Nontreponemal tests for syphilis

Last updated
Nontreponemal tests for syphilis
Purposetest for syphilis

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. [1] Centers for Disease Control and Prevention (CDC)-approved standard tests include the VDRL test (a slide test), the rapid plasma reagin (RPR) test (a card test), the unheated serum reagin (USR) test, and the toluidine red unheated serum test (TRUST). [2] These have mostly replaced the first nontreponemal test, the Wassermann test.[ citation needed ]

Nontreponemal tests

Syphilitic infection leads to the production of nonspecific antibodies that react to cardiolipin. This reaction is the foundation of “nontreponemal” assays such as the VDRL (Venereal Disease Research Laboratory) test and Rapid Plasma Reagin (RPR) test. Both these test are flocculation type tests that use an antigen-antibody interaction. The complexes remain suspended in solution and therefore visible due to the lipid based antigens. [3] [4]

All nontreponemal tests measure immunoglobulins G (IgG) and M (IgM) anti-lipid antibodies formed by the host in response both to lipoidal material released from damaged host cells early in infection and to lipid from the cell surfaces of the treponeme itself.[ citation needed ]

These nontreponemal tests are widely used for qualitative syphilis screening. However, their usefulness is limited by decreased sensitivity in early primary syphilis and during late syphilis, when a large number of untreated patients will be negative by these methods.[ citation needed ]

With nontreponemal tests, false-positive reactions can occur for a large number of reasons, the most common of which is other infections, both viral and bacterial. Additionally these tests may show false-negative when the patient's antibody titer is very high due to a hook effect (also called a prozone effect). Because of the issues with false positives, confirmation with a second treponemal test that is specific for T. pallidum antibodies is recommended. [5] [6]

The tests are relatively simple to perform and interpret, and can allow rapid return of results and are very cheap. However, they still require some laboratory equipment (especially the VDRL) and trained personnel to perform and interpret test reactions. [2]

Related Research Articles

<span class="mw-page-title-main">Syphilis</span> Sexually transmitted infection

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.

<span class="mw-page-title-main">Oligoclonal band</span> Marker in blood/cerebrospinal fluid testing

Oligoclonal bands (OCBs) are bands of immunoglobulins that are seen when a patient's blood serum, or cerebrospinal fluid (CSF) is analyzed. They are used in the diagnosis of various neurological and blood diseases. Oligoclonal bands are present in the CSF of more than 95% of patients with clinically definite multiple sclerosis.

<span class="mw-page-title-main">Wassermann test</span> Antibody test for syphilis

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.

<span class="mw-page-title-main">Rapid plasma reagin</span> Test for syphilis

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.

<span class="mw-page-title-main">Venereal Disease Research Laboratory test</span> 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, whereas other, more specific tests are used to diagnose the disease.

<span class="mw-page-title-main">Seroconversion</span> Development of specific antibodies in the blood serum as a result of infection or immunization

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.

The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.

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.

<span class="mw-page-title-main">Nonvenereal endemic syphilis</span> Medical condition

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.

<span class="mw-page-title-main">Neurosyphilis</span> Infection of the central nervous system in a patient with syphilis

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.

Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs. AIHA is a relatively rare condition, with an incidence of 5–10 cases per 1 million persons per year in the warm-antibody type and 0.45 to 1.9 cases per 1 million persons per year in the cold antibody type. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus.

Paroxysmal cold hemoglobinuria (PCH) or Donath–Landsteiner hemolytic anemia (DLHA) is an autoimmune hemolytic anemia featured by complement-mediated intravascular hemolysis after cold exposure. It can present as an acute non-recurrent postinfectious event in children, or chronic relapsing episodes in adults with hematological malignancies or tertiary syphilis. Described by Julius Donath (1870–1950) and Karl Landsteiner (1868–1943) in 1904, PCH is one of the first clinical entities recognized as an autoimmune disorder.

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.

<span class="mw-page-title-main">Anti-cardiolipin antibodies</span> Type of autoantibody

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.

<span class="mw-page-title-main">Heterophile antibody test</span> Diagnosistic test for infectious mononucleosis

The mononuclear spot test or monospot test, a form of the heterophile antibody test, is a rapid test for infectious mononucleosis due to Epstein–Barr virus (EBV). It is an improvement on the Paul–Bunnell test. The test is specific for heterophile antibodies produced by the human immune system in response to EBV infection. Commercially available test kits are 70–92% sensitive and 96–100% specific, with a lower sensitivity in the first two weeks after clinical symptoms begin.

<i>Treponema pallidum</i> particle agglutination assay Assay used for detection and titration of antibodies against the causative agent of syphilis

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.

<span class="mw-page-title-main">Meningeal syphilis</span> Medical condition

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.

<span class="mw-page-title-main">COVID-19 testing</span> Diagnostic testing for SARS-CoV-2 virus infection

COVID-19 testing involves analyzing samples to assess the current or past presence of SARS-CoV-2. The two main types of tests detect either the presence of the virus or antibodies produced in response to infection. Molecular tests for viral presence through its molecular components are used to diagnose individual cases and to allow public health authorities to trace and contain outbreaks. Antibody tests instead show whether someone once had the disease. They are less useful for diagnosing current infections because antibodies may not develop for weeks after infection. It is used to assess disease prevalence, which aids the estimation of the infection fatality rate.

Viral disease testing is the use of a variety of testing techniques for a variety of purposes, including diagnosing conditions, assessing immunity and understanding disease prevalence. The primary approaches include DNA/RNA tests, serological tests and antigen tests.

References

  1. Ratnam, S (2005). "The laboratory diagnosis of syphilis". Canadian Journal of Infectious Diseases & Medical Microbiology . 16 (1): 45–51. doi: 10.1155/2005/597580 . PMC   2095002 . PMID   18159528.
  2. 1 2 Larsen SA, Pope V, Johnson RE, Kennedy EJ Jr (1998). A Aanual of Tests for Syphilis (9th ed.). Washington, DC: American Public Health Association. ISBN   978-0875532349.
  3. Zhu, L.; Gu, X.; Peng, R.-R.; Wang, C.; Gao, Z.; Zhou, P.; Gao, Y.; Shi, M.; Guan, Z.; Sena, A. C. (2013). "Comparison of the Cerebrospinal Fluid (CSF) Toluidine Red Unheated Serum Test and the CSF Rapid Plasma Reagin Test with the CSF Venereal Disease Research Laboratory Test for Diagnosis of Neurosyphilis among HIV-Negative Syphilis Patients in China". Journal of Clinical Microbiology. 52 (3): 736–740. doi:10.1128/JCM.02522-13. PMC   3957747 . PMID   24335955.
  4. Nayak, Surajit; Acharjya, Basanti (2012). "VDRL test and its interpretation". Indian Journal of Dermatology. 57 (1): 3–8. doi: 10.4103/0019-5154.92666 . PMC   3312652 . PMID   22470199.
  5. Miller, JN (1975). "Value and limitations of nontreponemal and treponemal tests in the laboratory diagnosis of syphilis". Clinical Obstetrics and Gynecology. 18 (1): 191–203. doi:10.1097/00003081-197503000-00017. PMID   1091384.
  6. Morshed, MG (2014). "Current Trend on Syphilis Diagnosis: Issues and Challenges". Infectious Diseases and Nanomedicine II. Advances in Experimental Medicine and Biology. Vol. 808. pp. 51–64. doi:10.1007/978-81-322-1774-9_5. ISBN   978-81-322-1773-2. PMID   24595610.