Nontreponemal
Encyclopedia
Nontreponemal tests refer to a class of syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

 diagnostics that detect infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

 by indirect markers of infection. Nontreponemal Tests detect biomarkers that are released during cellular damage that occurs from the syphilis spirochete. In contrast treponemal tests look for antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 that are a direct result of the infection thus, anti-treponeme IgG, IgM and to a lesser degree IgA

Nontreponemal tests

Syphilitic infection leads to the production of nonspecific antibodies that react to cardiolipin
Cardiolipin
Cardiolipin is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. The only other place that cardiolipin can be found is in the membranes of most bacteria. The name ‘cardiolipin’ is derived from the fact that it was first...

. 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
Flocculation
Flocculation, in the field of chemistry, is a process wherein colloids come out of suspension in the form of floc or flakes by the addition of a clarifying agent. The action differs from precipitation in that, prior to flocculation, colloids are merely suspended in a liquid and not actually...

 type tests that use an antigen-antibody interaction. The complexes remain suspended in solution and therefore visible due to the lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

 based antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

s.

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.

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.

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.

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.
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