Reactive Serologic Tests For Syphilis Research Articles

Congenital Syphilis: A U.S. Perspective.

Congenital syphilis still represents a worldwide public health problem. If left untreated, it can lead to fetal demise and high neonatal morbidity and mortality. Unfortunately, in the last decade, there has been a resurgence of cases in the U.S. This review discusses the ongoing problem of this preventable congenital infection, vertical transmission and clinical manifestations while providing a guidance for the evaluation and management of infants born to mothers with reactive serologic tests for syphilis.

Prevalence of Treponema pallidum DNA among blood donors with two different serologic tests profiles for syphilis in São Paulo, Brazil.

The presence of Treponema pallidum DNA was assessed by real-time PCR in samples of blood donors with reactive serologic tests for syphilis. Treponema pallidum DNA was detected in two (1·02%) of 197 samples of VDRL>8, EIA+ and FTA-ABS+ donors, and in no sample from 80 VDRL−, EIA+ and FTA-ABS+ donors. Donors VDRL−, EIA+ and FTA-ABS+ lack demonstrable T. pallidum DNA in their blood and are unlike to transmit syphilis. Donors VDRL>8, EIA+ and FTA-ABS+ carry the risk of syphilis infectivity even in concomitance to antibodies detection. Serologic screening for syphilis may still play a role to prevent its transfusion transmission.

P2.101 HIV Status and Other Predictors of Successful Syphilis Treatment

Background Data addressing the question of whether HIV-positive patients respond as well to the recommended treatment for syphilis as HIV-negative patients are sparse. We examined data from reported early syphilis cases in San Francisco to identify factors related to serologic response to treatment. Methods San Francisco early syphilis cases diagnosed between 2006 and 2012 were analysed in terms of serologic response to treatment. Cases were excluded if the patient had any prior syphilis diagnosis reported, and only cases with an initial reactive serologic test for syphilis (STS) titer of 1:4 or higher were included. A successful serologic response to treatment was defined by a record of a non-reactive STS or a four-fold titer decrease within 12 months from treatment. Survival analysis and proportional hazards models were used to examine the relationship between demographic and risk factor data, including HIV status, and number of days until successful serologic response was documented. Results A total of 1664 first-time cases were examined. HIV-positive patients were significantly more likely to have a follow-up STS than other patients (p Conclusion Analysis of routine interview data found no evidence that HIV-positive patients failed to respond to standard syphilis treatments. However, the limits of surveillance data suggest the need for further research examining the relationship between immune status and response to treatment among HIV-positive patients.

Treatment of infants with reactive syphilis serology, New Jersey: 1992 to 1996.

Diagnosis of congenital syphilis is problematic: infants with congenital syphilis are often asymptomatic, and signs in symptomatic infants are frequently subtle and nonspecific. Furthermore, there are no readily available diagnostic tests that provide a definitive diagnosis. Previously, the diagnosis of congenital syphilis was based on a complex set of clinical and laboratory criteria, and only infants with clinically apparent illness or laboratory findings indicating congenital syphilis were classified as cases and reported to health departments and the Centers for Disease Control and Prevention (CDC). To systematize diagnosis and case-reporting, the CDC developed a standardized surveillance case definition in 1988. This case definition includes symptomatic infants as well as asymptomatic infants of mothers with untreated or inadequately treated syphilis during pregnancy. It is intended to be highly sensitive to better estimate the burden of disease in the community. Treatment guidelines for congenital syphilis are intentionally conservative and err on the side of overtreatment so that all potentially infected infants are treated. The congenital syphilis surveillance case definition is compatible with the American Academy of Pediatrics (AAP) and CDC treatment guidelines; thus, the number of infants identified and reported to state health departments and the CDC should reflect the number of infants treated. Hundreds of infants with reactive serologic tests for syphilis (STS) are reported each year to the New Jersey Department of Health and Senior Services (NJDHSS). The majority of these infants do not meet the case definition for congenital syphilis, and most are treated although treatment guidelines indicate that treatment is not necessary. To determine whether infants with reactive STS in New Jersey are being treated according to the AAP treatment guidelines. Medical records of newborns with reactive STS reported to NJDHSS between July 1, 1992, and June 30, 1996, were reviewed to determine status of infection and compliance with the AAP treatment guidelines. The 1995 NJDHSS Uniform Billing and Hospital Discharge Data was used to estimate the mean cost of hospitalization per day for infants with the diagnosis of congenital syphilis. Results. During the study period, 1669 newborns with reactive STS were reported to the NJDHSS Sexually Transmitted Disease Program. Medical record review was completed for 1480 infants (88%). Infants were classified by CDC surveillance criteria as follows: 0 confirmed cases; 515 (35%) presumptive cases; 16 (1%) syphilitic stillbirths; and 949 (64%) cases that did not meet the definition for congenital syphilis. Of the 512 presumptive cases that survived the immediate perinatal period, 478 (93%) were treated with antibiotics and 459 (90%) were treated according to the AAP treatment guidelines. Only 27 infants (6%) were treated with a single intramuscular dose of benzathine penicillin. Thirty-four infants (7%) were not treated; instead, their physicians chose to follow them clinically and serologically. All of those treated were asymptomatic, and most were born to mothers with a history of adequate treatment before or during pregnancy, but who were without serologic follow-up. Of the 949 infants that did not meet the case definition, 329 infants (35%) were not treated and 620 (65%) were treated with antibiotics. The 508 (82%) infants treated with antibiotics were treated with intravenous or intramuscular antibiotics for 10 days; only 62 (10%) were treated with a singular intramuscular dose of benzathine penicillin. According to NJDHSS Uniform Billing Hospital Discharge Data, 267 infants weighing >/= 2500 g were discharged with a diagnosis of congenital syphilis in 1995. The median number of hospital days for these infants was 10, and the mean cost of hospitalization per day was $1010. Sources of payment of hospital charges for most infants were public in

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T-lymphotropic virus via the transfusion of seronegative, infectious window-period blood. Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window-period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window-period donations is the number of post-screening HIV-infectious donations removed by STS. Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window-period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.

Clinical and Serologic Evaluation of Neonates for Congenital Syphilis: A Continuing Diagnostic Dilemma

Neonates born to women with reactive serologic tests for syphilis were studied; the total of 116 included 18 who were symptomatic, 60 asymptomatic but possibly infected, and 38 asymptomatic and probably uninfected. The fluorescent treponemal antibody-absorption (FTA-ABS) 19S IgM test and an IgM capture ELISA for Treponema pallidum, both treponema-specific assays, and the reverse enzyme-linked immunospot (RELISPOT), which detects immunoglobulin-secreting cells and is a nonspecific indicator of infection, were evaluated. Sensitivities among symptomatic neonates were 88% (IgM ELISA), 73% (FTA-ABS), and 78% (RELISPOT). Specificities ranged from 97% to 100%. A major problem has been the inability to identify which asymptomatic but possibly infected neonate is really uninfected. Among 41 such babies who had all three tests done, 93% were negative by all assays, suggesting they were uninfected or recently infected. Strategies to accurately identify the truly uninfected asymptomatic newborn would prevent the unnecessary hospitalization of all at-risk infants, resulting in improved quality of care and reduced costs.

IgM antibody to Treponema pallidum in cerebrospinal fluid of infants with congenital syphilis.

To characterize the neonatal IgG and IgM response to specific Treponema pallidum antigens in the cerebrospinal fluid (CSF) of infants with congenital syphilis. Cross-sectional survey. Newborn nursery and neonatal intensive care unit of a county hospital in Dallas, Tex. Twenty-one infants born to mothers with reactive serologic tests for syphilis were enrolled. Group 1 consisted of six infants with clinical and laboratory evidence of congenital syphilis; group 2, six asymptomatic infants born to mothers with untreated syphilis; and group 3, nine asymptomatic infants whose mothers were treated for syphilis before delivery. Random sample. Immunoblotting was used to examine the IgM and IgG reactivities of neonatal serum and CSF against T pallidum antigens. Among serum samples of all group 1 infants, a specific IgM response to T pallidum antigens with apparent molecular masses of 47, 45, and 17 kd was observed. Cerebrospinal fluid IgM reactivity to a 47-kd antigen of T pallidum was seen in four group 1 infants. Serum samples from two group 2 and three group 3 infants demonstrated IgM reactivity against the 47-kd antigen and, in some cases, against the 45-kd antigen of T pallidum. None of 15 group 2 and 3 infants had a positive CSF IgM immunoblot result. The IgG reactivity in CSF was similar in the three groups and was directed against T pallidum antigens with apparent molecular masses of 72, 59, 47, 45, 42, 37, 34, 17, and 15 kd. A specific IgM response to T pallidum antigens, particularly the 47-kd antigen, was detected in the CSF of some infants with clinical and laboratory evidence of congenital syphilis. The potential usefulness of this test for the diagnosis of congenital neurosyphilis merits further study.

The hard penile circumferential fold as the presenting finding in primary syphilis: Report of six cases

Six patients with firm circumferential folds located in the balanic sulcus of the penis were studied. The purpose of the study was to determine the origin of the lesions. These patients were examined clinically, with dark-field examination when possible and with a serologic test for syphilis. All patients had reactive serologic tests for syphilis and had enlarged, firm, nontender, inguinal lymph nodes. Although we were unable to prove with certainty that the origin of these folds was syphilitic, all patients had clinical and serologic findings that supported the diagnosis of primary syphilis.

Herpes simplex virus infection as a risk factor for human immunodeficiency virus infection in heterosexuals.

To determine if infection with herpes simplex virus (HSV) type 2 is associated with human immunodeficiency virus (HIV) type 1 infection among patients attending sexually transmitted diseases clinics, a case-control study was done on coded sera from 179 HIV-1-infected patients and 367 age-, race-, and gender-matched HIV-1-seronegative patients. Although only 13 (2.3%) of 546 patients had a history of genital herpes treatment, 72% and 56.6%, respectively, had serologic evidence of prior infection with HSV-1 and -2. HSV-1 antibody prevalence was similar among both patient groups; however, HSV-2 antibodies were more common among those infected with HIV-1. Among heterosexual men, 62.7% of those infected with HIV-1 had HSV-2 antibodies compared with 46.7% of those not infected (P less than .01). The HSV-2 seroprevalence among women with or without HIV infection was 78.1% and 57.7%, respectively (P less than .02). A history of intravenous drug use and a reactive serologic test for syphilis were each independently associated with HIV-1 infection in heterosexuals. These data suggest that the two most common causes of genital ulcerative disease in the United States, genital herpes and syphilis, may contribute to increased risk for HIV-1 infection among heterosexuals.

HIV-Related Characteristics of Migrant Workers in Rural South Carolina

After finding human immunodeficiency virus (HIV) infection in a migrant worker named as a syphilis contact, the South Carolina Department of Health and Environmental Control offered HIV counseling and testing and syphilis screening to migrant workers in the surrounding two-county area. In addition, a brief questionnaire was administered to document demographics and risk behavior. Of the 265 workers aged 16 and older in 15 migrant camps, 198 (75%) consented to the survey and testing. Of the 198 tested, 85% were male and 75% single. The median age was 39, with a range of 16 to 69 years. Twenty-five (13%) were HIV antibody positive, and 32 (16%) had reactive serologic tests for syphilis. Of the 166 workers who reported the frequency of condom use, 77 (46%) indicated they never use condoms. We conclude that there is a relatively high rate of HIV infection in these rural South Carolina migrant workers, whose behavior puts them at risk for HIV infection and other sexually transmitted diseases.

The association of syphilis with risk of human immunodeficiency virus infection in patients attending sexually transmitted disease clinics

A serologic survey of 4863 patients attending two inner-city sexually transmitted disease clinics was conducted in 1988 1 year after an initial survey to reassess the prevalence and associated risk factors for human immunodeficiency virus (HIV) infection. The HIV seroprevalence rates had not changed significantly (5.2% in 1987, 4.9% in 1988), and remained higher among men (5.6%) than among women (3.6%). The HIV seroprevalence increased steadily with age, to 34 years in women and to 39 years in men. Of patients with a reactive syphilis serologic test result, 24.3% were HIV infected compared with 3.5% of patients with a nonreactive test for syphilis. In multivariate analysis, a reactive serologic test for syphilis was significantly associated with HIV infection in all major risk behavior categories. Among heterosexuals who denied parenteral drug abuse, HIV infection rates were 6.8 and 8.7 times greater for women and men, respectively, who had a reactive serologic test for syphilis. Evidence of heterosexual transmission of HIV was further suggested by a change in HIV seroprevalence in women from 3.0% in 1987 to 3.6% in 1988, a male to female HIV infection ratio of 1.6, and 3.0% prevalence of infection among patients who denied established risk factors. This was most evident among those younger than 25 years, in whom 72% of infected women and 46.2% of infected men denied high-risk behaviors. These data demonstrate the strong association between syphilis and HIV infection and the importance of heterosexual HIV transmission in patients attending sexually transmitted disease clinics. This study underscores the need for a more comprehensive control program for sexually transmitted diseases, including syphilis and HIV infection.

The Association of Syphilis With Risk of Human Immunodeficiency Virus Infection in Patients Attending Sexually Transmitted Disease Clinics

A serologic survey of 4863 patients attending two inner-city sexually transmitted disease clinics was conducted in 1988 1 year after an initial survey to reassess the prevalence and associated risk factors for human immunodeficiency virus (HIV) infection. The HIV seroprevalence rates had not changed significantly (5.2% in 1987, 4.9% in 1988), and remained higher among men (5.6%) than among women (3.6%). The HIV seroprevalence increased steadily with age, to 34 years in women and to 39 years in men. Of patients with a reactive syphilis serologic test result, 24.3% were HIV infected compared with 3.5% of patients with a nonreactive test for syphilis. In multivariate analysis, a reactive serologic test for syphilis was significantly associated with HIV infection in all major risk behavior categories. Among heterosexuals who denied parenteral drug abuse, HIV infection rates were 6.8 and 8.7 times greater for women and men, respectively, who had a reactive serologic test for syphilis. Evidence of heterosexual transmission of HIV was further suggested by a change in HIV seroprevalence in women from 3.0% in 1987 to 3.6% in 1988, a male to female HIV infection ratio of 1.6, and 3.0% prevalence of infection among patients who denied established risk factors. This was most evident among those younger than 25 years, in whom 72% of infected women and 46.2% of infected men denied high-risk behaviors. These data demonstrate the strong association between syphilis and HIV infection and the importance of heterosexual HIV transmission in patients attending sexually transmitted disease clinics. This study underscores the need for a more comprehensive control program for sexually transmitted diseases, including syphilis and HIV infection.

The effects of case definition in maternal screening and reporting criteria on rates of congenital syphilis.

Reports of congenital syphilis in 1987 were reviewed to determine how new national guidelines for defining congenital syphilis would influence reported rates in Los Angeles County. After reviewing all reported reactive serologic tests for syphilis, we found 166 additional cases, resulting in a 426 percent increase in the 1987 reported rate of congenital syphilis. Rates of congenital syphilis are dependent upon surveillance practices, screening policies, and case definition.

Human immunodeficiency virus infection among patients attending clinics for sexually transmitted diseases.

To assess the prevalence and associated risk factors for human immunodeficiency virus (HIV) infection in patients attending inner-city clinics for sexually transmitted diseases in Baltimore, we screened 4028 patients anonymously, of whom 209 (5.2 percent) were seropositive for HIV. HIV-seropositivity rates were higher among men (6.3 percent) than women (3.0 percent) (P less than 0.001) and among blacks (5.0 percent) than whites (1.2 percent) (P less than 0.02). Among men, but not women, HIV seroprevalence increased markedly and steadily up to the age of 40. In men, HIV seropositivity was independently associated with increased age, black race, a history of homosexual contact, and the use of parenteral drugs. In women, a history of parenteral drug use or of being a sexual partner of a bisexual man or parenteral drug user were independently predictive of HIV seropositivity. In men, HIV seropositivity was also associated with a history of syphilis or a reactive serologic test for syphilis, and in women, with a history of genital warts. Since these associations were independent of the type and number of reported sexual partners, they raise the possibility that sexually transmitted diseases that disrupt epithelial surfaces may be important in the transmissibility of HIV. In addition, on a self-administered questionnaire, one third of HIV-infected men and one half of infected women did not acknowledge previous high-risk behavior for HIV exposure. These data suggest that patients at clinics for sexually transmitted diseases represent a group at high risk for HIV infection, and that screening, counseling, and intensive education should be offered to all patients attending such clinics.

Detection of Treponema pallidum by a Fluorescent Monoclonal Antibody Test

Definitive diagnosis of early syphilis currently requires dark-field microscopy and/or a newly reactive serologic test for syphilis. The efficacy of dark-field microscopy depends on the availability of a microscope, the skill of the clinician in obtaining a specimen, and the expertise of the microscopist. Serologic diagnosis may be affected by the delay between the appearance of the primary chancre and the onset of serologic reactivity. We used a pathogen-specific fluorescein-conjugated monoclonal antibody to examine lesion exudates from 128 consecutive patients and compared these data with results of dark-field microscopy, the rapid plasma reagin (RPR) test, and the fluorescent treponemal antibody-absorbed (FTA-Abs) test. The monoclonal antibody test demonstrated Treponema pallidum in 48 (73%) of 66 patients with infectious syphilis, while dark-field microscopy was positive for 52 (79%) of 66 patients. None of 62 patients without syphilis was positive by either test. The FTA-Abs test was reactive for 61 patients (92%) of the 66 with infectious syphilis. Thus the fluorescent monoclonal antibody test for detection of T. pallidum in direct smears is as sensitive and specific as dark-field microscopy for the diagnosis of infectious syphilis. It has the potential to provide a convenient, accurate means for definitive diagnosis of genital ulcer disease by health care personnel without ready access to dark-field microscopy.

Sexually transmitted diseases in females in a juvenile detention center.

Of 37 female adolescent prostitutes and 63 other females held in the King County, Washington, juvenile detention facility, 81 (81%) complained of vaginal discharge, and only eight (8%) had no genitourinary symptoms. The prevalence of genital infections among prostitutes and nonprostitutes was similar. Neisseria gonorrhoeae was found in 18 (18%) of 98 detainees tested, and Chlamydia trachomatis was found in 17 (20%) of 86 detainees tested; either organism was found in 27 (32%) of 85 tested for both organisms. Also, 38 (48%) of 80 tested had trichomoniasis. No detainees had syphilis. Sixty-seven (68%) of 98 responding detainees used no contraception. Such populations deserve the attention of public programs for control of sexually transmitted diseases and for family planning.

Rectal mass caused by Treponema pallidum: Confirmation by immunofluorescent staining

A 37-yr-old homosexual man presented with mild anorectal symptoms, a diffuse maculopapular rash, constitutional symptoms, and a reactive serologic test for syphilis. Sigmoidoscopy revealed a 2 × 2-cm indurated rectal mass 5 cm above the anal verge. Darkfield examination of rectal exudate revealed motile treponemes and rectal biopsy of the mass showed diffuse infiltration of plasma cells and lymphocytes. Large numbers of spirochetes were present on silver stain of the rectal biopsy specimen and these were shown to be Treponema pallidum by indirect immunofluorescence. The rectal mass and symptoms resolved following penicillin therapy. This case and a review of previously reported cases of anorectal syphilis emphasize the significance of these often neglected and misdiagnosed lesions of syphilis.

Immunology of syphilis.

Many advances have been made in solving microbiological and immu­ nological enigmas since 1905 when Schaudinn & Hoffmann (1) identified the causal organism of syphilis. However, over 60 years later we still are unable to grow virulent Treponema pallidum on artificial media, do not have a vac­ cine, know little about the immunological mechanisms of this disease, and are again seeing syphilis sweep the world in epidemic proportion. Many unanswered questions of host-parasite relationship are of concern to students of the disease. For example, what is the true relationship of the organism and its products to CIutton's joints and interstitial keratitis as seen in congenital syphilis or to the gumma of late syphilis? Nor can we answer why some infected individuals develop cardiovascular or neurosyph­ ilis while others manifest only a reactive serologic test for syphilis. It is not possible to present in the allotted space an extensive treatise on reports of a rather voluminous literature about various immunological as­ pects of naturally acquired and experimental syphilis. We will, instead, pre­ sent selected representative reports and pose further questions on the im­ munology of syphilis by. presenting certain research that we hope will stimu­ late your own interest in the field. Extensive reviews are those of Neisser (2), Chesney (3), Urbach & Beer­ man (4), and Magnuson (5). More recent papers on the subject are those of Wigfield (6) and Cannefax (7). Serologic tests for syphilis are not given detailed coverage in this review. Discussions of serologic tests for syphilis in current use can be found in ar­ ticles by Nicholas & Beerman (8), Wallace (9), and Gillespie & Brown (10).

False-Positive Reactions Among Narcotic Addicts

To the Editor:— I have noted the article inThe Journal, Jan. 28, 1961, entitled Biologic False-Positive Reactions for Syphilis Among Narcotic Addicts, in which the following sentence appears: The high proportion of non-reactive TPI tests among narcotic addicts with no history of syphilis and reactive STS provides direct evidence that certain drugs may induce BFP reactions. Unless other possible causes were thoroughly investigated, I wonder whether the conclusion that drugs have been demonstrated to cause biologic false-positive (BFP) reactions is justified. I should think the wording might be changed somewhat as follows: The high proportion of non-reactive TPI tests among narcotic addicts with no history of syphilis and reactive serologic test for syphilis ( STS ) is perhaps explained by the fact that addicts are subject to a number of conditions which are known to cause BFP reactions: viral hepatitis, malaria, and others. It may also be hypothesized that the chronic

Biologic False-Positive Reactions for Syphilis Among Narcotic Addicts

PRIOR to 1949, the occurrence of a reactive serologic test for syphilis (STS) in the absence of a history of lesions of the disease had been considered to be of equivocal significance by many investigators. In that year, the specific Treponema pallidum immobilization (TPI) test was developed by Nelson and Mayer 1 thus making available an accurate procedure for the differentiation of biologic false-positive (BFP) reactions from those due to infection with T. pallidum . Subsequently, numerous diseases and conditions have been observed to show BFP reactions, including collagen diseases, 2 pregnancy, 3 Brucella infection, and many others. During the past few years, increasing attention has been focused on the problem of narcotic addiction. Concomitant with this interest, it was observed that sera from many patients addicted to narcotics showed reactive STS. This report presents the incidence of BFP reactions among such individuals as measured by the TPI test. Methods