The evolution of disease: anthropological perspectives on epidemiologic transitions.

BACKGROUND: The model of epidemiologic transitions has served as a guiding framework for understanding relationships between patterns of human health and disease and economic development for the past several decades. However, epidemiologic transition theory is infrequently employed in epidemiology. OBJECTIVE: Moving beyond Omran's original formulation, we discuss critiques and modifications of the theory of epidemiologic transitions and highlight some of the ways in which incorporating epidemiologic transition theory can benefit theory and practice in epidemiology. DESIGN: We focus on two broad contemporary trends in human health that epidemiologic transition theory is useful for conceptualizing: the increased incidence of chronic inflammatory diseases (CIDs), such as allergic and autoimmune diseases, and the emergence and reemergence of infectious disease. RESULTS: Situating these trends within epidemiologic transition theory, we explain the rise in CIDs with the hygiene hypothesis and the rise in emerging and reemerging infections with the concept of a third epidemiologic transition. CONCLUSIONS: Contextualizing these trends within epidemiologic transition theory reveals implications for clinical practice, global health policies, and future research within epidemiology.

Brain evolution, the determinates of food choice, and the omnivore's dilemma.

A coevolutionary paradigm using a biocultural perspective can help to unravel the complex interactions that led to the contemporary pattern of eating. Evolutionary history helps to understand the adaptation of diet and its nutritional implications. Anatomical and behavioral changes linked to changing dietary patterns in the Paleolithic resulted in an adaptive framework that affects modern diet. The evolution of an expanding brain, a shrinking large intestine, and lengthening small intestine necessitated a demand for nutritionally dense foods. The key to these changes is an understanding of the response to the omnivore's dilemma. Omnivores in their search for new items to feed their varied diet (neophilia) have a challenge when they fear (neophobia) novel items that may be poisonous and can cause death. The inborn mechanism initiates palate fatigue (sensory-specific satiety) ensuring a variety of foods will be eaten. Variety will limit the impact of toxins ingested and provide a more balanced diet. The development of cuisine, a momentous event in history, mediated the conflict, and changed the course of human evolution. The cuisine, a biocultural construct, defines which items found in nature are edible, how these products are transformed into food, the flavors used to add a sensory dimension to foods, and rules of eating or etiquette. Etiquette defines how, when, and with whom we eat. Patterns of eating in the modern setting are the end product of the way that Homo sapiens evolved and resolved the omnivore's dilemma. Control of fire and cooking expanded the range of available foods by creating a class of foods that are "predigested." An essential element to the evolution of the human diet was the transition to agriculture as the primary mode of subsistence. The Neolithic revolution dramatically narrowed the dietary niche by decreasing the variety of available foods, with the shift to intensive agriculture creating a dramatic decline in human nutrition. The recent industrialization of the world food system has resulted in a nutritional transition in which developing nations are simultaneously experiencing undernutrition and obesity. In addition, an abundance of inexpensive, high-density foods laden with sugar and fats is available to a population that expends little energy to obtain such large numbers of calories. Furthermore, the abundant variety of ultraprocessed foods overrides the sensory-specific satiety mechanism leading to overconsumption.

Analysis of nutritional disease in prehistory: The search for scurvy in antiquity and today.

In this paper, we discuss the issues surrounding the study of scurvy, or vitamin C deficiency, in paleopathology, and highlight the work of Donald Ortner in advancing this area of research. This micronutrient deficiency impacts collagen formation and results in damage to a variety of bodily tissues. While clinical manifestations are observed routinely, the lack of specific signatures on bone makes paleopathological diagnosis difficult. Rapid growth in infants, children, and subadults provides abundant remodeled tissue and an increase in vascularization that makes identification possible in younger segments of the population. However, diagnosis of scurvy in adults remains problematic, given that diagnostic lesions are strikingly similar to those associated with rickets, osteomalacia, and other conditions. We argue that this confounding factor underscores the need for a broader anthropological approach to scurvy research that expands beyond differential diagnosis to include more accurate reconstruction of diets and available resources, greater consideration of the possibility - even likelihood - of multiple nutrient deficiencies simultaneously affecting an individual, and the patterning of these deficiencies along lines of status, sex, and age.

Genomics, the origins of agriculture, and our changing microbe-scape: time to revisit some old tales and tell some new ones.

Though agriculture is often viewed as one of humanity's crowning achievements, skeletal evidence indicates that dependence on domesticated plants and animals was accompanied by an increase in infectious disease. Scientists have proposed that many important infections emerged in the period following the advent of agriculture, as a result of newly dense populations and novel proximity to domestic animals that served as reservoirs for novel pathogens. Here, we review genomic evidence regarding pathogen origins, analyzing these data using the epidemiological transition framework. Genetic information has forced us to reconsider how and when many important pathogens emerged; it appears that a number of infections thought to result from contact with domesticated animals arose much earlier than agriculture was adopted. We also consider the broader effect of agriculture upon the microbiome, exploring potential consequences for human health. We end by discussing the changes in the human microbe-scape we are likely to see in the future.

Diet, residential origin, and pathology at Machu Picchu, Peru.

Pathological conditions in human skeletal remains provide a wealth of information about archaeological populations, but many are limited in their interpretive significance by their nonspecific etiologies. This study analyzes three common pathological conditions known to manifest in infancy and childhood in the skeletal population from Machu Picchu, Peru (N = 74) with published carbon, nitrogen, oxygen, strontium, and lead isotopic data (Turner et al.: J Archaeol Sci 36 (2009) 317-332; Turner et al.: Chungara: Revista de Antropología Chilena 42 (2010) 515-524) to distinguish early-life diet from residential origins as significantly associated with pathologies among the site's inhabitants. Analyses of variance indicate highly significant variation between enamel δ(18)O values, which serve as a rough proxy of local environment, and both cribra orbitalia (CO) and porotic hyperostosis (PH), generally understood to be markers of anemia. Results tentatively suggest that individuals manifesting these lesions may have lived closer to the arid coasts; however, no significant variation was found in parameters of diet (enamel δ(13) C(carbonate), dentin δ(13) C(collagen), dentin δ(15)N) by either CO or PH, suggesting that the primary factors causing anemia may have been more significantly related to residential origin rather than diet. Linear enamel hypoplasia (LEH) frequency significantly varied by both dietary and residential parameters, supporting models of LEH formation from a synergy of dietary and environmental factors. These results support previous research on the etiology of PH in the Andes; they also represent a useful approach to refining site-specific interpretations of pathological conditions in archaeological populations, and exploring etiological variation between populations.

The science behind pre-Columbian evidence of syphilis in Europe: research by documentary.

This article discusses the presentation of scientific findings by documentary, without the process of peer review. We use, as an example, PBS's "The Syphilis Enigma," in which researchers presented novel evidence concerning the origin of syphilis that had never been reviewed by other scientists. These "findings" then entered the world of peer-reviewed literature through citations of the documentary itself or material associated with it. Here, we demonstrate that the case for pre-Columbian syphilis in Europe that was made in the documentary does not withstand scientific scrutiny. We also situate this example from paleopathology within a larger trend of "science by documentary" or "science by press conference," in which researchers seek to bypass the peer review process by presenting unvetted findings directly to the public.

Treponema pallidum infection in the wild baboons of East Africa: distribution and genetic characterization of the strains responsible.

It has been known for decades that wild baboons are naturally infected with Treponema pallidum, the bacterium that causes the diseases syphilis (subsp. pallidum), yaws (subsp. pertenue), and bejel (subsp. endemicum) in humans. Recently, a form of T. pallidum infection associated with severe genital lesions has been described in wild baboons at Lake Manyara National Park in Tanzania. In this study, we investigated ten additional sites in Tanzania and Kenya using a combination of macroscopic observation and serology, in order to determine whether the infection was present in each area. In addition, we obtained genetic sequence data from six polymorphic regions using T. pallidum strains collected from baboons at two different Tanzanian sites. We report that lesions consistent with T. pallidum infection were present at four of the five Tanzanian sites examined, and serology was used to confirm treponemal infection at three of these. By contrast, no signs of treponemal infection were observed at the six Kenyan sites, and serology indicated T. pallidum was present at only one of them. A survey of sexually mature baboons at Lake Manyara National Park in 2006 carried out as part of this study indicated that roughly ten percent displayed T. pallidum-associated lesions severe enough to cause major structural damage to the genitalia. Finally, we found that T. pallidum strains from Lake Manyara National Park and Serengeti National Park were genetically distinct, and a phylogeny suggested that baboon strains may have diverged prior to the clade containing human strains. We conclude that T. pallidum infection associated with genital lesions appears to be common in the wild baboons of the regions studied in Tanzania. Further study is needed to elucidate the infection's transmission mode, its associated morbidity and mortality, and the relationship between baboon and human strains.

The origin and antiquity of syphilis revisited: an appraisal of Old World pre-Columbian evidence for treponemal infection.

For nearly 500 years, scholars have argued about the origin and antiquity of syphilis. Did Columbus bring the disease from the New World to the Old World? Or did syphilis exist in the Old World before 1493? Here, we evaluate all 54 published reports of pre-Columbian, Old World treponemal disease using a standardized, systematic approach. The certainty of diagnosis and dating of each case is considered, and novel information pertinent to the dating of these cases, including radiocarbon dates, is presented. Among the reports, we did not find a single case of Old World treponemal disease that has both a certain diagnosis and a secure pre-Columbian date. We also demonstrate that many of the reports use nonspecific indicators to diagnose treponemal disease, do not provide adequate information about the methods used to date specimens, and do not include high-quality photographs of the lesions of interest. Thus, despite an increasing number of published reports of pre-Columbian treponemal infection, it appears that solid evidence supporting an Old World origin for the disease remains absent.

Stature and robusticity during the agricultural transition: evidence from the bioarchaeological record.

The population explosion that followed the Neolithic revolution was initially explained by improved health experiences for agriculturalists. However, empirical studies of societies shifting subsistence from foraging to primary food production have found evidence for deteriorating health from an increase in infectious and dental disease and a rise in nutritional deficiencies. In Paleopathology at the Origins of Agriculture (Cohen and Armelagos, 1984), this trend towards declining health was observed for 19 of 21 societies undergoing the agricultural transformation. The counterintuitive increase in nutritional diseases resulted from seasonal hunger, reliance on single crops deficient in essential nutrients, crop blights, social inequalities, and trade. In this study, we examined the evidence of stature reduction in studies since 1984 to evaluate if the trend towards decreased health after agricultural transitions remains. The trend towards a decrease in adult height and a general reduction of overall health during times of subsistence change remains valid, with the majority of studies finding stature to decline as the reliance on agriculture increased. The impact of agriculture, accompanied by increasing population density and a rise in infectious disease, was observed to decrease stature in populations from across the entire globe and regardless of the temporal period during which agriculture was adopted, including Europe, Africa, the Middle East, Asia, South America, and North America.

Irrigation and infection: the immunoepidemiology of schistosomiasis in ancient Nubia.

Schistosomiasis has been deemed "the most important water-based disease from a global public-health perspective" in modern populations. To better understand the burden of schistosomiasis in ancient populations, we conducted immunologic examinations of desiccated tissue samples from two ancient Nubian populations, Wadi Halfa (N = 46) and Kulubnarti (N = 191). Saqia irrigated agriculture increases the available habitat for the aquatic vector snails and the risk of exposure. On the basis of evidence regarding the impact of saqia irrigation on schistosomiasis prevalence and transmission in modern populations, we predicted that the prevalence of Schistosoma mansoni infection would be higher in Wadi Halfa (saqia irrigation) than Kulubnarti (annual flooding). We also predicted that peak infection prevalence would occur at an earlier age within the Wadi Halfa population than the Kulubnarti population and that in both populations the prevalence of schistosomiasis would be higher in males than females due to differential water contact. The prevalence of S. mansoni was greater in the Wadi Halfa population (26.1%) than at Kulubnarti (9.4%) (P = 0.002). However, peak prevalence of infection did not occur in a younger age category within the Wadi Halfa population; prevalence of infection peaked at 66.7% in the mature adult age group (46+ years) in the Wadi Halfa population and at 16% in the later child age group (6-10 years) in the Kulubnarti population. There were no statistically significant differences in prevalence between males and females of either population. The impact of human alteration of the environment on the transmission of schistosomiasis is clearly shown in these populations.

The changing disease-scape in the third epidemiological transition.

The epidemiological transition model describes the changing relationship between humans and their diseases. The first transition occurred with the shift to agriculture about 10,000 YBP, resulting in a pattern of infectious and nutritional diseases still evident today. In the last two centuries, some populations have undergone a second transition, characterized by a decline in infectious disease and rise in degenerative disease. We are now in the throes of a third epidemiological transition, in which a resurgence of familiar infections is accompanied by an array of novel diseases, all of which have the potential to spread rapidly due to globalization.

Brief communication: Mass spectroscopic characterization of tetracycline in the skeletal remains of an ancient population from Sudanese Nubia 350-550 CE.

Histological evidence of tetracycline use has been reported in an ancient X-Group population (350-550 CE) from Sudanese Nubia (Bassett et al., 1980). When bone samples were examined by fluorescent microscopy under UV light at 490 A yellow-green fluorophore deposition bands, similar to those produced by tetracycline, were observed, suggesting significant exposure of the population to the antibiotic. These reports were met skeptically with claims that the fluorescence was the result of postmortem taphonomic infiltration of bacteria and fungi. Herein, we report the acid extraction and mass spectroscopic characterization of the antibiotic tetracycline from these samples. The bone samples were demineralized in anhydrous hydrogen fluoride which dissolved the bone-complexed tetracycline, followed by isolation by solid phase extraction on reverse-phase media. Chemical characterization by high pressure liquid chromatography mass-spectroscopic procedures showed that the retention times and mass spectra of the bone extract were identical to tetracycline when treated similarly. These results indicate that a natural product tetracycline was detectable within the sampled bone and was converted to the acid-stable form, anhydrotetracycline, with a mass + H of 427.1 amu. Our findings show that the bone sampled is labeled by the antibiotic tetracycline, and that the NAX population ingested and were exposed to tetracycline-containing materials in their dietary regime.

The sequence of the acidic repeat protein (arp) gene differentiates venereal from nonvenereal Treponema pallidum subspecies, and the gene has evolved under strong positive selection in the subspecies that causes syphilis.

Despite the completion of the Treponema pallidum genome project, only minor genetic differences have been found between the subspecies that cause venereal syphilis (ssp. pallidum) and the nonvenereal diseases yaws (ssp. pertenue) and bejel (ssp. endemicum). In this paper, we describe sequence variation in the arp gene which allows straightforward differentiation of ssp. pallidum from the nonvenereal subspecies. We also present evidence that this region is subject to positive selection in ssp. pallidum, consistent with pressure from the immune system. Finally, the presence of multiple, but distinct, repeat motifs in both ssp. pallidum and Treponema paraluiscuniculi (the pathogen responsible for rabbit syphilis) suggests that a diverse repertoire of repeat motifs is associated with sexual transmission. This study suggests that variations in the number and sequence of repeat motifs in the arp gene have clinical, epidemiological, and evolutionary significance.

On the origin of the treponematoses: a phylogenetic approach.

BACKGROUND: Since the first recorded epidemic of syphilis in 1495, controversy has surrounded the origins of the bacterium Treponema pallidum subsp. pallidum and its relationship to the pathogens responsible for the other treponemal diseases: yaws, endemic syphilis, and pinta. Some researchers have argued that the syphilis-causing bacterium, or its progenitor, was brought from the New World to Europe by Christopher Columbus and his men, while others maintain that the treponematoses, including syphilis, have a much longer history on the European continent. METHODOLOGY/PRINCIPAL FINDINGS: We applied phylogenetics to this problem, using data from 21 genetic regions examined in 26 geographically disparate strains of pathogenic Treponema. Of all the strains examined, the venereal syphilis-causing strains originated most recently and were more closely related to yaws-causing strains from South America than to other non-venereal strains. Old World yaws-causing strains occupied a basal position on the tree, indicating that they arose first in human history, and a simian strain of T. pallidum was found to be indistinguishable from them. CONCLUSIONS/SIGNIFICANCE: Our results lend support to the Columbian theory of syphilis's origin while suggesting that the non-sexually transmitted subspecies arose earlier in the Old World. This study represents the first attempt to address the problem of the origin of syphilis using molecular genetics, as well as the first source of information regarding the genetic make-up of non-venereal strains from the Western hemisphere.

Evolutionary, historical and political economic perspectives on health and disease.

The origin and rise of social inequalities that are a feature of the post-Neolithic society play a major role in the pattern of disease in prehistoric and contemporary populations. We use the concept of epidemiological transition to understand changing ecological relationships between humans, pathogens and other disease insults. With the Paleolithic period as a baseline, we begin with ecological and social relationships that minimized the impact of infectious disease. Paleolithic populations would have retained many of the pathogens that they shared with their primate ancestors and would have been exposed to zoonoses that they picked up as they adapted to a foraging existence. The sparse mobile populations would have precluded the existence of endemic infectious disease. About 10,000 years ago, the shift to an agricultural subsistence economy created the first epidemiological transition, marked by the emergence of infections, a pattern that has continued to the present. Beginning about a century ago, some populations have undergone a second epidemiological transition in which public health measures, improved nutrition and medicine resulted in declines in infectious disease and a rise in non-infectious, chronic and degenerative diseases. Human populations are entering the third epidemiological transition in which there is a reemergence of infectious diseases previously thought to be under control, and the emergence of novel diseases. Many of the emerging and reemerging pathogens are antibiotic resistant and some are multi-antibiotic resistant. Inequality continues to widen within and between societies, accelerating the spread of emerging and reemerging diseases.

Evolution of infectious disease: A biocultural analysis of AIDS.

The evolution of infectious disease can be understood from an ecological model that incorporates information from anthropology, epidemiology, and biomedicine. This model considers variables such as the pathogen, the host population, and the environment. In this model, the role that culture as well as other environmental variables plays in the transmission of infectious disease in human populations is considered. In addition, the sociocultural response and its impact on the disease process can be analyzed. The present AIDS epidemic is placed in an ecological and evolutionary context of the disease in hominid evolution. The interaction between Human Immunodeficiency Virus (HIV) and human populations is considered in this perspective. The ability of the virus to survive in semen and blood both increases as well as limits the possibility of transmission. Cultural practices that increase the transmission of blood and semen or increase sexual activity will obviously increase the potential risk of viral transmission. In societies that practice exchange of blood, blood transfusion, and where vaccinations with unclean needles exist or where there is intravenous (IV) drug use, the transmission of HIV by blood is enhanced. HIV which can cause a breakdown of the immunological system is paradoxically a very fragile pathogen. Replication occurs within T-cells, an important part of the immunological system. Outside of the blood or semen the virus dies quickly. From the perspective of the pathogen's adaptation, the virus has effectively solved the problem of survival. The fragile virus's long incubation period and its ability to survive in the presence of antibodies help to assure its transmission. HIV's ability to suppress the immunological system may assure its immediate survival, but this adaptation may cause the death of its host from other opportunistic pathogens that are usually not lethal.