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As one of the oldest known human diseases, leprosy or Hansen's disease remains a public health concern around the world with over 200 000 new cases in 2018. Most human leprosy cases are caused by Mycobacterium leprae , but a small number of cases are now known to be caused by Mycobacterium lepromatosis , a sister taxon of M. leprae . The global pattern of genomic variation in M. leprae is not well defined. Particularly, in the Pacific Islands, the origins of leprosy are disputed. Historically, it has been argued that leprosy arrived on the islands during nineteenth century colonialism, but some oral traditions and palaeopathological evidence suggest an older introduction. To address this, as well as investigate patterns of pathogen exchange across the Pacific Islands, we extracted DNA from 39 formalin-fixed paraffin-embedded biopsy blocks dating to 1992–2016. Using whole-genome enrichment and next-generation sequencing, we produced nine M. leprae genomes dating to 1998–2015 and ranging from 4-63× depth of coverage. Phylogenetic analyses indicate that these strains belong to basal lineages within the M. leprae phylogeny, specifically falling in branches 0 and 5. The phylogeographical patterning and evolutionary dating analysis of these strains support a pre-modern introduction of M. leprae into the Pacific Islands. This article is part of the theme issue ‘Insights into health and disease from ancient biomolecules’.

The Neolithic of southwest Asia, 11,600–7500 years ago, charts the earliest establishment of permanent settlements and changes in food procurement and community structure that transformed human lifeways. Our understanding of the social behaviors that impacted these shifting connections to place and group membership can be improved by studying how people moved across landscapes. Parts of southwest Asia have shown contrasting evidence for mobility practices, but little is known from the Northern Levant, a region key to the development and transmission of agriculture and settled life, particularly for the latest Neolithic stages. We measured strontium and oxygen isotope values in 71 human teeth from five archeological sites in Syria, spanning the entire Neolithic period. A shift to broadly local communities following the establishment of village life suggests consolidation of group membership and deep connections to particular locales, perhaps aimed at social cohesion. Mobility then increases in the later Neolithic, explaining the high degree of cross-regional connectivity witnessed archeologically. A sex-bias towards female mobility during this period may point towards the formation of patrilocal traditions. At our sites both non-local and local individuals were afforded similar burial treatment, suggesting inclusivity in group membership and mobile individuals connecting to new places in the landscape.

Human sacrifice in Mesoamerican cities was diverse and highly ritualized, and it remains incompletely understood. Knowing who was selected for ritual violence is essential for interpreting specialized mortuary deposits and furthering research on Mexica society. To understand the structure and variability of sacrificial and mortuary practices, we examine here three burial contexts from Tlatelolco, a densely populated city in the heart of the Triple Alliance. The interment contexts of Grupo Norte (n = 52) and Paso a Desnivel (n = 45) had been excavated from within the ceremonial center near the Tlatelolco Templo Mayor, and Atenantitech (n = 40) from a bordering calpulli or neighborhood. To establish which contexts are likely sacrificial deposits, we compare the age-at-death distributions, biological sex, and perimortem ritual trauma across these sites. We seek to understand if social status determined sacrificial inclusion by using metabolic and infectious disease as proxies for resource inequality. We find that the residential deposit approximates an attritional mortality distribution and that ceremonial center deposits primarily comprised non-adults, who also presented with significantly higher rates of metabolic and infectious disease than the non-adults from the residential site. Informed by previous studies and the ethnohistorical literature, we propose that impoverished individuals living on the margins of Mexica society were chosen as sacrificial victims. High prevalence of metabolic and infectious disease comorbidity indicates that these individuals endured long-term nutritional deficiency, apparently vitamin C. Further, variation in age, pathology, and perimortem treatment among ceremonial center deposits reveals the striking diversity of ritualized killings in a prominent Mexica city.   El sacrificio en mesoamérica fue en extremo diverso, con muy diferentes y complejos rituales, saber quién y porqué fue seleccionado, para ser consagrados en un lugar específico es fundamental para interpretar los depósitos mortuorios y avanzar en la investigación sobre la sociedad mexica. Para comprender la estructura y variabilidad de las prácticas mortuorias, examinamos tres contextos de entierros de Tlatelolco, una ciudad densamente poblada localizada en el corazón de la Triple Alianza. Los contextos de entierro de Grupo Norte (n = 52) y Paso a Desnivel (n = 45) habían sido excavados dentro del centro ceremonial cerca del Templo Mayor de Tlatelolco, y Atenantitech (n = 40) de un barrio o calpulli limítrofe. Para confirmar y explicar qué contextos son depósitos de sacrificio, comparamos las distribuciones de edad biológica al morir, el sexo y el trauma ritual perimortem en estos restos humanos. Buscamos esclarecer si el estatus social determina la inclusión sacrificatoria mediante el análisis de enfermedades metabólicas e infecciosas como parámetros de una desigualdad de recursos. Encontramos que los individuos del sitio de enterramientos residencial se aproxima a una distribución de mortalidad por deterioro físico y que los depósitos de restos humanos del centro ceremonial estaban compuestos principalmente por sujetos no adultos que a su vez presentan tasas significativamente más altas de enfermedades metabólicas e infecciosas que los no adultos del sitio residencial. Con base en estudios previos y la literatura etnohistórica, proponemos que algunos individuos con una calidad de vida menoscabada que vivían en los márgenes de la sociedad mexica, fueron elegidos como víctimas de sacrificio. La alta prevalencia de comorbilidad de enfermedades metabólicas e infecciosas indica que estas personas soportaron durante un largo plazo padecieron deficiencias nutricionales, aparentemente de vitamina C. Además, la variación entre la edad, la patología y el tratamiento perimortem entre los individuos de los depósitos mortuorios del centro ceremonial revela una sorprendente diversidad de rituales sacrificiales en una ciudad mexica prominente.

Background: Access to sample-level metadata is important when selecting public metagenomic sequencing datasets for reuse in new biological analyses. The Standards, Precautions, and Advances in Ancient Metagenomics community (SPAAM, https://spaam-community.github.io) has previously published AncientMetagenomeDir, a collection of curated and standardised sample metadata tables for metagenomic and microbial genome datasets generated from ancient samples. However, while sample-level information is useful for identifying relevant samples for inclusion in new projects, Next Generation Sequencing (NGS) library construction and sequencing metadata are also essential for appropriately reprocessing ancient metagenomic data. Currently, recovering information for downloading and preparing such data is difficult when laboratory and bioinformatic metadata is heterogeneously recorded in prose-based publications. Methods: Through a series of community-based hackathon events, AncientMetagenomeDir was updated to provide standardised library-level metadata of existing and new ancient metagenomic samples. In tandem, the companion tool 'AMDirT' was developed to facilitate automated metadata curation and data validation, as well as rapid data filtering and downloading.  Results: AncientMetagenomeDir was extended to include standardised metadata of over 5000 ancient metagenomic libraries. The companion tool 'AMDiRT' provides both graphical- and command-line interface based access to such metadata for users from a wide range of computational backgrounds. We also report on errors with metadata reporting that appear to commonly occur during data upload and provide suggestions on how to improve the quality of data sharing by the community. Conclusions: Together, both standardised metadata and tooling will help towards easier incorporation and reuse of public ancient metagenomic datasets into future analyses.

Tuberculosis (TB) is a deadly disease that infects millions of people annually. TB has a global distribution and remains a significant cause of mortality, despite decades of eradication campaigns and antibiotic development. TB is caused by genetically similar pathogens in the Mycobacterium tuberculosis complex (MTBC), and human infections are generally caused by human-associated strains, although humans can contract animal-associated strains. Skeletal evidence of TB on archaeological human skeletal remains and evolutionary dating of MTBC genomes reveal that TB has afflicted humans for approximately 6,000 years. Previous research has shown that MTBC pathogens were introduced into the Americas through a zoonotic transmission from seals and sea lions along the coasts of South America by at least 1000 CE.Characterizing the introduction and enigmatic intercontinental spread of a successful zoonotic transmission over hundreds of years provides valuable insight into the potential of zoonotic MTBC infections. Through the recovery and phylogenomic analysis of the first ancient MTBC genomes (n = 2) from pre-contact North America, I establish that there were multiple contemporaneous MTBC lineages circulating in human populations in the Americas. The high genomic diversity and deep divergence of strains from Mesoamerica suggest that TB was endemic in the region. To reveal the impact of TB within a Mesoamerican city, I examined human skeletons (n = 137) for evidence of disease from sacrificial and natural mortality burial contexts within Tlatelolco, a ceremonial precinct and interregional marketplace at the heart of the Aztec Empire (1300-1521 CE). I found that TB disproportionately affected sacrificial victims, who also exhibited evidence of food insecurity and resource inequality. These results mirror the socioeconomic patterns of TB distribution today. Further, I sampled broadly from sacrificial victims with skeletal evidence of TB not only for biomolecular confirmation of MTBC but also to uncover associations between skeletal TB manifestation and ability to recover ancient MTBC DNA. I identify 10 additional cases of MTBC at Tlatelolco and link ancient MTBC DNA recovery to TB skeletal lesion characteristics and age-at-death of the infected individual. Overall, this body of work combines paleogenomic and paleopathological data to highlight the impact of ancient TB zoonoses.

Abstract Background and objectives One Paleopathology is a novel concept in Paleopathology that extends the One Health paradigm into the past. A workshop at the University of Durham, UK, was held prior to the 2024 International Society for Evolution, Medicine, and Public Health (ISEMPH) meeting, firstly to define and expand the concept of One Paleopathology and secondly to generate transdisciplinary research and outreach under this framework. This article presents a logic model to evaluate how effectively the workshop met its goals. Methodology Two surveys were conducted, one immediately following the workshop and at the 1-year mark. These surveys assess the direct outputs from the workshop—tangible research and outreach products—as well as changes in participants’ attitudes toward One Paleopathology and the degree to which transdisciplinarity was incorporated into resulting projects. Results Both the outputs (direct products of the workshop activities) and outcomes (changes in knowledge or attitude because of the activities) of the workshop suggest that the goals are being met. The first goal, to define and expand the concept of One Paleopathology, was met, with participants expressing strong acceptance of the framework. The second goal—generating transdisciplinary research—is reflected in eight ongoing projects initiated at the workshop. Conclusions and implications The workshop structure and outcomes assessment presented here evaluate an initial effort in effecting conceptual change in the social sciences. Participants were enthusiastic about One Paleopathology, and over the following year new collaborations and research agendas aligned with the concept emerged. Importantly, participants reported integrating transdisciplinarity into their long-term research, indicating that the workshop had a sustained impact. Lay Summary This article describes the creation, content, and results of a One Paleopathology workshop held at the University of Durham (UK) in August 2024, prior to the annual meeting of the International Society of Evolutionary Medicine and Public Health (ISEMPH). The workshop goals included extending today’s One Health paradigm to include the past, fostering an appreciation of planetary health—past and present— and forging transdisciplinary relationships to address complex health challenges today. After the workshop, two participant surveys measured the effectiveness of the workshop in meeting these goals. The surveys suggest that researchers have sustained interest in this concept and will continue to extend their health-related research to reflect the integration of humans, animals, and the environment.

Background Access to sample-level metadata is important when selecting public metagenomic sequencing datasets for reuse in new biological analyses. The Standards, Precautions, and Advances in Ancient Metagenomics community (SPAAM, https://spaam-community.org) has previously published AncientMetagenomeDir, a collection of curated and standardised sample metadata tables for metagenomic and microbial genome datasets generated from ancient samples. However, while sample-level information is useful for identifying relevant samples for inclusion in new projects, Next Generation Sequencing (NGS) library construction and sequencing metadata are also essential for appropriately reprocessing ancient metagenomic data. Currently, recovering information for downloading and preparing such data is difficult when laboratory and bioinformatic metadata is heterogeneously recorded in prose-based publications. Methods Through a series of community-based hackathon events, AncientMetagenomeDir was updated to provide standardised library-level metadata of existing and new ancient metagenomic samples. In tandem, the companion tool 'AMDirT' was developed to facilitate rapid data filtering and downloading of ancient metagenomic data, as well as improving automated metadata curation and validation for AncientMetagenomeDir. Results AncientMetagenomeDir was extended to include standardised metadata of over 6000 ancient metagenomic libraries. The companion tool 'AMDirT' provides both graphical- and command-line interface based access to such metadata for users from a wide range of computational backgrounds. We also report on errors with metadata reporting that appear to commonly occur during data upload and provide suggestions on how to improve the quality of data sharing by the community. Conclusions Together, both standardised metadata reporting and tooling will help towards easier incorporation and reuse of public ancient metagenomic datasets into future analyses.

This chapter provides a description of osseous markers of metabolic disturbance experienced by infants and children from two very different types of communities bracketing the second millennium BCE: the urban dwellers at Harappa and rural village dwellers in west central India. Climate, economic, culture, and social changes led to the abandonment of settlements at the end of both of these periods. The chapter characterizes the experience of collapse and resilience in regard to specific health changes for the human populations that chose to remain in these settlements. Archaeological evidence suggests that the Late Jorwe represents a time of significant culture change and subsistence transition. The chapter considers evidence for abnormal porosity in the immature skeletons from Harappa and Inamgaon. The patterning of abnormal porosity and other pathological lesions in immature skeletal remains can suggest the presence of metabolic conditions like scurvy.

•Three live attenuated, recombinant S. Typhi vectors were evaluated as oral vaccines.•The target antigen was pneumococcal surface protein A (PspA) antigen.•IgG and IgA responses were measured using ELISA and ELISPOT assay. Live, attenuated, orally-administered Salmonella strains are excellent vectors for vaccine antigens and are attractive as vaccines based on previous use of S. Typhimurium in animals. A Phase I dose escalation trial was conducted to evaluate the safety and immunogenicity of three newly constructed recombinant attenuated Salmonella enterica serovar Typhi vaccine (RASV) vectors synthesizing Streptococcus pneumoniae surface protein A (PspA). The 3 S. Typhi strains used as vectors to deliver PspA were S. Typhi ISP1820; S. Typhi Ty2 RpoS−; and S. Typhi Ty2 RpoS+. Sixty healthy adults (median age 25.2 years) were enrolled into 4 Arms (total 15 subjects per Arm); within each Arm, subjects were randomized 1:1:1 into 3 Groups of 5. All subjects in the same Group received the same vaccine vector, and all subjects in the same Arm received the same titer of vaccine (107, 108, 109 or 1010CFU). Adverse events, safety, shedding, and IgG and IgA titers against Salmonella outer membrane proteins (OMPs), lipopolysaccharide (LPS) and PspA were evaluated. In the highest dose group, no subject experienced severe reactions or serious adverse events. Most adverse events were mild; one subject had a positive blood culture. No subject shed vaccine in stool. No statistically significant differences for post vaccination ELISA or ELISPOT results between Groups were detected. However, a limited number of ≥4 fold increases from baseline for IgA anti-OMPs, IgA and IgG anti-LPS, and IgA anti-PspA occurred for a few individuals as measured by ELISA, and IgA anti-OMPs as measured by ELISPOT assay. All three S. Typhi vectored pneumococcal vaccines were safe and well-tolerated. Immunogenicity was limited possibly due to pre-existing high antibody titers prior to vaccination. Increases in IgA were most often observed.

Collisions with windows are an important human-related threat to birds in urban landscapes. However, the proximate drivers of collisions are not well understood, and no study has examined spatial variation in mortality in an urban setting. We hypothesized that the number of fatalities at buildings varies with window area and habitat features that influence avian community structure. In 2010 we documented bird-window collisions (BWCs) and characterized avian community structure at 20 buildings in an urban landscape in northwestern Illinois, USA. For each building and season, we conducted 21 daily surveys for carcasses and nine point count surveys to estimate relative abundance, richness, and diversity. Our sampling design was informed by experimentally estimated carcass persistence times and detection probabilities. We used linear and generalized linear mixed models to evaluate how habitat features influenced community structure and how mortality was affected by window area and factors that correlated with community structure. The most-supported model was consistent for all community indices and included effects of season, development, and distance to vegetated lots. BWCs were related positively to window area and negatively to development. We documented mortalities for 16/72 (22%) species (34 total carcasses) recorded at buildings, and BWCs were greater for juveniles than adults. Based on the most-supported model of BWCs, the median number of annual predicted fatalities at study buildings was 3 (range = 0-52). These results suggest that patchily distributed environmental resources and levels of window area in buildings create spatial variation in BWCs within and among urban areas. Current mortality estimates place little emphasis on spatial variation, which precludes a fundamental understanding of the issue. To focus conservation efforts, we illustrate how knowledge of the structural and environmental factors that influence bird-window collisions can be used to predict fatalities in the broader landscape.