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Archaeological human remains with confirmed biomolecular evidence for Brucella species

Archaeological human remains with confirmed biomolecular evidence for Brucella species

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Today, brucellosis is the most common global bacterial zoonosis, bringing with it a range of significant health and economic consequences, yet it is rarely identified from the archaeological record. Detection and understanding of past zoonoses could be improved by triangulating evidence and proxies generated through different approaches. The comple...

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... of confirmed Brucella species retrieved from archaeological remains are limited (Table 4). ...
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... genomic DNA from two human skeletons from medieval Butrint, Albania (Table 4). The PCR targets used were the multi-copy element IS711 (formerly known as IS6510) ( Ouahrani et al., 1993) and DNA coding for the 31kDa membrane protein Bcsp31. ...
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... authors were careful to apply tuberculosis PCR methods which would detect similarly degraded templates (62-65 bp) so that this mycobacterial pathogen should also have been detected in bone extracts, if present. also used a high-throughput approach (metagenomic shotgun sequencing) to study DNA extracted and amplified from a calcified abdominal nodule present in an adult male burial from Geridu, Sardinia (Table 4). The remains displayed lesions of DISH (diffuse idiopathic skeletal hyperostosis) but were without obvious morphological evidence of brucellosis other than the presence of multiple calcified nodules, which have sometimes been associated with chronic brucellosis, amongst other pathologies ( Arcomano et al., 1977;Sevilla-López et al., 2011). ...
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... et al., 2008) but in only one instance has any evidence of Brucella DNA been detected. This observation was made in an adult female from Tyva, south Siberia (Table 4), where evidence of Mycobacterium bovis had already been found in specimens taken from lumbar vertebrae (L3/L4) displaying the classic spinal lesions of tuberculosis ( Murphy et al., 2009). The identification of Brucella DNA was a late observation made after the completion of the main aDNA analyses which had focused on the typing of M. bovis isolates retrieved from four burials of nomadic pastoralists. ...
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... 2. Routes of infection of Brucella spp. that result in skeletal lesions in domestic animals Table 3. Published zooarchaeological remains for which brucellosis is considered in the differential diagnosis or as a possible cause. Table 4. Archaeological human remains with confirmed biomolecular evidence for Brucella species Figure 1. ...
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... and tackling zoonoses: (A) the 'epidemiological triad' summarising factors influencing infectious disease (characteristics after Johnson-Walker and Kaneene 2018); (B) the integrative biocultural model (after McElroy 1990); (C) conceptualisation of One Health interventions; (D) key recoverable datasets for One Health investigations of past zoonoses. Medieval Butrint, Albania, 10 th to 13 th centuries AD Both osteological and molecular methods were applied to skeletal remains with macroscopic possible brucellar lesions (see Table 4). In this case the diagnosis is definitive; Brucella spp. ...

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... One Health has been defined by the World Health Organisation as an integrated, unifying approach to balance and optimize the health of people, animals and ecosystems (WHO, 2022). Past research into deep-time perspectives on One Health has sometimes focused on specific infectious diseases, such as brucellosis or leprosy (Bendrey et al., 2020;Urban et al., 2021), while others have attempted a broad theoretical overview of how zoonoses and environment might have interacted from a One Health perspective in past era (Kim and Agarwal, 2023;Rayfield et al., 2023). The study of health and disease in past populations is termed paleopathology (Gauer, 2022). ...
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The question posed is how deep-time perspectives contribute to tackling contemporary One Health challenges, improving understanding and disease mitigation. Using evidence from the field of paleopathology, it is possible to explore this question and highlight key learning points from the past to focus the minds of those making healthcare policy decisions today. In previous centuries urbanization led to poorer health for a wide range of indicators, including life expectancy, sanitation and intestinal parasites, airway disorders such as maxillary sinusitis, metabolic diseases such as rickets, and even conditions resulting from clothing fashions such as bunions. Modern concerns regarding the quality of urban air and rivers show we have still to incorporate these lessons. When we consider major infectious diseases affecting past societies such as bubonic plague, tuberculosis and leprosy, interaction between humans and wild mammal reservoirs was key. Wild red squirrels in Britain today remain infected by the medieval strain of leprosy that affected people 1,500 years ago. It is clear that the One Health focus on the interaction between humans, animals and their environment is important. Eradicating zoonotic infectious diseases from humans but not these reservoirs leaves the door open to their spread back to people in the future.
... Some least common species that can lead to brucellosis B. neotomae (infects desert wood rats) and B. ovis (affects sheep) (Zhou et al. 2020). The significance of brucellosis extends beyond its impact on animal health (Bendrey et al. 2020). Economically, brucellosis can result in substantial losses in livestock production due to reduced productivity, culling of infected animals, and trade restrictions imposed by importing countries (Unuvar et al. 2019). ...
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Brucellosis (Malta fever, Mediterranean fever, or undulant fever) is a zoonotic infectious disease caused by bacteria of the genus Brucella. This disease affects both humans and animals, posing significant public health and economic concerns worldwide. Brucellosis remains a prevalent global issue, particularly in regions with inadequate veterinary control and surveillance systems. The transmission of brucellosis occurs primarily through direct contact with infected animals or consumption of contaminated products such as unpasteurized milk, cheese, and meat. The disease can spread through inhalation of infected aerosols or contaminated environmental sources. Human-to-human transmission is rare but possible, mainly through sexual intercourse, vertical transmission from mother to child, or laboratory. Clinically brucellosis in humans varies widely showing a flu-like illness, with symptoms including fever, chills, sweats, fatigue, myalgia, and joint pain. In some cases, brucellosis can become chronic and lead to more severe complications, such as arthritis, endocarditis, neurologic disorders, and reproductive. The management of brucellosis involves a multidisciplinary approach, i.e. accurate diagnosis, appropriate treatment, and comprehensive surveillance and control measures. Antibiotics are the mainstay of therapy, typically administered for several weeks or months, depending on the clinical presentation and severity of the disease. Preventive measures include the implementation of vaccination programs for livestock, strict hygiene practices in animal husbandry, pasteurization of dairy products, and public education regarding the risks associated with consuming unpasteurized animal products. Control of brucellosis requires collaboration between veterinary and human health sectors, as well as active participation from governments, international organizations, and communities. Improved diagnostic methods, surveillance systems, and public awareness are crucial to reducing the burden of brucellosis and preventing its spread.
... Archaeologists can help address this problem by documenting the deeper history of humans in shaping diseases. However, archaeological methods, tools and data have not fully been leveraged in One Health approaches, with a few notable exceptions such as the One Health Archaeology Research Group at the University of Edinburgh and a handful of initiatives and researchers elsewhere [7][8][9][10][11]. ...
... New techniques in the 'omics' have opened doors to untangle past human-animal-environment interactions with relevancy for uncovering past epidemiological events [7,80]. This revolution has predominately been led by archaeogenomics made possible by ancient DNA (aDNA) from bone, dental calculus, seeds and palaeofaeces from animals, plants and humans. ...
... Many of these pathogens can infect multiple species that have long and close relationships with humans (i.e. Y. pestis in rodents, M. tuberculosis and Brucella in cows) and have been recovered from both archaeological and zooarchaeological assemblages [7,32,80]. ...
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The accelerating pace of emerging zoonotic diseases in the twenty-first century has motivated cross-disciplinary collaboration on One Health approaches, combining microbiology, veterinary and environmental sciences, and epidemiology for outbreak prevention and mitigation. Such outbreaks are often caused by spillovers attributed to human activities that encroach on wildlife habitats and ecosystems, such as land use change, industrialized food production, urbanization and animal trade. While the origin of anthropogenic effects on animal ecology and biogeography can be traced to the Late Pleistocene, the archaeological record—a long-term archive of human–animal–environmental interactions—has largely been untapped in these One Health approaches, thus limiting our understanding of these dynamics over time. In this review, we examine how humans, as niche constructors, have facilitated new host species and ‘disease-scapes’ from the Late Pleistocene to the Anthropocene, by viewing zooarchaeological, bioarchaeological and palaeoecological data with a One Health perspective. We also highlight how new biomolecular tools and advances in the ‘-omics’ can be holistically coupled with archaeological and palaeoecological reconstructions in the service of studying zoonotic disease emergence and re-emergence.
... Recent pandemics including COVID-19 have underscored the urgency to better understand and predict the impact of zoonotic diseases on human health. While we know zoonotic infections have affected our health throughout (pre)history, perhaps even before the context of agriculture (Bendrey et al. 2020). Global initiatives like the "One Health" program that emphasize the relationship between humans and animals as essential for ecosystem health was designed to have multiple sectors work together to on improved health outcomes, though it has seemed to fall short in unpacking the local and social determinants that lead to zoonotic spillovers. ...
... If the pattern of lesion occurrence in brucellosis cases was the same as it is today, we would expect that more differential diagnoses of brucellosis would be reported from ancient remains [10]. However, there are several reasons why brucellosis may be under-reported in paleopathological analyses of archaeological samples; it is likely mistaken for other diseases that similarly impact bone like tuberculosis, the bacterium had not left skeletal changes by the time of death [7,11,12], or the non-specific nature of the lesions precluded a diagnosis [12]. Support for the presence of brucellosis during the Medieval period includes an ancient genome identified from a pelvic nodule of an individual in Sardinia dating to c. 1300 CE; two individuals from Albania (c. ...
... If the pattern of lesion occurrence in brucellosis cases was the same as it is today, we would expect that more differential diagnoses of brucellosis would be reported from ancient remains [10]. However, there are several reasons why brucellosis may be under-reported in paleopathological analyses of archaeological samples; it is likely mistaken for other diseases that similarly impact bone like tuberculosis, the bacterium had not left skeletal changes by the time of death [7,11,12], or the non-specific nature of the lesions precluded a diagnosis [12]. Support for the presence of brucellosis during the Medieval period includes an ancient genome identified from a pelvic nodule of an individual in Sardinia dating to c. 1300 CE; two individuals from Albania (c. ...
... 1200 CE) with PCR products arising from lesioned ribs and vertebrae; and two French individuals from the 14th and 18 th C. CE where an infection was identified via paleopathology [13][14][15]. This limited DNA evidence compared to other infectious diseases could be due to improper sample selection [16], poor DNA preservation [12,17,18], or its mistaken diagnosis [18]. It is also possible that a focus on other diseases such as tuberculosis has meant that researchers have neglected possible evidence for brucellosis in the archaeological record. ...
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Brucellosis is a disease caused by the bacterium Brucella and typically transmitted through contact with infected ruminants. It is one of the most common chronic zoonotic diseases and of particular interest to public health agencies. Despite its well-known transmission history and characteristic symptoms, we lack a more complete understanding of the evolutionary history of its best-known species-Brucella melitensis. To address this knowledge gap we fortuitously found, sequenced and assembled a high-quality ancient B. melitensis draft genome from the kidney stone of a 14th-century Italian friar. The ancient strain contained fewer core genes than modern B. melitensis isolates, carried a complete complement of virulence genes, and did not contain any indication of significant antimicrobial resistances. The ancient B. melitensis genome fell as a basal sister lineage to a subgroup of B. melitensis strains within the Western Mediterranean phylogenetic group, with a short branch length indicative of its earlier sampling time, along with a similar gene content. By calibrating the molecular clock we suggest that the speciation event between B. melitensis and B. abortus is contemporaneous with the estimated time frame for the domestication of both sheep and goats. These results confirm the existence of the Western Mediterranean clade as a separate group in the 14th CE and suggest that its divergence was due to human and ruminant co-migration.
... Arguably, at least in some cases, this entailed a loss of dietary breadth (such as reduced consumption of meat and greater reliance on domesticated grains), reduced quality of diets (e.g., fewer micronutrients, such as iron), and increased vulnerability to food shortages, all of which could have resulted in declines in health (43). Domestication of animals, such as goats and sheep, led to the acquisition of diseases, such as Brucellosis, through ingestion of animal products, such as milk and cheese (44,45). Diets also influence the gut microbiome of both animals and humans and hence, play an important role in the general well-being of hosts by influencing nutrition, immune responses, and chronic diseases (46)(47)(48). ...
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This perspective draws on the record of ancient pathogen genomes and microbiomes illuminating patterns of infectious disease over the course of the Holocene in order to address the following question. How did major changes in living circumstances involving the transition to and intensification of farming alter pathogens and their distributions? Answers to this question via ancient DNA research provide a rapidly expanding picture of pathogen evolution and in concert with archaeological and historical data, give a temporal and behavioral context for heath in the past that is relevant for challenges facing the world today, including the rise of novel pathogens.
... There is limited historical, paleopathological and biomolecular evidence of brucellosis in human archaeological remains (Bendrey et al., 2020;Ortner, 2003;Roberts and Buikstra, 2019). The few examples of published macroscopically-based differential diagnoses of brucellosis in Eurasia also span a wide timeframe, 3700 BCE to 1500 CE (e.g., Brothwell, 1965;Capasso, 1999;Etxeberria, 1994;Hodgkins, 2002;Rashidi, 2001). ...
... However, if the tissues to which the bacterium is tropic (or to which it has localized) are sampled, success can be higher at either disease stage because the bacterium is concentrated in these areas (Castaño and Solera, 2009;Gotuzzo et al., 1986;Lim and Rickman, 2004). While further study of Brucella DNA in bone lesions needs to be undertaken to determine the value of sampling lesions (Bendrey et al., 2020), we did not identify Brucella DNA in the lesions we sampled, providing an additional data point against the utility of sampling lesions for pathogen DNA. While either acute or chronic brucellosis can lead to the formation of nodules via the calcification of granulomas, splenic and hepatic calcifications are common in the chronic form of the disease (Ariza et al., 2001;Doganay and Aygen, 2003;Torres et al., 2015;Williams and Crossley, 1982). ...
... Our success in recovering Brucella aDNA from the nodules likely relates to both the pathophysiology of the disease in the Blessed Saint and the preservation of the pathogen. In alignment with Bendrey et al. (2020), we recommend further research that uses samples from multiple tissues in archaeological remains in order to reduce the effects of sample bias. ...
Article
Objective To investigate variation in ancient DNA recovery of Brucella melitensis, the causative agent of brucellosis, from multiple tissues belonging to one individual Materials 14 samples were analyzed from the mummified remains of the Blessed Sante, a 14 th century Franciscan friar from central Italy, with macroscopic diagnosis of probable brucellosis. Methods Shotgun sequencing data from was examined to determine the presence of Brucella DNA. Results Three of the 14 samples contained authentic ancient DNA, identified as belonging to B. melitensis. A genome (23.81X depth coverage, 0.98 breadth coverage) was recovered from a kidney stone. Nine of the samples contained reads classified as B. melitensis (7−169), but for many the data quality was insufficient to withstand our identification and authentication criteria. Conclusions We identified significant variation in the preservation and abundance of B. melitensis DNA present across multiple tissues, with calcified nodules yielding the highest number of authenticated reads. This shows how greatly sample selection can impact pathogen identification. Significance Our results demonstrate variation in the preservation and recovery of pathogen DNA across tissues. This study highlights the importance of sample selection in the reconstruction of infectious disease burden and highlights the importance of a holistic approach to identifying disease. Limitations Study focuses on pathogen recovery in a single individual. Suggestions for further research Further analysis of how sampling impacts aDNA recovery will improve pathogen aDNA recovery and advance our understanding of disease in past peoples
... While an important contribution to our understanding of past and future epidemics, this is only one aspect of the story of any zoonotic epidemic. While still relatively few in number, examples of modeling incorporating zooarchaeological, geospatial, climate, ethnographic, and historical data alongside traditional bio archae ol o gi cal analyses offer an opportunity to create a fuller picture of the circumstances leading to and results of zoonotic outbreaks (e.g., Bendrey et al. 2019;Fournié et al. 2017;Gowland and Western 2012;Marciniak et al. 2018;Seetah et al. 2020;Smith-Guzmán et al. 2016). Gowland and Western (2012) provide an example of how modeling using multiple lines of evidence can overcome some of the limitations of traditional bioarchae ol o gi cal analyses in their analysis of malaria in Anglo-Saxon England. ...
... For example, the complex phylogenetic relationships of the Mycobacterium tuberculosis complex (e.g., Bos et al. 2014) and the range of potential reservoirs for plague (Green 2020) point to how the emergence, spread, and impact of zoonotic infections (and ultimately the evolution of human infections) are more complex and diverse than initially suspected. While specific disease identification in humans or animal skeletal remains is difficult and fraught with problems of specificity and preservation, an integrated perspective opens up a range of potential evidence beyond the identification of diseased individuals (Bendrey et al. 2019; One Health Archaeology Research Group 2020). The value of such interdisciplinary studies is being recognized in modeling approaches that bring together a range of specialities. ...
... The use of bioarchae ol o gi cal data in modeling of disease dynamics is currently somewhat limited, but combining bioarchae ol o gi cal evidence (including paleogenetics and paleoproteomics) with ecological, climate, geospatial, clinical, zooarchaeological, ethnographic, and historical data among others shows great potential for contributing to our understanding of past, present, and emerging zoonotic diseases. As argued by Bendrey et al. (2019), there are multiple sources of data. These can be used as proxies for aspects of the model shown in Figure 4. ...
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Zoonoses are significant in human histories, and in histories of other species and the environment. Diseases have been an important evolutionary force, not just the major epidemics but the quieter endemic diseases. These infectious diseases comprise complex events and cycles involving multiple actors (humans, animals, and microorganisms). Despite difficulties of preservation, identification, and interpretation, bioarchaeologists have often analyzed zoonotic diseases. However, these studies have tended to focus on an individual disease and its emergence as opposed to the human-animal interactions and complex environmental cycles that underlie zoonotic disease more broadly. In this paper, after a brief review of zoonotic disease and bioarchaeological studies of it, we provide three contemporary case studies that point to the complexity of human-animal interaction and the socioecological circumstances involved in disease. We argue that adopting a One Health framework, which is based on Rudolf Virchow’s insight as well as approaches that emphasize time depth, multiple analytical scales, evolutionary understandings, and a consideration of human ideas and not just practices, would contribute to making bioarchaeology relevant to contemporary and future issues beyond the epidemiological transition model as modified by Barrett and Armelagos (Barrett et al. 1998; Barrett and Armelagos 2013). Les zoonoses sont importantes dans l’histoire humaine, et en gros dans l’histoire d’autres espèces et de l’environnement. Les maladies ont été une force évolutive importante, non seulement les épidémies majeures, mais aussi les maladies endémiques les plus calmes. Ces maladies infectieuses comprennent des événements et des cycles complexes impliquant de multiples acteurs (humains, animaux et micro-organismes). Malgré les difficultés de préservation, d’identification et d’interprétation, les bioarchéologues ont souvent analysé les zoonoses. Cependant, ces études ont eu tendance à se concentrer sur la maladie individuelle et son émergence par opposition aux interactions homme-animal et aux cycles environnementaux complexes qui sous-tendent la maladie zoonotique de manière plus générale. Dans cet article, après un bref examen de la maladie zoonotique et des études bioarchéologiques de celle-ci, nous fournissons trois études de cas contemporaines qui soulignent la complexité de l’interaction homme-animal et les circonstances socio-écologiques impliquées dans la maladie. Nous soutenons que l’adoption d’un cadre One Health basé sur la vision de Rudolf Virchow ainsi que sur des approches mettant l’accent sur la profondeur temps, les échelles analytiques multiples, les compréhensions évolutives et la prise en compte des idées humaines et non seulement des pratiques, contribuera à rendre la bioarchéologie pertinente pour les problèmes contemporains et futurs au-delà le modèle de transition épidémiologique tel que modifié par Barrett et Armelagos (Barrett et al. 1998; Barrett et Armelagos 2013).
... Interactive socioecological systems giving rise to zoonoses (infectious diseases shared among different species) involve humans, animals, and pathogens in specific environments. Archaeological applications of the One Health perspective (Bendrey et al. 2019) acknowledge this essential link in an interdisciplinary setting. Their breaking with the anthropocentric approach and considering components in a holistic and integrated way is comparable to the endeavours of animal studies in humanities. ...
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... In total, while 41 individuals were reported in preliminary excavation reports [30,31], mostly from burials, Merrett's exhaustive analysis of the human remains from Ganj Dareh [77] identified a total of 116 distinct individuals represented by as little as single elements to nearly complete skeletons. Some of the buried individuals bear evidence of cranial deformation [78][79][80], while overall health conditions appear to have been rather good, with low incidence of cavities and occasional traces of porotic hyperostosis, likely caused by zoonotic brucellosis caused by sustained contact with ovicaprids [77,81,82]. Recent analyses of stable carbon, nitrogen and sulfur isotopes on 20 individuals indicate that the Neolithic occupants of Ganj Dareh all shared a diet largely based on C 3 plants, that subadults may have been weaned using supplement with distinct carbon values and that one of the older male individuals may have been a transhumant shepherd [83]. ...
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The Aceramic Neolithic site of Ganj Dareh (Kermanshah, Iran) is arguably one of the most significant sites for enhancing our understanding of goat domestication and the onset of sedentism. Despite its central importance, it has proven difficult to obtain contextually reliable data from it and integrate the site in regional syntheses because it was never published in full after excavations ceased in 1974. This paper presents the Ganj Dareh archive at Université de Montréal and shows how the documentation and artifacts it comprises still offer a great deal of useful information about the site. In particular, we 1) present the first stratigraphic profile for the site, which reveals a more complex depositional history than Smith’s five-level sequence; 2) reveal the presence of two possible pre-agricultural levels (H-01 and P-01); 3) explore the spatial organization of different levels; 4) explain possible discrepancies in the radiocarbon dates from the site; 5) show some differences in lithic technological organization in levels H-01 and P-01 suggestive of higher degrees of residential mobility than subsequent phases of occupation at the site; and 6) reanalyze the burial data to broaden our understanding of Aceramic Neolithic mortuary practices in the Zagros. These data help refine our understanding of Ganj Dareh’s depositional and occupational history and recenter it as a key site to improve our understanding the Neolithization process in the Middle East.