Syphilis

Characteristics of Spirochetes:

1)   Vary in size from 5 to 500 µm in length.

2)   Many of them are free-living saprophytes (microorganism that lives on dead), while a few are obligate parasites.

3)   Are thin, helical (0.1–0.5 × 5–20 µm), and Gram negative.

4)   Are also elongated, motile, and flexible bacteria, twisted spirally along the long axis, giving these bacteria the name spirochetes (Spira meaning coiled, chait meaning hair).

5)   The presence of endoflagella.

6)   Exhibit three types of motility: (a) flexion and extension, (b) corkscrew- like rotatory movement, and (c) translatory motion.

Examples of genera of Spirochetes: Treponema and Borrelia which causes diseases to human.

Common diseases occurred by Spirochetes:

Treponema:

Are short and slender spirochetes with fine spirals and pointed ends.

They are causative agent of syphilis.

Morphology:

1)   Is a thin, coiled spirochete. It measures 0.1 µm in breadth and 5–15 µm in length.

2)   Has six to ten sharp and angular coils.

3)   Is actively motile due to presence of endoflagella.

4)   Is too thin to be seen by microscopy in specimens stained by simple Gram or Giemsa staining.

5)   Can be stained by silver impregnation methods such as Levaditi’s method and Fontana’s method.

6)   Dark ground or phase contrast microscopy is useful for demonstrating the morphology and motility of live T. pallidum.

7)   Shows a trilaminar cytoplasmic membrane surrounded by a cell wall on electron microscope.

8)   Lack enzymes that are necessary to build many complex compounds, so it depends on host cells.

9)   Can be grown in cell culture at low oxygen concentration but for a few generations.

10)                  Has no obvious virulence factors such as toxins but it produces several lipoproteins that induce inflammatory immune response.

Culture:

It can’t be cultured in artificial culture media but it can be maintained inside rabbit testes. This strain of T. pallidum is called Nichole’s strain of T. pallidum.

Pathogenesis of syphilis:

On sexual contact, T. pallidum is transmitted from infected person to other one through mucous membrane or minor skin abrasions.

T. pallidum then invade skin at these lesions and multiply at site of infection.

T. pallidum spread via circulation and producing disseminated tissues.

Host immunity:

The treponemes rapidly penetrate the intact mucous membrane or minor skin abrasions and within a few hours enter the lymphatics and blood to produce a systemic infection. Treponemal antigens induce the production of specific treponemal antibodies and nonspecific reaginic antibodies and relapsing fever. These also induce development of cell-mediated immunity.

Stages of Syphilis:

T. pallidum causes: venereal syphilis (transmitted through sexual contact) and non-venereal syphilis (congenital syphilis and occupational syphilis).

Venereal Syphilis:

1)   Primary Stage Syphilis:

a)   Initial sign is small, hard base chancre which appears at site of infection 10 to 90 days.

b)   Occurs within 3 weeks from infection of host.

c)   Chancre is painless and an exudate of serum forms in center where this fluid is highly infectious and contains many spirochetes.

d)   Non-of these symptoms cause distress.

e)   During this stage, bacteria enter bloodstream and lymphatic system which distribute them widely in body.

2)   Secondary syphilis:

a)   Occurs within 2-10 weeks after primary stage and is most florid 3-4 months after infection.

b)   Is characterized by presence of mucocutaneous lesions which are discrete, macular pink to red, and measure 3–10 mm in diameter especially on palms and soles.

c)   Leads to formation of condylomata lata.

d)   Is associated with mild symptoms of headache, nausea, fever, and pain in the bones.

3)   Latent period:

During this period, there are no symptoms. And after 2 to 4 years of latency, the disease isn’t normally infectious except for transmission from mother to fetus.

4)   Tertiary stage syphilis:

a)   Develops within 3–10 years of infection.

b)   Gumma is a typical pathological lesion found on the skin, in the mouth, and in the upper respiratory tract leading to Gummatous Syphilis.

c)   Leads to cardiovascular syphilis that results in weakening of aorta.

d)   Leads to neurosyphilis that results in various symptoms: dementia, seizures, partial paralysis, loss ability to comprehend speech, or sight and hearing and tabes dorsalis.

Non-Venereal Syphilis:

1)   Congenital Syphilis:  

a)   It is the most severe outcome of syphilis in humans. The infection occurs by vertical transmission from mother to fetus during pregnancy.

b)   Pregnancy during primary or secondary is likely to produce stillbirth (dead fetus).

2)   Occupational Syphilis:

It is a condition that may occur in medical and paramedical workers handling a case of secondary syphilis. The lesion develops usually on the palm of infected health workers.

Diagnosis of Syphilis:

Diagnosis of syphilis is complex because each stage of the disease has unique requirements.

Diagnosis fall in 3 general groups: a) visual microscopic examination, b) non-treponemal serological test, c) treponemal serological test.

1)    visual microscopic examination:

Dark-field microscopy is useful for diagnosis of primary, secondary or congenital syphilis by demonstration of treponemes in the clinical specimen.

Direct fluorescent antibody T. pallidum (DFA-TP) is a sensitive and better method for direct detection of treponemal antigen in the exudates for diagnosis of syphilis. The test used fluorescent- tagged T. pallidum antibodies and is 85–92% sensitive.

2)   Non-treponemal serological tests:

At secondary stage, when spirochetes have invaded almost all body organs, serological test are reactive.

Non-treponemal serological tests are so called because they are non-specific and don’t detect antibodies produced against spirochetes itself but detect regain-type antibody.

Regain-type antibody are apparently response to lipid materials that body produces due to indirect reaction to infection by syphilis.

The antigen used in this test is extract of beef heart (cardiolipin) that seems to contain lipids similar to those that stimulate regain-type antibody.

These tests will detect about 70-80 % of primary syphilis and 99% of secondary syphilis.

Examples:

a)   Wasserman complement fixation test:

Ø The test originally employed a watery extract of the lesion of a syphilitic fetus as the antigen.

Ø This antigen was substituted by an alcoholic extract of ox heart tissue supplemented with lecithin and cholesterol.

Ø This antigen was finally replaced by using cardiolipin antigen, a purified lipid extract of the bovine heart tissue supplemented with lecithin and cholesterol.

b)  Kahn’s tube flocculation test.

c)   VDRL test:

Ø Is slide flocculation test.

Ø This is a simple and more rapid test, which uses cardiolipin antigen with added lecithin and cholesterol.

Ø In a positive test, the cardiolipin antigen reacts with reagin antibodies present in the infected serum and forms visible clumps. In a negative test, cardiolipin continues to remain as uniform crystals in the serum.

Ø Sensitivity of this test:

·      The test is 60–75% sensitive in primary syphilis.

·      The test is 100% sensitive in secondary syphilis.

Ø The test is usually negative in tertiary or third stage of syphilis, in early primary syphilis, latent acquired syphilis, and late congenital syphilis.

Ø The main disadvantage of VDRL test is that it shows biological false positive (BFP) reactions.

d)  Rapid plasma reagin (RPR) test:

The test uses VDRL antigen containing finely divided carbon particles suspended in choline chloride.

3)   Treponemal serological tests:

They are tests that react directly with spirochetes.

These tests use (a) live T. pallidum strains (T. pallidum immobilization test), (b) killed T. pallidum (T. pallidum agglutination test, T. pallidum immune adherence test, and fluorescent treponemal antibody test), or (c) T. pallidum extracts as antigens (TPHA test and EIA [enzyme immunoassay]).

Examples:

1)   T. pallidum immobilization test:

Ø TPI test was the first specific treponemal test.

Ø The test is performed by incubating live T. pallidum strains with test serum in the presence of complement. If the serum contains treponemal antibodies, the treponemes become immobilized, which can be demonstrated under dark ground microscope.

Ø Because of its complexity and difficulty in maintaining live treponemal strains, this test is no longer used.

2)   T. pallidum agglutination test:

Ø uses killed T. pallidum suspension inactivated by formalin.

Ø The test is performed by mixing the formalin inactivated suspension of T. pallidum with patient’s serum. If antibodies are present in the serum, it leads to agglutination of treponemal antigen, which can be demonstrated by dark ground microscopy.

Ø The test is no longer used, because it is non-specific and is associated with false positive reactions.

3)   T. pallidum immune adherence test:

Ø In this test, a suspension of inactivated treponemes is incubated with test serum, complement, and fresh heparinized whole blood from normal individuals.

Ø If antibodies are present, treponemes are found to adhere to the erythrocytes. If antibodies are absent, the treponemes do not adhere to the erythrocytes.

4)   Fluorescent treponemal antibody test:

Ø FTA is an indirect immunofluorescence (IIF) test, which uses acetone fixed smears of T. pallidum on the slides.

Ø The test is performed by adding a drop of test serum to the smear on the slide followed by washing and re-incubating the smear with fluorescent labeled antihuman immunoglobulin.

Ø FTA absorption (FTA-Abs) is a modification of FTA test, which shows high sensitivity and specificity.

Ø The test is almost specific and is considered as a standard reference test in syphilis serology.

Ø The FTA-Abs test is positive in 80% primary syphilis, 100% secondary syphilis, and 95% tertiary syphilis.

5)   TPHA test.

6)   Enzyme immunoassay.

Treatment of syphilis:

Penicillin is the drug of choice for treatment of all the stages of syphilis.

Azithromycin or Doxycycline or tetracycline may be used for nonpregnant patients allergic to penicillin.

Jarish-Herxheimer reaction is a noted complication observed following therapy with antibiotics which is characterized by chills, rigors, and increase in temperature and tachycardia.