| Venereal Disease Research Laboratory test | |
|---|---|
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| Purpose | blood test for syphilis |
The Venereal Disease Research Laboratory test (VDRL) is a blood test for syphilis and related non-venereal treponematoses that was developed by the eponymous US laboratory. The VDRL test is used to screen for syphilis (it has high sensitivity), whereas other, more specific tests are used to diagnose the disease.
The VDRL type test was invented before World War I, with its first iteration being that developed by August Paul von Wasserman with the aid of Albert Neisser in 1906. The VDRL test, as it is largely still done today, was developed in 1946 by Harris, Rosenberg, and Riedel. [1] The lab was renamed to the Treponemal Pathogenesis and Immunology Branch of the United States Public Health Service.[ citation needed ]
The VDRL is a nontreponemal serological screening for syphilis that is also used to assess response to therapy, to detect central nervous system involvement, and as an aid in the diagnosis of congenital syphilis. The basis of the test is that an antibody produced by a patient with syphilis reacts with an extract of ox heart (diphosphatidyl glycerol). It therefore detects anti-cardiolipin antibodies (IgG, IgM or IgA), visualized through foaming of the test tube fluid, or "flocculation".[ citation needed ]
The rapid plasma reagin (RPR) test uses the same antigen as the VDRL, but in that test, it has been bound to several other molecules, including a carbon particle to allow visualization of the flocculation reaction without the need of a microscope. Many other medical conditions can produce false positive results, including some viruses (mononucleosis, hepatitis), drugs, pregnancy, rheumatic fever, rheumatoid arthritis, lupus, and leprosy.[ citation needed ]
The syphilis anti-cardiolipin antibodies are beta-2 glycoprotein independent, [2] whereas those that occur in antiphospholipid syndrome (associated to lupus for example) are beta-2 glycoprotein dependent, and this can be used to tell them apart in an ELISA assay. [3] This test is very useful as the trend of titres are correlated to disease activity (i.e. falling titres indicate successful treatment). It has a very good sensitivity for syphilis, except in late tertiary form.[ citation needed ]
There are a number of treponemal-specific tests such as the fluorescent treponemal antibody-absorption (FTA-ABS) test, T. pallidum hemagglutination assays (TPHA), and the microhemagglutination assay (MHA-TP).[ citation needed ]
The MHA-TP is used to confirm a syphilis infection after another method tests positive for the syphilis bacteria. The MHA-TP test detects antibodies to the bacteria that cause syphilis and can be used to detect syphilis in all stages, except during the first 3 to 4 weeks. This test is not done on spinal fluid. The MHA-TP test is rarely used any more. [4] Treponema pallidum particle agglutination assay (TP-PA) and the Toluidine red unheated serum test (TRUST), which may be used to confirm a positive VDRL result, are more specific for syphilis than non-treponemal tests and in the presence of a positive test, more likely indicate active infection. Unfortunately, other treponemal infections such as yaws, bejel, and pinta and possibly nonpathogenic commensal treponemes can result in a positive. Not all these disease are venereal; it has been recommended that a careful explanation of this fact be included with test results. [5]
Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. The signs and symptoms of syphilis vary depending in which of the four stages it presents. The primary stage classically presents with a single chancre though there may be multiple sores. In secondary syphilis, a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet. There may also be sores in the mouth or vagina. In latent syphilis, which can last for years, there are few or no symptoms. In tertiary syphilis, there are gummas, neurological problems, or heart symptoms. Syphilis has been known as "the great imitator" as it may cause symptoms similar to many other diseases.
Treponema pallidum, formerly known as Spirochaeta pallida, is a microaerophilic spirochaete bacterium with subspecies that cause the diseases syphilis, bejel, and yaws. It is transmitted only among humans. It is a helically coiled microorganism usually 6–15 μm long and 0.1–0.2 μm wide. T. pallidum's lack of either a tricarboxylic acid cycle or oxidative phosphorylation results in minimal metabolic activity. The treponemes have a cytoplasmic and an outer membrane. Using light microscopy, treponemes are visible only by using dark-field illumination. T. pallidum consists of three subspecies, T. p. pallidum, T. p. endemicum, and T. p. pertenue, each of which has a distinct associated disease.
Antiphospholipid syndrome, or antiphospholipid antibody syndrome, is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS can lead to blood clots (thrombosis) in both arteries and veins, pregnancy-related complications, and other symptoms like low platelets, kidney disease, heart disease, and rash. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease. Diagnosis is made based on symptoms and testing, but sometimes research criteria are used to aid in diagnosis. The research criteria for definite APS requires one clinical event and two positive blood test results spaced at least three months apart that detect lupus anticoagulant, anti-apolipoprotein antibodies, and/or anti-cardiolipin antibodies.
Yaws is a tropical infection of the skin, bones, and joints caused by the spirochete bacterium Treponema pallidum pertenue. The disease begins with a round, hard swelling of the skin, 2 to 5 cm in diameter. The center may break open and form an ulcer. This initial skin lesion typically heals after 3–6 months. After weeks to years, joints and bones may become painful, fatigue may develop, and new skin lesions may appear. The skin of the palms of the hands and the soles of the feet may become thick and break open. The bones may become misshapen. After 5 years or more, large areas of skin may die, leaving scars.
The Wassermann test or Wassermann reaction (WR) is an antibody test for syphilis, named after the bacteriologist August Paul von Wassermann, based on complement fixation. It was the first blood test for syphilis and the first in the nontreponemal test (NTT) category. Newer NTTs, such as the RPR and VDRL tests, have mostly replaced it. During the mid-20th century, in many jurisdictions, including most US states, applicants for a marriage license were required by law to undergo a Wassermann test.
The rapid plasma reagin test is a type of rapid diagnostic test that looks for non-specific antibodies in the blood of the patient that may indicate an infection by syphilis or related non-venereal treponematoses. It is one of several nontreponemal tests for syphilis. The term reagin means that this test does not look for antibodies against the bacterium itself, Treponema pallidum, but rather for antibodies against substances released by cells when they are damaged by T. pallidum. Traditionally, syphilis serologic testing has been performed using a nontreponemal test (NTT) such as the RPR or VDRL test, with positive results then confirmed using a specific treponemal test (TT) such as TPPA or FTA-ABS. This algorithm is currently endorsed by the U.S. Centers for Disease Control and Prevention (CDC). In addition to screening for syphilis, a titer can be used to track the progress of the disease over time and its response to therapy. The traditional algorithm using an NTT followed by a TT remains the standard in many parts of the world.
In immunology, seroconversion is the development of specific antibodies in the blood serum as a result of infection or immunization, including vaccination. During infection or immunization, antigens enter the blood, and the immune system begins to produce antibodies in response. Before seroconversion, the antigen itself may or may not be detectable, but the antibody is absent. During seroconversion, the antibody is present but not yet detectable. After seroconversion, the antibody is detectable by standard techniques and remains detectable unless the individual seroreverts, in a phenomenon called seroreversion, or loss of antibody detectability, which can occur due to weakening of the immune system or decreasing antibody concentrations over time. Seroconversion refers the production of specific antibodies against specific antigens, meaning that a single infection could cause multiple waves of seroconversion against different antigens. Similarly, a single antigen could cause multiple waves of seroconversion with different classes of antibodies. For example, most antigens prompt seroconversion for the IgM class of antibodies first, and subsequently the IgG class.
Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection, against other foreign proteins, or to one's own proteins. In either case, the procedure is simple.
Pinta is a human skin disease caused by infection with the spirochete Treponema carateum, which is morphologically and serologically indistinguishable from the bacterium that causes syphilis. The disease is endemic to Mexico, Central America, and South America.
Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the endemicum subspecies of the spirochete Treponema pallidum. Bejel is one of the "endemic treponematoses", a group that also includes yaws and pinta. Typically, endemic trepanematoses begin with localized lesions on the skin or mucous membranes. Pinta is limited to affecting the skin, whereas bejel and yaws are considered to be invasive because they can also cause disease in bone and other internal tissues.
Heterophile antibodies are antibodies induced by external antigens.
Neurosyphilis is the infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics, the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurological presentation in early syphilis. Tertiary syphilis symptoms are exclusively neurosyphilis, though neurosyphilis may occur at any stage of infection.
The fluorescent treponemal antibody absorption (FTA-ABS) test is a diagnostic test for syphilis. Using antibodies specific for the Treponema pallidum species, such tests would be assumed to be more specific than non-treponemal testing such as VDRL but have been shown repeatedly to be sensitive but not specific for the diagnosis of neurosyphilis in cerebrospinal fluid (CSF). In addition, FTA-ABS turns positive earlier and remains positive longer than VDRL. Other treponemes, such as T. pertenue, may also produce a positive FTA-ABS. The ABS suffix refers particularly to a processing step used to remove nonspecific antispirochetal antibodies present in normal serum.
β2-glycoprotein 1, also known as beta-2 glycoprotein 1 and Apolipoprotein H (Apo-H), is a 38 kDa multifunctional plasma protein that in humans is encoded by the APOH gene. One of its functions is to bind cardiolipin. When bound, the structure of cardiolipin and β2-GP1 both undergo large changes in structure. Within the structure of Apo-H is a stretch of positively charged amino acids, Lys-Asn-Lys-Glu-Lys-Lys, are involved in phospholipid binding.
Anti-cardiolipin antibodies (ACA) are antibodies often directed against cardiolipin and found in several diseases, including syphilis, antiphospholipid syndrome, livedoid vasculitis, vertebrobasilar insufficiency, Behçet's syndrome, idiopathic spontaneous abortion, and systemic lupus erythematosus (SLE). They are a form of anti-mitochondrial antibody. In SLE, anti-DNA antibodies and anti-cardiolipin antibodies may be present individually or together; the two types of antibodies act independently. This is in contrast to rheumatoid arthritis with systemic sclerosis (scleroderma) because anti-cardiolipin antibodies are present in both conditions, and therefore may tie the two conditions together.
In autoimmune disease, anti-apolipoprotein H (AAHA) antibodies, also called anti-β2 glycoprotein I antibodies, comprise a subset of anti-cardiolipin antibodies and lupus anticoagulant. These antibodies are involved in sclerosis and are strongly associated with thrombotic forms of lupus. As a result, AAHA are strongly implicated in autoimmune deep vein thrombosis.
A nontreponemal test (NTT) is a blood test for diagnosis of infection with syphilis. Nontreponemal tests are an indirect method in that they detect biomarkers that are released during cellular damage that occurs from the syphilis spirochete. In contrast, treponemal tests look for antibodies that are a direct result of the infection thus, anti-treponeme IgG, IgM and to a lesser degree IgA. Nontreponemal tests are screening tests, very rapid and relatively simple, but need to be confirmed by treponemal tests. Centers for Disease Control and Prevention (CDC)-approved standard tests include the VDRL test, the rapid plasma reagin (RPR) test, the unheated serum reagin (USR) test, and the toluidine red unheated serum test (TRUST). These have mostly replaced the first nontreponemal test, the Wassermann test.
The Treponema pallidum particle agglutination assay is an indirect agglutination assay used for detection and titration of antibodies against the causative agent of syphilis, Treponema pallidum subspecies pallidum. It also detects other treponematoses.
The first recorded outbreak of syphilis in Europe occurred in 1494/1495 in Naples, Italy, during a French invasion. Because it was spread by returning French troops, the disease was known as "French disease", and it was not until 1530 that the term "syphilis" was first applied by the Italian physician and poet Girolamo Fracastoro. The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann in 1905 at the Charité Clinic in Berlin. The first effective treatment, Salvarsan, was developed in 1910 by Sahachiro Hata in the laboratory of Paul Ehrlich. It was followed by the introduction of penicillin in 1943.
Meningeal syphilis is a chronic form of syphilis infection that affects the central nervous system. Treponema pallidum, a spirochate bacterium, is the main cause of syphilis, which spreads drastically throughout the body and can infect all its systems if not treated appropriately. Treponema pallidum is the main cause of the onset of meningeal syphilis and other treponemal diseases, and it consists of a cytoplasmic and outer membrane that can cause a diverse array of diseases in the central nervous system and brain.