VDRL antibodies enhance phagocytosis of Treponema pallidum by macrophages.

Although reactivity in nontreponemal tests develops in patients with untreated syphilis, no immunologic function has been ascribed to these antibodies. This study demonstrates that rabbit antibodies induced by immunization with VDRL antigen and VDRL antibodies affinity-purified from syphilitic rabbit serum enhance phagocytosis of Treponema pallidum. The proportion of macrophages ingesting treponemes in the presence of these antisera was 45% +/- 5% and 27% +/- 4%, respectively, versus 14% +/- 3% for normal serum (P < .

Characterization of the serum requirement for macrophage-mediated killing of Treponema pallidum ssp. pallidum: relationship to the development of opsonizing antibodies.

Serum pools were collected from rabbits bled at various times after intra-testicular infection with Treponema pallidum ssp. pallidum. These were tested for their ability to opsonize T.

Opsonization of Treponema pallidum is mediated by immunoglobulin G antibodies induced only by pathogenic treponemes.

Rabbit antisera to Leptospira interrogans, Borrelia hermsii, and Treponema phagedenis biotype Reiter, reactive to shared spirochetal antigens, failed to enhance phagocytosis of Treponema pallidum by macrophages, while immunoglobulin G to Treponema pallidum subsp. pertenue and Treponema paraluiscuniculi promoted phagocytosis. Opsonic antibodies are directed to pathogen-restricted, not shared spirochetal, antigens.

A subpopulation of Treponema pallidum is resistant to phagocytosis: possible mechanism of persistence.

While untreated syphilis infection is characterized by spontaneous resolution of early lesions, a few organisms evade the host immune response and persist for many years. Macrophages are generally recognized as the effector cell responsible for bacterial clearance, and phagocytosis is enhanced by immune serum. This study examined the susceptibility of Treponema pallidum isolated at various stages of lesion resolution to opsonization and phagocytosis by macrophages in vitro.

Macrophage-mediated killing of opsonized Treponema pallidum.

The ability of proteose peptone-induced normal rabbit peritoneal macrophages to kill Treponema pallidum subspecies pallidum in vitro is demonstrated. Treponemes and 10% heated immune or normal sera were incubated with macrophages at a ratio of 1:200. After 2-10 h of incubation, these mixtures were injected intradermally at duplicate sites on normal rabbits.

Identification of spirochetes related to Treponema pallidum in necrotizing ulcerative gingivitis and chronic periodontitis.

Background: Spirochetes are commonly associated with periodontal disease, but it is not known whether these treponemes are pathogenic or merely opportunistic. We sought to determine whether spirochetes present in periodontal disease share antigens thought to be unique to spirochetes that are known pathogens.

Methods: We examined dental plaque from 24 healthy subjects, from ulcerative sites in 17 patients with ulcerative gingivitis, and from areas of involvement in 19 patients with chronic periodontitis, using an immunocyto-chemical technique with monoclonal antibodies against pathogen-specific determinants on 47-kd and 37-kd molecules from Treponema pallidum subspecies pallidum.

An experimental model of early central nervous system syphilis.

Although up to 40% of patients with early syphilis have evidence of central nervous system (CNS) invasion by Treponema pallidum, the pathogenesis of CNS syphilis is not understood. A rabbit model that mimics early CNS involvement in humans was developed and characterized. Mild cerebrospinal fluid pleocytosis was evident 2 weeks after intracisternal inoculation of T.

Efficacy of azithromycin for therapy of active syphilis in the rabbit model.

Azithromycin was shown to be as effective as standard benzathine penicillin and erythromycin in the therapy of active syphilis in the rabbit model. Following production of primary chancres by intradermal inoculation of 10(6) Treponema pallidum, groups of six rabbits were treated with benzathine penicillin (200,000 units im weekly for two weeks), erythromycin base (30 mg/kg/day orally four times daily for 15 days) or azithromycin (30 mg/kg/day given orally once or twice daily for 15 days); one group was untreated. Daily darkfield (DF) microscopic examinations of chancre aspirates were conducted to identify motile organisms.

Efficacy of cefmetazole in the treatment of active syphilis in the rabbit model.

Cefmetazole, a cephamycin-type antibiotic, was shown to be as effective as standard benzathine penicillin for therapy of active syphilis in the rabbit model. Four groups of six adult male rabbits were inoculated intradermally with 10(6) Treponema pallidum per site, producing primary syphilitic lesions. One week following infection, groups of rabbits were treated with benzathine penicillin (200,000 U intramuscularly weekly for 2 weeks) or cefmetazole (20 or 40 mg/kg per day intramuscularly in four divided doses for 15 days); one group was untreated.

Development of cellular immunity to individual soluble antigens of Treponema pallidum during experimental syphilis.

The contribution of individual specific molecules of Treponema pallidum subspecies pallidum to cellular immunity in experimental syphilis was evaluated by combining the techniques of Ag identification and purification with the lymphocyte proliferation assay. Proliferative responses of splenic lymphocytes from syphilitic rabbits to complex treponemal Ag and Con A were vigorous throughout the course of intratesticular infection (6, 10, 17, 30, and 210 days). Normal rabbits did not respond to any treponemal preparations and all rabbits failed to respond to normal rabbit testicular Ag (NRT).

Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment.

Study Objectives: To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement.

Patients: Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period.

Specificity of antibodies from patients with pinta for antigens of Treponema pallidum subspecies pallidum.

Inhabitants of a remote Panamanian village were examined for clinical and serological evidence of pinta infection. Of 104 persons examined, 21 (20%) had clinical evidence of active or inactive pinta, and 54 (52%) were seropositive. Sera were evaluated for antibody to individual Treponema pallidum antigens.

Roxithromycin (RU 965): effective therapy for experimental syphilis infection in rabbits.

Roxithromycin (RU 965), a new macrolide antibiotic, was shown to be effective for therapy of active syphilis in rabbits. Dark-field-positive lesions were produced in adult male rabbits by intradermal inoculation of approximately 10(6) Treponema pallidum organisms at each of 11 sites. Beginning 7 days after infection, six animals per group were treated with benzathine penicillin G (200,000 U, intramuscularly, weekly for 2 weeks) or roxithromycin (15 mg/kg of body weight, orally, twice daily for 15 days); six animals were not treated.

IgG and IgM antibody reactivity to antigens of Treponema pallidum after treatment of syphilis.

The persistence or loss of IgG and IgM antibody specificities for individual polypeptides of Treponema pallidum after therapy for syphilis was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and by the Western blot technique. Both IgG and IgM antibodies to as many as 12 treponemal antigens, including a major 47-kdalton molecule, were evident in plasma from patients with untreated primary syphilis. IgM reactivity declined rapidly and uniformly after therapy, whereas IgG persisted despite some diminution in intensity of staining.

Ceftriaxone therapy for asymptomatic neurosyphilis. Case report and Western blot analysis of serum and cerebrospinal fluid IgG response to therapy.

A 27-year-old man with documented hypersensitivity to penicillin was treated intramuscularly for asymptomatic neurosyphilis with ceftriaxone (1 g daily for 14 days). After treatment the serum titer in the VDRL (Venereal Disease Research Laboratory) test declined from 32 to four dilutions. Lumbar punctures at months 3, 6, 9, and 28 after treatment revealed normalization of the cell count in cerebrospinal fluid and a decline in the VDRL titer in cerebrospinal fluid from four to one dilution(s).

Characterization of the humoral immune response of the rabbit to antigens of Treponema pallidum after experimental infection and therapy.

The development of IgM and IgG antibody responses to antigenic molecules of Treponema pallidum was examined in intratesticularly and intradermally infected rabbits by use of immunofluorescence (IF) and Western blotting techniques. IgM antibody was first detectable on day 6 following intratesticular infection and reached maximal IF titers during the period of clinical orchitis (days 10-17). IgG reached peak IF titers in the resolution period following clearance of most organisms from the testes (after day 17).

Chronicity of infection with Treponema paraluis-cuniculi in New Zealand white rabbits.

Popliteal lymph nodes from eight New Zealand white rabbits with clinical or serological evidence of naturally acquired infection with Treponema paraluis-cuniculi were transferred to rabbits that had not been exposed to this infection. Lymph nodes from two rabbits successfully transmitted infection. The nodes from one of these rabbits transmitted infection during both the acute and chronic stages of infection.

Antigens of Treponema pallidum recognized by IgG and IgM antibodies during syphilis in humans.

IgG and IgM antibody specificities for antigens of Treponema pallidum Nichols strain were determined by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the western blot technique in sera from patients with untreated syphilis, normal persons, persons with biologic false-positive tests for syphilis, and sexual contacts of persons with infectious syphilis. IgG reactivities of sera from individuals with primary syphilis varied considerably but consistently exhibited strong reactivity to a 48-kilodalton band. Sera from patients with secondary and early latent syphilis uniformly demonstrated reactivity to 22 separate polypeptide antigens; decreased reactivity was seen in late latent syphilis.

Characterization of monoclonal antibodies to Treponema pallidum.

Thirteen hybrid cell lines which produce mouse monoclonal antibodies to Treponema pallidum, the causative agent of syphilis, have been established. All of the monoclonal antibodies react with T. pallidum, Nichols strain, in ELISA and in immunofluorescence assays, but do not react with normal rabbit testicular tissue in the ELISA.

Experimental neonatal syphilis. II. Immunological responses of neonatal rabbits to intradermal inoculation with Treponema pallidum (Nichols strain).

The immunological competence of neonatal rabbits inoculated intradermally with Treponema pallidum was examined. Both cellular responses and the production of humoral antibody to specific T. pallidum antigens and to nonspecific antigens or mitogens were investigated.

Antigenic cross-reactivity between Treponema pallidum and other pathogenic members of the family Spirochaetaceae.

The antigenic cross-reactivity between Treponema pallidum and several pathogenic members of the family Spirochaetaceae was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting techniques. Blots of T. pallidum antigens were incubated with antiserum from rabbits infected or immunized with T.

Clinical course and treatment of venereal spirochaetosis in New Zealand white rabbits.

Ten sporadic cases of venereal spirochaetosis, caused by Treponema paraluis-cuniculi, were seen in New Zealand white rabbits in two years. An equal number of males and females were affected. Females tended to have milder clinical signs than males.

Efficacy of aztreonam in treatment of experimental syphilis in rabbits.

The efficacy of aztreonam (SQ 26,776) in the therapy of active syphilis infection was evaluated in the rabbit model. Aztreonam was effective in treating active syphilis at a dose of 25 mg/kg given intramuscularly twice daily for 10 days; doses of 2.5 and 0.

Treponema paraluis-cuniculi infection in a commercial rabbitry: epidemiology and serodiagnosis.

The epidemiology of Treponema paraluis-cuniculi infection in a commercial rabbit breeding facility was described using several serologic tests. The Venereal Disease Research Laboratory, rapid plasma reagin, microhemagglutination and fluorescent treponemal antibody-absorption tests were used to detect antibodies to T paraluis-cuniculi. Young adult New Zealand white rabbits, tested prior to entry into the breeding program, were nearly always free of T paraluis-cuniculi infection.