Syphilis Dr. Mohammad Shakeeb, MD Specialist in clinical pathology/Microbiology and immunology

TREPONEMA PALLIDUM AND SYPHILIS Morphology and identification T pallidum are slender spirals measuring about 0.2 μm in width and 5–15 μm in length. The spiral coils are regularly spaced at a distance of 1 μm from one another The organisms are actively motile, rotating steadily around their endoflagella even after attaching to cells by their tapered ends.

Culture Pathogenic T pallidum has never been cultured continuously on artificial media, in fertile eggs, or in tissue culture. Antigenic Structure The outer membrane surrounds the periplasmic space and the peptidoglycan– cytoplasmic membrane complex.

The endoflagella are in the periplasmic space hyaluronidase invasiveness of the organism T pallidum subspecies pallidum has hyaluronidase that breaks down the hyaluronic acid in the ground substance of tissue and presumably enhances the invasiveness of the organism. Cardiolipin is an important component of the treponemal antigens.

Humans with syphilis develop antibodies capable of staining T pallidum by indirect immunofluorescence, immobilizing and killing live motile T pallidum and fixing complement in the presence of a suspension of T pallidum or related spirochetes.

The spirochetes also cause the development of a distinct antibody-like substance, reagin, which gives positive complement fixation (CF) and flocculation test results with aqueous suspensions of cardiolipin extracted from normal mammalian tissues Both reagin and antitreponemal antibody can be used for the serologic diagnosis of syphilis.

Pathogenesis, Pathology, and Clinical Findings  Acquired Syphilis.  Congenital Syphilis.

 Acquired Syphilis Natural infection with T pallidum is limited to the human host. Human infection is usually transmitted by sexual contact. The infectious lesion is on the skin or mucous membranes of genitalia.

In 10–20% of cases, however, the primary lesion is intrarectal, perianal, or oral. T pallidum can probably penetrate intact mucous membranes, or the organisms may enter through a break in the epidermis. Spirochetes multiply locally at the site of entry, and some spread to nearby lymph nodes and then reach the bloodstream.

Within 2–10 weeks after infection, a papule develops at the site of infection (“hard chancre”) breaks down to form an ulcer with a clean, hard base (“hard chancre”) The inflammation is characterized by a predominance of lymphocytes and plasma cells. This “primary lesion” always heals spontaneously, but 2–10 weeks later, the “secondary” lesions appear.

These consist of a red maculopapular rash anywhere on the body, including the hands and feet, and moist, pale papules (condylomas) in the anogenital region, axillae, and mouth. The patient may also have syphilitic meningitis, chorioretinitis, hepatitis, nephritis (immune complex type), or periostitis.

The secondary lesions also subside spontaneously. Both primary and secondary lesions are rich in spirochetes and are highly infectious. Contagious lesions may recur within 3–5 years after infection, but thereafter the individual is not infectious.

In about 30% of cases, early syphilitic infection progresses spontaneously to complete cure without treatment. In another 30%, the untreated infection remains latent (principally evident by positive serologic test results). In the remainder, the disease progresses to the “tertiary stage”.

characterized by : development of granulomatous lesions (gummas) in the skin, bones, and liver degenerative changes in the central nervous system (meningovascular syphilis, paresis, tabes); or cardiovascular lesions (aortitis, aortic aneurysm, aortic valve insufficiency).

In all tertiary lesions, treponemes are very rare. exaggerated tissue response must be attributed to hypersensitivity to the organisms.

 Congenital Syphilis A pregnant woman with syphilis can transmit T pallidum to the fetus through the placenta beginning in the 10th–15th weeks of gestation. Some of the infected fetuses die, and miscarriages result; others are stillborn at term.

Others are born live but develop the signs of congenital syphilis in childhood interstitial keratitis. Hutchinson’s teeth. Saddlenose. Periostitis. variety of central nervous system anomalies.

Adequate treatment of the mother during pregnancy prevents congenital syphilis. In congenital infection, the child makes immunoglobulin M (IgM) antitreponemal antibody.

Diagnostic Laboratory Tests Specimens tissue fluid expressed from early surface lesions for demonstration of spirochetes by either dark-field microscopy or immunofluorescence and nucleic acid amplification. Blood can be obtained for serologic tests. cerebrospinal fluid (CSF) is useful for Venereal Disease Research Laboratory (VDRL) testing.

Dark-Field examination A drop of tissue fluid or exudate is placed on a slide, and a coverslip is pressed over it to make a thin layer. The preparation is then examined under oil immersion within 20 minutes of collection with dark-field illumination for typical motile spirochetes.

Immunofluorescence Tissue fluid or exudate is spread on a glass slide, air dried, and sent to the laboratory. It is fixed, stained with a fluoresceinlabeled antitreponeme antibody, and examined by means of immunofluorescence microscopy for typical fluorescent spirochetes.

Nucleic Acid Amplification Tests Molecular assays are most useful when testing is performed on genital ulcers. Serologic Tests for Syphilis Nontreponemal tests Treponemal antibody tests

Nontreponemal tests Nontreponemal tests used as screening tests for syphilis used to follow the efficacy of therapy. they are not very sensitive in early syphilis, and the results may not turn positive until a few weeks after initial infection false-positive results can occur with many other diseases; and there may be a prozone phenomenon, particularly in secondary syphilis.

The antigens in these tests contain measured amounts of cardiolipin, cholesterol, and purified lecithin the cardiolipin was extracted from beef heart or liver with added lecithin and cholesterol to enhance reaction with syphilitic “reagin” antibodies. Reagin is a mixture of IgM and IgG antibodies reactive with the cardiolipin–cholesterol– lecithin complex.

The VDRL and tests require microscopic examination to detect flocculation. rapid plasma reagin (RPR) test has colored particles that become caught in the mesh of the antigen–antibody complex, allowing the tests to be read without microscopic magnification.

The nontreponemal tests can give quantitative results using serial twofold dilutions. An estimate of the amount of reagin present in serum can be expressed as the titer. Quantitative results are valuable in establishing a diagnosis and in evaluating the effect of treatment.

Positive nontreponemal test results develop after 2–3 weeks of untreated syphilis and are positive in high titer in secondary syphilis. Positive nontreponemal test results typically revert to negative, often in 6–18 months and generally by 3 years after effective treatment of syphilis. A positive nontreponemal test result late after treatment for syphilis suggests ineffective treatment or reinfection.

The VDRL test is standardized for use on CSF, and the result becomes positive in patients with neurosyphilis.

Treponemal antibody tests Treponemal antibody tests The treponemal tests measure antibodies against T pallidum antigens. The tests are used to determine if a positive result from a nontreponemal test is truly positive or falsely positive.

microhemagglutination T pallidum (MHA- TP) fluorescent treponemal antibody absorbed (FTA-ABS) test. These tests are not useful for screening or after therapy because, once positive, they usually remain so for life except for the immunocompromised.

TREATMENT Treponema pallidum remains exquisitely sensitive to penicillin, which is the preferred treatment in all stages. In primary, secondary, or latent syphilis, persons hypersensitive to penicillin may be treated with doxycycline.