A nontreponemal test (NTT) is a

blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...

for diagnosis of infection with

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...

. Nontreponemal tests are an indirect method in that they detect

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

s that are released during cellular damage that occurs from the syphilis

spirochete A spirochaete () or spirochete is a member of the phylum Spirochaetota (also called Spirochaetes ), which contains distinctive diderm (double-membrane) Gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or ...

. In contrast, treponemal tests look for

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

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 (a slide test), the

rapid plasma reagin The rapid plasma reagin test (RPR test or RPR titer) 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 ...

(RPR) test (a card 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 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 nontrepon ...

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Nontreponemal tests

Syphilitic infection leads to the production of nonspecific antibodies that react to

cardiolipin Cardiolipin (IUPAC name 1,3-bis(''sn''-3’-phosphatidyl)-''sn''-glycerol, "''sn''" designating stereospecific numbering) is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. ...

. This reaction is the foundation of “nontreponemal” assays such as the VDRL ( Venereal Disease Research Laboratory) test and

Rapid Plasma Reagin The rapid plasma reagin test (RPR test or RPR titer) 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 ...

(RPR) test. Both these test are

flocculation In colloidal chemistry, flocculation is a process by which colloidal particles come out of Suspension (chemistry), suspension to sediment in the form of floc or flake, either spontaneously or due to the addition of a clarifying agent. The actio ...

type tests that use an

antigen-antibody interaction Antigen-antibody interaction, or antigen-antibody reaction, is a specific chemical interaction between antibodies produced by B cells of the white blood cells and antigens during immune reaction. The antigens and antibodies combine by a process ca ...

. The complexes remain suspended in solution and therefore visible due to the

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

based

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s. All nontreponemal tests measure

immunoglobulin An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

s 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 The hook effect refers to the prozone phenomenon, also known as antibody excess, or the postzone phenomenon, also known as antigen excess. It is an immunologic phenomenon whereby the effectiveness of antibodies to form immune complexes can be impa ...

(also called a prozone effect). Because of the issues with false positives, confirmation with a second treponemal test that is specific for ''

Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a Microaerophile, microaerophilic, Gram-negative bacteria, gram-negative, spirochaete bacterium with subspecies that cause the diseases syphilis, bejel (also known as endemic ...

'' 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.

References

{{Reflist Sexually transmitted diseases and infections Immunologic tests