Sexually TransmittedInfectionBOND KING (SUNIL)NITISHRAHUL CHAUDHARY
Morphology of Treponema pallidium Member of the order Spirachaetales family Treponemateceae genus - Treponema Darkfield illumination Three genera :- Borelia, Treponema, Leptospira Genus treponema has four principal pathogenic species
PATHOGENIC SPECIES 1)T. Pallidum – responsible for human syphilis. 2)T. Pertenue – Etiologic agent for Yaws and Pinta. 3)T. Carateum - same as pertenue 4)T. Cuniculi – responsible for rabbit syphilis.
1) T. Pallidum Close- colied, thin regular spiral organism 6-15 u, 8-24 coils width is seldom more than 0.25 u Periplast or capsular structure Multiplies by transverse fission, active phase occurs about every 30 hrs.
In aqueous media, young treponemas spins vigorously in more viscous media, they propel themselves in a tissue they show flexibility. Cork screw motility is due to the internal periplasmic flagella. Extremely susceptible to a variety of physical and chemical agents which rapidly destroy them. Viable or motile up to 15 days when kept at 35 degree celcius under anaerobic condition containing serum albumin CHON,CO2.
Cannot be recovered in blood , serum or plasma stored at 4 degree celcius more than 48 hrs. May remain alive for 5 days in tissue specimens from diseased animals. Suspension of treponemes frozen at (-70 degree celcius) or lower frozenin glycerol is viable for years. Both humoral and cell-mediated immune responses are involved.
Antitreponemal anticardiolipin antibodies are product Inflammatory response is initated (lymphocytes, macrophages, plasma cells) Immune complexes are formed, the organism is walled off in lesions ,the disease has atendency or remission stage.
WassermannAntigen(compliment fixn. Test, non-treponemal The original forth of wassermann test an extract of liver containing many treponemes from human fetuses with congenital syphilis was used as antigen. The ligand was isolated from carrdiac muscle and identified as a phospholipid, diphosphatidglycerol called cardiolipin which is normal constituents of host tissue. Free cardiolipin is a hapten and must be bound to a suitable carrier to be antigenic. The microbial cell a foreign carrier and the bound cardiolipin is the immunologic determinant.
Treponemal Antigens In treponemes, two classes of Ag have been recognized 1. Those restricted to one or more species 2. Those shared by many different spirochetes. Reiter treponeme Reiter treponeme a spirochete reputed to be cultivable non virulent variant of T. Pallidum can be used as Ag.
Stages of syphilis (correlation with test results) Syphilis in human is ordianarily transmitted by sexual contact. Infected males, T. Pallidum are present in lesions on the penis or discharged from deeper genitourinary sites along with the seminal fluid. Infected females, the lesions are commonly located in the perianal region or the labia, vaginal wall or cervix. In some cases the primary infection is extragenital usually in or about the mouth.
1. Primary stage (early) T. Pallidum enter the skin through small breaks capable of passing through intact mucous membranes which is carried by the blood stream to every organ of the body. Chancre develops at the site of entrance within 10- 60 days. Chancre usually begins as a papule, breakdown to form a superficial ulcer. Chancre in males occurs at the sulcus of penis or inside the urethra.
In females the chancre occurs at the labia majora or minora, fourchette, clitoris, cervix, uterus or urethral orifice. Persists for 1- 5 week, positive result is between the 1st and 3rd week after the appearance of chancre.
2. Secondary stage Usually occurs from 6-8 weeks after the appearance of the primary chancre. About 1/3 of the cases it occurs before the chancre disappears. Symptoms are generalized rash( involving the mucus membrane) Lesions may develop in the eyes ,joints or CNS Lesions subsides spontaneously after 2-6 weeks. Serologic test are invariably positive. In some cases the primary and secondary stages go unnoticed.
3.The late latent stage Occurs after the 2nd year of infection. Disease is contagious(communicable disease) at this stage. There are no clinical signs and symptoms positive serologic test. May lost for many years or even for the rest of patient’s life. For more than 4 years it is rarely communicable except between mother and fetus.
4. Tertiary stage Lesions are usually seen from 3-10 years after the primary stage. The lesions (gummata) usually located on the skin, mucous membranes, subcutaneous and sub mucous tissues, joints, muscles and ligaments Serious manifestations when lesions are present in the nervous system (causing general paralysis) cardiovascular system(aortic aneurysm) eyes (permanent blindness) In about ¼ of untreated cases this stage is asymptomatic.
Antibodies in syphilisDevelopment Individuals infected with T. Pallidum produce specific and non specific antibodies. Specific Abs. are directed against the pathogen T. Palladum / Treponemal Abs. Non-treponemal Abs./Non-specific Abs. are directed against CHON(protein) Ag. Group common to pathogenic spirochetes.
Specific antibodies in early or untreated early latent syphilis are predominantly IgM and 23% in untreated late latent stage. IgG levels are devoted in the secondary stage. Non-specific IgA antibodies increase significantly during the course of untreated syphilis.
Production of Immunity Resistance to reinfection increases 3 months after infection. Termination of the disease by treatment renders the individual susceptible to reinfection. Protective immunity against syphilis can be induced by vaccines containing nonviable T. Palladum but the need for high volume dosage and the difficulties in the production of sufficient quantities of T.Palladum hampers the use of vaccines It is possible that there is no complete immunity to T. Palladum.
Treatment of syphilis(correlation with test result) If infected patients are treated before the appearance of the primary chancre, it is probable that the serologic test will remain non-reactive. If the treatment is given before the appearance of reagin the test is usually negative. After the appearance of reagin the test usually become negative 6 months after treatment.
In the secondary stage of disease test usually become non-reactive within 12- 18 months after treatment. After secondary stage treatment has variable effects on serologic test result If patient is treated 10 yrs or more after the onset of disease results can be expected to change a little. Individuals who are allergic to penicillin and usually treated with tetracycline. Pregnant women are treated with erythromycin.
Syphilis and blood transfusion It may be transmitted by blood transfusion when fresh blood is used. Blood stored at 4 degree Celsius for 4 days or more is unlikely to transmit syphilis. STS are standard procedures for all blood donation.
Neurosyphilis (syphilis of CNS)A. Asymptomatic Neurosyphilis Reactive serologic test for syphilis. No sign/symptoms of CNS involvement Examination of CSF reveals as increase in cell, total CHON (protein) positive reagin test.B. Meningovascular Neurosyphilis There are definite sign and symptoms of CNS damage CSF is always abnormal increase in cell and total CHON and a positive reagin test. Meningeal or vascular involvement.
C. Parechymatous Neurosyphilis Presents paresis (incomplete paralysis) or tabes dorsalis (degeneration) of dorsal columns of the spinal cord and of sensory nerve trunks with wasting.
Conginital syphilis Acquired fetal life from the maternal circulation through the placental passage of T.Palladum. More likely to occur when the mother is suffering from early syphilis. Adequate treatment of the mother before the 18th weak of pregnancy prevents infections of the fetus because penicillin will cross the placenta in adequate amount.
Lesions of the 1st 2 year of life are infectious and resemble those of secondary syphilis in the acquired form of the disease. Late lesions appearing from the 3rd year onward are mostly of gummatous type and are non-infectious. The stigmata are the scars or deformities resulting from early or late lesions that have healed.
Disease related to syphilis1. YAWS Caused by T. pertenue indistungishable from T.palladum the only different in the disease is character of the lesions (more persistent). Scar formation develops at the site of secondary infection. Lesions are granulomatous or wart-like, tertiary stage is characherized by modular or ulcerative necrosis Can be treated by penicillin Non- venereal transmission by direct contact.
2. PINTA Caused by T. carateum, nonvenereal disease endemic in central and south america. Usually occurs in childhood and is contracted through skin contact. Initial lesion is commonly found in the legs, starts with a papulae soon forms a circular scaly patch known as pintid. Penicillin is effective in treatment
3. BEJEL Nonvenereal syphilis No primary lesions seen Secondary lesions contact consists of generalized popular and papulosquamous eruptions. Tertiary lesions may be observed in subcutaneous tissue, skin and bones. Penicillin is effective in treatment unless cotraindication by allergy.
4. RABBIT SYPHILIS T.cuniculi is the causative agent. A natural venereal infection of rabbits. Producing minor lesions of the genetalia.
Serologic test for syphilisPRINCIPLES Infection of human with T. palladum provokes in the host a complex Ab response Based on the detection of one or more of the Abs.* 2 known types of Antibodies1. Non-treponemal Abs or reagin which reacts with lipid Ag (antigen)2. Treponemal Abs which react with T. palladum and closely related strains.
Reagin test for syphilis VDRL (Venereal Disease Research Laboratory ) slide test - nonspecific antigen - cardiolipin is used PCT (plasmacrit) RPR ( rapid plasma reagin test) Unhealed serum reagin test RPRC (rapid plasma reagin circle card)
Treponemal test TPI (Treponema palladum inhibition test) TPCF (treponema palladum complement fixation test) RPCF (reiter CHON(protein) complement fixation test) FTS-ABS- specific to T. palladum.