Syphilis

Presentors: Anne Franceleen U. DaluraDaniel Abidin

Reference

Immunology and Serology in Laboratory Management: 4th Edition

By: Mary Louise Turgeon

Internet

Objectives

To be able to know how the characteristics of syphilis

To be able to know the s/s of the different stage of syphilis

To be able to know the different lab. tests involved for syphilis determination

Table of Contents

I. Introduction ----------------------------- 5II. Etiology------------------------------------ 6III. Epidemiology----------------------------7IV. Signs and Symptoms----------------- 11

Syphilis

The disease syphilis was reported in the literature as early as 1495.

In 1905 it was discovered that syphilis was caused by a spirochete type of bacteria, Treponema pallidum (originally called Spirochaeta pallida).

Wassermann test, the first diagnostic blood test and was developed in 1906.

Penicillin, drug of choice in the treatment of this disease.

EtiologySpirochaetales and Treponemataceae(family order) (family) Treponema

(genus)

T. Pallidum T. Pertenue T. Carateum( 3 clinically significant/pathogenic)

Direct examination with darkfield microscopy Appear as: fine, spiral (8-24 coils), approximately 6-15

um long, have trilaminar outer membrane Remain viable for up to 5 days in tissue specimen

Epidemiology

Pathogenic treponemes are transmitted almost uniformly by direct contact.

Three treponematoses: Yaws, Pinta and Bejel – are

rarely seen in the United States but are prevalent in other countries.

Yaws, pinta, and bejel- are diseases caused by bacteria closely related to T. Pallidum.

In these infections the skin or oral lesions contain many spirochetes that may be transmitted by personal, but not necessarily venereal, contact.

These infections are generally acquired during childhood.

The risk of acquiring syphilis from a single sexual exposure to an infected partner is unknown

A high percentage of partners do seek medical treatment within 90 days of contact.

The incidence of syphilis is highest in women age 20 to 29 years and in men 30-39 years.

Syphilis can be acquired by kissing a person with active oral lesions

Very few cases of transfusion-acquired syphilis have been reported.

During the first half of the twentieth century, however, syphilis was a major blood-borne infectious disease easily transmitted through the prevailing method o direct donor-to-patient blood transfusion.

Cases have been reported of children who have acquired syphilis by sharing a bed with an infected parent.

Syphilis may be transmitted transplacentally to the fetus.

Treponema-Associated Diseases in Humans

BACTERIA ASSOCIATED DISEASE

1.Treponema pallidum2.T. Pallidum (variant)3.T. Pertenue4.T. carateum

-Syphilis-Bejel-Yaws-Pinta

Signs and Symptoms

The progression of untreated syphilis is generally divided into stages:

Initially, T. Pallidum penetrates intact mucous membranes or enters the body through tiny defects in the epithelium.

Patients are said to be ‘incubating syphilis’. The incubation period usually lasts about 3 weeks but can range from 10-90 days.

Primary Syphilis At the end of the incubation period, a

patient develops a characteristic primary inflammatory lesion called chancre.

The chancre begins as a papule and erodes to form a gradually enlarging ulcer with a clean base and indurate edge. Generally, it is relatively painless.

In most cases, only a single lesion is present, but multiple chancres are not rare.

Chancres are typically located around the genitalia, but in about 10% of cases, lesions may appear almost anywhere else on the body (throat, lip, hands).

In males, spirochetes are present in the lesion on the penis or discharged from deeper sites with semen.

In females, infected lesions are usually located in the perineal region or on the labia, vaginal wall, or cervix.

If the lesion is located inside the urethra, the only symptom may be a scanty, serous urethral discharge.

The primary chancre will persists for 1-5 weeks and will heal completely in about 4-6 weeks, even without treatment.

Secondary syphilis Secondary stage is characterized by a

generalized illness that usually begins with symptoms suggesting a viral infection: headache, sore throat, low grade fever, and occasionally a nasal discharge.

Blood tests reveal a moderate increase in leukocytes with a relative increase in lymphocytes.

The disease progresses with the development of lymphadenopathy and lesions of the skin and mucous membranes.

Patients may also develop condylomata lata, flat lesions resembling warts in moist areas of the body (around anus, vagina).

Secondary syphilis usually resolves within 2-6 weeks, even without therapy.

Latent syphilis After resolution of untreated secondary

syphilis, the patient enters a latent noninfectious state in which diagnosis can be made only by serologic metods.

During the first 2-4 years of infection, one fourth of patients will have one or more mucocutaneous relapses in which the manifestation of secondary syphilis reappears.

During these relapses, patients are infectious, and the underlying spirocetemia may be passed transplacentally to the fetus.

Late (tertiary) syphilis The first manifestations of late syphilis are

usually seen from 3-10 years after primary infection.

About 15% of untreated syphilitic individuals eventually develop late benign syphilis, characterized by the presence of destructive granulomas.

Of untreated patients, 10% develop cardiovascular manifestations.

In about 8% of untreated patients, late syphilis the CNS. Initially, CNS disease is asymptomatic and can be detected only by examination of CSF.

Meningovascular syphilis usually manifests as a seizure or cerebrovascular (stroke).

Congenital syphilis congenital syphilis is caused by

maternal spirochetemia and transplacental transmission of the microorganism. The typing of congenital syphilis is according to age at diagnosis.

The early stage is seen in children under 2 years old who are untreated. Symptoms of the untreated early age can include rash, condyloma latum, bone changes, hepatosplenomegaly, jaundice, or anemia.

The late stage is seen in children over 2 yrs old who are untreated. Symptoms of the untreated late stage include eighth nerve deafness, keratitis, and Hutchinson’s teeth, as well as arthropathy and neurosyphilis.

Two classes of antigen have been recognized in treponemes:

1. Antigens restricted to one or a few species

2. Antigens shared by many different spirochetes.

Specific and nonspecific antibodies are produced in the immunocompetent host.

Specific antibodies against T. Palidum and nonspecific antibodies against the protein antigen group common to patohgenic spirochetes are formed.

Immunological Manifestations

Specific antitreponemal antibodies in early or untreated early latent syphilis are predominantly Igm antibodies.

The early immune response to infection is rapidly followed by the appearance of IgG antibodies, which soon become predominant. The greater elevation in IgG concentration is seen in secondary syphilis.

Nontreponemal antibodies, often called reagin antibodies, are produced by infected patients against components of their own or other mammalian cells.

Classic serological methods for syphilis measure the presence of the following two types of antibodies:

1. Nontreponemal mtds.- Rapid Plasma Reagin (RPR) test

2. Treponemal mtds.- Fluorescent treponemal antibody adsorption (FTA-ABS) test- Microhemaggutination for Treponema allidum (MHA-TP) test.

Darkfield microscopy - the test of choice for patients with

primary syphilis- a darkfield examination is also suggested for immediate results in cases of secondary syphilis, with a titer follow-up test.

Nontreponemal mtds.- RPR is the most widely used nontreponemal serologic procedure.-RPR test can be performed on unheated serum or plasma using a modified VDRL antigen suspension of choline chloride with EDTA.

- RPR card test antigen also contains charcoal for macroscopic reading.

Treponemal mtds FTA-ABS and MHA-TP represent treonemal

methods. The T. Pallidum immobilization (TPI) test is obsolete.

These 2 specific trepnemal antigen tests can confirm reactive (Positive) reagin tests but should not be used as primary screening methods.

FTA-ABS and MHA-TP can be used to confirm that a positive nontreonemal test result has been caused by syphilis rather than other biologic conditions that can produce a positive serologic result.

These tests also can determine quantitative titers of antibody, which is used for following response to therapy.

An ELISA for syphilis antibody is available, but it is not widely used at present.

The ELISA method, however, does offer a sensitive and specific alternative to existing methods.

Tests Primary stage Secondary stage

Late

Nontreponemal(reagin tests) - RPR - automated reagin test(ART)

80% 99% 1%0%

Specific treponemal tests - FTA-ABS - TP-HA; MHA-TP

85%65%

100%100%

95%95%

Sensitivity of common serologic tests for syphilis

Rapid Plasma Reagin Card testPrinciple:

- RPR test is designed to detect reagin, an antibody-like substance present in serum.

Specimen collection and preparation- patient must be positively identified when the specimen is collected.- specimen is to be labelled at bedside and must include the patient’s full name, date of collection, patient’s hospital identification number. The phlebotomist’s initials should also appear on the label.- blood should be drawn aseptic technique.- (specimen) minimum of 2 ml of clotted blood (red-top evacuated tube). After allowing the blood to clot, centrifuge the specimen and allow the serum to remain in the original tube.

Fluorescent Treponemal antibody Absorption test

Principle:FTA-ABS test is a direct method of observation.

- Not recommended for screening, it is the most sensitive serologic procedure in the detection of primary syphilis.

- patient must be positively identified when the specimen is collected. specimen is to be labelled at bedside and must include the patient’s full name, date of collection, patient’s hospital identification number. The phlebotomist’s initials should also appear on the label. - blood should be drawn aseptic technique.- required specimen is a minimum of 2ml of clotted blood (red-top evacuated tube).

Specimen collection and preparation

- the specimen should be centrifuged and the serum removed from the clot.- before testing the serum should be heated at 56ºC for 30 minutes if never inactivated, or 10 minutes at 56ºC if inactivated more than 4 hours before testing.