Between the years of 1999 and 2001, during the excavation of the Praça da Figueira (Lisbon, Portugal), several human osteological remains from various chronological periods were discovered. Amongst them several skeletons are known to be related with the Hospital Real de Todos-os-Santos (Royal Hospital of All Saints-RHAS), which had an important role. The hospital history begun in 1492 and ended in 1755 largely as a consequence of the Lisbon earthquake. Of the skeletons exhumed, one in particular, the adult female Sk. 1310 showed significant pathological changes. The bone lesions characterized by new bone deposition, with a symmetric and disseminate pattern, were found in the upper limbs, distal end of femurs and in tibia and fibula diaphyses. A bowing deformity with "sabre shape" morphology was also observed in the tibiae. The most striking lesions, characterized by healed nodular cavitations and similar to those of caries sicca, were recorded on the frontal bone. Considering the value of a complete description, as well as the application of multiple lines of enquiry for a reliable differential diagnosis, three distinct techniques were applied and compared: visual examination, imagiology and histology. The results showed that the macroscopic analysis coupled with conventional X-ray analysis were fundamental to obtain a possible diagnosis of acquired syphilis. In contrast, the CT-scan and the histological analyses were less informative. The application of a new scoring system also supports a diagnosis of acquired syphilis. This case-study constitutes the first evidence of syphilis associated with the RHAS, supporting historical data on the pivotal role that this hospital had on the treatment of several conditions, namely, syphilis.

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Syphilis is one of the most exciting diseases explored in paleopathology and, therefore, tracing back its origin and development has provided a prolific debate. The combination of paleopathological data with historical sources, iconography, and archaeological contexts were the primary sources used to reconstruct its historical path. However, there are some limitations to paleopathological diagnosis due to the nature of bone reaction to stimuli. In addition, historical sources are subjected to a bias of social and cultural nature and the knowledge of those who wrote them. Hence, ancient DNA analysis offers the possibility of acquiring proof of cause by identifying pathogens in an organism. We undertook a metagenomic study of a skeleton exhumed from the Royal Hospital of All Saints (Portugal), renowned for treating syphilis from the 16th century onwards. The skeleton had previously been diagnosed with syphilis according to paleopathological analysis. However, the metagenomics analysis showed no presence of the pathogen associated with syphilis (i.e., Treponema pallidum) but revealed pathogenic microorganisms related to respiratory diseases (pneumonia), nonspecific bone infections (osteomyelitis), and oral bacterial pathologies as well as Hansen’s disease (also known as leprosy). The results are exciting and demand a reappraisal of the observed bone changes, recontextualizing their characterization as syphilis related. They prove that past reconstruction of health and disease diagnoses based on assessing human osteological remains of known context (such as a syphilitic hospital) may bias interpretations and, therefore, caution is recommended, not forgetting that the absence of evidence is not evidence of absence (in this case of syphilis) in life.

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