Syphilitic infection impairs immunity by inducing both apoptosis and pyroptosis of CD4+ and CD8+ T lymphocytes.

Syphilis is an important health problem worldwide; however, few studies have probed the impact of syphilitic infection on T cell turnover. The mechanisms behind the frequency of T cell subset changes and the associations between these subsets during syphilitic infection remain unclear. Herein, we used a cell-staining method and flow cytometry to explore changes in T cell subpopulations and potential contribution of apoptosis and pyroptosis that triggered therein. We investigated caspase-1-mediated pyroptosis and caspase-3-mediated apoptosis of CD4+ and CD8+ T cells, the major effector lymphocytes with pivotal roles in the pathogenesis of infectious diseases. We found that the levels of caspase-1 and caspase-3 increased in both the circulation and intracellularly in CD4+ and CD8+ T cells. Caspase-1 showed a continual increase from early latent stage infection through to phase 2 disease, whereas caspase-3 increased through to phase 1 disease but declined during phase 2. In addition, serum levels and intracellular expression of caspase-1 and caspase-3 were positively correlated. Overall, this study increases our understanding of how syphilitic infection influences CD4+ and CD8+ T-cell turnover, which may help with designing novel and effective strategies to control syphilis infection and prevent its transmission.

Reported Cases of Neurosyphilis Among Early Syphilis Cases-United States, 2009 to 2015.

The surveillance of neurosyphilis, an uncommon but severe consequence of syphilis, is complex; surveillance classification of neurosyphilis requires a lumbar puncture and cerebrospinal fluid analysis. We examined the prevalence of reported neurosyphilis among primary, secondary, and early latent syphilis cases reported in the United States from 2009 to 2015. Overall, the prevalence of reported neurosyphilis from 2009 to 2015 was low (0.84%); however, this is likely an underestimate of the true burden in the United States.

Prevalence Estimates of Complicated Syphilis.

We reviewed 68 cases of possible neurosyphilis among 573 syphilis cases in King County, WA, from 3rd January 2012 to 30th September 2013; 7.9% (95% confidence interval, 5.8%-10.5%) had vision or hearing changes, and 3.5% (95% confidence interval, 2.2%-5.4%) had both symptoms and objective confirmation of complicated syphilis with either abnormal cerebrospinal fluid or an abnormal ophthalmologic examination.

[Clinical features and serologic analysis of latent syphilis].

OBJECTIVE: To summarize the clinical features and analyze the serologic test results of latent syphilis. METHODS: The clinical data of 601 patients with latent syphilis who were treated in the sexually transmitted disease centre of Peking Union Medical College Hospital between January 2001 and November 2007 were retrospectively analyzed. RESULTS: Of the 601 cases of latent syphilis, there were 174 cases of early latent syphilis(EL), 170 cases of late latent syphilis(LL), and 257 cases of unknown latent syphilis. Male to female ratio was 0.74:1256 males and 345 females, respectively). Patients aged 20-39 years accounted for the largest proportion. Non-marital sexual intercourse was the main route of infection. Forty-six patients (7.65%) were co-infected with other sexually transmitted diseases. A total of 251 cases of latent syphilis (41.76%) were confirmed when the patients were receiving tests for other sexually transmitted diseases or suspected sexually transmitted diseases. Of the 601 patients with EL, LL and unknown latency, the proportion of serum rapid plasma reagin(RPR) titers higher than or equal to 8 were 72.99% (127/174), 52.94% (90/170), and 60.31%(155/257), respectively. Compared with the early syphilis, serological negative conversion rate was significantly lower after treatment for l2 months in the early latent syphilis patients (P=0.044). CONCLUSION: Education and awareness raising on syphilis should be strengthened to lower the prevalence of latent syphilis.

Anticuerpos IgM e IgA anti Treponema pallidum en pacientes en distintos estadíos de sífilis / Anti treponema pallidum IgM and IgA antibodies in patients in different stages

Se efectuó la detección de anticuerpos treponémicos IgM e IgA en pacientes con distintos estadíos de sífilis por un método de captura de anticuerpos en fase sólida y posterior revelado por hemaglutinación (SPHA-M y SPHA-A). Se evaluaron con SPHA-M 167 muestras séricas, 63 correspondían a pacientes con sífilis sin tratamiento (12 primarias, 18 secundarias, 23 latentes y 10 reinfecciones) y 104 pacientes que habían recibido tratamiento. En 62/167 de las muestras se evaluaron también los anticuerpos IgA, 30 pertenecían a pacientes sin tratamiento (2 primarias, 12 secundarias, 10 latentes y 6 reinfecciones). Las 32 muestras restantes correspondían a pacientes tratados. En la población de los 63 pacientes no tratados se detectó IgM específica en el 25 por ciento de casos de sífilis primaria, en el 100 por ciento de las secundarias y reinfecciones y en el 78,3 por ciento de latencias, pero sólo se encontró IgM específica en el 4,8 por ciento de sífilis tratada. En 30 pacientes no tratados la IgA específica se detectó en 1 de 2 casos de sífilis primaria, en el 100 por ciento de las secundarias y reinfecciones y en el 60 por ciento de sífilis latentes. En sífilis tratada sólo en el 6,2 por ciento se encontró IgA específica. Los anticuerpos IgA coexistieron en todos los casos estudiados con los IgM. El seguimiento post tratamiento de 7 pacientes mediante SPHA-M y VDRL indicó que entre 1 y 5 meses el SPHA-M se negativizaba, mientras la reactividad de la VDRL persistía aún al año de completado el tratamiento. La presencia de IgM y/o IgA específica evaluada según esta metodología permite caracterizar a la sífilis activa en todos los estadíos, excepto en la sífilis primaria. El seguimiento en base a los resultados de SPHA-M reproduce más fielmente la respuesta terapéutica que el seguimiento convencional con VDRL

Anticuerpos IgM e IgA anti Treponema pallidum en pacientes en distintos estadíos de sífilis / Anti treponema pallidum IgM and IgA antibodies in patients in different stages

Se efectuó la detección de anticuerpos treponémicos IgM e IgA en pacientes con distintos estadíos de sífilis por un método de captura de anticuerpos en fase sólida y posterior revelado por hemaglutinación (SPHA-M y SPHA-A). Se evaluaron con SPHA-M 167 muestras séricas, 63 correspondían a pacientes con sífilis sin tratamiento (12 primarias, 18 secundarias, 23 latentes y 10 reinfecciones) y 104 pacientes que habían recibido tratamiento. En 62/167 de las muestras se evaluaron también los anticuerpos IgA, 30 pertenecían a pacientes sin tratamiento (2 primarias, 12 secundarias, 10 latentes y 6 reinfecciones). Las 32 muestras restantes correspondían a pacientes tratados. En la población de los 63 pacientes no tratados se detectó IgM específica en el 25 por ciento de casos de sífilis primaria, en el 100 por ciento de las secundarias y reinfecciones y en el 78,3 por ciento de latencias, pero sólo se encontró IgM específica en el 4,8 por ciento de sífilis tratada. En 30 pacientes no tratados la IgA específica se detectó en 1 de 2 casos de sífilis primaria, en el 100 por ciento de las secundarias y reinfecciones y en el 60 por ciento de sífilis latentes. En sífilis tratada sólo en el 6,2 por ciento se encontró IgA específica. Los anticuerpos IgA coexistieron en todos los casos estudiados con los IgM. El seguimiento post tratamiento de 7 pacientes mediante SPHA-M y VDRL indicó que entre 1 y 5 meses el SPHA-M se negativizaba, mientras la reactividad de la VDRL persistía aún al año de completado el tratamiento. La presencia de IgM y/o IgA específica evaluada según esta metodología permite caracterizar a la sífilis activa en todos los estadíos, excepto en la sífilis primaria. El seguimiento en base a los resultados de SPHA-M reproduce más fielmente la respuesta terapéutica que el seguimiento convencional con VDRL (AU)

Lumbar puncture for evaluation of latent syphilis in hospitalized patients. High prevalence of cerebrospinal fluid abnormalities unrelated to syphilis.

OBJECTIVE: To determine the prevalence of abnormal neurologic findings and cerebrospinal fluid abnormalities in hospitalized patients with serologic evidence of latent syphilis. DESIGN: Cross-sectional survey. METHODS: Consecutively admitted hospital inpatients from an inner-city population were screened for serologic evidence of syphilis with reactive plasma reagin and confirmatory fluorescent treponemal antibody absorption assays. In those with reactive tests, such clinical findings as a history of treatment for syphilis, neurologic abnormalities, presence of human immunodeficiency virus infection, and rapid plasma reagin titer were correlated with cerebrospinal fluid white blood cell count, protein level, and VDRL result. RESULTS: Of 490 consecutive patients, 52 (11%) had serologic evidence of syphilis. Forty-three (83%) of these underwent lumbar puncture. Of the 43, 31 (72%) were seronegative for human immunodeficiency virus and 12 (28%) were seropositive. No patient had a reactive cerebrospinal fluid VDRL test. Cerebrospinal fluid abnormalities were seen in 32% of human immunodeficiency virus-seronegative patients and in 67% of human immunodeficiency virus-seropositive patients. Cerebrospinal fluid abnormalities were not predicted by history of treatment for syphilis, abnormal neurologic findings, or an elevated rapid plasma reagin titer. Cerebrospinal fluid IgG indexes in patients with elevated cerebrospinal fluid protein levels suggested that the protein abnormalities were not caused by local antibody production. Nonreactive cerebrospinal fluid fluorescent treponemal antibody absorption tests suggest that the cerebrospinal fluid abnormalities were not the result of neurosyphilis. CONCLUSIONS: There was a high prevalence of cerebrospinal fluid abnormalities in hospitalized patients with latent syphilis detected by routine screening. Because of the nonspecificity of the cerebrospinal fluid findings, routine lumbar puncture for such patients appears to contribute little to the treatment of latent syphilis.

[Specific IgM tests in syphilis diagnosis]. / Spezifische IgM-Teste in der Syphilis-Diagnose.

A total of 359 sera of untreated patients with syphilis were examined by three methods for the detection of Treponema pallidum specific IgM antibodies, the 19S-IgM-FTA-ABS test, the IgM solid phase haemadsorption assay (IgM-SPHA), and the IgM Captia assay. The results were compared and evaluated. In primary syphilis, the 19S-IgM-FTA-ABS and IgM-captia yielded reactive results in all patients, whereas only 40% were positive in the IgM-SPHA; the corresponding values for early latent syphilis wee 96.0%, 89.8% and 73.1%, respectively. In secondary syphilis, the reactivity of one serum out of 27 was missed by IgM captia and that of another, by the IgM-SPHA. Mean values (ELISA units = extinction/cut-off) of IgM-captia were higher in primary (2.25) than in secondary syphilis (1.70). In neurosyphilis, only the IgM-SPHA test detected reactivity in all sera, sensitivity for 19S-IgM FTA-ABS and IgM-Captia was 50.0% and 23.1%, respectively. Specificity of the IgM-Captia test results, determined in 386 sera, was 91.2%. The results of specific IgM tests are essential in the diagnosis of congenital syphilis as well as in the recognition of reinfection; they indicate the need for treatment and are useful in the assessment of the effectiveness of therapy.

Presence of IgE class antibodies with cardiolipinic and treponemal specificity in syphilis. Quantitative evaluation by IgE prist radio-immuno-assay.

60 serum samples (reactive in VDRL, ELISA-Reiter, FTA-Abs tests) from 25-45 years old male patients with untreated latent syphilis (EL) (30 cases) and persistent positive treated syphilis (ET+) (30 cases) were tested for IgE by IgE-PRIST. On 30 sera from 25-45 years old male healthy persons, normal mean value for serum IgE was established: 159.63 +/- 124.09 U/ml. Cardiolipin and group treponemal IgE fractions were indirectly calculated by the difference between the specific activity induced by sera as such and that induced by sera absorbed with cardiolipin and group treponemal sorbents. In EL, total IgE level was 197 +/- 107 U/ml; cardiolipin IgE -24.9 +/- 8.3 U/ml and group treponemal IgE 35.8 +/- 6.6 U/ml. In ET, total IgE value was 152.6 +/- 122.5 U/ml, cardiolipin IgE -11 +/- 10.5 and group treponemal IgE -26.6 +/- 14.2 U/ml. Summing up the two specificities, the total specific IgE represent about 1/3 from total IgE in EL and 1/5 in ET+. Taking into account the short half-life (2-3 days) of IgE presence of a significant proportion of specific IgE in those two stages proves, by their continuous synthesis paralleling antigenic stimulation, the presence in various tissular zones of viable treponemas as sources of antigens.

[The dynamics of Treponema-specific blood immunoglobulins in early forms of syphilis]. / Dinamika treponemospetsificheskoi immunoglobulinemii pri rannikh formakh sifilisa.

The study has involved 73 patients with syphilis, 31 female and 42 male ones, aged 18-42. Four of these suffered from primary seronegative, 14 from primary seropositive, 21 from secondary fresh, 22 from secondary recurrent, and 12 from early latent seropositive syphilis. Peripheral blood sera were under study. Treponema-specific antibodies of the IgM and IgG classes were titered by enzyme immunoassay. The detected changes in Treponema-specific immunoglobulinemia are in good correlation with clinical staged pattern of syphilis and antiinfectious immunity status.

[The immune status of homosexuals ill with different forms of syphilis]. / Immunnyi status gomoseksualistov, bol'nykh razlichnymi formami sifilisa.

Status of the cell-mediated, humoral immunity, and nonspecific defense factors were examined before and after specific therapy in 40 homosexuals suffering from secondary relapsing and latent early syphilis. The findings evidence that changes in the cell-mediated immunity of homosexual syphilitics essentially differ from those in heterosexuals with syphilis: decreased count of T-helpers and elevated one of T-suppressors evidence impaired ratio of T-lymphocyte subpopulations and immunoregulatory cell imbalance. A significantly increased level of C4 complement component was observed, evidencing a deficiency of the complement system. These data call for the development of a scheme of immunocorrective therapy for homosexuals suffering from syphilis.

[Clinico-immunologic characteristics of patients with seroresistant syphilis]. / KLiniko-immunologicheskaia kharakteristika bol'nykh serorezistentnym sifilisom.

Clinical and immunological analysis of patients with seroresistant syphilis has revealed a number of immunological shifts. The authors emphasize that only immunologically based therapy may be prescribed to patients with seroresistant syphilis.

[Immunologic aspects of the pathogenesis of latent and seroresistant forms of syphilis]. / Immunologicheskie aspekty patogeneza skrytykh i serorezistentnykh form sifilisa.

Studies of the cellular and humoral immunity in patients with latent and seroresistant syphilis have revealed decreased content of T-lymphocytes and elevated levels of B- and antigen-reactive lymphocytes. Reduced T-cell level is due to a decrease of the T-suppressor subpopulation. Unlike latent syphilis, seroresistant form is associated with a complete disappearance of the theophylline-sensitive subpopulation, whereas T-lymphocytes are represented mainly by the theophylline-resistant (helper) subpopulation. Effective therapy of patients with seroresistant syphilis has normalized the counts of T- and B-antigen-reactive lymphocytes, and theophylline-sensitive cells appear in the blood. These data give grounds to prescribe immunostimulating therapy to patients with seroresistant syphilis.

[Clinico-laboratory parallels in changes in the cerebrospinal fluid and the immune status of patients with early stages of syphilis]. / Kliniko-laboratornye paralleli izmenenii spinnomozgovoi zhidkosti i sostoianiia immunnogo statusa u bol'nykh rannimi stadiiami sifilisa.

A total of 135 patients with early syphilis were examined, 24 of these with primary seropositive, 31 with secondary new, 70 with secondary relapsing, and 10 with latent early condition. Abnormal shifts were revealed in the cerebrospinal fluid of 51 (37%) patients, in 28 of these Stages I-II shifts, Stages II-III shifts in 10, and Stages III-IV shifts in 13 patients. Clinically the patients with abnormal liquor developed multiple chancres, erosive papules, leukoderma, alopecia, neutrophilia; these patients had suffered from various diseases in the past. Immunologic examinations have detected manifest noncoordination of the immune system: increased counts of the T-lymphocytes and plasmacytes, reduced counts of B-lymphocytes, depressed primary immune response, disordered immunoglobulin ratio.