Improved understanding of the differential diagnosis of endemic treponematoses is needed to inform clinical practice and to ensure the best outcome for a new global initiative for the eradication of yaws, bejel, and pinta.Traditionally, the human treponematoses have been differentiated based upon their clinical manifestations and epidemiologic characteristics because the etiologic agents are indistinguishable in the laboratory.Serological tests are still considered standard laboratory methods for the diagnosis of endemic treponematoses and new rapid point-of-care treponemal tests have become available which are extremely useful in lowresource settings.In the past ten years, there has been an increasing effort to apply polymerase chain reaction to treponematoses and whole genome fingerprinting techniques have identified genetic signatures that can differentiate the existing treponemal strains; however, definitive diagnosis is also hampered by widespread unavailability of molecular diagnostics.We review the dilemmas in the diagnosis of endemic treponematoses, and advances in the discovery of new diagnostic tools. MethodsReferences for this review were identified through searches of PubMed and WHO databases from January 1, 1905 to January 1, 2013, by use of terms ''yaws,'' ''pian,'' ''bejel,'' ''pinta,'' ''carate,'' ''endemic Treponematoses,'' and ''Treponema pallidum.''Many articles were identified through searches in the authors' personal files.Articles resulting from these searches and relevant references cited in those articles were reviewed.Articles published in English, French, Spanish, and Portuguese were included.
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