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Serological diagnosis of erythema migrans disease and related disorders.

An indirect immunofluorescence technique for the determination of antibodies against ixodid tick spirochetes is described. Differences in the reactivity between Ixodes ricinus spirochete and Ixodes dammini spirochete antigens were not observed. Cross-reacting antibodies against Treponema pallidum and Treponema phagedenis can be eliminated by quantitative absorption with T. phagedenis. Cross-reactions with leptospira were not observed by immunofluorescence. In the IgM test, false negative reactions caused by high-titered specific IgG antibodies or false positive reactions caused by rheumatoid factor occur. This can be avoided by testing the IgM fraction (19S-IgM-test) or using sera previously treated with anti-IgG serum. Significantly elevated antibody titers against ixodid tick spirochetes were observed in 45% of 44 cases with erythema migrans disease, in 72% of 29 cases of lymphocytic meningoradiculitis, in all of nine patients with acrodermatitis chronica atrophicans and in all of four investigated patients with lymphocytoma (lymphadenosis benigna cutis).

Acrodermatitis↗

Detection of Treponema pallidum in lesion exudate with a pathogen-specific monoclonal antibody.

The diagnosis of early syphilis currently requires dark-field microscopic or serologic demonstration of Treponema pallidum infection. Dark-field microscopy is not widely available and is complicated by the numerous saprophytic spirochetes which are present at oral and rectal mucosal surfaces. Serologic tests are positive in only 70 to 90% of patients with primary syphilis, and several days may be required for results to become available. We used a pathogen-specific, fluorescein-conjugated monoclonal antibody to examine lesion exudates from 61 patients for the presence of T. pallidum and compared the data with results of dark-field microscopy and serologic testing. The direct fluorescent-antibody technique revealed the presence of T. pallidum in 30 of 30 patients with early syphilis, and dark-field microscopy was positive for 29. Serologic tests were reactive for 27 of 30 patients with syphilis; in the 3 patients with nonreactive serologic tests, chancres had been present for 4, 6, and 21 days. Although 7 of 31 patients without syphilis had spiral organisms seen on dark-field microscopy, the direct fluorescent-antibody test was negative for all 31. The presence of nonpathogenic spirochetes was subsequently verified in 5 of 7 patients by using a second monoclonal antibody which reacts with nonpathogenic, as well as pathogenic, treponemes and related spirochetes. The demonstration of T. pallidum by using fluorescein-conjugated monoclonal antibodies is intrinsically specific and is as sensitive as dark-field microscopy for the diagnosis of early syphilis. This method provides a convenient, accurate means for the diagnosis of syphilis by health care providers, many of whom lack access to dark-field microscopy.

Antibodies, Bacterial↗

The placental lesions in congenital syphilis. A study of six cases.

Placentas from six mothers with serological tests suggestive of recent syphilitic infection and whose babies were suspected of being or proven to be infected by Treponema pallidum are described. One placenta from this series was large, bulky and pale, while the other 5 were without remarkable gross features. In all cases, the associated histological lesions were 1) hypercellular areas in the terminal and stem villi and 2) a focal peri- and/or intravillous polymorphonuclear concentration with or without necrosis. The former change which was the most frequent was characterized by an apparent increase of villous stromal cells, ultrastructurally identified as mesenchymal cells and Hofbauer cells. In addition, numerous fetal monocytes were found in the villous vascular lumina. The findings described here and in the literature suggest that congenital syphilis is associated with a spectrum of placental changes. We believe that these changes depend on the immunological reaction of the fetus. According to the sequence of events described in untreated patients, we distinguish two morphological phases: 1) an inductive phase without placental changes and 2) a reactive phase characterized by a predominantly lymphocytic inflammatory infiltration of the villi, followed by a reaction of mononuclear phagocytes.

Chorionic Villi↗

Bovine digital dermatitis and severe virulent ovine foot rot: a common spirochaetal pathogenesis.

A potential pathological role for spirochaetes in bovine digital dermatitis (bovine DD) and severe virulent ovine foot rot (SVOFR) has been considered and a treponeme isolate obtained from each disease in the UK. In this work, we have investigated the hypothesis that the two diseases may have a shared (common) spirochaetal aetiology. Experiments were designed to identify serological similarities and differences between the two spirochaetes; an enzyme-linked immunosorbent assay (ELISA) was developed to detect anti-treponeme antibodies in the sera of cows and sheep against the two-treponeme isolates. Sera were further tested for antigen reactivity by Western blotting. Cattle and sheep with bovine DD and SVOFR, respectively, had increased seropositivity rates to both treponeme isolates, with different patterns of reactivity between farms. In some cattle herds, significant correlations were shown between antibodies to bovine DD treponemes and SVOFR treponemes (P<0.001). In other herds, there was no apparent cross reaction, suggesting the presence of more than one treponeme in bovine DD on some farms. There was no significant correlation between the two treponeme isolates when ELISA-tested against 58 sheep sera from SVOFR cases (P>0.05); sheep showed strong evidence of reactivity to one or the other treponeme antigens, but never to both. Western blotting against both treponeme antigens showed that they frequently displayed different antigen epitopes, although some minor bands were common to both organisms. The data suggest that there are a number of spirochaetes in UK farms, which could be involved in the pathogenesis of either bovine DD or SVOFR.

Animals↗

A reappraisal of the value of the IgM fluorescent treponemal antibody absorption test in the diagnosis of congenital syphilis.

To re-evaluate the usefulness of the IgM fluorescent treponemal antibody absorption test in the diagnosis of congenital syphilis, three groups of infants were investigated. Group 1 infants showed that the test was always negative in normal neonates born to seronegative mothers. From Group 2 infants we determined the standardization of the test using commercially prepared conjugate to allow the maximum exclusion of false positive and negative results. Studies on Group 3 neonates confirmed that the standardized test was extremely successful in determining whether or not an asymptomatic infant was infected with Treponema pallidum. Finally it was shown that the standardization of the test varies with different commercially prepared conjugates. From the investigation it was concluded that the IgM FTA test, if suitably standardized, was a highly successful method for diagnosing congenital syphilis, especially in asymptomatic neonates.

Black or African American↗

Pachymeningitis luetica: a case report.

Pachymeningitis luetica is extremely rare in developed countries. We describe a 41-year-old male patient with pachymeningitis luetica, multiple ischaemic infarctions, and severe hydrocephalus. The delay in making the diagnosis contributed to patient's death. Rapid diagnosis is essential on the slightest suspicion of an infection by Treponema pallidum, because timely treatment with antibiotics is effective.

Adult↗

Primary syphilis remains a cause of oral ulceration.

After many years the incidence of infective syphilis (infection with Treponema pallidum) is increasing in the United Kingdom. This may reflect changes in sexual attitudes and behaviour, altering trends in HIV disease, and increased foreign travel. Oral disease as a consequence of primary syphilis is rare. The present report details two patients presenting to an oral medicine clinic in London, within a 6-month period in 1999, with oral ulceration as their only clinical manifestation of undiagnosed primary syphilis. The oral aspects of early syphilis and the need for dentists to be aware of changing epidemiological trends in relevant infectious diseases are highlighted.

Adult↗

[Acute hepatitis as the leading symptom of secondary syphilis].

HISTORY AND CLINICAL FINDINGS: A 44-year-old heterosexual man reported having been jaundiced for 4 days. He drank little alcohol. There was no history of venereal disease. INVESTIGATIONS: Laboratory tests indicated marked cholestasis (alkaline phosphatase 1589 U/I, gamma-GT 449 U/I), but only moderately raised transaminases (GOT 66 U/I, GPT 230 U/I), with a bilirubin level of 4.8 mg/dl. Ultrasonography revealed diffuse parenchymal damage in the liver, while endoscopic retrograde cholangiopancreatography showed no abnormalities. Viral hepatitis was excluded by serological tests. Histology of a liver biopsy showed inflammatory infiltration of the portal areas and of the liver parenchyma. Routine syphilis serology indicated fresh infection with Treponema pallidum. There was a healing painless ulcer in the area of the sulcus coronarius of the genitals. TREATMENT AND COURSE: 2.4 mill. I.U. benzathine benzylpenicillin were administered intramuscularly. This rapidly improved his condition and liver function tests became normal. CONCLUSION: In case of hepatitis of uncertain genesis syphilis should be considered as a possible cause, even in the absence of other signs of the disease.

Acute Disease↗

Cutaneous lesions of secondary syphilis are highly angiogenic.

BACKGROUND: The role of angiogenesis in infectious processes is poorly studied. Some viruses have been linked to angiogenesis, but the role of bacteria and protozoa in inducing angiogenesis in chronic infections is poorly understood. OBJECTIVES: We examined the role of angiogenesis in syphilis, a common and often difficult-to-treat infectious disease, especially in the setting of HIV/AIDS. METHOD: Microvessel counts were performed on 27 paraffin-fixed sections of secondary syphilis by staining with monoclonal antibodies against CD31. In addition, immunohistochemistry was performed using antibodies against vascular endothelial growth factor (VEGF) to determine whether increased angiogenesis may be mediated, in part, through increased production of VEGF. RESULTS: The CD31 mean microvessel count in secondary syphilis sections was significantly higher than in normal control sections. VEGF intensity appeared increased in the patients with secondary syphilis. CONCLUSIONS: Infection with Treponema pallidum results in increased angiogenesis in secondary syphilis. The mechanism for increased angiogenesis may involve elaboration of angiogenic cytokines, such as VEGF and epidermal growth factor.

Endothelial Growth Factors↗

Cost-effectiveness of antenatal screening for syphilis.

Routine obstetric screening for all prenatal checkups is an important issue. A study was conducted to ascertain the effectiveness of an antenatal screening program for syphilis. Charts of pregnant women for a 9-year period from 1982 to 1990 at the American University of Beirut were reviewed. Demographic data and the results of screening for syphilis were collected. In a total of 23,145 patients screened (with a biological false-positive rate of 0.3%), serological evidence of Treponema pallidum infection occurred in 0.27% of patients. The outcome in infants was satisfactory in all cases where appropriate antibiotic therapy was instituted antenatally. Thus antenatal screening for syphilis in our setting is a cost-effective program.

Adult↗

Syphilitic lymphadenopathy. Histology and human immunodeficiency virus status.

Few reports on syphilitic lymphadenopathy have appeared in 20 years, and none have compared findings in patients with and without human immunodeficiency virus (HIV) infection, despite the recent epidemic spread of syphilis and HIV. Twelve cases of syphilitic lymphadenopathy were studied and grouped according to HIV status. Patients were 21 to 62 years old (median, 29 years); 7 were men, 5 were women. Biopsy sites were cervical (7 cases), inguinal (4), and axillary (1) lymph nodes. All patients had evidence of syphilis. Rapid plasma reagin titers ranged from 1:32 to 1:512. Treponemal hemagglutination was positive in all cases tested. Spirochetes were found with Steiner staining in 2 cases. HIV testing was positive in 4, negative in 2, and unknown in 6 cases. Lymph nodes were enlarged and often fragmented due to capsular fibrosis and chronic inflammation, with focal obliteration of the subcapsular sinus. Follicular and interfollicular hyperplasia was seen in all cases and was usually marked, with prominent vascular proliferation, plasma cells, immuno-blasts, histiocytes, and occasional neutrophils. Follicle lysis and granulomas suggestive of unconfirmed toxoplasmosis were each seen in 1 case, and Kaposi sarcoma in 2, all in HIV-positive patients. Lymphoplasmacytic infiltration was marked, especially in interfollicular areas, with peri-vascular plasma cell cuffing in all cases and obliterative endarteritis in about half (7 of 12, 56%). Immunostaining for CD45RO (UCHL-1), CD20 (L26), kappa, lambda, and CD68 (Kp-1) revealed a mixed population of T cells, polyclonal B cells, and interfollicular histiocytes. Distribution of T and B cells (immunoarchitecture) was essentially normal and similar in all cases, regardless of HIV status. Syphilis produces essentially identical findings in lymph nodes in both HIV-positive and HIV-negative patients. The morphologic findings described should prompt evaluation for infection with Treponema pallidum and, in light of the current epidemic, HIV.

Adult↗

Treatment of seropositive primary syphilis: an evaluation of 196 patients.

One hundred seventy-five patients with primary infection with Treponema pallidum were treated with benzathine penicillin G, 2.4 million units given intramuscularly weekly for two weeks for a total of 4.8 million units. Twenty-one patients with primary syphilis who were allergic to penicillin were treated with oral tetracycline, 500 mg four times daily for 12 days for a total of 24 gm. All 196 patients had resolution of their lesions, and all were seronegative within one year. White patients presented for treatment earlier than black patients. The duration of symptoms prior to presentation for treatment was positively correlated with the height of the serologic titer in the rapid plasma reagin card test. Patients who had high titers before treatment became seronegative less rapidly than patients who had low pretreatment titers.

Adolescent↗

Primary herpes simplex and primary syphilis: a description of seven cases.

This report describes the cases of seven patients who had primary genital infection with herpes simplex virus and whose initial nontreponemal and treponemal tests for syphilis were nonreactive. On routine posttreatment examination, a change in the consistency of the ulcers was noticed, and the inguinal nodes, which had been soft and tender, were hard and non-tender. The morphologic changes indicated the probable presence of concomitant primary infection with Treponema pallidium, which was confirmed serologically for all seven patients and by a positive darkfield examination for two patients. Clinicians should be aware that different sexually transmitted diseases often coexist. Patients who have primary genital herpes should be followed clinically and serologically until recovery is complete.

Adolescent↗

Transfusion syphilis: a case report.

An infant girl acquired syphilis after exchange transfusion with fresh whole blood in 1977 in Rotterdam. She showed typical features of early infectious syphilis three and a half months after the transfusion. The parents had no histories or clinical or serologic signs indicative of syphilis. Although the blood donor had negative serologic tests for syphilis shortly before giving the blood, later examination indicated that he must have become infected with Treponema pallidum shortly before donation of the blood used in the transfusion of the infant.

Exchange Transfusion, Whole Blood↗

Introductory address: gonorrhea today.

The counterattack to the resurgence of one of the commonest infectious diseases, gonorrhea, still consists of epidemiologic measures, correct clinical and microbiological diagnosis, and effective treatment. Few antibiotics effective against Neisseria gonorrhoeae fulfill the criteria of the World Health Organization (i.e., the antibiotic should be effective, safe, free from side effects, capable of aborting simultaneously acquired or coexisting infection with Treponema pallidum or Chlamydia trachomatis, should entail a low incidence of postgonococcal urethritis, and should not be the sole antibiotic used for other, more serious conditions). Therefore, current attention is focused on the use of thiamphenicol for the treatment of uncomplicated urogenital, rectal, and oropharyngeal gonorrhea caused by both beta-lactamase-producing and non-beta-lactamase-producing Neisseria gonorrhoeae.

Aminoglycosides↗

Untargeted metabolomics in a prospective cross-sectional observational study reveals differences in plasma and cerebrospinal fluid between asymptomatic neurosyphilis and serofast syphilis.

Asymptomatic neurosyphilis (ANS), a diagnostically elusive complication of Treponema pallidum infection, necessitates invasive cerebrospinal fluid (CSF) analysis for detection. This study investigated metabolic differences between patients with ANS and those with serofast syphilis. Using untargeted metabolomics, we analyzed plasma and CSF from 15 patients with ANS, 15 patients with serofast syphilis, and 16 healthy controls via liquid chromatography-mass spectrometry. Univariate statistical analyses identified differential metabolites, followed by pathway enrichment through Kyoto encyclopedia of genes and genomes enrichment analysis and biomarker evaluation. Plasma analysis identified dysregulated tryptophan metabolism as a central feature in ANS, with key alterations in 4-(2-aminophenyl)-2,4-dioxobutanoic acid and 2-formylaminobezaldehyde. Comparative analysis further distinguished ANS through perturbations in inositol phosphate metabolism in both plasma and CSF. Spearman correlation analysis identified positive associations of the plasma biomarkers 1D-myo-inositol-1,3,4,6-tetrakisphosphate, inositol-1,3-bisphosphate, 4-(2-aminophenyl)-2,4-dioxobutanoic acid, and 2-formylaminobezaldehyde with CSF total protein. Our findings suggest that dysregulation in tryptophan and inositol phosphate metabolism may play an important role in ANS pathogenesis, warranting further confirmatory studies.

Humans↗

The ability of peripheral blood mononuclear cells (PBMC) of syphilitic patients to produce IL-2.

The cell-mediated immune response of importance in protection against Treponema pallidum, is distinctly suppressed in some stages of the disease. This may be a result of decreased ability of cells to produce IL-2, or IL-2 absorption by different factors. The experiments were designed to evaluate the ability of peripheral blood mononuclear cells (PBMC) of patients with different stages of syphilis to produce IL-2, and to investigate the causes which could possibly limit its activity. The ability of the PBMC of syphilitic patients to produce IL-2 develops at the beginning of the disease, reaching a maximum in primary seropositive syphilis. In the next stages of the disease this capability is distinctly lowered. The lowest was in malignant syphilis and tabes dorsalis, i.e. during severe disease. Absorption of adherent cells from PBMC increased the ability of lymphocytes to produce IL-2. The highest level of this interleukin was observed at the stages of the disease where suppression was the deepest. Sera of both control and syphilitic patients contained IL-2 inhibitor. Its level was the highest in early and late latent syphilis where no symptoms of disease were present. In all syphilitic sera a distinctly elevated level of soluble IL-2 receptors (sIL-2R) was also found. Its high level was noted in sera of patients in which PBMC had the weakest ability to produce IL-2. These findings suggest that sIL-2R may be bound to IL-2 and in this way would lead to weakening of T cell function and of resistance against Treponema pallidum infection.

Antibodies↗