SPIROCHETES, Syphilis Lecture Notes

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SPIROCHETES

–     Spirochetes are heterogeneous group of spiral motile bacteria.
–     Strains of medical importance:
–          1-Treponema pallidum.
–          2-Borellia.
–          3-Leptospira.

Classification of Treponemas:
–     The genus Treponema (T.) contains both pathogenic and nonpathogenic species .
–     Nonpathogenic treponemas may be part of the normal flora of the intestinal tract, the oral cavity, or the genital tract.
The pathogenic species are:
–     T. pallidum subspecies pallidum cause Syphilis.
–     T. pallidum subspecies pertenue cause Yaws.
–     T. pallidum subspecies carateum cause Pinta .
–      T. pallidum subspecies endemicum cause Bejel.
Treponema pallidum subspecies pallidum
(T. pallidum):Transmission:
–     T. pallidum is an obligate parasite of humans (the only reservoir).
–     It is transmitted by sexual contact with lesions of skin and mucous membranes (of genitalia, mouth, and rectum) containing spirochaetes.
–     It is also transmitted from pregnant mother’s to their fetuses  (after 18th week of gestation) leading to miscarriage, still birth, or congenital syphilis, rarely, through blood transfusion

Pathogenesis and Immune Response:
–     Organisms gain entrance through the abraded -skin or onto mucous membrane surfaces,attach by their tips to host cells.
–      within few hours, significant numbers of organisms leave the local site and are carried to the regional lymph nodes.
–      Dissemination occurs via the circulation.
–     T pallidum are highly invasive pathogens which disseminate soon after inoculation.
–     they induce inflammatory processes.
–     They have hyaluronidase which breaks hyaluronic acid in the ground substances of tissue.
–     Immunity to syphilis is incomplete. Antibodies to the organism are produced but do not stop the progression of the disease.
–      Patients with early syphilis who have been treated can contract syphilis
.
–     There are more than 100 protein antigens
–     In human infection antigens of T pallidum stimulate the development of two kinds of antibodies:
Reagin antibodies:
–     They are non specific antibodies directed against some antigens widely distributed in normal tissues e.g. cardiolipin extracted from beef heart.
–     They give positive complement fixation and flocculation tests.
–      They are found in patient’s serum after 2-3 weeks of untreated syphilitic infection.

Specific antitreponemal antibodies:

–     They react only with pathogenic strains of T pallidum. They are tested  by immunofluorescence and agglutination tests.
Clinical Manifestations of Syphilis:
The disease passes through three stages:

–     Primary stage (Primary Syphilis):
    After incubation period of 4-5 weeks, the spirochaetes multiply at the site – of inoculation and a local, painless, hard, well circumscribed ulcer (chancre) usually forms on the genetalia in 2-10 weeks.
–     Regional lymphadenopathy occurs which is usually bilateral
–     Chancre and lymph nodes contain organisms and the disease is communicable.
–     After 2 to 6 weeks of symptoms, this primary lesion heals spontaneously.
Follow..Clinical Manifestations of Syphilis:
–     Secondary stage (Secondary Syphilis)
–     2-4 months after appearance of primary chancre, spirochaetes reach blood stream and disseminate leading to 2ry stage of syphilis .
–     Lesions may appear as skin rash, or moist papules on the skin and mucous membranes.
–      Moist lesions on the genetalia are called condylomas.
Follow…Clinical Manifestations of Syphilis:
–     Tertiary Stage (Tertiary Syphilis) :
–     The spirochetes become localized in some organs and tissues.
–     Tertiary syphilis is characterized by appearance of chronic granuloma (gammas) in skin, bones, or internal  organs after years if infection is untreated.
–      Nervous manifestations and cardiovascular affection occurs later in the disease.
–     Disease is not communicable at this stage.
Congenital syphilis
–     Infection can be transmitted from infected mother to fetus within the first trimester resulting in miscarriage or still birth.
–     If born alive leads to congenital syphilis.
congenital syphilis:
–     Early congenital syphilis:
–     Signs are apparent before the age of two years, include mucocutaneous lesions, osteochondritis, anemia, and hepatosplenomegaly.
–     Late congenital syphilis:
–     In late congenital syphilis, three commonly observed manifestations, called Hutchinson’s triad, are interstitial keratitis, notched incisors, and eighth-nerve deafness.

Laboratory Diagnosis of Syphilis:
–      Direct Methods:

–     through Demonstration of spirochetes in syphilitic lesions.
–     Specimens:
–    include freshly collected exudates from primary and secondary lesions e.g. chancre and condyloma, after cleaning with warm saline.
Morphology and staining :
     Treponemas are helically shaped with regular narrow spaced coils.
     They are motile through undulation of axial filaments resulting in rotation about the long axis, flexion and true movement.
Treponemas are so thin that they don’t stain by ordinary stains and can be seen only by:
–     Dark field examination:
–     as motile spirals. Fontana stain: as brown spiral organisms.
–     Direct Immunofluorescence:
–      A smear stained by a fluorescein labelled
     anti-treponemal serum and examined by immunofluorescence microscope will show typical shaped fluorescent spirochetes.
*N.B: Within a few hours of antibiotic treatment, spirochaetes will not be found in lesions.

Culture:
–     Pathogenic Nichol’s strain never grows on bacteriologic media or in cell cultures.
–      Non pathogenic Reiter strain can be cultured anaerobically in vitro & related antigenically to
     T pallidum.
Indirect Methods (serological tests):
–     These tests use either nontreponemal or treponemal antigens.
–     Non-Treponemal Antigen Tests (non specific):
–     The antigens employed are lipids extracted from normal mammalian tissue, which is purified cardiolipin of beef heart
    (
1. Flocculation tests:
–     VDRL (Venereal Disease Research Laboratory) test.
–     RPR (Rapid Plasma Reagin) test.
–     USR (Unheated Serum Reagin) test.
–     TRUST (Toluidine red unheated serum test).
–     All of the four tests are based on the fact that the particles of the lipid antigen remain dispersed with normal serum but flocculate when combining with reagin.
–      The VDRL and USR tests require microscopic examination to detect flocculation, whereas the RPR and TRUST have added coloured particle and can be read without microscopic examination.

2. Complement fixation test
(Wasserman reaction):
–     It is a laborious test and it has been almost completely replaced by the flocculation tests.
–     Non specific serologic tests are usually positive in primary and secondary syphilis.
–     Non specific antibodies decrease with treatment
–     specific antibodies remain for life. Non-specific tests can be done to test effectiveness of treatment and as screening test for syphilis.
Treponemal Antibody Tests (specific tests):
–     These tests involve the use of specific treponemal antigens.
–     Specific antibodies appear in serum 2-3 weeks after infection and results are positive in most cases with primary syphilis.
–      These tests remain positive for life even after effective treatment and can not be used to follow up the response to treatment.
1-Fluorescent Treponemal Antibody Absorption (FTA-ABS) test:
–     It is indirect IF technique.
–      It is the first to become positive in early syphilis.
–     It is routinely positive in secondary syphilis and usually remains positive many years after effective treatment.
2-T. pallidum -particle agglutination (TP-PA) test:
–     In this test gelatin particles sensitized with T .pallidum subspecies pallidum antigens are agglutinated by antibodies from the serum of patients with syphilis.
–     It is similar to FTA-ABS test in sensitivity and specificity.
3- T. pallidum immobilization (TPI) test:
–     Because this test employs live treponema it is time consuming, expensive and technically demanding, so it is superseded by other tests.
–     It is still done in some reference laboratories for research purposes.
Treatment:
–     Infection is treated with penicillin G penzathine.
–     Patients with neurosyphilis receive high dose of intravenous penicillin for 10 to 14 days.
–     Penicillin-allergic, nonpregnant patients with early syphilis can be treated with tetracycline.
–      A Jarisch-Herxheimer reaction can follow treatment of secondary syphilis.
–     This systemic reaction is associated with the rapid death of treponemal.
–     Between 2 and 12 hours after antibiotic therapy, headache, malaise, slight fever, chills, muscle aches, and intensification of syphilitic lesions occur.
–     These manifestations resolve in fewer than 12 hours.
    Borrelia:
•    Causative agent of relapsing fever  and Lyme disease.
•    Both transmitted by insects (lice ,flee or ticks.)
•                                 Leptospira:
•    It is the causative agent of Weil,s disease (infectious jaundice.)

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