Assessing diagnostic certainty for scurvy and rickets in human skeletal remains

Objectives

Identifying scurvy and rickets has important implications for understanding adaptations and variability among past communities, and bioarchaeologists now regularly evaluate these conditions. Due to the increased number of studies, cases with less clear-cut lesions and variable preservation are now frequently reported. Despite an improved understanding of the biological mechanisms for disease expression, there is a lack of consensus on the language used to express diagnostic certainty, limiting comparability. This article aims to address these issues and provide recommendations on more consistent diagnostic terminology using widely accepted diagnostic methodology based on biological mechanisms.

Materials and Methods

We review diagnostic terms used in bioarchaeology by considering published cases of rickets, scurvy and co-occurrence alongside M.B.B.'s past project notes. We also consider differences in the diagnosis of rickets and scurvy in living and archeological individuals.

Results

We provide recommendations on a framework that can be used to show diagnostic certainty in cases of rickets, scurvy, and co-occurrence. Core lesions of rickets and scurvy are used alongside a limited lexicon of diagnostic terminology based on the Istanbul protocol.

Discussion

It is not the number of lesions that determines whether an individual is assigned to a particular diagnosis category, but rather the range and expression of lesions present. Avoiding a “tick-list” approach to core lesions of these diseases will be critical to ensure that identifying rickets and scurvy continues to contribute to understanding adaptations and variability among past communities. The framework allows more consistency in diagnostic certainty, facilitating greater comparability in research.     

Probable evidence of scurvy in subadults from archeological sites in Peru

Subadult scurvy is not well documented in archeological human remains despite the existence of many biomedical references indicating that bone changes do occur in some cases and, because of this, should be observable in human burials. There are several potential reasons for this gap in our knowledge of scurvy. Not all children who suffered from scurvy died of the disease or from other causes when they had scurvy. Scurvy may not leave characteristic bone changes in every case of the disease. Some of the pathological conditions associated with scurvy have been known for many years, but these features may be rare or difficult to differentiate from other pathological conditions. Recently a lesion of the skull has been described that is probably pathognomonic for scurvy, specifically porous and sometimes hypertrophic lesions of the greater wing of the sphenoid. This lesion is bilateral and highly associated with evidence of inflammation at other anatomical sites in the skull. A survey of subadult skulls (N = 363) in the human skeletal collection from Peru at the National Museum of Natural History, Smithsonian Institution, reveals a prevalence of 10% of skulls that exhibit plausible evidence of scurvy. Some cases of scurvy also have cribra orbitalia that has been attributed to anemia. In most of the Peruvian scurvy cases, anemia is an unlikely possibility because there is no evidence of marrow hyperplasia. This highlights the need for caution in using lesions of the orbit as an indicator of anemia when there is no other evidence of this disease elsewhere in the skeleton. Anatomical evidence of scurvy offers the potential of providing new and important evidence of diet in archeological human populations.     

Scurvy in the Great Irish Famine: evidence of vitamin C deficiency from a mid-19th century skeletal population

Scurvy has increasingly been recognized in archaeological populations since the 1980s but this study represents the first examination of the paleopathological findings of scurvy in a known famine population. The Great Famine (1845-1852) was a watershed in Irish history and resulted in the death of one million people and the mass emigration of just as many. It was initiated by a blight which completely wiped out the potato-virtually the only source of food for the poor of Ireland. This led to mass starvation and a widespread occurrence of infectious and metabolic diseases. A recent discovery of 970 human skeletons from mass burials dating to the height of the famine in Kilkenny City (1847-1851) provided an opportunity to study the skeletal manifestations of scurvy-a disease that became widespread at this time due to the sudden lack of Vitamin C which had previously almost exclusively been provided by the potato. A three-scale diagnostic reliance approach has been employed as a statistical aid for diagnosing the disease in the population. A biocultural approach was adopted to enable the findings to be contextualized and the etiology and impact of the disease explored. The results indicate that scurvy indirectly influenced famine-induced mortality. A sex and stature bias is evident among adults in which males and taller individuals displayed statistically significantly higher levels of scorbutic lesions. The findings have also suggested that new bone formation at the foramen rotundum is a diagnostic criterion for the paleopathological identification of scurvy, particularly among juveniles.     

Skeletal manifestations of infantile scurvy

Recent investigations of human skeletal material from the historic St. Martin's cemetery, England, found a range of abnormal lesions in six infants that are almost certainly related to scurvy. Porous and proliferative bone lesions affecting the cranial bones and scapulae were found, and this paper presents images obtained using both macroscopic and scanning electron microscope examination of the lesions. Previous work on infantile scurvy (Ortner et al., 1997-2001) relied heavily on changes at the sphenoid, which is often missing in archaeological bone, so the identification of changes attributable to scurvy on other cranial bones and the scapulae is encouraging. The ability to recognize changes related to scurvy on a range of bones will ensure an enhanced potential for recognition of this disease in future research involving archaeological bone. Research on historical documents from Birmingham dating to the eighteenth and nineteenth centuries, combined with the probable cases of scurvy identified, supports the view that the paucity of cases of infantile scurvy from the archaeological record reflects a lack of understanding and recognition of bone manifestations, rather than a lack of occurrence in this period. Changes linked to scurvy were only found in infants from the poorer sections of the community from St. Martin's, and this is almost certainly linked to patterns of food consumption and may be related to shortages of potatoes, due to blight, experienced during this period.     

Evidence of probable scurvy in subadults from archeological sites in North America

The authors surveyed subadult human skeletons from Native American archeological sites in the United States for evidence of skeletal lesions associated with scurvy. Geographic regions surveyed include the Midatlantic area, the Southeast (Florida), the Southwest, and the Plains. The prevalence of probable subadult scurvy ranged from zero in the Plains samples to 38% in a small sample from Florida. These data indicate the likelihood that scurvy was a significant childhood disease in many Native American groups. Reasons for variation in prevalence remain speculative but include regional and seasonal variation in food types and abundance, cultural patterns of storage and utilization, periodic food shortages, and the relative importance of corn in the diet. These factors are part of a nutritional complex that is related to disease prevalence which can be studied through evidence seen in archeological human remains.     

Rib lesions in chronic pulmonary tuberculosis

The diagnosis of skeletal tuberculosis in human remains has traditionally been based upon the detection of secondary skeletal lesions which result from hemotogenous dissemination of tubercle bacilli (e.g., Pott's disease). Since such lesions develop in less than 7% of cases of human tuberculosis, the paleodemography and paleoepidemiology of this disease have been difficult to assess from skeletal remains. This study presents a new diagnostic approach to tuberculosis, focusing on the skeletal manifestations of chronic pulmonary disease (which comprises approximately 90% of human-form tuberculosis). Four hundred forty-five skeletal remains from persons dying of tuberculosis during the first half of the 20th century were examined. A total of 70/445 (16%) exhibited skeletal lesions in one or more locations as a response to infection. Of these 70, 39 (56%) were found to display a specific set of lesions restricted to the internal aspect of the ribs. These lesions take one of two forms: (1) diffuse periostitis or (2) localized abscess, and appear to correspond to areas of chronic pulmonary infection. The diffuse type of rib lesion is more commonly observed than the localized type. In our observations (and according to the natural history of tuberculosis) the occurrence of chronic pulmonary tuberculosis is usually mutually exclusive with hematogenous dissemination to secondary bone locations. Thus, the detection of rib lesions in cases of chronic pulmonary disease increases the absolute sample size of skeletal tuberculosis by a factor of two in this study.     

Brief communication: Oxygen isotopes as a biomarker for sickle‐cell disease? Results from transgenic mice expressing human hemoglobin S genes

The origins of sickle-cell disease (SCD) are well understood, as are its evolutionary pressures on humans and pathological presentation. However, because it has not been possible to identify SCD in archaeological contexts, its biocultural effects on past populations are unknown. Previous research investigating oxygen isotope fractionation during respiration among anemics suggests that oxygen isotopes in bone apatite may provide a biological marker for SCD in skeletal remains. This pilot study reports δ(18) O ratios in bone apatite of transgenic laboratory mice expressing human SCD globins and compares them to healthy control mice. The δ(18) O ratios of sick mice are significantly lower than those of healthy mice (-5.6‰ vs. -4.5‰; P = 0.002), and the sickest mice exhibit the lowest ratios of all (mean δ(18) O = -5.8‰). These preliminary results suggest that this method may be usefully applied to skeletal materials of past human populations whose diets and water sources do not differ substantially.     

Investigating the specificity of periosteal reactions in pathology museum specimens

The relationship between periosteal new bone formation and a number of infectious and metabolic conditions frequently seen in archeological human skeletal remains was investigated by studying human long bones demonstrating periosteal new bone formation archived in two London, UK, pathology museums: the St. George's Hospital Pathology Museum and the Hunterian Museum. The samples were subjected to macroscopic and radiographic analysis to determine if the characteristics of their periosteal lesions were specific to the corresponding disease states. The results demonstrated that no qualitative or quantitative characteristics of the periosteal reactions emerged that were specific to individual disease states. It was established that disease progression, rather than disease type, was the most important determinant of periosteal lesion appearance. A critical analysis of the bioarcheology literature pertaining to the recording and interpretation of periosteal reactions determined that the varied pathogenesis of periosteal new bone formation has been largely ignored in favor of a diagnosis of "nonspecific infection." Assumptions regarding the infectious etiology of periosteal lesions have become embedded into the bioarcheology literature potentially skewing the results of skeletal population-based paleoepidemiological studies.     

New approaches to the study of disease in archeological New World populations.

One of the objectives of paleopathology is to clarify the role of disease in the evolution of human groups. The recovery of DNA and immunoglobulins from archeological human skeletal tissue offers a method for enhancing and expanding our knowledge about the presence and significance of disease in past human populations. DNA also might reveal the presence of genetic disease. Immunoglobulins recovered from archeological bone indicate some of the diseases to which an individual was exposed during life. This information also provides supporting evidence for anatomical observations of skeletal disease. This is illustrated by the identification of treponemal antibody in an archeological skeleton that has gross lesions suggestive of treponematosis. Similar biochemical methods could be applied to other research problems to clarify the presence of various syndromes of the inflammatory erosive arthropathies, such as rheumatoid arthritis, in New World archeological populations. Some of these syndromes are associated with DNA sequences and specific proteins that are recoverable from archeological skeletal tissue.     

Morbidity in the marshes: using spatial epidemiology to investigate skeletal evidence for Malaria in Anglo-Saxon England (AD 410-1050)

Concerns over climate change and its potential impact on infectious disease prevalence have contributed to a resurging interest in malaria in the past. A wealth of historical evidence indicates that malaria, specifically Plasmodium vivax, was endemic in the wetlands of England from the 16th century onwards. While it is thought that malaria was introduced to Britain during the Roman occupation (AD first to fifth centuries), the lack of written mortality records prior to the post-medieval period makes it difficult to evaluate either the presence or impact of the disease. The analysis of human skeletal remains from archaeological contexts is the only potential means of examining P. vivax in the past. Malaria does not result in unequivocal pathological lesions in the human skeleton; however, it results in hemolytic anemia, which can contribute to the skeletal condition cribra orbitalia. Using geographical information systems (GIS), we conducted a spatial analysis of the prevalence of cribra orbitalia from 46 sites (5,802 individuals) in relation to geographical variables, historically recorded distribution patterns of indigenous malaria and the habitat of its mosquito vector Anopheles atroparvus. Overall, those individuals living in low-lying and Fenland regions exhibited higher levels of cribra orbitalia than those in nonmarshy locales. No corresponding relationship existed with enamel hypoplasia. We conclude that P. vivax malaria, in conjunction with other comorbidities, is likely to be responsible for the pattern observed. Studies of climate and infectious disease in the past are important for modeling future health in relation to climate change predictions.     

Tracing patterns of activity in the human skeleton: An overview of methods, problems, and limits of interpretation

Studies of patterns of activity in human skeletal remains have grown in number over the last few years. Different methods have been used to reconstruct activity patterns in past populations. In this review of the available literature the common themes of these studies have been isolated in order to show that many studies do not truly conform to the standards of the field. Inadequate sample size, too far-reaching conclusions and neglect of other possible explanations are among the problems easily recognised in the literature. Many assumptions are lacking a sound experimental basis, and it becomes increasingly evident that there are many more problems and limits of interpretations than have been usually acknowledged in the recent past. It also appears that many results, which have been interpreted in terms of sexual division of labour may, in fact, be expressions of the intrinsic sexual dimorphism of Homo sapiens and not culture- or population-specific peculiarities. Acknowledging the results of many studies from the field of sports medicine it appears doubtful that adult patterns of activity can truly be isolated from those which stem from the formative years of the human skeleton during the subadult growth period. A more cautious approach to the interpretation of data and a return to more basic research are needed to adequately address all the possibly confounding issues when trying to reconstruct patterns of activity from archaeological skeletal remains.     

Technical note: The use and misuse of threshold diagnostic criteria in paleopathology

Weighted threshold diagnostic criteria approaches have emerged for diseases that involve skeletal/bony tissue that are readily diagnosed in the field of paleopathology such as Vitamin C deficiency (scurvy), Vitamin D deficiency (rickets) and treponemal disease. These criteria differ from traditional differential diagnosis in that they involve standardized inclusion criteria based on the lesion's specificity to the disease. Here I discuss the limitations and benefits of threshold criteria. I argue that while these criteria will benefit from further revision such as inclusion of lesion severity, and the incorporation of exclusion criteria, threshold diagnostic approaches have considerable value in the future of diagnosis in the field.     

Anatomy of a serial killer: differential diagnosis of tuberculosis based on rib lesions of adult individuals from the Coimbra Identified Skeletal Collection, Portugal

The role of new bone formation on visceral surfaces of ribs in the diagnosis of tuberculosis (TB) in past human populations has been explored by many researchers, using both skeletal remains with known causes of death and archaeological samples. This study focuses, firstly, on adult skeletons from the Coimbra Identified Skeletal Collection in Portugal and investigates the skeletal manifestations of individuals known to have died from TB; secondly, this study focuses on the role of rib lesions in the diagnostic criteria for TB. One hundred and fifty-seven males and 106 females aged between 22-87 years were examined; causes of death were assigned as pulmonary TB, extrapulmonary TB, and pulmonary non-TB; a control group, extrapulmonary non-TB, was selected from the remaining individuals. Of individuals with rib lesions, 85.7% (69/81) had pulmonary or extrapulmonary TB as an assigned cause of death, while 17.8% (16/90) of individuals with rib lesions had a non-TB cause of death. Rib lesions were significantly more common in individuals who had died from TB, although the lesions cannot be considered pathognomonic for TB. In individuals dying from pulmonary TB, ribs in the central part of the rib cage were most affected, at their vertebral ends. The lower part of the rib cage may be a marker for peritoneal TB, and "coral-like" new bone formation on ribs may be an indicator of neoplastic disease. Further work on rib involvement in TB in clinical contexts, and the study of further documented skeletal collections, are recommended.     

Brief Communication: A likely case of scurvy in a rural Early Classic Maya burial from Actun Uayazba Kab,Belize

A Maya burial of a late adolescent (Burial 98‐3) found in the rockshelter entrance of Actun Uayazba Kab (AUK), Belize, displays a combination of lesions that is consistent with scurvy. Signs include large, active lesions on the posterior surfaces of maxilla; relatively mild porotic hyperostosis along the midline of the skull on the parietals and occipital; cribra orbitalia; potential pinprick lesions on the greater wings of sphenoid and temporal; reactive lesions on the palate, temporal lines of frontal and parietals, and external and internal surfaces of zygomatics; small lesions on the popliteal surfaces of both femora; and periodontal disease. Identification of scurvy at AUK potentially informs the analysis of other primary burials and scattered bone found there and at other nearby sites, which often reveal evidence of nonspecific lesions that are usually attributed to anemia and infection, but that are also consistent with scurvy. The social and ecological context of this Protoclassic (0–AD 300) individual, who lived in a rural agricultural community with no evidence of complex social hierarchy, contrasts with typical discussions of disease among the Maya, which tend to focus on the degrading effects of overcrowding and resource deficiencies. While scurvy has been largely overlooked in the Maya area, this study supports earlier arguments for its presence that were based largely on clinical and ethnographic analogies and suggests the need to incorporate scurvy into broader synergistic models of ancient health. Am J Phys Anthropol 155:476–481, 2014. © 2014 Wiley Periodicals, Inc.     

Osteological and molecular identification of Brucellosis in ancient Butrint, Albania

Ancient skeletal remains can harbor unique information about past civilizations at both the morphological and molecular levels. For instance, a number of diseases manifest in bone, some of which have been confirmed through DNA analysis, verifying their presence in ancient populations. In this study, anthropological analysis of skeletal remains from the ancient Albanian city of Butrint identified individuals with severe circular lytic lesions on their thoracic and lumbar vertebrae. Differential diagnosis suggested that the lesions resulted from pathologies known to affect these skeletal regions, such as tuberculosis (TB) or brucellosis. Relevant bones of two adolescent males from the 10th to 13th century AD that displayed the lesions, along with unaffected individuals, were collected in the field. Genetic screening of the skeletal samples for TB was repeatedly negative, thus additional testing for Brucella spp.-bacteria of livestock and the causative agent of brucellosis in humans-was conducted. Two Brucella DNA markers, the IS6501 insertion element and Bcsp31 gene, amplified from the affected vertebrae and/or ribs, whereas all unaffected individuals and control samples were negative. Subsequent DNA sequencing confirmed the presence of the brucellar IS6501 insertion element. On the basis of the skeletal lesions, negative tests for TB, and positive Brucella findings, we report a confirmed occurrence of brucellosis in archaeologically recovered human bone. These findings suggest that brucellosis has been endemic to the area since at least the Middle Ages.     

Subadult health and disease in prehistoric Tonga, Polynesia

This article focuses on the differential diagnosis of pathologic lesions recorded on the limbs and crania of 17 subadults from two pre-European burial mounds in Tonga, western Polynesia. All affected subadults were between the ages of 6 months and 3 years at death. The lesions described consist primarily of subperiosteal new bone deposition on the limbs and endocranial surface. However, the presence of cribra orbitalia in a number of individuals indicates concurrent iron-deficiency anaemia. A differential diagnosis of haematogenous osteomyelitis, congenital syphilis, yaws, scurvy, hypervitaminosis A, trauma, Caffey's disease, and iron-deficiency anaemia is discussed. It was concluded that the most likely cause for the lesions observed is a synergistic relation between infection (weanling diarrhoea, yaws) and metabolic disease (scurvy and possibly hypervitaminosis A). Trauma is not ruled out as contributing to the development of some pathologic lesions. It is concluded that, in the Pacific Islands at least, multiple causes for skeletal pathology in subadults should be considered rather than a single aetiology.     

Maxillary sinusitis as an indicator of respiratory health in past populations

Chronic infectious respiratory disease in a past human population is investigated through the quantification of maxillary sinusitis among Iroquoian horticulturists. Three hundred forty-eight right and left maxillae of a Southern Ontario Iroquoian skeletal sample, Uxbridge Ossuary, ca. AD 1440, were examined for evidence of chronic infection (minimum number of individuals = 207: 114 adults, 22 adolescents, 38 juveniles and 33 infants). Modern clinical criteria were applied to differentiate lesions of respiratory and dental origin. Osseous lesions of the maxillary sinuses were observed in 50% of the individuals examined. These lesions are morphologically consistent with nonspecific lesions observed in other past populations that have been attributed to the presence of pathogens. The prevalence of maxillary sinusitis increases with age. Osseous changes suggestive of maxillary sinusitis of respiratory origin are at a maximum prevalence in juveniles and adolescents. In adults, infection of dental origin becomes a confounding factor in the identification of sinusitis of respiratory origin. Fifteenth century Iroquoians were experiencing high airborne pathogen levels and poor indoor air quality. The prevalence of maxillary sinusitis and the exploration of the origin of tissue injury may contribute to our reconstruction of the quality of life and the respiratory health status of past human populations.     

Current Status and Challenge of Pseudorabies Virus Infection in China

Pseudorabies(PR), also called Aujeszky's disease, is a highly infectious disease caused by pseudorabies virus(PRV).Without specific host tropism, PRV can infect a wide variety of mammals, including pig, sheep, cattle, etc., thereby causing severe clinical symptoms and acute death. PRV was firstly reported in China in 1950 s, while outbreaks of emerging PRV variants have been documented in partial regions since 2011, leading to significant economic losses in swine industry.Although scientists have been devoting to the design of diagnostic approaches and the development of vaccines during the past years, PR remains a vital infectious disease widely prevalent in Chinese pig industry. Especially, its potential threat to human health has also attracted the worldwide attention. In this review, we will provide a summary of current understanding of PRV in China, mainly focusing on PRV history, the existing diagnosis methods, PRV prevalence in pig population and other susceptible mammals, molecular characteristics, and the available vaccines against its infection.Additionally, promising agents including traditional Chinese herbal medicines and novel inhibitors that may be employed to treat this viral infection, are also discussed.     

Bioarchaeological research in Croatia--a historical review

The study of human skeletal remains from archaeological sites gives us the opportunity to answer important questions about the lifestyle of past populations. The discipline that studies human skeletal remains is known as bioarchaeology. This paper provides a historical review of bioarchaeological research in Croatia. It is based on the available published material that analyzes human skeletal remains from archaeological sites located on the Croatian territory covering time span from the Neolithic period to the late Middle Ages.