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Syphilis in adults.

Syphilis is a sexually transmitted disease with protean manifestations resulting from infection by Treponema pallidum. It is systemic early from the outset, the primary pathology being vasculitis. Acquired syphilis can be divided into primary, secondary, latent, and tertiary stages. The infection can also be transmitted vertically resulting in congenital syphilis, and occasionally by blood transfusion and non-sexual contact. Diagnosis is mainly by dark field microscopy in early syphilis and by serological tests. The management in the tropics depends on the diagnostic facilities available: in resource poor countries, primary syphilis is managed syndromically as for anogenital ulcer. The introduction of rapid "desktop" serological tests may simplify and promote widespread screening for syphilis. The mainstay of treatment is with long acting penicillin. Syphilis promotes the transmission of HIV and both infections can simulate and interact with each other. Treponemes may persist despite effective treatment and may have a role in reactivation in immunosuppressed patients. Partner notification, health education, and screening in high risk populations and pregnant women to prevent congenital syphilis are essential aspects in controlling the infection.

Adult↗

Lack of endotoxin in Borrelia hispanica and Treponema pallidum.

Borrelia hispanica from infected guinea pigs and Treponema pallidum from testicular syphilomas of rabbits were assayed for the presence of endotoxin with the Limulus lysate test. A suspension of Borrelia, containing 1.3 X 10(8) spirochetes/ml, was nonreactive both when it was tested as intact organisms, and when tested after disruption of the spirochetes by sonication. Eight different suspensions of treponemes, ranging from 0.6 X 10(9) to 3 X 10(9) treponemes/ml, were negative at a 1:10 dilution and were no more active than control suspensions of normal rabbit testes. Therefore, it was concluded that T. pallidum, as well as the Borrelia, possessed no endotoxin.

Animals↗

Macrophage-mediated suppression of con A-induced IL-2 production in spleen cells from syphilitic rabbits.

Blast transformation studies have indicated a diminished T cell response in spleen cell preparations from rabbits infected with Treponema pallidum. IL-2 synthesis by T lymphocytes is required for proliferation of these cells. Thus, Con A-induced IL-2 generation was measured in syphilitic animals infected for 9 to 14 days. IL-2 production in the infected rabbits was only one-half that observed for uninfected rabbits. This marked decrease in IL-2 was not caused by decreased IL-1 secretion by adherent cells from infected animals because similar levels were found in both infected and uninfected splenic cultures. This decrease was also not caused by an increase in infected spleen cell adsorption of IL-2; similar numbers of receptors for this IL were present in Con A-stimulated infected and uninfected splenic preparations. The inhibited IL-2 production in infected spleen cells was reversed upon removal of the adherent cells and also elevated upon addition of indomethacin to the cultures. PGE levels were also elevated in splenic cultures from infected animals. Finally, IL-2 synthesis, when evaluated at various days postinfection, showed that at 4 days, splenic cells generated twice as much IL-2 as uninfected cells. At 9 to 14 days, IL-2 levels were dramatically decreased (50% lower than that observed in uninfected cultures), and suppression of IL-2 by adherent cells was observed as late as 35 days post-infection. We propose that premature down regulation (suppression) of IL-2 secretion is mediated by adherent cells via a cyclo-oxygenase product, most likely PGE. These results may explain why most, but not all, treponemes are cleared during infection, and why the secondary manifestations of the disease occur.

Animals↗

Transmission of parasitic and bacterial infections through blood transfusion within the U.S.

The American public has become aware that viral infections can be transmitted by blood transfusions; however, less attention has been paid to nonviral agents that are similarly transmitted. Although donors are tested routinely for serologic evidence of Treponema pallidum infection (syphilis), there are no other bacterial infections for which donors are routinely tested, and no testing is done routinely to detect parasitic infections. Although current preventive strategies appear effective in preventing the transmission of nonviral agents by transfusion, changing population demographics, increased travel and immigration, and increased occurrence of certain asymptomatic bacterial infections in blood donors may require new policies to maintain the safety of the U.S. blood supply. This review focuses on the parasitic and bacterial infections that might pose a risk to transfusion recipients in the U.S.

Babesiosis↗

DNA probes for the identification of Haemophilus ducreyi.

Haemophilus ducreyi ATCC 33922, a virulent, well-characterized strain, was used to construct a genomic library in a bacteriophage expression vector. Three DNA fragments were selected for use as probes on the basis of their ability to encode H. ducreyi-specific proteins, as demonstrated by reactivity with rabbit polyclonal antiserum. With DNA-DNA hybridization, the three probes, labeled with 32P, reacted strongly with 16 strains of H. ducreyi obtained from a variety of sources. Thirty-seven other bacterial isolates, representing 33 different species and including organisms likely to be encountered in the urogenital tract, were also tested with the three probes. Twenty-eight of these isolates, including the genital pathogen Neisseria gonorrhoeae, showed no hybridization with the probes. In addition, herpes simplex virus-infected tissue culture cells and Treponema pallidum-infected rabbit testicular fluid were also completely nonreactive. Nine isolates, six belonging to other Haemophilus species and three belonging to Pasteurella species, reacted weakly with the probes when approximately 3.0 x 10(7) to 6.0 x 10(7) CFU was tested. When 10(5) to 10(6) CFU of these organisms was tested, the weak reactions could no longer be seen. Yet this number of H. ducreyi still reacted strongly. In fact, the three probes consistently detected 10(4) CFU of H. ducreyi in pure and mixed cultures and even produced a weak signal when only 10(3) CFU was present. It is clear from our results that use of these probes will greatly facilitate the laboratory diagnosis of this genital pathogen.

Animals↗

Cell-mediated immunity during syphilis.

Evidence is presented which reinforces the complexity of the host-parasite interaction during the course of syphilis. Infection with Treponema pallidum evokes a complicated antibody response and an assortment of cell-mediated immune reactions in the host. It appears that humoral immunity plays a minor role towards the complete elimination of syphilitic infection while the cellular limb of the immune response may be an important host defence mechanism. Information now available indicates that a state of anergy, or immunosuppression, exists in the early stages of human and experimental rabbit syphilis based upon negative skin reactions to T. pallidum antigen(s), the abnormal histological appearance of lymphoid organs, and impaired in vitro lymphocyte reactivity. It is also evident that in the later stages of the disease cellular immunity becomes activated as delayed type skin reactions can normally be elicited in tertiary syphilitics and lymphocyte behaviour in cell culture appears normal. Several mechanisms have been invoked to explain the delay in an effective immune response against syphilitic infection and the duration of the disease: (1) a capsule-like substance on the outer surface of virulant T. pallidum may act as a barrier against treponemicidal antibody; (2) this material and other biological properties of virulent treponemes could enable spirochaetes to escape being engulfed by macrophages and other phagocytic cells; (3) antigenic competition among different treponemal antigens causing partial tolerance; (4) T. pallidum infection may bring about the elaboration of immunosuppressive substances of host or treponemal origin which inhibit the proper function of lymphocytes, macrophages, and other cell types.

Animals↗

Immune studies in infants with congenital syphilis.

Seventeen neonates with congenital syphilis were studied to determine the immune response of the fetus following intra-uterine infection with Treponema pallidum. The results were compared with those from healthy controls matched for gestational age, birth weight and sex. B cells, IgM, and circulating immune complexes were significantly elevated in the infected newborns. There were no differences in lymphocyte transformation to phytohaemagglutinin (PHA) and in the CD3, CD4, and CD8 lymphocytes between infants with congenital syphilis and controls. Newborns with congenital syphilis have a heightened humoral response but no quantitative abnormality in cell-mediated immunity. Speculation on the role of the circulating immune complexes is presented.

Antigen-Antibody Complex↗

Unusual infections in humans.

Nine cases of unusual infections in humans are presented. In each case, we present the clinical history, histopathologic changes (if indicated), morphologic features of the causative organism, diagnosis, discussion, differential diagnosis, therapy, and current literature. All of the cases are illustrated with pertinent photographs. The nine cases are as follows: (i) acanthocephaliasis, the first acquired human infection by Moniliformis moniliformis in the United States; (ii) dipylidiasis, an uncommon infection caused by the dog tapeworm, Dipylidium caninum; (iii) granulomatous amebic encephalitis, caused by the recently identified leptomyxid group of amebae; (iv) schistosomiasis, a dual infection of the urinary bladder with the rare presentation of both adult worms and eggs of Schistosoma haematobium and Schistosoma mansoni in tissue sections; (v) syphilitic gastritis, an uncommon presentation of Treponema pallidum infection, in a patient with an additional incidental infection by Helicobacter pylori; (vi) microsporidiosis, the only infection caused by a Pleistophora sp. in humans; (vii) sporotrichosis, a rare disseminated infection caused by Sporothrix schenckii with numerous yeast cells in the scrotum; (viii) angiostrongyliasis, the first and only infection caused by Angiostrongylus costaricensis acquired in either Puerto Rico or the United States; and (ix) botryomycosis of the skin and subcutaneous tissue, caused by gram-positive cocci with an unusually large number of granules.

Adult↗

Molecular analysis of Filifactor alocis, Tannerella forsythia, and treponema denticola associated with primary endodontic infections and failed endodontic treatment.

The aim of this study was to investigate the presence of strict anaerobes such as Filifactor alocis, Tannerella forsythia, and Treponema denticola in primary and secondary root-infected canals with periapical lesions by molecular analysis and the association of these species with specific endodontic signs and symptoms. Microbial samples were taken from 100 root canals, 50 with necrotic pulp tissues (NPT, primary infection), and 50 with failed endodontic treatment (FET, secondary infection). DNA was extracted from the samples, which were analyzed for the presence of three endodontic pathogens using species-specific primers and PCR. F. alocis were isolated from 23 canals with NPT and 12 canals with FET; T. forsythia from 12 canals with NPT and three canals with FET; T. denticola from 19 canals with NPT and 12 canals with TEP. Suggested associations were found between primary infection and the presence of F. alocis and T. forsythia (both p < 0.05). In particular, associations were found between: pain and F. alocis; swelling and F. alocis; tenderness to percussion and T. forsythia; mobility and T. forsythia and T. denticola; wet canals and F. alocis, T. forsythia, and T. denticola; purulent exsudate and F. alocis, T. forsythia and T. denticola; abscess and F. alocis, T. forsythia, and T. denticola (all p < 0.05). The findings of this study indicated that F. alocis, T. forsythia, and T. denticola seem to be associated with endodontic signs and symptoms. Additionally, F. alocis and T. forsythia were detected more frequently in teeth with necrotic pulp than in teeth with failing endodontic treatment.

Bacteroides↗

Aberrant secondary antibody responses to sheep erythrocytes in rabbits with experimental syphilis.

Rabbits infected with Treponema pallidum have strikingly depressed in vivo immunoglobulin G responses to sheep erythrocytes. To gain further insight into the nature of this suppression, the immune responses of splenic and peripheral blood lymphocytes from infected rabbits to sheep erythrocytes were studied in vitro. Spleen cells from rabbits that had been sensitized with sheep erythrocytes during active syphilis had greatly decreased immunoglobulin M and G responses after in vitro incubation with sheep erythrocytes, when compared to the results obtained with cells from sensitized uninfected animals. Suppressor cells could be demonstrated in peripheral blood lymphocytes of control rabbits 6 months after sensitization with sheep erythrocytes; these cells could be removed by nylon wool filtration. When primary sensitization with sheep erythrocytes was carried out during active syphilis, these suppressor cells were not detectable in peripheral blood lymphocytes 6 to 9 months later. These findings provide further evidence that induction of immune responses may be abnormal early in treponemal infection and may help to explain the failure of the host to produce antibodies which eradicate the organism during the first 2 to 3 months of infection.

Animals↗

Reinfection primary, secondary, and latent syphilis: the serologic response after treatment.

An infection with Treponema pallidum does not confer solid immunity to reinfection. Consequently, it is not unusual for the physician to see a patient with reinfection syphilis. In this study there were 36 patients who, after having an initial infection with T. pallidum, became reinfected with the primary, secondary, or latent stage of syphilis. The titers of antibody to T. pallidum during reinfection were consistently higher than those during the first infection, and the serologic responses to treatment were always slower.

Adolescent↗

Microbial etiology of periodontal diseases. Where are we? Where are we going?

Many studies indicate a strong association of Actinobacillus actinomycetemcomitans with localized juvenile periodontitis. Species associated with adult periodontitis include Bacteroides forsythus, Porphyromonas gingivalis, Prevotella intermedia, A. actinomycetemcomitans, and Wolinella recta. Capnocytophaga species may be important in pubertal gingivitis. An unnamed spirochete related to Treponema pallidum has been identified in acute necrotizing ulcerative gingivitis lesions. Species isolated from prepubertal periodontitis, peri-implantitis, pericoronitis, and human immunodeficiency virus gingivitis and periodontitis are similar to those isolated from periodontal and gingival infections. Species identification in combination with clinical characteristics facilitates periodontal diagnosis. DNA probes, immunoassays, and benzoyl-arginine naphthylamide reactivity methods can be used to indicate putative pathogens in plaque samples. Microbial identification aids in antibiotic selection and planning a treatment regimen.

Actinomyces↗

Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment.

PURPOSE: To evaluate evidence that concurrent infection with human immunodeficiency virus (HIV) alters both the natural history of syphilis (by increasing the frequency of early neurosyphilis) and the response to penicillin. DATA IDENTIFICATION: Review of major works on syphilis in the English language and files maintained since 1971, supplemented by a systematic search using Index Medicus and MEDLARS. DATA EXTRACTION: The works mentioned above were critically reviewed for information on early neurosyphilis and, where relevant, HIV infection. RESULTS OF DATA ANALYSIS: The central nervous system is regularly involved in early syphilis. Standard recommended doses of benzathine penicillin provide cerebrospinal fluid levels that are probably at the borderline of efficacy, and cure relies on treatment and an adequate host immune response. Early neurosyphilis, appearing within 2 years of onset of infection with Treponema pallidum, was uncommon in the prepenicillin era and usually occurred after inadequate therapy. This complication was exceedingly rare in the first three decades of penicillin use. In contrast, in the past decade, 40 patients with HIV infection have been reported to have asymptomatic neurosyphilis, or syphilitic meningitis, cranial nerve abnormalities (predominantly in cranial nerves II and VIII), or cerebrovascular accidents, singly or together. In 40% of cases, HIV infection was first diagnosed when neurologic symptoms appeared. Of the 38 patients for whom information was available, 18 had the acquired immunodeficiency syndrome (AIDS), 7 had AIDS-related complex, and 13 had antibody to HIV. Sixteen had previously been treated for syphilis, of whom 5 (31%) had received benzathine penicillin within the previous 6 months. Preliminary data also suggest that skin lesions and VDRL (Venereal Disease Research Laboratory) antibody in HIV-infected patients with secondary syphilis respond more slowly to conventional penicillin therapy. CONCLUSION: Intensive therapy and follow-up observation is indicated for early syphilis in HIV-infected subjects. Novel approaches to treatment deserve systematic evaluation.

HIV Infections↗

Transcriptome of Treponema pallidum: gene expression profile during experimental rabbit infection.

RNA transcript levels in the syphilis spirochete Treponema pallidum subsp. pallidum (Nichols) isolated from experimentally infected rabbits were determined by the use of DNA microarray technology. This characterization of the T. pallidum transcriptome during experimental infection provides further insight into the importance of gene expression levels for the survival and pathogenesis of this bacterium.

Animals↗

Brainstem ocular motility defects and AIDS.

Ocular motility manifestations of focal brainstem dysfunction were the initial clinical features in three patients with human immunodeficiency virus (HIV) infection. These included conjugate gaze palsy with ipsilateral facial paresis, bilateral abducens palsy and a gaze paresis, and homolateral internuclear ophthalmoplegia and abducens nerve paresis. Two patients had focal brainstem lesions as evidenced on neuroimaging. The third showed concurrent infection with Treponema pallidum.

Acquired Immunodeficiency Syndrome↗

Early oral presentation of lues maligna in a patient with HIV infection. A case report.

We present a case of a patient infected with the human immunodeficiency virus who developed syphilis manifested by atypical early oral and skin ulcerations. The profound immune defects associated with human immunodeficiency virus may lead to an altered clinical presentation and a more aggressive course in patients infected with Treponema pallidum. The unusual clinical manifestations observed in this case emphasize the importance of considering secondary syphilis in the differential diagnosis of any inflammatory mucosal and skin disorder in patients with the human immunodeficiency virus.

AIDS-Related Opportunistic Infections↗

Detection and functional characterization of early appearing antibodies in rabbits with experimental syphilis.

Following testicular infection of rabbits with Treponema pallidum, different antibodies become detectable initially at the time of healing. Experiments were performed to determine a functional role for these antibodies. Rabbits were sacrificed after 4-8 days. Treponemal numbers steadily increased for 10-12 days. Thereafter, host defenses were sufficiently stimulated to begin clearing the organisms. Antibodies in serum and antibodies localized at the site of infection were quantitated using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) techniques. Anti-treponemal IgG was detected as early as day 4. Quantities of antibody correspondingly increased with time following infection. Treponema pallidum was harvested 7 and 14 days postinfection and tested for surface antibodies. With increasing days postinfection, more antibody was found on the organisms. Two functional properties of these antibodies were shown. Sera from 24 of 45 rabbits infected for 14 days immobilized T. pallidum in the presence of complement and 14-day sera blocked the attachment of T. pallidum to tissue culture cells. We suggest that antibody-mediated, complement-dependent immobilization of T. pallidum and blockage of attachment are at least partially responsible for healing of testicular lesions.

Animals↗

Sensitivity of treponemal tests for detecting prior treated syphilis during human immunodeficiency virus infection.

To evaluate the sensitivity of treponemal tests as a marker of prior syphilis in individuals with human immunodeficiency virus (HIV) infection, the syphilis serology of 109 homosexual men with a documented history of treated syphilis was compared with records of prior results and confirmed on stored serum samples. None of the HIV-seronegative individuals lost reactivity to a treponemal test, whereas 7% of the seropositive asymptomatic individuals and 38% of those with symptomatic HIV infection had loss of reactivity. Symptomatic HIV infection was associated with loss of reactivity, as a T4 lymphocyte count less than 200 X 10(6)/1, a T4-to-T8 ratio less than 0.6, a single prior episode of syphilis, and a low VDRL titer at the time of the last documented episode of syphilis. Although no conclusions can be drawn about the sensitivity of treponemal tests in patients with active syphilis and HIV infection, these data suggest that treponemal tests may not identify those previously infected with Treponema pallidum.

Adult↗