high-risk heterosexual communities. Thus, syphilis prevention programs should rely on serologic testing at the community level to plan effective intervention strategies.

Failure of the Treponema pallidum lmmobilization Test to Provide Additional Diagnostic Information about Contemporary Problem Sera

Two hundred forty-five sera submitted to the Center for Disease Control, Atlanta, Ga., (CDC) were analyzed serologically in an attempt to demonstrate the diagnostic value of the Treponema pallidum immobilization (TPI) test when performed in addition to the fluorescent treponemal antibody-absorption (FTA-Abs) test. Diagnoses for the patients whose sera were tested were based on information supplied by the referring physicians. Fifty-four per cent of the diagnostic problems were resolved merely by the finding of a negative result with the FTA-Abs test. There was agreement between the serologic results of the referring laboratory and those of the CDC for 76% of sera tested by the Venereal Disease Research Laboratory test and for 71% of sera tested by the FTA-Abs test. For patients with treponemal disease, the sensitivity of the TPI test was 56% and that of the FTA-Abs test was 78%. When the FTA-Abs test was reactive, a negative TPI test was not significantly associated with systemic lupus erythematosus (P > 0.6) or other collagen vascular disease (P > 0.6), nor was a positive TPI test associated with treponemal disease (P > 0.09). It is concluded that once the result of the FTA-Abs test is known, the TPI test does not provide additional diagnostic information.