Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact1. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World2. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch3, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.

Diagnosis of pulmonary tuberculosis (TB) usually includes laboratory analysis of sputum, a viscous material derived from deep in the airways of patients with active disease. As a diagnostic sample matrix, sputum can be difficult to collect and analyze by microbiological and molecular techniques. An alternative, less invasive sample matrix could greatly simplify TB diagnosis. We hypothesized that Mycobacterium tuberculosis cells or DNA accumulate on the oral epithelia of pulmonary TB patients, and can be collected and detected by using oral (buccal) swabs. To test this hypothesis, 3 swabs each were collected from 20 subjects with active pulmonary TB and from 20 healthy controls. Samples were tested by using a polymerase chain reaction (PCR) specific to the M. tuberculosis IS6110 insertion element. Eighteen out of 20 confirmed case subjects (90%) yielded at least 2 positive swabs. Healthy control samples were 100% negative. This case-control study supports past reports of M. tuberculosis DNA detection in oral swabs. Oral swab samples are non-invasive, non-viscous, and easy to collect with or without active TB symptoms. These characteristics may enable simpler and more active TB case finding strategies.

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Two of humankind's most socially and psychologically devastating diseases, tuberculosis and leprosy, have been the subject of intensive paleopathological research due to their antiquity, a presumed association with human settlement and subsistence patterns, and their propensity to leave characteristic lesions on skeletal and mummified remains. Despite a long history of medical research and the development of effective chemotherapy, these diseases remain global health threats even in the 21st century, and as such, their causative agents Mycobacterium tuberculosis and M. leprae, respectively, have recently been the subject of molecular genetics research. The new genome-level data for several mycobacterial species have informed extensive phylogenetic analyses that call into question previously accepted theories concerning the origins and antiquity of these diseases. Of special note is the fact that all new models are in broad agreement that human TB predated that in other animals, including cattle and other domesticates, and that this disease originated at least 35,000 years ago and probably closer to 2.6 million years ago. In this work, we review current phylogenetic and biogeographic models derived from molecular biology and explore their implications for the global development of TB and leprosy, past and present. In so doing, we also briefly review the skeletal evidence for TB and leprosy, explore the current status of these pathogens, critically consider current methods for identifying ancient mycobacterial DNA, and evaluate coevolutionary models. Yrbk Phys At the close of the first decade of the 21st century, a number of factors converge to make a review of mycobacterial disease timely. The first of these is the re-emergence of human tuberculosis (TB) in epidemic proportions on a global scale. As emphasized in the section on Mycobacterial diseases: The Historical, Epidemiological, and Ecological Context Section, by the mid-point of the 20th century the disease was thought to be conquerable and by the 1980s, conquered. How wrong these predictions were! TB, termed ''the white plague'' during the 19th century, has a very long history as a health burden to humankind, which continues today. A thorough knowledge of the coevolution of humans and pathogenic mycobacteria may inform development of treatment and prevention methods.A second important factor making a review of mycobacterial disease timely involves the emergence of new techniques in molecular biology. The development of the polymerase chain reaction (PCR) method for amplifying DNA, advancements in sequencing technology, as well as the availability of mycobacterial genome sequences have revolutionized our knowledge of contemporary mycobacterial genetic variation. These advances permit scientists not only to explore global patterning within species, but also to make phylogenetic inferences and understand the evolutionary relationships between mycobacterial strains. In turn, molecular biologists and anthropologists have used this technology to identify...

Although the Mycobacterium tuberculosis complex (MTBC) infects a third of all humans, little is known regarding the prevalence of mycobacterial infection in nonhuman primates (NHP). For more than a century, tuberculosis has been regarded as a serious infectious threat to NHP species. Advances in the detection of MTBC open new possibilities for investigating the effects of this poorly understood pathogen in diverse populations of NHP. Here we report results of a cross-sectional study using well-described molecular methods to detect a nucleic acid sequence (IS6110) unique to the MTBC. Sample collection was focused on the oral cavity, the presumed route of transmission of MTBC. Buccal swabs were collected from 263 macaques representing 11 species in four Asian countries and Gibraltar. Contexts of contact with humans included free ranging, pets, performing monkeys, zoos, and monkey temples. Following DNA isolation from buccal swabs, the PCR amplified IS6110 from 84 (31.9%) of the macaques. In general, prevalence of MTBC DNA was higher among NHP in countries where the World Health Organization reports higher prevalence of humans infected with MTBC. This is the first demonstration of MTBC DNA in the mouths of macaques. Further research is needed to establish the significance of this finding at both the individual and population levels. PCR of buccal samples holds promise as a method to elucidate the mycobacterial landscape among NHP, particularly macaques that thrive in areas of high human MTBC prevalence.

This study focuses on hands and feet as indicators of sex and stature for Native Americans, hitherto relatively neglected in this regard. The study was performed on a large, well‐preserved prehistoric skeletal sample from west‐central Illinois. Discriminant functions are presented which determine sex with accuracies exceeding 87%. Those functions are then tested on three other Native American samples and found to have similar high degrees of accuracy. The utility of hand and foot bones for estimation of femur length (and subsequent inclusion in stature estimation equations) is also explored. While indirect estimation of stature is determined to be possible in this manner, it is suggested that these and other stature estimation techniques that have large standard errors may be of limited archaeological or forensic value. © 1998 John Wiley & Sons, Ltd.

Osseous manifestation of infectious disease is of paramount importance to paleopathologists seeking to interpret ancient health, but the relationships among infectious agent exposure, development of disease, and skeletal involvement are complex. The outcome of an exposure strongly depends on multiple factors, including ecology, diet, nutrition, immune function, and the genetics of pathogen and host. Mycobacterial diseases are often studied in ancient remains but also are especially influenced by these factors; individual and population differences in severity and course are apparent following onset of active disease. The osteological record for these diseases represents the complex interplay of host and pathogen characteristics influencing within- and among-individual skeletal lesion prevalence and distribution. However, many of these characteristics may be assessed independently through the archaeological record. Here, we explore the contributions of dietary protein and iron to immune function, particularly the course and outcome of infection with Mycobacterium tuberculosis. We emphasize how nutrition may influence the dissemination of bacilli to the skeleton and subsequent formation of diagnostic lesions. We then generate models and hypotheses informed by this interplay and apply them to four prehistoric New World areas. Finally, discrepancies between our expectations and the observed record are explored as a basis for new hypotheses.

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