Palaeohistopathology of Treponematosis in Human Bone

Abstract

Treponematosis, comprising yaws, venereal syphilis, bejel, and pinta, has a long history of infection in human populations and continues to have significant global health impacts. As such, skeletal manifestations and pathophysiology of this disease are of interest in palaeopathology and medicine. Histology, the study of microscopic tissue structure, has been applied in paleopathological analyses of treponematosis in an extremely limited manner, mostly in case studies through qualitative descriptions. In this thesis, 65 archaeological individuals are examined for qualitative (histomorphology) and quantitative (histomorphometry) histology to evaluate microscopic effects of treponematosis on bone. The tibia, a bone commonly manifesting treponematosis lesions, was sampled in adult Pacific islander skeletal remains recovered from Taumako, Solomon Islands (~440-150ybp), a region of ancient and ongoing treponemal endemicity. A unique case of the frontal bone exhibiting an advanced diagnostic lesion of treponematosis - caries sicca - is also examined for histological changes using skeletal remains from a different Pacific site in Tonga, 'Atele (~460ybp). Histology sections were produced following methods appropriate for archaeological bone and examined using optical microscopy under transmitted and polarised light in individuals with no macroscopically visible pathology (n=40) and those showing lesions associated with treponematosis (n=25). Histomorphological features identified in this study, including grenzstreifen, polsters and agate bone, were compared to published cases, and their diagnostic value was evaluated. Histomorphometric variables included bone vascularity and vascular canal area measuring localised bone blood supply. Univariate and multivariate statistical analyses were conducted to compare the two groups of individuals. The histomorphological features identified in this thesis were found to be diagnostically associated with treponematosis. Analyses of histomorphometric data found that bone samples from individuals diagnosed with treponematosis, but not in those without pathology, were poorly vascularised (p<0.001) and had higher porosity (p<0.001) alongside an abnormal cortical bone transition into trabecular structure. Multivariate analyses using discriminant functions revealed that individuals with no pathology and those with advanced microstructural changes can be clearly separated based on their quantitative histology. Examination of the caries sicca lesion observed three distinct morphological regions indicating complex cell building (osteoblastic) activity and resorptive (osteoclastic) features occurring within the lesion. The morphological results indicate that features such as grenzstreifen, polsters and agate bone may more aptly indicate slow progressing infectious disease processes, reflecting the biological reaction of bone to chronic infections, including treponematosis, rather than specific pathological conditions as has been previously suggested. For the first time, the quantitative results suggest that bone produced as a response to long term treponemal infection is poorly vascularised, porous, and experiences changes that have detrimental quality effects on bone microarchitecture whereby cortical structure transitions into trabeculae-like spicules. Multivariate functions were also found to have potential application as a diagnostic tool in palaeopathology. Finally, it was discovered that caries sicca lesions may form through a complex interplay and imbalance of osteoblastic and osteoclastic activity. This thesis contributes new knowledge about bone histological responses in treponematosis and advocates for incorporating histology in the paleopathological toolkit to improve the existing interpretations of past human experiences of infectious disease. Show more