BackgroundSince the first recorded epidemic of syphilis in 1495, controversy has surrounded the origins of the bacterium Treponema pallidum subsp. pallidum and its relationship to the pathogens responsible for the other treponemal diseases: yaws, endemic syphilis, and pinta. Some researchers have argued that the syphilis-causing bacterium, or its progenitor, was brought from the New World to Europe by Christopher Columbus and his men, while others maintain that the treponematoses, including syphilis, have a much longer history on the European continent.Methodology/Principal FindingsWe applied phylogenetics to this problem, using data from 21 genetic regions examined in 26 geographically disparate strains of pathogenic Treponema. Of all the strains examined, the venereal syphilis-causing strains originated most recently and were more closely related to yaws-causing strains from South America than to other non-venereal strains. Old World yaws-causing strains occupied a basal position on the tree, indicating that they arose first in human history, and a simian strain of T. pallidum was found to be indistinguishable from them.Conclusions/SignificanceOur results lend support to the Columbian theory of syphilis's origin while suggesting that the non-sexually transmitted subspecies arose earlier in the Old World. This study represents the first attempt to address the problem of the origin of syphilis using molecular genetics, as well as the first source of information regarding the genetic make-up of non-venereal strains from the Western hemisphere.

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We report on a case of gastric syphilis in a patient with chronic dyspepsia. The diagnosis was established by serology and the demonstration of spirochetes in diffusely inflammed gastric mucosa by staining with a fluorescent monoclonal antibody specific for pathogenic treponemes and by the detection of specific treponemal DNA sequences by a real-time PCR. CASE REPORTA 35-year-old man with dyspepsia of long duration was subjected to gastric endoscopy on two occasions in January and February 2005 at a private clinic in Portugal. He was found to have multiple, nonhealing, gastric ulcers that failed to respond to proton pump inhibitor therapy. A workup for Helicobacter pylori infection was negative, and no antibiotic therapy was prescribed. Subsequently, a diffuse gastric mucosal thickening was observed, raising suspicion for a neoplastic process. Eventually, a distal gastrectomy was performed on the patient at the University Hospital of Coimbra in Coimbra, Portugal. The antral mucosa appeared to be erythematous and edematous, with irregular nodular masses. The gastric body mucosa, however, had a normal appearance. Numerous lymph nodes were isolated from both curvatures of the stomach, as well as from the hepatic and celiac chains, for histopathologic examination. The resected gall bladder was unremarkable, and no stones were found.No evidence of neoplasia but, rather, a diffuse destructive inflammatory gastritis was found. Notably, no parasites, viral inclusions, or H. pylori was found on initial microscopic evaluation. Paraffin-embedded material and tissue sections were sent to the Gastrointestinal Pathology Service of the Massachusetts General Hospital for evaluation. The examination confirmed the presence of a dense diffuse mucosal lymphoplasmacytic infiltrate with only scattered residual glandular elements and intraluminal abscesses (Fig. 1). An ill-defined granulomatous process was also noted. Although the inflammation was primarily mucosal, some inflammation spilled over into the superficial submucosa, where a perivascular distribution of the lymphohistiocytic and plasma cellrich infiltrate raised the possibility of gastric syphilis. On the basis of this information, the patient was subsequently investigated and was found to be human immunodeficiency virus (HIV) negative; but serologic testing revealed a reactive polyclonal hypergammaglobulinemia, a positive Venereal Disease Research Laboratory blood test titer of 1:16, and a Treponema pallidum hemagglutination assay value of 1:1,028. Despite a noncontributory Warthin-Starry staining result, gastric syphilis was strongly considered; and the paraffin-embedded thin sections of resected tissue were forwarded to the Laboratory Reference and Research Branch, Division of STD Prevention, Centers for Disease Control and Prevention (CDC) in Atlanta, Ga., for direct fluorescent-antibody staining for pathogenic treponeme detection and PCR for treponemal DNA detection. At the CDC, formalin-fixed thin sections (thickness, 10 m) were deparaffinized by standard procedures a...