Bacterial Infections

Chapter 11

Bacterial Infections Charlotte A. Roberts1 and Jane E. Buikstra2 1

Durham University, Durham, England, 2Arizona State University, Tempe, AZ, United States

INTRODUCTION The bacterial infections tuberculosis (TB), leprosy, treponematosis, brucellosis, glanders, actinomycosis, nocardiosis, and plague form the subject matter of this chapter. While infections may be caused by viruses, fungi, parasites, and protozoa, the most common organisms causing infectious disease are bacteria. Tuberculosis and leprosy, and to a lesser extent treponemal disease (TD), are the bacterial infections most often reported in paleopathology. Plague is the only bacterial infection solely affecting soft tissue that is reported here, as it has received considerable recent biomolecular attention (see Chapter 8). Actinomycosis, glanders, and nocardiosis rarely affect the skeleton but are included to maintain continuity from Ortner (2003).

TUBERCULOSIS Introduction Tuberculosis (TB) is a chronic infectious disease caused by one of the species of the Mycobacterium tuberculosis complex (MTC) (Table 11.1). Along with leprosy, it is one of the more common mycobacterial diseases recorded in skeletal remains, although a very low percentage of people who contract the both infections develop bone changes. Mycobacterium tuberculosis, Mycobacterium africanum, and Mycobacterium canettii are the most significant organisms for humans, their principal hosts (Grange, 2014). Humans are also secondary hosts for M. bovis and M. caprae. Many animals, both wild and domestic, may contract TB and thus are a risk for transmission to humans and vice versa (Pfeiffer and Corner, 2014: Table 28.1; also see Mays, 2005 on the evidence of TB in ancient animals). Direct spread of the relevant MTC organisms occurs via droplet transmission between humans. Mycobacterium bovis is also transmitted to humans through ingestion of infected animal products, e.g., meat and milk.

Tuberculosis is a reemerging disease. In 2016, 10.4 million people fell ill with TB, and 1.7 million died; 40% of HIV-related deaths were also due to TB (human immunodeficiency virus). TB is the ninth leading cause of death worldwide and the leading cause of death from a single infectious agent (WHO, 2017a,b). Thus, the statement by Smith (1988) that tuberculosis had been “defeated” was nullified by 1993, when the World Health Organization declared a global TB emergency. Risk factors include poverty, poor living conditions and malnourishment, migration, specific occupational risks such as working with animals and their products, vitamin D deficiency, HIV, and stress. TB is treated with a suite of antibiotics, which has led to a drug resistance due to adaptation by the pathogen (Lange et al., 2018). Sanatoria were opened in the 19th and 20th centuries for care and treatment of people with TB (Bryder, 1988; Macdonald, 1997). Treatments included rest, a good diet, graded exercise, and surgery, although their efficacy continues to be debated. In the more distant past, more puzzling treatment methods are described, including “Touching for the King’s Evil” in Europe (Crawfurd, 1911), alongside herbal remedies. Historically, TB has been stigmatized and this remains a challenge for those who have TB today (Mason et al., 2016).

Pathology If a person becomes infected with TB via droplet transmission, a primary pulmonary focus forms, followed by single or multiple foci in the regional hilar lymph nodes, found on the medial aspect of each lung. The lymphatic system carries lymph, a clear fluid that contains white blood cells, including lymphocytes that attack infective organisms. Lymph nodes are part of the lymphatic system and occur in groups in specific parts of the body where lymph is drained to rid the body of toxins and other waste products (e.g., in the groin, armpits, and neck).

Ortner’s Identification of Pathological Conditions in Human Skeletal Remains. DOI: https://doi.org/10.1016/B978-0-12-809738-0.00011-9 © 2019 Elsevier Inc. All rights reserved.

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322 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

TABLE 11.1 Members of the Mycobacterium tuberculosis Complex (Grange, 2014: Table 3.1) Species

Principal Hosts

Mycobacterium tuberculosis

Humans

Mycobacterium africanum

Humans

Mycobacterium bovis

Cattle, deer, elk, bison, badger, opossum

Mycobacterium canettii

Humans

Mycobacterium caprae

Goat

Yes

Mycobacterium microti

Vole, hyrax, llama

Very rare

Mycobacterium mungi

Banded mongoose in Botswana

Very rare

Mycobacterium pinnipedii

Seal, sealion

Very rare

The initial focal lesions of TB form the primary TB complex. Typically, this is an acute systemic disease of childhood, which is commonly acquired through droplet transmission (Wainwright, 2014). The transmission of TB via contaminated animal products is much less frequent and occurs through the intestinal pathway with formation of a primary complex in the wall of the intestines and mesenteric lymph nodes. The pathogenesis of TB depends on the size of the inoculum, the virulence of the organism, and the immune resistance of the host. Therefore, a person with a compromised immune system is more susceptible to infection than an individual who is not immunocompromised. In most instances (in Western populations), the primary complex heals without leading to a progressive disease. If the primary complex fails to heal, the lung (or intestinal) lesion progresses, and tubercle bacilli may be disseminated through the bloodstream and/or lymphatic systems to other organs and tissues, including the skeleton (secondary TB; Wainwright, 2014). Secondary TB is usually a chronic disease of adults due to reactivation of dormant bacilli or reinfection. Again, the number of organisms and the immunological defence capacity of the person determine whether early hematogenous dissemination will eventually lead to fatal miliary tuberculosis, with multiple small tubercles in the tissues involved, and/or tuberculous meningitis, or to isolated organ TB, including the bones of the skeleton. Organ TB may not make its appearance until years after the early dissemination of the bacteria and it is precipitated by lowered immune system strength, poor host resistance due to malnutrition, other diseases, or possibly local trauma. Because dormant primary pulmonary foci may harbor viable organisms for many years, late hematogenous dissemination also may become the source of organ TB. Skeletal TB is, with rare exceptions, the result of limited hematogenous dissemination. Whether or not the secondary TB is the result of activation of dormant tubercle bacilli or the introduction of new TB organisms, the

Humans as Secondary Hosts?

Yes

immune system quickly recognizes the pathogens and may initiate a very aggressive immune response. This response attacks the pathogen but also can destroy normal organ tissues that are nearby, with potentially serious dysfunction of affected organs. This overly aggressive response by the host’s immune response illustrates an important dimension of disease, i.e., the adverse consequences of hyperimmunity. This problem is confronted in other pathological conditions such as rheumatoid arthritis.

Statistical Data Estimating the frequency of tuberculosis prior to the identification of M. tuberculosis by Robert Koch in 1882 is problematic because people combined different primary lung diseases into a single category known as “consumption” (Roberts and Manchester, 1995: 135; Roberts and Cox, 2003: Chapter 6). References to TB in early documentary sources are also challenging because the disease shares common signs and symptoms with other lung diseases such as pneumonia and lung cancer (see Mitchell, 2011 for a general overview). There is, however, a strong probability that TB was a significant cause of morbidity in England during the medieval period. This morbidity increased until about the middle of the 19th century when, in Europe and the United States at least, its frequency began to decline for reasons that continue to be debated (Davies et al., 1999). Although extrapolating information from TB data between the date of discovery of the organism (1882) and the introduction of antibiotic treatment (B1950) requires caution, data can provide insight on the impact of TB that may be applied to earlier periods. For example, TB mortality in Germany in 1892 was 260 per 100,000 living inhabitants. For the beginning of the 20th-century (1901) data are only available for part of Europe and the United

Bacterial Infections Chapter | 11

States, covering mortality from pulmonary TB. Within this subset, TB mortality ranges from 111 to 289 per 100,000 living inhabitants. The age and sex distribution of all tuberculosis deaths for Western Europe, the United States, and Canada for 1949 were published by the International Union Against Tuberculosis in 1964. While earlier data show a predominance of male over female TB-related deaths, with ratios of almost 2:1, more recently the morbidity difference between the sexes has disappeared (Resnick and Niwayama, 1995a: 2462). However, such figures can be deceptive. While women have a higher resistance to infectious disease per se (Nhamoyebonde and Leslie, 2014), they may be less likely to be diagnosed due to sociocultural factors that prevent or delay their access to clinics for diagnosis and treatment. However, one must appreciate that the data for 1892 and 1901 are already modified by successful surgery, and the figures for 1949 by the early availability of effective chemotherapy. Therefore, these data represent a lower prevalence than one should expect in earlier periods. Even so, in the official yearbook for 1956 West Germany reported 20,342 people affected by TB, with an incidence of 3358 (Kastert and Uehlinger, 1964). Total TB mortality in West Germany has, however, steadily declined, especially in infants and children. Among 560 people autopsied who had died from fatal hematogenous TB from 1923 through to 1932, 115 had involvement of the skeleton (21%). Of these, 58 were limited to the skeleton, whereas 21 showed tuberculous foci in other organs, 12 showed active pulmonary tuberculosis, and 24 organ and lung TB (Kastert and Uehlinger, 1964: 447). In general, skeletal tuberculosis affects only about 3% of those with pulmonary and about 30% of those with extrapulmonary TB (Kastert and Uehlinger, 1964: 444, 445). The distribution and frequency of tuberculosis in bones and joints in a large clinical series (1752 individuals) prior to 1892 was published by Alfer (1892) (Table 11.2). Of these, 91 presented with multiple tuberculous bone and joint lesions. The age distribution of the same series is shown in Table 11.3. It indicates the great preponderance of skeletal tuberculosis affecting infants and children, but the age distribution today has changed, with patients of all ages being affected (Resnick and Niwayama, 1995a: 2462). However, in low-incidence countries an older age is particularly associated with TB, i.e., those born when TB was common (Abubakar and Aldridge, 2014).

323

TABLE 11.2 Locations of Bone Lesions in Skeletal Tuberculosis Listed in Order of Decreasing Frequency Location

No. of Instances

Bones Spine

239

Tarsals and metatarsals

184

Carpals and metacarpals

109

Ribs

67

Tibia and fibula

49

Radius and ulna

48

Phalanges of fingers

38

Temporal bone

33

Phalanges of toes

31

Pelvis

27

Sternum

21

Femur

14

Humerus

10

Mandible

9

Scapula

8

Orbital margin

7

Parietal bone

5

Frontal bone

5

Maxilla

5

Sacrum

3

Zygoma

2

Patella

2

Clavicle

2

Occipital bone

1

Coccyx

1

Joints Knee

281

Hip

241

Elbow

113

Ankle

43

Shoulder

28

Wrist

20

Metacarpal phalangeal

5

Metatarsal phalangeal

4

General Pattern of Bone and Joint Tuberculosis

Sternoclavicular

4

Acromioclavicular

1

Bone TB affects 3% 5% of people with untreated TB (Jaffe, 1972). This frequency can vary across different

Source: After Alfer, 1892.

TABLE 11.3 Age Distribution of Skeletal Tuberculosis in Bones and Joints Listed in Order of Decreasing Frequency Years old* Location

0 5

5 10

10 15

15 20

20 25

25 30

30 35

35 40

40 45

45 50

50 55

55 60

60 65

65 70

70 75

75 80

Spine

89

59

32

23

9

10

3

6

3

1

4

Tarsals and metatarsals

9

20

26

38

14

10

10

7

6

8

Carpals and metacarpals

16

12

16

23

12

5

1

5

3

6

11

9

9

5

2

1

2

2

4

2

9

10

7

2

2

1

1

2

Bones

Ribs

4

9

8

5

Tibia and bula

12

5

7

x8

3

Radius and ulna

6

9

6

8

4

2

5

5

1

7

5

1

2

3

1

Phalanges of fingers

15

7

4

4

1

2

2

Temporal bone

6

4

2

3

7

5

2

1

Phalanges of toes

2

6

5

7

1

Pelvis

1

1

3

7

5

3

1

Sternum

1

Femur

2

Humerus

1

2

Scapula Orbital margin1

2

Frontal bone Maxilla Mandible

1

Parietal bone Sacrum

2

Zygoma Occipital bone Coccyx

1

1

1

1

1

1

1

3

1 3

1

2

1 2

Eˆ1

1

1 1 1

1

1

2

2

3

1 1

2

1

1 1

3

2

1

Clavicle

2

2

Eˆ1

1

Patella

1

3

1

1

1

1

2

1

1

1

1

1

1

2

3

1

1

3

1

2

2

1

1

1

1

3

2

2

2

2

1

1

1

2

1

1

1

1

1

Joints Knee

47

52

47

37

20

11

23

11

11

3

2

8

6

Hip

58

59

43

46

9

11

6

4

1

1

3

Elbow

7

14

14

21

12

9

6

5

9

8

5

2

Ankle

5

9

10

5

2

1

1

3

2

2

6

3

5

3

1

1

2

2

1

1

5

3

1

3

2

1

3

1

1

1

1

1

2

1

5

4

3

Shoulder Wrist

1

Metacarpal phalangeal joints Metatarsal phalangeal joints

1

Sternoclavicular joint

1

3

3

2 2

3 1

1

6

5

1

Acromioclavicular joint Multiple foci

19

13

Overlap in age categories is from Alfer and is not resolved here.

Source: After Alfer, 1892.

14

11

4

3

1

326 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

sources, and there may be a higher prevalence in children. For example, Roberts and Bernard (2015) and Bernard (2003) report a 12% frequency rate for children hospitalized in a sanatorium during the 1930s 1950s. Tubercle bacilli circulating in the bloodstream can enter the bones of the skeleton, particularly in areas of hematopoietic (red) marrow, which has a high circulatory and metabolic rate. Thus, the areas of cancellous bone are favored, rather than the cortex or medullary cavity. Any bone of the skeleton can potentially be affected, but some are more frequently involved than others. In adults, the metaphyses and epiphyses of long bones are especially at risk. In infants and young children, the distribution of hematopoietic marrow involves much more of the skeleton. Therefore, tuberculous foci often occur in the tubular bones of the hands and feet (metacarpals, metatarsals, and phalanges) and in ossification centers of the tarsal and carpal bones, in addition to occasional diaphyseal lesions in long bones. Lewis (2018: 156 162) usefully summarizes the clinical literature on the bones most commonly affected in children. The vertebrae, ribs, and sternum have hematopoietic marrow throughout life, and so TB of the spine is observed at all ages. In the lower spine, the specialized paravertebral venous plexus of Batson seems to provide the optimum vascular environment for the bacteria (Resnick and Niwayama, 1995a: 2464). The flat bones, particularly the cranial vault, are more commonly involved in infants and children than adults. Tuberculous arthritis is intimately linked to infectious involvement of the bones of the adjacent joints and for that reason will be discussed here. Tuberculous arthritis may begin in the synovial membrane, in the bone, or simultaneously in both. This is explained by the joint’s blood supply both to the epiphysis and joint capsule. In an advanced stage, the original focus often cannot be ascertained. The morphology of tuberculous lesions in dry bones is not specific and overlaps considerably in appearance with manifestations of other bone infections, but some bone changes are more specific than others. For example, the spine is considered a very useful part of the skeleton for TB diagnosis in an archeological skeleton (more specific evidence), while endocranial new bone formation, periostosis on the ribs, and pleural calcification are considered nonspecific (see summary in Roberts and Buikstra, 2003: 99 107). However, there are some general characteristics of diagnostic value, in addition to the age distribution of skeletal lesions. TB, in its exudative phase, permeates marrow spaces, devitalizes areas of cancellous bone and this leads to the formation of centrally located sequestra (caries). The proliferative granulomatous phase leads to local destruction and cavitation in cancellous bone (Resnick and Niwayama, 1995a). In either case very little, if any,

perifocal reactive bone formation is elicited, and often bones will show perifocal or general osteoporosis. In long bones, TB tends to remain localized, mostly in the metaphyses or epiphyses. In contrast to purulent osteomyelitis, massive sequestra, especially of cortical bone, are rare. Periosteal reactive new bone is limited or absent, except in the small tubular bones in infants and children where destruction or sequestration of the cortex and the formation of an expanded shell of periosteal reactive bone occurs as tuberculous dactylitis or spina ventosa (Resnick and Niwayama, 1995a: 2477). Similar changes affecting part of an involved long bone are also observed in the young age groups. Perforation of the cortex with formation of an extraosseous abscess, with or without pustulous perforation of the skin, is common. Traces of such an abscess can sometimes be seen in the presence of reactive periosteal bone in the vicinity of the opening and, occasionally, ossification of the abscess wall. In joints, destruction of the articular surface may be minimal if the process is limited to the synovium. Undermining and resorptive grooving of the articulating bones frequently occurs along the line of the synovial membrane or ligamentous attachments. If the process started in the bone, or involves bone extensively, destruction of the articular surface and the epiphyses often occurs, with formation of cancellous sequestra and/or cavitation. Substantial reactive new bone formation as a secondary osteoarthritis following partial destruction of the joint can occur. Skeletal TB can heal without specific therapy. Small tuberculous foci, particularly in infants and small children, may leave no trace because the area is removed during subsequent growth and remodeling. Foci destroying a growth plate will leave a growth deficit and/or deformity in the young age groups. Foci in the vicinity of a growth plate may lead to excessive growth. This is no different to the effect of osteomyelitis. Joint TB may heal with obliteration of the joint cavity, often terminating in bony ankylosis with varying degrees of bone mass loss in the constituent bones. After healing, the spongiosa undergoes remodeling along altered stress lines but never reaches the original density of cancellous bone (Kastert and Uehlinger, 1964: 467). The bone changes of TB and their understanding have benefitted in recent decades from research on documented skeletal collections such as the Robert J. Terry Collection (Smithsonian Institution, Washington DC, United States), the Hamann Todd Collection (Cleveland Museum of Natural History, Ohio, United States), and the Coimbra Identified Skeletal Collection curated at the Department of Anthropology, University of Coimbra, Portugal. Bone changes have also been the recent subject of discussion in relation to antibiotic treatment (Holloway et al., 2013a,b; Steyn et al., 2013). For example, Steyn et al. (2013)

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argues that today more skeletal TB is seen because people live longer with the infection due to long-term antibiotic use, giving more time for lesions to develop. In addition, Wilbur et al. (2008) consider the effect of diet on the expression of TB in archeological skeletons, finding that iron and protein are important for immune function and infection outcome in TB, and that diet may influence the potential for TB to disseminate from the lungs to the skeleton. General frailty, which may be related to having TB, may also lead to poorer growth of the bones of the skeleton (e.g., see Mansukoski and Sparacello, 2018). The order in which affected bones are considered within this chapter reflects how frequently they are affected, starting with the most commonly involved area, the spine.

327

FIGURE 11.1 Kyphotic spine in a person with tuberculosis. Courtesy: Peter Davies.

The Spine Vertebral TB (also named tuberculous spondylitis, or Pott’s disease, after Percival Pott who first named it in the 18th century) is, in practically all clinical and autopsy studies, the most common and most characteristic skeletal change associated with the TB. In earlier times, the disease usually began in childhood. This age distribution seems to be changing, with older individuals being affected more often today (Resnick and Niwayama, 1995a: 2464). For example, a rapid decline in incidence for those over 7 years of age was reported in a welldocumented, post-1920 series of 1490 individuals (Sorrel and Sorrel-Dejerine, 1932). The fourth, fifth, sixth, and seventh decades showed only 100, 50, 18, and 2 new people affected, respectively. Because the disease takes a very chronic course, people with active or healed lesions may be observed at any age. Destruction of the vertebral bodies is usually purely lytic, leading to cavitation. As a result of this process, vertebral collapse can occur and may be combined with a pathological fracture (Fig. 11.2) and a kyphotic deformity of the spine (Figs. 11.1 and 11.2). Small wedge-shaped remnants of the affected vertebrae often remain in contact with their end plates and are displaced anteriorly or posteriorly by the collapse. Extension of TB to adjacent vertebrae mostly occurs through the area of the nucleus pulposus of the intervertebral disc. Central spongiosa sequestra can also occur (Fig. 11.2B). The most common site for TB infection in the spine is the first lumbar vertebra, with the frequency of occurrence decreasing with distance from this vertebra (Resnick and Niwayama, 1995b: 2436). The lower spine is the primary focus in skeletal TB at all ages (see Fig. 11.3). Autopsy data on the frequency of involvement for individual vertebrae show that in about 80% of clinical and autopsy cases at least two adjacent vertebrae are involved (Fig. 11.3), whereas three or more were affected

in about 10% of the total. Multiple foci separated by intact vertebrae were also observed in about 4% of people. The part of the vertebra involved in skeletal TB is almost exclusively the vertebral body and overwhelmingly its anterior portion (Resnick and Niwayama, 1995a: 2464). Even after extensive destruction of one or several adjacent vertebral bodies, extension into the vertebral arches is uncommon, and the true intervertebral joints (apophyseal facets) and spinous processes are almost never destroyed. When the posterior elements of the vertebrae are involved, neurological compromise is a common complication (Resnick and Niwayama, 1995a: 2464; see also Travlos and Du Toit, 1990). A site in the vertebral column where posterior element involvement is more common is suboccipital TB involving the atlas and the axis. Because of the rudimentary bodies of these vertebrae, their intervertebral joints are commonly involved (Oehlecker, 1924: 242). Isolated tuberculous foci in posterior elements of vertebrae are extremely rare. Sorrel and Sorrel-Dejerine (1932: 500) observed only three cases of isolated spinous process destruction, and one with lumbar transverse process involvement, in a large sample of individuals with skeletal TB. A common complication of vertebral TB is extension to adjacent soft tissues (Resnick and Niwayama, 1995a: 2465). When this occurs, a unilateral or bilateral paravertebral (psoas) abscess develops that can be accompanied by an associated fistula. A connective tissue sack encapsulates the abscess (Fig. 11.4). The skeletal response to the presence of a paravertebral abscess is highly variable. There may be flared, shell-like bony extensions from the affected vertebra at the site where the abscess initially exits the bone (Fig. 11.5). Distinguishing between bone abnormalities resulting directly from an active tuberculous focus and the changes that are secondary reactions to the

FIGURE 11.2 Spinal TB, partly healed, involving thoracic (T) vertebrae 7 and 8 and the first lumbar (L) vertebra, with kyphotic deformity: (A) lateral view, showing fusion of vertebrae and periosteal new bone; (B) cut surface, showing vertebral body involvement at two sites (arrows), T8 and L1. Note the sequestrum in L1 (lower arrow) (52-year-old female, IPAZ autopsy S901 from 1948).

Location on Spine

Number of Vertebrae C1 C2 C3 C4 C5 C6 C7 T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 L1 L2 L3 L4 L5 S1 S2 S3 S4 S5

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 FIGURE 11.3 Distribution of lesions in 62 autopsies of people with vertebral tuberculosis (after Kastert and Uehlinger, 1964) (C 5 cervical, T 5 thoracic, L 5 lumbar, S 5 sacralr).

FIGURE 11.4 Tuberculosis of the dorsolumbar spine with kyphosis and evidence of a large right psoas abscess (adult, PMUG, no number).

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329

FIGURE 11.5 Healed spinal TB with kyphosis (thoracic vertebrae 6 9) and a paravertebral abscess (thoracic 10 to lumbar 1): (A) lateral view; (B) cut surface (48-year-old female with pleural (visceral) and miliary tuberculosis, who died in 1936; IPAZ S 793 ).

presence of the paravertebral abscess overlying the bone can be challenging. A psoas abscess may also affect the proximal femur and the pelvic bones, leading to bone formation, destruction, or both. In Johannsson’s (1926) clinical series of 86 individuals with TB, 32 developed only an abscess, 22 had an abscess and fistula, and 2 had fistulae only. The psoas abscess extends usually downward, following the line of gravity, beneath the anterior longitudinal ligament and along the fascial plane of the psoas muscle, occasionally showing ossification of the abscess wall (Fig. 11.6). It may become an important source of contact infection for additional vertebrae, especially below the original focus. The tuberculous process erodes the cortical surface and slowly extends into the anterior portion of the vertebral bodies (Figs. 11.7 and 11.8). Such secondary extension into adjacent ribs is occasionally observed. The lower spine of a 17-year-old woman who had TB (Robert J. Terry Anatomy Collection) presented no evidence of destruction of any vertebral body. Therefore, the extensive reactive bone formation is probably a response to an overlying paravertebral abscess (Fig. 11.9A and B). There is a lytic focus in the pelvis associated with reactive

FIGURE 11.6 Ossification in the wall of a right tuberculous psoas abscess extending to the femur; secondary to spinal tuberculosis (55year-old male, FPAM 2894).

330 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 11.8 Lumbosacral TB with kyphosis and a prevertebral (sacral) abscess. Notei the almost complete destruction of the lumbar vertebral bodies alongside lytic lesions of the sacrum (the individual was about 10 years old, FPAM 1493).

FIGURE 11.7 Tuberculosis of the lumbar vertebrae. Anterior destruction of lumbar vertebrae 3 5 by an abscess anterior to the vertebrae (prevertebral); marked kyphotic angulation (20-year-old male, FPAM 3583).

periostosis on the right iliac crest (Fig. 11.9C and D) and a destructive lesion probably associated with a draining sinus on the inferior margin of the left eighth rib (Fig. 11.9E). Reactive bone formation is also seen in association with a fairly limited lytic focus (Fig. 11.10A) in the first lumbar vertebra of a 19-year-old man who also died of tuberculosis (Robert J. Terry Anatomy Collection). Reactive bone formation adjacent to the lytic focus (Fig. 11.10B) and extending superiorly onto the lower thoracic vertebrae suggests a paravertebral abscess. Evidence of pleural periostosis associated with a lytic

focus eroding the inferior margins of the fifth and sixth right ribs argues for the presence of a draining sinus from a tuberculous focus in the thoracic vertebrae (Fig. 11.10C). Collapse of one or several vertebral bodies, with vertebral arches and spinous processes remaining, leads to a sharply angular kyphosis (gibbus). This deformity was observed in about 60% of individuals with spinal TB in the preantibiotic era (Reinhart, 1932). The kyphosis is most marked in the thoracic spine (Fig. 11.5), whereas lumbar lesions may terminate with ‘telescoping’ of the defect rather than severe angulation (Girdlestone, 1965: 81:3). Healing may occur with permanent preservation of the deformity by fusion of the vertebral body remnants. Formation of new spongiosa and of cortex is rather meager, and residual cavity defects may remain. There is usually secondary bony ankylosis between the true intervertebral joints of the involved segment and often ossification of the interspinous ligaments. If a sharp kyphosis develops in childhood, increased height of the vertebrae below due to compensatory growth is often observed. In some cases, a lateral deformity (scoliosis) may occur as a consequence of lateral destruction of one or more vertebral bodies rather than the much more common anterior destruction.

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331

FIGURE 11.9 Spinal TB without vertebral collapse but with reactive bone formation on the lower vertebral bodies: (A) anterior view of the L1 S5 vertebrae showing extensive reactive new bone formation probably in response to an overlying abscess; (B) detail of L5 S1 vertebrae; (C) lytic focus on the right ilium with bone destruction; (D) reflected right sacroiliac joint showing subchondral bone destruction; (E) pleural surface of left eighth and ninth ribs with a lytic focus on the inferior margin of the eighth rib (17-year-old female, Robert J. Terry Anatomy Collection; NMNH 382085329).

A differential diagnosis for these bone changes includes osteomyelitis and healed compression fractures of the vertebral body. In osteomyelitis, the extensive destruction of several vertebral bodies leading to the sharply angulated kyphosis is uncommon. Paravertebral abscesses are also less frequently observed and, if present, may extend above the lesion as well as below because

they form rapidly. In a healed fracture with angular deformity usually only one vertebra is involved, and there is much less extensive destruction of the vertebral body. Isolated TB of the sacrum and of the coccyx is rare (David, 1924). Abscess formation is a frequent complication, and in the case of the coccyx, total sequestration is not unusual (Konschegg, 1934).

332 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 11.10 Tuberculosis with spinal and rib involvement: (A) anterior view of T11 S5 vertebrae; note the lytic focus on the vertebral body of L1; (B) detail of lytic focus with only minimal remodeling; (C) pleural surface of the right ribs 4 6 showing destructive remodeling with reactive bone formation (19-year-old male, Robert J. Terry Anatomy Collection; NMNH 382085-129).

Finally, with respect to spinal TB, caution is urged regarding lytic ‘lesions’ in vertebral centra that have been described to be related to TB (Baker, 1999). These present as circumferential apertures appearing halfway between the superior and inferior end plates. These holes may represent normal vascularization or other developmental process (Scheuer and Black, 2000: 190), although it is not possible to discount co-occurrence of normal ‘developmental’ holes or vascularization compounded by a pathological process. While some aDNA analysis of

such skeletons with these lesions has been positive for TB (e.g., Haas et al., 2000), this does not mean that the lesions can be objectively and directly linked to TB.

The Hip Tuberculosis of the hip joint is the second most frequent skeletal lesion after tuberculous spondylitis. All statistical series agree that the majority of people who contract hip TB develop it in childhood and that its onset after 25 years

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of age is rare (Johannsson, 1926: 159; Sorrel and SorrelDejerine, 1932: 309). In Sorrel and Sorrel-Dejerine’s study of 995 individuals with hip TB, the highest incidence occurred between 4 and 6 years of age, with a second smaller peak around puberty. There were only 28 people in their fourth decade, 11 in their fifth decade, and 4 who developed hip TB after 50 years of age. In most cases, the lesion starts with an osseous focus (Konschegg, 1934: 461, 462). The anatomy of the hip joint enables early access of the bacteria into the joint space, not only into the acetabulum and femoral epiphyses but also the metaphysis of the femoral neck. In the “Kastert series,” one-third of the individuals with hip TB had an origin with an extra-articular focus (Kastert and Uehlinger, 1964: 508). In addition to the usual hematogenous route, direct extension to the hip joint occurred through long-standing abscesses from vertebral or pelvic TB. However, in advanced stages of the disease, the point of origin could not be determined. In a study of 416 individuals with hip TB reported by Vacchelli (1922, cited in Kremer and Wiese, 1930: 202), the distribution of involvement was total destruction of the femoral head and acetabulum (22; 0.5%), diffuse involvement of the femoral head and acetabulum (220; 52%), diffuse synovial TB

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(52; 52%), and isolated osseous tuberculous foci (122; 2.9%). The isolated foci were distributed as follows: femoral head (60; 14.4%), femoral neck (24; 9.2%), acetabulum (30; 9.4%), and greater trochanter (8; 4.1%). The foci in the femoral head or neck may be small cavitating lesions or larger triangular foci with a spongiosa sequestrum in the center. These lesions may represent ‘territories’ of terminal arteries. Acetabular foci predilect the posterior part of the superior rim and the cartilage-free center around the origin of the round ligament (Fig. 11.11). Lesions in the neck of the femur are often adjacent to the medial inferior cortex (Girdlestone, 1965: 44, 45). Extension of primarily synovial TB into the bone occurs along the synovial attachment on the neck of the femur. The weight-bearing articular surfaces are preserved for the longest period. Ultimately, destruction may be very extensive with an upward-sloping extension of the acetabulum, leading to partial or complete dislocation of the remnant of the femoral head and/or neck (Figs. 11.12 and 11.13). If the dislocation is complete, a new acetabulum is formed on the lateral surface of the iliac wing. In contrast to the appearance of a congenital dislocation of the hip, the head of the femur is more eroded and there is no groove for the round

FIGURE 11.11 Tuberculous arthritis of the left hip, 3 months after resection of the femur; evidence of upward subluxation: (A) lateral view; periosteal build up on the ischium, probably secondary to a cold abscess—one that lacks the classic signs of inflammation and is often associated with tuberculosis of the bone; (B) medial view; hypervascularity of acetabular base (66-year-old female with chronic pulmonary tuberculosis; DPUS 7641, autopsy 880 from 1912).

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FIGURE 11.13 Destructive arthritis of the right hip with upward subluxation; probably tuberculosis. Note the severe osteoporosis of the femur and ilium and the iliac shelf secondary to subluxation (88-year-old female with pulmonary and lymph node tuberculosis who died in 1954; IPAZ autopsy 1445, museum number 5947).

FIGURE 11.12 Tuberculous arthritis of the right hip with upward subluxation, partly healed. Note the restoration of the subchondral bone plate on the partly destroyed femoral head (16-year-old male, who died of tuberculous meningitis in 1936; IPAZ S325).

ligament, which is destroyed by the infection before the dislocation occurs. The original acetabulum is not rudimentary in TB, and the new acetabulum shows evidence of infection. If there is extensive necrosis and destruction of the acetabulum, its pelvic aspect can have lytic defects (Fig. 11.14); perforation of its floor with central dislocation of the remnants of the proximal femur can also occur (Fig. 11.15). Me´nard (1900) observed 105 people with acetabular perforation in the course of 268 hip resections for TB, and Tregubow (1929) reported 12 acetabular perforations in a series of 500 radiologically studied individuals with hip TB. In people with hip TB where healing has taken place, bony ankylosis usually occurs. Growth deficits also may be observed. Differential diagnosis is mainly between tuberculous and nontuberculous septic arthritis. The septic process is rapid and bone destruction is much more limited. Dislocation upwards or centrally is not observed. Bony ankylosis as a final outcome usually reveals little, if any, bone loss of the joint constituents.

Complete destruction of the femoral head is seen only in infants with septic arthritis, which is usually accompanied by osteomyelitis of the shaft. Statistically, hip TB is much more common than septic arthritis. Tuberculosis of the greater trochanter of the femur is an uncommon but characteristic lesion. Sorrel and SorrelDejerine (1932: 70) reported 32 instances of TB of the trochanter (11 in children and 21 in adults) in 6578 individuals with skeletal TB (0.4%), and McNeur and Pritchard (1955) reported 38 affected individuals treated at the Royal National Orthopaedic Hospital (London, England) over a period of 35 years. The age distribution was 30 individuals between 10 and 40 years of age, three children below 10, and five individuals over 40 years of age. The infection may start in the trochanteric bursa or in the bone. It takes a very chronic course and has a great tendency to recur over many years. The lesion tends to remain localized to the trochanteric region, which is progressively destroyed (Fig. 11.16). The cavity often contains a sequestrum of cancellous bone (Sorrel and Sorrel-Dejerine, 1932: 70). Abscess and fistula formation are common. This actually represents the most identifiable tuberculous bone lesion of adults with the exception of spinal TB. It is relatively little known except to orthopedists, although a number of studies have been published (Meyerding and Mroz, 1933; Wassersug, 1940; Alvik, 1949; Ahern, 1958). After the acetabulum, the sacroiliac joint is the most common joint involved in pelvic TB (Fig. 11.17), usually by extension of a lumbosacral focus unilaterally or bilaterally. This is observed more often in young adults than

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FIGURE 11.14 Tuberculosis of the left hip: (A) anterior view; (B) medial view. Note the destruction of the femoral head with exposure of porotic spongiosa and perforations of the involved acetabulum (adult, IPMI KM 352).

FIGURE 11.15 Tuberculous arthritis of the right hip with complete destruction of the acetabulum and central dislocation of the remnant of the femoral head; notice the sparsity of reactive new bone: (A) lateral view; (B) medial view (male about 30 years old; IPAZ 1940, old no. 2167).

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FIGURE 11.16 Tuberculosis of the left hip with destruction of the femoral head and perforation of the acetabulum, and tuberculosis of the left ilium and of both sacroiliac joints. Notice minimal reactive new bone in all affected areas (15-year-old, FPAM 5669, who died in 1895).

FIGURE 11.18 Chronic TB of the right greater trochanter with a fistulating abscess; the hip joint was unaffected. Notice the scalloped destruction of the greater trochanter (54-year-old female with a pulmonary tuberculous focus who died in 1924; FPAM, Jubila¨umspital 857; autopsy).

FIGURE 11.17 Tuberculosis of the spine and left ilium; reactive new bone in the wall of a cold abscess in the left inguinal area. Notice the round defect in the ilium, and erosion and bony build up in the inguinal area (28-year-old male; FPAM 2488, autopsy 33582 from 1853/54).

in children. Unlike in brucellosis, isolated sacroiliac TB is very rare. In their large series, Sorrel and Sorrel-Dejerine (1932: 501) observed only two affected individuals, compared to 114 people who had secondary lumbosacral involvement. There may be considerable destruction of

the sacral wing with some reactive osteosclerosis (Kremer and Wiese, 1930: 198). Healing with bony fusion may lead to asymmetrical pelvic deformity. Isolated tuberculous foci in the ilium are rare, usually consisting of round or oval cavities with or without a central sequestrum, perforation of the cortex, or fistula (Konschegg, 1934: 409 410). However, extension of a psoas abscess into the ilium can occur (Fig. 11.18). It is thus worth noting whether there is any reactive new bone formation (or destruction) evident along the track of the psoas muscle from the spine to the lesser trochanter of the femur (i.e., on the internal surface of the ilium and over the iliopubic eminence). This may reflect a psoas abscess due to TB. TB rarely affects the pubis. However, if the pubis is involved, both sexes are affected about equally and most instances concern older children and young adults.

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The largest study is that of Fares and Pagani (1966). About half of 27 individuals with pubic TB showed other adjacent or remote tuberculous skeletal foci. There is apparently no relationship to trauma or parturition. The lesion in adults is usually close to the symphysis, which may be also involved. In these cases, both pubic bones may be affected (Kremer and Wiese, 1930: 195). The lesion is lytic and destructive, occasionally with the formation of small sequestrae. Abscess formation and fistulas are common. In children, the lesion may be medial to the hip joint because of the incomplete ossification of the pubic area. Similar lesions occur in the ischial ramus (14 ischial compared to 20 pubic lesions in Sorrel and Sorrel-Dejerine, 1932: 76). In addition, occasionally an isolated lesion can occur in the ischial tuberosity, similar to the more common lesion in the greater trochanter (Blankoff, 1927).

The Knee Tuberculosis of the knee joint occurs about as often as or even more frequently than hip TB (Fig. 11.19). Again, the majority of instances begin in infancy, childhood, and adolescence. For example, Johannsson (1926: 177) observed 50% before the age of 5 years, with about an equal distribution between the sexes. In Sorrel and SorrelDejerine’s study (1932: 247) of 558 individuals, 34 infants developed knee TB in the first year of their lives, and only 51 people developed it after age 20. Most hip TB starts as synovial tuberculosis, and it may remain in this area. However, extension of the synovial infection can occur along the capsular insertions of the femur and tibia and along the attachments of the cruciate ligaments. Linear cortical erosion and undermining destruction of the adjacent portion of the articular surface occurs. Significant amounts of localized destruction of the femoral condyles or of the tibial plateau are observed only if a primary or simultaneous hematogenous osseous focus is present, with or without sequestrum (Fig. 11.19). Such foci are more often found in the femoral condyles or in the tibial epiphysis, but rarely in the patella or fibula. Kønig (1906: 112) observed patella involvement in 50 people of 720 considered. In 33 (46%) of these, the patella was the only focus, with or without secondary extension to the knee joint. In healing, fibrous or bony ankylosis results. If bone destruction was absent or limited, differentiation from the bone changes of the end stage of rheumatoid or septic arthritis may be impossible. Both rheumatoid arthritis and TB affecting the knee are usually accompanied by osteoporosis of the involved limb. Tuberculous and septic arthritis are more often unilateral than rheumatoid arthritis. In severe instances, particularly in children, dislocation and valgus or varus deformity of the knee is observed, depending on the

FIGURE 11.19 Tuberculosis of the knee that recurred after previous surgery; notice the destruction of subarticular bone and the minimal reactive new bone formation (13-year-old female who died in 1899; DPUS 3921).

relationship of the affected area to the growth plate. Generally, adults have less destructive bone changes than infants (Sorrel and Sorrel-Dejerine, 1932: 267).

The Ankle (Distal Tibia and Fibula) and Tarsal Bones Tuberculosis of the ankle most commonly involves the tibiotalar joint (Fig. 11.20), and much less commonly the talocalcaneal joint. The lesion is most common in

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FIGURE 11.20 Tuberculous arthritis of the right ankle with extensive destruction of the distal tibial epiphysis and partial ankylosis, with remnants of the talus; histologically proven, and of 9 years duration. Initiated by crushing trauma (25-year-old male who died in 1930; PMES 2 FT 16(1)).

children. In the study of Sorrel and Sorrel-Dejerine (1932: 210), the tibiotalar joint was involved in 185 individuals, of whom 121 were below 13 years of age and only 64 were adolescents or adults. The maximum age of onset occurs at 3 years. In most cases the process seems to start with a hematogenous osseous focus. In most people, the primary bone focus is the talus, less commonly the distal tibia, and rarely the fibula. Ossification of the talus begins at birth and essentially fills the cartilage model at 2 years of age, leaving only the articular cartilage between the ossification center and the adjacent joints. This explains why isolated TB of the talus without involvement of the adjacent joints is not observed (Sorrel and Sorrel-Dejerine, 1932: 210). However, early extension into the tibiotalar joint and also, but less often, into the talocalcaneal joint is common. In tibiotalar TB of talar origin, the talus is cavitated and often ultimately destroyed. Where the tibia was the original origin, significant destruction involves the distal tibial epiphysis and sometimes the metaphysis. Healing always leads to tibiotalar bony ankylosis. In people with

advanced TB of the ankle, the talocalcaneal joint frequently becomes involved at any age. If the talus is completely destroyed, tibiocalcaneal bony ankylosis develops with an uptilted position of the calcaneus. This would not be the case in ankylosis following juvenile chronic arthritis. Because the ankle is a weight-bearing joint, limited perifocal osteosclerosis does occur. Isolated involvement of the talocalcaneal joint usually occurs due to secondary extension of a calcaneal focus. This bone change, limited to the lower ankle joint, is observed only in older children between the ages of 7 and 16 (Sorrel and Sorrel-Dejerine, 1932: 207). Healing terminates with broad bony fusion of the talus and calcaneus. After the talus, of the tarsal bones, the calcaneus is most frequently affected. Sorrel and Sorrel-Dejerine (1932: 207) observed 131 individuals with calcaneal TB but only 29 for all other tarsal bones. The explanation for the frequent and often isolated involvement of the calcaneus rests with its development. An ossification center usually appears as early as the last trimester of intrauterine life and ossification is not completed until 17 18 years of age. This makes it a highly vascular area available for tuberculous seeding in infancy and early childhood, whereas thick layers of the cartilage still separate the focus from the adjacent joint cavity (Sorrel and SorrelDejerine, 1932: 268). In early childhood, central TB of the calcaneus is fairly frequent and may heal without permanent traces because of the effect of growth and remodeling. At age 7 9 years, an apophyseal ossification center appears on the posterior portion of the calcaneus, and during later childhood tuberculous foci adjacent to the anterior surface of the posterior growth plate appear. The lesion usually shows a cavity with a central spongiosa sequestrum and often some perifocal osteosclerosis. After termination of growth in the adult, tuberculous foci of the calcaneus readily break through or around the articular cartilage into the talocalcaneal joint, and from there spread to the tibiotalar joint (Sorrel and Sorrel-Dejerine, 1932: 59 60). In Sorrel and Sorrel-Dejerine’s study, the cuboid bone was much less often involved and most of the patients were children (11 children, two adults). The ossification of the cuboid bone begins at 3 months of age and terminates at 9 10 years. Occasionally, the navicular bone was involved in older children (six children, one adult). Ossification of the navicular bone begins at 21/2 5 years and terminates between 10 and 12 years of age. The cuneiform bones are rarely involved; if destroyed, medial deflection of the foot may occur. Foci like these may remain isolated in children and may heal without joint involvement (Sorrel and Sorrel-Dejerine, 1932: 63 65). In adults, tarsal bones may be affected in extensive TB of the ankle. A differential diagnosis between TB and subacute osteomyelitis based on isolated tarsal lesions may be impossible in dry bone.

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ischemic necrosis and/or penetration of the thin cortex. The cortex may be resorbed rapidly or form a sequestrum. The elevated periosteum forms a new bony shell that accounts for the ballooned appearance of the involved bone (Fig. 11.21). These lesions often accompany other skeletal manifestations of TB. If the child does not die from TB located elsewhere, the lesion usually heals. Destruction of the growth plate in metacarpals and metatarsals and, less commonly, of phalanges, may lead to marked shortening of the digit after healing. If this is not the case, evidence of the healed lesion will disappear in remodeling. Very similar lesions are produced by osteomyelitis, congenital syphilis (CS), and sickle cell anemia. However, those foci are usually singular, and expansion of the involved bone is usually much less marked. In children, tuberculous dactylitis spares the interphalangeal joints. In adults, the phalanges may be involved, but only rarely does the lesion extend into the joint. The body of these bones is not expanded by the disease process (Girdlestone, 1965: 183).

The Shoulder

FIGURE 11.21 Tuberculous dactylitis (spina ventosa) of a first metacarpal. Notice expanded involucrum surrounding the remnant of the diseased bone; the epiphyses are spared (PMES 1 FT 12(1)). NB: This image appears may be a composite of bones from different individuals.

The Tubular Bones of the Hands and Feet The most frequent localization of skeletal TB in infancy and early childhood is the often multiple involvement of phalanges, metacarpals, and metatarsals (tuberculous dactylitis or spina ventosa). Sorrel and Sorrel-Dejerine (1932: 2) reported that, among 4660 children with skeletal TB, 649 had spina ventosa (15%), with 1 10 foci in individual patients. Bailleul (1911: 4) reported that in 274 patients there were 495 lesions of spina ventosa, of which 381 were located in the hands and 114 in the feet (80% and 39%, respectively). The age distribution in Johannsson’s (1926: 144) study was: 15% affected in the first year, 62% affected below 3 years of age, and 77% affected below 5 years. The lesion rarely occurred after 10 years of age. Of his patients, 50% showed solitary lesions. The affected sites were the fingers (108), metacarpals (68), metatarsals (32), and toes (11). In infancy and early childhood, these short tubular bones still have hematopoietic marrow throughout the shaft, and a focus will readily occupy the whole diaphysis, leading to

Tuberculosis of the shoulder is much less common than that of the hip or knee. For example, Kastert and Uehlinger (1964: 517) report only 77 cases (4.7%) among 2457 patients with skeletal TB. It may be observed at any age, but it appears in adults more often than in children. Males are more affected than females, and the right side is three times more affected than the left for both sexes (Kremer and Wiese, 1930: 291). The complicated relationship of the shoulder joint to the synovial sheath of the long biceps tendon and to the subdeltoid bursa favor extensive synovial involvement. If osseous foci are present, they are more frequently found in the head or proximal metaphysis of the humerus than in the scapula (Fig. 11.22). In children, cavities with sequestra occur in the epiphysis and metaphysis of the proximal humerus (Sorrel and Sorrel-Dejerine, 1932: 165 168). In the synovial form, extension to the humerus occurs along the capsular attachment, creating a resorption groove on the lateral aspect of the humeral head. In children, shoulder TB may heal. In adults, extensive destruction of the humeral head and of the glenoid fossa is common. Occasionally the acromion and clavicle may also be involved (Fig. 11.23). Abscess formation and fistula are less frequent than in other large joints. In a differential diagnosis, septic arthritis is the main consideration. Bone destruction in septic arthritis is usually much less extensive and the lateral grooving and undermining defect on the humeral head are not observed. The scapula is very rarely involved, except by extension of TB of the shoulder joint into the glenoid fossa or the acromion.

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In hematogenous TB of the scapula, the vertebral margin is predilected (Kremer and Wiese, 1930: 301).

The Elbow

FIGURE 11.22 Tuberculosis of the humeral head with cavitation; sequestrum removed (resection example). Note the exposed porotic hypervascular bone with little reactivity (17-year-old female; PMWH W0709).

In many studies, TB of the elbow is the most frequent joint affected of the upper extremity (50%; Kremer and Wiese, 1930: 304). Most lesions develop at between 1 and 20 years of age (Kønig, 1906: 141; Cheyne, 1911: 328). In the period between 1918 and 1928, Sorrel and Sorrel-Dejerine (1932: 121) observed TB of the elbow in 164 children and 72 adults. Osseous foci, if present, were most common in the distal humerus, secondly the proximal ulna, and least in the proximal radius. Kønig (1906: 141 142) found bony foci in 91 of 128 patients (75%), with 43 cases involving the distal humerus (mostly in the lateral condyle), 36 cases including the ulna (olecranon), and 2 cases engaging the proximal radius. In people with advanced TB, several of the adjacent bones may be involved. In very young children, a central tuberculous focus in the olecranon may be present as part of multiple skeletal foci (fingers, toes, calcaneus, zygoma). This is a cavitating lesion with a central sequestrum and reactive periostosis resembling spina ventosa. In cases like these, the joint may not be affected (Sorrel and SorrelDejerine, 1932: 121). After 6 years of age, the joint is often involved by extension of the ulnar focus through the joint cartilage. This leads to deeper excavation of the trochlear notch of the ulna, with elongation of its coronoid process. In children, the process may heal with fibrous ankylosis. In adults, destruction of the adjacent bones may be extensive, and usually the head of the radius is the least and last affected. Healing usually terminates in bony ankylosis (Fig. 11.24). Ankylosis without major bone loss may be impossible to differentiate from erosive arthropathy or septic arthritis. Periarticular osteophytosis can occur in extensive capsular involvement (Fig. 11.25).

The Wrist and Carpal Bones

FIGURE 11.23 Cavitating TB of the lateral portion of a right clavicle. Notice the scarcity of reactive bone (an adult with tuberculous arthritis of the shoulder who died prior to 1920 ;PMES 1. FT. 5 (2)).

The wrist consists of three partly separated joints: the radiocarpal joint, the intercarpal joints, and the carpometacarpal joint. Any one or all of them may be involved in TB. The following discussion is mainly based on the detailed study of Sorrel and Sorrel-Dejerine (1932: 91 120). They observed 63 instances of TB in these joints in children and 51 instances in adults. The location and manifestation of the lesions vary greatly in different age groups. In children, the carpometacarpal joint is mainly involved and the radiocarpal joint is spared. In adults, the process usually begins in the radiocarpal joint and spreads rapidly throughout the joint compartments of the wrist (Fig. 11.26). The difference in age groups is explained by the anatomy and maturation of the

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FIGURE 11.24 Tuberculosis of the right elbow with bony ankylosis between the radius, ulna, and humerus. Notice the marked involvement and enlargement of the distal humerus. The defect of the olecranon process is artificial (amputated from a child; PMES 2 FT 7(4)).

constituent bones. In children below 4 years of age, the carpus is mainly a block of cartilage with minimal focal ossification. At this stage, carpal TB is not observed. From 4 12 years of age, carpal ossification centers become larger and more numerous. At this time, localized carpometacarpal involvement is observed because adjacent bones are still protected by thick layers of unossified cartilage. The carpometacarpal joint is uncommonly involved by extension of spina ventosa of an adjacent metacarpal. In general, an active growth plate serves as a barrier to the extension of TB to the adjacent joint. Metacarpals 2 5 are devoid of a proximal growth plate. These localized joint lesions may heal, along with healing of the accompanying spina ventosa, leading to bony fusion between individual carpals and metacarpals. With increasing age, the cartilage cover diminishes and extensive joint involvement becomes the rule. In children and adults, the joint lesion may originate directly in the synovium or by contact with tuberculous tenosynovitis. Osseous destructive foci are not infrequently present in

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FIGURE 11.25 Tuberculosis of the right elbow. Notice exposure of subchondral porotic spongiosa on all the joint surfaces and partial destruction of the radial head. The periarticular new bone formation suggests extensive capsular involvement (68-years-old; IPAZ 1969, old number 253).

FIGURE 11.26 Tuberculosis of the left wrist: wet preparation with soft tissue attached, showing extensive destruction of the distal radius, ulna, carpal bones, and carpometacarpal joints of 1-year duration (56-year-old male with pulmonary tuberculosis who died in 1876; WM S82.1).

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the distal radial epiphysis and/or metaphysis of adults. The disease rapidly spreads through the entire wrist and, in contrast to the type seen in infants, the proximal row of carpal bones is more severely involved. In healing, with various degrees of bone loss, the entire carpus becomes a solid bone block, fused to the radius and often to the base of the metacarpals.

The Shaft of Long Bones Tuberculosis of the shaft of long bones is uncommon. It is almost exclusively observed in children and frequently as a manifestation of multiple skeletal foci, particularly spina ventosa. Sorrel and Sorrel-Dejerine (1932: 2, 21) observed about 100 instances in infants and children compared to 649 children with spina ventosa. The lesion consists of eccentric cavitation, usually in the metaphysis, with a small sequestrum (Fig. 11.27), and is often marked by reactive periosteal bone formation over the overlying cortex (Fig. 11.28). Thus, in children, there is considerable resemblance to the appearance of spina ventosa (Figs. 11.29 and 11.30). In adults, the lesion is extremely rare, and periosteal bone formation is meager (Fig. 11.31). Perifocal osteoporosis may be followed in long-standing cases by perifocal osteosclerosis. A certain differentiation from

FIGURE 11.27 Tuberculosis of the lateral epicondyle of the right humerus. Notice the smooth cavity with a porotic sequestrum and minimal reactive new bone in the vicinity (adult; DPUS 5989, French catalog no. 834).

FIGURE 11.28 Tuberculosis of the medial epicondyle of the right humerus. Notice the central lytic focus with moderate periosteal reactive bone. The joint is not involved (adult; DPUS 5982, French catalog no. 827).

FIGURE 11.29 Tuberculosis of the proximal left ulna with extension to the elbow joint and humerus; posterior view. Notice the bulbous expansion of the new ulnar cortex with a single cloaca, destruction of the olecranon, and erosion of the humerus (child; PMES 2. FT. 7 (6)).

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osteomyelitis and Brodie’s abscess may be impossible on dry bone. The frequency of involvement in descending order is the tibia, ulna, radius, humerus, femur, and fibula (Konschegg, 1934: 422). While TB of the shafts of long bones is uncommon, hypertrophic pulmonary osteoarthropathy (HPOA) may be caused by TB (Assis et al., 2012). Florid new bone formation on long and short tubular bones occurs in this condition and is commonly seen on the lower-limb long bones (Resnick and Niwayama, 1995c). Assis et al.’s (2012; see also Binder and Saad, 2017) study of skeletons with known cause of death curated in the Coimbra Identified Skeletal Collection, Portugal, found that the risk of developing HPOA was greater in people who had died from TB. While not pathognomonic for TB, HPOA is one of the nonspecific changes in the skeleton that could be associated with TB.

Ribs

FIGURE 11.30 Tuberculosis of the proximal radius with enlargement of a new cortex and multiple perforations (cloaca/sinuses); the epiphysis and articular surface are spared (6-year-old girl with tuberculosis of the cervical lymph nodes, who died prior to 1900; PMES 1 FT 10(2)).

Tuberculous involvement of one or several ribs is not rare. Sorrel and Sorrel-Dejerine (1932: 84 88) observed 93 instances (56 children and 37 adults.) The infection is usually hematogenous, but direct extension from paravertebral abscesses and other adjacent tuberculous foci can occur (Kremer and Wiese, 1930: 283). The hematogenous foci predilect the area near the osteocartilaginous border

FIGURE 11.31 Healed TB of the distal femur with partial ankylosis of the knee and severe osteoporosis due to disuse: (A) external view; note periosteal hyperostosis; (B) cut surface; note cavitation in the femoral metaphysis and severe osteoporosis (68-year-old male; IPAZ 6052; surgical example MB 6936 dated to 1955).

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and may involve the cartilage secondarily (Kastert and Uehlinger, 1964: 515). The process creates a lytic lesion with fusiform enlargement of the involved area and often perforations of the cortex lead to chest wall abscesses. Periosteal reactive bone formation is usually rather meager. The middle ribs are more often affected than the upper or lower ones and secondary involvement of adjacent ribs can occur (Konschegg, 1934: 407). It is rare for the clinical literature to reference new bone formation on ribs as a result of any pulmonary disease (but see Eyler et al., 1996: enlarged ribs on radiographs likely due to new bone formation); the predominant bone change for TB on ribs is described as lytic. This may be explained by the subtle new bone formation seen on dry bone not being visible on a radiograph. Research on modern (late 19th early 20th centuries) documented human skeletons of individuals known to have died from TB suggests that rib involvement (Fig. 11.32) is most likely to occur in people with TB than for any other pulmonary affliction (Kelley and Micozzi, 1984; Roberts et al., 1994; Santos and Roberts, 2001, 2006). Lung diseases inflame the pleura, and they can thus affect bone because the pleura attaches to the visceral surfaces of the ribs. This can stimulate an inflammatory reaction on the rib surface. Like many skeletal lesions stimulated by disease, there are multiple potential causes for these periosteal bone-forming lesions (e.g., pneumonia, chronic bronchitis, lung cancer, and any situation where poor air quality is present), but research suggests that the type of bone formed and the position of the reactive new bone on the rib cage can help focus on a specific diagnosis (Santos and Roberts, 2006). However, differentiation from osteomyelitis, other infectious conditions affecting the pleura, fibrous dysplasia, and

Langerhans cell histiocytosis may be very difficult on dry bone. Rib lesions such as those described here have formed the focus of several studies in paleopathology, including Lambert (2002), who considered them indicative of exposure to poor air quality in prehistoric Puebloan people from Southwestern Colorado, and Nicklish et al. (2012) who concluded that the rib lesions of people buried at early Neolithic sites in central Germany were the result of TB (based on positive DNA data). The latter study made the assumption that the lesions were caused by TB, although this cannot be proven. The pleura may be also be calcified in TB, but other lung diseases can cause this pathological change, and sometimes pleura have been found archeologically (Donoghue et al., 1998).

Sternum The sternum is much less frequently involved in TB than the ribs. Kønig (1906: 155) observed that ribs are five times more often affected compared to the sternum. The most frequent location is in the manubrium (Fig. 11.33). These lesions may extend into the sternoclavicular joint and involve the medial portion of the clavicle. The sternal lesion is mostly lytic and may perforate the anterior or posterior cortex or both. In a differential diagnosis, erosion of the manubrium by an aortic aneurysm must be considered.

The Skull The skull is a rare area to be affected in TB, except in young children. Tuberculosis involvement of the skull is separated into three areas: cranial vault, cranial base, and face.

FIGURE 11.32 Reactive periostosis of the pleural surface of the left ribs 7 and 8 from a patient who died with tuberculosis (female 18 years old, Robert J. Terry Anatomy Collection, NMNH 382085306).

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FIGURE 11.33 Tuberculosis of the sternum (posterior view), probably by direct extension from TB of the visceral layer of the pleura. Note destruction of the manubrium and body of the sternum with a moderate amount of reactive new bone (PMWH WO 706).

Cranial Vault This is the most common location of cranial TB. Sorrel and Sorrel-Dejerine (1932: 78) observed 21 individuals with vault TB (16 children and five adults). In a statistical survey (Straus, 1933), the distribution of cranial TB was as follows: frontal bone, 86; parietal bone, 86; occipital bone, 18; and temporal bone, 16. The majority of those affected were infants and children below 10 years of age. The infection is usually spread through a hematogenous route to the cranial vault. In children, the lesions are often multiple and secondary to or coexistent with other active tuberculous skeletal foci (Sorrel and Sorrel-Dejerine, 1932: 79 80). The presence of hematopoietic marrow and the growth activity in the cranium at this age determine the frequency of involvement. The most characteristic lesion is a round lytic focus of not more than 2 cm in diameter, with or without a “moth-eaten” central sequestrum, terminating in complete perforation of the inner and outer tables (Fig. 11.34; see also Hackett, 1976: 51). There is often abscess formation and a fistula with transcutaneous elimination of the sequestrum. The lesion

FIGURE 11.34 Tuberculosis of the cranial vault: (A) external view; notice little reactive new bone around the frontal bone defect and a porous sequestrum in the parietal bone lesion; (B) endocranial view; the frontal bone lesion is broader based on the inner table (adult; DPUS 4584).

frequently crosses suture lines. The margin of the typical lesion shows active resorption with minimal reactive bone formation at the margins of the lesion. However, in some cases large destructive lesions can occur with considerable marginal bony repair (Fig. 11.35).

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FIGURE 11.35 Cranial TB with a lytic lesion penetrating both tables of the skull on the left frontal bone just above the greater wing of the sphenoid bone: (A) left lateral view of the skull; (B) interior view of the skull. Note that the area of bone destruction is much larger on the interior surface (female 17 years old, Robert J. Terry Anatomy Collection; NMNH 382085-329).

FIGURE 11.36 Tuberculosis of the cranial vault secondary to tuberculous external pachymeningitis (diffuse inflammation of the dura mater): (A) ectocranial view showing small perforation of the outer table; (B) endocranial view; notice the lesions are much larger on the inside; (C) left lateral view, showing healing (12-year-old female who died in 1914 ; FPAM Jubila¨umspital 40).

Spread along the internal periosteum of the cranial vault, perifocal bone resorption, and hypervascularity are often observed. In juveniles, the lesions have to be differentiated from Langerhans cell histiocytosis and metastatic neuroblastoma. Solitary lesions of Langerhans cell histiocytosis usually do not contain a central sequestrum and do not cross suture lines. Multiple lesions of

reticulosis usually do not spare the skull base. Metastatic neuroblastoma often shows a marked osteoblastic reaction. In adults, the cranial vault lesion is almost always solitary and often much larger than in infants and children. In addition to the hematogenous route, extension from tuberculoma of the brain or dura does occur (Fig. 11.36). The process is characterized by a chronic

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FIGURE 11.37 Tuberculosis of the right parietal bone: (A) ectocranial view; notice the small perforation in the exposed diploe; (B) endocranial view, showing the larger defect on the inner table sloping to a smaller perforation on outer table (55-year-old female who died of tuberculosis in 1896; ANM 2480, autopsy 658-(16)).

progressive destruction of the cranial vault with irregular margins. Major sequestration is uncommon, in contrast to osteomyelitis, and bony reaction is very limited or absent, in contrast to tertiary acquired syphilis. The defect of the inner table is usually larger than that of the outer (Fig. 11.37), whereas in tertiary syphilis the greater defect is usually external and the inner table may be completely intact (Erdheim, 1932: 355). Metastatic cancer of the skull is another differential diagnostic option (Hackett, 1976: 50). In archeological skeletons, involvement (or not) of the two tables of the skull may have been a developing lesion at death. Thus, the end result might have been more extreme. Another lesion of the inner table may also be seen in skeletons of individuals who had TB. The lesion consists of a cluster of vascular lines on the inner table that are probably the result of hypervascularity stimulated by a tuberculosis focus in the adjacent soft tissue (Fig. 11.38). There has been some discussion and debate about the causes of these endocranial lesions (Schultz, 1999; Hershkovitz et al., 2002; Lewis, 2004) alongside endocranial destructive lesions (Kappelman et al., 2008; Roberts et al., 2009). These studies conclude that multiple etiologies should be considered in a differential diagnosis, such as normal bone growth in nonadults, scurvy, and TB meningitis.

FIGURE 11.38 Vascular lesions of the inner table of the skull, possibly resulting from reaction to an adjacent soft-tissue tuberculous lesion (female 18 years old, Robert J. Terry Anatomy Collection, NMNH 382085-306).

Cranial Base The base of the skull is rarely involved in TB. However, tuberculous otitis media is quite common in infants; in an early 20th-century report it represented 50% of middle ear infections in the first year of life and about 3% at all

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FIGURE 11.39 Cranial TB with a lesion in the right frontal bone and left middle ear: (A) lateral view, showing exposed diploe and posterior penetration of the inner table; (B) basal exterior view, showing involvement of the left middle ear, necrosis of the mastoid process, and extension to the base of the sphenoid bone (from a child about 8 years old who died in 1837; DPUS 5266, French catalog no. 779).

ages (Fraser and Stewart, 1936: 402). There is occasional destruction and sequestration of the petrous portion and mastoid process of the temporal bone by secondary extension of mucosal middle ear TB (Krause, 1899: 54) (Fig. 11.39). Occasionally, the base of the occipital bone in the vicinity of the foramen magnum may be affected in suboccipital TB of the atlas and axis (malum suboccipitale) (Fig. 11.40). Facial Bones In small children, focal TB of the inferior lateral orbital margin is not uncommon, including the maxilla, especially at the junction with the zygoma. Involvement of the zygoma itself is also seen frequently. Chronic TB of the zygomatic arch may lead to an abscess, which typically ascends the temporal squama along the temporal muscle (Fig. 11.41). In most instances, there are multiple skeletal TB foci elsewhere. These facial lesions are superficial, leading to small sequestra that are frequently eliminated by fistulae (Krause, 1899: 54 55; Kremer and Wiese, 1930: 153 155). The bony walls of the nasal cavity may be secondarily affected by extension of mucosal TB (Fig. 11.42). The facial bones also can be secondarily involved by longstanding TB of the facial skin and soft tissues (lupus vulgaris: Fig. 11.43), which often leads to destruction of the nasal bones, as in leprosy (Figs. 11.44 and 11.45).

FIGURE 11.40 Tuberculosis of the cranial base and atlas with superficial erosion of the anterior surface of the cervical vertebrae suggestive of a paravertebral abscess. This person had a sudden death by compression of the medulla (55-year-old male with chronic pulmonary tuberculosis; PMWH WO 702).

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FIGURE 11.41 Cranial TB with destruction of the left zygomatic arch and involvement of the temporal bone and mastoid process with periosteal reaction to the subtemporal abscess. Separate foci in the frontal and left parietal bones (adolescent who died in 1837; DPUS 5268, French catalog 778a).

FIGURE 11.42 Tuberculosis of the cranium with a right frontal bone and basal lesion: (A) ectocranial view, showing small sieve-like perforation of the outer table; (B) endocranial view, showing large dura-based lesion crossing the coronal suture; (C) endocranial view of destructive lesion of the sphenoid-ethmoid bone area; (D) exterior view of the skull base (10-year-old female, ANM 2439 who died in 1870).

FIGURE 11.42 Continued

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FIGURE 11.42 Continued

FIGURE 11.43 Lupus vulgaris—skin TB. Lupus vulgaris exulcerans ˜ r Rongeante: Albert. (Hebra); Synon: Lupus; Lupus exedens; DartrA Bears number: Plate III. Credit: Welcome Collection (free to use with attribution: https://wellcomecollection.org/works/yduk4vpk? query 5 lupus 1 vulgaris).

FIGURE 11.44 Craniofacial TB in lupus vulgaris, with destruction of the nose: (A) anterior view, showing porotic erosion around the nasal aperture and maxilla; extensive destruction of the mandible; (B) left lateral view, showing multiple superficial erosive lesions of the cranial vault and extensive destruction of the mandibular angle (12-year-old male with pleural TB and meningitis who died in 1888; FPAM 5001, autopsy 87916).

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(or any other animal that can be infected—see Introduction above) could have acquired the disease by breathing similar aerosols. Dissemination of the bacteria from the gastrointestinal tract to other sites within the affected person is always a possible complication of gastrointestinal TB acquired from animals. However, from Brosch et al.’s (2002: 3685) research we now know that the M. bovis species did not precede M. tuberculosis and that “M. tuberculosis and or M. canettii are most closely related to the common ancestor of the tubercle bacilli.” Nevertheless, whatever the evolutionary scenario, the transmission of a bovid or other MTC zoonotic disease to people and vice versa could have occurred at almost any time in ancient human history, and this continues to be the case today. For example, our hunter-gatherer ancestors could have eaten contaminated meat of animals and acquired the disease. When humans adopted farming, this gave the requisite conditions for both the animal and human form of TB to thrive. Higher population density promoted the spread of M. tb from human to human and closer association of humans with their animals facilitated the transmission of the MTC organisms to humans. Stable populations with many potential new hosts would have been an important factor in developing an endemic disease. FIGURE 11.45 Cranial TB in lupus vulgaris, with partial destruction of the nasal bones, conchae, nasal septum, maxilla, and palate, along with periostosis of the mandible; 10-year duration (15-year-old male who died prior to 1920; PMES 1 FT 2(1)).

It may potentially also cause underlying bone destruction (Roberts et al., 1998). In infants, the mandible occasionally also shows hematogenous foci near its angle. These lesions may be very similar to foci of Langerhans cell histiocytosis. In adults, in advanced stages of open pulmonary TB, extension of oral mucosal lesions into the alveolar process of the mandible uncommonly and, even less often, of the maxilla has been described (Zandy, 1896).

Paleopathology Tuberculosis is one of several diseases that can be transmitted between humans and animals. The prevailing hypothesis until 2002 had been that TB was first transmitted to humans by cattle or their bovid ancestors through the ingestion of meat or milk of infected animals (Brosch et al., 2002). This caused the gastrointestinal form of the disease, which is not spread from person to person. Cattle probably contracted the disease in antiquity through breathing in the organism-laden aerosol of infected cattle, which is one of the modes of transmission in cattle today (Pfeiffer and Corner, 2014). Humans in contact with cattle

Old World Evidence Finding the earliest evidence of TB continues to be a tantalizing quest in paleopathology, which extends to early work, such as that of Bartels (1907), who reported on a Neolithic skeleton found near Heidelberg, Germany. The fourth and fifth thoracic vertebrae had collapsed and fused with the somewhat abnormal sixth vertebra, creating an angulation often, but not exclusively, seen in spinal TB. Roberts (2015) and Roberts and Buikstra (2003: 129 213) provide helpful summaries on more recent research on the antiquity of TB in both the New and Old Worlds (see also special issue of Tuberculosis, 2015). Roberts (2012) discusses developments in understanding of this ancient disease, and Roberts and Brickley (in press) discuss the synergies between infectious and metabolic diseases. Pa´lfi et al. (1999) also remains a good source of information. The survey of paleopathological evidence here cannot be allencompassing, but it provides a reasonable overview both temporally and geographically. Aufderheide and Rodriguez-Martin (1998: 126) note the lack of convincing evidence of spinal lesions potentially caused by TB in any reports on Paleolithic human remains. This remains the case as this volume goes to press. There is also limited evidence, although increasing over recent years, of Pott’s disease occurring in the Neolithic period at about the time when human groups

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were beginning to live in large, settled communities. This is a strong argument for the association between infectious disease and increasing population size, dependence on agriculture, the domestication of animals, and the emergence of urbanism. However, spinal destruction

possibly attributable to Pott’s disease has been reported in skeletons from two sites in Italy dated to between 3500 and 4000 BC (Formicola et al., 1987; Canci et al., 1996), and more recently a 3500 BC skeleton with multifocal TB was reported from Liguria, Italy (Sparacello et al. 2017 FIGURE 11.46 Multifocal tuberculosis. Pollera cave skeleton 21, Liguria, Italy (Sparacello et al., 2017); (A) Lateral and superior view of the proximal left humerus; new bone formation, and destruction of the surface in contact with the growth plate and the underlying remodeled trabeculae. (B) Detail of the inferior margin of the right scapula, visceral view. (C) Inferior view of the fourth cervical vertebral body. (D) Inferior view of the ninth thoracic vertebral body. (E) Sternal ends of three ribs with lytic lesions and proliferative bone. (F) Left, the right ischium: absence of the ischio-pubic ramus; Right, anterior view of the lesion. Courtesy: Vitale Sparacello.

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FIGURE 11.46 Contiuned

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and see Fig. 11.46). Two early skeletons with TB from Hungary are also described by Ko¨hle et al. (2014) at the site of Versend-Gilencsa (late Neolithic or 6000 BC), and by Masson et al. (2016) dated to 5000 BC. Germany also claims Neolithic evidence for TB dated to 5400 4800 BC (Nicklish et al., 2012). People living in the Neolithic Yaoi period in Japan are further reported to have skeletal evidence of TB (Suzuki and Inoue, 2007: c.300 BC to AD 300), as have those living in Korea (Suzuki et al., 2008: 1st century BC). In the Middle East a skeleton was also reported by Ortner (1979) from a site in Jordan that is dated to the Early Bronze IA period (c.3100 BC), and there is evidence for a prehistoric skeleton with TB in England from the Iron Age, 300 BC (Mays and Taylor, 2003). Not surprisingly, Egyptian skeletal remains have revealed evidence of TB, too (Derry and Elliot-Smith, 1909; Elliot-Smith and Dawson, 1924; Derry, 1938). For example, Elliot-Smith and Ruffer (1910) reported probable TB in an Egyptian mummy dating from the 21st Dynasty (c.1000 BC). There was extensive destruction of the last four thoracic and first lumbar vertebrae. Inferior to the lesion on the lumbar vertebra was a swelling in the soft tissue, which Elliot-Smith and Ruffer judged to be a paravertebral abscess within the psoas muscle. Although no tubercle bacilli were found in any of the soft-tissue lesions, the morphological evidence for TB is strong. Indeed, although discounting much of the purported evidence for TB in ancient Egyptian remains, Williams (1929: 869 873) concluded that the evidence for TB in Egyptian human remains was convincing. Morse et al. (1964) and Buikstra et al. (1993) reached a similar conclusion. Since the early 20th century, there has been further work on TB in Egypt. Dabernat and Crubezy (2010) report multiple bone TB in a child from Predynastic Upper Egypt (3200 3100 BC). The macroscopic evidence for TB in human remains from the Old World is clearly convincing, and some of it is of very early in date. There has also been considerable ancient DNA analysis of remains since the early 1990s to identify TB in such remains, and this has included exploring the evolution of the MTC organisms (see Chapter 8).

New World Evidence The study of TB in the New World has a contentious history that extends across more than 100 years. A number of themes and tensions common to paleopathology as a discipline are illustrated here. These include: (1) early contributions primarily by medical doctors; (2) concern for a lack of contextual information; (3) tensions between medical doctors, whose opinions reflect their patient experience, and anthropological scholars whose inferences develop from historical and global literature reviews; and (4) the genomic revolution that began in the 1990s (see

Chapter 8). Our discussion is organized around two basic questions: (1) Was TB present in the Western Hemisphere prior to European contact? and (2) If present, what was its phylogeography—when did it enter the New World and how did it spread? Was There Pre-Columbian Tuberculosis? This discussion begins with the earliest proposed evidence of TB. In the 18th and 19th annual reports of the Peabody Museum at Harvard, Whitney (1886) described three skeletons with bone changes he attributed to TB. This was among other anomalies, injuries, and diseases that he observed in archeologically recovered bones from North American “native races”. Whitney was a clinical pathologist and anatomist, as well as the appointed curator of the Warren Anatomical Museum at the Harvard Medical School (1879 1921). The three individuals he described included an individual from a “stone-grave mound, near Nashville, Tennessee “(Whitney, 1886: 445), who presented with vertebral body destruction and kyphosis extending from C4 to T5. Attention also was called to ceramic water bottles from stone box graves with artwork identified by Whitney as kyphotic upper spines. The other two examples, also from stone box graves, involved the right knee and left ankle. Thus, Whitney established an American tradition of evaluating both diseased bones and artistic representations. In his important early 20th-century report on TB among native populations of the American West, Aleˇs Hrdliˇcka (1909) argued that TB must have been absent or perhaps rare in pre-Columbian America. He based his conclusion on the paucity of securely dated prehistoric skeletal examples, the lack of reports by the earliest settlers and elderly Native Americans, the absence of traditional remedies, the recent virulence of the disease, and the apparent absence of an immune response. While Hrdliˇcka’s conclusions were logical at the turn of the 20th century (Buikstra, 1981a), skeletal evidence continued to accumulate (see summaries in Buikstra, 1981b, 1999; Roberts and Buikstra, 2003), convincing the prominent medical historian, Erwin H. Ackerknecht (1955) that TB existed in the Americas prior to 1492. During the 1960s, however, two physicians/paleopathologists, Dan Morse (1961, 1967, 1969) and Aidan Cockburn (1963), concluded that TB was not present in pre-Columbian America. Morse’s criteria for recognizing TB in ancient populations were grounded in his clinical experience with TB and his avocational interest in archeology (Rose and Burke, 2012). Morse (1961) was rigorous in his approach to paleopathology, establishing six criteria by which TB could be recognized in skeletal remains, concluding that, in his opinion, there was no convincing pre-Columbian evidence of TB in the Americas. As Buikstra (1981a)

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concluded two decades later, the tension between medical opinion and archeological evidence was based partly upon sampling bias—archeologists, such as Ritchie (1952), selected and presented extreme pathological examples to medical specialists. Medical specialists, on the other hand, increasingly based their conclusions on patients whose treatments had attenuated the disease course. “The anthropological bias was therefore toward the extreme, whereas Morse’s clinical experience would have tended toward the other end of the continuum” (Buikstra, 1981a: 9). Cockburn’s (1963) skepticism developed from his opinion that there were not sufficiently large, settled groups in the pre-Contact Americas, that Native Americans presented classic symptoms of groups experiencing TB for the first time, and that there were no domesticated animals to serve as an intermediate host (Buikstra, 1981a). As reported by Stone and Ozga (Chapter 8), we now know that domesticated animals were not necessary for the development of TB in ancient American people. We also know that there were large settled communities across the Americas prior to Colombian contact, and we have clear evidence that the TB strain introduced by Europeans (Lineage 4) was distinctly different from the pre-Colombian strain present in South America (Lineage 6) (Bos et al., 2014). The accumulation of skeletal and desiccated softtissue evidence for ancient TB in South America (Allison et al., 1973, 1981) stimulated further excavations in the arid western Andes (Buikstra, 1995). Pioneering molecular studies associated with this region yielded PCR products compatible with TB (Salo et al., 1994; Arriaza et al., 1995). As Stone and Ozga report in Chapter 8, PCR methods are subject to limitations that are overcome largely through next-generation sequencing approaches, which have confirmed the presence of MTC ancient DNA in 1000-year-old skeletons from the Osmore River drainage in Peru´. Similar limitations apply to a number of other PCR aDNA results from North America (e.g., Rothschild et al., 2001). Phylogeography of American Tuberculosis One of the reasons that American TB largely has been ignored in histories of infectious disease is explained by the popular evolutionary narrative—human TB derived from M. bovis when pastoralists came into close contact with domesticated host animals in the Eastern Mediterranean. There is no place for an American TB in this scenario. As we now know from genomic studies, however, the human TB forms are more complex, and therefore more ancient than those affecting other species originating in Africa. This antiquity permits reconstructions of global histories, including transfer to the Americas through human migrations. While this model

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seems plausible and may still explain ancient TB in North America, the “jump” of TB back to humans from Lineage 6 pinnipeds is now supported by empirical evidence (Bos et al., 2014). Additional studies will be required to document and hypothesize spread of this form of TB throughout South America during the first millennium AD and subsequently to North America by traders from Ecuador by AD 1000 (Buikstra, 1999).

Skeletal Examples All manifestations of skeletal TB can also occur in any one of several other infectious diseases as well as other pathological processes, including cancer (Chapter 21) and trauma (Chapter 9). This similarity in expression between TB and other diseases is a reason for caution, particularly for destructive lesions of bone other than vertebrae. However, careful description of visible bone lesions and a knowledge of the effect of TB on the bones does permit reasonable inferences about the presence of TB. In the remaining paragraphs of this discussion of the paleopathology of TB, a few examples are given from both the Old and New Worlds where a diagnosis of TB is plausible, if not probable. One of the earliest examples of probable TB is from the site of Bab edh-Dhra in Jordan (Ortner and Frolich, 2008). The skeleton (burial 73) represents a young male about 18 years old at the time of death, who was excavated from a shaft tomb chamber numbered A100E (Ortner, 1979). Tombs of this type are associated mostly with the Early Bronze IA phase (c.3200 3000 BC), and the pottery from this chamber is compatible with the earlier part of this range. The pathological changes are limited to the lumbar vertebrae, which all show evidence of antemortem damage (Fig. 11.47A). However, the most severe changes are seen in L3 L5, with a major portion of the inferior body of L4 destroyed by a pathological process. Reactive bone formed as an extension of the left body of L4, and this extension contains an opening that probably included a sinus draining the infectious focus destroying the body (Fig. 11.47B). The lower thoracic vertebrae from an individual buried at an archeological site in Giza, Egypt, provides another early example of probable TB (Fig. 11.48). The site is dated to between 3000 and 2200 BC, and the skeleton is curated at the Peabody Museum of Archaeology and Ethnology, Harvard University, Massachusetts (Catalog no. 59315). The vertebral bodies of T8 T12 have been destroyed, resulting in marked kyphosis and fusion of the remaining bone tissue. Medieval evidence of possible TB from the cemetery associated with the Hospital of St James and St Mary Magdalene, Chichester, England, is dated to between

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FIGURE 11.47 L1 L5 vertebrae, with destruction of the inferior portion of the L4 vertebral body and reactive new bone formation particularly on the left lateral portion of the remaining L4 body and the body of L5: (A) anterior view; (B) detail of reactive new bone formation on L4 with a cloaca for draining pus from the infectious focus (male about 18 years old at the time of death, from shaft tomb chamber A100E; burial no. 73 from Bab edh-Dhra in Jordan.

1200 and the 17th century AD (Magilton et al., 2008). The individual highlights some of the problems in differential diagnosis. This skeleton from burial 211 represents a person about 12 14 years of age at the time of death. The lesions of interest occur primarily on the five lumbar vertebrae and the sacrum (Fig. 11.49). The predominant abnormality consists of small lytic depressions in the margins of the vertebral bodies, with considerable periosteal reactive bone formation (Fig. 11.49A and B). What appears to be a groove for a draining sinus occurs on the right superior surface of the first sacral segment (Fig. 11.49C). The posterior surface of the right lamina of the second and third lumbar vertebrae show the development of reactive, porous, periosteal bone that is indicative of an inflammatory process active at the time of death (Fig. 11.49D). Diagnosis of TB in this case is troublesome for two reasons: (1) there is no collapse of the affected vertebral bodies and (2) the involvement of the posterior elements of L2 and L3. Certainly, mycotic infection (Chapter 12) and other bacterial infectious diseases (this chapter) need to be considered seriously in a differential diagnosis. In particular, involvement of the posterior elements is very rare in TB, although it can occur. A diagnosis of TB is preferred slightly over other options because the disease was prevalent in England at that time. Although the

FIGURE 11.48 Probable evidence of spinal TB from an individual buried at a site in Giza, Egypt: right oblique view of T7 T12 vertebrae. Probable female, 14 years old; with permission of PMH, catalog no. 59315.

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FIGURE 11.49 Possible TB, staphylococcal, or mycotic infection affecting the lumbar vertebrae and sacrum: (A) L1 S4 vertebrae with cavitation and reactive new bone formation; (B) detail of periostosis of L2 L4 vertebrae; (C) cavitation of the superior right S1 vertebra; (D) posterior view of the vertebral arches of L2 L4 vertebrae; notice the periostosis particularly on the lamina of L3 (arrow). Vertebral arch involvement is possible but unusual in tuberculosis, suggesting an alternative diagnostic option of staphylococcal or mycotic infection (adolescent; UB burial no. C-211).

skeletal manifestations in this case are unusual for skeletal TB, it certainly could be a relatively uncommon expression of this disease. Ortner and Bush (1993) described a remarkable 11 13 year-old child with probable spinal TB from the site of Abingdon, Oxfordshire, England. The site is dated to about AD 1640. The primary evidence of disease occurs in the spine where the vertebral bodies of T7 L1 were partially to completely destroyed (Fig. 11.50). In all, seven vertebral bodies were affected. This is more than

typically occurs in spinal TB and highlights the need for caution in relying too heavily on the common clinical manifestations of disease in the differential diagnosis of skeletal paleopathology. Conditions in antiquity may have been quite different and this could have affected the expression of skeletal diseases. A final Old World skeleton provides evidence supporting the antiquity of TB in Asia. Burial 3 comes from the Unoki site in Japan and is dated to between the 4th and 8th centuries AD (Fig. 11.51). Photographs of this

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FIGURE 11.50 Left lateral view of T4 L3 vertebrae with severe destruction of the vertebral bodies of T7 through L1. Tuberculosis is the probable diagnosis although the number of vertebrae involved is unusual for this disease (adolescent; Abingdon in Oxfordshire, England, dated to about AD 1640).

individual were provided through the courtesy of Dr. Takao Suzuki, who described this skeleton (Suzuki, 1978, 1985). The pathological bone consists of the lower thoracic vertebrae of an adult female. The marked kyphosis is apparent in the lateral radiograph. The New World evidence of possible bone TB in archeological skeletons is presented to illustrate the antiquity and diverse morphology associated with this disease in this part of the world. The first example comes from a child’s skeleton from Pueblo Bonito, New Mexico (NMNH 327127). The archeological date for the cultural materials from this site is AD 950 1250. The right femur of this skeleton measures 265 mm (without the epiphyses), which indicates an age at death of about 8 10 years. This estimate is in good agreement with age based on dental eruption. Estimation of sex in a child’s skeleton of this age is not reliable (Scheuer and Black, 2000: 215 216, 342 343). Although some of the bones are damaged or missing, the majority are present, including some of the hands and feet. There is no grossly

FIGURE 11.51 Lateral radiograph of the lower thoracic vertebrae of burial no. 3 exhibiting probable Pott’s disease (Unoki, Japan).

observable evidence of disease in any of the bones except the vertebrae. The 1st through the 5th cervical vertebrae are missing, although the 6th and 7th are normal. The 1st through the 10th thoracic vertebrae are present and normal. The pathological process begins with the 11th thoracic vertebra (Fig. 11.52). The superior surface of the body of this vertebra is normal, as are the transverse, spinous, and articular processes. Cavitation is seen on the anterior and left portion of the vertebral body. An enlarged canal resembling a cloaca occurs in the left sector of the body. The inferior surface of the body is eroded from the central to the left side. All elements of the vertebral arch are normal. The anterior body of the 12th thoracic vertebra is destroyed, leaving a scalloped spongy surface in the remaining bone. There is no bony fusion and the spinous, transverse, and articular processes are normal. The first lumbar vertebra is the most extensively affected bone, with almost complete destruction of the body. The left pedicle is fused to the body of L2. All vertebral processes are normal; however, there is slight deformation apparent in the lamina. This suggests the possibility of

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FIGURE 11.52 Slight to pronounced destruction of the vertebral bodies of the 11th thoracic through 1st lumbar vertebrae probably due to TB: (A) destruction of the thoracic and lumbar (arrow) vertebrae has resulted in kyphosis; there has been a limited amount of healing; (B) the right lateral view of the lower vertebrae; note the large cavity (arrow) on the remnant of the body of T12 (NMNH 327127; scale in centimeters).

compensatory remodeling after the destruction of the vertebral body. The superior surface of the body of L2 is eroded and fused with the remnant of Ll. The inferior body is intact but has slight exostoses on its left side. All processes are normal. The third through the fifth lumbar vertebrae are all normal except for slight evidence of deformity on L5, which, like the deformation seen in the lamina of L1, may be a reaction to the abnormal biomechanical loading caused by kyphosis resulting from the collapse and fusion of L1 and L2. Radiographs of the vertebrae demonstrate the anterior angulation (kyphosis) of the normal axis of the spine. The collapse of the vertebrae produced an angle of about 110 degrees (170 180 degrees is normal). The radiograph also shows evidence of a bony response to the deformity in the form of reinforced trabecular bone in the affected vertebrae. Radiographs of the femur suggest two, and possibly three, Harris’ lines, indicative of acute disease or malnutrition episodes at various times before death. The skull is badly fragmented and deformed by taphonomic changes subsequent to death and burial. However, there is no evidence of disease on the skull. The erupted teeth are normal. The age of the individual and the morphology of the lesion are compatible with a diagnosis of TB, although other diseases are possible.

The second example (Fig. 11.53) is a skeleton from Illinois (NMNH 381853). While associated archeological evidence may suggest a date before AD 400, making this skeleton one of the earliest examples of TB in the New World, the association of the burial with other materials from the site is problematic and thus the date uncertain. The age at death of this male individual was about 20 24 years. Only a few of the bones of the hands and feet are present. None of these bones shows any evidence of disease. The bones of the upper extremity are normal. In the pelvis, the sacrum is missing. There are no gross lesions of the innominate bones, although the left ilium is visibly less flared than the right. In the lower extremities, the left tibia is missing, although the right is normal, as are both fibulae. Comparative measurements of the two femora are presented in Table 11.4 and suggest differences that could be due to pathological processes. The left femur is more gracile than the right. The neck and head of the left femur are more nearly in line with the long axis of the shaft than the right (Fig. 11.53B). This condition (coxa valga) is typical when partial to complete paralysis of the limb occurs during the growth phase. The abnormally large neck-shaft angle of the left femur, the reduced size of the shaft diameters, and the diminished flair of the left ilium suggest partial paralysis of the left limb, perhaps caused

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FIGURE 11.53 Probable spinal TB in an archeological skeleton from Illinois; (A) right lateral view of the vertebral column; the entire vertebral body of T8 is destroyed and the posterior remnant is fused with T9 (arrow); (B) anteroposterior radiograph of the right and left femora, the fibulae, and the right tibia; compare the left femur with the right, noticing the diminished diameter of the midshaft and the increased neck-shaft angle of the left femur; (C) detailed view of the major lytic and kyphotic focus in the vertebrae; the body of T8 is completely missing and the partially eroded body of T7 is resting on the partially destroyed body of T9 (arrow); (D) lateral radiograph of the area of angulation of the spine; osteosclerosis is apparent in the partially destroyed remains of the T9 body (arrow) and in the body of T10 (NMNH 381853).

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TABLE 11.4 Comparative Measurements of the Left and Right Femur in an Archeological Skeleton With Possible Tuberculosis From Illinois (NMNH 381853) Left

Right

Measurement

(mm)

(mm)

Maximum length

428

421

Maximum midshaft diameter

27

29

Minimum midshaft diameter

18

21

Neck-shaft angle

152

136

by the collapse of the vertebrae. In the vertebral column (Fig. 11.53A) the first cervical vertebra is missing. The remaining cervical vertebrae are normal, as are the first three thoracic vertebrae. On T4, there is a lytic lesion on the anteroinferior surface of the vertebral body, with a similar but smaller lesion on the right portion of the body. T5 T7 have a slight periosteal bony reaction on both sides of the posterior portion of the body. The inferior articular surface of the body of T7 is eroded but shows evidence of circumscription, although there is no exuberant bone formation. The body of T8 is destroyed, with the posterior remnant fused with T9 (Fig. 11.53C and D). Both inferior articular facets are fused with their corresponding facets on T9, producing an anterior angulation. The superior plate of the body of T9 is destroyed. There is some peripheral reactive bone formation, with a large bony spur on the right lateral portion of the vertebral body. In T10 the articular surface of the vertebral body is intact. There are bilateral bony spurs on the vertebral body with slight cavitation on the anterior surface. T11 and T12 are missing. The first lumbar vertebra has slight erosion of the superior articular surface of the body and lateral bony spurs, with anterior cavitation. The inferior articular surface of the vertebral body is normal. Both L2 and L3 show evidence of destructive lesions on the anterior parts of their bodies. There is a reactive spur joining L2 and L3 on the right portion of their respective bodies, with a draining sinus affecting primarily the bodies of L3, L4, and L5; the sacrum is normal. The skull and mandible were badly damaged postmortem and not available for study. The bony spurs, fusion of T8 and T9, and draining sinuses are all suggestive of a chronic condition with life prolonged well beyond the acute stage. The abnormality of the left femur suggests an onset during growth and an illness lasting at least 7 10 years. An Inuit skeleton from the Yukon River in Alaska (NMNH 345394) illustrates possible TB of the hip (Fig. 11.54). The burial is from the historic period. The estimated age on the basis of epiphyseal union and pubic

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symphysis morphology is 18 22 years. The abnormally small size of the long bones and the distorted shape of the pelvis make sex estimation difficult but the individual was most likely female. The upper extremities are normal and, although small, suggest robust muscle activity. The bones of the hands are small but appear normal. There is no evidence of disease in the vertebrae either grossly or in the radiograph. The sacrum is normal, although small. The right innominate bone is small and somewhat deformed in response to the pathological condition in the left hip. The left innominate bone is grossly deformed, but the major focus of the infection is the acetabulum. The acetabulum is very shallow, an effect created by the destruction of the acetabular rim and its articular surface with subsequent remodeling and healing. There are large, well-organized osteophytes in the posterior rim area and a pronounced cavity in the inferior rim area. A welldeveloped bony ridge on the anterosuperior margin of the acetabulum is suggestive of upward migration and subluxation of the joint. There is a large cavitation extending through the acetabulum in the fovea region. The overall gracility of the innominate bone is exemplified by the very delicate ischial ramus. The left femoral head is destroyed, with subsequent cavitation. This destruction likely took place in late childhood with diminished growth of the bone following the acute phase of the disease. The measurements of the two femora highlight the differences in growth occurring after the onset of the disease (Table 11.5). The measurements of femoral length do not include the diseased femoral heads, and thus reflect the diminished growth of the pathological left femur. Notice that the left tibia has undergone accelerated growth, perhaps in an attempt to compensate for the shortened left femur. Indeed, the total length of the femur plus the tibia for the two sides is virtually identical. This, however, would have left the left leg somewhat shorter than the right due to the destroyed femoral head and the pathological superior subluxation of the hip joint. The resulting abnormal gait undoubtedly contributed to the deformity of both innominate bones. In addition to diminished growth in length (endochondral ossification), there is reduced appositional growth (intramembranous ossification) of the shaft diameter. Although the left tibia has undergone compensatory growth in length exceeding that of the right side, its development in midshaft diameter is relatively deficient, suggesting only limited use of the limb in locomotion. The powerful development of the arms may be the result of using some type of crutch. The developmental difference between the legs is also seen in the bones of the feet. The left metatarsals have attained the same length as the right, but they have visibly narrower shafts. Curiously, there is a lytic lesion in the right talocalcaneal joint, which has affected the medial articular surface of both bones. The lesion is

362 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 11.54 Possible TB of the left hip in an archeological skeleton: (A) radiograph of the major long bones of the lower extremity, anteroposterior view; note that the bones of the left leg are more gracile; (B) anterior view of the right and left femora; the femoral head of the left femur has been destroyed, the lesser trochanter is elongated and the shaft diameter of the left femur is much smaller; (C) detailed view of the left hip joint; note that the lytic process has produced a hole (arrow) that penetrates completely through the wall of the acetabulum (NMNH 345394).

somewhat circumscribed, indicating containment of the disease process. The relationship of this lesion to the disease process in the left leg remains problematical. Bone lesions from TB in locations other than the spine are indistinguishable from septic arthritis and some other diseases that can destroy the joint. In view of the obvious problems in differential diagnosis it is, of course, appropriate to avoid dogmatic assertions. In addition to TB, osteomyelitis and septic arthritis are important entities in the differential diagnosis. In TB, it has been noted that the active phase leads to destruction and cavitation in the cancellous bone with little perifocal reactive bone. This

description certainly applies to the destructive process in the femoral head of this individual. There is no evidence of a sequestrum or involucrum as would tend to occur in osteomyelitis, nor is there fusion of the joint, which is a common sequela in both septic arthritis and TB of the hip. Furthermore, TB of the hip is second in frequency to the involvement of the spine in bone TB and is the most common destructive lesion of the hip. Dislocation and perforation of the acetabulum in the region of the fovea are also associated with hip TB. Although ankylosis is a common sequela if healing occurs, the early death of this individual would have precluded this result. Furthermore,

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TABLE 11.5 Comparative Measurements of the Left and Right Femur and Tibia in a Skeleton With Possible Tuberculosis of the Hip (NMNH 345394) Left

Right

(mm)

(mm)

Length from medial condyle to greater trochanter

332

340

Maximum midshaft diameter

20

22

Minimum midshaft diameter

15

20

Length from lateral condyle to medial malleolus

299

290

Maximum midshaft diameter

18

20

Minimum midshaft diameter

13

15

Measurement Femur

Tibia

FIGURE 11.55 Possible TB resulting in destruction of the left sacroiliac joint in a skeleton from the Pecos Pueblo site in New Mexico, dated to between AD 1300 and 1838 (with permission of PMH; catalog no. 59811, now repatriated).

subluxation is not typical in septic arthritis. Although other diseases obviously cannot be ruled out, this skeleton does provide an example of what TB of the hip could look like in an archeological skeleton. Possible TB of the sacroiliac joint was also found in the pelvis of a skeleton from the Pecos Pueblo site in New Mexico. The site is dated between AD 1300 and 1838. Until its recent repatriation and reburial, the human remains from this site were curated at the Peabody Museum of Archaeology and Ethnology, Harvard University (Catalog no. 59811). This skeleton was from an adult female about 40 years of age when she died. The pathological process affected the left sacroiliac joint with destruction of virtually the entire subchondral bone surface and there were two large lytic defects penetrating through the entire ilium (Fig. 11.55).

LEPROSY Introduction Leprosy is a chronic infectious disease caused by either Mycobacterium leprae or Mycobacterium lepromatosis, bacteria closely related to the MTC. In M. leprae infections, the development and progression of the disease is chronic and often extends over decades, especially if left untreated. It is primarily a skin, nerve, and upper respiratory tract condition, but it can affect the skeleton and various bodily organs. The earliest signs are usually skin lesions and motor nerve impairment (e.g., “clawed” hands). The disease affects the peripheral, especially sensory, nerves, leading to loss of sensory perception in affected areas such as the hands and feet. The autonomic

364 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

nerves are also affected. Due to nerve damage, muscle activity can be affected. The bacteria are transmitted via exhalation and inhalation of droplets containing the organism, similar to transmission of the MTC (Richardus et al; http://www.who.int/news-room/fact-sheets/detail/leprosy). How humans acquired the disease is unknown. An animal host may have been a factor, but environmental sources of the bacteria are seeing increased consideration for transmission. For example, the same genotype of M. leprae has been found in soil and skin samples from people with leprosy (Turankar et al., 2012). Previous work of this type in coastal Norway by Kazda et al. (1990) and Irgens (1981) suggested that sphagnum bog vegetation was a source of M. leprae. High humidity is needed for sphagnum moss (found only in the north and west areas of Norway). This research found noncultivable acid-fast bacilli in sphagnum samples where leprosy was present in the 19th-century population who lived on farms surrounded by sphagnum. Noteworthy is that in recent years a new mycobacterial species causing diffuse lepromatous leprosy (M. lepromatosis) has been identified through molecular analysis (Han et al., 2008; 2015). Termed Lucio’s Phenomenon in Mesoamerica, M. lepromatosis has been reported to affect humans in several parts of the world, and phylogenetic work has shown that M. lepromatosis is closer to leprosy’s most recent common ancestor (MRCA) than M. leprae (Singh et al., 2015), which makes it older than M. leprae. As yet, M. lepromatosis has not been identified in human remains biomolecularly, and it is not known how it may affect the skeleton. For that reason, all subsequent discussion of leprosy will focus upon M. leprae unless M. lepromatosis is specifically relevant. Following sequencing of M. leprae (Cole et al., 2001) and aDNA analysis of skeletons from a range of sites and periods, we are beginning to better understand the origin and evolution of leprosy (e.g., see Monot et al., 2005, 2009; Schuenemann et al., 2013; Donoghue et al., 2015). Modern DNA studies by Monot have shown that leprosy likely originated in the Near East or Africa around

100,000 years ago and spread east via north (Silk Road) and south routes, and much later to the Americas via colonization and the slave trade. There is a reported predominance of the disease in males over females in a ratio of 2:1 (Faget and Mayoral, 1944), but the figures belie the facts. While women have a stronger immune resistance to infectious disease, they are less likely to come forward for diagnosis for a variety of reasons (e.g., lack of money or time to travel to clinics). Adolescents and adults contract leprosy more than infants and children overall, but detection methods, as for sex-related frequency data, will affect the figures ultimately published. M. leprae is most commonly found in humans but is also known to infect some nonhuman primates and the armadillo (e.g., Truman, 2005; Meyers et al., 1985). In recent years both M. leprae and M. lepromatosis have also been identified in red squirrels in the United Kingdom and Ireland (Meredith et al., 2015). M. leprae is acid-fast and Gram-positive, and it causes a very chronic granulomatous infection (a collection of immune cells). Although transmission of bacteria from an infected human host to another host can occur easily, disease occurs in less than half of the people exposed to the pathogen. The response by the body to M. leprae is among the most variable of any infectious disease. In individuals who experience the actual disease following exposure, its manifestations range from very mild (tuberculoid or paucibacillary) through one or more intermediate stages to very severe (lepromatous or multibacillary). The reason for this variability are largely due to the immune response of the person with the disease (Ridley and Jopling, 1966; see Fig. 11.56). Skeletal involvement can occur across the spectrum, although the skeletal manifestations are more extensive and severe in lepromatous leprosy. The skeletons of people with lepromatous leprosy in the past will likely be the ones we recognize in the archeological record. Leprosy is a declining disease today. According to the World Health Organization (2017a,b), “there were 214,783 new “cases” in 2016, with 75% of them FIGURE 11.56 The Ridley and Jopling (1966) immune spectrum.

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identified in Southeast Asia. Brazil (25,218), India (135,485), and Indonesia (16,826) had the highest numbers.” While the trend is a decline, the numbers belie the continuing challenge that people with leprosy today experience. Beyond the “new cases”, there are many more “cured” people who have been stigmatized, perhaps because of impairments that are outwardly visible. They may have lost jobs as a result and thus are living in poverty, sometimes isolated from the rest of their community. In the past, there is clear evidence that a number of people with leprosy were also stigmatized (e.g., see Roberts, 2011); some were admitted to leprosy hospitals or leprosaria, but support for the latter inference is scarce in the archeological record. Increasingly, evidence is showing that people with leprosy were more accepted within their communities than believed (e.g., see Rawcliffe, 2006; Demaitre, 2007; Roberts, forthcoming). Nevertheless, stigma and related marginalization has prevailed in the historical literature for centuries, and much of this has been due to its apparent description in the Bible. As a result, even into the 19th and 20th centuries, people were taken away from their communities and placed in often remote regions such as on islands (e.g., Molokai in Hawaii - Law, 2010).

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preferred by M. leprae. It should be noted that in both living and archeological skeletons, more foot than hand bone damage is noted. A useful overview of the effect of leprosy on the skeletons of children is provided by Lewis (2018: 167 171, and Table 7.2 provides a summary of the bone changes found in archeological contexts).

Direct Effects of M. leprae

Pathology

The direct effects of the M. leprae bacteria are seen in the skull with destruction of the nasal bones, nasal septum, turbinate bones, and the hard palate (Job et al., 1966). The characteristic features frequently found in RMS include the resorption and eventual disappearance of the anterior nasal spine, rounding/remodeling of the edges and widening of the nasal aperture, resorption, recession, and remodeling of the alveolar process of the maxilla (with or without loss of the upper incisor teeth), and sometimes nasal structure collapse (Fig. 11.57). Similar nasal lesions can occur in tertiary syphilis, lupus vulgaris (TB), leishmaniasis, and cancer (see Manchester, 1983). The oral and nasal surfaces of the palatal bones may also experience inflammatory pitting and possible destruction, as well as leprogenic odontodysplasia (Danielsen, 1970). The latter is characterized by constriction and shortening of the roots of the permanent maxillary incisors, which is caused by M. leprae. There has been little archeological

Skeletal involvement is generally thought to affect about 3% 5% of people with untreated leprosy (Paterson and Rad, 1961). However, in one study of 483 people with leprosy, 306 (63%) had radiologically identified bone lesions (Esguerra-Gomez and Acosta, 1948). The facial, hand, and foot bones are affected most commonly, reflecting inhalation of the bacteria into the nasal and oral areas, along with damage to peripheral nerves. There have been three significant leprosy hospital cemetery populations studied in the last 50 or so years, two being located in England: St James and St Mary Magdalene, Chichester (Magilton et al., 2008), and St Mary Magdalene, Winchester (Roffey and Tucker, 2012). These examples have added to our knowledge not only of medieval leprosy in England, but also the bone changes associated with the infection. Such studies have complemented and extended the work of the medical doctor Vilhelm MøllerChristensen (e.g., 1953), who pioneered the study of leprosy in skeletal remains. He investigated the skeletons from the cemetery associated with a medieval Danish leprosy hospital (Naestved) and described for the first time in archeological skeletons the pathological changes that occur in the bones of people with leprosy. These included facies leprosa, later renamed rhinomaxillary syndrome, or RMS (Andersen and Manchester, 1992), and hand and foot bone changes. The changes of RMS reflect the cooler temperature of exposed mucous membranes and skin

FIGURE 11.57 Lateral view of a person with leprosy showing collapse of the nasal structures. Figure 70 in Mitsuda (1952) Atlas of leprosy. Okayama, Japan, Chot Foundation. ¯ okai ¯

366 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

evidence of leprogenic odontodysplasia found, to date (e.g., Matos and Santos, 2013), but Danielsen’s (1970) work showed that the condition was only present in individuals with marked RMS. Lepromatous osteomyelitis is also a direct feature of leprosy. However, it is an uncommon and frequently insignificant lesion, which may take decades to develop and involves only a small portion of a bone. For example, in one study only 5.6% of people with lepromatous leprosy showed specific lepromatous leprosy-related disease (Faget and Mayoral, 1944). If present, the small bones of the extremities (phalanges, metacarpals, and metatarsals) are targeted. Further, erosions of the cranial vault, underlying lepromatous leprosy scalp lesions, may be observed but are also rare.

Indirect Effects of M. leprae The indirect effects of leprosy relate to M. leprae’s impact on the sensory, motor, and autonomic nerves, with subsequent damage to soft tissues and bones. Sensory nerve involvement in leprosy leads to anesthesia and subsequent trauma and ulceration of the hands and feet (Fig. 11.58). If ulcers are left to develop, the bones are ultimately affected. In the hand, anesthesia often begins in the ulnar nerve, and therefore the terminal phalanx of the fifth finger is usually involved first (Hopkins, 1928). Resorption of the ends of the distal hand phalanges progresses proximally, and occasionally includes the metacarpals, but the resorption usually goes no further down the hand. There may, however, be carpal disintegration. The intertarsal, metatarsophalangeal, and interphalangeal joints in the foot can all be involved, and tarsal disintegration can occur. Severe osteoarthritis, and even neuropathic arthropathy similar to a Charcot’s joint can be seen in the ankles and feet of people with advanced leprosy. In addition, the existing anesthesia facilitates traumatically induced damage and secondary infections. Other conditions, such as spina bifida, may also lead to anesthesia and ulceration. Joint degeneration, with a similar

FIGURE 11.58 Ulcer of the heel in leprosy.

pathogenic mechanism, is seen in advanced rheumatoid arthritis, but in leprosy no primary arthritic changes are seen. Diabetes and even frostbite are other diagnostic options that should be considered for the metatarsal changes. The bone changes due to motor nerve degeneration potentially involve damage and even paralysis of muscles, muscle groups, ligaments, and tendons. This may lead to subluxation and dislocation of the interphalangeal joints, hyperextension of the metacarpophalangeal joints and the metatarsophalangeal joints, and hyperflexion of interphalangeal joints of the hands and feet. The latter cause “claw” hand (ulnar nerve) and “claw” foot (posterior tibial nerve) deformities. Although not pathognomonic of leprosy because other conditions could cause “claw hands” (e.g., “stroke” or cardiovascular accident), these deformities potentially lead to “grooves” on the palmar surfaces of the proximal hand phalanges and the plantar surfaces of the proximal foot phalanges (Enna et al., 1971; Andersen and Manchester, 1987). A “dropped foot” can further occur due to loss of the longitudinal and transverse arches of the foot, but this is not pathognomonic of leprosy, either. Such changes can cause strain on the ligaments that attach to the dorsal surfaces of the tarsal bones and “dorsal tarsal bars”, but again, these conditions are not pathognomonic for leprosy (Andersen and Manchester, 1988; see also Fig. 11.59). Deformities in the hands and feet, as a result of motor nerve damage, can predispose people to trauma and subsequent ulcers as a result of the synergy between motor and sensory nerve damage. Facial nerve involvement in leprosy may lead to paralysis and the inability to close the eyelids, or lagophthalmos (Fig. 11.60) and subsequent eye infection. Deformities will also affect the progression of any associated leprosy-related sepsis (septic arthritis, osteitis, osteomyelitis). Secondary bacterial invasion of the bones and joints may modify the appearance of the skeletal

FIGURE 11.59 Tarsal bars showing on a radiograph of the foot, and clawing of the toes.

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367

and is fractured (acro-osteolysis; Andersen et al., 1992). In the foot, concentric resorption starts in the proximal phalanges and distal metatarsals, with a cup and peg deformity eventually occurring at the joints, the latter being a change that may also affect the hands. This resorptive change can terminate in subluxation and dislocation. In addition to concentric atrophy there may be erosive changes in the hands and feet. The remaining fragments continue to remodel and may develop a teardrop profile. The affected metacarpals and metatarsals can eventually become pointed at their distal ends, although a complete cortex on the tapered remnants of involved bones is observed (Cooney and Crosby, 1944).

Periostosis of Limb Bones

FIGURE 11.60 Lagophthalmos of the eyes. Figure 69 in Mitsuda (1952), Atlas of leprosy. Okayama, Japan, Chot Foundation. ¯ okai ¯

lesions of leprosy in the terminal phase, and the hands or feet may be almost completely destroyed. Even secondary tuberculous arthritis is not uncommon (Beitzke, 1934a: 611). In seven of eight autopsied people with leprosy, active pulmonary TB was found (Brutzer, 1898). The specific granulomatous bone lesions, especially in the phalanges of the hands and feet, very closely resemble those observed in sarcoidosis (Paterson and Job, 1964: 432). Mutilations also occur in both diseases. Differentiation of these lesions on dry bone alone may be impossible, but sarcoidosis is a rare disease today. If it occurred at all, it was probably rare in antiquity too, which should be considered in differential diagnosis. When the autonomic nerves are affected, there is disruption of sympathetic parasympathetic nerve balance leading to loss of arteriole control and osteoclast osteoblast harmony. This can cause slow, progressive, concentric atrophy/remodeling of the diaphyses of the metacarpals, metatarsals, and proximal and mid phalanges and “knife-edge”/mediolateral remodeling of the metatarsals (Enna et al., 1971). Concentric atrophy in leprosy is a process that involves resorption = and remodeling of the cortex, resulting in a gradual loss of the diaphyseal diameter and medullary cavity in the hand and foot bones, although the cortex itself is maintained until late in the process. Concentric atrophy may continue until the diaphysis is unable to withstand biomechanical stress

Møller-Christensen (1953) frequently found subperiosteal new bone formation on the tibia and/or fibula in skeletons from medieval Denmark. This was suggested to be a likely reaction to leprous involvement of the feet. Other studies of skeletons with leprosy have also noted this bone change (e.g., Lewis et al., 1995; Roberts, 2002; Magilton et al., 2008; Roffey and Tucker, 2012), and new bone formation has also been found on the radius and ulna, perhaps reflecting involvement of the hands, as opposed to the feet (Lewis et al., 1995). While periostosis has many etiologies, its presence with bone changes that are more certain to be associated with leprosy supports its relationship with the infection. Patients with leprosy can have swollen legs due to infection of the feet, leading to chronic venous stasis (Price, 1961), which could be an explanation for lower-leg bone periosteal reaction (Jopling and McDougall, 1988). Even so, this bone change cannot be claimed to be pathognomonic. Bone reaction to overlying skin ulcers is also not pathognomonic for leprosy, but may be present in the form of circumscribed new bone formation (Boel and Ortner, 2013).

Other Bone Changes Associated With Leprosy There are a number of co-morbidities that should be considered when diagnosing leprosy. Osteopenia and osteoporosis in patients with leprosy have been recorded (Ishikawa et al., 1999), especially in men when the testes are affected. Hearing problems (Awasthi et al., 1990) and upper and lower respiratory tract involvement (Kaur et al., 1979) may also occur. In one study of ear bones in skeletons with and without leprosy, Bruintjes (1990) found over 50% had erosive lesions. Maxillary sinusitis is also associated with people who have leprosy today (Hauhnar et al., 1992), and this has been noted in archeological skeletons (Boocock et al., 1995), likely as a result of the infection entering the nasal passages and causing an inflammatory response in the upper respiratory tract. Poorer oral health has also been described in people with

368 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 11.61 Cribra orbitalia in a child with leprosy. (Child about 12 years old from the medieval (c. AD 1175 1600) hospital cemetery at Naestved, Denmark; DNM burial no. 127).

leprosy (e.g., see Reichart et al., 1976), and although dental disease has been recorded in the teeth and jaws of skeletons with leprosy, no detailed studies of the evidence have been done in comparison to nonleprous skeletons. Trauma has been explored in relation to leprosy infection utilizing a subset of individuals with and without leprosy buried in a medieval leprosy hospital cemetery at Chichester (Judd and Roberts, 1998). This study explored whether leprotic infection predisposed individuals to fractures, but no differences in fracture frequency were found between people with and without leprosy. Finally, cribra orbitalia (Fig. 11.61) was identified by MøllerChristensen (1965) as being present in 69.7% of 99 skeletons at the medieval Naestved site in Denmark. While many etiologies were proposed, e.g., eye infection due to lagophthalmos (also suggested by Ortner, 2006), it is possible that this is an adaptive response to leprosy, i.e., a high pathogen load (see Stuart-Macadam, 1992).

Diagnosis of Leprosy in Skeletal Remains Møller-Christensen and Hughes (1966) argued that a diagnosis of lepromatous leprosy was convincing only when facies leprosa (RMS) was accompanied by bilateral periostosis of the tibiae and fibulae. However, in people diagnosed with leprous bone changes today, a more varied combination of bone changes occurs. Individual immune responses undoubtedly influence the expression of leprosy in both the soft tissues and the skeleton, and thus variations in which bones would ultimately be affected are expected. When only an archeological skeleton is available for diagnosis, which may be poorly preserved, the diagnostic process becomes challenging. Lepromatous leprosy, as discussed above, is the most likely diagnosis

in an archeological context. Tuberculoid leprosy diagnostic criteria—bilateral or unilateral hand and foot bone involvement and no RMS—have been proposed, based on Portuguese leprosarium archives (Matos, 2009). Other methods for evaluating leprosy in the past have estimated the specificity and sensitivity of leprosy-related lesions and calculated leprosy frequency (Boldsen, 2001). In reaching a diagnosis of leprosy in an archeological skeleton, one needs to pay particular attention to the overall pattern of skeletal involvement. As noted, some of the skeletal changes that result from leprosy also occur in other skeletal diseases. However, if the skeleton is well preserved, a combination of lesions in different parts of the skeleton (face, hands, and feet) provide a relatively certain diagnosis of leprosy, i.e., the RMS, in combination with atrophy and truncation of the fingers and toes, would appear to be almost pathognomonic for leprosy. Where leprosy is endemic, there will almost certainly be some archeological skeletal evidence that shows a pattern that can be attributed to this disease with a high degree of certainty.

Paleopathology Leprosy is a disease in which features identified in archeological human remains have been of value in the diagnosis of living patients. While medical practitioners knew that leprosy affected the skeleton, the detailed changes identified by Møller-Christensen (1965: 603) had not been previously described. Today, the distribution of leprosy is virtually worldwide. Similarly, the evidence of leprosy (M. leprae) in the ancient Old World is very convincing, but its potential presence in pre-Columbian New World populations has yet to receive empirical support (Cochrane, 1964: 10; Aufderheide and Rodriguez-Martin, 1998: 149; Roberts: www.international textbookofleprosy.org/). There is archeological evidence of leprosy in skeletons from three continents: Africa, Asia, and Europe (see Roberts, forthcoming; also see Roberts et al., 2002). It was particularly common in Europe, as seen in evidence from Denmark, Hungary, Sweden, and the United Kingdom. In recent years, more skeletal evidence has been published, which is contributing to our understanding of leprosy’s geographical distribution and timeline (e.g., Blau and Yagodin, 2005 and Taylor et al., 2009—Central Asia; Robbins Schug et al. 2009—India; Belcastro et al., 2005, Mariotti et al., 2005, and Rubini and Zaio, 2009—Italy; Boldsen, 2005, 2008 and Boldsen and Mollerup, 2006— Denmark; Baker and Bolhofner, 2014—Cyprus; Lunt, 2013—Scotland; Likovsky´ et al., 2006—Bohemia; Suzuki et al., 2013—Japan).

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The earliest evidence of leprosy appears to be in Hungary (3700 3600 BC—Hadju et al., 2010), India (2000 BC—Robbins Schug et al., 2009), and possibly Turkey (2700 2300 BC—Angel, 1969). This predates the earliest record in historical documents from China (Lu yu (Analects) 500 BC) and India (Atharva Veda 1400 BC). However, most burials are from the late medieval period of Europe (12th 16th centuries AD). Leprosy saw a decline from the 14th century onwards, possibly resulting from the rise of the related disease, tuberculosis (Manchester, 1984; see also Stone et al., 2009 on the synergies between leprosy and tuberculosis). Note that very few skeletons have been found with both diseases (e.g., see Donoghue et al., 2005; Weiss and Møller-Christensen, 1971). In 1798, with the death of the last person with leprosy in the Shetland Islands of Scotland, the disease died out in Britain, although it continued to be a minor problem in continental Europe (Cochrane, 1964: 7). For example, leprosy was present in Norway through the 19th century (Fig. 11.62), with a few new “cases” being reported as late as the 1940s (Kazda et al., 1990). Prior to the genomic work by Monot et al. (2005, 2009), a number of scholars developed theories about how leprosy had been introduced to the Western world. Andersen (1969: 123), e.g., proposed that it came with the soldiers of Alexander the Great returning from their military campaign in India in 327 326 BC. One of the problems, however, in using historical documents for studying the history of leprosy is the vague description of diseases and imprecision in the use of terms (see also Mitchell, 2011, for a general discussion about historical record use in understanding the history of disease). As an example of the challenges in knowing what diseases are being described, MacArthur (1953: 8) quite rightly suggested that the term “leprosy” was used in the past for nonspecific skin diseases, elephantiasis, smallpox, bubonic plague, mange, etc. He further suggested that many of the people segregated into leprosy hospitals in the medieval period may have had diseases other than leprosy. This has proved true in some of the most recent work on skeletons with leprosy (e.g., Magilton et al., 2008), but at the cemetery associated with the medieval leprosy hospital in Winchester, England, a majority of skeletons had bone changes of leprosy (Roffey and Tucker, 2012), as was also seen at Naestved, Denmark (Møller-Christensen, 1953). It can be argued that the often-devastating consequences of a diagnosis of leprosy may have been a significant factor in ensuring that the diagnosis was carefully undertaken and the criteria used in diagnosis rigorously applied. Nevertheless, there is increasing evidence for people with leprosy being buried in community cemeteries (e.g., see Roberts, forthcoming; Baker and Bolhofner, 2014; Lunt, 2013). It is unclear whether this means diagnosis

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FIGURE 11.62 A restored 18th-century leprosy hospital in Bergen, Norway; the hospital was founded in the early 15th century: (A) courtyard; (B) hospital atrium with patients’ rooms and attending physicians’ offices surrounding the atrium.

was ineffective, or that people were indeed welcome in their communities. Leprosy (M. leprae) was introduced into the New World during the colonial period, and therefore archeological evidence of skeletons with leprosy should be rare and limited to the post-Contact period. MøllerChristensen and Inkster (1965: 12), for example, reference a skull found in 1866 on Vancouver Island, off the coast of Canada, which they suggest had RMS. Leprosy remains a condition rarely mentioned in New World paleopathology in the post-Contact period. Certainly, it is one of the least contagious of transmissible infectious diseases (Browne, 1970: 640). Thus, its introduction into the New World would not have had nearly the impact of other infectious diseases, such as malaria, measles, and smallpox. In the remaining pages of this section, examples of leprosy in skeletons from archeological sites in Denmark and England are described and discussed. The objective

370 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

of presenting these skeletons is to highlight the different manifestations of skeletal leprosy.

Naestved, Denmark Among the best documented archeological examples of skeletons with leprosy are those that were excavated by the late Vilhelm Møller-Christensen at Naestved, Denmark. This town was the site of a medieval hospital for people with leprosy and was part of a complex called the St. Jorgen’s Hospitals, which were built throughout Denmark (Møller-Christensen, 1953: 14 15). Most of the 200 individuals excavated show bone changes attributable to leprosy. Møller-Christensen’s experience with analyzing the skeletons from the Naestved cemetery provides significant insight regarding the bone changes to be expected from this disease (Møller-Christensen, 1961). As we have seen, the major foci for the disease are the bones of the face and the small bones of the hands and feet, although other bones may be affected. The skull lesions include rounding and enlargement of the pyriform (nasal) aperture, destruction of the anterior nasal spine, and destructive remodeling of the alveolar process of the anterior maxilla (Figs. 11.63 and 11.64). Less commonly, a lytic focus will destroy a portion of the hard palate (Fig. 11.65). As discussed above, there are a number of differential diagnostic options for these facial changes. However, Møller-Christensen (1965: 604) indicates that in leprosy, pathological changes are not found on the

FIGURE 11.64 Rhinomaxillary remodeling in a skeleton with leprosy. Note the alveolar recession and the narrowed rounded margins of the pyriform (nasal) aperture (adult female about 16 years old from the medieval cemetery associated with the hospital of St. James and St. Mary Magdalene, Chichester, England ;UB burial no. C-360).

FIGURE 11.65 Destructive focus in the hard palate of a skeleton with leprosy (adult female from the medieval (c. AD 1175 1600) cemetery associated with the hospital at Naestved, Denmark; BMNH 1962.1.1.2).

FIGURE 11.63 Rhinomaxillary remodeling in a skeleton with leprosy: Note the rounded margins of the pyriform (nasal) aperture (adult male about 45 years old from the medieval cemetery associated with the hospital of St. James and St. Mary Magdalene, Chichester, England; UB burial no. C-19).

skull vault. This contrasts with venereal syphilis (VS), where changes on the cranial vault can be present. This is certainly a helpful criterion for differentiating leprosy from VS, but should not be considered absolute because the absence of cranial vault lesions may be counterbalanced by other lesions considered consistent with VS.

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FIGURE 11.66 Destruction of the majority of each metatarsal and many of the phalanges of the left foot—with phalangeal concentric atrophy—in a skeleton with leprosy (adult from the medieval (c. AD 1175 1600) hospital cemetery at Naestved, Denmark; DNM burial no. 254). Note that some of the phalanges have been glued the incorrect way round.

The postcranial lesions are most pronounced in the extremities, particularly the hands and feet, including concentric atrophy of the shafts of the tubular bones (Fig. 11.66) and shortened phalanges (Fig. 11.67) (Møller-Christensen, 1965: 15). The bony destruction affects the subarticular and more highly vascularized bone in the epiphysis adjacent to the articular surface. This process compromises the joint, leading to collapse and a cupping deformity of the joint. Møller-Christensen also provided archeological evidence of the pressure erosion resulting from flexion contractures of the hand (Fig. 11.68), and this has been reported in more recent work on other skeletons (e.g., Magilton et al., 2008). The indentations caused by the pressure erosions occur on the proximal phalanges on their distal palmar surfaces (Fig. 11.69).

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FIGURE 11.67 Destruction of some of the metacarpophalangeal joints and truncation of some of the phalanges in the left hand of a skeleton with leprosy. Note also the presence of multiple cartilaginous exostoses on the humerus and radius (adult male from the medieval (c. AD 1175 1600) hospital cemetery at Naestved, Denmark; DNM burial no. 2).

FIGURE 11.68 Flexion contracture in the fingers (phalangeal joints) of the left hand of a skeleton with leprosy (adult from the medieval (c. AD 1175 1600) hospital site at Naestved, Denmark; DNM burial no. 407X).

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FIGURE 11.69 Proximal and middle phalanges of the left and right third fingers in a skeleton with leprosy. Note the palmar grooving of the distal proximal phalanges that is the result of flexion contracture (adult male about 40 years old from the medieval cemetery for the hospital of St. James and St. Mary Magdalene, Chichester, England; UB burial no. C-44).

Chichester, England The skeletal remains excavated from the cemetery associated with the medieval hospital of St. James and St. Mary Magdalene in Chichester, England, provide an important window on leprosy in medieval England. This is the largest leprosy hospital cemetery to be excavated to date in England. Most of the skeletal evidence for leprosy of the facial bones includes enlargement and rounding of the pyriform (nasal) aperture, where a smooth surface indicative of a very slow, chronic process is present. Clearly destruction has taken place, but evidence of active resorption is rare. However, two skeletons with active rhinomaxillary destructive remodeling are part of the skeletal sample from Chichester. The first of these skeletons (burial no. 187) with relevant bone changes is represented by the skull of an 17 20-yearold male (Ortner and Connell, 1996). The maxillary bone surrounding the pyriform (nasal) aperture is porous with fine depressions in its cortical surface (Fig. 11.70A C). Evidence of active inflammation is also seen on the nasal floor and the hard palate (Fig. 11.70D and E). The second skeleton discussed here (burial no. 354) is represented by

FIGURE 11.70 Early rhinomaxillary changes in leprosy: (A) anterior view of the rhinomaxillary area of the skull; note the presence of porosity probably resulting from inflammation in the bone surrounding the pyriform (nasal) aperture; (B) detail of porous lesion on the right maxilla; (C) porous bone surface in the left nasal passage; (D) porous bone surface of the nasal floor; (E) abnormal porosity of the oral surface of the hard palate (adult male about 18 years old from the medieval cemetery for the hospital of St. James and St. Mary Magdalene, Chichester, England; UB burial no. C-187).

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FIGURE 11.71 Early rhinomaxillary changes on the margins of the pyriform (nasal) aperture. Note the porosity and remodeling of the edge of the aperture (adult male about 27 years old from the medieval cemetery for the hospital of St. James and St. Mary Magdalene, Chichester, England; UB burial no. C-354).

FIGURE 11.72 Alveolar resorption in the maxilla of a skull with leprosy (adult male about 26 years old from the medieval cemetery for the hospital of St. James and St. Mary Magdalene, Chichester, England; UB burial no. C-350).

FIGURE 11.70 Contiuned

the skull of an adult male about 20 25 years of age at death. In this case, the erosive change is largely limited to the margins of the pyriform (nasal) aperture with minimal evidence of inflammatory bone changes on the maxillary bone surfaces away from the margins (Fig. 11.71). The alveolar process associated with the premaxilla is affected by this destructive remodeling. This, of course,

undermines the support for the upper incisor loss observed in patients with long-standing leprosy (Fig. 11.72). If the onset of leprosy occurs during dental development, the dental roots may not develop to their full size; this is a condition Møller-Christensen (1978: 123) called dens leprosus or leprogenic odontodysplasia (Fig. 11.73). As seen at Chichester, abnormalities in the lower-leg bones may be extensive. Neurological problems of the foot tend to result in destructive remodeling of the foot, particularly affecting the metatarsals and phalanges. The

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FIGURE 11.73 Radiograph of leprogenic odontodysplasia of the incisor teeth, resulting in almost complete failure of dental root development (child about 9 years of age from the medieval (c. AD 1175 1600) hospital site at Naestved, Denmark; DNM burial no. 1).

FIGURE 11.75 Severe destructive remodeling that has greatly reduced the diaphyses of the left metatarsals, leaving only the proximal metaphysis and the remnants of the former diaphysis. (Adult male from the medieval cemetery associated with the hospital of St. James and St. Mary Magdalene, Chichester, England; UB burial no. C-62).

FIGURE 11.74 Metatarsals and proximal phalanges of the right foot of a skeleton with leprosy. Notice particularly the “blade-like” remodeling of the fifth metatarsal (adult from the medieval (c. AD 1175 1600) hospital site at Naestved, Denmark; DNM burial no. Z).

expression of this pathological process can be relatively mild (Fig. 11.74), but can result in major bone loss with severe disfigurement and loss of biomechanical function (Fig. 11.75). Because of the loss of sensation, injuries to the foot may go unnoticed and untreated. Secondary infections are a common complication and they tend to become chronic. These secondary infections can stimulate periostosis that may extend from the primary site in the foot to the tibia and fibula. In contrast with other conditions, such as treponematosis, reactive new bone formation is most severe near the ankle and diminishes in severity toward the knee (Fig. 11.76).

FIGURE 11.76 Periostosis of the lower tibia and fibula that is probably the result of a chronic infection of the foot (adult male about 35 years from the medieval cemetery for the hospital of St. James and St. Mary Magdalene, Chichester, England; UB burial no. C-88).

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TREPONEMATOSIS, TREPONEMAL INFECTION, OR TREPONEMAL DISEASE (TD) Introduction Whether the treponematoses—venereal syphilis (VS), yaws, endemic syphilis (ES) (also known as bejel), and pinta—are caused by different species of treponeme or by variants of the same species is still unresolved. Until the 1990s, the bacteria causing all the “syndromes” were indistinguishable using any known histological, immunological, or molecular biological methods (Hoeprich, 1989: 1022). Research on the DNA of bacteria causing TD has identified a difference between the bacterium associated with VS and that which causes nonvenereal TD (Centurion-Lara et al., 1998). However, this difference occurred in a segment of DNA that did not code for protein (flanking region). It is therefore considered unlikely that the difference had any relationship to the clinical manifestations of the syndromes (Lukehart, 1997, personal communication). Nevertheless, this research was an important step in initially clarifying the relationship between the pathogens causing the different clinical syndromes of TD which had been (and are) used to diagnose TD in an archeological skeleton dated to the historic period in the New World (Kolman et al., 1999). The geographic distribution of the nonvenereal treponemal syndromes tends to be limited to specific climatic zones. Pinta is a skin disease found in people in the Americas, yaws is a disease usually associated with tropical indigenous populations, and bejel is found mostly among indigenous populations in drier areas of subtropical North Africa, the Near East, and temperate Asia (but it is not found in the Americas). Bejel may have also occurred in northern Europe during the 17th and 18th centuries (Hoeprich, 1989: 1032). VS has a global distribution today and a contested past. There are several interrelated bioarcheological, historical, medical, and biological issues that contribute to the diverse opinions that exist about TD. Resolution of these issues has important implications for our understanding of the evolution and history of host pathogen interactions, as well as the historical questions embedded in the arguments about where the disease originated and how it spread from one geographical area to others. These issues continue to be debated as more skeletal evidence is found and critiqued, older evidence is reexamined (e.g., see Cook, 1976; Powell and Cook, 2005; Cook and Powell, 2012; Harper et al., 2011; de Melo et al., 2010), and new developments in modern and ancient DNA analysis of TD are incorporated (e.g., Montiel et al., 2012, and see Chapter 8). Unfortunately, the limited and mostly unsuccessful work regarding DNA analysis of skeletons with

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TD has not expanded our understanding of this infection in archeological contexts. While ancient and modern genomes of both leprosy and TB have been sequenced, TD genomic data are ambiguous and of limited utility in understanding the archeological record. As Stone and Ozga suggest (Chapter 8): “Data from modern strains indicate that T. pallidum subspecies pertinue and endemicum cluster with each other and that the TMRCA [the most common recent ancestor] for T. pallidum pallidum is estimated to have evolved around AD 1611 1859, long after the first historical reports of syphilis (Arora et al. 2016). This late date may reflect the limitations in geographic strain diversity in the available data, particularly in strains from Africa, or it could reflect the success of a particular set of strains to the detriment of more virulent strains, since there is some indication of more severe disease in early reports of syphilis.” A fundamental biological question is: are the four different clinical syndromes of TD caused by one or more different bacteria (see description below of the syndromes)? If a single pathogen is responsible for all four clinical syndromes, then the clinical differences between the syndromes must be explained by other factors that can affect the expression of infectious disease (see Table 11.6). We have seen in the discussion of leprosy that a single organism has the capacity to elicit a very broad range of responses from a host. At one end of the spectrum, the person may be completely unaware of the presence of the pathogen. At the other extreme, a person may develop severe disfigurement and/or suffer premature death. In the case of leprosy, the major factor in these differences is variation in the immune response of the person infected. This

TABLE 11.6 Factors That Can Affect the Expression of Infectious Disease in the Human Host Host Factors

Pathogen Factors

Age of onset

Biology of the pathogen

Age of the host

Pathogen reaction to host’s immune response

Adequacy of the host’s diet Gender differences in immune reactivity

Size of the inoculum

Exposure of the host to pathogens

Reproductive strategy of the pathogen

Immune response of the host General health of the host Portal of entry of the pathogen Social factors (e.g., population density) Efficacy of treatment

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highlights the possibility of population-based genetic variation in the immune response, resulting in different patterns of skeletal involvement in different human groups. If, on the other hand, more than one bacterium is responsible for at least some of the clinical variation between the syndromes, pathogen differences become a more important factor in understanding the clinical syndromes. It is, of course, possible that both differences in the pathogen and in the human immune response are responsible for the different clinical manifestations of TD and subsequent bone changes. All of these options have significant implications for our understanding of the evolutionary adjustments made by the host and the bacteria. For example, one potential evolutionary strategy for the pathogen is to evolve a very flexible relationship with the host, including the ability to infect a person via multiple pathways and respond to variation in immune responses. Another potential strategy would be for the bacterium to specialize in a restricted entry portal and vigorously counter a limited range of host immune responses. The following subsections address the evolutionary history of TD, the biology of the treponemal organism, and the bioarcheological evidence of TD. It addresses the following questions: 1. Is the pathogen that causes TD highly specialized in its relationship to the human host or is it an organism that adjusts easily to different host conditions and responses? 2. Do the different syndromes of TD exhibit distinguishable differences in their skeletal manifestations? and 3. Does the bioarcheological evidence address the issues of where and when the various syndromes developed?

Pathology The following discussion of TD is limited to the three syndromes that affect the skeleton: yaws, bejel or (ES), and VS. Individuals working with desiccated soft tissues in the Americas should, however, be aware of the possibility that pinta may be the cause of skin lesions. In all the treponematoses, the infecting organisms enter the body through the skin or mucous membrane near the skin’s surface. In bejel and yaws, the infection may locate anywhere on the body surface via direct contact between an open sore of an affected person with a break in the skin of another person. The age of onset in both bejel and yaws tends to be in childhood (Resnick and Niwayama, 1995a). VS is a sporadic disease that, because of its venereal mode of transmission, can occur in any human population, primarily affecting sexually active adults and infants who receive the bacterium via the placenta or during childbirth (congenital syphilis CD). In all three treponematoses, the organisms are disseminated throughout the body and reach the skeleton via the bloodstream.

Treponemal bacteria tend to affect skeletal elements with minimal overlying soft tissue. The reasons for this are not entirely clear. Jaffe (1972: 921) hypothesizes that these bones are more commonly affected by trauma and may thus make it easier for bacteria to enter the body. Bacteria also tend to reproduce optimally at very specific temperatures (see also the relevant discussion above for leprosy). The slightly cooler temperatures of bone located close to the skin surface may be an attractive environment for the treponeme. This predilection for affecting bone closer to the skin surface creates a pattern of skeletal involvement in TD that, when combined with the typical crater-like lesions containing the stellate radiating lines, is virtually pathognomonic for skeletal treponematosis. However, not all skeletons with TD have this characteristic type and/or pattern of skeletal lesions, and it is these skeletons that provide a diagnostic challenge in archeological contexts. The absence or poor preservation of skulls weaken the diagnosis, as does the knowledge that periostosis of long bones can have many etiologies (see Chapter 10). There is ongoing debate about differences between the syndromes in their skeletal manifestations. Hackett (1976), whose seminal work on diagnostic criteria for TD is a “must read” for any paleopathologist, argued that the distribution of lesions within the skeleton of VS, bejel, and yaws are so similar that diagnostic differences for individual skeletons cannot be made with certainty. In generating his diagnostic criteria, Steinbock (1976: 86 169), on the other hand, suggested that some differences in the typical pattern of bone involvement did exist between the three syndromes. It is certainly possible that slight differences in the type and distribution of bone lesions may exist for each of the three syndromes. However, a review of the current medical literature indicates a very considerable similarity in the bone lesions. When one is confronted with one or two skeletons with TD, as often happens, differential diagnosis between the three syndromes is likely to be difficult, if not impossible.

Yaws Bone lesions are somewhat more common in yaws than either VS or bejel. Estimates of skeletal involvement in patients with the disease range between 5% and 15% (Steinbock, 1976: 142 143). In a study of 101 individuals conducted by Goldman and Smith (1943), bone lesions were found in various skeletal elements with the following frequencies: tibia (46), fibula (20; 19 associated with the tibia), femur (13), ulna (10), humerus (9), radius (7; six times alongside the ulna), spine (5), clavicle (4), hand bones (4), foot bones (4), skull (3), ribs (3), and pelvis (2). Because yaws is usually acquired in childhood, the most active lesions are seen in children and in adolescents. Many lesions are similar to those seen in congenital

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FIGURE 11.77 Dactylitis of the right hand caused by yaws: (A) view of the hand; note the swelling in the area of both the metacarpals and the phalanges; (B) radiograph of the hand; note the enlargement of some metacarpals and phalanges (male 2 years old, from the monograph on yaws by Hackett, 1976, Figs. 47 and 48; “case” 241).

syphilis. This is particularly true of the often symmetrical dactylitis of the spina ventosa type (Fig. 11.77) and periostosis (Hackett, 1957: 14 15). If the child survives into adulthood, the early bone lesions of yaws may completely heal without leaving permanent bone changes. Another finding frequently observed in yaws is “bending” or “bowing” of the tibia (boomerang leg) (Fig. 11.78), which is very similar to the saber tibia of CS and usually develops before 15 years of age (Wilson and Mathis, 1930). Jaffe (1972: 921, 937) distinguishes between true bowing and pseudo-bowing of the tibia. In the former, the long axis of the tibia is abnormally curved. Pseudo-bowing is the result of periosteal reactive bone formation on the anterior and medial surfaces of the tibia without any distortion of the long axis. True bowing tends to be associated with subadult TD and pseudo-bowing with adults. Hackett (1936: 54 56) describes disseminated radiological lucencies in the anterior cortex in the early stages of yaws followed by anterior cortical thickening and bending. In the late stages, the posterior concave cortex is thickened and the anterior cortex thinned, as in late-stage deformities in rickets. Rarely, the fibula is also deformed and occasionally the radius and ulna show similar bending (Hackett, 1936: 52 4). These changes are indistinguishable from deformities of rickets and may not be due to yaws alone. Bending of the long bones also needs to be differentiated from normal variation.

The bone changes in the late stages of yaws show destructive dactylitis of single hand phalanges. The long bones, especially the tibia and the bones of the forearm, may show periostosis and osteomyelitis with gummata (focal infective destructive lesions containing bacteria, white blood cells—mostly lymphocytes—and connective tissue) very similar to tertiary VS. Indeed, Buckley and Dias (2002) have noted that the position of the lymph nodes and lymphatic vessels is the same as the characteristic pattern of skeletal involvement in TD. In contrast to the early stages of yaws, the overlying soft tissues frequently ulcerate and thus open the way for secondary pusforming infections, pus being a fluid containing bacteria and dead white blood cells produced in infected tissue (Hackett, 1976: 16). Skull changes due to yaws include chronic lesions of the vault characterized by central destruction surrounded by reactive bone formation that creates the crater-like lesion of classic caries sicca. Hackett (1976) has provided a careful description of the development of these lesions because they also occur in VS. The lesions begin with a roughly circular cluster of holes penetrating the outer table of the skull that are linked in the living patient to gummas. Lesions of the facial bones include the formation of periosteal reactive new bone on the maxilla (goundou) and destruction of the bones of the nasal cavity with penetration of the hard palate (gangosa).

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FIGURE 11.78 Radiograph of saber tibia in yaws: notice the bowed and elongated tibia with anterior cortical osteoporosis and posterior cortical thickening (48-year-old Javanese male with yaws since childhood; studied by W.G.J. Putschar at Orthopedic Rehabilitation Center, Solo, Java, Indonesia).

FIGURE 11.79 Radiograph of osteomyelitis from yaws affecting the left elbow, showing destructive areas and periosteal reactive new bone formation particularly on the metaphysis (male 14 years old, from the monograph on yaws by Hackett, 1976, Fig. 11.1; “case” 284).

One of the clinical manifestations of yaws is swelling in the joints (Hoeprich, 1989: 1024, 1026). Less well known are the erosive arthropathies of the joint and juxtaarticular bone that also occur (Sengupta, 1985: 195). In Hackett’s remarkable study of bone lesions in patients with yaws in Uganda (1947), he included at least two individuals (#284 and #368) with destructive joint disease. Individual #284 was a young male of 14 years of age who had suffered from yaws for at least 7 years. He had a painful swelling of the left elbow for a year before being examined by Hackett. The radiograph shows considerable

periosteal new bone formation in the metaphysis, particularly of the distal humerus. Although Hackett calls attention to this abnormality, he did not describe clear evidence of joint destruction also apparent in the lateral radiograph (Fig. 11.79). Individual #368 was a girl aged 12 years who had had yaws since infancy. The first interphalangeal joint of her left hand was destroyed, resulting in the abnormal angulation of the finger distal to that joint (Fig. 11.80). In yaws, lesions can also destroy the diaphysis of the hand phalanges resulting in a shortened finger (Fig. 11.81) and reduced biomechanical function.

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FIGURE 11.80 Joint destruction of the left hand in yaws: (A) note the enlarged joints and abnormal angulation of the proximal interphalangeal joints of the second, fourth, and fifth digits; (B) radiograph of the hand showing the joint destruction of the proximal interphalangeal joints (female 12 years old, from the monograph on yaws by Hackett, 1976, Figs. 116 and 117; “case” 388).

FIGURE 11.81 Diaphyseal destruction of the middle phalanx of the right middle finger: (A) shortened middle finger; (B) radiograph of the right hand showing loss of the diaphysis of the middle third phalanx (male 18 years old, from the monograph on yaws by Hackett, 1976, Figs 114 and 115; “case” 239).

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In the clinical literature on TD, VS is regarded as the only treponemal disease that is associated with a congenital variant. However, there is also evidence of congenital yaws (Hoeprich, 1989: 1026). Almost certainly, congenital variants of both VS and yaws are related to the age of onset for the syndrome. In the early phase of TD, spirochetes in the bloodstream can lead to spirochetemia. Transplacental transmission of the organism is much more likely during this early stage (Resnick and Niwayama, 1995a: 2493). Although yaws is most often acquired in childhood, well before sexual maturity and a first pregnancy, some women will acquire the disease later in life and may have the early stage of yaws when they become pregnant and thus are likely to transmit the disease to the fetus.

Bejel (or Endemic Syphilis or Treponarid) Bejel is most commonly associated with the dry areas of the Middle East and Africa, although there is evidence that in the past it occurred in other areas, including northern Europe (Hoeprich, 1989). In a survey of 25,000 people in Bechuanaland (now Botswana), 26% showed latent and 1.4% active bejel (Murray et al., 1956: 991). In this study, the predilected skeletal locations for lesions were the tibia and ulna. Bone lesions were not seen in children less than 2 years old (Murray et al., 1956: 1000) and congenital transmission of bejel is not known to occur today (Hoeprich, 1989: 1033). In a study from Syria, the changes observed resemble those of acquired or late-stage CS. They consisted mostly of periosteal new bone formation causing a fusiform (spindle-shaped) enlargement of long bones but little, if any, medullary cavity changes. Intracortical, sharply lytic, rounded gummas are occasionally found. Reactive new bone formation on the tibia (Fig. 11.82) produces the classic saber tibia when viewed laterally. The term “saber” has been used to describe the appearance because it looks like the curved bladed weapon (Rost, 1942: 321 323; see also Fig. 11.83). Periostosis and gummas in the short bones of the hands and feet have also been observed in people from Bosnia (Grin, 1935: 482). Charcot joints are not observed in bejel, unlike in VS (Rost, 1942: 323; Murray et al., 1956: 1001). Destructive nasal lesions leading to perforation of the hard palate occur (Grin, 1935: 482; Murray et al., 1956: 1000) but are rare (Hoeprich, 1989: 1033).

FIGURE 11.82 Radiograph of a tibia and fibula of a person with bejel showing the classic saber shin (tibia) from periosteal new bone formation on the anterior and medial surfaces. Adult male, courtesy: Dr. George El-Khoury, Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

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FIGURE 11.83 Saber shin and skin ulceration (Figure 4 from “La syphilis he´re´ditaire tardive”) Credit: Wellcome Collection. Free to use with attribution (https://wellcomecollection.org/works/rmzedejx? query 5 syphilis).

Venereal Syphilis (VS) Syphilis transmitted through sexual contact is known as acquired or VS, terms used to distinguish this type of syphilis from that transmitted transplacentally to the developing fetus of an infected mother (CS). The latter is discussed below. In view of the mode of transmission, it is obvious that, in most cases, acquired syphilis begins after sexual maturity. Following an incubation period of several weeks following infection, the initial or primary phase of the disease occurs, followed by the secondary and tertiary stages. The primary stage begins with the appearance of the chancre (painless ulcer on the genitals) and ends with the involvement of the regional lymph nodes, to which the bacteria migrate. The secondary stage begins with dissemination of the bacteria through the bloodstream, characterized by a transitory skin rash and mucous membrane lesions. The borderline between the secondary and the tertiary stages is not as clearly defined. However, the tertiary stage is mostly characterized by progressive involvement of different organs, including the skeleton. It is in this stage that the tissue reaction may assume a distinct

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granulomatous appearance of nodular foci with a central necrosis (gumma). The characteristics of the inflammation at all stages is more chronic, with lymphocytes and plasma cells predominating. Neutrophils and leukocytes (white blood cells that fight infection) are not prominent, and there is no significant formation of pus. Hypervascularity is usually marked. In the secondary stage periostosis with reactive new bone formation is not uncommon. These changes are usually transitory and leave no characteristic permanent alterations on the bone. Estimates for the prevalence of VS in the late 19th/ early 20th centuries vary. In Europe, before about 1910, about 10% of inhabitants in cities gave positive serological reactions for VS, although this is not identical to active disease (McElligott, 1960). In a survey of 2000 individuals with VS in Norway from 1890 to 1920, Gjestland (1955) found that approximately 1% of the patients had bone lesions. The combination of these figures would result in a frequency of syphilitic bone lesions of about 1 in 1000 Europeans in the time period before effective treatment was discovered (Hackett, 1976: 114). Other estimates of the prevalence of bone lesions in patients with VS vary from less than 1.5% to as many as 20% (Resnick and Niwayama, 1995a: 2496). This variation highlights the need for caution in reconstructing the paleoepidemiology of treponematosis on the basis of the prevalence of the disease in archeological human remains. Paleopathology’s main interest centers on the bone lesions of the tertiary stage. The key reference point for understanding the skeletal manifestations of VS are the bones from documented individuals with VS in pathology collections that date to before the advent of effective treatment (approximately before 1910). Two ethically questionable studies of people with untreated VS have occurred in the United States (the Tuskegee study, between 1932 and 1972; Rockwell et al., 1964) and Norway (between 1890 and 1910; Giestland, 1955). These provided observations of the effects of VS on the human body, including the bones of the skeleton, in untreated people. Although paleopathology has focused on the skeletal manifestations of VS, treatment of skin lesions associated with VS may have altered the course of the disease. In Europe, mercury has been used in ointments and in other treatments since the medieval period, continuing into the 19th century (Quetel, 1990: 28 31, 60; Ioannou et al., 2015a,b). Skeletons of people with VS who were treated in the late 19th century show severity of skeletal involvement that far exceeds any archeological skeletal evidence. In the following pages one of these skeletons will be presented as an example that argues for the possibility that treatment using mercury might have been a factor in this uncommon manifestation of skeletal lesions. Related to mercury treatment, recent work has highlighted the effects of this substance, particularly on the dental changes of CS (Kepa et al., 2012: Poland; Ioannou et al., 2015a,b: south

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TABLE 11.7 Localization of 945 Tertiary Syphilitic Bone Lesions in Order of Decreasing Frequency Bone

No.

Tibia

248

Nose and palate

238

Skull

179

are characterized by an excessive osteosclerotic response to the infection. In many instances adjacent mucosal surfaces, as in the nasopharyngeal area, and overlying skin, as on the scalp or shin, or other soft tissue are involved and ulcerated. The most characteristic lesions are those with a gummatous destruction and perifocal osteosclerotic reaction involving the periosteum and the underlying bone (for a detailed analysis of morphological features and their relative diagnostic specificity, see Hackett, 1976). The lesions usually develop between 2 and 10 years after the infection, but may occasionally occur earlier or much later. Often, more than one bone is affected and involvement tends to be bilateral. Although any bone can be the location of a lesion, there are a few areas that are greatly predilected: the tibia, the bones surrounding the nasal cavity, and the cranial vault. These three locations combined represent about 70% of all tertiary bone lesions in VS. These are followed in decreasing frequency by bones with large amounts of cancellous bone (rich in hematopoietic marrow—ribs, sternum), and the other long bones of the extremities. A survey of frequency from the greatest series of Fournier (1906, as cited in Beitzke, 1934b: 471) is given in Table 11.7. The spine is an exception to the behavior of other cancellous bones; it is rarely affected by VS. When it is affected, the most common site are cervical vertebrae (Jaffe, 1972: 938).

Ulna

37

Ribs

35

Sternum

29

Clavicle

27

Metacarpals

21

Humerus

20

Radius

17

Femur

16

Mandible

14

Fibula

12

Spine

9

Nasal bone

9

Fingers

7

Pelvis bone

5

Metatarsals

4

Scapula

4

Ribs and sternum

3

The Skull

Tarsals

3

Toes

3

Maxilla

3

Patella

1

Carpals

1

Transient cranial periostosis is common in the earlier stages of VS, but this is not diagnostic. However, in the tertiary stage of the infection, the most common location of lesions in clinical patients is in the skull, particularly in the perinasal area and the cranial vault (see Fig. 11.84). These lesions represent the most specific diagnostic features. The main focus is on the gummatous, osteoperiostotic cranial vault lesions, the majority of which begin in the frontal bone. As the disease develops, new lesions may occur in the adjacent parietal and facial bones. Less commonly, the first lesion in the cranial vault begins in a parietal bone, while the occipital bone may be involved when a person is severely affected, but it is usually spared, even if the process extends to the lambdoid suture. The characteristic lesion of VS was classically described by Virchow (1858, 1896) as “caries sicca.” Hackett (1976: 30 49) revived this phrase, added more detail to the developmental stages of the lesion, and designated the most diagnostic feature for VS in dry bone. The lesion begins at or near the osteoperiosteal border, and is usually of the outer skull table. It elicits hypervascularity that, on inspection of the outer table of a skull, reveals itself in the form of grouped and fine vascular foramina. This initial change has the same reaction as that observed in TB and metastatic cancer. However, in the

Source: After Fournier, 1906.

Australia). We therefore need to be very careful before assuming that skeletal evidence of any disease from the preantibiotic era is typical of the natural, untreated expression of the disease. Throughout human history medical practitioners used various substances to treat their patients, and some of these treatments could easily have had adverse effects on the patients that could affect the skeletal manifestations. The tertiary bone changes of VS are the result of either chronic nongranulomatous inflammation or granulomatous (gummatous) processes. In many cases, a combination of the two is present. Both of these changes can affect a localized area of the bone or the entire bone. The inflammation may begin on the periosteum or in the bone. Ultimately, however, the periosteum and cortex, and more rarely the medullary cavity, are involved. All tertiary bone lesions

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FIGURE 11.84 Tertiary syphilis of the face. Figure 492 of Stokes (1927).

latter two, the inner skull table is predilected and ultimately shows the larger defect. In osteolytic metastatic cancer, due to its frequently rapid development, fullthickness destruction of both tables and the intervening diploic space is common, resulting in a hole with a nonreactive border that is crenelated (has notches). In TB, in addition to involvement of the inner table, reactive bone formation tends to be a late development and may not be apparent in some individuals. The syphilitic lesion leads to a focal destructive remodeling of the outer skull table and part of the diploic space by granulation tissue, but it often spares the inner table almost completely. As part of this remodeling there is a strong sclerotic response in the bone surrounding the lytic focus, forming a sclerotic base and an elevated sclerotic margin around the defect (Fig. 11.85). Microscopically, focal bone necrosis is common and may well be a major stimulant to reactive sclerosis in the process of remodeling (Axhausen, 1913). However, pus formation is not significant and large sequestra usually do not form. In the chronic course of VS, even if untreated, individual foci will heal but new foci will form in the vicinity. The healed individual caries sicca lesions leave a depressed, sclerotic, radially grooved stellate scar (Fig. 11.86). This is somewhat less obvious in confluent healed areas (Fig. 11.87). The process continues and leads to confluent pitting in a circinate (“circular and rolled up inwards”) arrangement surrounded by reactive bone, with partly smooth and partly hypervascular surfaces (Fig. 11.88). In advanced confluent (merging) caries sicca lesions, the diploe may be markedly thickened and

FIGURE 11.85 Tertiary syphilis of the cranial vault, ectocranial view. These are relatively early lesions with central destruction and peripheral reactive bone. The inner table shows only minimal diffuse reactive bone deposition (adult; ANM 2232).

sclerotic, whereas the inner table exhibits only minor reactive new bone formation (Fig. 11.89). Destruction and perforation of the full thickness of the cranial vault does occur, especially when secondary pyogenic osteomyelitis is present, but even then the changes on the inner

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FIGURE 11.86 Tertiary syphilis of the cranial vault, ectocranial view; multiple small cavitating lesions with advanced and partly complete healing; inner table unchanged (adult; ANM 2468).

FIGURE 11.87 Tertiary syphilis of the cranial vault with considerable healing (HM; P717).

FIGURE 11.88 Extensive tertiary syphilis of the cranial vault with advanced sclerotic healing (adult WM S50a.2 from 1828).

FIGURE 11.89 Confluent caries sicca lesions of the skull vault caused by tertiary syphilis: (A) skull vault; (B) radiograph showing variation in mineral density and greatly thickened bone (adult; PMS 9/1.372E).

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FIGURE 11.90 Infectious defect of the frontal bone covered by scarred soft tissue; probably tertiary syphilis with superimposed osteomyelitis; 25-year duration (58-year-old male; PMES 1E.B.1(4) from 1899).

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FIGURE 11.92 Tertiary syphilis of the nasal cavity, anterior view, showing widening of the nasal cavity, complete destruction of the nasal septum and large perforation of the hard palate (old female ANM 2423).

FIGURE 11.93 Tertiary syphilis of the nasal cavity with destruction of the hard palate and perforations of the palatal bone; exterior basal view (24-year-old male with VS (WM HR 4.1 from 1848). FIGURE 11.91 Tertiary syphilis of the cranial vault, surface view (wet preparation), showing multiple scalp ulcerations exposing the affected bone (GHPM; 3914 from 1914).

table are less pronounced (Fig. 11.90). Major sequestra are seen in skulls with VS-related bone lesions in European contexts, often showing darker discoloration of the necrotic bone. This is due to exposure of the affected bone when the scalp is ulcerated and this probably largely represents the result of secondary pyogenic (pus forming) infection (Fig. 11.91). In contrast to the sequestra in pyogenic osteomyelitis, these sequestra will have a “worm-eaten” appearance, indicating their involvement in the disease process before becoming necrotic. Hackett (1976: 57) did not find sequestra in skulls of native

Australian individuals affected by bejel or yaws. He attributes this to the presumed absence of pyogenic infections in these populations. The facial bones most often affected by tertiary VS are the nasal bones, the bony nasal septum, the hard palate, the turbinate bones, and the lateral walls of the maxillary antrum. These bones are involved secondary to soft-tissue involvement of the nasal mucous membranes in VS. The thin bones are often destroyed and this destruction can extend with perforation of the nasal septum, the hard palate, and of the medial walls of the maxillary sinuses (Figs. 11.92 11.94). The nasal cavity appears enlarged and empty in the dry skull. However, in

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FIGURE 11.94 Nasomaxillary tertiary syphilis with extensive endonasal destruction and some sclerotic healing, destruction of the palate, and involvement of the maxilla (43-year-old female; ANM 2221 from 1889).

FIGURE 11.96 Frontonasal tertiary syphilis with active destruction of the nasal bones and medial orbital walls, healed margin of enlarged nasal aperture, and completely healed lesions of the frontal bone (adult; WM HS 50a.2 from 1841; lines on the forehead are shadows from the plastic box containing the skull).

FIGURE 11.97 Destructive remodeling of the pyriform (nasal) aperture with perforation of the hard palate in a person with tertiary syphilis (female 30 years old; WM RCS S50a.3).

FIGURE 11.95 Cranionasal tertiary syphilis, mostly healed: notice scarring of the nasal and frontal bones, and preservation of the inferior nasal spine (43-year-old male ANM 2000 from 1893).

contrast to neoplastic destruction in this area, the margins of the defect are bordered by smooth sclerotic bone. In contrast to leprosy, the frontal bone is usually involved, perforation of the nasal septum and hard palate is common, the sclerotic response is marked, and the inferior nasal spine may be spared (Fig. 11.95). The zygoma, the nasal bones, and the medial aspects of the orbital walls may be affected by direct extension of the process from the frontal bone (Fig. 11.96). Destruction of the bony support of the bridge of the nose results in “syphilitic saddle nose”. Nasal lesions can also penetrate the palate

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the vertebral bodies are most commonly affected and the arches and processes are rarely involved (Jaffe, 1972: 938). The Long Bones The tibia is approximately 10 times more often the site of lesions in VS than any other long bone of the extremities. The lesions of long bones can be separated into nongummatous and gummatous osteoperiosis. The nongummatous lesions are suggestive but probably not diagnostic of treponemal infection (Fig. 11.99). It should be noted that Hackett (1976: 87 90) puts them

FIGURE 11.98 Cranionasal tertiary syphilis, external basal view, showing active destruction of the palate, and sclerotic scarring of the nasal roof with extension to the sphenoid bone (30-year-old male; FPAM 1552; autopsy 8826 from 1834).

(Fig. 11.97). The skull base is rarely involved, but extension of the nasopharyngeal process into the sphenoid bone does occur (Fig. 11.98), resulting in marked sclerosis of the area (Schinz et al., 1951, 1952: 627). The Spine Osteomyelitis consequent to VS in the spine is rare (Whitney and Baldwin, 1915), and the changes in dry bone would not be diagnostic in themselves. The outcome may be kyphosis, after destruction of adjacent vertebrae, similar to TB. In contrast to TB, a paravertebral abscess is missing, which may not be obvious on dry bone. In addition, and in contrast to Pott’s disease, the cervical vertebrae are affected three times as often as any other segment in the instance of VS infection of the spine (Beitzke, 1934b: 510; Jaffe, 1972: 938). This may suggest extension from nasopharyngeal mucosal lesions rather than being of hematogenous origin. However, like TB,

FIGURE 11.99 Tertiary syphilis affecting the left tibia complicated by a skin ulcer: note the mid diaphyseal involvement and the erosion at the ulcer base below. The medullary cavity was filled with reactive bone (27-year-old female; ANM 2914 from 1872).

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FIGURE 11.100 Tertiary syphilis affecting the distal left femur (P374) with periostosis and sclerotic plaques of new bone (HM 374).

into his “on trial” category of diagnostic lesions, and therefore continued caution should be taken if these lesions are to be attributed to treponematosis per se without any more specific bone changes. The localized form of nongummatous periostosis in VS may leave elevated, plaque-like new bone on the cortex of bones that have a major overlying layer of muscle, such as the femur (Fig. 11.100), or surface parallel lamellar type new bone of varying thickness and density on bones close to the skin surface, such as the ulna and clavicle (Figs. 11.101 and 11.102). Extensive periosteal thickening is often combined with cortical thickening, including on the endosteal surface. Diffuse nongummatous osteoperiosis tends to leave the bone thicker and heavier than would be

FIGURE 11.101 Treponemal related lesions of the right ulna (P372) with periostosis and slight pitting (HM 372).

FIGURE 11.102 Treponemal related lesions of the left clavicle (P369) with diffuse periosteal bone and focal pitting (HM 369).

expected for the age and sex of the individual. The entire surface, with the exception of the cartilage-covered articular surfaces, may be involved. The periosteal bony buildup may be thick and becomes firmly merged with

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the old cortex of the bone. The outer bone surface is rough and markedly hypervascular. In the late stages of nongummatous osteoperiosis, the medullary canal may be completely filled with sclerotic trabeculae, while the definition of the old cortex may be less obvious due to Haversian canal resorption. This means that in crosssection the bone appears uniformly, coarsely cancellous, with loss of the distinction of the cortex and medullary cavity. A differential diagnosis of Paget’s disease may be considered, but differentiation can be made microscopically by observing the absence of typical Paget’s disease mosaic patterns. Gummatous osteoperiostitis is a much more characteristic lesion for VS. In its localized form, it may

result in a tumor-like enlargement of the affected area of the bone (Axhausen, 1913). In dry bone the marked hypervascular, periosteal, bony buildup surrounds a scooped-out defect that extends into the cortex. This corresponds with the location of a destructive gumma in the soft tissues of a living person. At times, the scooped-out lesions are smaller and several are grouped together, resembling the picture of caries sicca in the cranium (Fig. 11.103), but individual gummatous defects on long bones tend to be larger than on the skull. The underlying cortex is hyperostotic and endosteal new bone formation may encroach upon the medullary canal (Fig. 11.104). In some cases, larger defects are seen in the layer of hypervascular

FIGURE 11.103 Tertiary syphilis affecting the right femur; anterior view with massive gummatous periostosis and typical snail-track pattern (55-year-old male; PMUG 3466).

FIGURE 11.104 Treponemal related lesions of the left femur with fusiform hyperostosis and medullary osteosclerosis: (A) anterior view, showing snail-track pitting, especially on the metaphysis; (B) cut section showing extensive medullary sclerosis (adult; WM S 50b.1 from 1831).

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FIGURE 11.104 Contiuned

periosteal new bone, exposing the deep cortex (Fig. 11.105) and sometimes small sequestra. These lesions must not be confused with cloacal openings (sinuses) of osteomyelitis; major sequestra are not present, and the margins of the defects are rough and thin, not smooth and sclerotic. Hackett (1976: 82, 93 97) accepts this form of osteoperiostosis as diagnostic of treponemal infection. Central gummas of the medullary cavity occur in the form of larger lytic lesions surrounded by a marked perifocal reactive sclerosis. This lesion may not be differentiated with assurance from a Brodie’s abscess (variant of subacute osteomyelitis), although the sclerosis is more marked than in the latter. Pathological fractures in bones weakened by osteoperiostosis in VS are not uncommon.

FIGURE 11.105 Tertiary syphilis affecting the cranial vault: (A) anterior view, showing quiescent external defect with sclerotic healing; (B) cranial vault showing more active destructive lesions in both parietal bones; (C) left arm bones; notice absence of sequestra and cloacae (scale in centimeters) (45-year-old female; PMUG 2647, autopsy 6262 from 1874).

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FIGURE 11.105 Contiuned

The Joints Arthritis occasionally occurs during the secondary stage of VS and affects the large joints (shoulder, elbow, knee, including Clutton’s joint in CS). This bone damage is transitory and leaves no changes visible on dry bone. However, occasionally, an epiphyseal gumma may perforate into a joint and lead to gummatous arthritis (Axhausen, 1913). The perforation predominantly occurs near the margin of the articular cartilage (Freund, 1933). Subsequent bone changes, if present, are not significantly different from other forms of arthritis, particularly osteoarthritis. Only the presence of the gummatous bone lesion may be a clue to a treponemal etiology. Indirect suspicion of VS infection may be aroused by observation of pressure erosions (aneurysms) of the sternum, ribs, or thoracic vertebrae or from findings of a Charcot joint (neuropathic arthropathy that can be related to the presence of VS). However, not all aneurysms of the thoracic aorta are due to VS and not all neuropathic arthropathies are the result of tabes dorsalis (nerve degeneration associated with the tertiary stage of VS). Two complete skeletons of patients who had VS from the Pathology Museum of the University of Strasbourg, France, illustrate skeletal manifestations that are unusual in both the severity of chronic bone destruction and in the bones that are affected. The first skeleton (# 4479) is that of a male aged 51 years whose body was accessioned to the anatomy laboratory in 1907. This means that most of this person’s life was lived in the

FIGURE 11.106 Tertiary syphilis of the skeleton: (A) posterior view of the skeleton showing involvement of virtually all bones; (B) lateral view of the skull and cervical vertebrae showing involvement of the mandible, lesions on the inferior portion of the occipital bone, and fusion of the diarthrodial joints including the occipital condyles through the sixth cervical vertebra; (C) severe involvement of the clavicles and sternum; (D) extensive destruction of the right scapula and ribs; (E) lateral view of the right femoral diaphysis, showing a penetrating defect surrounded by periosteal buildup of bone; (F) posterior midshaft of the right tibia and fibula (51-year-old male with visceral and cerebral syphilis; DPUS 4479, autopsy 697 from 1907).

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FIGURE 11.106 Contiuned

late 19th century. Ortner (2003:289) stated that “Bone involvement in the first of these skeletons (Fig. 11.106) far exceeds the involvement encountered in archeological human remains of treponematosis that I have

studied. It seems likely that this patient had a severely compromised immune response to the pathogen.” The second skeleton (# 5527) does not have an associated date but the higher catalog number suggests that it is

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FIGURE 11.107 Tertiary syphilis of the total skeleton: (A) anterior view; (B) syphilitic lesions of both arms; posterior view, showing symmetrical involvement of both humeri; (C) lesions of the bones of both legs, anterior view, showing especially marked symmetrical involvement of both tibiae (adult male; DPUS 5527 from before 1820).

from a somewhat later time period. This skeleton is more typical of VS-related skeletal lesions (Fig. 11.107), and the comparison between the two skeletons provides an insight into the skeletal involvement of syphilis at the extreme end of severity.

Congenital Syphilis (CS) CS was a common disease with a high mortality prior to the development of effective treatment for the infected mother during pregnancy. Among 4500 consecutive autopsies at Johns Hopkins Hospital, Baltimore, Maryland,

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United States, before 1933, there were 189 fatalities with CS, only two of which were older than 4 years (Smith, 1933). In CS, the treponemal infection is transmitted transplacentally from the infected mother to the fetus, most commonly during the early acute phase of the disease. The result is fetal death followed by miscarriage in the first half of pregnancy, fetal death with delivery of a premature or mature diseased stillborn fetus, or delivery of a living infected infant. If the infection is mild, it may not manifest itself for several years (syphilis congenita tarda). In severe infections, all organs and tissues of the fetus are permeated with numerous treponemal organisms. Because the immune capacity to mount an inflammatory response is not yet developed in the first half of pregnancy, such aborted fetuses show no tissue changes. Furthermore, such fetuses are unlikely to be recovered during archeological excavations and therefore are not seen in paleopathological research. In premature and full-term stillborns, as well as in actively infected newborn living infants, characteristic skeletal changes are almost always present in the form of CS-related osteochondritis, inflammation of the cartilage or bone, or both (Jaffe, 1972: 910 917). This is the result of hematogenous dissemination of the bacterium to the fetus in utero. It affects all areas of enchondral growth in the entire skeleton, but is most marked in the fastest-growing metaphyses (distal femur and proximal tibia). The lesions are symmetrical. They consist of accumulation of calcified cartilage adjacent to an area of lucency due to poor bone formation (Fig. 11.108). In radiographs of long bones, this area appears as a zone of increased density (Fig. 11.109). This may represent merely a toxic effect on enchondral (within cartilage) ossification (“passive osteochondritis” of Schneider, 1923 1924: 205) or be the result of formation of syphilitic granulation tissue in this area (“active osteochondritis” of Schneider 1923 1924: 205). Similar disturbances of enchondral growth are seen in a variety of conditions and are not diagnostic of CS (Caffey, 1939). These fetal and neonatal alterations pose a challenge for differential diagnosis in archeological human remains. In surviving infants, transverse metaphyseal pathological fractures through this weakened area of the metaphysis not uncommonly occurs (Parrot’s pseudoparalysis). Because before walking, the infant’s arms are more mechanically stressed than the legs, the distal humerus is the predilected site of such fractures. This osteochondritis heals in the infant, even if untreated. CS-related periostosis often develops during infancy, mostly following the osteochondritis. Occasionally, it has already begun in intrauterine life and is present at birth. It consists of usually symmetrical, circumferential deposition of subperiosteal bone on the shafts of long bones. The trabeculae in this bone deposit often show a radial arrangement. This change is frequently transitory but may be recognizable

FIGURE 11.108 Syphilitic osteochondritis of distal femur (wet preparation): notice the broadened and irregular area of provisional calcification at the metaepiphyseal junction (2-month-old male; WM S 51.2 from 1910).

on infant bones under conditions of ideal preservation (Fig. 11.110). Similar periosteal bone deposits may occur on the cranial vault (Fig. 11.111). Gummatous periostosis and osteomyelitis occasionally occur in CS, especially in older children who have passed through mild, unrecognized, and untreated manifestations in infancy (syphilis congenita tarda) (Wimberger, 1925: 307 370). In this age group, bone involvement is neither so frequent nor so generalized as in infants but comes

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FIGURE 11.109 Radiograph of the long bones of an infant with probable congenital syphilis with the zone of increased density near the growth plate (NMNH 249602).

FIGURE 11.111 Congenital syphilis of the cranial vault with periosteal bony build up on both frontal and parietal bones. The mother had extensive ulcerated nasofacial syphilis (1-year-old; PMWH WO 734 from 1886; the lines on the skull vault are shadows from the box containing the skull).

FIGURE 11.110 Long bone with subperiosteal new bone formation on the shaft in congenital syphilis (31/2-month-old infant; WM S 51.1 from 1880).

closer to the distribution and appearance of VS (Fig. 11.112) (Pendergrass et al., 1930). Only 32 of 462 patients (6.9%) over 13 years of age with late-stage CS showed active bone changes in Smith’s 1933 study. The

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FIGURE 11.112 Long bones of a 12-year-old child with tertiary congenital syphilis: (A) left femur; note the periosteal new bone formation and the snail-track patterns in the bone; (B) bisected left femur with cortical resorption and medullary reactive new bone; notice absence of medullary penetration and sequestrum; (C) fibula, ulna, and radius (bisected), showing similar lesions (ANM 2999, 3163, 3166, 3185).

FIGURE 11.113 Tertiary congenital syphilis affecting the radius and ulna bilaterally (all bones bisected longitudinally): notice pitting destruction and marked hyperostosis without cloacae or sequestra (about 6 years old; ANM 3386).

lesions in the long bones predilect the tibia, ulna, and radius (Fig. 11.113). Skull lesions occur but usually appear as multiple, rounded, destructive foci without the characteristic features of the caries sicca sequence (Fig. 11.114). The saddle nose in CS may be mainly the result of disturbed enchondral ossification of the base of the skull. In adolescents, the tertiary bone lesions may more closely resemble those observed in adults, and differentiation of a late stage of congenital from VS may be impossible without clinical data (Figs. 11.115 and 11.116). Occasionally, extensive involvement of the facial bones can occur in CS (Fig. 11.117). Nongummatous periostosis results in osteosclerosis (hardening of the bone with increased density) with the subperiosteal new bone deposits ultimately merging with the underlying cortex. The most characteristic lesion of this type is the so-called saber tibia of Fournier (1886: 265 269). Such tibial bowing results from abnormally stimulated growth (“true bowing”). The appearance of bowing can also be created by layered bone deposition on the anterior and medial surfaces, known as “pseudo-bowing.” In CS, excessive growth of the tibia is stimulated by the disease. The fibula experiences normal growth in length and shape. True bowing in CS is the result of the differential growth of the tibia which ends up remaining fixed by ligaments and tendons to the shorter fibula (Jaffe, 1972: 921). As previously mentioned, similar bony buildup on the anterior tibial surface occurs in nongummatous periostosis of VS (Fig. 11.118). In this case,

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FIGURE 11.114 Congenital syphilis with a destructive lesion of the right side of the frontal bone involving both tables: (A) ectocranial view. (B) endocranial view (8-month-old female; ANM 2233 from 1865).

FIGURE 11.115 Tertiary cranial syphilis (congenital?): note active and healing lesions in the frontonasal area, a widened nasal aperture, loss of the nasal septum and inferior nasal spine, and perforation of the palate (16-year-old male; ANM 2009 from 1870).

FIGURE 11.116 Anterior view of a skull with destruction of the nasal bones and involvement of the zygomas; the frontal bone lesion is partly healed. The young age raises the question of tertiary and congenital syphilis (17-year-old female; ANM 2427).

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however, the tibia is not abnormally elongated and curved, and the posterior contour remains straight. One method of distinguishing between the two types of bowing is to determine whether the interosseous line of the

FIGURE 11.117 Child with congenital syphilis showing sclerotic healing of the frontal and nasal bones: (A) anterior view of the skull; the teeth are normal; (B) lateral view of the skull showing an active frontoparietal lesion (8-year-old with a history of syphilis; OM F 133).

tibia is straight. If it is, the bowing is of the pseudo type. If the interosseous line is curved in any direction, but particularly in the anteroposterior axis, then true bowing has occurred. Syphilitic dactylitis used to be more frequently observed in congenital than in acquired syphilis. It

FIGURE 11.118 Treponemal disease affecting the right tibia showing the characteristic saber morphology: (A) lateral view, showing anterior periosteal new bone deposition; (B) lateral radiograph showing anterior cortical thickening and preservation of the medullary cavity (adult Caucasian male; Pathology Department of the University of Otago, New Zealand). Courtesy: Dr. Bruce Ragsdale, Central Coast Pathology Consultants, Inc., San Luis Obispo, California.

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recent research on these abnormalities has reviewed the literature (Hillson and Grigson, 1998). However, the combination of defective dental formation in association with systemic manifestations of skeletal disease particularly affecting the facial bones, ulna, and tibia does provide a relatively high degree of confidence in a diagnosis of CS, although yaws is possible in geographical areas where this syndrome is endemic. Although there are a variety of skeletal changes occurring in different phases of CS (see Lewis, 2018: 178 182 for an overview of the skeletal changes), the findings must be critically evaluated in relationship to the context of the skeletal observations. Individual lesions may not be distinguishable from TB or other infectious changes.

Paleopathology

FIGURE 11.118 Contiuned

concerned the fingers more often than the toes and predilects the basal phalanges. The condition often affected more than one finger and was frequently bilateral but not symmetrical. The appearance, especially in small children, may closely simulate that of spina ventosa in TB, with widening of the diameters of the phalanges and formation of a thin, bony shell. In adults there is less expansion and more reactive osteosclerosis. Hutchinson’s and Moon’s teeth, although present in a variable number of individuals with CS, have been questioned in their specificity (Kranz, 1927: 263), and more

Considerable scientific and scholarly debate about the history of TD has focused on the origin of VS, with special attention to an “epidemic” of VS in Italy following the return of Columbus’s first voyage. As also reviewed in Chapter 8, some have argued that Columbus’ crew returned from the Americas with VS (the Columbian hypothesis; Crosby, 1969). Others have proposed that the disease was present in Europe and/or Africa prior to the late 15th century (pre-Columbian hypothesis, e.g., Livingstone, 1991). A further alternative identifies a global treponemal distribution that adapted to local circumstances (the Unitarian theory; Cockburn, 1961; Hackett, 1963; Hudson, 1965, 1968). Several summaries have emphasized skeletal evidence, with support distributed across the theories (Baker and Armelagos, 1988; Dutour et al., 1994; Harper et al., 2011; Meyer, 2002; Powell and Cook, 2005). These different and conflicting opinions are based on four distinct, but not necessarily mutually exclusive, sources of information: (1) historical documents, (2) archeological human remains, (3) theories about the evolution and adaptation of pathogens and the host’s immune response, and (4) molecular evidence. We briefly discuss each of the data categories below.

Historical Documents Bru¨hl (1880) cites many primary historical sources, including early chroniclers of colonial life in the Americas, such as Oviedo and Las Casas, who supported the view that VS existed in the New World at the time of its discovery by Europeans. He also cites Diaz de Isla, the physician who treated Columbus’ men for presumed VS. Bloch (1901, 1908, 1911) provides a review of older relevant source material and concludes that all available statements indicate that VS first appeared in the Old World during the years 1493 1500. He also argues that there is

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no historical evidence to show that the disease existed in Europe before that time. Dennie (1962: 61 63) notes that VS was particularly virulent after its initial introduction from the New World and subsequently became milder. He argues that this reflects the normal progress of a newly introduced disease and thus supports the theory of a New World origin for VS. In an opposing argument, Holcomb (1941) cites early descriptive medical reports of a disease process attributed by the early writers to leprosy. However, he (1941: 151 152) indicates that many of these purported people with leprosy were clearly affected by VS, in terms of both their appearance and the venereal mode of transmission (leprosy is not transmitted in this way). He concluded that VS in a congenital and acquired form certainly prevailed in Europe long before the discovery of America (1941: 167). This conclusion is supported by a description reported by Thorndike (1942: 474) on a disease process resembling VS dated to AD 1412. Elsewhere in the Old World, Hyde (1891: 117) stated that the ancient medical literature of China, Greece, India, and Italy contained unmistakable proof that early in the world’s history genital lesions were known to occur from sexual contact. However, Crosby (1969: 219) offers an opposing opinion that there is no unequivocal description of VS in the ancient Old World medical literature. In particular, Crosby cites Wong and Wu (1936: 218), who argued that no Chinese writer had ever described a disease which could be attributed to VS.

Skeletal Remains In discussing the evidence for pre-Columbian VS in the New World, we are primarily limited to human remains. There are two fundamental requirements to explore the theories describe above: (1) an unambiguous identification of TD and (2) a convincing pre-Columbian date. The earliest reference to VS in New World skeletons is from Jones (1876: 66), who reported on archeological skeletons from Tennessee. Indeed, this early discussion appears to have been the basis for subsequent reports in which other authors concluded that VS was present in populations in the New World before Columbus (e.g., Lamb, 1898). Morgan (1894) challenges Jones’ conclusions, calling into question both the diagnosis of VS and the pre-Columbian date. Much other purported evidence of VS has been reported in New World skeletons. One of the most respected early 20th-century scholars studying these skeletons was H.U. Williams, a pathologist, who concluded on the basis of a critical review of published work and his own observations that the case for pre-Columbian syphilis was probable beyond reasonable doubt (Williams, 1932: 978). He found the evidence for Old World skeletal syphilis before 1490 to be much less convincing. Turning to

the northern regions of the New World, Holcomb (1940: 189) concluded that VS probably did not exist among the Inuit or the Aleutian Islanders until after contact with Russian sailors and traders during the 18th century. Although a comprehensive review of the recent published literature documenting the history of TD through archeological human remains is beyond the scope of this work, a brief summary is provided below. Key overviews that should be consulted for paleopathological evidence of TD are Baker and Armelagos (1988), Dutour et al. (1994), Harper et al. (2011), Meyer et al. (2002), and Powell and Cook (2005). There have been a number of relatively recent publications on skeletal evidence for the treponematoses from North America (e.g., Hutchinson and Richman, 2006; Jacobi et al., 1992; Mansilla and Pijoan, 1995; Marden and Ortner, 2011; Nystrom, 2011). Even so, the conclusions voiced by Cook and Powell (2005) in their summary chapter remain convincing: (1) that treponematosis was present and variable in pre-Columbian North America and (2) that nearly all reports of VS prior to 1500 in the New World are inconclusive. This echoes other opinions (e.g., Baker and Armelagos, 1988). For the Old World, there is less consensus. A conference summary of evidence (Dutour et al., 1994) concluded that TD was certainly in the European population before AD 1492, and that a plausible case could be made for VS being the syndrome associated with this early expression of the disease. By contrast, Harper et al. (2011) argued that there was no TD in Europe prior to 1500, based upon their evidence-based survey. Isolated examples of TD, including VS, continue to be offered (e.g., Cole and Waldron, 2011, 2012, 2015; Zuckerman et al., 2012; Mays et al., 2003 Mays and Vincent 2009; Mitchell, 2003; Steyn and Henneberg, 1995). The most convincing evidence to date, however, is that of Walker et al. (2015), who report a temporal sequence of TD evidence from the medieval burial ground of St. Mary Spital, London (United Kingdom). Their extensive research program, which investigated 5387 skeletons that spanned the period between 1220 and 1539, presents convincing evidence for TD, likely VS. The rising prevalence during the most recent period suggests to the authors that their data may reflect the late 15th-century epidemic reported in historical documents.

Theories of Disease Evolution The third source of speculation on the history of TD is based on evolutionary theoretical reconstructions. In essence, these concepts about the TDs suggest that they have evolved with humans, migrated with them throughout the world, and thus were endemic in both the Old and New Worlds long before Columbus (Hudson, 1968;

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Cockburn, 1961; Hackett, 1976). Although not phrased in evolutionary terms, the concept of TDs being endemic in both Europe and the Americas goes back to an early report by Krumbhaar (1936: 232), who stated: “Personally, I regard as most convincing the theory of the existence of syphilis in both continents as far back as prehistoric times.” Similarly, Stewart and Spoehr (1952) speculate that TD existed in the Old and New Worlds but different strains of the bacteria had developed while isolated from each other. When contact between European explorers and indigenous Americans occurred, they “traded” strains of treponemal organisms to which neither had developed any immunity. This, they suggest, is the reason for the VS epidemic in Europe after the return of Columbus and the increase in bony lesions possibly attributable to VS in post-Columbian indigenous human remains in the New World. Stewart and Spoehr’s (1952) observations on the increase in VS-type lesions in postColumbian indigenous American skeletons are significant because of Stewart’s extensive experience with New World skeletal remains. In several papers, Hudson attempted to reconstruct the evolutionary history of the treponemal organism. In one of his earlier papers (1958: 23), he suggests that the treponeme evolved from a saprophyte (a microorganism that is closely related to the treponemal organism) early in human evolutionary history through the introduction of such an organism into a break in the skin. He further speculates that this event may have taken place in Central Africa in an environment similar to the rainforests of today (Hudson, 1965: 890 891). Such an early disease would probably have been similar to yaws of today, where the organism survives on moist skin. Crucial to an understanding of Hudson’s evolutionary history of TD is the concept that the treponemal organisms represent a “biological gradient” rather than separate species. In this scheme, the various treponemal syndromes or diseases reflect adaptations by the same microorganism to varying environmental conditions. Thus, when humans moved to more temperate regions, the organism migrated to the moister regions of the body (the mouth, axillae, and crotch), creating a new disease syndrome that Hudson (1965: 891) called endemic syphilis (or bejel or treponarid). Hudson (1965: 895) argued that VS developed alongside the development of cities, with improved hygiene associated with city life. In addition, the increased use of clothing in temperate climates prevented the frequent skin contact in children necessary for the transmission of endemic syphilis. Following human migration to the New World, the development of South American TD (pinta) was, in Hudson’s reconstruction, the result of a local adaptation in which the treponeme was again introduced to environmental conditions similar to those found in Central Africa (Hudson, 1965: 892).

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Hudson recognized the inherent question in his theory, which is: why did VS not develop sooner in the evolutionary process if all TDs are the result of adaptations of a single species? In response to this question, he noted that immunity to the treponeme would be acquired during childhood as the result of exposure to non-VS, so that venereal transmission after sexual maturity was not possible until children no longer contracted the disease (Hudson, 1965: 892). One cannot help but wonder about the manner in which Columbus’s immunologically naive sailors might have reacted to American treponematosis, whether or not a strain of TD was present in the Old World at that time. Hackett (1963) took a somewhat different approach in reviewing the origin and history of TD. Although recognizing that the organisms associated with the four TDs are indistinguishable microscopically, he continued to distinguish the diseases as clinical entities (Hackett, 1963: 9). In Hackett’s evolutionary scheme, TDs began in the Afro-Asian landmass around 15,000 BC. This was the syndrome pinta, which spread throughout the world and subsequently became isolated in America. Yaws also developed in the Afro-Asian landmass through mutation of the pinta treponeme and spread throughout the Old World. ES evolved from yaws during the drying trend following the last Pleistocene glaciation. As in Hudson’s reconstruction, Hackett associates the development of VS with the emergence of cities. However, he suggests that the disease was mild until a virulent mutation towards the end of the 15th century AD gave rise to the European epidemic attributed to the return of Columbus from the New World (and documented in historical literature). Subsequent to this event, VS spread throughout the world during European colonial expansion in the 16th and 17th centuries (Hackett, 1976: 38). Like Hudson, Hackett does find a likely association between the evolution of TDs and the environment, particularly the climate. However, these two scholars differ on the evolutionary mechanism. Hudson supports the concept of a pluripotential organism; Hackett invokes multiple mutations and different organisms. Cockburn (1963: 74) noted that, through time, human populations tend to become genetically resistant to infectious pathogens. This trend, when combined with Crosby’s observation (1969: 219) that the typical evolutionary development of an infectious disease is characterized by decreasing virulence and will result in chronic disease, does seem to fit the pattern of infectious disease that is encountered in archeological human remains. It is, however, inadequate to explain all the host pathogen relationships that occur in infectious diseases, some of which (e.g., cholera, dysentery, and plague) involve a very virulent illness often with rapid and high mortality (Ewald, 1994: 1 13). Virtually all infectious diseases that

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affect the skeleton are chronic diseases in which skeletal involvement often occurs as a late manifestation of the disease. It is thus likely that the evolutionary path of these pathogens was towards less virulence, combined with increasing genetic resistance to the pathogen in the human host population. This raises the possibility that even milder forms of the disease could have developed, along with an improved host response, in which the skeleton was not affected, as is the case with pinta today. Recent, empirical evidence concerning cycles of VS is relevant to our consideration of TD epidemiology. Grassley et al. (2005) report modern cycles of VS peaking every 8 11 years due to protective immunity. Walker et al. (2015) suggest that this may explain the chronological difference in the evidence for TD noted at medieval St. Mary Spital, referenced above.

Molecular Evidence As detailed in Chapter 8, Kolman et al. (1999) used PCR and immunological approaches to identify VS in a historical period individual from Easter Island. Other researchers have been unsuccessful in identifying VS in adult remains (Barnes and Thomas, 2006; Bouwman and Brown, 2005; Von Hunnius et al., 2006). As Barnes and Thomas (2006) emphasize, such results illustrate the fact that the T. pallidum subsp. pallidum is common in individuals only during the acute, early stages of the disease, when there are no bony changes. Those with skeletal evidence of tertiary syphilis have few pathogens in their bodies. For this reason, screening young adults in the same skeletal series wherein older adults present suspected evidence of tertiary syphilis should be more productive than sampling extremely pathological individuals. Similarly, the probability of recovering ancient pathogens increases when screening neonates with dental or skeletal changes compatible with CS. Montiel et al. (2012) have reported PCR products from two 16th- to 17th-centuries infants recovered from a crypt in southwest Spain. In summary, while aDNA analyses hold promise for clarifying the phylogeography of TD, to date molecular studies have not contributed significantly to our knowledge.

Skeletal Examples Congenital Syphilis Traditionally, a congenital variant of TD was only thought to occur in VS. However, this can occur in yaws but is still not reported in bejel. The major factor in the transplacental transmission of a treponeme appears to be the timing of the early acute phase of the disease and timing of the pregnancy of the female. When both occur at about the same time, transplacental infection of the

developing fetus can occur. If this infection occurs relatively late in pregnancy, then survival of the infant is possible. Obviously, the mode of transmission is a major factor in the prevalence of congenital TD. The early stage of VS is much more likely to be associated with pregnancy than yaws. This means that the most probable diagnosis of congenital TD will be VS. However, the fact that archeological evidence of congenital TD is still very uncommon might be an argument for a nonvenereal cause in these “cases.” Two examples of probable congenital TD in New World archeological skeletons demonstrate the skeletal manifestations of this disease that include defective dental development, systemic periostosis that affects the major long bones, and at least in one individual nasofacial lesions that would have been associated with the classic saddle nose indicative of CS. The first of these two skeletons is from a 6- to 7-year-old Native American child from Virginia, United States. The sex of the child is unknown. There were no European artefacts found at the site. Both the pottery types and the presence of stone pipes suggest a date before AD 1400. Although a later date cannot be ruled out, this evidence points to the preColumbian period. Lesions on the skull are confined to the face and forehead (Fig. 11.119A). There is some postmortem damage to the skull, which complicates the picture. The lesion on the forehead is located near the midline and measures about 35 mm by 45 mm. It may extend to the left of the frontal bone, but postmortem damage precludes confirmation. The lesion itself consists of periosteal new bone formation, which shows only slight evidence of porosity (Fig. 11.119B). The most markedly abnormal bone tissue occurs around the nose. The nasal bones and the maxillary bone adjacent to the nasal bones, along with the nasal aperture, have thickened, porous, periosteal new bone on their external surfaces (Fig. 11.119D). The remaining portions of the maxilla appear to be normal. There is a slight degree of porosity of the orbital roof. There are plaques of porous, periosteal new bone on the inferior and anterior portions of the mandibular body. This is accompanied by a slight expansion in the thickness of the body on the left side. The maxillary deciduous incisors are missing on the left side. However, both right maxillary incisors have marked hypoplastic defects (Fig. 11.119C). Indeed, some of the defects were so severe that, for example, the lower portion of the right lateral incisor appears to have broken off antemortem. There is a less severe hypoplastic defect on the left deciduous maxillary canine. The enamel of the right canine has been damaged postmortem, although there is a slight trace of a defect on this tooth too. The deciduous

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FIGURE 11.119 An archeological skeleton with probable congenital syphilis: (A) anterior view of the skull; note the abnormal periosteal, reactive bone (arrows) on the frontal, nasal, and maxillary bones; (B) detailed view of the frontal bone lesion; (C) detailed view of the hypoplastic development of some of the deciduous dentition; note the hypoplastic enamel lines and the loss of a portion of the crowns of some of the defective incisors (arrows); (D) detailed view of the periosteal reactive new bone on the nasal and maxillary bones; (E) anterior view of the femora, tibiae and left fibula; note that the diaphyses of the tibiae (arrows) are much thicker than the diaphyses of the femora; (F) a detailed view of the expansive periosteal new bone on the left tibia; (G) laterosuperior view of the right fifth metatarsal; note the thickened porous nature of the periosteal reactive new bone; (H) superomedial view of the right fifth metatarsal; note the diminished amount of reactive bone on the medial aspect (arrow) (6- to 7-year-old child from an archeological site in Virginia; NMNH 379177).

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FIGURE 11.119 Continued

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and first permanent molars are normal, as is the emerging permanent left central incisor. The dentition of the mandible is less severely affected. The central incisors are hypoplastic with antemortem loss of the superior portions of their crowns. The lateral incisors have a very slight enamel defect. The remaining teeth appear to be normal, although the severe caries of both deciduous second molars suggests weakened enamel. Caries of the lower left first deciduous molar has resulted in a periapical lesion on the left side. All of the major long bones of the postcranial skeleton exhibit porous, periosteal lesions. The severity and thickness of these lesions vary and are significant in reaching a preferred diagnosis. Both scapulae are normal, as is the manubrium. Both clavicles have periosteal new bone deposits on the anterior medial aspect of their diaphyses; the metaphyses are normal. Both humeri have patchy, periosteal new bone deposits, which are limited to the diaphysis. Involvement is slight and there is no appreciable expansion of the cortex. The radii are somewhat damaged but clearly indicate a general deposition of periosteal new bone on their diaphyses, which is more severe distally. There is slight enlargement of the diaphysis, and the metaphysis is normal. A similar distribution of periosteal new bone occurs on the ulnae, but the diaphyseal enlargement is more marked. This increase in cortical thickness occurs through the apposition of periosteal bone, but this is also associated with an enlarged marrow space, although there appears to be a net increase in the thickness of the cortex. Many of the smaller bones of the hands were not recovered during excavation, although all the metacarpals were present. In general, they exhibited a low-grade, diaphyseal periostosis, which resulted in slight enlargement of their diaphyses. All bones appeared to have been affected to approximately the same degree except the fourth metacarpal, which was only slightly affected on the right and was normal on the left. The vertebrae and pelvis were normal, as were the existing fragments of ribs. There was slight periostosis on the femora, which was limited to the anterior distal diaphyses and metaphyses with involvement extending almost to the growth plate. Both tibiae were greatly enlarged, with clear evidence of active periostosis. The major foci of bone formation were the anterior proximal portions of the diaphyses (Fig. 11.119E and F). However, the entire shafts were abnormally thickened. There was also marked true bowing along the mediolateral axis. The appearance of bowing in the anteroposterior axis is due to the anterior build up of abnormal bone and not because of true bowing in this axis. The fibulae were less severely affected with a similar lesion. The major focus was the mid to

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distal portion of the shafts with the right fibula somewhat more affected than the left. Many of the smaller bones of the feet are missing. Both tali were normal, although the calcanei exhibited periostosis. The involvement was more severe on the right calcaneus. The metatarsals showed a bilateral pattern of involvement, in which the first and fifth metatarsals were most severely affected. The fifth metatarsal, in particular, exhibited a much more severe condition than that seen on the other metatarsals (Fig. 11.119G and H) and both the first and fifth metatarsals were more severely affected than any of the metacarpals. The overall pattern of bone changes in this skeleton showed that the bones that had minimal overlying or adjacent tissue were most severely affected. The bones affected include the frontal, nasal, and adjacent maxillary bones, the ulnae, tibiae, and first and fifth metatarsals. The position of the marked hypoplastic defect on the incisors indicate that it would have developed in utero because that portion of the tooth develops at about the seventh fetal month. This indicates a congenital disease and, in combination with the pattern of relatively severe lesions in the skeleton, suggests CS. Hutchinson (1909: plate 31) illustrates the upper incisor and canine teeth of a 3-year-old child with CS. The canine teeth are normal but the incisor teeth have hypoplastic defects, which resulted in part, or all, of the crown breaking off (Fig. 11.120; see also Fig. 11.121). The second example of probable congenital TD is illustrated in the skeleton of a child about 3 years of age from the Fisher site in Virginia, United States. The site is dated to about AD 925. While the site was being excavated by Howard MacCord, Don Ortner was invited to remove this burial along with an adult burial whose

FIGURE 11.120 Drawing of upper incisor and canine teeth of a 3year-old child with congenital syphilis; note that the crowns are partly to completely missing from the incisors. Redrawn from Hutchinson, 1909, Plate 31, Figure 3, facing page 460.

406 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 11.121 Child with possible CS from the Fisher site in Virginia, dated to c. AD 925: (A) anterior maxilla and mandible; note the enamel hypoplasia and malformed dental crowns as well as the deformed root (arrow) of the left, upper central incisor; (B) left lateral view of the maxilla and mandible; note the hypoplastic crowns of the first and second deciduous molars (arrows); (C) occlusal view of the upper and lower dentition; note the severe caries (arrows) resulting from the hypoplastic crowns; (D) left and right tibiae with periosteal reactive woven bone formation (arrow) (child ca. 3 years old; NMNH 385786).

skeleton had the classic pattern of pathological changes associated with TD, including “saber” tibiae. The adult skeleton will be discussed in the section on the paleopathology of adult TD. Preservation of the skeleton was less

than ideal, but the teeth were preserved and show severe developmental defects that affected the formation of the enamel and also the root formation of the left upper central incisor (Fig. 11.121A C). The long bones available

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for study exhibited a porous periostosis that was particularly pronounced on the tibiae (Fig. 11.121D). The combination of dental pathology that developed in utero, along with the evidence of systemic periostosis, provides

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plausible evidence for a diagnosis of CS. The presence of an adult skeleton with unequivocal skeletal signs of TD buried a few meters away makes this diagnosis even more likely.

FIGURE 11.122 Adult treponemal disease from the Fisher site in Virginia, dated to c. AD 925; this burial was within a few feet of the child’s skeleton seen in Fig. 11.122: (A) anterior view of the frontal bone showing classic caries sicca lesions (arrow); (B) right and left inferior clavicles with lytic foci and reactive periostosis; (C) lower ribs with lytic foci and periostosis; (D) right and left humeri, ulnae, and radii with destructive lesions of the diaphyses and periostosis; (E) radiograph of destructive lesion of the left humerus diaphysis showing sclerosis at the margins of the lesion; (F) right and left femurs, tibiae, and fibulae with classic saber shin of the tibiae and periostosis of the lower left femur; (G) radiograph of the right and left femurs, tibiae, and fibulae with classic saber shin of the tibiae; (H) left metatarsals and proximal phalanges with destructive lesions of the first metatarsal and periostosis; (I) CAD drawing of the distribution of lesions in this skeleton; triangles indicate a predominately bone-destroying process; circles indicate a predominately bone-forming process. C 5 bone destruction with well-defined margin and evidence of repair; D 5 central destruction with marginal bone formation; E 5 D-type lesion but in the repair phase; B1 5 smooth compact bone; B2 5 porous compact bone (adult c. 30 years old; NMNH 385788).

408 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 11.122 Contiuned

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409

FIGURE 11.122 Contiuned

Adult Treponemal Disease In a differential diagnosis of any infectious disease in archeological human remains, it is very helpful to have a “classic” example of the disease from a site that provides strong evidence that the disease was present in the group being studied. This is illustrated with another human burial of an adult male about 30 years of age also from the Fisher site in Virginia. The skull of this skeleton exhibited lytic lesions of the frontal bone (Fig. 11.122A) that are certainly possible for a diagnosis of TD but not necessarily pathognomonic. The pathological changes apparent on the postcranial bones provide the most convincing evidence of TD. Destructive lesions occur on the clavicles (Fig. 11.122B) and lower ribs (Fig. 11.122C). The upper extremity also has multifocal destructive lesions (Fig. 11.122D and E). However, the most diagnostic feature is the presence of bilateral saber tibiae (Fig. 11.122F and G). The bones of

the feet, particularly the left first metatarsal, have lytic lesions accompanied by periostosis that has enlarged the diaphysis (Fig. 11.122H). The overall pattern of skeletal involvement includes multifocal, often bilateral, lesions that may be lytic but in which periosteal reactive new bone formation is a major component (Fig. 11.122I). A classic example of caries sicca is seen in the skull of an adult female Native American from Arkansas. This skeleton was excavated by Clarence Moore during fieldwork conducted in 1909 and 1910. Moore (1910: 258) believed that the burial was pre-Columbian, and a date between AD 1350 and 1500 is likely. The bones that were recovered included a fragmentary skull, the right clavicle, both humeri, the left radius and proximal ulna, the distal right radius, the proximal right tibia, the shaft of the right fibula, and the right talus and calcaneus. Of these bones, the skull, left ulna, both femora, and the left tibia have obvious lesions. The right calcaneus has slight periostosis

410 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 11.123 Probable acquired treponemal disease in a Native American skeleton from Arkansas; site dated between AD 1350 and 1500: (A) right lateral view of the skull; note that the reactive bone is minimal below the area of the temporalis muscle attachment; (B) detailed view of the irregular, lumpy outer table of the right parietal bone; this is a typical bony reaction to gummatous lesions; (C) anterior view of the femora and tibiae; (D) detailed view of the medial side of the right femur near the midshaft; note the bony bridging that took place over blood vessels (white arrows) and the undercut periosteal bone (black arrow). Such lesions are typical of bony reactions in treponemal disease (adult female; NMNH 258778).

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of its superior and lateral cortex. The other bones were unaffected. The lesions of the skull (Fig. 11.123A and B) were most pronounced on the cranial vault and were much less apparent on bone underlying the temporal muscle mass. However, both temporal bones show a thickened, irregular, and slightly porous surface. The major focus for the lesions was the external table, although some of the lesions penetrated to the inner table and others seemed to originate there. However, inner table involvement was

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much less extensive. Broken sections of the frontal and parietal bones revealed a thickening of the skull, with almost complete filling in of the diploe with compact bone. The lesions of the external table were typical gummatous lesions characterized by a mixture of bone formation and destruction, creating an irregular lumpy appearance. In this case, the smoothed surfaces of the lesions indicate a long-term chronic condition. The left orbital roof was not recovered, but the right orbital roof exhibited slight periostosis, which may or may not be

FIGURE 11.124 Probable acquired treponemal disease in an adult female skull from a historic site in Alaska: (A) anterior view exhibits an active, bony reaction typical of a gummatous condition; (B) detail of lesions on the frontal bone; (C) left lateral view; (D) detailed view of the reactive new bone on the left parietal bone showing destructive foci but with some reactive bone formation (NMNH 280095).

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associated with the disease process affecting the rest of the skeleton. The proximal left ulna was the only long bone of the upper limb that exhibited abnormality. The lesion consisted of an enlarged proximal metaphyseal cortex with slight porosity. Because of the rotation of the biceps tendon and the biceps tubercle of the radius, the superior lateral portion of the metaphysis could not participate in this expansion, creating a depression in this region of the ulna. The insertion of the brachial muscle was markedly rough, with spicules occurring on the periphery of the insertion area. The joint surface itself showed slight breakdown on the coronoid portion, which may reflect an expansion of the disease process into the joint. However, the joints of the affected bones of the lower extremity were unaffected. The abnormal new bone of the left femur was restricted to the proximal shaft and metaphysis (Fig. 11.123C). The lesion did not extend to the trochanters or the femoral neck. The disease process had resulted in concentric thickening of the cortex, which was most pronounced on its posterior aspect. The surface was generally smooth with isolated regions of slight porosity. Muscle attachments in the affected area were noticeably rugose. The entire shaft of the right femur was abnormal, somewhat more so distally than proximally (Fig. 11.123C and D). The lesion consists of thickening (new bone) with isolated patches of porosity. The proximal muscle attachments appeared normal. However, there was considerable thickening of the bone with a very irregular surface in the distal region of the linea aspera. The anterior surface revealed raised plaques of new bone and bony spicules, which appear to be bridging over superficial blood vessels. There were no cloacae. The pathological lesions of the ulna and femur are very typical of conditions occurring in long bones of known examples of TD, and in Ortner’s experience are not found together in other infectious diseases. A very similar pattern of abnormal bone was seen on the left proximal tibia. The abnormal new bone had isolated foci of porosity. There were occasional, slightly raised plaques of new bone and bony bridges that would originally have lain over superficial blood vessels. The attachments of the proximal parts of the attached posterior muscles and ligaments, including the soleus, popliteus, and the tibial collateral ligament, were markedly rugose (wrinkled). The surface appearance suggests that the periosteal new bone grew around the ligament attachments but did not affect the attachment area. The radiological picture for both femora and the left tibia revealed the thickened cortex. The outline of the original cortex was still apparent but had become cancellous in focal areas of the three bones. The endosteal surfaces of the cortex did not encroach on the medullary cavity, as often

happens in osteomyelitis and occasionally in osteitis and periostosis. A now reburied skull excavated from an Inuit site on St. Lawrence Island, Alaska, demonstrates the progression of lesions from the frontal bone to the posterior portions of the skull. The mandible and postcranial bones were not recovered. Regrettably, the date for the burial is unknown, but other skeletons collected at the same time were thought to postdate Russian contact, which began during the 1740s. The skull is from a female and the maxillary teeth, except the right canine, had been lost before death. The canine tooth is badly worn which, with the loss of teeth, suggests an age at death well into adulthood. The lesions were largely confined to the skull vault, although there was a focus on the left parietal bone superior to the mastoid process, which also involved the adjacent temporal bone (Fig. 11.124). Although the most obvious lesions are confined to the outer table of the skull, the external lesions penetrated to the endocranial surface in the region of the left mastoid process (Fig. 11.124D), the right parietal bone, and the posterior sagittal suture. There is considerable fine porosity on the endocranial surface of the vault with some lytic depressions about 0.5 cm in diameter, particularly on the right parietal bone. The lesions in the frontal bone region of the outer table (Fig. 11.124B) reveal a fairly typical, coalescing, lytic-blastic response associated with the chronic healing phase of TD. In the posterior portion of the skull, the lesions are more active and predominantly lytic (Fig. 11.124C). However, there is slight reactive new bone at the margins of the more active lesions. The general picture in this case was that of a more chronic course of the disease process with considerable healing in the frontal bone region, but with lesions that become progressively destructive toward the posterior portion of the skull. This pattern of healing lesions on the frontal bone with more active lesions in the posterior portion of the skull is also seen in a skull of an adult female native Australian. The degree of tooth wear suggested an age in excess of 30 years. It dates to before 1920 and probably is much older. Currently the skull is curated in the Pathology Museum of the Royal College of Surgeons of Edinburgh. The frontal bone exhibits extensive, but mostly healed, lesions (Fig. 11.125A). However, the lesions become more destructive towards the occipital region (Fig. 11.125B and C). The most active lesions are seen in the occipital bone, and they extend up into the left parietal bone (Fig. 11.125B). The skull has been sectioned and reveals a sclerotic diploe similar to that seen in the archeological skeleton from Arkansas described earlier. Two skeletons with TD from archeological sites in England provide important insight into the skeletal manifestations of this disease and its history in England. The

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FIGURE 11.125 Probable treponemal disease in an adult native Australian: (A) anterior view of the skull; note the healed nature of the frontal bone lesions and the sclerotic diploe in the sectioned portion of the frontal bone; (B) posteriorlateral view, showing active lesions on the occipital and posterior parietal bones; (C) top view of the skull, showing the more active nature of the lesions towards its posterior portion (PMES 1GD1(116)).

first represents that of a young adult female about 22 years of age (Roberts, 1994). The skeleton was excavated from the Blackfriars site in Gloucester, which was archeologically dated to between AD 1240 and 1538, but radiocarbon dated to 1438 1635 (uncorrected for the marine component of the diet). This skeleton is of particular interest because of the extent of the bone involvement in such a young person, and it raises the possibility that this may be originally the result of CS. It is also of interest, being one of the first skeletons studied to explore the impact of mobility on the spread of infectious disease. Stable isotope analysis applied to this skeleton to explore the person’s origin showed that the person originated in

western England and moved to Gloucester after the age of 8 years (Mongomery, 2002). The frontal and facial bones exhibit healing and active lesions (Fig. 11.126A). The nasal bones were involved and the region around the nasal bones is depressed and suggestive of the “saddle nose” depression primarily associated with CS. Destruction of bone within the nasal antrum was extensive and penetrated the hard palate, leaving a major defect in that tissue (Fig. 11.126B). The bones of the pectoral girdle including the sternum, clavicles, and the spines of the scapulae have destructive lesions (Fig. 11.126C). The ribs and upper extremity bones have destructive lesions and reactive periosteal

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FIGURE 11.126 Treponemal disease, probably venereal syphilis, in a skeleton from the Blackfriars site in Gloucester, England, dated between 1240 and 1538 AD: (A) anterior view of the skull with a large, active, lytic lesion of the frontal bone and extensive destructive remodeling of bone around the nose; there is also a healed lytic lesion (arrow); (B) hard palate with a large lytic lesion with periostosis surrounding the lytic focus; (C) clavicles, sternum, and fragmentary spine of the scapulae with multifocal lytic foci and reactive bone formation; (D) left 8th and 9th ribs with lytic lesions and periostosis; (E) right and left humeri, ulnae, and radii with lesions of the diaphyses; note particularly the destructive lesion of the right radial head; (F) detail of radial head with complete destruction of the subchondral bone; (G) right and left femurs, tibiae, and fibulae with blastic lesions of the left tibia midshaft and the distal right tibia (adult female about 22 years old; Blackfriars burial no. 77).

bone formation (Fig. 11.126D and E). The subchondral bone of the right radius was completely destroyed (Fig. 11.126F). Periosteal reactive new bone formation also occurred on the lower-limb bones (Fig. 11.126G). The lesions tended to be bilateral, although not necessarily symmetrical. Other than TD of some type, there are no good diagnostic options. A plausible case can be made for a young adult expression of CS, but the use of the site could be post-Columbian. A further example of TD from England is that of a medieval skeleton from the friary site of Hull Magistrates Court, Hull, dated to 1316 1539 (Roberts et al., 2012; Boylston et al., 2001). The skeleton has been radiocarbon dated and the date corrected for the marine component of the diet to 1492 1657 (95% confidence interval) (Harper et al., 2011). The skeleton of interest is burial no. HMC 1216 and is from a male about 17 25 years of age. Skeletal involvement in this case is remarkable with virtually every lesion that can occur in treponematosis occurring

somewhere in the skeleton. Skull lesions occur mostly on the frontal and facial bones (Fig. 11.127A). Classic caries sicca lesions can be seen on the frontal bone over the nose (Fig. 11.127B). Over the left orbit an early stage in Hackett’s caries sicca sequence can be seen as a roughly circular lesion with fine holes penetrating through the cortical surface (Fig. 11.127C). The bones of the nasal antrum are missing postmortem but the destructive process affecting this area of the face can be assumed on the basis of a destructive lesion of the hard palate (Fig. 11.127D). This skeleton is one of the very few examples of TD from an archeological site that shows involvement of the vertebral column. As indicated earlier in this chapter, the most common site for such involvement is the cervical spine and this skeleton shows periosteal reactive bone formation on the upper cervical vertebrae (Fig. 11.127E). A periosteal lesion composed of proliferative porous bone occurs on the anterior surface of the right clavicle (Fig. 11.127F). Other forms of infectious osteomyelitis

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FIGURE 11.127 Treponemal disease, probably venereal syphilis, in a skeleton (burial HMC 1216) from the Hull Magistrate’s site in Hull, England, dated between 1317 and 1539 AD: (A) anterior view with caries sicca of the frontal bone; (B) detail of midline lesions of the frontal bone; (C) earlystage porous caries sicca (arrow) with a healing stage of that type of lesion just above; (D) view of the hard palate, showing a lytic focus; (E) vertebral body of C3 with periostosis; (F) right clavicle midshaft with woven reactive new bone formation; (G) left radius: diaphysis with a lytic focus and woven reactive bone surrounding the focus; (H) left femur diaphysis with chronic periosteal new bone development; (I) left fibula distal diaphysis with a lytic focus surrounded by reactive woven bone; (J) CAD drawing of the distribution of bone lesions in this case; triangles indicate a predominately bone-destroying process; circles indicate a predominately bone-forming process; D 5 central destruction with marginal formation; E 5 D-type lesion but in the repair phase; F 5 focal porous destruction; B2 5 porous compact bone; B3 5 striated compact bone.

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FIGURE 11.127 Contiuned

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rarely affect the clavicle and the presence of this lesion on this bone is a helpful criterion in a differential diagnosis. Reactive periosteal new bone formation is seen on several of the long bones. One of these lesions occurs on the distal diaphysis of the left radius (Fig. 11.127G). The central portion of the lesion is composed of woven bone and contains a central lytic focus that is not a cloaca. Note the absence of a smooth margin within the opening that would be composed of smooth, dense compact bone in a cloaca. At the margins of the lesion, particularly where it grades into the normal compact bone, the bone in the lesion is denser, indicating a slower development of the abnormal bone. Lesions in the lower-extremity bones exhibit both the reactive periostotic bone formation associated with a nongranulomatous infection (Fig. 11.127H) and lesions associated with a granulomatous focus (Fig. 11.127I) that are very similar to lesions occurring in the upper extremity bones. Differential diagnosis of this skeleton really offers no reasonable alternative to treponematosis. The lesions of the skull are classic manifestations of caries sicca and the overall type and distribution of the skeletal lesions in this case fit this diagnosis to the exclusion of any other (Fig. 11.127J). The question of whether this is VS or a nonvenereal treponematosis remains an issue that may be resolved in the future if aDNA analysis develops for this infection (see Chapter 8). Another possible Old World example of treponematosis is from a site in or near El Kurrew in Egypt that is dated to between AD 300 and 700. The skeleton provides some insight regarding the antiquity of this disease in North Africa. The skeleton is from a male about 42 years of age and is part of the collection of the Peabody Museum of Archaeology and Ethnology, Harvard University, United States (catalog no. N3913). The importance of the skeleton is complicated by the fact that there has been some commingling with bones of at least one other individual. However, the type and distribution of abnormal bone lesions is congruent and argues for the pathological bones belonging to a single skeleton. The features most indicative of treponematosis occur on the skull (Fig. 11.128A) and are limited to the frontal and parietal bones. The lesions are indicative of a granulomatous destructive condition that was probably inactive at the time of death. The skull lesions are multifocal (Fig. 11.128B) and consist of depressed foci with stellate lines radiating from the central focus of destruction. There is no evidence of significant change in the bones of the face, maxilla, the palate, or the area around the nose. The mandible is normal. On the left humerus there is a large erosive lesion in the para-articular area between the humeral head and the greater tubercle (Fig. 11.128C). This is a large depression that in its shortest axis is almost a centimeter in width and

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in its longest axis probably 12 or 13 mm in length with a depth of 3 4 mm. The lesion is well circumscribed, with dense compact bone in the destroyed area indicative of healing. Erosive joint changes do occur in treponematosis, and the presence of this condition supports the evidence apparent in the skull. The vertebrae are normal except for the sacrum, which shows evidence of chronic proliferative periostosis in the anterior midline. The femora exhibit proliferative periostosis in the distal half of their diaphyses, grading into the metaphyseal area that involves the entire circumference of the bone (Fig. 11.128D). Like the lesions seen on the skull, this lesion appears to have been inactive at the time of death. A left tibia that may be associated with this skeleton has a large lesion on its anteromedial aspect at about midshaft. The lesion is porous and could have been associated with a chronic skin ulcer overlying that area. There is no evidence of any other pathology in this tibia or in the right tibia. The type and distribution of bone lesions argue for a diagnosis of treponematosis, although other infectious conditions such as osteomyelitis should be considered. The geographical association of this individual suggests a specific diagnosis of bejel, and this instance may be one of the earliest examples of this disease. A skeleton with probable yaws from a native Australian site near Coolah dated to the post-European period provides a remarkable example of the skeletal manifestations of TD and the severity of joint lesions that can occur. The skeleton is from an adult female and is curated by the Shellshear Museum of the University of Sydney (catalog # 136). An understanding of the pathological lesions is complicated by postmortem destruction. However, most of the destructive foci have clearly sclerotic margins that are indicative of an antemortem process. In the skull, there are multiple granulomatous lesions on the frontal bone (Fig. 11.129A and B). The lesions are depressed with sclerotic margins indicative of healing. Some of the lesions have the stellate rays of classic caries sicca. The postcranial skeleton exhibits multiple lesions that include periosteal reactive bone formation, but also some of the most remarkable destructive lesions that Ortner had ever encountered. The left clavicle shows an enlargement of the shaft (Fig. 11.129C). In the right scapula the coracoid process and the subchondral bone of the glenoid cavity have been destroyed antemortem (Fig. 11.129D). This destruction corresponds with antemortem destruction of virtually the entire right humeral head (Fig. 11.129E and F). Although not as severe, the left humeral head also shows some loss of subchondral bone and juxta-articular erosive lesions (Fig. 11.129F). Both humeri exhibit extensive periosteal reactive new bone formation in the distal diaphysis and metaphysis, and the right humerus has a large lytic focus on the posterior midshaft area (Fig. 11.129E) that is surrounded by

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FIGURE 11.128 Possible treponemal disease in a skeleton dated to between 300 and 700 AD: (A) anterior view of the skull with multiple caries sicca lesions of the frontal bone; (B) detail of frontal bone lesions; (C) para-articular erosion of the proximal humerus; (D) right and left femur with periosteal lesions on the distal femora. Adult male about 42 years of age, with permission, PMH N3913.

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FIGURE 11.129 Probable yaws in a post-European skeleton from a site near Coolah, Australia: (A) anterior view of the skull showing caries sicca of the skull vault; some of the lesions may be postmortem but there is clear evidence of healed lesions (arrow); (B) detail of frontal bone lesions showing healed carries sicca; (C) right and left superior clavicles with lytic foci and periosteal new bone formation on the left; (D) destruction of subchondral bone of the glenoid cavity of the right scapula; (E) right and left humeri with large midshaft lesion of the right accompanied by extensive reactive new bone formation; (F) subchondral bone and juxtaarticular erosions of the right and left humeral heads; destructive remodeling particularly of the proximal right humerus (right image); (G) anterior view of the right tibia and fibula showing a large antemortem destructive lesion of the proximal tibia and periosteal reactive bone on the diaphyses; (H) detail of proximal lesion of the tibia demonstrating the reactive new bone formation deep in the lesion (arrow) (adult female; SM 136).

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FIGURE 11.130 Tibial lesions attributed to yaws or endemic syphilis in a skeleton from Australia dated to pre-European contact: (A) posterior view of tibiae; (B) medial view of tibial lesions. AIAC SF 19:27, in Hackett (1978); photograph courtesy: Dr. C. J. Hackett and the South Australian Museum.

dense, reactive bone formation. The bones of the forearm have multiple sites of reactive new bone formation. Most of the bones of the hands and feet are missing. There are some lytic lesions on the bone surfaces, but some of this may be the result of postmortem processes. Despite considerable postmortem destruction, there do appear to be lytic foci with reactive bone on at least two of these ribs, indicating axial involvement of bone in the disease process. The vertebrae are all missing postmortem. The left femur has a healed fracture of the diaphysis with poor alignment and much of the pathology appears to be related to trauma. The right femur is relatively normal. The right proximal, anterior tibia has a large, antemortem destructive lesion that certainly encroaches on the joint surface itself but is largely metaphyseal (Fig. 11.129G). There has been considerable remodeling and formation of compact bone at the margins of the lytic focus (Fig. 11.129H) indicating the antemortem nature of the disease process and that the disease had become chronic, at least at this site. The distal end of the tibia shows a lumpy kind of remodeling bone formation and

proliferation that have been seen in other bones in this particular skeleton. On the left fibula, there is an irregular enlargement of the diaphysis with spicules extending from some of the areas of the interosseous ligament. The right tibia and fibula are relatively normal in appearance. Hackett (1978) describes several examples of bone lesions in pre-European skeletons from Australia. He attributes these lesions to yaws or endemic syphilis because VS is not thought to have been present until European contact. The long-bone lesions of one of these skeletons are shown in Fig. 11.130. The lytic lesions in this case have the appearance of a granulomatous condition in contrast with the smoother surface of nongranulomatous periosteal reactive new bone seen in some examples of adult VS.

BRUCELLOSIS Introduction Brucellosis (undulant fever) is a bacterial infection caused by several Brucella species in which domestic animal

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hosts play an important role (zoonoses). It is endemic in Saudi Arabia, South America, Spain, Italy, and the Midwestern United States (Resnick and Niwayama, 1995a). The most common animal hosts for infection transmission to humans are cattle, sheep, goats, pigs, and dogs, but camels, buffalo, deer, antelope, elk, and caribou may also be affected. Ingestion of infected (and unpasteurized) dairy products is the most common mode of transmission. People can also contract brucellosis via droplet infection and through close contact with animals. Today, veterinary surgeons, abattoir, and meat-packing workers are those most at risk. Entry of the organism through breaks in the skin or through the mucous membranes is possible in people doing these jobs, but this can also happen if animals are being hunted, slaughtered, and consumed (https://www.cdc.gov/brucellosis/transmission/ index.html). Brucellosis is classed as one of the most common zoonotic diseases in developing countries (El-Sayed and Awad, 2018) and is now known to be transmissible from human to human as well as from animals to human. The evolutionary history of brucellosis and other zoonoses of domestic animals is closely linked to the history of animal domestication in human societies. Research in zooarcheology has added much to our understanding of the presence of animal domestication (Zeder, 2008, 2017). Generally speaking, the current evidence for the first domestication of sheep, goats, cattle, and pigs appears to be around 10,500 years ago, with dogs a little later, around 7000 8000. The earliest confirmed domesticated dog has been found in China and dated to the early Neolithic (7000 5800 BCE) (Larson et al., 2012). As skeletal involvement in brucellosis is relatively common, it seems likely that skeletal evidence of this disease could be found in human remains at any time during the past 10,000 years. To date, there has been little evidence published (but see Curate, 2006; Mays, 2007; Mutolo et al., 2011), likely in part because differentiating skeletal evidence of this disease from other diseases that can affect the skeleton is a challenging exercise and is not possible in every case.

Pathology Brucella is a genus of Gram-negative rods (bacilli) containing three species pathogenic to domestic animals and, through them, to humans: Brucella abortus, which causes miscarriage in cattle and horses; Brucella melitensis, mainly affecting goats in the Mediterranean area, transmitted to humans primarily through infected milk; and Brucella suis in domestic pigs, transmitted through infected meat. The human disease is a chronic infection of the lungs and other organs, characterized by recurring bouts of fever—undulant fever (Spink, 1956). The skeleton is frequently involved through a hematogenous route.

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However, skeletal changes are usually quite rare (Resnick and Niwayama, 1995a), although they can vary in frequency from 2% to 70%, but they are especially high in B. melitensis infections (Jaffe, 1972: 1048). Adult males are affected much more frequently than females (Glasgow, 1976). The most common skeletal lesion in adults is in the spine or the sacroiliac joint (Madkour and Sharif, 1989: 92; Rajapakse, 1995). Ganado and Craig (1958) observed 130 instances of spondylitis in 6300 patients with brucellosis. Long bones are rarely involved in brucellosis infections. Kelly et al. (1960) observed in 36 people the following localizations of lesions: spine, 17; humerus, 3; femur, 2; ilium, 1; hand, 1; foot, 1. The spinal lesions are located predominantly in the vertebral bodies, especially of the lower thoracic, lumbar, and lumbosacral areas, often involving more than one vertebra (Lowbeer, 1948, 1949; Madkour and Sharif, 1989: 92). Unlike TB, brucellosis of the spine does not result in collapse of the vertebral bodies and angular deformity (Madkour and Sharif, 1989: 114). Brucellosis can occur in children and tends to affect the major joints of the skeleton (hip and knee), but it rarely affects the spine or sacroiliac joint (Madkour and Sharif, 1989: 90; al-Eissa et al., 1990). The earliest and most common lesion of the spine occurs as a small destructive focus on the superior, anterior margin of the vertebral body. This destructive early phase is followed by sclerotic repair of the lytic focus, often resulting in bone formation extending around the margin of the lesion, creating the “parrot’s beak” feature on lateral radiographs (Mohan et al., 1990). In the later phases of the disease, further infectious involvement of the disk results in its destruction and the end plates of the vertebral bodies. Loss of joint space and ankylosis of the vertebral bodies can occur (Madkour and Sharif, 1989: 110). Lytic cavitation of vertebral bodies is rarely severe but external and radiographic observations indicate that it may penetrate the vertebral end plate and extend through the nucleus pulposus of the disk into the next vertebral body (Fig. 11.131). The cancellous bone within the focus is destroyed without formation of a significant sequestra. The cortex also may be perforated, leading to periosteal abscesses. Because the skeletal manifestations are slow in developing, there is ample time for reactive bone to form and sclerosis occurs in affected vertebrae (Mohan et al., 1990: 66). In contrast to TB, which it resembles in several ways, complete collapse of the vertebrae with kyphosis is usually not observed (Keenan and Metz, 1972; Madkour and Sharif, 1989: 111), and paravertebral abscesses are also rare (Kelly et al., 1960; Glasgow, 1976) and, when they occur, they tend to be small (Mohan et al., 1990: 66). Another common site of involvement in the skeleton is the sacroiliac joint (Rajapakse, 1995: 165).

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FIGURE 11.131 Sagittal radiograph of a patient with brucellosis showing destructive lesions of the anterior vertebral bodies with reactive bony projections (parrot’s beak). Adult male; courtesy: Dr. George Y. El-Khoury, Dept. of Radiology, University of Iowa Hospitals and Clinics, Iowa city, Iowa.

Paleopathology As the spread of brucellosis between humans is very rare (Glasgow, 1976: 283), the presence of the disease depends on the presence of domestic hosts, including cattle, horses, goats, sheep, pigs, and dogs. Clearly, if brucellosis was endemic in the past, it should be seen in archeological skeletons. However, brucellosis received little attention at the time of writing of the 2nd edition of this volume, and still remains rarely mentioned in paleopathology. Brothwell (1965b: 690, 692 693) reports bone inflammation in Early Bronze Age skeletal remains from Jericho in the Near East, which he tentatively identifies as brucellosis. However, he attributed the diseased lower lumbar vertebrae to infectious arthritis. Although the description of the Jericho skeleton is incomplete, the disease involves the two fibulae and the lumbar spine.

One fibula is irregular and has a somewhat thickened shaft; the other is also enlarged but has no evidence of active infection. Capasso (1999) reports vertebral lesions in 16 adults from the skeletal sample recovered from the Roman site of Herculaneum in Italy (AD 79). Osteolysis of the superior vertebral margins, with a sclerotic response typical of brucellosis, occurs in each of the skeletons. Supporting a diagnosis of brucellosis, he also notes the Roman use of untreated milk from sheep and goats in their diet. The argument is that brucellosis would almost certainly have been endemic in Roman society, and one should expect to find evidence of the disease in the vertebrae of Roman skeletons. One of the pathological skeletons in the National Museum of Natural History, Washington, DC, has lesions that possibly can be attributed to brucellosis. This individual is a female skeleton from Norway accessioned by the museum in 1904. The estimated age at death on the basis of epiphyseal fusion and pubic symphysis morphology is 20 25 years. The archeological date is unknown. The skull of this skeleton is normal. Unfortunately, there is some mixture of bones from other skeletons. This problem is particularly apparent with the hand and foot bones, in which at least four individuals are represented. However, there is no obvious evidence of disease in any of these bones, and therefore in all likelihood the hands and feet were not affected by disease in this case. Of the remaining bones of the upper extremity, only the left humerus is abnormal, with the head of the humerus affected. Indeed, on superficial inspection, the affected bone could easily be confused with postmortem damage due to the burial environment. However, the presence of periosteal reactive new bone peripheral to the destroyed area on the humeral head provides evidence of a pathological process. The humeral head itself has been eroded, leaving exposed somewhat cavitated spongy bone, in which there has been no osteoblastic response to the disease process. However, the picture of the lytic process is obscured by what is undoubtedly some postmortem damage to the pathological bone. The glenoid cavity of the left scapula exhibits a similar destructive pathological process obscured by postmortem damage. Here, again, there is a slight perifocal bony reaction. The left radius and ulna are normal. The radiograph of the humerus indicates much more extensive involvement than is seen macroscopically. The cortex is much thinner than in the right humerus, and the appearance of the bone resembles a fairly coarse, “net like” structure, suggesting multiple foci for the disease process. The entire left humerus is virtually affected. The cervical vertebrae are all normal, as are the first three thoracic vertebrae. An initial radiograph of the thoracic and lumbar vertebrae indicated that the fourth through the sixth thoracic vertebrae were markedly

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osteoporotic. However, comparison of the corresponding articular facets and shape of the vertebral bodies revealed that these vertebrae were from another individual. Initially, this fact was not obvious because both the size and the color of these vertebrae were appropriate. This problem serves to highlight the need to ensure that all bones associated with a pathological skeleton actually belong to a single individual, and that great care must be taken to prevent mixing bones during excavation and subsequent processing and frequent handling. The seventh and eight thoracic vertebrae are normal. However, T9 has a large lytic process that has created a cavity in the body. The inferior plate of the body is largely destroyed, and there is a hole 1 cm in diameter into the neural canal. There is no marked evidence of bony reaction to the disease process. The tenth thoracic vertebra contains a similar lesion except that the superior plate of the body is involved. Thus, the vertebral bodies adjacent to a single intervertebral disk are affected. The anterior cortex of the bodies of the tenth thoracic through to the second lumbar vertebrae have enlarged vascular foramina but are otherwise normal. There is a suggestion of a lytic cavity inside the body of L3. On the anterior cortex of the body of L4 there are four depressed lytic lesions, which are not linked. In the largest of these, there is slight scalloping, suggesting coalescence of two or more lytic foci. The fifth lumbar vertebra exhibits slightly reactive new bone on the lateral cortex of the body. In the sacrum, the anterior surface of the first and second bodies shows slight erosion and reactive bone. However, the left and right articular surfaces of the sacrum show an extensive lytic process with multiple foci (Fig. 11.132). The large cavities created by the disease process subsequently have been well circumscribed. There is a corresponding circumscribed, lytic destruction on the articular portion of the innominate bone and the adjacent bone. However, the cavities are somewhat larger than those in the sacrum. The major lesion on the left innominate bone measures 25 by 40 mm, and on the right, 20 by 30 mm. Both cavities are at least 10 mm deep. The long bones of the lower extremities are all normal with the exception of the left femur. In this bone, there is a well circumscribed lytic lesion 15 by 18 mm and approximately 5 mm deep, which is lateral to the lesser tubercle on the posterior diaphysis. Some of the edges of this lesion have been broken postmortem, suggesting that the lesion was a cyst rather than a shallow depression during life. Differential diagnosis for this individual must include, in addition to brucellosis, TB, osteomyelitis, mycotic infections, and cancer. The lesions of greatest significance are the lytic cavities found in the corresponding end plates of the ninth and tenth thoracic vertebrae. The appearance of the two cavities suggests an initial focus for the disease in the intervertebral disk. This is an unlikely focus for

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FIGURE 11.132 Brucellosis of the vertebral bodies, with multifocal cavitating abscesses with perforation of intervertebral disk. Histological section. Courtesy: Dr. L. Lowbeer, Tulsa, Oklahoma.

TB, osteomyelitis, or mycotic infections, but is typical for brucellosis (Glasgow, 1976: 286). The fact that the vertebral bodies have not collapsed argues against TB, but the person may have died before that collapse occurred. The radiological appearance of the humerus has at least a superficial resemblance to patterns seen in multiple myeloma (or in solitary multiple myeloma lesions, called a plasmacytoma), although the irregular distribution of the lytic process argues against this disease. Another example of vertebral involvement in disease highlights some of the diagnostic ambiguities confronting the paleopathologist in interpreting skeletal disease in archeological human remains. The skeleton is from an archeological site in Tysfjord, Nordland, Norway. It is that of a young male about 18 20 years of age at the time of death and is thought to be associated with the native people known for their close herding association with caribou. The vertebral bodies from the mid-thoracic through the lumbar vertebrae exhibit multifocal lytic lesions with minimal sclerosis in the margins of the lesion (Fig. 11.133A and B).

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There is no evidence of vertebral body collapse despite partial destruction of the superior end plate of the third lumbar vertebra (L3) and corresponding, though less severe, cavitation of the inferior end plate of L2 (Fig. 11.133C). The type and distribution of spinal lesions would be very atypical for TB. The vertebral body destruction seen in L2 and L3 could reflect a fairly severe manifestation of

FIGURE 11.133 Large circumscribed, lytic lesion in the sacroiliac subchondral bone surface of the right innominate bone (arrow) with multiple lytic foci on the corresponding surface of the sacrum, possibly due to brucellosis (adult female skeleton from Norway; NMNH 227474).

brucellosis. However, the multiple cavities seen on the other vertebral bodies are not typical of brucellosis but could occur in echinococcosis and fungal disease. The ambiguity arises from comparisons with modern clinical examples, which often represent relatively early phases and perhaps less severe skeletal manifestations in the expression of brucellosis that responds well to antibiotic treatment. We can only make inferences about what brucellosis would look like in a completely untreated individual where death occurred after a lengthy course of disease. Another instance in which brucellosis should be considered in differential diagnosis is from a historic archeological site in Merida, Mexico. The skeleton is from a female about 35 45 years of age at the time of death and is curated at the Peabody Museum of Archaeology and Ethnology, Harvard University. The pathological lesions are multifocal and largely destructive with minimal evidence of repair. The lesion most compatible with a diagnosis of brucellosis is a destructive focus of the right sacroiliac joint (Fig. 11.134A). The left sacroiliac joint is completely fused, and there are multiple destructive foci in the thoracic vertebrae (Fig. 11.134B and C). Other lytic foci are seen in the sternal body (Fig. 11.134D) and the left distal femur adjacent to the lateral aspect of the medial condyle (Fig. 11.134E). The complete destruction of the T5 body and the inferior body of T6 does not fit the usual clinical manifestation of brucellosis. Fungal infection, echinococcosis, and metastatic carcinoma need to be considered in differential diagnosis (Fig. 11.135). FIGURE 11.134 Multifocal lytic lesions of the T8 L3 vertebrae, possibly the result of brucellosis. (A) Anterior view of T8 L3 vertebrae. Note the multifocal lytic lesions. (B) Right three-quarter view of T10 T12 vertebral bodies, showing the lytic foci with the sclerotic margins. (C) L1 L2 vertebral body end plates reflected to show cavitation (male, about 19 years of age from an archeological site near Tysfjord, Norland, Norway; UO 1338).

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FIGURE 11.135 Multifocal lytic lesions possibly due to brucellosis. (A) Reflected right sacroiliac joint subchondral bone, showing lytic lesions; (B) Lateral view of T2-T9, showing destruction of vertebral bodies but also some less severe lytic sites; (C) Detail of lytic lesions of T6 T9; (D) Lytic focus on the body of the sternum. (E) Lytic focus on the distal left medial condyle of the femur (adult female about 42 years of age from a historic archeological site in Merida, Mexico). With permission of the Peabody Museum of Archaeology and Ethnology, Harvard University, Cambridge, Massachusetts, Catalog No. 61016.

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there have been no examples of naturally occurring glanders since the 1940s. Nevertheless, instances of it affecting humans are reported from Africa, Asia, the Middle East, and Central and South America (https://www.cdc. gov/glanders/exposure/index.html).

Pathology

FIGURE 11.136 Lumbar vertebral body of a skeleton, with possible brucellosis, from the archeological site of Bab edh-Dhra, Jordan dated to about 3100 BC (burial from tomb A108NW).

A possible example of brucellosis occurs in the spine of an adult from the site of Bab edh-Dhra in Jordan (tomb A108NW). This is a secondary burial and there is some mixture between the burials found in the tomb chamber so that the association of the affected vertebra with other bones in the tomb is problematic. The lumbar vertebra shows destruction of the anterior part of the superior body with a large osteophyte extending in an anterosuperior axis (Fig. 11.136). Other diagnostic options certainly exist for this lesion, including osteoarthritis and earlystage TB. The radiograph of this vertebra shows a large area of trabecular sclerosis adjacent to the lesion. This would be atypical of osteoarthritis but could occur in early-stage TB. However, the most probable diagnostic option is brucellosis, and this may be an early example of this disease.

GLANDERS Glanders is included in this chapter to emphasize that while it is rare today, it may have been an important infection for our ancestors and the animals with which they interacted. People who work with or are exposed to animals with the infection are most at risk, e.g., veterinary surgeons and people working with horses or processing their meat. Today, humans rarely contract the infection, with the last person with glanders in Britain being reported in 1928 (https://www.gov.uk/guidance/glanders-and-farcy#how-to-spot-glanders-and-farcy). In the United States

Glanders is an infectious disease caused by Burkholderia mallei and primarily affects horses, donkeys, and mules (e.g., see Ghori et al., 2017), but other mammals can also contract this bacterial disease (e.g., goats, dogs, and cats). It is caused by the Gram-negative bacterium Pseudomonas mallei. The disease is transmissible from animals to humans via contact with tissues or body fluids of infected animals (https://www.cdc.gov/glanders/). The nasal mucosa is frequently involved and often the portal of entry. In humans, the bacteria can also enter the body through cuts and abrasions, or through bacteria-laden droplets in the air from animals. Glanders may result in a localized infection (ulcer and lymph node involvement), or affect the respiratory tract (pneumonia, pulmonary abscesses, and pleural effusion), or the bloodstream (where if untreated, death rapidly ensues). If the infection becomes chronic, multiple abscesses develop in the muscles and skin of the arms and legs, lungs, spleen, and/or liver. Bone lesions in glanders are rare. The organism may affect the periosteum from adjacent soft-tissue abscesses and skin ulcers, and in archeological skeletons the signs of bone damage underlying soft-tissue involvement may be considered (as in lupus vulgaris—TB of the skin). While hematogenous osteomyelitis in glanders can occur, it is very rare (Beitzke, 1934c). The part of the skeleton most often affected is the skull, secondary to nasal and oral mucosal lesions. Involvement causing defects of the nasal bones, nasal septum, and the ethmoid and sphenoid bones has been observed. Destruction of the turbinate bones with perforation into the maxillary sinuses, and perforations of the hard palate may also occur. Cranial vault lesions secondary to ulcers of the scalp have also been noted. Other bone lesions in glanders are almost exclusively limited to the bones of the lower extremities, particularly the tibia. The lower-extremity lesions may present as periostosis or osteomyelitis, and occasionally with secondary infection by staphylococci which modify the picture towards the appearance of “ordinary” osteomyelitis. Joint involvement in glanders is not rare, occurring mostly by extension from adjacent soft-tissue lesions and only occasionally secondary to an epiphyseal bone focus. In 27 examples of people studied with glanders affecting the joints gathered from the literature, Beitzke (1934c)

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found the distribution as follows: knee, 16; elbow, 4; ankle, 4; toes, 2; fingers, 1; tarsus, 1. Bone lesions in glanders are not pathognomonically diagnostic in dry bone. The main reason to mention them is to point out their similarity to tertiary syphilis and to some lesions seen in leprosy.

ACTINOMYCOSIS AND NOCARDIOSIS Actinomycosis is a very rare noncontagious bacterial infection that is seen across the world today, but rarely in the West. The Actinomycetes bacteria causing this condition normally live in the body commensally (meaning that they live within the host without injury to the body). It is only when they get into the linings of the gastrointestinal tract—including the oral and nasal cavities—that they cause problems. Actinomycosis cannot be passed from human to human (https://www.nhs.uk/conditions/ Actinomycosis/). There are three presentations of the infection: cervicofacial, thoracic, and abdominal (Finch et al., 2002). Possible causes of each include poor oral hygiene and dental decay, along with oral surgery (cervicofacial), inhaling the bacteria via contaminated food and drink into previously damaged lungs (thoracic), and involvement of the cecum, situated at the start of the large intestine (abdominal). While rare today, the disease was likely a challenge for populations in the past who would have struggled to maintain oral hygiene and prevent food and drink contamination.

Pathology Gram-positive bacterial species of the genus Actinomyces have the potential to cause actinomycosis in humans (Finch et al., 2002). Some of them include Actinomyces israelii, Actinomyces bovis, Actinomyces naeslundii, Actinomyces viscosus, and Actinomyces odontolyticus (Resnick and Niwayama, 1995a). At one time, these organisms were thought to be fungi, and this association is seen in the name of the genus. However, the pathogen is indeed a bacterium and closely related to another bacterial genus Nocardia, which will also be discussed briefly at the end of this section. After a person is infected in the face, lung, or gastrointestinal tract, Actinomyces can spread hematogenously to the liver, spleen, kidneys, brain, and bones and joints. The disease can also spread from an adjacent soft-tissue focus to another area of the body, such as bone. Infection is normally a secondary complication of injury to the tissue that permits entry via the oral cavity to the internal organs and tissues. However, as the pathogens spread through tissue, they are not limited to fascial planes or vascular

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pathways. This means that they can affect almost any area of the skeleton that is in relative proximity to an infective focus (as for lupus vulgaris in TB and possibly for glanders—see above). This can create an almost random pattern of skeletal involvement, and thus the skeletal manifestations do resemble those caused by fungi. In a study including of 486 individuals with human actinomycosis, Gra¨ssner (1929, cited in Beitzke, 1934d: 540) reported 73 instances of skeletal involvement (15%). The mandible, the flat bones of the axial skeleton, and the major joints of the appendicular skeleton are mainly affected in actinomycosis (Resnick and Niwayama, 1995a). Of 60 clinical instances reported by Baracz (1902), 55 involved the head and neck, 3 were thoracic lesions, and 2 were abdominal lesions. Involvement of the mandible tends to result in the development of periosteal reactive new bone that may appear as irregular mounds of abnormal bone similar to the lumpy jaw that occurs in actinomycosis of cattle. Thoracic involvement can lead to destruction of the ribs and sternum or the pectoral girdle (Smego and Foglia, 1998). Abdominal and pelvic actinomycosis tends to be the most indolent (causes little or no pain) of the various clinical syndromes, and because of this, might be expected to affect the bones of the lower spine and pelvis. Lytic lesions and sclerosis are the key bone changes. Note that pleuritis can occur in this condition, and thus the ribs may be affected by inflammatory new bone formation (and destruction). As noted, the bones are usually affected by direct extension of the infection from adjacent soft-tissue lesions. This means that, in most instances, the bone infection starts on the periosteal surface and frequently remains limited to it. The frequency of actinomycotic lesions in the different bones in Gra¨ssner’s study (1929) was as follows: vertebrae 37%, mandible 25%, ribs 10%, maxilla 8%, extremities 5%, skull base 4%, pelvis 4%, sternum 3%, zygoma 3%, and clavicle 1%. The periosteal involvement usually leads to hypervascularity, which is noticeable on the dry bone by the increased number and size of vascular channels and foramina. In addition, there is usually a varying degree of reactive subperiosteal new bone formation of porous or solid character. There is superficial erosion of the cortex and a varying degree of destruction of the adjacent cancellous bone, with little or no endosteal sclerotic response, in contrast to bacterially induced osteomyelitis. Formation of sequestrated bone is also rare. The most characteristic lesion is that of the spine (Young, 1960), with frequencies decreasing across the segments: thoracic . lumbar . cervical . sacral (Beitzke, 1934d: 554). Because the spine is usually infected from spreading pleural, abdominal, or cervical soft-tissue

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FIGURE 11.137 Actinomycotic periostosis of the lumbosacral spine and left ilium, secondary to actinomycosis of the sigmoid colon, left ovary, and soft tissue anterior to the sacrum (21-year-old female; FPAM 5315, autopsy 93144 from 1891).

FIGURE 11.138 Actinomycosis of the cervical spine. Note the periosteal reactive new bone, including the transverse processes and superficial erosion of the vertebral bodies (53-year-old male with actinomycosis of the cervical soft tissues and both lung apices; UGPM autopsy 203 from 1907).

FIGURE 11.139 Actinomycosis of the fifth lumbar vertebra and sacrum. Notice pitted transcortical erosions based on the periosteum (46-year-old female; FPAM 5649 from 1897).

lesions in broad contact with its anterior surface, the anterior periosteum of several vertebral bodies may be involved (Fig. 11.137). The transverse processes and, in the thoracic portion, attached ribs are often affected (Fig. 11.138). The involvement of the vertebral bodies, if present, starts anteriorly and seldom extends very deep into their structure (Fig. 11.139). Vertebral collapse and kyphosis hardly ever occur. The neural arches and spinous processes are usually spared but can be affected (Resnick and Niwayama, 1995a), and the intervertebral discs are usually preserved, as well. Lumbosacral actinomycosis may spread to the pelvic bones (Fig. 11.140), but this is not pathognomonic to actinomycosis. Mandibular lesions are mostly limited to periosteal reactive new bone formation of moderate extent, with occasional destruction and focal necrosis of the underlying bone, especially of the alveolar process. Central involvement of the mandible, possibly through a dental alveolus, leading to cavitation and expansion of the bone, is very rare in humans. By contrast, mandibular involvement is the most frequent type of actinomycosis observed in bovine and equine animals infected with A. bovis, which is usually not pathogenic for humans. In actinomycosis of the maxilla the adjacent paranasal sinuses, facial bones (zygoma), and middle and inner ear may become involved. Destruction of the mastoid process and the petrous part of the temporal bone has been observed. In the small and flat bones (ribs, sternum, pelvis), the destruction may be more extensive, creating a

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FIGURE 11.140 Actinomycosis of the lumbar spine and left innominate bone, showing mainly periosteal reactive new bone deposition and hypervascularity with focal erosion of the cortex: (A) internal view; (B) external view (18-year-old male; FPAM 5686, autopsy 130155-1353 from 1909).

“worm-eaten” appearance and large cortical perforations. Actinomycosis of the long bones is, as noted, rather rare and probably mostly the result of hematogenous dissemination from a pulmonary focus. The area most frequently affected is the metaphysis. Extensive destruction of the cortex with reactive periosteal new bone formation may be observed, but large cortical sequestra, as in bacterial osteomyelitis, do not occur. Focal cavitation may closely resemble a Brodie’s abscess, but perifocal osteosclerosis is usually slight or wanting. Joint involvement may occur secondarily to lesions in adjacent bones. This is most often the case in the costovertebral joints and less commonly in intervertebral joints (Beitzke, 1934d: 563). Nocardia is also a genus of the Actinomycetes group of Gram-positive bacteria that includes four species that

can cause disease in humans (Resnick and Niwayama, 1995a: 2505). They are Nocardia asteroides, Nocardia brasiliensis, Nocardia farcinica, and Nocardia caviae. The most common pathogen for humans is N. asteroides. In contrast to Actinomyces, the organism grows aerobically and stains acid-fast. Infections occur through the pulmonary route and mostly are confined to the lung and pleural cavity (Pizzolato, 1971: 1064 1066), but infection via the gastrointestinal route or after skin trauma can occur (Resnick and Niwayama, 1995a). In rare instances, hematogenous spread to bones and joints occurs, and the tubular or flat bones are involved. The lesions predilect cancellous areas and mainly consist of lytic cavitation, often complicated by fistulae (Fig. 11.141). There is little, if any, reactive bone formed. Immunocompromised individuals are at highest risk.

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FIGURE 11.141 Radiograph of nocardia osteomyelitis of the pubis with a fistula, proven by culture (27year-old female with pulmonary cavity actinomycosis; MGH 1293348).

PLAGUE Introduction To complete this chapter on bacterial infectious diseases, plague will be mentioned briefly, even though it does not directly affect the skeleton. Plague is caused by the bacterium Yersinia pestis. It is a zoonosis that is found in small mammals (e.g., black rats; but see Hufthammer and Walloe, 2013) and their fleas (http://www.who.int/en/ news-room/fact-sheets/detail/plague). There are three types of plague: bubonic (bite from an infected flea that leads to painful and swollen lymph nodes), septicemic (the bacteria spread via the bloodstream from bites of infected fleas or from handling infected animals), and pneumonic (people can inhale droplets containing the infection, or it can develop from bubonic or septicemic plague after it spreads to the lung). Untreated pneumonic plague is always fatal, as it would have been in the past. The latter is the only type that can be transmitted from human to human, while the other two types are spread from animals to humans via insects or other vectors. People with septicemic plague can develop black skin and other tissues (fingers, toes, and nose), and these structures may eventually necrose (die). This form is contracted via inhaling infectious droplets or from untreated bubonic or septicemic plague after the bacteria has spread to the lungs (https://www.cdc.gov/plague/symptoms/index.html). The last plague epidemic in the United States was in 1925/26, but it is now confined to rural areas of the west and southwest (https://www.cdc.gov/plague/maps/index. html). On a worldwide scale, plague occurs not only in North America but also in South America (especially Peru), Africa, and Asia. African regions have dominated global distributions since the 1990s, especially those of the

Democratic Republic of Congo and Madagascar. A useful summary of the history of the plague is provided by the Centers for Disease Control and Prevention (https://www. cdc.gov/plague/history/index.html). The World Health Organization states that between 2010 and 2015, there were 3248 people affected by the plague worldwide, including 584 deaths (http://www.who.int/en/news-room/ fact-sheets/detail/plague).

Paleopathology There have been three major plague pandemics during the past two millennia: the 6th-century Justinian Plague, the 14th-century “Great” or Black Death, and “Modern” outbreaks beginning in the 19th century. Millions of people have died throughout history from this infection. This makes it important for paleopathologists to remember that although the plague does not affect the skeleton, there are other characteristics of archeological skeletons and their context that can help us to reconstruct the history of the plagues. This includes not only features of human remains that give us an insight into plague demography, but also funerary contexts. In addition, molecular methods have convincingly addressed questions about earlier plague pandemics (Bos et al., 2011; Schuenemann et al., 2011; Wagner et al., 2014; see Chapter 8). Demographic studies of skeletal populations have considered the proposition that specific age and sex groups may have been preferentially affected; much of this work has centered around the AD 1348/49 East Smithfield cemetery in London (e.g., Margerison and Knusel, 2002; DeWitte, 2009, 2015; see also Gowland and Chamberlain, 2005 on Bayesian analysis and demography). DeWitte (2009) found that sex did not strongly affect risk of death,

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and that health in general was already declining in the 13th century, which might have led to a higher mortality during the Black Death (DeWitte, 2015). Identifying plague pits is a challenge. Historical evidence for plague is crucial (e.g. see data on the London Bills of Mortality in Roberts and Cox, 2003), and in some instances grave accompaniments such as coins may be informative (Gilchrist and Sloane, 2005). The most convincing evidence, however, is the identification of the pathogen Y. pestis, which has now been recovered from remains dating to the Justinian Plague and the Black Death (Bos et al., 2011; Schuenemann et al., 2011; Wagner et al., 2014). This molecular evidence recovered from ancient dental pulp cavities illustrates the power of genomic analyses in the identification of past infectious diseases that in particular do not affect the skeleton.

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