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Syphilis: an update.

Syphilis can be spread during the practice of dentistry by direct contact with mucosal lesions of primary and secondary syphilis or blood and saliva from infected patients. The dentist also can play an important role in the control of syphilis by identification of the signs and symptoms of syphilis, patient education, and referral. The incidence of syphilis and the impact of control measures are presented with the emphasis on the past 5 years. The signs and symptoms of primary, secondary, latent, and late (tertiary) syphilis are reviewed. Current medical treatment is presented. The oral manifestations of syphilis are discussed as well as the dental management of the infected patient.

Anti-Bacterial Agents↗

Lumbar puncture in the evaluation of possible asymptomatic congenital syphilis in neonates.

OBJECTIVE: To evaluate the usefulness of lumbar puncture (LP) in the initial evaluation of symptom-free infants for congenital syphilis. STUDY DESIGN: We retrospectively studied infants who had successful LPs and were born to untreated or inadequately treated seropositive women between 1990 and 1993 in two hospitals in Washington, D.C. We identified 329 such symptom-free infants (syphilis group). The cerebrospinal fluid (CSF) VDRL was reactive in two (0.6%) infants. The CSF leukocyte and protein concentrations of these infants were compared with those in 84 symptom-free control infants who were born to seronegative women and who had LPs performed in 1993 to rule out sepsis because of associated risk factors. Control infants had negative results for bacterial cultures (CSF and blood) and bacterial antigen tests (CSF and urine). RESULTS: Thirty control subjects and 67 infants in the syphilis group had traumatic taps (CSF erythrocytes > 500 x 10(6)/L), and hence were excluded from the analysis of cell count and proteins. Birth weights and gestational ages were similar in both groups. The CSF leukocyte and protein values were similar in the syphilis group and in control infants: mean CSF leukocytes 7.7 x 10(6)/L (mean 7.7/mm3, range 0 to 57/mm3, SD 8.8) versus 6.9 x 10(6)/L (mean 6.9/mm3, range 0 to 31/mm3, SD 7), p = 0.5, and mean protein concentration 981 mg/L (range 270 to 2280 mg/L, SD 376) versus 936 mg/L (range 360 to 1750 mg/L, SD 368), p = 0.96, respectively. The combination of CSF leukocyte values > 5 x 10(6)/L (> 5/mm3) or protein values > 400 mg/L (> 40 mg/dl) was found in 97.8% of the infants in the syphilis group, compared with 95.3% of the control group. CONCLUSION: Because of the low yield of reactive CSF VDRL and the similar CSF leukocyte and protein values in the syphilis group and the control infants, the role of routine LP in the initial evaluation of symptom-free infants for congenital syphilis should be reconsidered.

Case-Control Studies↗

The hospital cost of congenital syphilis.

OBJECTIVE: To determine the hospital cost of caring for newborn infants with congenital syphilis. STUDY POPULATION: All live-born singleton neonates with birth weight greater than 500 gm at an inner-city municipal hospital in New York City in 1989. METHODS: We compared the characteristics of 114 infants with case-compatible congenital syphilis with those of 2906 infants without syphilis. Cost estimates were based on New York State newborn diagnosis-related groups (DRG) reimbursements adjusted for length of stay, birth weight, preterm delivery, and selected maternal risk factors, including infection with the human immunodeficiency virus, cocaine use during pregnancy, and history of injected drug use. RESULTS: For infants with congenital syphilis, the unadjusted mean cost ($11,031) and the median cost ($4961) were more than three times larger than those for infants without syphilis (p < 0.01). After adjustment, congenital syphilis was associated with an additional length of hospitalization of 7 1/2 days and an additional cost of $4690 (both p < 0.01) above mean study population values (7.13 days, $3473). CONCLUSIONS: Based on the number of reported cases (1991 to 1994), the average annual national cost of treating infants with congenital syphilis is approximately $18.4 million (1995 dollars). This estimate provides a benchmark to assess the cost-effectiveness of strategies to prevent, diagnose, and treat the disease.

Adult↗

Emergency department-based surveillance for syphilis during an outbreak in Philadelphia.

STUDY OBJECTIVE: To identify missed opportunities for syphilis treatment during an outbreak. DESIGN: Prospective prevalence survey. SETTING: Urban hospital emergency department. PARTICIPANTS: Nine hundred sixty-one persons aged 15 to 44 years seeking medical attention in the ED who were not suspected of having any sexually transmitted disease (STD) at the time of their visit. INTERVENTION: Serologic testing for syphilis and public health follow-up as needed. MEASUREMENTS AND MAIN RESULTS: Twenty-one non-STD patients (2%) had untreated early syphilis, and 22 (2%) had positive serology but were lost to follow-up. Among 271 STD patients seen in the ED during the same period, 15 cases (6%) were detected. We estimate that 80 or more additional untreated early syphilis cases would have been identified had all 15- to 44-year-old patients entering the ED been tested. The cost of screening was $251 per case detected. CONCLUSION: Patients not suspected of having any STD account for most early syphilis cases among all ED patients. Screening and on-site treatment for syphilis should be offered to all young adults seeking medical attention in the ED during syphilis outbreaks.

Adolescent↗

Impact on perinatal mortality of missed opportunities to treat maternal syphilis in rural South Africa: baseline results from a clinic randomized controlled trial.

OBJECTIVE: To demonstrate the impact on perinatal mortality of inadequate treatment for maternal syphilis despite adequate screening. METHOD: In 12 clinics providing antenatal care in Hlabisa, South Africa 1783 pregnant women were screened for syphilis at their first antenatal visit between June and October 1998. Pregnancy outcome was determined among those with syphilis. RESULTS: A total of 158 women were diagnosed with syphilis: prevalence 9% (95% CI 8-10%). Mean gestation at first antenatal visit was 24 weeks. Thirty women (19%) received no treatment and 96 (61%) received all three recommended doses of penicillin. Among those receiving at least one dose, mean delay to the first dose was 20 days. Among those fully treated mean delay to treatment completion was 34 days. Pregnancy outcome was known for 142 women (90%) and there were 17 perinatal deaths among 15 women (11%). Eleven of 43 women (26%) who received one or fewer doses of penicillin experienced a perinatal death whilst only four of 99 women (4%) who received two or more doses of penicillin did so (P = 0.0001). Protection from perinatal death increased with the number of doses of penicillin: linear modelling suggests that one dose reduced the risk by 41%, two doses by 65% and three doses by 79%, compared with no doses. A dose-specific, categorical model confirmed reduction in risk by 79% for all three doses. CONCLUSION: Despite effective screening, many pregnant women with syphilis remain inadequately treated, resulting in avoidable perinatal mortality. Delays in starting and finishing treatment, as well as incomplete treatment occur. Near-patient syphilis testing in the antenatal clinic with early treatment could improve treatment of syphilis and reduce perinatal mortality, and a randomized trial to test this is underway.

Adolescent↗

Predictive value of past and current screening tests for syphilis in blood donors: changing from a rapid plasma reagin test to an automated specific treponemal test for screening.

BACKGROUND: This study evaluated the change from a rapid plasma reagin (RPR) test to an automated specific treponemal test (PK-TP) in screening for syphilis in blood donors. STUDY DESIGN AND METHODS: A cross-sectional seroprevalence analysis was performed on 4,878,215 allogeneic blood donations from 19 American Red Cross Blood Services regions from May 1993 through September 1995. Positive predictive values relative to the confirmatory fluorescent treponemal antibody absorption test (FTA-ABS) were calculated. Differences in seroprevalence were compared in RPR and PK-TP tests for 1) unconfirmed and confirmed tests, 2) first-time and repeat donors, and 3) "recent" versus "past" infections. Donation data from three additional Red Cross regions were evaluated for repeat donation patterns of blood donors who had a donation that was positive in a serologic screening test for syphilis. The value of RPR and PK-TP tests as surrogate markers for HIV infection was compared. RESULTS: Reactive rates were lower but the positive predictive values was higher for the PK-TP test than for the RPR test. Initially, donors screened by PK-TP were more likely to be confirmed as positive than were donors screened by RPR, but these rates became comparable. It is estimated that a single HIV window-period donation was removed by serologic testing for syphilis each year of this study period. CONCLUSIONS: The change to the PK-TP test resulted in a lower repeatedly reactive rate, better prediction that a confirmed-positive test for syphilis would occur in testing in the FTA-ABS, fewer donations lost, and comparable deferral rates. Because of the high rate of reactivity to serologic testing for syphilis among donors previously confirmed positive for syphilis, indefinite deferral after a confirmed-positive index donation may be warranted. Serologic testing for syphilis is ineffective as a marker of HIV-infectious window-period donations.

Antibody Specificity↗

Syphilis in children: congenital and acquired.

Syphilis rates in women and congenital syphilis rates have declined steadily in the United States in recent years. However, syphilis remains a worldwide public health problem, with more than 12 million cases in adults and more than half a million pregnancies affected yearly. Prenatal screening and treatment programs are limited or nonexistent in many developing countries. The genome of Treponema pallidum, one of the smallest among prokaryotes, has been sequenced, but methods for continuous in vitro cultivation of the microbe remain elusive. There are no promising candidates for future vaccines at this time. Serologic testing, for both specific treponemal and nontreponemal antibodies, continues to be a primary means of diagnosis. Penicillin remains the drug of choice for congenital and acquired syphilis in childhood. The diagnosis of syphilis beyond early infancy raises concerns for possible child sexual abuse, although progression of congenital syphilis may account for some cases. Syphilis is a potentially eradicable disease, but this can be achieved only with sustained international will and cooperation to fund the necessary screening and treatment programs.

Adult↗

[Stage 3 syphilis of the mouth cavity].

BACKGROUND: Untreated syphilis or lues is a chronic infectious disease. It is caused by treponema pallidum, which is most commonly transmitted by sexual contact and occasionally by blood transfusion or by intrauterine infection. If the disorder is not treated, its clinical course can be chronic, persisting for decades. During this time, a variety of morphological signs occur depending on the stage of the disease. CASE REPORT: We describe a case of tertiary syphilis in the oropharynx with a defect of the soft palate. In a 37-year-old woman, the first symptom was a dryness of the throat followed by a feeling of foreign body in the palate area. The patient had a history of sexual contact with a man who had had syphilis ten years ago, and our initial suspicion was confirmed by a final diagnosis of tertiary syphilis. Signs of primary or secondary syphilis were not observed. RESULTS: In the course of diagnostic procedures both further manifestatons of syphilis and other infectious or malignant causes were excluded. The serological results showed a typical constellation of Treponema and non-Treponema serum reactions. The histopathological examination of an exploratory excision from the soft palate showed granulomatous changes with peripheral participation of plasma cells. We initiated appropriate antibiotic therapy, using clemizole penicillin G over a period of 21 days, which induced healing of the soft palate. CONCLUSIONS: A defect of the soft palate was diagnosed as a very rare sign of tertiary syphilis.

Adult↗

Azithromycin-resistant syphilis infection: San Francisco, California, 2000-2004.

BACKGROUND: The incidence of syphilis has been increasing in the United States since reaching a nadir in 2000. Several clinical trials have demonstrated that treatment with oral azithromycin may be useful for syphilis control. After reports of azithromycin treatment failures in San Francisco, we investigated the clinical and epidemiologic characteristics of patients with syphilis due to azithromycin-resistant Treponema pallidum infection. METHODS: We reviewed city-wide case reports and conducted molecular screening for patients seen at the San Francisco metropolitan STD clinic (San Francisco City Clinic) to identify patients who did not respond to azithromycin treatment for syphilis or who were infected with azithromycin-resistant T. pallidum. We conducted an epidemiologic investigation and retrospective case-control study to identify risk factors for acquiring syphilis due to azithromycin-resistant T. pallidum. RESULTS: From January 2000 through December 2004, molecular screening of 124 samples identified 46 azithromycin-resistant T. pallidum isolates and 72 wild-type T. pallidum isolates. Six instances of treatment failure were identified through record review. In total, we identified 52 case patients (one of whom had 2 episodes) and 72 control patients. All case patients were male and either gay or bisexual, and 31% (16 of 52) were infected with human immunodeficiency virus. Investigation of patient-partner links and a retrospective case-control study did not reveal a sexual network or demographic differences between cases and controls. However, 7 case patients had recently used azithromycin, compared with 1 control patient. Surveillance data demonstrated that azithromycin-resistant T. pallidum prevalence increased from 0% in 2000 to 56% in 2004 among syphilis cases observed at the San Francisco City Clinic. CONCLUSIONS: Azithromycin-resistant T. pallidum is widespread in San Francisco. We recommend against using azithromycin for the management of syphilis in communities where macrolide-resistant T. pallidum is present and recommend active surveillance for resistance in sites where azithromycin is used.

Anti-Bacterial Agents↗

Risk factors for syphilis among incarcerated women in Rhode Island.

Syphilis remains a significant problem in the United States. The prison environment is an ideal location to identify and treat syphilis. We undertook this study to describe the correlates and risk factors for syphilis among incarcerated women in Rhode Island. The study design was a review of all cases of syphilis identified through routine screening in the state prison and a case control study. Between 1992 and 1998, among 6,249 incarcerated women, 86 were found to have syphilis; of these, 29 were primary and secondary cases representing 49% of infectious cases of syphilis in women in the state. The prison environment offers a unique opportunity for the diagnosis and treatment of syphilis.

Adult↗

Strategies for syphilis prevention in the 1990s.

Reconfiguring and refocusing syphilis control and prevention programs in the United States is required by the changing epidemiology and sociology of syphilis as well as by the importance and magnitude of human immunodeficiency virus (HIV) prevention efforts. An updated strategic approach to syphilis prevention might involve three categories, or tiers, of prevention activities. Tier 1 activities involve the basic elements or tools of prevention programs, such as screening, treatment, partner notification, or behavior change counseling. Tier 2, or prevention effectiveness activities, represent ways to select among the basic prevention elements and to specify how they should be applied in particular epidemiologic situations to yield the greatest impact on disease transmission and persistence from available resources. Tier 3 involves strategic linkages to and alignment with other broad public health programs and initiatives to help accomplish the substantive work of syphilis control and to promote sustained advocacy and public support for syphilis prevention efforts. Although efforts within and across these tiers of syphilis prevention activities should and do reinforce each other, they also compete for resources: Tier 2 activities have been particularly in need of enhancement for many years. Tier 3 activities are especially important in the mid-1990s because, after the major epidemic of the late 1980s, syphilis rates are on the decline, making it urgent but difficult to sustain prevention efforts.

Contact Tracing↗

A serosurvey of Haemophilus ducreyi, syphilis, and herpes simplex virus type 2 and their association with human immunodeficiency virus among female sex workers in Lagos, Nigeria.

BACKGROUND AND OBJECTIVES: To determine the prevalence rates of serological reactivity of Haemophilus (H.) ducreyi, Treponema pallidum, and herpes simplex virus type 2 (HSV-2) antibodies among female sex workers (FSWs) and their association with human immunodeficiency virus (HIV) antibody status. STUDY DESIGN: Cross-sectional, standard serological assays were used for syphilis, HSV-2 and HIV; a modified enzyme-linked immunosorbent assay (ELISA) was used to detect specific anti-H. ducreyi immunoglobulin (Ig) G and IgA antibodies. RESULTS: Seroprevalence rates were 86% for anti-H. ducreyi IgG and 69% for anti-H. ducreyi IgA; 4% for rapid plasma reagin (RPR) and Treponema palladium hemagglutination assay (TPHA) confirmed syphilis; 59% for HSV-2; 12% for HIV-1 and 2% for HIV-2. Lower-class FSWs were significantly more likely than upper-class FSWs to be H. ducreyi seropositive (IgG: OR = 42.7; IgA: OR = 7.6) and have current or past syphilis infection (RPR: OR = 3.5; RPR and TPHA: OR = 4.5). The presence of syphilis increased significantly with older age (P-trend < 0.001). Non-Nigerian FSWs had significantly higher reactivity to chancroid (IgG: OR = 3.5; IgA: OR = 1.8) and borderline reactivity to syphilis (RPR: OR = 1.6; TPHA: OR = 2.0). A history of sex with non-Nigerian Africans was significantly associated with chancroid reactivity and borderline significant with syphilis serostatus. H. ducreyi seropositivity was significantly more likely in FSWs with HSV-2 (OR = 2.4) and syphilis (OR = 5.6). Chancroid and HSV-2 antibodies were also more common in HIV-infected FSWs. CONCLUSION: The prevalence of H. ducreyi antibodies is the highest rate that has been reported. Our findings underscore the importance of an effective program to control GUDs as part of the strategy to prevent the potentially explosive spread of HIV in Nigeria.

Adolescent↗

Strategies for syphilis prevention: findings from surveys in a high-incidence area.

BACKGROUND: The persistence of syphilis in the United States suggests that a better understanding is needed of the potential for various public health approaches to prevent the spread of the disease. STUDY DESIGN: The authors conducted surveys of 92 persons with early syphilis, 56 uninfected sexual contacts, and 143 neighborhood controls in the Baton Rouge, Louisiana area. The surveys collected information regarding sexual behavior, access to and use of healthcare services, encounters at sites at which serologic screening for syphilis could be done, and exposure to interventions designed to prevent HIV infection. RESULTS: All groups reported high-risk sexual behavior. Cases and contacts were more likely than controls to report two or more sex partners in the previous year, but the three groups were similar in the percentage reporting five or more sex partners. Cases had poor access to health care and by some measures this access was less than that of controls. The potential screening site visited most frequently by cases was the public hospital emergency room (40%). Cases were less likely to have been exposed to programs designed to prevent HIV infection than uninfected contacts and controls combined (odds ratios, 0.51-0.66). CONCLUSIONS: Persons with syphilis were not unlike others in their neighborhoods, suggesting that syphilis is a sentinel event that indicates an entire neighborhood is at risk. Improvements in access to health care for sexually transmitted disease-related symptoms, screening in sites such as public hospital emergency rooms, and emphasizing sexual risk-reduction interventions may limit the spread of syphilis in these neighborhoods. To prevent syphilis in the long term, public health programs should also try to better understand and change other community-level socioeconomic factors that influence sexual behavior.

Adult↗

Missed opportunities for congenital syphilis prevention in an urban southeastern hospital.

BACKGROUND: Despite recent declines in syphilis rates nationally, recent outbreaks suggest that prevention of congenital syphilis remains an ongoing public health problem. GOALS: To identify missed opportunities for congenital syphilis prevention during prenatal care. STUDY DESIGN: Retrospective medical record review of 157 live birth or stillbirth deliveries that involved cases of congenital syphilis from Grady Memorial Hospital (Atlanta, GA). RESULTS: The hospital congenital syphilis prevalence was 8.2 cases per 1,000 live births. Six percent of case patients were HIV positive. Opportunities for earlier maternal screening, treatment, or diagnosis were missed in 60% of case patients who received timely prenatal care. Congenital syphilis cases attributable to preventable missed opportunities were significantly more common among case patients with fewer prenatal visits (66% versus 28%, P = 0.01). CONCLUSION: Provider efforts to reduce congenital syphilis in high-risk populations receiving prenatal care should focus on (1) screening patients at the first opportunity, at both the first prenatal visit and during the third trimester (i.e., 28 weeks); (2) performing on-site testing and same-day treatment; (3) providing appropriate treatment to infected women with penicillin allergy; (4) referring sex partners for treatment to prevent reinfection; and (5) screening all pregnant women attending emergency clinics.

Adult↗

Pedal interdigital condylomata lata: a rare sign of secondary syphilis.

BACKGROUND: Condylomata lata of the toe webs are uncommon manifestations of secondary syphilis. Considering the recent decline in the incidence of syphilis in the United States, such lesions are likely to present infrequently. In some cases, this phenomenon may be the only physical sign of syphilis; therefore, it is important that a high index of suspicion is maintained when evaluating toe web lesions in patients at epidemiologic risk for syphilis. GOALS: A case of secondary syphilis presenting solely with interdigital condyloma lata in the toe web spaces is reported, and similar cases reported in the literature are reviewed. STUDY DESIGN: This article documents the diagnosis of secondary syphilis based on a positive serology in conjunction with the development of interdigital condyloma lata as the only physical finding suggestive of lues. RESULTS: The latter lesions resolved after appropriate, adequate antibiotic therapy. CONCLUSIONS: A case of condylomata lata of the toe webs without other pertinent physical findings is presented. Analogous to lesions typically seen in the anogenital region, moist exophytic toe web plaques may represent condyloma lata and thereby be a sign of secondary syphilis. The differential diagnosis includes tinea pedis, erythrasma, macerated corns, verrucae, and several tropical mycoses (chromomycosis, mycetoma).

Adult↗

Responding to a community outbreak of syphilis by targeting sex partner meeting location: an example of a risk-space intervention.

BACKGROUND: Effective syphilis control and elimination require community effort and innovative case-finding techniques, especially to identify infected persons from core transmission groups. GOAL: To summarize the implementation and outcomes of a community-oriented response to a localized outbreak of syphilis directed at sex partner meeting places. STUDY DESIGN: Syphilis surveillance and rapid response data from a 7-month period were analyzed for risk behaviors, sex partner meeting locations, field investigation outcomes, and social and sexual network connections. RESULTS: Four (6%) of the sixty-nine persons tested were confirmed syphilis reactors, of whom three were new cases. A sexual and needle-sharing network of 15 persons was identified that included two of the new syphilis cases. These two had not been found through standard field investigation. CONCLUSIONS: Targeting interventions to sex partner meeting places may effectively complement traditional syphilis control tools and find previously unidentified syphilis cases in high-morbidity areas.

Adult↗

Outbreaks of syphilis in rural Texas towns, 1991-1992.

Between 1986 and 1990, rates of primary and secondary syphilis increased 134% in rural counties in the South. Reasons for the increases are speculative. During the 14 months ending in October 1992, outbreaks in four eastern Texas counties provided an opportunity to characterize syphilis in rural Texas. We reviewed records for 118 patients and 339 sex partners. Three outbreaks were concentrated in neighborhoods where crack cocaine dealers conducted business and exchange of sex for drugs or money was common; the fourth outbreak involved out-of-town prostitutes who visited undocumented alien workers. Among the 118 syphilis cases, 15 (13%) were primary, 35 (30%) were secondary. Most patients were black (105, 89%); the male-female ratio was 1:1. One woman gave birth to an infant with congenital syphilis. Almost half of the sex partners were infected. HIV pretest counseling was completed for only 55 patients (47%), and only 23 (19%) were tested for the human immunodeficiency virus. These four rural outbreaks of syphilis associated with crack cocaine and the exchange of sex for drugs or money mirror recent urban syphilis outbreaks. Patients in these rural syphilis outbreaks are at risk for HIV infection, but HIV testing has not been emphasized by public health workers.

Adult↗

Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi.

OBJECTIVE: To determine the association between maternal syphilis and HIV mother-to-child transmission (MTCT). DESIGN: Prospective cohort study. METHODS: Pregnant women admitted at Queen Elizabeth Central Hospital (Malawi) in late third trimester were screened for HIV (by HIV rapid tests) and syphilis (by rapid plasma regain test and Treponema pallidum hemagglutination assay). HIV-infected women and their infants received nevirapine, according to the HIVNET 012 protocol. They were followed up at 6 and 12 weeks postpartum. Infant HIV infection was diagnosed by DNA PCR. FINDINGS: Of the 1155 HIV-infected women enrolled, 1147 had syphilis test results, of whom 92 (8.0%) were infected. Only 751 HIV-positive women delivered live singleton infants who were tested for HIV at birth. Of these, 65 (8.7%) were HIV-infected, suggesting in utero (IU) HIV MTCT. Of the 686 infants who were HIV-negative at birth, 507 were successfully followed up. Of these, 89 (17.6%) became HIV-infected, suggesting intrapartum/postpartum (IP/PP) HIV MTCT. Maternal syphilis was associated with IU HIV MTCT, after adjusting for maternal log10 HIV-1 viral load and low birth weight (LBW) [adjusted relative risk (ARR), 2.77; 95% CI, 1.40-5.46]. Furthermore, maternal syphilis was associated with IP/PP HIV MTCT (ARR, 2.74; 95% CI, 1.58-4.74), after adjusting for recent fever, breast infection, LBW and maternal log10 HIV-1 viral load. CONCLUSION: Maternal syphilis is associated with IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections.

Adult↗