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Cerebrospinal fluid findings in asymptomatic patients with reactive serum fluorescent treponemal antibody absorption tests.

It is common to examine the cerebrospinal fluid in untreated or inadequately treated asymptomatic patients with a reactive serum fluorescent treponemal antibody absorption (FTA-ABS) test before initiating antibiotic therapy for syphilis. This prospective study evaluated the usefulness of such examination. Four hundred thirty-two patients over 40 years old, reporting for annual physical examination, had a serum FTA-ABS test. Thirty-seven (8.6%) patients and 2 of 4 spouses were reactive repeatedly. Of the 39 patients with reactive tests, 7 had a history of penicillin therapy for syphilis, 5 had received heavy metal therapy, and 27 had no history of syphilis. These 39 patients had a neurological examination, serum VDRL, Treponema pallidum immobilization (TPI), and repeat FTA-ABS tests by two other laboratories. The TPI test was reactive in 30 (77%). Four had nonspecific neurological signs. Routine CSF examination (cells, total protein, VDRL, glucose, IgG%) on 30 patients with a history of inadequate treatment had a low diagnostic yield. Two patients had an unexplained total protein elevation (57 and 61 mg/dl) and 1 had a mildly increased IgG% (15%). All cell counts, VDRL tests, and glucose levels were normal. Agarose electrophoresis demonstrated one or more CSF immunoglobulin bands in 10 (36%) of 28 patients, possibly representing an immunological marker of past or latent central nervous system infection.

Adult↗

Delayed hypersensitivity, immune deviation, antigen processing and T-cell subset selection in syphilis pathogenesis and vaccine design.

T-cell mediated delayed-type hypersensitivity (DTH) is the predominant immune mechanism for clearing tissues of infecting organisms in the primary lesion of syphilis. Here, Stewart Sell and Pei-Ling Hsu propose a strategy for vaccination against syphilis in which selective induction of DTH may be accomplished by using BCG vectored vaccines containing selected DNA sequences for T. pallidum antigens.

Animals↗

The role of hemolysin(s) in the pathogenesis of Serpulina hyodysenteriae.

Serpulina (Treponema) hyodysenteriae, an anaerobic beta hemolytic spirochaete, is the etiologic agent of swine dysentery. Not much is known at present about the virulence factors of S. hyodysenteriae. However, the hemolysin production of this bacterium is generally accepted to be a virulence factor. To study the exact role of hemolysin production in the pathogenesis of swine dysentery, the gene encoding a hemolysin, tly, was cloned and its nucleotide sequence determined. After inactivation of this gene, the virulence of a tly-minus mutant in mice was tested. The mutant had reduced hemolysis indicating that the tly-encoded hemolysin was not the only hemolysin produced by S. hyodysenteriae. Mice infected with the tly-minus mutant had fewer cecal lesions than mice infected with the wild-type S. hyodysenteriae. It was concluded that the tly-encoded hemolysin might be an important virulence factor, but not the only one. Since it was demonstrated that spirochaetes can be transformed through electroporation, this has made a genetic approach to elucidate the pathogenesis of spirochaetal infections possible.

Animals↗

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↗

Syphilis seroprevalence among pregnant women and its role as a risk factor for stillbirth in Maputo, Mozambique.

OBJECTIVE: To elucidate the role of current syphilis as a risk factor for foetal death. METHODS: Sera were obtained from 57 women with third trimester foetal death (cases) and 58 women with foetus alive (controls) matched for age and parity. All sera reactive in qualitative Rapid Plasma Reagin (RPR) analyses were tested with serial twofold dilutions to determine endpoint flocculation titres and tested with the micro-haemagglutination assay for Treponema pallidum (MHA-TP). Placental biopsies were sectioned and stained by haematoxylin-eosin and Warthin-Starry for light microscopy. SETTING: Central Hospital, in Maputo, Mozambique, from January 1990 to June 1991. RESULTS: The MHA-TP was reactive in 42% of cases and in 12% of controls (OR = 5.3; 95% CI: 1.9-15.4). The RPR card test was reactive at the dilution of 1.32 or greater in 28% of cases and in 7% of controls. All these results were confirmed by MHA-TP (OR = 5.3; 95% CI: 1.5-15.4). In 9/28 (32%) MHA-TP seroreactive women (7 cases and 2 controls) placental morphological changes indicated syphilitic infection. CONCLUSION: MHA-TP seroreactivity and high titre RPR were associated with stillbirth. Morphological changes presumptive of syphilis infection were found in 32% placentas histologically studied. Syphilis is a risk factor for foetal death in Maputo, Mozambique.

Case-Control Studies↗

Carrion's disease (Bartonellosis bacilliformis) confirmed by histopathology in the High Forest of Peru.

Bartonellosis or Carrion's disease is endemic in some regions of Peru, classically found in the inter-Andean valleys located between 500 and 3200 meters above sea level. We report the case of a 43 year-old male patient, farmer, who was born in the Pichanaki district (Chanchamayo, Junin), located in the High Forest of Peru. He presented with disseminated, raised, erythematous cutaneous lesions, some of which bled. The distribution of these lesions included the nasal mucosa and penile region. Additionally subcutaneous nodules were distributed over the trunk and extremities. Hematologic exams showed a moderate anemia. Serologic studies for HIV and Treponema pallidum were negative. The histopathologic results of two biopsies were compatible with Peruvian wart. Oral treatment with ciprofloxacin (500 mg BID) was begun. Over 10 days, the patient showed clinical improvement. This is the first report of a confirmed case of bartonellosis in the eruptive phase originating from the Peruvian High Forest, showing the geographical expansion of the Carrion's disease.

Adult↗

Immunologic and structural characterization of the dominant 66- to 73-kDa antigens of Borrelia burgdorferi.

The 66- to 73-kDa proteins of Borrelia burgdorferi are dominant immunogens and expressed in all strains of B. burgdorferi. The humoral response to these Ag occurs relatively early during the course of infection. Two-dimensional Western blot analysis of this group of Ag revealed them to consist of a tetrad of proteins with apparent molecular mass of 66, 68, 71, and 73 kDa. Furthermore, in this study we demonstrate the 66-kDa protein to be a potent inducer of lymphoproliferation in the patient immune to B. burgdorferi. Monospecific polyclonal antibodies and mAb demonstrate that each of these proteins was immunologically distinct. However, direct amino acid sequence of the 66- and 68-kDa Ag was almost identical and had a high level of sequence similarity to the GroEL heat-shock protein (Hsp60) of Escherichia coli and the 60-kDa immunodominant protein of Treponema pallidum. The amino terminal sequence of the 71- and 73-kDa proteins of B. burgdorferi was almost identical and these proteins had remarkable sequence similarity to the DnaK heat-shock protein of E. coli (Hsp70). It appears likely, therefore, that proteins related to the heat-shock family are potent immunogens of B. burgdorferi.

Amino Acid Sequence↗

Polypeptides of Treponema pallidum: progress toward understanding their structural, functional, and immunologic roles. Treponema Pallidum Polypeptide Research Group.

Treponema pallidum subsp. pallidum, the spirochete that causes syphilis, is unusual in a number of respects, including its small genome size, inability to grow under standard in vitro culture conditions, microaerophilism, apparent paucity of outer membrane proteins, structurally complex periplasmic flagella, and ability to evade the host immune responses and cause disease over a period of years to decades. Many of these attributes are related ultimately to its protein content. Our knowledge of the activities, structure, and immunogenicity of its proteins has been expanded by the application of recombinant DNA, hybridoma, and structural fractionation techniques. The purpose of this monograph is to summarize and correlate this new information by using two-dimensional gel electrophoresis, monoclonal antibody reactivity, sequence data, and other properties as the bases of polypeptide identification. The protein profiles of the T. pallidum subspecies causing syphilis, yaws, and endemic syphilis are virtually indistinguishable but differ considerably from those of other treponemal species. Among the most abundant polypeptides are a group of lipoproteins of unknown function that appear to be important in the immune response during syphilitic infection. The periplasmic flagella of T. pallidum and other spirochetes are unique with regard to their protein content and ultrastructure, as well as their periplasmic location. They are composed of three core proteins (homologous to the other members of the eubacterial flagellin family) and a single, unrelated sheath protein; the functional significance of this arrangement is not understood at present. Although the bacterium contains the chaperonins GroEL and DnaK, these proteins are not under the control of the heat shock regulon as they are in most organisms. Studies of the immunogenicity of T. pallidum proteins indicate that many may be useful for immunodiagnosis and immunoprotection. Future goals in T. pallidum polypeptide research include continued elucidation of their structural locations and functional activities, identification and characterization of the low-abundance outer membrane proteins, further study of the immunoprotective and immunodiagnostic potential of T. pallidum proteins, and clarification of the roles of treponemal proteins in pathogenesis.

Amino Acid Sequence↗

Production and characterization of a polyclonal antiserum against Spiroplasma mirum (ATCC 29335).

Spiroplasma mirum (ATCC 29335), an American tick isolate, was cultivated and its purity was controlled using electron microscopy and Tricine-SDS-PAGE. In the SDS-PAGE analysis, the protein pattern of the antigen used revealed a polypeptide profile (35 bands) with an approximate molecular weight of 161 kDa to 10.5 kDa. This strain was used to immunize two rabbits. The produced antisera did not cross-react with Mycoplasma pneumoniae, Salmonella minnesota, Borrelia burgdorferi, Treponema pallidum but did still react in Western blot analysis with Spiroplasma mirum at a dilution of 1:128.000. This specific and sensitive antiserum was used to examine 72 midgut smears of Berlin ticks (lxodes ricinus) individually by direct immunofluorescence. In 26 samples, we could demonstrate fluorescent structures, but we were not able to culture spiroplasmas from these samples.

Animals↗

Genital ulcer disease in men in Durban, South Africa.

OBJECTIVE: To study the microbial aetiology of genital ulcer disease (GUD) in men. DESIGN: Microbiological and clinical assessment of genital ulcers in men. SETTING: City Health sexually transmitted diseases clinic, King Edward VIII Hospital, Durban, South Africa. PARTICIPANTS: 100 Zulu men with genital ulcers who had not received antibiotics in the previous four weeks. RESULTS: Syphilis was diagnosed in 42%, chancroid in 22%, donovanosis (granuloma inguinale) in 11%, genital herpes in 10% and lymphogranuloma venereum (LGV) in 6%. No pathogens were identified in 24%. Mixed infections were detected in 14 men, in whom 13 had syphilis. Five men had HIV-1 antibodies. Neisseria gonorrhoeae was isolated from the ulcers and urethra in seven men and from the urethra alone in five. Scabies was diagnosed clinically in eight. CONCLUSIONS: All the major causes of GUD are prevalent in Zulu men in Durban. Primary syphilis was the commonest and was invariably present in mixed infections. Donovanosis was under-reported and was associated with a long delay before presentation. In this population, genital ulcers other than superficial lesions should be treated with anti-syphilitic therapy and oral antibiotics effective against chancroid and donovanosis.

Adolescent↗

Observation of an unusually large spirochete in endodontic infection.

Spirochetes in the root canal have been investigated only to a minor extent. Oral spirochetes have been detected particularly in the periodontal pocket, where small, medium-sized and large morphotypes have been reported. In the present darkfield and scanning electron microscopic study we describe a spirochete isolated from the root canal that is 7 times longer (140 microns long) and 5 times thicker (2 microns thick) than usual for treponemes.

Aged↗

Association of hepatitis C virus infection with false-positive tests for syphilis.

The prevalence of false-positive reactions for syphilis (reactive rapid plasma reagin [RPR] test and nonreactive fluorescent treponemal antibody absorption [FTA-ABS] test) among patients at sexually transmitted disease (STD) clinics was assessed to evaluate the association between false-positive RPR reactions and hepatitis C virus (HCV) infections. Among 2672 patients, 400 (15.0%) had antibodies to HCV (anti-HCV) and 254 (9.5%) had a reactive RPR test. Of the 254 reactive RPR tests, 231 (90.1%) were also positive by FTA-ABS, leaving 23 false-positive RPR reactions. After excluding the 231 patients with positive FTA-ABS tests, false-positive RPR tests were found in 9 (2.7%) of 330 anti-HCV-positive patients compared with 14 (0.6%) of 2154 anti-HCV-negative participants (relative risk, 4.5; 95% confidence interval, 1.9-10.9; P = .0017). These data demonstrate that HCV infection is associated with false-positive RPR test results. However, because of the high prevalence of syphilis among STD patients, the RPR test remains a strong indicator of syphilis in this setting.

Adolescent↗

Serological screening tests for syphilis in pregnancy: results of a five year study (1983-87) in the Oxford region.

Between 1983 and 1987, 62 out of 76519 pregnancies in 51 mothers had a positive miniaturised Treponema pallidum haemagglutination assay (TPHA) test--1 in 1234, or 0.81 per 1000 births. About two thirds of these mothers had syphilis and the remainder non-venereal treponematoses such as yaws or pinta. Antenatal screening identified 13 patients with previously unknown acquired syphilis, 11 of whom were given antibiotics during pregnancy. There were six fetal losses among the 62 TPHA positive pregnancies, but none had evidence of congenital syphilis. No live born child in this study group showed stigmata of congenital syphilis. It is concluded that despite the current low incidence of syphilis in the United Kingdom it is imperative to continue antenatal serological screening and to emphasise the importance of early adequate treatment of the infection.

Cost-Benefit Analysis↗

Epidemiology of sexually transmitted diseases in Río Cuarto, Argentina.

Sexually transmitted diseases (STD) are a group of transmittable diseases acquired fundamentally through sexual contact. STD are a social problem resulting from demographic explosion and changes in sexual conduct, which affects teenagers and adults of all socioeconomic strata. The goal of this work was to establish the actual state of the different STD within the studied population. Samples of vaginal fluids, endocervical materials and urethral exudates taken from 2,630 patients during five years were processed. 1,341 samples tested positive to one or more of the microorganisms, 1,099 corresponding to female patients and 242 to male patients. The microorganisms found in women were: Gardnerella vaginalis (39.1%), Candida albicans (21.3%), Trichomonas vaginalis (16.8%), Chlamydia trachomatis (11.5%); Neisseria gonorrhoeae (3.4%), Mycoplasma hominis (2.6%); Ureaplasma urealyticum (4.1%) and Treponema pallidum (1.6%). Associations were: Gardnerella vaginalis with Trichomonas vaginalis (6%), Gardnerella vaginalis with Candida albicans (5.1%); Trichomonas vaginalis with Neisseria gonorrhoeae (2.2%) and Gardnerella vaginalis with Chlamydia trachomatis (2.1%). In men, gonococcic urethritis represented 37.8%, non-gonococcic urethritis 55.4% and Treponema pallidum 6.8%. A decrease in syphilis, gonococcic urethritis and gonococcic cervicitis was observed, increasing the prevalence of non-gonococcic urethritis and cervicitis. This study showed that in our environment the actual tendency of STD is still high.

Adolescent↗

Biological activity of a peptidoglycan extracted from Leptospira interrogans: in vitro studies.

Peptidoglycan (PG) has been isolated from some species of spirochaetes, including Leptospira interrogans. Although leptospiral PG has been chemically characterized, no study has been carried out on its potential biological activity. Since PG of Treponema and Borrelia is biologically active both in vivo and in vitro, we investigated the capacity of a leptospiral PG preparation to induce relevant biological effects. PG extracted from L. interrogans strain Teramo was mitogenic at 0.1 microgram ml-1 for human peripheral blood mononuclear cells (PBMC) since it increased the PBMC fraction positive for Ki-67, an antigen expressed by human proliferating cells; at 4 micrograms ml-1, PG was able to induce complement consumption and to stimulate leucocyte phagocytosis and the metabolic burst of resting as well as phagocytosing leucocytes. These findings indicate that Leptospira PG may play a role in modulating the immunocompetent cell functions and suggest that PG can contribute to the host response during Leptospira infection.

Cell Division↗

The benzoyl-DL arginine-naphthylamide (BANA) test and polymerase chain reaction measurement of pathogenic bacteria can assess the severity of periodontal disease.

The benzoyl-DL arginine-naphthylamide (BANA) test for detecting digesting peptidase and polymerase chain reaction (PCR) measurement of pathogenic bacteria were performed in 15 patients with periodontal disease. The number of Porphyromonas gingivalis, Bacteroides forsythus and Treponema denticola, which are the most potent accelerators of alveolar bone resorption, were determined. Attachment loss and the BANA test showed significant close correlations with the number of pathogenic bacteria as well as with the tooth mobility and pocket depth. In conclusion, the BANA test and PCR measurement of bacteria are useful methods for detecting pathogenic bacteria that promote alveolar tissue destruction.

Adolescent↗

Role of the chymotrypsin-like membrane-associated proteinase from Treponema denticola ATCC 35405 in inactivation of bioactive peptides.

The ability of washed whole cells of Treponema denticola ATCC 35405 to hydrolyze (inactivate) substance P, bradykinin, and angiotensin I was studied. Substance P was attacked primarily at the Phe-8-Gly-9 bond by a chymotrypsin-like proteinase (CTLP), at Pro-4-Gln-5 by an endo-acting prolyl oligopeptidase (POPase), and at Gln-5-Gln-6 by an endopeptidase (FALGPA-peptidase). Bradykinin was cleaved at Phe-5-Ser-6 by the FALGPA-peptidase and at Pro-7-Phe-8 by the POPase. Angiotensin I was rapidly converted to angiotensin II by the CTLP, and both angiotensin I and angiotensin II were further hydrolyzed at Pro-7-Phe-8 by the POPase. All these enzymes were assumed to be cell associated and were easily extracted with a mild (0.05 to 0.1%) Triton X-100 treatment. Because it was conceivable that the hydrolysis of substance P at the Phe-8-Gly-9 bond was catalyzed by a CTLP described earlier (V.-J. Uitto, D. Grenier, E. C. S. Chan, and B. C. McBride, Infect. Immun. 56:2717-2722, 1988), the enzyme was purified to homogeneity by means of conventional fast protein liquid chromatography procedures. For kinetic studies, Phe-8(4-nitro)-substance P (NSP) (absorption maximum at 309.2 nm, epsilon = 545 M-1 cm-1) was synthesized to replace substance P as a substrate in kinetic studies. In reversed-phase chromatography, both NSP and substance P gave identical results with both whole cells and the purified enzyme. The CTLP has a mass of 95 kDa, and its activity is suggested to be based on an active seryl residue, on an active imidazole group, and on an active carboxyl group but not on metal cations. The enzyme hydrolyzes N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroaniline (SAAPFNA, a typical chymotrypsin substrate) at a high rate and several proteins, such as calf thymus histone, human plasma fibrinogen, milk caseins, and gelatin. Among the substrates tested, substance P showed the highest affinity (Km = 0.22 mM) for the purified enzyme. Depending on conditions, clinically applicable chlorhexidine levels (3.2 mmol/liter, or 0.2%) strongly activated (up to fourfold) the hydrolysis of SAAPFNA by whole cells and the purified CTLP. The hydrolysis of NSP by whole cells and purified CTLP was slightly inhibited by chlorhexidine. The results demonstrated the versatility and the effectiveness of the outer membrane of T. denticola in occasioning a rapid breakdown and inactivation of human bioactive peptides and other peptidolytic catalyses.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features.

Syphilis is a chronic disease with a waxing and waning course, the manifestations of which have been described for centuries. It occurs worldwide, and the incidence varies significantly with geographic location. Transmission is mainly by sexual contact. The causative organism, Treponema pallidum, was first described in 1905, but because of the inability to culture the organism and the limitations of direct microscopy, serologic testing is the mainstay of laboratory diagnosis. The disease has been arbitrarily divided into several stages. The primary stage is defined by a chancre at the site of inoculation. The secondary stage is characterized by a polymorphic rash, lymphadenopathy, and other systemic manifestations. A variable asymptomatic latent period follows, which for epidemiologic purposes is divided into early (<1 year) and late (>1 year) stages. The early stages (primary, secondary, and early latent) are potentially infectious. The tertiary stage is the most destructive and is marked by cardiovascular and neurologic sequelae and gummatous involvement of any organ system. Congenital infection may result in protean early or late manifestations. Unlike many other bacteria causing infectious diseases, the organism remains sensitive to penicillin, and this remains the mainstay of therapy.

HIV Infections↗