Heritage Of A Deadly Disease Pinpointed With Help From Iceland’s Genealogical Database

A collaboration of scientists from Iceland and the United States has used Iceland’s genealogical database* to trace the ancestors of patients suffering from hereditary cystatin C amyloid angiopathy (HCCAA). Analysis shows that the deadly mutation in the cystatin C gene, L68Q, derives from a common ancestor born roughly 18 generations ago, around 1550AD.

This dominantly inherited disease, which is due to a mutation in cystatin C (L68Q), strikes young adults with healthy blood pressure. The disease results in death from repeated brain haemorrhages, on average by the age of 30. The origin of the mutation causing HCCAA was previously unknown, but using DNA haplotype analysis* the scientists have shed light on the history of this autosomal dominant disease that has high penetrance in contemporary Icelanders.

The scientists found that 200 years ago, obligate carriers of the mutation lived a normal life span compared to the control population (their spouses). In carriers born around 1820, however, a trend of shortening life span began, resulting in an average life span of only 30 years in people born around 1900. This 30-year lifespan has stayed constant since then in both men and women.

At the same time, a matrilinear effect appeared whereby those who inherited the mutation from the mother died earlier. For carriers born after 1900, the difference is a loss of 9.4 years for those who inherited the mutation from their mothers rather than their fathers. Based on this information, the authors propose that the traditional diet of the nation (which in the past consisted largely of whey-preserved offal as well as meat, dried fish, and butter) “protected” the mutation carriers for almost 300 years until the Icelandic diet changed early in the early 19th century, exemplified by drastic increases in imported carbohydrates and salt.

This finding has implications for studies of Alzheimer’s disease as cerebral amyloid angiopathy (CAA) is almost universally found in Alzheimer’s patients and normal cystatin C protein is one of the proteins found in amyloid in brains of Alzheimer’s patients. Studies are underway to try to elucidate the risk factors with the hope of providing a preventive stategy for cystatin L68Q carriers.

*By deCODE Genetics

Palsdottir A, Helgason A, Palsson S, Bjornsson HT, Bragason BT, et al. A Drastic Reduction in the Life Span of Cystatin C L68Q Carriers Due to Life-Style Changes during the Last Two Centuries. PLoS Genet, 4(6): e1000099 DOI: 10.1371/journal.pgen.1000099

Know Your Pathology: Spina Bifida

Probably the most common developmental defect reported archaeologically is spina bifida (Roberts and Manchester, 2005: 55). This ‘neural tube defect’ varies in frequency worldwide today, although there are indications that the highest frequencies are found in the British Isles, e.g. 62 of 5607 babies for 1998, and that the lowest frequencies are in Japan, with North America in between (Roberts and Manchester, 2005: 55). Males are more frequently affected than females generally, and genetic and environmental factors are potential causes, these including deficiences in maternal folic acid (vitamin B12), zinc and selenium during foetal development (Roberts and Manchester, 2005: 55).

It is the occulta type, rather than cystica, that is described most frequently (Roberts and Manchester, 2005: 55). Spina bifida occulta is the incomplete fusion of the posterior neural arches of the sacral segments and/or lumbar vertebrae (Roberts and Manchester, 2005: 55). No structures such as the spinal cord protrude out through the space and thus no complications such as infection or paralysis occur (Roberts and Manchester, 2005: 55). In living persons the condition often remains undetected unless X-rays are taken. Spina bifida cystica, on the other hand, is often fatal (Roberts and Manchester, 2005: 55). Three types of severity have been described (Aufderheide and Rodriguez-Martin, 1998: 61):

• meningocele – involves the protrusion of the nerve roots and meninges through the defect, with the spinal cord remaining in the canal and a covering of skin in place,
• myelomeningocele – involves the added protrusion of the spinal cord without normal skin covering,
• myelocele – involves the non-closure of the skin and meninges at the defect, the infection of which usually results in death.

It is unlikely that individuals in the past would have survived such a severe defect, which perhaps explains why there is so little evidence archaeologically (Roberts and Manchester, 2005: 56). If someone did survive, potential complications would include paralysis, incontinence and hydrocephalus (Roberts and Manchester, 2005: 56). For example, a 14-16 year old individual from Florida has been described with spina bifida cystica from lumbar vertebrae 3 to the 2nd sacral vertebrae with subsequent disuse atrophy of some of the bones: this may represent paralysis as a result of the condition (Roberts and Manchester, 2005: 56). More data is available for spina bifida occulta. For the early medieval period in Britain, three sites reporting absolute frequencies (percentage of sacra affected) give frequencies of 8.7% (Roberts and Cox, 2003), while other authors have indicated an average rate of 2.7% for some early British populations (Brothwell and Powers, 1968).

References:

Aufderheide, AC and Rodriguez-Martin, C. 1998. The Cambridge encyclopedia of human palaeopathology. Cambridge: Cambridge University Press.

Brothwell, D and Powers, R. 1968. Congenital malformations of the skeleton in earlier man, pp 173 – 203. In DR Brothwell (ed) Skeletal biology of earlier human populations. Symposia of the Society for the study of Human Biology Volume 8. London: Pergamon Press.

Roberts, C and Cox, M. 2003. Health and disease in Britain: prehistory to the present day. Stroud: Sutton Publishing.

Roberts, C and Manchester, K. 2005. The Archaeology of Disease. Third Edition. Stroud: Sutton Publishing

How long can TB survive?

A note on the environmental persistence (or otherwise) of Mycobacterium tuberculosis in 300-year-old Hungarian mummies can be found over at MicrobiologyBytes.

A trephinated skull from Germany

A review of new research is presented in Nature Precedings regarding a skull radiocarbon dated to 1940 calBC (late Neolithic – early Bronze Age) from Germany, which exhibits signs of trephination.

The authors say:

The skull fragment includes large parts of the cranial vault including both frontal bones down to the left orbital rim, the right parietal, and both occipital regions. The whole cranial base as well as the facial bones and the left temporal regions are missing. It is the only part left of the original skeleton of an adult male. The skull fragment shows two manipulations: In the left frontal-region one notes a hole with a diameter of 30 x 25 mm which results from a funnel-shaped trephination with the outer size of 53 x 50 mm. The diameter of the rim varies from 10 ­ 12 mm. The diploe of the bone is not visible which means that the trephination must have been survived for a longer period of time. The configuration of the defect and the angulation of its edge indicate that the trephination was performed by the scraping-technique. A second defect involves the left occipital region partially crossing the lambdoid suture. It consists of two small and one larger skull fragments which have grown together forming a typical consolidated depressed skull fracture. The depth of the defect is approximately 10 mm at its maximum. Its diameter measures 35 x 24 mm.

They speculate that the individual received two simulataneous injuries, one of which was trephined whilst the second healed without medical intervention. However, as they note, two chronologically differing traumatic incidents are possible of which only one was severe enough to be in need of surgical measures. Alternatively, the intact skull may have been trephined in the left frontal region because of the temporo-occipital injury to prevent complications, e.g. a suspected haematoma under a local bruise of the skin.

Reference: Piek, Juergen, Lidke, Gundula, and Terberger, Thomas. Ancient Trephinations in Neolithic People – Evidence for Stone Age Neurosurgery?. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1615.1&gt; (2008)

Know Your Pathology: Cleft Palate

A cleft palate is a bony defect that is due to the failure of bone union between the two halves of the palate during foetal development. It may be associated with a defect of the upper lip and bone beneath, called the cleft or hare lip (Roberts and Manchester, 2005: 51). The modern incidence of the two conditions is 1 in 700 live births, but of cleft palate alone it is 1 per 1,000 live births (Roberts and Manchester, 2005: 51). Prevalence rates reported for live births for cleft lip with or without cleft palate and cleft palate alone varies within different racial groups.The highest prevalence rates for are reported for Native Americans and Asians. Africans have the lowest prevalence rates (Wikipedia).

The two problems of cleft palate/lip and cleft palate alone are in fact somewhat distinct entities with different causative factors (Roberts and Manchester, 2005: 51). Cases of cleft palate are multifactorial in cause but have a strong family history and are therefore predominantly genetic in origin (Roberts and Manchester, 2005: 51). It is presumed that the problem was probably as common in the past as it is today (and is seen more in females). However, cleft lip frequency does not vary as much as cleft palate among populations and may possibly be more related to environmental influences (Roberts and Manchester, 2005: 51).

Most babies with a cleft lip can be breastfed. However, some babies have difficulty creating a seal around the nipple and may not be able to breastfeed. Cleft palate can also cause problems with speech, tooth development and hearing (because the tube that connects the ear to the palate (the Eustachian tube) can be affected) (BUPA factsheet). Neonates with cleft palate, therefore require potentially time-consuming and laborious care. This may be provided in western societies today, but may have been unacceptable or even impossible in earlier societies, for example, in hunter-gatherer populations (Roberts and Manchester, 2005: 52). Neonatal death of babies with this condition may, therefore, have been common in the distant past. Such deaths may have been motivated by socio-economic attitudes. The respiratory and speech problems that can be associated with cleft palate, in addition to not being able to feed properly and the potential outward disfigurement (for those with cleft lip also) could have attached stigma to, and the ostracism of, people affected, especially in past communities where the condition was little understood (Roberts and Manchester, 2005: 52).

The preservation of fragile neonatal skulls is rarely good enough to allow a diagnosis of cleft palate to be made. Even diagnosing the condition in adult skeletons is fraught with difficulty because of the fragility of the palate bones, and the problem of distinguishing post-mortem breakage from ante-mortem cleft palate (Roberts and Manchester, 2005: 52). There are, however, reported examples from archaeological contexts: a child from 6th-7th century AD Britain, crania exhibiting both cleft palate and hare lip from 2,000-4,000 BP California, and an 11th-12th century AD British male aged 40-50 years old (Roberts and Manchester, 2005: 52).

References:

BUPA Factsheet: http://hcd2.bupa.co.uk/fact_sheets/Mosby_factsheets/cleft_lip.html (accessed April 1, 2008).

Roberts, C and Manchester, K. 2005. The Archaeology of Disease. Third Edition. Stroud: Sutton Publishing

Wikipedia contributors, “Clefting prevalence in different cultures,” Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Clefting_prevalence_in_different_cultures&oldid=201055636 (accessed April 1, 2008).

Trepanation: The Legacy of Ancient Brain Surgery

Jim Myres at Scientific Blogging discusses an interesting history of skull surgery in ‘Trepanation: The Legacy Of Ancient Brain Surgery‘.

What were the chances of surviving the Black Death?

From the latest edition of Current Archaeology (No. 217):

Why did some people survive the Black Death, and others succumb? At the time of the plague – which ravaged Europe from 1347 to 1351, carrying off 50 million people, perhaps half the population – various prophylactics were tried, from the killing of birds, cats and rats to the wearing of leather breeches (protecting the legs from flea bites) and the burning of aromatic spices and herbs.

Now it seems that the best way of avoiding death from the disease was to be fit and healthy. Sharon DeWitte and James Wood of the University of Albany, New York, have examined 490 skeletons from the East Smithfield plague pit in London and found that the Black Death was selective in picking off the already frail. Lesions (damaged bone) associated with earlier episodes of infection, under-nutrition or other forms of physiological stress were present in most of those buried at East Smithfield, where the dead were stacked five deep in the mass graves on a site hurriedly opened on land donated by the Bishop of London.

“This actually contradicts what many have assumed about the epidemic,” says Dr De Witte. “The pattern we observed is of the Black Death targeting the weak, though it did also kill some people who were otherwise healthy. This is consistent with an emerging disease striking a population with no immunity.”

Domestication of the donkey

An international group of researchers has found evidence for the earliest transport use of the donkey and the early phases of donkey domestication, suggesting the process of domestication may have been slower and less linear than previously thought.

Based on a study of 10 donkey skeletons from three graves dedicated to donkeys in the funerary complex of one of the first Pharaoh’s at Abydos, Egypt, the team, led by Fiona Marshall, Ph.D., professor of Anthropology at Washington University in St. Louis, and Stine Rossel of the University of Copenhagen, found that donkeys around 5,000 years ago were in an early phase of domestication. They looked like wild animals but displayed joint wear that showed that they were used as domestic animals.

“Genetic research has suggested African origins for the donkey,” said Marshall. “But coming up with an exact time and location for domestication is difficult because signs of early domestication can be hard to see. Our findings show that traces of human management can indicate domestication before skeletal or even genetic changes.”

The previously unpublished research was presented in “Domestication of the Donkey: New Data on Timing, Process and Indicators” in the March 10 online edition of the Proceedings of the National Academy of Sciences.

Domestication of the donkey from the African wild ass was a pivotal point in human history. It transformed ancient transport systems in Africa and Asia and the organization of early cities and pastoral societies.

The research team examined the 5,000-year-old Abydos skeletons along with 53 modern donkey and African wild ass skeletons. Analysis showed that the Abydos metacarpals were similar in overall proportions to those of wild ass, but individual measurements varied. Mid-shaft breadths resembled wild ass, but mid-shaft depths and distal breadths were intermediate between wild ass and domestic donkey.

Despite this, all the Abydos skeletons exhibited a range of wear and other pathologies on their bones consistent with load carrying. Morphological similarities to wild ass show that despite their use as beasts of burden, donkeys were still undergoing considerable phenotypic change during the early dynastic period in Egypt. This pattern is consistent with recent studies of other domestic animals that suggest that the process of domestication is slower and more complicated than had been previously thought.

Source: EurekAlert!

Know Your Pathology: Treponematosis

Treponematosis is “a chronic or subacute infection caused by microorganisms called spirochetes of the genus Treponema. On the basis of clinical and geographic variation, the infection is divided into four types: pinta, yaws, bejel (or endemic syphilis) and venereal syphilis” (Aufderheide and Rodríguez-Martín, 1998: 154). There is debate about whether these are different diseases caused by different bacterial species within the genus, or whether they are different clinical manifestations of infection by one species, Treponema pallidum (Aufderheide and Rodríguez-Martín, 1998: 154):

• Pinta is the most geographically restricted of the four syndromes. It is limited to the tropical regions of America, from Mexico to Ecuador. Treponema carateum is responsible for the disease;
• Yaws or frambesia affects especially those populations with a low level of hygiene in tropical or subtropical humid areas. It is caused by Treponema pertenue;
• Bejel (endemic syphilis or non-venereal syphilis) is present in rural populations in temperate and subtropical non-humid regions, and caused by Treponema pallidum endemicum;
• Venereal syphilis is the most ubiquitous of the four syndromes, occurring primarily in urbanised populations in all geographic regions. It is caused by Treponema pallidum pallidum.

Except for pinta, which does not involve bone, the other syndromes produce nearly identical lesions upon the skeleton (Steinbock, 1976: 94). These lesions represent a late stage that marks the generalised spread of bacteria within the body. Inflammatory changes of a mainly destructive nature occur within the skeleton, although considerable repair and regeneration can often also be demonstrated. Venereal syphilis may be either congenital or acquired, congenital syphilis being transmitted in utero via the infected mother. The most severe of the forms, it is characterised not only by inflammatory changes in most tissues of the body, but also by the affection of arterial circulation and the nervous system (Roberts and Manchester, 1995: 151).

The gross bone destruction, called a gumma, is not dissimilar to non-specific osteomyelitis. However, treponemal osteomyelitis is accompanied by extensive regeneration. Consequently, the bone becomes much altered in appearance. The frequency of bone involvement ranges from about 3-5 percent of all cases of yaws to 10-12 percent of all cases of venereal syphilis, with endemic syphilis lying somewhere between the two. In yaws the most commonly affected bone is the tibia, resulting in the distinctive ‘sabre shin’, with the other bones only being affected to a lesser extent, the skull in particular being infrequently involved. Skull involvement is also uncommon in endemic syphilis, but may result in extensive destruction of the nasal and jaw regions. As with yaws, the ‘sabre shin’ shape is often seen, the tibia again being the most commonly affected element (Roberts and Manchester, 1995: 152).

As with the other previously described treponemal diseases, the tibia is the most commonly affected element of venereal syphilis, but multiple bone involvement is frequently noted. It may also result in destructive changes of the joints, such as the characteristic ‘Charcot’s joint’. In contrast to yaws and endemic syphilis, the skull is frequently affected, exhibiting a ‘worm-eaten’ appearance called caries sicca (Roberts and Manchester, 1995: 153).The diagnostic criteria most frequently used to establish the presence of treponemal disease in dry bones are by Hackett (1976).

The epidemiology and spread of treponemal disease has been the subject of much debate, with controversy raging over whether a New or Old World origin for the condition was more likely, the transatlantic voyage of Christopher Columbus being a date of great significance to epidemiologists. It is still unclear when, where and how the currently recognised clinical forms developed, and how they are related to one another from an evolutionary standpoint. Identifying the form of treponemal disease from the physical examination of skeletal remains is often impossible, although attempts have been made to make such a differentiation at population level and it is possible that ancient DNA analysis may aid in this (Mitchell, 2003: 122). For example, the causative agent of venereal syphilis, Treponema pallidum pallidum, has recently been extracted from a two hundred-year-old skeleton from Easter Island using a combination of immunological assay and DNA analysis (Kolman et al., 1999). The oldest dated case of treponematosis in the Middle East comes from Israel, and dates to 1290-1420 AD, during the Mamluk period just after the Crusades (Mitchell, 2003). Pre-Columbian dates have also been given for cases from Britain (Mays et al., 2003) and the United States of America (Hutchinson and Weaver, 1998).

Buckley and Tayles (2003) examined a prehistoric Pacific Island sample for diseases such as yaws, leprosy and malaria. Each type of bone change was recorded, with each type of pathological change also being given a numerical code. This code indicated the type of observed change and whether it was primarily osteoblastic activity, osteoclastic activity, or a mixed response. The presence of lesions was identified macroscopically. Diffuse pitting and/or apposition of new bone on the cortical aspect is an indication of osteoblastic activity as a response to an infectious or non-infectious mechanism. Active (unremodelled) or remodelled lesions were coded as such, the authors stating that “active osteoblastic lesions display a fibrous, vascular, porous, and irregular layer of new bone that has a scab-like appearance over the normal smooth cortex”, in contrast to remodelled lesions that “is usually smooth in appearance, and more organised than new woven bone.” Lesions that developed as a result of osteoclastic activity were identified by lytic foci in the cortical bone and/or trabeculae. Distortion of the normal shape, such as diaphyseal bowing, was also noted as pathological (Buckley and Tayles, 2003: 306). These lesions were then placed into either Osteoblastic (OB) or Osteoclastic (OL) grades 1-4 (Buckley and Tayles, 2003: 306-307), which are described in the article, with photographic illustrations of most, but not all, classes. Hackett’s (1976) coding criteria was used for recording classic gummatous caries sicca lesions of the cranial vault (Buckley and Tayles, 2003: 307).

In an attempt to control some of the limitations of estimating lesion prevalence within a population, the prevalence was estimated using both the individual and skeletal element as denominators. An ‘individual’ was defined by the presence of certain bone elements that are most frequently affected by systemic disease. Those selected, with at least one of each being needed, were the femur, tibia, clavicle, ulna and either the hands or feet for the minimum definition of an ‘observable individual’ (Buckley and Tayles, 2003: 308). This selection criteria was not as strict for the sub-adults due to the fact that sub-adult bones are more readily affected by pathological change. This was useful for increasing the sample size given the fragmentary nature of most of the sub-adult skeletons. Therefore, a sub-adult burial that included the tibia and any two other limb bones were included as individuals (Buckley and Tayles, 2003: 310).

Cranial material was recorded for all observable individuals as complete (presence of all cranial elements, whether articulated or fragmentary), partial (presence of some cranial elements, may be missing the frontal), or absent (no cranial material present). A burial was retained as an individual regardless of cranial preservation, however the presence of the frontal bone and a partial or complete naso-maxillary region was deemed ideal (Buckley and Tayles, 2003: 310).

All bones present were included in the analysis using the skeletal element as the indicator of prevalence, whether complete or partial, and from observable individuals or not. Left and right elements were combined to increase the sample sizes and the bones were sub-divided according to age group. It was considered that sex-related distributions of lesions could be best analysed using observable individuals and so were not studied using skeletal element as the denominator (Buckley and Tayles, 2003: 311). One limitation of the current study was the lack of systematic recording of joint pathology, which may have distorted the prevalence of lytic lesions affecting the joints (Buckley and Tayles, 2003: 310).

The status and severity of lesions in observable individuals was assessed; status 1 indicating several bones were affected and all lesions were active at death, status 2 indicating the presence of active lesions, but with some remodelling at the time of death, and status 3 indicated solely remodelled lesions (Buckley and Tayles, 2003: 310-311). In contrast, the lesions assessed by skeletal element were first classified into three main groups: active OB, remodelled OB, or OL. Cranial lesions were considered separately (Buckley and Tayles, 2003: 311).

It was found that more than half of the observable individuals (57 of 101) had post-cranial lesions, with similar prevalence for all age groups and both sexes. Less than one quarter had cranial lesions and the prevalence decreased with age. However, lesions were present in a low proportion of post-cranial elements overall, although the major long bones, especially the tibia, were most frequently affected. The lesions were effectively all active in sub-adults, whilst in adults there was a mixture of active and remodelled lesions (Buckley and Tayles, 2003: 313-316), a diagnosis of yaws being proposed as the most likely to fit the pattern displayed at the site (Buckley and Tayles, 2003: 321).

This methodology seems particularly useful as it does not require any specialist, or expensive equipment, and would be readily adoptable by most osteoarchaeologists. The categories seem a little crude at times, however this is not uncommon with those methodologies based upon macroscopic examination, and the classes do at least provide a baseline for comparison between populations. Better illustration of the various classes, by photographs of all grades for example, would have been useful in order to help decrease inter-observer variation.

It is worth noting, however, that bone lesions caused by treponemal disease are frequently very similar to non-specific bone diseases, particularly in the long bones. The use of polarised light in light microscopy can illuminate elements of the internal bone structure such as the arrangement of collagenous fibres, and this can make visible structures typically built up by different diseases. At the micro-level, telltale signs of treponemal disease are polsters and grenzstreifen (Schultz, 2001: 126).

Polsters are frequently found in the chronic treponemal diseases of the long bones, and consist of “parallel lamellae arranged at the periosteal level in the form of pillow-like newly built bone formations demarcated by periosteal blood vessels developed during the course of the inflammatory process” (Schultz, 2001: 126). These show a homogeneous structure due to the generally slow growth, in contrast to haematogenous osteomyelitis, which has a much more rapid growth pattern, and thus a more irregular structure (Schultz, 2001: 126). ‘Grenzstreifen’ or ‘grenzlinie’ can be observed in chronic treponemal diseases. This is a “very fine line or a narrow, band-like structure that represents the original external surface of the bone shaft (remains of external circumferential lamellae) and newly built lamellae that originate during the first infection of the periosteum due to the pathological process” (Schultz, 2001: 126).

In contrast to leprosy, treponemal diseases such as endemic syphilis include not only alterations in the subperiosteal bone, but also osteoclastic changes in the endosteal bone and the bony trabeculae of the medullary cavity, as well as in the compact bone of the affected elements (Schultz, 2001: 128). Palaeohistopathological analysis can, therefore, be an important tool for diagnosing conditions such as this in archaeological specimens, helping to discount non-specific conditions that are similar at a macromorphological level.

References:

Aufderheide, A. C and Rodríguez-Martín, C. 1998. The Cambridge Encyclopedia of Human Paleopathology. Cambridge: Cambridge University Press.

Buckley, H. R, and Tayles, N. 2003. Skeletal pathology in a prehistoric pacific island sample: issues in lesion recording, quantification, and interpretation. American Journal of Physical Anthropology 122: 303-324.

Hackett, C. 1976. Diagnostic criteria of syphilis, yaws and treponarid (treponematosis) and of some other diseases in dry bone (for use in osteo-archaeology). Berlin: Springer-Verlag.

Hutchinson, D. L, and Weaver, D. S. 1998. Two cases of facial involvement in probable treponemal infection from Late Prehistoric coastal North Carolina. International Journal of Osteoarchaeology 8: 444-453.

Kolman, C. J, Centurion-Lara, A, Lukehart, S. A, Owsley, D. W, and Tuross, N. 1999. Identification of Treponema pallidum subspecies pallidum in a 200-Year-Old skeletal specimen. Journal of Infectious Diseases 180: 2060-2063.

Mays, S, Crane-Kramer, G, and Bayliss, A. 2003. Two probable cases of treponemal disease of medieval date from England. American Journal of Physical Anthropology 120: 133-143.

Mitchell, P. D. 2003. Pre-Columbian treponemal disease from 14th century AD Safed, Israel, and implications for the medieval Eastern Mediterranean. American Journal of Physical Anthropology 121: 117-124.

Roberts, C., and Manchester, K. 1995. The Archaeology of Disease. 2nd Edition. Stroud: Alan Sutton Publishing Ltd.

Schultz, M. 2001. Paleohistopathology of bone: a new approach to the study of ancient diseases. Yearbook of Physical Anthropology 44: 106-147.

Steinbock, R. T. 1976. Paleopathological Diagnosis and Interpretation: Bone Diseases in Ancient Human Populations. Springfield: Thomas Books.

Know Your Pathology: Leprosy

Leprosy, also known as Hansen’s disease, is “a chronic infectious disease of humans, affecting skin, nasal tissues, peripheral nerves and bones caused by Mycobacterium leprae” (Aufderheide and Rodríguez-Martín, 1998: 141). Co-existing with tuberculosis in many regions of the world today, the leprosy bacilli are transmitted either by inhalation or by direct contact into an open wound from an infected individual. Unlike tuberculosis, however, leprosy is not readily communicable. Those who acquire the condition have frequently been in prolonged contact with infected individuals (Larsen, 1997: 104). This perhaps explains the fact that today this is a disease with high rural incidence, clustering in families (Manchester and Roberts, 1989: 267).

Neurotrophic changes are commonly seen in advanced leprosy. Destruction of the sensory nerves with ensuing anaesthesia and circulatory alterations lead to slowly progressive atrophy of terminal phalanges, resorption progressing proximally, even as far as the metapodials in some instances. Severe degenerative arthritis and neuropathic arthropathy, similar to Charcot’s joint, can be seen in weight-bearing joints such as ankles and feet. In addition, the existing anaesthesia facilitates traumatic mutilations and secondary infections  (Ortner and Putschar, 1981: 177). Such paralysis also predisposes the individual to fractures caused by clumsiness or uncoordination (Judd and Roberts, 1998: 53).

If the affected individual has good immunological resistance the disease is confined to the nerves, producing what is known as the tuberculoid form of the disease. If resistance is poor then the lepromatous form occurs. Borderline cases can, and do, occur, however. Skeletal changes occur in both forms, but they are more frequent in the lepromatous form (Waldron, 2001: 101). Disruption of the muscles in the lower limbs and hands, as well as paralysis of the ulnar nerves, results in claw-hand deformities. Whilst such paralysis can be difficult to determine in archaeological specimens, in at least one instance a groove has been identified on the volar surface of the distal end of the proximal phalanx, a lesion also noted in the radiographs of modern patients (Andersen and Manchester, 1987: 78). Similar loss of motor function in the feet leads to the collapse of the longitudinal arch and the development of pes planus, or flat foot. The tensile stress this imparts to the ligaments is likely to be the cause of exostoses found at the sites of attachment (Andersen and Manchester, 1988: 52-54).

Facies leprosa of the skull shows atrophy of the anterior nasal spine, in most cases combined with central atrophy of the alveolar process. This is classified into three degrees (Møller-Christensen and Inkster, 1965: 11):

I° – in which there is a well-defined reduction of the spine;
II°- in which there is an advanced nasal spine atrophy although a distinct but very small nasal spine remains;
III° – in which there is a complete obliteration of the nasal spine.

The atrophy of the maxillary alveolar process and inflammatory changes of the superior surface of the hard palate are also classified into three degrees in a similar manner (Møller-Christensen and Inkster, 1965: 11). Further bone changes are set out in Møller-Christensen (1961).

The deformations associated with advanced leprosy led to sufferers being segregated, especially during the medieval period with theologians portraying the disease as the chastisement of God. The concept of the leper hospital did not really develop until the eleventh century AD, the third Lateran Council issuing orders for the isolation of lepers in 1179 (Rawcliffe, 1995: 14), at which point there was a sudden explosion in the numbers of these institutions. This suggests that either leprosy was becoming more common, that disease generally was becoming more common, or that society was becoming more charitable (Manchester and Roberts, 1989: 268). Alternatively, it may be viewed as part of a wider crusade against heretics, Jews, homosexuals, and anyone else whose behaviour was viewed as suspicious (Rawcliffe, 1995: 14).

The cross-immunity of leprosy and tuberculosis may explain the decline in leprosy towards the fourteenth century when there is a coincident rise in tuberculosis (Manchester and Roberts, 1989: 269). This relationship is not simple, nor universal, and appears to be affected by multiple variables. However, it may be this that explains the burial of two leprous males and tuberculous female from the Iron Age of South East Asia (Tayles and Buckley, 2004: 253).

A study aimed primarily at the epidemiological analysis of leprosy in medieval Denmark devised a simple recording form that allowed them to generate large amounts of data relatively quickly. In this the osteological changes were recorded in seven locations (Boldsen, 2001: 383):

1. the edge of the nasal aperture;
2. the anterior nasal spine;
3. the alveolar process on the premaxilla;
4. the palate;
5. subperiosteal exostoses on the fibula;
6. porotic hyperostosis on the fibula;
7. the fifth metatarsal

Whilst it is acknowledged that some symptoms are best described as a multi-stage sequence of events, for the sake of simplicity all were recorded simply as 1) present or 2) absent. Zero indicated the condition was unobservable in that skeletal element. This coding could then be analysed using statistical packages to describe the frequency and prevalence of the disease (Boldsen, 2001: 383). Such simplicity does make this recording system easy to apply, and also easy to duplicate by other researchers. Scoring changes merely as present or absent reduces the likelihood of inter-observer error, which, on the whole, is more likely to arise with examples of minor change. It does, however, possibly over-simplify the sequence of many of the symptoms, and has the effect of grouping together all sufferers with the condition regardless of the degree of advancement. This could mean that some more subtle nuances of patterning are lost.

Many skeletal changes are considered characteristic of leprosy, however, others such as tibial periostitis may be caused by several different infections. The identification of Mycobacterium leprae DNA can, therefore, be very useful in confirming a diagnosis (Wilson, 1999: 14), and this is an approach that is becoming more common as the techniques involved in the study of ancient DNA improve. An example of this is a case from Byzantine Israel where the presence of M. lepra was used to differentiate between leprosy and a condition known as Madura foot, or Mycetoma (Spigelman and Donoghue, 2001).

Palaeohistopathological analysis can help to differentiate diseases such as leprosy from other specific infections like treponemal disease and from non-specific conditions. For example in lepromatous periostitis polster-like structures that are rudimentarily developed and relatively flat can be observed, in contrast to those of treponematosis which tend to be well-developed (Schultz, 2001: 126). Furthermore, in contrast to chronic treponemal disease, there are no observable grenzstreifen in chronic leprosy (Schultz, 2001: 128).

References:

Andersen, J. G and Manchester, K. 1987. Grooving of the proximal phalanx in leprosy: a palaeopathological and radiological study. Journal of Archaeological Science 14: 77-82.

Andersen, J. G and Manchester, K. 1988. Dorsal tarsal exostoses in leprosy: a palaeopathological and radiological study. Journal of Archaeological Science 15: 51-56.

Aufderheide, A. C and Rodríguez-Martín, C. 1998. The Cambridge Encyclopedia of Human Paleopathology. Cambridge: Cambridge University Press.

Boldsen, J.L. 2001. Epidemiological approach to the paleopathological diagnosis of leprosy. American Journal of Physical Anthropology 115: 380-387.

Judd, M. A, and Roberts, C. A. 1998. Fracture patterns at the medieval leper hospital in Chichester. American Journal of Physical Anthropology 105: 43-55.

Larsen, C. S. 1997. Bioarchaeology: Interpreting behavior from the human skeleton. Cambridge: Cambridge University Press.

Manchester, K, and Roberts, C. 1989. The palaeopathology of leprosy in Britain: a review. World Archaeology 21 (2): 265-272.

Møller-Christensen, V. 1961. Bone Changes In Leprosy. Bristol: John Wright & Son Limited.

Møller-Christensen, V, and Inkster, R.G. 1965. Cases of leprosy and syphilis in the osteological collection of the Department of Anatomy, University of Edinburgh. Danish Medical Bulletin 12 (1): 11-18.

Ortner, D. J, and Putschar, W. G. J. 1981. Identification of Pathological Conditions in Human Skeletal Remains. Smithsonian Contributions to Anthropology 28. Washington and London: Smithsonian Institution Press.

Rawcliffe, C. 1995. Medicine and Society in Later Medieval England. Stroud: Sutton Publishing.

Schultz, M. 2001. Paleohistopathology of bone: a new approach to the study of ancient diseases. Yearbook of Physical Anthropology 44: 106-147.

Spigelman, M and Donoghue, H. D. 2001. Brief communication: unusual pathological condition in the lower extremities of a skeleton from ancient Israel. American Journal of Physical Anthropology 114: 92-93.

Tayles, N and Buckley, H. R. 2004. Leprosy and tuberculosis in Iron Age Southeast Asia? American Journal of Physical Anthropology 125: 239-256.

Waldron, T. 2001. Shadows in the Soil: Human Bones and Archaeology. Stroud: Tempus Publishing.

Wilson, L. E. 1999. Leprosy in Scotland. Unpublished MA dissertation. University of Leicester.