The paleopathological evidence on the origins of human tuberculosis: a review.

Tuberculosis (TB) has been one of the most important infectious diseases affecting mankind and still represents a plague on a global scale. In this narrative review the origins of tuberculosis are outlined, according to the evidence of paleopathology. In particular the first cases of human TB in ancient skeletal remains are presented, together with the most recent discoveries resulting from the paleomicrobiology of the tubercle bacillus, which provide innovative information on the history of TB. The paleopathological evidence of TB attests the presence of the disease starting from Neolithic times. Traditionally, it was thought that TB has a zoonotic origin, being acquired by humans from cattle during the Neolithic revolution. However, the biomolecular studies proposed a new evolutionary scenario demonstrating that human TB has a human origin. The researches show that the disease was present in the early human populations of Africa at least 70000 years ago and that it expanded following the migrations of Homo sapiens out of Africa, adapting to the different human groups. The demographic success of TB during the Neolithic period was due to the growth of density and size of the human host population, and not the zoonotic transfer from cattle, as previously hypothesized. These data demonstrate a long coevolution of the disease and its human host. Understanding the changes of TB through time thanks to the advances in the field of paleopathology can help to solve the present problems and understand the future evolution of TB.

Atlas occipitalisation associated with other anomalies in a 16th century skeleton from Sardinia (Italy).

Archaeological excavations carried out in the plague cemetery of 16th century Alghero (Sardinia) brought to light the skeleton of a male aged 35-45 years, showing anomalies of the atlas. A macroscopic and radiological study has been carried out. The first cervical vertebra is fused with the skull base, resulting in an occipitalisation of the atlas. Absence of the costal element of the left foramen transversarium, resulting in an open anterior foramen transversarium, and posterior arch defect are also observed. The atlanto-occipital junction is a complex structure, susceptible to develop different patterns of congenital defects. These anatomical variations of atlas should be considered in modern clinical practice in order to formulate a correct diagnosis and to conceive an appropriate treatment. Osteoarchaeological cases are important as, beside to ascertain the presence of congenital defects in past populations, allow an in-depth study in dry bones, which can help modern medicine in interpreting anatomical variations. We present an association of congenital anomalies of the atlanto-occipital junction, a condition rarely documented in ancient and modern human skeletal remains.

A probable case of non-syndromic brachycephaly from 16th century Sardinia (Italy).

The skeleton of a 9- to 10-year-old child showing a case of skull malformation due to premature bilateral closure of the coronal suture was encountered during the excavation of a Sardinian plague cemetery ("Lo Quarter") dating to the 1582-1583 Alghero plague outbreak. The skull is deformed, with increased bi-parietal diameter, marked frontal and parietal bosses, shallow orbits, and a palpable ridge perpendicular to the coronal suture. Digitate impressions are observable on both fronto-parietal regions of the skull's inner table. Since the splanchnocranium has not preserved, it is impossible to verify if facial anomalies might have been present. Although the cranial appearance might be reminiscent of different genetic syndromes, the absence of obvious hand and feet anomalies is a hallmark for non-syndromic brachycephaly.

Rheumatoid arthritis in Cardinal Carlo de' Medici (1595-1666): a confirmed macroscopic, radiologic and molecular diagnosis.

OBJECTIVES: The paleopathological study of the skeletal remains belonging to Cardinal Carlo de' Medici (1595-1666), son of Ferdinando I (1549-1609) and Cristina of Lorena (1565-1637), has been presented previously. A diagnosis of Klippel-Feil syndrome, tuberculosis and a polyarthopathy, interpreted as rheumatoid arthritis, was suggested. A revision of this case based on the analysis of the historical documents and of some radiological images of Carlo's bones has been proposed recently; according to the Authors, the Cardinal was affected by the 'Medici syndrome', a combined Psoriatic-DISH arthropathy. This revision offers us the opportunity to discuss this complex case, comparing different points of view, and to present the results of the molecular analyses carried out on Carlo's bone samples. We looked for the genetic risk factors of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We also searched for the primary candidate genes of RA and PsA, i.e. DR4 or DR1 and Cw6 or DR7 respectively, the latter predisposing also for psoriasis. METHODS: An original molecular protocol was applied to achieve an aDNA uncontaminated by exogenous sources and almost intact, starting from one of the Cardinal's rib pieces. The allele risk factors for both diseases were identified by PCR-SSP assay as HLA genotyping methodology. RESULTS: Our data assigned Carlo the genotype DRB1*04/*11 for HLA-DRB locus and Cw*04/*12 for HLA-C locus. CONCLUSIONS: Since Carlo was infected by M. tuberculosis during infancy and was carrying the DR4 variant but not the Cw6, he surely had a predisposition to RA, not to PsA and/or psoriasis. The diagnosis of RA is thus confirmed.

Eleonora of Toledo (1522-1562): Evidence for tuberculosis and leishmaniasis co-infection in Renaissance Italy.

Clinical reports for Eleonora of Toledo (1522-1562), the wife of Cosimo I de' Medici, imply that during her 28th year she developed pulmonary tuberculosis, which was complicated by an attack of pernicious malaria, killing her at age 40. Eleonora's autopsy indicated that she had severe lung lesions consistent with chronic pulmonary infection. To clarify her disease status, we performed paleomolecular investigations. Our results identified ancient DNA from the Mycobacterium tuberculosis complex (MTB), along with Leishmania infantum (VL). Our data are of particular interest since in Tuscany the endemic foci of L. infantum are widely distributed and overlapped with those of malaria prior to its eradication. Although we can only speculate about Eleonora's true state of health, this clear evidence of long-term co-infection with MTB and VL is of major medical and biological interest since the co-evolution of the two pathogens and host-pathogen interactions in co-infected individuals are still not fully understood.

Historical sources about diseases, death and embalming regarding the family of Jean Antoine Michel Agar, Minister of Finance of Gioacchino Murat.

Among the mummies preserved in the Basilica of San Domenico Maggiore in Naples, there are the bodies of the wife and three children of Jean Antoine Michel Agar, Minister of Finance of Naple's Kingdom during the Monarchy of Joachim Murat (1808-1815). Between 1983 and 1987 paleopathological analyses were performed; in particular, X-ray examination allowed investigation of the health status of the Agar family members and reconstruction of the embalming processes used to preserve the bodies. In addition, an analysis of the historical and archival documents was carried out, to formulate hypotheses about the causes of death, demonstrating how these sources could become important instruments to obtain diagnoses and pathological histories.

Antonio Ascenzi (1915-2000), a pathologist devoted to anthropology and paleopathology.

Antonio Ascenzi is well known within the scientific community for his original contributions to morbid anatomy and in particular for his studies on the fields of bone biology, bone biomechanics, haematology and congenital heart disease. Additionally, Ascenzi was also interested in human evolution and applied his deep knowledge of pathology to ancient human remains, conducting research in paleoanthropology on fossilized Neanderthal specimens found in Italy. The name of Ascenzi is linked with the discovery and study of the most ancient Italian bone fossils, namely the Ceprano skull, an early specimen of Homo erectus. Furthermore, his pioneering researches on the Uan Muhuggiag and Grottarossa mummies and his rigorous studies on several aspects and problems concerning the pathologies of past human populations made him a pioneer in the fields of Italian mummiology and paleopathology. The thread that linked his diversified research interests outside and within human anthropology was a profound passion for the search and discovery of scientific truth.

[Rheumatic diseases at the court of the Medici of Florence: the so-called "gout" of the Medici]. / Le malattie reumatiche alla corte medicea di Firenze: la cosiddetta "gotta" dei Medici.

According to the archive documents several members of the Medici family of Florence suffered from gout. The word "gout", with which the Renaissance physicians indicated pain episodes localised to hands, feet, spine and shoulders, was in general improperly used, and hint other nosological entities. A paleopathological investigation carried out on the skeletal remains of the Grand Dukes of Florence and their relatives, revealed the true nature of the diseases they suffered from, allowing to diagnose two cases of diffuse idiopathic skeletal hyperostosis (DISH), a case of rheumatoid arthritis in an advanced stage, and a case of gout.

Rheumatoid arthritis, Klippel-Feil syndrome and Pott's disease in Cardinal Carlo de' Medici (1595-1666).

OBJECTIVE: A paleopathological study was carried out on the she skeletal remains of Cardinal Carlo de' Medici (1595-1666), son of the Grand Duke Ferdinando I (1549-1609) and Cristina from Lorraine (1565-1636), to investigate the articular pathology described in the archival sources. METHODS: The skeletal remains of Carlo, buried in the Basilica of San Lorenzo in Florence, have been exhumed and submitted to macroscopic and radiological examination. RESULTS: The skeleton of Carlo revealed a concentration of different severe pathologies. Ankylosis of the cervical column, associated with other facial and spine anomalies suggests a diagnosis of congenital disease: the Klippel-Feil syndrome. In addition, the cervical segment presents the results of the tuberculosis (Pott's disease) from which the Cardinal suffered in his infancy. The post-cranial skeleton shows an ankylosing disease, mainly symmetrical and extremely severe, involving the large as well as small articulations, and characterized by massive joint fusion, that totally disabled the Cardinal in his last years of life. CONCLUSIONS: The final diagnosis suggests an advanced, ankylosing stage of rheumatoid arthritis.