Evolution of human tuberculosis: A systematic review and meta-analysis of paleopathological evidence
Introduction
Many studies have investigated tuberculosis (TB), as it is a major cause of mortality worldwide. The World Health Organization (2010) reports that approximately one third of the world's population are infected and nearly 2 million die from the disease each year. The causative agent of TB is primarily Mycobacterium tuberculosis, a member of the family Mycobacteriaceae, which includes soil dwelling organisms and commensals (Al-Sarie et al., 1996). M. tuberculosis itself is labeled as a pathogen, rather than a commensal, but many individuals live with the bacteria without experiencing signs or symptoms of disease. In fact, it only causes active disease in approximately 10% of individuals, frequently in times of lowered immunity (World Health Organization, 2010).
In cases of active TB, three to five percent of individuals develop bone lesions and these can occur in any region of the body (Steinbock, 1976, Ortner, 2003). TB is usually diagnosed in skeletal remains through spinal lesions; specifically osteolytic lesions on the anterior regions of thoracic and lumbar vertebrae. Vertebral bodies are destroyed, potentially leading to angular kyphosis and fusion of vertebrae. Typically only between one and four vertebrae are involved and neural arches as well as posterior elements are spared. Other diseases such as brucellosis, fungal infections, pyogenic osteomyelitis and a variety of neoplastic growths can also produce similar lesions, complicating differential diagnoses (Steinbock, 1976). Other skeletal lesions are used in combination to produce “most likely” diagnoses and include lesions on the articular surfaces of the joints and on long or flat bones. The hip and knee are frequently involved; making up 15–30% and 10–20% of all non-spinal cases, respectively (Steinbock, 1976). Endocranial lesions and dactylitis can also help to diagnose TB infection, though are rather less commonly used. Two recent studies of TB in Hungarian, French and Italian samples have focused on bone lesions resulting from the disease (Giacon, 2008, Maczel, 2004). Several observations including vertebral hypervascularisation, rib periostitis, endocranial changes and periosteal new bone formation (particularly of the femur) were identified as potentially useful and may be used in future diagnostic work. Rib lesions can also occur from pulmonary TB, however these are subtle lesions, mainly appearing as regions of bone resorption or periosteal new bone formation (Roberts and Buikstra, 2003). Some studies of rib lesions in archaeological samples and skeletal collections have been conducted to investigate an association with TB (Pfeiffer, 1991, Mays et al., 2002, Raff et al., 2006, Santos and Roberts, 2006). However these lesions can be caused by a large number of other conditions and consequently are unreliable on their own for the diagnosis of TB. Finally, calcification of the pleura has been considered almost pathognomonic for TB as no other diseases are commonly diagnosed this way (Donoghue et al., 1998, Pálfi et al., 1999, Lombardi and Caceres, 2000, Molnár and Pálfi, 1994).
Studies of DNA from modern strains of M. tuberculosis can yield some insight into the molecular evolution of the bacteria through time (Brosch et al., 2002), but these do not focus specifically on the ancient organisms or the disease they caused in humans.
A large number of paleopathological studies have reported cases of TB in archaeological remains, but this does not help to give a clear image of the co-evolution of the pathogen and host through time. Rather, single and occasionally multiple cases are described, showing only that TB was present in the population. There have been attempts at bringing together the numerous publications (Roberts and Buikstra, 2003, Pálfi et al., 1999, Roberts et al., 2009), but further analysis is needed in this area, for reasons such as limited geographical coverage of previous publications.
Since descriptions of palaeopathological TB cases and ancient and modern DNA studies do not provide a clear view of the co-evolution of humans and the bacterium through time, we conducted a meta-analysis of all cases available in the literature. Two null hypotheses were tested: (1) the frequency of bone lesions due to TB did not change through time and (2) the distribution of lesions throughout the skeleton did not change over time. While meta-analyses are usually rigorous with selection criteria, our study includes, as a starting point, all cases of palaeopathological cases of tuberculosis in the literature as this is the only information available.
Section snippets
Materials and methods
A literature search was conducted using a number of online databases including Academic OneFile, Academic Search Premier, Anthropology Plus, Google Books, Google Scholar, JSTOR, PubMed, ScienceDirect, Scopus, Web of Science and WileyInterScience. Other references were also consulted such as publications by Steinbock (1976), Ortner (2003), Roberts and Buikstra (2003), Dutour et al. (2003) and Brothwell and Sandison (1967). Additionally, other authors and colleagues were generous enough to mail
Frequency of lesions
A total of 530 palaeopathological TB cases from 221 gravesites were summarised, these derived from 151 references. The results of the literature review are shown in Table 3. A search of 14 databases yielded a total of 1389 references, 779 of which were removed as duplicates and 514 of which contained no relevant information. An additional 28 references were obtained by following up reference lists in other articles and 27 were received from Professor Antónia Marcsik, Professor Jane Buikstra,
Discussion
It is possible that not all cases have been included in our meta-analysis, and hence, our results and interpretation may change if further literature becomes available. However, the inclusion of several additional cases to the over 500 cases that we have used here, would be unlikely to change the results substantially. There are also other aspects of the data that were not investigated during this analysis. For example, the presence of multiple extra-spinal lesions was not addressed separately
Conclusions
Frequency of bone lesions due to tuberculosis decreased significantly through time. Lesion distribution was shown to change from mainly spinal lesions in early time periods to extra-spinal lesions (or both spinal and extra-spinal) in later time periods. We hope that these observations can lead to further research and interpretations of the co-evolution of host and pathogen through time.
Acknowledgements
The authors would like to acknowledge those who helped compile the references for this work, including Professor Antónia Marcsik, Professor Jane Buikstra, Associate Professor Ladislava Horáčková, Mi-Ra Kim, Dr. Sandra Lösch, Tamás Hajdu, Professor Eugen Strouhal, Dr. Tina Christensen, Dr. Dunai Józsefné, Sándor Évinger, Professor Charlotte Roberts, Tessa Campbell, Dr. Abigail Bouwman and Professor Rimantas Jankauskas. Acknowledgement also goes to Professor Frank Rühli and the Centre for
References (131)
- et al.
DNA from Mycobacterium tuberculosis complex identified in North American, pre-columbian human skeletal remains
J. Archaeol. Sci.
(1998) Infectious diseases in Egypt
Infect. Dis. Clin. North Am.
(2004)- et al.
New skeletal tuberculosis cases in past populations from Western Hungary (Transdanubia)
HOMO
(2011) - et al.
Mycolic acids and ancient DNA confirm an osteological diagnosis of tuberculosis
Tuberculosis
(2001) - et al.
Tuberculosis on the north coast of Peru: skeletal and molecular paleopathology of late pre-Hispanic and postcontact mycobacterial disease
J. Archaeol. Sci.
(2010) - et al.
Paleopathology of the Kechipawan site: health and disease in a south-western Pueblo
J. Archaeol. Sci.
(1992) - et al.
High-throughput mass spectrometric analysis of 1400-year-old mycolic acids as biomarkers for ancient tuberculosis infection
J. Archaeol. Sci.
(2010) - et al.
Tuberculosis among Iron Age individuals from Tyva, South Siberia: palaeopathological and biomolecular findings
J. Archaeol. Sci.
(2009) - et al.
Molecular evidence for tuberculosis in an ancient Egyptian mummy
Lancet
(1997) - et al.
Paleopathology in osseous remains from the 16th century. A survey of rheumatic diseases
J. Rheumatol.
(1998)
History of Human Life Span and Mortality
The population of Zalavár in the Middle Ages
Acta Archaeol.
Cases of tuberculosis at ‘Ain Ghazal, Jordan
Paléorient
A case of skeletal tuberculosis from Roman Towcester
Int. J. Osteoarchaeol.
Pre-columbian tuberculosis in Northern Chile: molecular and skeletal evidence
Am. J. Phys. Anthropol.
PCR diagnostics of Mycobacterium tuberculosis in historic human long bone remains from 18th century burials in Kaiserebersdorf, Austria
BMC Res. Notes
An Ancient DNA Study of Tuberculosis in Europe
A new evolutionary scenario for the Mycobacterium tuberculosis complex
Proc. Natl. Acad. Sci. U. S. A.
Diseases in Antiquity
The Caribou Eskimo: general and specific disease
Am. J. Phys. Anthropol.
Differential diagnosis: an epidemiological model
Yrbk Phys. Anthropol.
Tuberculosis in the Americas: current perspectives
Paleodemography: context and promise
Paleodemography: critiques and controversies
Am. Anthropol.
A Viking-age valley in Iceland: the Mosfell Archaeological Project
Med. Archaeol.
Evaluating the emergence of tuberculosis in South Africa
Am. J. Phys. Anthropol.
New evidence of tuberculous spondylitis from Neolithic Liguria (Italy)
Int. J. Osteoarchaeol.
Lectures on the pathology of tuberculous diseases of bones and joints
Br. Med. J.
Official Year Book of the Commonwealth of Australia
Examination of Mycobacterium leprae and Mycobacterium tuberculosis DNA in samples I/11, VI/24 and VI/27 of the Székesfehérvár material
Mycobacterium tuberculosis complex DNA in calcified pleura from remains 1400 years old
Lett. Appl. Microbiol.
The White Death: A History of Tuberculosis
Paléoépidémiologie de la tuberculose en Guadeloupe: le cimetière d’esclaves de l’Anse Sainte-Marguerite
Epidemiology of infectious diseases in the past: yersin, koch, and the skeletons
Human treponematosis and tuberculosis: evidence from the New World
Am. J. Phys. Anthropol.
Angular kyphosis of the spine: Mal de Pott identification in a mummy prehispanic Guane Colombia
Chungara (Arica)
Prevalence of human tuberculosis in Medieval population of Lithuania based on ancient DNA analysis
Anc. Biomol.
Evidence of spinal tuberculosis at the beginning of the fourth millennium BC from Arene Candide cave (Liguria, Italy)
Am. J. Phys. Anthropol.
The story of 12 Chachapoyan mummies through multidetector computed tomography
Eur. J. Radiol.
Outbreak of tuberculosis in a 2000-year-old Chinese population
Kansenshogaku Zasshi
Diseases of the spine in South American mummies
Neurosurgery
Rheumatoid arthritis, Klippel-Feil syndrome and Pott's disease in Cardinal Carlo de’ Medici (1595–1666)
Clin. Exp. Rheumatol.
Molecular evidence for different stages of tuberculosis in ancient bone samples from Hungary
Am. J. Phys. Anthropol.
Proportion of dying children in paleodemographical studies: Estimation by guess or by methodical approach?
Przegl. Antropol.
Reconstructing medical knowledge in ancient Pompeii from the hard evidence of bones and teeth
A preliminary report on the paleodemography of the K2 and Mapungubwe populations
Hum. Biol.
Cited by (61)
Bi(bli)oArch-Italia: An open-access bibliographic database for human bioarchaeological studies in Italy
2022, Journal of Archaeological Science: ReportsOldest evidence of tuberculosis in Argentina: A multidisciplinary investigation in an adult male skeleton from Saujil, Tinogasta, Catamarca (905–1030 CE)
2020, TuberculosisCitation Excerpt :Tuberculosis is an infectious disease that has affected humans since at least 10,000 years ago [1–6].
Multiparameter prediction control of in vitro drug delivery into mycobacterium smegmatis induced by microbubble-enhanced sonoporation
2020, European Journal of Pharmaceutics and Biopharmaceutics