Andean paleopathological research has significantly enhanced knowledge about the geographical distribution and evolution of tuberculosis (TB) in pre-Columbian South America. In this paper, we review the history and progress of research on ancient tuberculosis (TB) in the Andean region, focusing on the strengths and limitations of current approaches for the molecular detection of ancient pathogens, with special attention to TB. As a case study, we describe a molecular screening approach for the detection of ancient Mycobacterium tuberculosis in individuals from Late Intermediate Period (1000–1400 CE) contexts at the site of Huari, Peru. We evaluate 34 commingled human vertebrae and combine morphological assessments of pathology with high throughput sequencing and a non-selective approach to ancient pathogen DNA screening. Our method enabled the simultaneous detection of ancient M. tuberculosis DNA and an evaluation of the environmental microbial composition of each sample. Our results show that despite the dominance of environmental DNA, molecular signatures of M. tuberculosis were identified in eight vertebrae, six of which had no observable skeletal pathology classically associated tuberculosis infection. This screening approach will assist in the identification of candidate samples for downstream genomic analyses. The method permits higher resolution disease identification in cases where pathology may be absent, or where the archaeological context may necessitate a broad differential diagnosis based on morphology alone.

安第斯山脉古病理学研究极大地增进了人们对哥伦布前南美洲结核病（TB）地理分布和演变的了解。本文综述了安第斯地区古代结核病（TB）研究的历史和进展，重点介绍了目前用于古代病原体分子检测的方法的优势和局限性，其中特别关注了TB。作为案例研究，我们描述了一种用于检测古代结核分枝杆菌的分子筛选方法在秘鲁Huari站点的中晚期（1000-1400 CE）背景下的个体中。我们评估34混合的人类椎骨，并结合高通量测序和古代病原体DNA筛选的非选择性方法结合病理形态学评估。我们的方法能够同时检测古代结核分枝杆菌的DNA并评估每个样品的环境微生物组成。我们的结果表明，尽管环境DNA占主导地位，但结核分枝杆菌的分子特征在8块椎骨中被发现，其中6块没有可观察到的骨骼病理学经典相关的结核病感染。这种筛选方法将有助于鉴定用于下游基因组分析的候选样品。该方法可以在缺乏病理或考古背景可能需要仅根据形态学进行广泛差异诊断的情况下，对疾病进行更高分辨率的识别。