Weil-Felix test
Encyclopedia
The Weil-Felix test is an agglutination test for the diagnosis of rickettsial infections. It was first described in 1916. By virtue of its long history and of its simplicity, it has been one of the most widely employed tests for rickettsia
on a global scale, despite being superseded in many settings by more sensitive and specific diagnostic tests.
spp. and certain serotypes of non-motile Proteus
spp., a phenomenon first published by Edmund Weil and Arthur Felix
in 1916. The serum of patients diagnosed with epidemic typhus was found to agglutinate in the presence of bacteria now known as Proteus vulgaris
. Ensuing work elucidated that it was in fact the somatic (O) antigen that cross-reacted with anti-rickettsial antibodies, and furthermore, that different Proteus O antigens would cross-react with different species of Rickettsia.
Typhus group rickettsiae (Rickettsia prowazekii
, R. typhi
) react with P. vulgaris OX19, and scrub typhus (Orientia tsutsugamushi
) reacts with P. mirabilis
OXK. The spotted fever
group rickettsiae (R. rickettsii
, R. africae
, R. japonica
, etc.) react with P. vulgaris OX2 and OX19, to varying degrees, depending on the species.
The Weil-Felix test suffers from poor sensitivity and specificity
, with a recent study showing an overall sensitivity as low as 33% and specificity of 46%. Other studies have had similar findings. As a result, it has largely been supplanted by other methods of serology, including indirect immunofluorescence
antibody
(IFA) testing, which is the gold standard
. However, in resource-limited settings, it still remains an important tool in the diagnosis and identification of public health
concerns, such as outbreaks of epidemic typhus.
saline as a diluent, a series of tubes containing twofold dilutions of patient serum are made with a final volume of 1 mL. A drop of antigen suspension is added to each tube, and the mixture is incubated at 50-55 °C for 4-6 hours. A positive tube would show visible flocculation or granulation, which is accentuated when the tube is gently agitated. The titre corresponds to the most dilute tube in the series that still shows positivity. Generally, a titre of ≥1:320 is considered diagnostic.
Rickettsia
Rickettsia is a genus of non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci , rods or thread-like . Being obligate intracellular parasites, the Rickettsia survival depends on entry, growth, and replication within the cytoplasm of eukaryotic host cells...
on a global scale, despite being superseded in many settings by more sensitive and specific diagnostic tests.
History and Basis for Test
The basis of the test is the presence of antigenic cross-reactivity between RickettsiaRickettsia
Rickettsia is a genus of non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci , rods or thread-like . Being obligate intracellular parasites, the Rickettsia survival depends on entry, growth, and replication within the cytoplasm of eukaryotic host cells...
spp. and certain serotypes of non-motile Proteus
Proteus
In Greek mythology, Proteus is an early sea-god, one of several deities whom Homer calls the "Old Man of the Sea", whose name suggests the "first" , as protogonos is the "primordial" or the "firstborn". He became the son of Poseidon in the Olympian theogony In Greek mythology, Proteus (Πρωτεύς)...
spp., a phenomenon first published by Edmund Weil and Arthur Felix
Arthur Felix
Arthur Felix, FRS was a Polish bacteriologist and serologist.Arthur Felix was the son of Theodor Felix, who had a interest in printed textiles and who encouraged his son to study textile dye chemistry. Felix studied chemistry in Vienna and was awarded a D.Sc...
in 1916. The serum of patients diagnosed with epidemic typhus was found to agglutinate in the presence of bacteria now known as Proteus vulgaris
Proteus vulgaris
Proteus vulgaris is a rod-shaped, Gram negative bacterium that inhabits the intestinal tracts of humans and animals. It can be found in soil, water and fecal matter. It is grouped with the enterobacteriaceae and is an opportunistic pathogen of humans...
. Ensuing work elucidated that it was in fact the somatic (O) antigen that cross-reacted with anti-rickettsial antibodies, and furthermore, that different Proteus O antigens would cross-react with different species of Rickettsia.
Typhus group rickettsiae (Rickettsia prowazekii
Rickettsia prowazekii
Rickettsia prowazekii is a species of gram negative, Alpha Proteobacteria, obligate intracellular parasitic, aerobic bacteria that is the etiologic agent of epidemic typhus, transmitted in the feces of lice. In North America, the main reservoir for R. prowazekii is the flying squirrel. R...
, R. typhi
Rickettsia typhi
Rickettsia typhi is a species of the genus Rickettsia.It is the causative agent of Murine typhus.The genome is similar to that of Rickettsia prowazekii.-References:...
) react with P. vulgaris OX19, and scrub typhus (Orientia tsutsugamushi
Orientia tsutsugamushi
Orientia tsutsugamushi is the causative organism of scrub typhus, and the natural vector and reservoir is probably trombiculid mites ....
) reacts with P. mirabilis
P. mirabilis
P. mirabilis may refer to:* Pisaura mirabilis, a spider species* Proteus mirabilis, a Gram-negative, facultatively anaerobic bacterium species...
OXK. The spotted fever
Spotted fever
A spotted fever is a type of tick-borne disease which presents on the skin.Types include:* Mediterranean spotted fever* Rocky Mountain spotted fever* Queensland tick typhus...
group rickettsiae (R. rickettsii
Rickettsia rickettsii
Rickettsia rickettsii is a unicellular, gram-negative coccobacillus that is native to the New World. It belongs to the spotted fever group of Rickettsia and is most commonly known as the causative agent of Rocky Mountain spotted fever . By nature, R...
, R. africae
Rickettsia africae
Rickettsia africae is a species of Rickettsia.It can cause African tick-bite fever....
, R. japonica
Rickettsia japonica
Rickettsia japonica is a species of Rickettsia.It can cause Japanese spotted fever....
, etc.) react with P. vulgaris OX2 and OX19, to varying degrees, depending on the species.
The Weil-Felix test suffers from poor sensitivity and specificity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
, with a recent study showing an overall sensitivity as low as 33% and specificity of 46%. Other studies have had similar findings. As a result, it has largely been supplanted by other methods of serology, including indirect immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
antibody
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...
(IFA) testing, which is the gold standard
Gold standard
The gold standard is a monetary system in which the standard economic unit of account is a fixed mass of gold. There are distinct kinds of gold standard...
. However, in resource-limited settings, it still remains an important tool in the diagnosis and identification of public health
Public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population health...
concerns, such as outbreaks of epidemic typhus.
Procedure
The Weil-Felix Test can be done as either a slide or a tube test. The antigens necessary (OX2, OX19, and OXK) can be obtained commercially.Slide Method
On a solid surface (glass slide, tile, card), a small amount (50-100 μL) of the patient’s serum is placed. A single drop of the desired antigen is added, and the resulting suspension is mixed and then rotated for one minute. Visible agglutination is indicative of a positive result, and corresponds roughly to a titre of 1:20. Positive results can be further titrated using the tube method, which is more labour-intensive.Tube Method
Using 0.25% phenolPhenol
Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...
saline as a diluent, a series of tubes containing twofold dilutions of patient serum are made with a final volume of 1 mL. A drop of antigen suspension is added to each tube, and the mixture is incubated at 50-55 °C for 4-6 hours. A positive tube would show visible flocculation or granulation, which is accentuated when the tube is gently agitated. The titre corresponds to the most dilute tube in the series that still shows positivity. Generally, a titre of ≥1:320 is considered diagnostic.