Index Introduction Materials and Methods Results Discussion References

Introduction

Treponematosis is a chronic infection caused by the microorganism spirochetes, of the genus Treponema. Four forms of treponematosis, i.e. pinta, yaws (endemic treponematoses), endemic syphilis (bejel), and venereal syphilis, have been recognized thus far. Each form is associated with distinctive geographic, climatic, and socio-cultural features. Of these, all but pinta produce skeletal lesions. Non-venereal forms of treponematosis have not yet been eliminated and are currently thought to affect at least 2.5 million persons (Antal et al., 2002).

From the paleopathogical point of view, cases of these treponemal infections, except for pinta which affects only the skin, have been increasingly documented throughout the world. In addition to the accumulation of paleopathogical cases of treponematosis, major discussions have focused on the origin and distribution of the three osteologic forms of treponematosis.

In Asia, there is little paleopathological evidence of treponematosis. A possible case of an adult female skull from the Samar cave in the Philippine Islands showing typical lesions was reported by Borobia Melendo and Mora Postigo (1995). Strong paleopathological evidence of treponematosis, probably yaws, comes from the skeletal remains of early Chamorroans in the Mariana Islands (Stewart and Spoehr, 1952; Suzuki, 1986; Rothschild and Heathcote, 1993). Although paleopathological evidence of treponematosis before 1510 is not known in Japan, a number of cases showing typical lesions in the skull as caused by venereal syphilis are known after this date, from various archeological sites of the late Muromachi and Edo period (Suzuki, 1984, 1991).

In the present study, we report possible cases of treponematosis from prehistoric human skeletal remains dating from the Bronze Age of China (1000 BC–500 AD), and discuss their significance in relation to the history of treponematosis introduction and epidemiology of this problematic infection in the ancient Middle East and other areas of Asia.

Materials and Methods

Skeletal remains from three archaeological sites, namely the Lijiashan, Ahatelashan, and Shangsunjia sites, in the northern part of Qinghai Province, China dated to about 1500–3000 BP, were subjected to visual examination.

Qinghai is located northeast of the Qinghai-Tibetan (Qing-Xizang) plateau, which forms a large part of the ‘roof of the world’, more than 3000 m above sea level. Neighboring Xinjiang to the west was an important area for ancient ‘Silk Road’ traffic to and from Central Asia. Qinghai, as well as Xinjiang, was one of the main areas of contact and movement between the eastern and western civilizations and between various cultures of the Eurasian continent (Figure 1). Qinghai contains headwaters of both the Changjiang (Yangtze) and Huanghe (Yellow) rivers. The climate of Qinghai is typically continental and highland, i.e. notably cooler and drier with an average temperature of −5.6 to 8.6°C throughout the year. Today, besides the Han population, various minority populations, such as the Huizu, Tibetan, Tuzu, Russian, and Mongolian people, comprise about 40% of the Qinghai region (Roufu and Yip, 1993). Among these minorities, the Huizu (Huihuis) are thought to have migrated to this area from Central Asia, as they are mostly Persian and Arabic in descent. These people were classified as ‘Se Mu’ people (people with colored eyes), and distinguished from other ethnic groups, such as the Mongolians, Han, and Uygur, during the Yuan Dynasty. The Tibetan (or Zang) people, who originated from the mountainous region of Tibet, have their own culture and religion influenced by a long-term feudal system of serfdom based on the integration of religion and politics dating from the 7th century AD.

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Figure 1. Map showing the Qinghai province and three archeological sites belonging to the Bronze Age reported in the present study.

The first inhabitants of the Qinghai region were paleolithic hunter-gatherers who used sophisticated stone blade and bone instruments at about 30000 BP. Archeological research was first carried out during the 1920s, by J.E. Anderson, who discovered the Neolithic and Bronze Age archeological sites in the Qinghai region. According to Chinese archeologists, a major prehistoric civilization, the Majiayao culture, flourished in the region from about 6000 to 4000 BP. This culture is characterized by an apparent overall increase in population, accompanied by tremendous amounts of earthenware pottery, and the development of burial rites. From about 3500 BP, the prehistoric pottery culture was overlain by a distinctly different Bronze Age culture. The Bronze Age culture is characterized by less flamboyant ceramics and a knowledge of bronze and iron technologies, including fine weaponry. At that time, stock farming and nomadic life were so developed that various and local nomadic cultures such as the Kayue, Xigdian, and Noumuhong flourished in this area. During the Bronze Age, people worked in both agriculture and animal husbandry, producing fine woolen clothes, cattleskin shoes, as well as precious stone and copper ornaments.

The skeletal remains used in this study belong to the Kayue culture dated to about 500 BC to 150 AD. These skeletons were excavated during the 1970s from the Shangsunjia (S), Lijiashan (L), and Ahatelashan (A) sites, all of which are located near the capital of the Qinghai province, Xinin. The remains are now housed in the Xian Branch of the Institute of Archaeology, Chinese Academy of Social Sciences.

The parts of the skeletal remains we examined are limited to the skull and major long bones, i.e. the humerus, ulna, radius, femur, tibia, and fibula, as shown in Table 1. No elements of the vertebral column, pelvic bones, scapulae, claviculae, and smaller hand and foot bones exist in the collection, as they were abandoned during excavation. With a few exceptions, it is impossible to identify whether a skull and long bones belong to the same individual because of lack of definitive registration documents.

The skeletal remains are well preserved and were examined by gross (visual) observation by one of the authors (S.T.). Neither X-ray examination nor microscopic observation were possible because the institute branch, used as a storage of archeological materials, is not equipped with the necessary equipment. Inflammatory changes were specifically and macroscopically recognized on the basis of such periosteal reactions as pitting, striation, and bark-like hyperostosis.

Results

In the skeletal series that we examined during the course of the present study, many remains showed evidence of pathological change including trauma (injury, fracture, and amputation), benign bone tumors, congenital abnormalities, metabolic disorders, periodontal diseases, and inflammatory lesions. In the present study, we focused on inflammatory changes that are thought to have been caused by infectious disease, particularly those that appear in the long bones. We observed a total of fifteen individuals (twelve from the S site, two from the L site, and one from the A site) with macroscopic inflammatory lesions in their lower extremities, as shown in Table 2.

Among these cases, the bone that was most often affected was the tibia. For example, in the S series, the frequencies were 4.6% (6/131) and 7.8% (10/130) in the right and left sides, respectively. All but two cases showed evidence of periostitis exhibiting slight pitting with surface striation, thin bark-like bone proliferation, and uneven plaque-like hyperostosis, all of these limited to the periosteal region.

There were two cases (M-981 and A-non-registered) diagnosed here as chronic osteomyelitis with specific pathological features. A case of an adult male from the S series (M-981, Figure 2) showed irregular sclerotic hyperostosis in the distal half of the diaphysis of both femora and the left tibia. Both femora showed slight fusiform swellings with a roughened surface in their distal parts. Particularly in the right femur, there were marked and well-circumscribed, plaque-like periosteal buildups, elevated on the irregular and sclerotic cortical surface of the distal half of the shaft (Figure 3, Figure 4).

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Figure 2. The femora of M-981 from the S series showing irregular sclerotic hyperostosis with fusiform swelling in the distal half of the diaphysis.

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Figure 3. Anterior (a) and posterior surfaces (b) of the right femur of M-981. These close-up views show marked plaque-like periosteal buildups and irregular surface with vascular impressions.

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Figure 4. Close-up view of posterior surface of the distal right femur of M-981 showing the irregular surface in detail.

With regards to the differential diagnosis of this particular case, primary osteogenic osteosarcoma, pyogenic osteomyelitis, Paget’s disease, and treponematosis should be considered (Aufderheide and Rodriguez-Martin, 1998; Mays et al., 2003). The bilateral and widespread nature of the pathological change seen in these bones of the lower extremity, however, do not usually occur except in the case of treponematosis. Primary osteogenic osteosarcoma almost exclusively involves only one bone (Suzuki, 1987), while skeletal treponematosis often appears bilaterally as in the case presented here. Pyogenic osteomyelitis may result in considerable new bone formation and is characterized with sequestrum and cloacae formation. Paget’s disease may create enlarged bones with pitted and porous surfaces; however, in the present case, which certainly appears to exhibit an infectious lesion, such a possibility may be eliminated.

The second case of chronic osteomyelitis is an isolated right tibia from the A series (Figure 5), of which there remains only the proximal three-quarters of the shaft without any registration number or individualized documentation. The remaining shaft of the tibia shows very marked hypertrophy, but the proximal joint surface is not involved and shows normal morphology.

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Figure 5. An isolated right tibia showing sclerotic swelling of the entire shaft.

The lesion on this tibia is characterized by sclerotic swelling of the entire shaft with irregular new bone proliferation and vascular impressions. The entire shaft is greatly expanded by these irregular bone growths. Visual examination through the broken distal part of the shaft revealed that the medullary cavity is filled with trabecular bone, and evidently narrowed by thickening of the cortex. As to its differential diagnosis, osteogenic osteosarcoma can be ruled out because of a lack of characteristic features of this lesion. There is neither sequestrum nor cloaca formation, which are frequently seen in hematogenous and pyogenic osteomyelitis. Furthermore, sclerosing osteomyelitis of Garré is usually characterized by remarkable sclerosing of the lesion without any cloacal opening (Suzuki, 1991); however, the presence of vascular impressions allow elimination of this possibility. Therefore, the characteristics seen in this case probably represents treponematosis.

Discussion

The two cases of chronic infectious bone changes, described above, from the Bronze Age of inland China are highly consistent with the characteristics of treponematosis. However, there are some limitations to a definitive diagnosis of these cases. One limitation is the lack of X-ray examination, particularly in the first case, which precludes determination of medullary cavity narrowing due to thickening of the cortex. However, the macroscopic observations that establish the characteristic morphologies of the lesions are considered sufficiently reliable for the diagnosis of treponematosis. Another caution is the low frequency of lesions seen in each of the three skeletal series. There were no skulls showing characteristic treponemal lesions, which is the most commonly affected site in venereal syphilis. Among the skeletal samples examined, the frequency of treponemal lesions in the femur and tibia were 0.6% and 0.5%, respectively. These frequencies are clearly lower than the percentiles of yaws or endemic syphilis previously reported (Rothschild and Heathcote, 1993).

Nevertheless, the authors are convinced that the diagnosis of these two cases is treponematosis due to the distribution of the lesions, i.e. similar bilateral lesions in the femora in the first case, and characteristic morphology of the lesion in the second case. Among the four forms of treponematosis, the two cases presented here are most likely to have resulted from (non-venereal) endemic syphilis, based on geographical and chronological evidence. Even today, using morphological, immunological, or serological evidence, the different forms of treponematosis are indistinguishable; they are essentially distinguished on the basis of epidemiological characteristics and clinical manifestations. In contrast to yaws, which mainly affects rural populations in rainforest areas where high levels of humidity and rainfall prevail, endemic syphilis is prevalent in regions with dry, hot, and temperate climates, and is endemic in rural and semi-urban communities living in low hygienic conditions (Antal et al., 2002). It used to be endemic in northern Europe, in the Balkans, Russia, southern Africa, the Middle East and eastern Mediterranean, and Mongolia. Slight improvements in personal hygiene and living standards according to social and economic improvements may alter the clinical course and transmission of endemic syphilis.

In the early stage of endemic syphilis, primary lesions are rarely seen except in the mouth and lips. Characteristic secondary lesions include a periostitis involving the long bones as in yaws. In the late stage, gummata of the nasopharynx, skin and bone (e.g. gangosa) are common and may progress to destructive chronic ulcers. The development of sabre tibia caused by chronic osteomyelitis, which resembles that seen in the second case presented in this paper, can be observed. Regarding frequency of bone involvement in endemic syphilis, bone lesions are relatively uncommon even in late stages. According to the review by Steinbock (1976), only 1.1–3.6% of cases of non-venereal syphilis exhibited bone lesion. Furthermore, unlike venereal syphilis, the cranial vault is rarely affected by non-venereal syphilis, comprising only 4% of ninety-nine cases that involved bone (Murray et al., 1956). Although the distribution and morphology of skeletal lesions of endemic syphilis are indistinguishable from those of yaws and venereal syphilis, the tibia and femur are the most commonly affected bones as seen in the above cases from ancient China.

As to the historical context of epidemiology of endemic syphilis, there are no available data on the prevalence of this condition in ancient China as well as in other parts of the world. From 1952 to 1964, the World Health Organization operated a global control program against endemic treponematoses. During initial treatment surveys, 300 million examinations were carried out. During this program more than 50 million persons with clinical and latent infections were treated in 46 countries, reducing overall disease prevalence by more than 95% (Antal and Causse, 1985). According to Meheus and Antal (1992), in the early 1980s, the global number of patients with endemic treponematoses was estimated at 2.5 million, 75% of which were children. Since that time, most national governments have ceased collecting epidemiological data on endemic treponematoses, because acknowledgement of the existence of endemic treponematoses carries the stigma of underdevelopment (Antal et al., 2002). Thus, the current extent of the disease situation is not fully known. Endemic foci in former yaws- and bejel-endemic areas remain in many parts of the world. Today, foci of endemic syphilis (bejel) still exist in the Middle East, including southeast Turkey, with high seroprevalence particularly in children under five years of age.

On the problematic issue of the origin, transformation, and prevalence of treponematosis, there are two major theories; the unitarian theory and the nonunitarian theory. The nonunitarian theory, proposed by Hackett (1963, 1967), is consistent with the evidence of treponematosis presented in this paper. According to Hackett (1967), who maintains that mutational changes account for the four different clinical patterns of human treponematosis, an initial mutation in the treponemal strain took place by about 10000 BC, transforming pinta, the first form of treponematosis, into yaws, the second form. The second mutational change occurred at around 7000 BC and changed the clinical features from those of yaws to endemic syphilis.

This new form of treponeme was adapted to a warm and arid climate and “an uninterrupted block of endemic syphilis extends from Africa through western into central Asia, comprising deserts and semi-deserts, often with nomadic populations” (Hackett, 1967: p. 159). From the map in which Hackett estimated the extent of endemic syphilis at about 7000 BC (Hackett, 1967: p. 159), the most northeastern region of prevalence corresponds to the inland parts of China including the Qinghai province. Endemic syphilis appeared at about 7000 BC, and was transmitted from the eastern Mediterranean region to inland China probably via the ancient ‘Silk Road’. In fact, the Xinjiang province, which neighbors the Qinghai province to the east, is one of the main areas of contact and movement between eastern and western populations of the Eurasian continent. One of the authors (K.H.) studied 274 skulls collected from nine ancient cemeteries in Xinjian, dating from about 1800 BC to 300 AD, and based on cranial measurement analysis, suggested that the source of racial morphological characteristics of the ancient populations of this area was not unitary and there were at least three branches of Europeans and more than one type of Asian (Han, 1994).

In Qinghai, as well as in Xinjian, there must have been racial contact between Europeans and indigenous Asians. According to studies of Chinese archeologists, the ancient culture of this area, including those of Central Asia, Qinghai, Xinjian, Kazakhstan, and the Altai, was deeply affected by and interacted with each other (Tao, 1993). In this context, treponematosis seems to have been transmitted and spread by nomadic people from the Mediterranean or the Middle East region into the central part of China which had an adequate climate for the new type of treponematosis, endemic syphilis.