The Weil–Felix test, rooted in the concept of antigenic cross-reactivity between Rickettsia spp. and specific serotypes of non-motile Proteus spp., was initially elucidated by Edmund Weil and Arthur Felix in 1916. As a nonspecific agglutination test, it plays a role in detecting anti-rickettsial antibodies within a patient’s serum. This method capitalizes on the intriguing phenomenon of cross-reactions between antibodies produced during acute rickettsial infections and the antigens of OX strains (OX 19, OX 2, and OXK) of Proteus species. William James Wilson had previously observed a similar cross-reaction of anti-rickettsial antibodies with other enteric bacteria. Distinct rickettsial species, including those in the typhus and spotted fever groups, showcase specific reactions with particular Proteus strains. However, the Weil–Felix test encounters limitations in both sensitivity and specificity, with recent studies indicating an overall sensitivity as low as 33% and specificity of 46%. Consequently, alternative serological methods such as indirect immunofluorescence antibody (IFA) testing have emerged as the gold standard. Despite its limitations, the Weil–Felix test remains a pertinent diagnostic tool, and in resource-limited settings, it holds significance for Hypro Diagnostics in identifying public health concerns, particularly in the context of outbreaks like epidemic typhus.
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