Syphilis is typically acquired by the direct contact of mucous membranes during sexual intercourse. The disease begins with a lesion at the point of entry, usually a genital ulcer. After healing of the ulcer, the organisms spread systemically, and the disease returns weeks later as a generalized maculopapular rash called secondary syphilis. The disease then enters a second eclipse phase called latency. The latent in- to decades later. Tertiary syphilis is characterized by focal lesions whose locale de- termines the injury. Isolated foci in bone or liver may be unnoticed, but infection of the cardiovascular or nervous systems can be devastating. Progressive dementia or a ruptured aortic aneurysm are two of many fatal outcomes of untreated syphilis.
T. pallidum is anexclusively human pathogenunder naturalconditions.In most cases,infection is acquired from direct sexual contact with an individual who has an active pri-mary or secondary syphilitic lesion. Partner notification studies suggest transmission oc- curs in over 50% of sexual contacts where a lesion is present. Less commonly, the diseasemay be spread by nongenital contact with a lesion (eg, of the lip), sharing of needles byintravenous drug users, or transplacental transmission to the fetus within approximately the first 3 years of the maternal infection. Late disease is not infectious. Modern screen-ing procedures have essentially eliminated blood transfusion as a source of the disease.Since 1990, the number of reported new cases of syphilis in the United States has been declining; levels are now below 40,000 per year. Approximately 20% of cases are primary or secondary syphilis; the remainder are latent or tertiary disease. Worldwide, syphilis remains a major public health problem, with an estimated 12 million new cases annually.
When certain strains of T. pallidum are inoculated into the skin, cornea, or testicle of ani-mals lesions resembling primary syphilis can be produced, but there is no model for the other stages of disease. Because of our inability to grow the organism in culture, our knowledge of disease mechanisms is limited to the following extrapolations based on ob-servations of human disease and experiments in animal models.
The spirochete reaches the subepithelial tissues through inapparent breaks in the skin or possibly by passage between the epithelial cells of mucous membranes, where it multi-plies slowly with little initial tissue reaction. This may be due to the relative paucity of ex-posed antigens on the surface of the organism, but no specific reasons are known. As lesions develop, the basic pathologic finding is an endarteritis. The small arterioles show swelling and proliferation of their endothelial cells. This reduces or obstructs local blood supply, probably accounting for the necrotic ulceration of the primary lesion and subse-quent destruction at other sites. Dense, granulomatous cuffs of lymphocytes, monocytes, and plasma cells surround the vessels. Although the primary lesion heals spontaneously the bacteria disseminate to other organs by way of local lymph nodes and the bloodstream.
For reasons that are not understood, syphilis is then silent until the disseminated sec-ondary stage develops and then silent again with entry into latency. Although evasion of host defenses is clearly taking place, the mechanisms involved are unknown. The appear-ance of new epitopes in outer membrane proteins (OMPs) has been demonstrated during the course of experimental infections, but T. pallidum strains found in secondary lesions have not been demonstrated to differ antigenically from those in primary lesions. The or-ganism has been observed to bind host proteins, immunoglobulins, and complement to its surface without sacrificing viability or motility. T. pallidum may be able to put on a host-like molecular “disguise” and thus avoid immune recognition.
The inflammatory response to immune complexes, spirochetal lipoproteins, and com-plement in arteriolar walls accounts for some of the injury in syphilitic lesions. The granulo-matous nature of the lesions in late syphilis is consistent with injury caused by delayed-type hypersensitivity responses prolonged by persistence of the spirochetes. In all of this, no tox-ins, virulence factors, or other molecules can yet be linked with specific features of syphilis.
Clinical observations suggest an immune response in syphilis which is vigorous but slow and imperfect. Immunity to reinfection does not appear until early latency, and for at least one third of those infected the subsequent host response is successful in clearing most but not all of the treponemes.
The immune mechanisms involved are far from clear but appear to involve both humoral and cell-mediated responses. Resistance to reinfection is correlated with appearance of antitreponemal antibody which is able to immobilize and kill the organism. Exposed treponemal OMPs are the most probable target of these antibodies. Cell-mediated responses appear to be dominant in syphilitic lesions with T lymphocytes (CD4+ and CD8+) and macrophages the primary cell types present. Activated macrophages play a major role in the clearance of T. pallidum from early syphilis lesions. The relapsing course of primary and secondary syphilis may reflect shifts in the balance between developing cellular immunity and suppression of T lymphocytes. Syphilis in immunocompromised patients such as those with acquired immunodeficiency syndrome may present with unusually aggressive or atypical manifestations.