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Pathogenesis of maternal-fetal syphilis revisited.

Although congenital syphilis has been recognized for several centuries and an efficient treatment with penicillin became available more than a half-century ago, the disease is still with us. Inability to culture in vitro the causative agent, Treponema pallidum, and the lack of an adequate animal model have prevented exploration of the various immunopathological events affecting the natural course of congenital infection. The purpose of this review is to analyze the disease in the context of recent knowledge acquired from human and experimental animals, particularly from the guinea pig model of congenital and neonatal syphilis, and to describe how the infection interacts with the maternal-fetal unit and how it is further modulated by the conceptus' ontogenic development. We also attempt to elucidate several old immunologic concepts and misconceptions that have remained unchallenged for too long.

Animals↗

Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features.

OBJECTIVE: To define clinical and laboratory features that identify patients with neurosyphilis. METHODS: Subjects (n=326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/ microL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result. RESULTS: Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer > or =1 : 32 increased the odds of neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4+ T cell count < or =350 cells/ microL conferred 3.10-fold increased odds of neurosyphilis in HIV-infected subjects. Similar results were obtained when neurosyphilis was more stringently defined as a reactive CSF VDRL test result. CONCLUSION: Serum RPR titer helps predict the likelihood of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis.

Adolescent↗

Sexually transmitted diseases in sexually abused children.

To determine the prevalence and pattern of sexually transmitted diseases among sexually abused children, we evaluated 532 victims under 14 years of age for the presence of Neisseria gonorrhoeae and Treponema pallidum. Twenty-five girls with vaginal discharge and six children with perineal skin lesions underwent more detailed microbiologic examination. Thirty-four infections were identified in 33 children. Gonorrhea was present in 25 (4.7%) of the 532 children, and other sexually transmitted diseases were identified in nine children. Rates of gonococcal infection were higher for children with multiple episodes of abuse (8.1%), delayed reporting (7.4%), and for children evaluated for "suspicion of abuse" without a specific history (28%). Eight gonococcal infections (32%) were discovered at sites not involved in the abuse, according to the child's history. Eleven (44%) infected children were asymptomatic. Routine cultures of oropharyngeal and anogenital sites detected clinically unsuspected cases of oral, vaginal, and rectal gonorrhea. These data suggest that routine cultures are indicated for sexually abused children.

Adolescent↗

Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment.

Periodontal disease is perhaps the most common chronic infection in adults. Evidence has been accumulating for the past 30 years which indicates that almost all forms of periodontal disease are chronic but specific bacterial infections due to the overgrowth in the dental plaque of a finite number of mostly anaerobic species such as Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola. The success of traditional debridement procedures and/or antimicrobial agents in improving periodontal health can be associated with the reduction in levels of these anaerobes in the dental plaque. These findings suggest that patients and clinicians have a choice in the treatment of this overgrowth, either a debridement and surgery approach or a debridement and antimicrobial treatment approach. However, the antimicrobial approach, while supported by a wealth of scientific evidence, goes contrary to centuries of dental teaching that states that periodontal disease results from a "dirty mouth." If periodontal disease is demonstrated to be a risk factor for cardiovascular disease and stroke, it will be a modifiable risk factor since periodontal disease can be prevented and treated. Since the antimicrobial approach may be as effective as a surgical approach in the restoration and maintenance of a periodontally healthy dentition, this would give a cardiac or stroke patient and his or her physician a choice in the implementation of treatment seeking to improve the patient's periodontal condition so as to reduce and/or delay future cardiovascular events.

Anaerobiosis↗

Syphilitic meningitis in HIV-patients with meningeal syndrome: report of two cases and review.

Few patients with symptomatic neurosyphilis present with signs and symptoms of acute meningitis. Here we report two cases of syphilitic meningitis diagnosed in HIV patients with meningeal syndrome. The first case, a 30-year-old black bisexual male, had concurrent meningeal and ocular syphilis with persistent unusually low CSF glucose levels. He responded well to 21 days of intravenous penicillin therapy. The second case was a 55-year-old female with epilepsy, depression, behavioral disorder and confusion. The diagnosis of HIV infection was made after onset of the syphilitic meningitis. She was treated with 21 days i.v. penicillin with improvement in her clinical condition. The clinical aspects of combined neurosyphilis and HIV infection, plus special features of diagnosis and treatment are discussed.

AIDS-Related Opportunistic Infections↗

Cutaneous manifestations of syphilis : recognition and management.

After a marked decline in the number of syphilis cases in the context of AIDS prevention campaigns, a significant increase has been observed in states of the former Soviet Union since 1994. In recent years, outbreaks have also been reported in the US, Canada, and several European countries. The current epidemic in the US and in different parts of Europe has largely involved men who have sex with men, many of whom are infected with HIV. Since a misdiagnosis of syphilis can have serious consequences for the patient and also for pregnancies and newborns, clinicians should be aware of the many manifestations of syphilis and difficulties in the diagnosis and management of the disease. Younger clinicians in particular are no longer familiar with the diverse clinical symptoms and the complex diagnostics of syphilis. Patients co-infected with HIV may present with atypical clinical manifestations and laboratory test results. Furthermore, through its association with an increased risk of HIV infection, syphilis has acquired a new potential for morbidity and mortality, and the diagnosis of syphilis should be routinely considered in patients with uveitis, sudden deafness, aortic thoracic aneurysm, or pregnancy. Only a minority of syphilis infections are detected in the primary stage. This may be because of atypical locations and, occasionally, atypical morphology of the lesions; however, it may also be because of the difficulty of detecting the pathogen. In the secondary stage, which is clinically extremely diverse, the diagnosis is confirmed serologically. There is a need for increased awareness of the symptoms and signs of acute infections, together with a willingness to consider the diagnosis of syphilis in patients with vague symptoms. An increasing number of diagnostic tests (both specific and nonspecific) are now available. However, in the absence of clinical symptoms or in cases with a low titer or inconsistent test results, diagnosis of syphilis can be difficult or even impossible. Treatment and follow-up should follow current guidelines designed for the involved area. In this article, the cutaneous manifestations of syphilis and their diagnostic and therapeutic management are described in detail.

Anti-Bacterial Agents↗

Bilateral treponema periostitis.

Symmetrical exuberant periostitis is a rare disease caused by variety of infectious and non-infectious causes. Treponematosis is one of the rare causes of this condition. We report a patient who presented with left arm swelling, secondary to onion peel periostitis of the humerus, which was caused by Treponema species.

Child↗

[The solid-phase hemadsorption (SPHA) test in syphilis reinfection].

In patients with re- and multiple syphilitic infections the titres of VDRL-, FTA- and SPHA-tests were compared. Among reinfections in which the VDRL gave no or initially no hint for a new infection, the SPHA is significantly reactive. The increase of IgG in the FTA-test confirmed the specificity of a new infection.

Antibodies, Bacterial↗

Prevalence of viral and bacterial sexually transmitted pathogens in Jamaican pregnant women.

In this study we investigated the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, human immunodeficiency virus type I (HIV-I), human T cell lymphotropic virus type 1 (HTLV-1) and hepatitis B virus (HBV) infections in 200 pregnant women attending antenatal clinics at the University Hospital of the West Indies. 19% of the women had at least one pathogen: C. trachomatis was found in 16%, HTLV-1 in 2%, HIV-1, HBV and N. gonorrhoeae each in 0.5% C. trachomatis infection was more prevalent in women less than 20 years of age (31%) than in those 20 years and older (16%; OR = 0.43; chi 2 = 5.66; p < 0.05). The study demonstrates the need for identification of sexually transmitted pathogens in antenatal women for syndromic management of genital infections as part of the strategy for prevention and control of HIV/AIDS (acquired immunodeficiency syndrome) in Jamaica.

Adolescent↗

Treponema pallidum in leukoderma syphiliticum demonstrated by electron microscopy.

Punch biopsies from syphilitic leukoderma lesions and from unaffected skin in 3 patients with secondary syphilis were studies in the transmission electron microscope. In one of the patients the pigment disorder was not preceded by any visible syphilids, and in the biopsy from the leukodermal skin in this patient Treponemata pallidium were demonstrated around vessels and inside nerve fibres in which the myelin sheaths of the axons showed evidence of degeneration. In the other 2 patients the depigmented areas appeared while macular and papular syphilitic lesions were healing. In the biopsies from the leukodermal lesions of these 2 patients and from unaffected skin of all 3 patients, no treponemes were demonstrated. The study indicates that syphilitic leukoderma is not invariably a post-inflammatory phenomenon, but the pigmented skin lesions may themselves represent stigmata of an active syphilitic infection.

Adult↗

Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis.

The tprK gene in the syphilis spirochete, Treponema pallidum subsp. pallidum, undergoes antigenic variation in seven variable (V) regions. tprK is highly variable within T. pallidum strains, and a method has been developed to derive clones of T. pallidum that express a single, unique tprK sequence. Rabbits were infected with three different T. pallidum clones or the parent strain from which the clones were derived, and their sera were examined by immunoassay for antibody reactivity against synthetic peptides representing the TprK V regions from each clone. The parent strain expresses many different V region sequences, and infection with this strain induced antibody responses against a wide variety of V regions. In rabbits infected with the Chicago C clone, antibodies developed against all of the V regions except V1, while antibodies developed against only V5, V6, and V7 in Chicago A-infected rabbits. During Chicago B infection, antibodies developed against all of the V regions except V1 and V3. Antibodies were highly specific for the V regions of the infecting clone, and cross-reactivity was rare. The demonstration that the V regions elicit a variant-specific antibody response supports the hypothesis that TprK variants may help organisms to avoid the developing immune response in infected individuals, contributing to the ability of T. pallidum to establish chronic infection.

Amino Acid Sequence↗

Identification of Treponema pallidum subspecies pallidum in a 200-year-old skeletal specimen.

Treponema pallidum subsp. pallidum, the causative agent of venereal syphilis, was detected in a 200-year-old skeletal specimen from Easter Island. An initial diagnosis of treponemal infection was confirmed by extensive purification of immunoglobulin that reacted strongly with T. pallidum antigen. Extracted DNA exhibited a single-base polymorphism that distinguished T.p. subsp. pallidum from 4 other human and nonhuman treponemes. Extensive precautions against contamination of the subject matter with modern treponemal DNA were employed, including analysis of archaeological and modern specimens in 2 geographically separate laboratories. Molecular determination of historical disease states by using skeletal material can significantly enhance our understanding of the pathology and spread of infectious diseases.

Antigens, Bacterial↗