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Syphilis.

In the last half of the 20(th) century, medicine has made tremendous inroads against syphilis chiefly owing to the introduction of penicillin and vigorous public health initiatives. Yet, the world continues to be burdened by this disease. Since 2000, overall rates of syphilis have risen in the US and throughout the world. Furthermore, through its association with an increased risk of HIV infection, syphilis has acquired a new potential for morbidity and mortality. The aim of this review is to survey the latest knowledge about syphilis, including pathogenesis and host response, clinical manifestations, diagnostic methods and, especially, treatment and follow-up.

Algorithms↗

Treatment of primary and secondary syphilis: serologic response.

Eighty-eight patients with their first attack of primary syphilis and 101 patients with secondary syphilis were treated with penicillin G benzathine, 2.4 million units intramuscularly each week for 2 consecutive weeks, for a total of 4.8 million units. The serum of all patients with primary syphilis became negative within 1 year and of those in the secondary stage, within 2 years. This report confirms three previously published articles on the serologic response to treatment in a grand total of 588 patients with primary syphilis and 623 patients in the secondary stage.

Adult↗

Serological distinction between syphilis and Lyme borreliosis.

The serological distinction of an immune response to the agent of syphilis, Treponema (T.) pallidum, and Lyme disease borreliae is difficult due to the existence of cross-reacting antibodies. In this study, the immunoblot technique is used to compare the immune response of sera from patients with syphilis or Lyme borreliosis to either T. pallidum or Borrelia (B.) burgdorferi. Patients with syphilis showed an IgG response to the 17 and 15 kDa antigens of T. pallidum, whereas sera from patients with Lyme borreliosis-especially in late stages of the disease-reacted with the 95 and 19-17 kDa antigens of B. burgdorferi. Thus, IgG antibodies against low molecular weight antigens of T. pallidum (17, 15 kDa) or B. burgdorferi (19-17 kDa) may represent useful markers for the serological diagnosis of syphilis or Lyme borreliosis.

Antibodies, Bacterial↗

Laboratory methods of diagnosis of syphilis for the beginning of the third millennium.

Despite that the whole genome of T. pallidum, the causative agent of syphilis, has been sequenced, syphilis is, and will remain for some time, diagnosed by direct clinical observation and by laboratory methods. This review presents comprehensively most of the practical techniques used for direct detection of T. pallidum and lists all practical methods for phospholipid and treponemal antibodies detection. It describes most novel tests for syphilis, discusses problems with sero-creossreactivity in Lyme disease, immune responses in HIV-syphilis coinfected patients, and reviews serologic responses to antibiotic treatment.

Anti-Bacterial Agents↗

Outbreak of early syphilis in an institution for the care of adults with mental disorders.

This paper describes the features of an outbreak of early syphilis in an institution for the care of adults with mental disorders. A case-note review was performed. In the period June to November 2001, 87 cases of syphilis were diagnosed [25 primary, 21 secondary and 41 early latent syphilis in 983 inmates (crude attack rate 8.9%)]. Among them 82 were heterosexual, four were homosexual or bisexual, and for one case sexual preference was not established. About half the cases were known to be promiscuous. The initial case was not identified. Penicillin therapy was administered to all cases and all known or suspected sexual contacts. Sporadic cases of syphilis have, however, continued to emerge from time to time. Institutions for patients with mental disorders are vulnerable to sexually transmitted diseases, and special strategies should be devised for their control.

Adolescent↗

Alterations in the course of experimental syphilis associated with concurrent simian immunodeficiency virus infection.

Case reports suggest that the course of syphilis is altered in patients infected with human immunodeficiency virus (HIV). To investigate this issue, a model of syphilis in rhesus macaques with and without simian immunodeficiency virus (SIV) was developed. After intradermal inoculation with Treponema pallidum, 2 SIV-infected monkeys had persistent ulcerative primary lesions and 1 developed secondary syphilis. Two SIV-uninfected controls developed transient nonulcerative primary lesions. Only the controls showed consistent VDRL antibody responses. In contrast, reciprocal antibody titers to T. pallidum detected by microhemagglutination were higher in SIV-infected animals (greater than or equal to 20,480) than controls (greater than or equal to 1280). All 4 animals developed a full range of T. pallidum antigen-specific antibodies shown by immunoblot and had similar peak lymphocyte proliferative responses to T. pallidum antigens. These results support the contention that retrovirus-induced immunodeficiency delays clearance of T. pallidum from sites of infection and may impair the humoral immune response to syphilis.

Animals↗

The continuing legacy of the Tuskegee Syphilis Study: considerations for clinical investigation.

The Tuskegee Study, an observational study of over 400 sharecroppers with untreated syphilis, was conducted by the U.S. Public Health Service to document the course of the disease in blacks, and racial differences in the clinical manifestations of syphilis. The men were not told they had syphilis, not given counseling on avoiding spread of the disease, and not given treatment throughout the course of the study. The study became the longest (1932-1972) nontherapeutic experiment on humans in the history of medicine, and has come to represent not only the exploitation of blacks in medical history, but the potential for exploitation of any population that may be vulnerable because of race, ethnicity, gender, disability, age or social class. It is important for physicians who will be caring for an increasingly diverse nation to understand the lasting implications of this study for their patients, but the effects of the Tuskegee Syphilis Study are demonstrated most strikingly by unsuccessful attempts at improving representation of minority patients in clinical trials.

Black or African American↗

Syphilis: a review and update of this 'new' infection of the '90s.

Reported cases of primary, secondary and congenital syphilis are reaching epidemic proportions in the United States. Several factors have been associated with this increase, including budget reductions for syphilis-control programs, the growing use of cocaine among women of childbearing age and the practice of trading sex with multiple partners for illegal drugs. This article reviews the pathogenesis, clinical stages and presentation, serologic testing, treatment, and pertinent patient education for syphilis. Recommendations for the identification and prevention of syphilis are provided.

Adolescent↗

Indocyanine green angiography anomalies in ocular syphilis.

OBJECTIVE: To report indocyanine green (ICG) angiography anomalies in ocular syphilis. DESIGN: A noncomparative, interventional case series. PARTICIPANTS: Eight patients (16 eyes) affected by ocular syphilis. METHODS: All patients presenting with a diagnosis of active ocular syphilis between January 1994 and December 2001 were evaluated by a standard fluorescein and ICG angiography protocol. ICG angiography was repeated after completion of systemic antitreponemal and antiinflammatory treatment. RESULTS: ICG angiography anomalies were detected in 12 (75%) of 16 eyes. Two types of anomalies were observed: late-phase scattered hyperfluorescent spots (11 eyes) and persistent staining of retinal vessels (1 eye). Of these 12 eyes, 4 had no alteration by concomitant fluorescein angiography. When ICG angiography was repeated (5 +/- 1 weeks after the beginning of treatment), ICG angiography anomalies disappeared. CONCLUSIONS: ICG angiography may be a valuable tool in the assessment of patients with active ocular syphilis. Retinal and choroidal vascular anomalies can be determined that would otherwise go undetected by funduscopy and/or fluorescein angiography. It can also be useful in monitoring antitreponemal therapy.

Anti-Bacterial Agents↗

A survey of 251 patients with acute syphilis treated in the collaborative penicillin study of 1943-1950.

The dramatic and apparently curative effect of penicillin for the treatment of acute syphilis led to follow-up studies for only comparatively brief periods, and the acceptance of the long-term benefit of penicillin has rested on uncontrolled clinical impressions. More certainty about the efficacy of penicillin was sought by a follow-up review of 251 patients treated between March 1944 and December 1950 under the Penicillin Study of the Office of Scientific Research and Development (OSRD) and continued under U. S. Public Health Service after World War II. Eighty-eight patients were interviewed and examined. Telephone conversation or correspondence was had with 43 subjects; an additional nine are known to be living but did not respond to letters. Thirty-two patients died greater than or equal to 20 years after treatment, and 21 patients died within less than 20 years of treatment. Fifty-eight patients could not be found. Treatment failures were documented. Syphilis was not shown to be the cause of disability or death, except for a patient with meningovascular syphilis who died soon after initial treatment. Disabilities recorded and deaths documented revealed only diseases common to any middle-aged population. The outcomes of 17 pregnancies of women treated for acute syphilis were documented. Blood samples obtained from the 88 subjects examined were tested at the Center for Disease Control (Atlanta, Ga.); the results are recorded and discussed. Methods for locating the patients are described, and the psychosocial findings for the 88 patients interviewed are presented. The study has confirmed the clinical impressions of the therapeutic effectiveness of penicillin, which have been accepted for greater than 30 years.

Acute Disease↗

Late benign syphilis of the skin.

Two cases of late cutaneous syphilis are presented. After treatment for secondary syphilis in 1957 and retreatment for rising VDRL titers ten years later, one patient had developed a nodular syphilid. The other had several gummas. He had two quantitative nonreactive vDRL tests and a negative Treponema pallidum immobilization (TPI) test, but two reactive fluorescent treponemal antibody absorption (FTA-ABS) tests. Syphilis was suspected histologically and was confirmed by the specific serologic testing, the characteristic clinical presentation, and the prompt response to penicillin treatment. The clinical, serologic, histologic, therapeutic, and pathogenetic aspects of late benign syphilis of the skin are discussed.

Adult↗

Reliability and criterion-related validity of self-report of syphilis.

OBJECTIVE: To determine the test-retest reliability, sensitivity and specificity, and criterion-related validity of the Risk Behavior Assessment (RBA) syphilis questions. The RBA is a standardized instrument that has been used in several studies of STDs in drug users. METHODS: For the test-retest reliability study, 219 injection drug users completed the RBA twice within a 48-hour period. To determine criterion-related validity, 207 individuals, who also completed the RBA, were tested with the rapid plasma reagin test (RPR), and 206 individuals were also tested with the Serodia Treponema pallidum particle agglutination test (TP-PA). RESULTS: The test-retest reliability for the question "How many times have you been told by a doctor or a nurse that you had syphilis?" was 0.78. The test-retest reliability for the question "In what year were you last treated for syphilis?" was 0.89. For the comparison of self-report with the RPR test, the sensitivity of self-report was 46.2% and the specificity was 95.7%. For the comparison of self-report with the TP-PA test, the sensitivity of self-report was 37% and the specificity was 97.7%. CONCLUSIONS: Self-reports of syphilis infection history were found to have good reliability, excellent specificity, and moderate sensitivity. These characteristics need to be taken into account in any study using these self-report items.

Adult↗

The prozone phenomenon with syphilis and HIV-1 co-infection.

The prozone phenomenon in syphilis testing refers to a false negative response resulting from overwhelming antibody titers which interfere with the proper formation of the antigen-antibody lattice network necessary to visualize a positive flocculation test. This prozone effect in syphilis testing can be expected in cases of disproportionately high antibody titers, such as secondary syphilis, or with human immunodeficiency virus (HIV) coinfection. Clinicians need to remain familiar with the protean manifestations of syphilis to be able to exclude the prozone phenomenon.

Adult↗

Ribonucleic acid antigen from the Reiter treponeme used in an ELISA for antibodies in syphilis.

Purified RNA from Treponema phagedenis biotype Reiter was used as antigen in an enzyme-linked immunosorbent assay (ELISA) for IgG antibodies in syphilis. The RNA ELISA was compared with the fluorescent treponemal antibody absorption test (FTA-ABS), the Treponema pallidum immobilization test (TPI), and with two ELISAs using purified flagellum from the Reiter treponeme as antigen (flagellum ELISA), and sonified Reiter treponeme culture as antigen (sonicate ELISA). A total of 729 sera from patients with and without syphilis were studied. The RNA ELISA had a lower sensitivity (P less than 0.01) in primary syphilis than the flagellum ELISA, the sonicate ELISA, and the FTA-ABS. In treated syphilis the RNA ELISA was also less sensitive than the TPI (P less than 0.01).

Animals↗

Clinical study on syphilis in Abu Dhabi with special stress on the unusual presentation of the disease.

Seventy-nine cases of syphilis were the material of this study. Unusual presentations of primary syphilis were found in 42.5% of cases; explanations are given for these findings. Other aspects of the unusual presentations of the disease were studied with special stress on the occurrence of itching in the course of secondary syphilis. The authors emphasize that pruritus as a presenting symptom in the presence of skin lesion suggestive of syphilis should not blind the physician to the possibility that Treponema pallidum may be the etiologic agent.

Adolescent↗

Analysis of western blotting (immunoblotting) technique in diagnosis of congenital syphilis.

The diagnosis of congenital syphilis in apparently healthy infants continues to be problematic. Immunoglobulin M antibodies specific for a subset of Treponema pallidum antigens have been detected by Western blotting (immunoblotting). In the present study we investigated the sensitivity and specificity of this method. We tested 26 infants aged 0 to 4 months who fulfilled the accepted criteria for the diagnosis of congenital syphilis. There were 14 symptomatic infants. Sera from 13 of these infants were positive for the 47-kDa treponemal antigen (92% sensitivity). The remaining 12 infants were clinically asymptomatic when tested at birth but subsequently displayed features consistent with the disease. Reactive blots (antibodies to the 47- and/or the 15-kDa antigens) were noted in 10 of the 12 infants (83% sensitivity). Thirty infants whose mothers had syphilis were monitored and shown to be uninfected. Nonreactive blots were seen in sera from 27 infants, while sera from 3 older infants had false-positive tests (90% specificity). The Western blotting technique is sensitive (even in the diagnosis of clinically inapparent cases) and, in the absence of immunoglobulin M rheumatoid factor, is a useful confirmatory test for congenital syphilis.

Antibodies, Bacterial↗

Quantitative microhaemagglutination assay for Treponema pallidum antibodies in experimental syphilis.

The quantitative microhaemagglutination assay for Treponema pallidum antibodies (MHA-TP) was studies in 52 untreated and treated rabbits with experimental syphilis. Rabbits with incubating experimental syphilis were cured or inadequately treated with penicillin G and some cured rabbits were later reinfected. MHA-TP conversion occurred within 45 days in untreated rabbits. Titres reached peak levels about four months after inoculation and remained relatively high for up to two years. The quantitative MHA-TP test differentiated between rabbits cured of experimental incubating syphilis and those untreated and inadequately treated. MHA-TP titres decreased after treatment given six or 12 months after inoculation but reversion did not occur. MHA-TP conversion or significant increases in titre occurred as soon as seven days after reinfection and preceded corresponding changes in a quantitative non-treponemal test. The MHA-TP is useful as a screening test for treponemal antibodies in rabbits. The quantitative MHA-TP in humans after treatment for syphilis and reinfection deserves further study.

Animals↗

Autolymphocytotoxins in syphilis.

Nineteen of 23 serum samples from patients with secondary syphilis, six of 24 from patients with primary syphilis, and four of seven from patients with early latent syphilis had complement-dependent autolymphocytotoxic reactivity at 15 degrees C. After treatment, the reactivity was decreased. It was not directed only against autologous lymphocytes but also against allogeneic lymphocytes. Sephadex G-200 gel filtration showed that the lymphocytotoxins were present in the IgM-containing exclusion peak. Furthermore, serum samples that had high antibody titres in the Reiter protein complement-fixation test or Wassermann-Kolmer reaction also had a high frequency of cold-reacting autolymphocytotoxins. This indicates that the autolymphocytotoxic reactivity is related to the humoral response in syphilis.

Adolescent↗