HISTORY NOTE: It penetrates (1) intact mucous membrane or (2) or
through tiny defects (e.g. wound) in skin. 15th & 16th centuries indicates an epidemic that swept multiplies locally and causes an ulcerative lesion known as across Europe. It was believed that Columbus and his chancre (highly contagious stage). It also disseminates to sailors brought the disease to Europe from the Americas. local regional lymph nodes, enter the lymphatic system Others believe that the organism was already in Europe and then the circulatory system. but underwent spontaneous mutation. Spirochetemia occurs is when T. pallidum enters the The organism was identified in 1905 as Spirochaeta circulatory system. pallida (old name). NOTE: Chancre plays an important role in the transmission. GENERAL INFORMATION (2) PERINATAL ROUTE Treponema pallidum is causative agent of human *Especially during the last trimester of pregnancy. syphilis. NOTE: Congenital transfer is very evident in the latent A spirochete bacterium of the family Spirochaetaceae – stage of syphilis. Newborn using cord cells are screened causing venereal disease (STD). for Ab of syphilis and representation of the current state of Can only be viewed using infection of the mother. o Dark field microscopy – direct examination of the (3) BLOOD CONTAMINATION (rare) movement of spirochetes o Direct fluorescent antibody staining and Because it has a short survival period in blood. detecting antibodies in serum or CSF. Can’t survive in citrated blood at 4 *C for no longer it contains 8-24 coils and 6 -15 um long. than 72 hours. contains trilaminar outer membrane similar to g (-) bacteria. (4) NOTE: Transmission can also be due to: Wasserman test (obsolete test)- the first diagnostic blood 1. Migration or travel – ex. SARS/MERS-CoV test for syphilis (1906) 2. Mutation Penicillin is a drug of choice. Cannot be cultured on artificial media – but can be SIGNS/SYMPTOMS inoculated using experimental animals (rabbit) Untreated syphilis is a chronic disease with subacute NOTE: Treponema remains viable up to 5 days in tissue symptomatic periods separated by asymptomatic specimen (from diseased host or from cryoprotected intervals, during which the diagnosis can be made specimens). serologically. Other names It penetrates intact mucous membrane or through tiny o Syphilis defects (e.g. wound) in skin. o Great Pox Spirochetemia occurs is when T. pallidum enters the o Evil Pox circulatory system. o Spanish Disease Incubation time: ~3 Weeks (10-90 Days) o French Disease o Italian Disease STAGES Medically important Treponema (genus) includes the ff. 1. Primary It occurs at the end of incubation period Appearance of transient, painless firm chancre 3 weeks after initial infection. o Develops papule then become ulcerated which consequently develop as chancre (3 weeks after infection) o Some appear as early as 10 days or as late as 3-4 months after infection o May appear almost everywhere in the body. TRANSMISSION o Regional adenopathy (swelling of lymph (1) DIRECT CONTACT nodes can be seen for those infected. o It depends where the chancre is Kissing – if the person has an active oral lesion (chancre) predominantly located. Sexual contact- especially male having sex with male. o If the chancre is predominantly seen on Men is easier to get infected than women genitalia, probably the patient develops o You know what’s the reason inguinal adenopathy. Sharing of bed Dx note: Can be detected using Microscopic evaluation. If Meningovascular syphilis (5-10 y of infection) fluid is spread on a glass slide and examined with a dark field Pia mater & arachnoid inflammation microscope, the spirochete can be seen. Parenchymatous syphilis Manifests general paresis, joint degeneration and tabes 2. Secondary dorsalis (demyelination of dorsal root and ganglia It occurs after the appearance of chancre (2-8 wks.) Tabes dorsalis is characterized by a gait disturbance and bladder symptoms. A generalized illness (e.g. fever, sore throat, nasal discharge, increased WBC count) Dx note: if RPR is negative but with hi-suspicion of The most infective stage Neurosyphilis, perform FTA-abs It also progresses to generalized adenopathy. For CSF, perform VDRL Macular lesions are now common IMMUNOLOGIC MANIFESTATIONS Appearance of condylomata lata. Palms and soles are the prominent sites of rashes. Antigen may be observed in human syphilis If you’re immunocompetent enough, it will resolve (1) Antigen restricted to t. pallidum within 2-6 wks. (self-limiting) (2) Antigen shared by different spirochetes Dx: Screening test : RPR and VDRL Antibodies may be observed in human syphilis Confirmatory test: TP-PA (1) Specific Antibody for T. pallidum a. IgM- rises on untreated early latent syphilis 3. Latent (hidden stage) b. IgG- rises on the subsequent stages of syphilis If the body can’t resolve the disease, it will progress to (2) Nontreponemal antibodies (Reagin antibody) latent stage. Not specific because it can be falsely Note: It is a non-infectious stage increase in Can be detected only in serological methods. (a) infectious diseases Still, some of the patient develop relapses (or simply Measles they have a manifestation of secondary syphilis) for Chickenpox the first 2- 4 years. Hepatitis o Relapses are extremely rare after 4 infectious mononucleosis years of latency. leprosy tuberculosis All the stages are infectious except the latent stage but not in the case if patient develop relapses. leptospirosis malaria It is during this time that the disease can be rickettsial disease transferred from the mother to the fetus. trypanosomiasis Dx note: serologic test is the only indication due to low abs-ag lymphogranuloma venereum concentration (b) noninfectious conditions 4. Tertiary (late syphilis) Autoimmune disorders Occurs 3 to 10 years after the primary infection. Drug addiction old age about 1/3 of the patient enters latent stage will Pregnancy progress to tertiary syphilis. Recent immunization 15% of untreated individual develops benign syphilis, Blood transfusion characterized by destructive granulomas or gummas Connective tissue disorder resembling segments of circles. Skeletal system is the most frequently affected. Food for thought…. 10% develops cardiac manifestation (aortic arch) Note: T. pallidum is not just the accountable of the diseases 8% involves CNS disease e.g. Neurosyphilis manifestation of syphilis but the effect of the immune system o CSF –Specimen choice itself, -as our body fights the bacteria, there will be a collateral OTHER SIGNIFICANT disorder cause by Syphilis damage may happen or simply our healthy cells will be destroyed by our immune system (pathophysiologic response) (1) Congenital syphilis due to the substance secreted by our leukocyte which is Can be prevented by early detection (30 supposedly intended only to syphilis bacteria. That is why days b4 delivery) immunosuppression of cell mediated immunity is Early stage children (<2 yo) manifestations important to prolong the survival of infected patient. include: anemia, condyloma latum and *Why cell mediated immunity? hepatosplenomegaly. It’s because cell-mediated immunity is not specific for destroying Late stage children (>2yo) foreign substances that’s why collateral damage occurs like…. 8th nerve deafness, keratitis and granulomatous infection (gumma) --it is the Hutchinson’s teeth-collectively known as effect of delayed hypersensitivity in the Hutchinson’s triad. immune host not from syphilis; syphilis is the one who triggers it. (2) Neurosyphilis Glomerulonephritis It includes…. Meningeal syphilis (>1 yr of infection) Charity Rojas. | L.M Brain & spinal cord Dx note: Requires inactivation of complement by heating in LABORATORY METHODS order to reduce the interfering substances. DIRECT OBSERVATION (1) Dark field microscopy- primary syphilis test of TREPONEMAL METHOD (More SPECIFFIC) choice (1) Fluorescent Treponemal Antibody Absorption (2) Direct/indirect microscopy- alternative choice Test (FTA-ABS) because it doesn’t need to require live specimen. PRINCIPLE: Indirect Fluorescent Immunoassay REAGENT ANTIGEN: Nichol’s strain dried and fixed on NON-TREPONEMAL METHOD (Less SPECIFIC) slide Determines the presence of Reagin ABSORBENT: Reiter Treponemes (nonpathogenic Reagin composed of cardiolipin, cholesterol and lecithin. strains T. pallidum) (1) Rapid plasma Reagin (RPR) / Carbogen test PRINCIPLE: Flocculation with coagglutination of the NOTE: Source of Ab – patient’s serum carbon particles Source of Ag – Nichol’s strain (nonviable strain of T. SERUM: undiluted, not heated pallidum from testicular tissue of the rabbits. REAGENT: Cardiolipin Ag, colorless alcoholic solution containing cardiolipin, lecithin, charcoal, choline chloride & (1) Patient’s serum (diluted in absorbent coming from thimerosal Reiter Treponemes) (2) Then it is layered over into the slide – Slide is already ROTATOR: 100 rpm for 8 min. RING DIAMETER: 18 mm fixed with T. pallidum ANTIGEN DELIVERY NEEDLE: gauge 20 needle, 60 (3) If the patient is positive (+) – Abs bind to the bacteria drops/mL (4) Abs will coat Treponema and add fluorescein A qualitative test in which undiluted serum is mixed with Isothiocyanite (FITC), a labeled anti-human cardiolipin antigen and microscopic charcoal particles on a immunoglobin – this combines with patient’s IgG cardboard slide. After a mechanical rotation for an (untreated infection) & IgM (current infection) Abs that appropriate length of time, the test is examined for are adhering to T. pallidum and results in a visible test macroscopic agglutination of the charcoal particles. reaction when examined by fluorescence It measures IgG and IgM microscopy. RPR is more sensitive than VDRL (5) POSITIVE PATIENT: Presence of fluorescence Note: Flocculation is the reaction with the soluble Ag with the soluble Ab forming fine particles (2) Hemagglutination Treponemal Test for Syphilis Undiluted serum (From patient) (HATTS) + Cardiolipin Ag (found in reagent) o PRINCIPLE: Hemagglutination + Charcoal particle (found in kit) o REAGENT ANTIGEN: Glutaraldehyde stabilized ------------(then swirl or mechanical rotation) ----------- turkey RBC coated with Treponemal antigen. formation of AGGLUTINATION/CLUMPING (+) *Read microscopically (3) Microhemagglutination T. pallidum Test (MHA- (2) Venereal Disease Research Laboratory (VDRL) TP) o PRINCIPLE: Hemagglutination PRINCIPLE: Flocculation o REAGENT ANTIGEN: Tanned formalin sheep RBC SAMPLE: serum or CSF coated with Treponemal antigen SERUM: Heated serum (50uL serum (56°C for 30 min) REAGENT: cardiolipin, cholesterol, lecithin NOTE: Both are following the hemagglutination principle specifically with the RBC clumping but they differ with the source. ROTATOR: 180rpm for 4 min (serum VDRL) RING DIAMETER: 14 mm (serum VDRL) (4) T. pallidum Immobilization Test (TPI) ANTIGEN DELIVERY NEEDLE: o Most specific for syphilis (Gold Standard) o Qualitative serum VDRL – gauge 18 needle o PRINCIPLE: Ab produced against T. pallidum plus without bevel that will deliver 60 drops of complement can immobilize the live treponemes. antigen suspension/mL o (+): >50% immobilized treponemes o Quantitative serum VDRL – gauge 19 needle o SOURCES: 1. Non-pathogenic Reiter stain that will deliver 75 drops of antigen 2. Pathogenic Nichol’s strain suspension per mL or gauge 23 needle with/without bevel that will deliver 100 drops LABORATORY *Imunochromatographic method of saline/mL. o CSF VDRL – gauge 21 0r 22 needle that will Add 10uL of plasma or serum (20uL of blood) deliver 100 drops/mL Add 4 drops of assay diluent into the assay diluent well. o REPORTING Nonreactive – no clumps INTERPRETATION: Weakly reactive – small clumps Interpret test results in 5-20 minutes after adding the assay Reactive – medium or large clumps diluent. Do not read test results after 20 minutes. Reading too FALSE (+) includes late can give false results. Malaria, Systemic lupus erythematous, rheumatoid arthritis, pregnancy Book: includes HIV, HSV, leprosy Charity Rojas. | L.M