7000 year-old tuberculosis cases from Hungary - Osteological and biomolecular evidence.

This study derives from the macroscopic analysis of a Late Neolithic population from Hungary. Remains were recovered from a tell settlement at Hódmezovásárhely-Gorzsa from graves within the settlement as well as pits, ditches, houses and as stray finds. One of the most important discoveries from these remains was evidence of tuberculosis. Pathological analysis of the seventy-one individuals revealed numerous cases of infections and non-specific stress indicators on juveniles and adults, metabolic diseases on juveniles, and evidence of trauma and mechanical changes on adults. Several cases showed potential signs of tuberculosis and further analyses were undertaken, including biomolecular studies. The five individuals were all very young adults and included a striking case of Hypertrophic Pulmonary Osteopathy (HPO) with rib changes, one case with resorptive lesions on the vertebrae, two cases with hypervascularisation on the vertebrae and periosteal remodelling on the ribs, and one case with abnormal blood vessel impressions and a possible lesion on the endocranial surface of the skull. The initial macroscopic diagnosis of these five cases was confirmed by lipid biomarker analyses, and three of them were corroborated by DNA analysis. At present, these 7000-year-old individuals are among the oldest palaeopathological and palaeomicrobiological cases of tuberculosis worldwide.

Detection and molecular characterization of 9,000-year-old Mycobacterium tuberculosis from a Neolithic settlement in the Eastern Mediterranean.

BACKGROUND: Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis. It has no environmental reservoir and is believed to have co-evolved with its host over millennia. This is supported by skeletal evidence of the disease in early humans, and inferred from M. tuberculosis genomic analysis. Direct examination of ancient human remains for M. tuberculosis biomarkers should aid our understanding of the nature of prehistoric tuberculosis and the host/pathogen relationship. METHODOLOGY/PRINCIPAL FINDINGS: We used conventional PCR to examine bone samples with typical tuberculosis lesions from a woman and infant, who were buried together in the now submerged site of Atlit-Yam in the Eastern Mediterranean, dating from 9,250-8,160 years ago. Rigorous precautions were taken to prevent contamination, and independent centers were used to confirm authenticity of findings. DNA from five M tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex. CONCLUSIONS/SIGNIFICANCE: Human tuberculosis was confirmed by morphological and molecular methods in a population living in one of the first villages with evidence of agriculture and animal domestication. The widespread use of animals was not a source of infection but may have supported a denser human population that facilitated transmission of the tubercle bacillus. The similarity of the M. tuberculosis genetic signature with those of today gives support to the theory of a long-term co-existence of host and pathogen.