5 курс / Пульмонология и фтизиатрия / Clinical_Tuberculosis_Friedman_Lloyd_N_,_Dedicoat

Introduction

Evidence for the presence of TB in the past The antiquity of TB from a global perspective Humans, urbanization, and industrialization Historical and pictorial data

Biomolecular evidence for TB from ancient skeletal remains Overview of data from ancient human remains

TB in the nineteenth and twentieth centuries Conclusion

Acknowledgments References

INTRODUCTION

Tuberculosis is now a conquered disease in the British Isles and the rest of the industrialised world.1

How wrong can one be? In the late 1980s, we thought that ­tuberculosis (TB) was an infection that had been controlled and almost eradicated from the developed world. However, emergence and re-emergence of infectious diseases plague the developed and the developing world today, and the medical profession struggles to cope.2 In 2016, there were 10.4 million people who fell ill with TB, with 1.7 million dying from the disease; 40% of HIV deaths were due to TB. TB is the ninth leading cause of death worldwide and the leading cause from a single infectious agent.3 However, TB has the potential to “develop frequency rates with the status of the ‘big killer’ again” as we live through the twenty-first century.4

TB was as important in our ancestors’ world as it is today; of course, the difference between past and present is that, in theory, we now have drugs to successfully treat the disease, health education programs to prevent TB from occurring, and mechanisms and infrastructure to ensure that poverty is not a precursor to the development of the infection. However, having coping mechanisms does not mean that TB will be controlled. In some respects, they can complicate the situation; one could argue that because one of the major predisposing factors for TB is poverty, if poverty

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could be alleviated then TB would decline, as would many other diseases.5

Our ancestors perhaps may have been in a better position to combat TB, assuming they recognized that poverty led to infection. They certainly did not have to deal with one of the key predisposing factors today—human immunodeficiency virus (HIV),6 or so we assume. Today, the combination of poverty, HIV, and drug resistance makes for a challenging and terrifying situation for many people. The cause of TB, its associated stigma, and the different political regimes and cultures around the world can vary considerably, which then affects the treatments provided, the opportunity for access to and uptake of those treatments and their effectiveness, alongside implementation of preventive measures.7,8 We also have to consider the possibility that treatment outcomes for men, women, and children with TB (or any health problem) may be different.9

Here, we focus on the long history of TB as seen mainly in skeletal remains from archeological sites. First, we will consider the primary evidence for TB in the past—in the remains of people themselves—chart the distribution of the infection through time from a global perspective, and consider historical data for the presence of the disease in the distant past. We will also examine remarkable new developments from biomolecular analyses of the tubercle bacillus in human remains that are currently illuminating aspects of the history of TB. Finally, we argue that looking at TB from a deep-time perspective can aid in understanding the problem today.

EVIDENCE FOR THE PRESENCE OF TB

IN THE PAST

Scholars studying TB in our ancestors draw on a number of sources. The primary evidence derives from people themselves (Figure 1.1) who were buried in cemeteries throughout the world that have been excavated over the years and that contribute to the understanding of humankind’s long history. Bioarcheologists study human remains, with paleopathology specifically focused on the study of ancient disease. Secondary sources of evidence “flesh out” the skeletal remains that we study. For example, we might consider historical sources that document TB frequency at particular points in time in specific parts of the world—something we cannot glean from the skeletal remains. Written accounts will also tell us something about whether attempts were made to treat TB and how. Illustrations in texts may indicate that the infection was present in the population and also show the deformity and/ or disability that accompanied it. The following sections consider this evidence in more detail, highlighting the strengths and limitations of our data.

Diagnosis of TB in skeletal and mummified remains

Being able to securely identify TB in human remains excavated from an archeological site proves the presence of the disease in a population. This compares with a written description of the infection whose signs and symptoms may be confused with other respiratory diseases.10 Although historical sources may provide us with more realistic estimates of TB frequency in the past, we have to be sure that the diagnosis was precise. We would argue that this is not always possible.

It has been suggested that in the 1940s and 1950s, the skeletal structure was affected in approximately 3%–5% of people with pulmonary TB (PTB), but this rose to around 30% for extrapulmonary TB.11 In a recent study it was found that today more skeletal TB is being seen. This is because people are living longer due to long-term antibiotic use. This gives more time for lesions to develop.12 The spine is most affected, with the hip and knee

Figure 1.1  Skeleton in the ground before excavation.

being common joints that are involved. Skeletal damage is the end result of post-primary TB spreading hematogenously or via the lymphatic system to the bones. Without biomolecular analysis, we cannot identify TB in the skeletons of those people who suffered primary TB. Initial introduction of TB into a population will also lead to high and rapid mortality because of the lack of previous exposure; no bone damage would be expected. As time goes by and generations have been exposed to TB, we might expect to see it in their skeletons. In humans, TB caused by

Mycobacterium tuberculosis and Mycobacterium bovis can cause skeletal damage, but there are suggestions that the latter is much more likely to do this.13 Skeletal evidence indicates a chronic longterm process that people could have endured for many years, also suggesting that they had a relatively robust immune system.14 However, diagnosis of TB in skeletal remains can be challenging. Unambiguous pathological lesions have to be distinguished from normal skeletal variants and changes due to post-mortem damage. Some circumstances, such as very dry, waterlogged, and frozen environments, may preserve whole bodies very well.15 If soft tissues are preserved (e.g. in mummies), the potential amount of retrievable data can be impressive, and diagnosis of disease can be easier. Nevertheless, most archeological evidence for TB is gathered from skeletons rather than from preserved bodies.

Disease can affect the skeleton only in two ways, through bone formation and in bone destruction, although both can be found together. In studies of paleopathology, such changes are recorded for each bone of the skeleton, their distribution pattern noted and differential diagnoses provided. Because the skeleton can react only in limited ways to disease, the same changes can occur with different diseases. This is why providing a detailed description of the lesions and a list of possible differential diagnoses, based on the presence and distribution of the lesions (and clinical information), is essential if diagnoses are to be verified and/or re-evaluated in the future. This point is emphasized repeatedly.14,16–19 Recognition of TB relies mainly on the presence of destructive lesions in the spine, termed Pott’s disease after Percivall Pott, the nineteenth-century physician who first described the changes. The bacilli focus on the red bone marrow, and there is gradual destruction of the bony tissue. Jaffe11 indicates that 25%–50% of people with skeletal TB will develop spinal changes. Once the vertebral integrity is lost, the structure collapses and angulation (kyphosis) of the spine develops (Figure 1.2), sometimes followed by fusion of vertebrae (ankylosis).

Other parts of the skeleton may also be affected, for example, the hip and knee joints (Figure 1.3), and non-specific changes can occur that may be related to TB (e.g., new bone formation on ribs: Figure 1.4).20–24

Most paleopathologists will diagnose TB using spinal evidence. However, it is not possible to detect all people with TB using this approach. Over the last 25 years or so, methods developed in biomolecular science have been applied to the diagnosis of disease in skeletal and mummified remains. This approach, discussed in more detail later in this chapter, includes considering the remains of a human without any evidence of disease who may have died before bone damage, as well as remains with pathological changes. TB has been the main focus of ancient biomolecular studies, with its diagnosis based upon identifying ancient DNA (aDNA) and mycolic acids of the tubercle bacillus.25,26 Although

Figure 1.2  Spinal tuberculosis in a 17th century English person buried at Abingdon Abbey, Oxfordshire.

there can be inevitable problems of survival and then extraction of ancient biomolecules from human remains,27 this new line of evidence alongside modern genomic data indicating susceptibility and resistance genes has already significantly revised our models of human–pathogen (TB) co-evolution.28,29

Historical and pictorial data

We are not historians or art historians, and therefore we are not trained in the analysis and interpretation of texts and illustrations related to the history of disease and medicine.

Figure 1.4  New bone formation on the visceral (internal) surface of ribs (a non-specific bone change possibly related to TB of the lungs).

Even so, we recognize that historical sources can generate interpretative problems. The signs and symptoms of TB may include shortness of breath, coughing up blood, anemia and pallor, fatigue, night sweats, fever, pain in the chest, and the effects of associated skeletal changes (e.g., kyphosis of the back and paralysis of the limbs). Clearly, all these features, visible to an author or artist, could be associated with other health problems. For example, pallor may be seen in anemia, shortness of breath in chronic bronchitis, and coughing up blood in cancer of the lung. Likewise, kyphotic deformities of the back may be the result of osteoporosis of the spine or trauma. Biases abound in written sources including the interpretation of causes of death rates said to reflect TB. For example, Hardy30 reminds us that because TB was associated with stigma in the nineteenth century, it was not always recorded as a cause of death. In addition, people could have had more than one condition contributing to their death, and we must not assume that those who diagnosed disease in the past were competent to make a correct diagnosis. Even today, some causes listed on death certificates may not be correct.31 Despite these problems, we will consider some of this evidence following our discussion of skeletal data.

Figure 1.3  Probable joint tuberculosis (knee joint).

THE ANTIQUITY OF TB FROM A

GLOBAL PERSPECTIVE

Before embarking on a temporal and global perspective of TB, we should emphasize that North America and parts of Europe have received much more archeological attention than many other parts of the world.32 There are many regions into which paleopathologists have not yet ventured and, therefore, evidence for TB is, to date, absent from these areas. This does not mean that the disease did not exist there in the past, just that the evidence has not been sought (or excavated). This presents a challenge to scientists who wish to trace and map the origin, evolution, and transmission of TB globally. With this caveat in mind, we first consider the factors that were probably important in the development of TB in past human populations.

What led to TB appearing in human populations?

EVIDENCE RELATING TO ANIMALS AND DOMESTICATION

If we think about farming and domestication in the Near East, domesticated sheep and goats were present by 8000 bc; by 6500 bc, this situation had occurred in Northern Europe, the Mediterranean, and India.33

In the New World, domestication is believed to have been established in Central Mexico by 2700 bc, in the eastern United States by 2500 bc, and in the South Central Andes in South America by 2500 bc.34 Assuming that domesticated animals were infected by TB, and if animal to human transmission is accepted, a potential for transmission was clearly present. However, prior to domestication, hunter-gatherers could have contracted the disease through capture, butchery, and consumption of their (wild) kill. Corroborative data from Kapur et al.35 suggest that mycobacterial species first appeared 15,000–20,000 years ago, long before domestication, and while this work has been debated as to its authenticity, Rothschild et al.36 have revealed M. tuberculosis complex aDNA in the remains of an extinct, long-horned bison from North America dated to 15,870 (±230 years) bc. Brosch et al.37 have furthermore indicated, based upon the genomic structure of tubercle bacilli, that M. tuberculosis did not evolve from M. bovis. Other researchers suggest that TB is the culmination of a global history originating in Africa, thereby affecting our hominine ancestors and extending more than 3 million years in the Old World.38 Clearly from the genomic data it has been found that different phylogenetic lineages of Mycobacterium tuberculosis complex (MTBC) are associated with different geographic regions. These data will further help elucidate the long history of co-evolution of TB in humans and other animals.39

HUMANS, URBANIZATION, AND

INDUSTRIALIZATION

Today, transmission of the human form of TB requires close contact with those infected. Because earlier peoples lived in small, mobile groups, they seldom formed settled communities.40 With the development of agriculture, population density increased rapidly, thus enabling density-dependent diseases such as TB to flourish. Even so, it was not until the 1100s AD in North America and the late medieval period (twelfth to sixteenth centuries ad) in Europe that the disease really increased.4

During this period in Europe, conditions were ideal for a marked increase in TB. Poverty, the development of trade, and the migration of people from rural communities to urban centers (usually for work) enabled the transmission of TB to previously unexposed people. In addition, working with animals and their products also may have exposed populations to the infection. For example, processing animal skins in the tanning industry, working with bone and horn, and processing food products from animals all placed people at risk for the infection. Working in industries that produced particulate pollution, such as in the textile trade,

also irritated the lungs and probably predisposed people to TB. The post-medieval period and the Industrial Revolution provided potentially explosive conditions for TB. Of special interest here is the suggestion that people who have been urbanized for a long time become resistant to TB through natural selection.41 This may explain part of the decline of TB starting in the late nineteenth and early twentieth centuries.42

We might also ask what people consumed in the past and whether their diet was balanced and nutritious. Quality of diet affects immune systems and how strong their resistance is to infection. If people become malnourished, they are more susceptible to TB; for example, iron and protein are important for immune function and infection outcome in TB, and diet may influence the potential for TB to disseminate from the lungs to the skeleton.43 Skeletal and dental evidence suggests that health tends to deteriorate with increasing social complexity and the development of agriculture,44–46 when diets were less varied. People ate less protein, which is needed to produce antibodies to fight infection, and wheat lacks certain amino acids.

As is the case today, many risk factors would have influenced the prevalence of TB in the past, especially population density and poverty. Animals—initially thought to have been central to the development and maintenance of TB in humans—prob- ably became a key factor more recently, rather than at the time of domestication (see Chapter 22).

Skeletal remains from the Old World

It can be argued that archeological human remains are the primary evidence for estimating the timing of TB’s first appearance, but it is emphasized that biomolecular models predict co-evolution over a much longer time period when compared with the skeletal evidence for the disease.35,38 We can define the Old World as the world that was known before a European presence in the Americas, comprising Europe, Asia, and Africa.47 Most of the evidence of TB in human remains in the Old World comes from Europe, reflecting the intensity of study by paleopathologists compared with the rest of the Old World (Figure 1.5).48 In some areas, this may be due to non-survival of human remains, non-excavation and/or analysis, and particular funerary rites that do not preserve remains well.4 However, those Old World areas with no evidence may truly be areas with no TB in the past. We can divide the extant data into three broad areas in the Old World, which reflect similar climatic and environmental features: the Mediterranean, Northern Europe, and Asia and the Pacific islands.

THE MEDITERRANEAN

Italy has some of the earliest evidence of skeletal TB in the world, although earlier evidence has been recently reported for Northern Europe (see the next section). A female skeleton aged around 30 years at death is dated to 3800 (±90) bc and comes from the Neolithic cave of Arma dell’Aquila in Liguria,49 and a child who lived 4500 years ago with probable TB has been found more recently in Pollera Cave, also in Liguria.50 In the Near East, there are early skeletons with TB from Bab edh-Dhra in Jordan, dated 3150–2200 bc,51 although Israel does not show evidence of the disease until ad 600, at the monastery of John the Baptist in the Judean Desert.52

Egypt reveals evidence of TB dated to 4000 bc,53 although there is no definite evidence from sub-Saharan Africa. Data on TB in human remains have been published since early last century in this part of the world.54 The most widely cited data are from the mummy Nesperehān who was excavated in Thebes, where a psoas abscess and spinal changes were recorded; this established TB’s presence in Egypt between 1069 and 945 bc.53 In 1938, Derry’s summary55 indicated that the earliest occurrence dated to 3300 bc, although Morse et al.53 record evidence from Nagada dated to as early as 4500 bc. In Egypt, there has been considerable research on soft-tissue evidence for TB. For example, Nerlich et al.56 and Zink et al.57 isolated and sequenced DNA from lung tissue from a male mummy found in a tomb of nobles (1550–1080 bc), providing a positive diagnosis for TB.

Spain comes next in chronological sequence with possible TB in skeletal remains dated to the Neolithic.58 TB appears in Greece by 900 bc.59 Since Angel’s work, there have been very little skeletal data on TB from Greece, but by the fifth century bc, Hippocratic writings described the infection.60 France, like Lithuania and Austria (Northern Europe), reveals TB around the fourth century ad.61–63 Evidence has appeared in early, late, and post-medieval southeast France, but northern France has probably seen the most extensive paleopathological effort,61 with nearly 2500 skeletons being examined from 17 sites dated to between the fourth and twelfth centuries ad. Twenty-nine skeletons with TB were identified, and most came from urban sites. Other Mediterranean countries, such as Serbia,64 Turkey,65 and Portugal,66 provide the first evidence of the infection much more recently—in the medieval period (from around the twelfth century ad). At that time, there appeared to be significant numbers of groups with TB.4 It should also be noted that controversial data from Israel dated to 7250– 6160 bc have been published.67,68

NORTHERN EUROPE

In Northern Europe, the Neolithic site of Zlota (5000 bc) in Poland reveals some of the earliest published evidence for TB.69 As in many other European countries, the frequency of the disease increased during the later medieval period. Data from the Bronze Age site of Manych, in southern Russia, suggest TB was present by 1000 bc,64 but there is much more paleopathological work to be done in that huge country. More recently, data have been presented from Germany and Hungary, suggesting early evidence dated to 5450–4775 bc and 4970–4600 bc, respectively.70–72

In Denmark, the presence of TB begins during the Iron Age (500–1 bc) at Varpelev, Sjælland.73 In Britain, the first evidence has been recovered from an Iron Age site at Tarrant Hinton, Dorset, dated to 400–230 bc.74 Austria and Lithuania have skeletal evidence by the fourth century ad, and for Austria this coincides with the late Roman occupation.

The United Kingdom has had a long history of paleopathological study and, therefore, the evidence for TB is much more plentiful there than in other countries. Of particular interest in Britain is research that contradicts the idea that TB in rural human populations was most likely the result of transmission from animals. aDNA analysis of human remains at the rural medieval site of Wharram Percy suggests that TB was the result of M. tuberculosis and not M. bovis.75

In Lithuania, extensive work has documented the frequency of TB in skeletal remains,76 with the record beginning at the late Roman site of Marvelé. In addition to diagnostic skeletal lesions, remains from Marvelé also produced positive aDNA results for the M. tuberculosis complex.77 Over time, TB frequencies increased, along with population density and intensification of agriculture. Jankauskas78 suggests that cattle probably transmitted the infection to humans, and in the early medieval period he found that people appeared to be surviving the acute stages of the infection.

By the seventh century ad, Norway and Switzerland feature in the history of TB,79 followed by Hungary, and then by Sweden and the Netherlands during the eleventh to thirteenth centuries ad, respectively. There also has been extensive published work in Hungary documenting the frequency of TB over time.80–82 Clearly, TB was fairly common in the seventh to eighth centuries and also in the fourteenth to seventeenth centuries; an obvious gap in the evidence in the tenth century may be due to the Hungarian population’s semi-nomadic way of life at that time (burial sites not identified). Skeletal and mummified remains from Hungary that display TB have also been subject to extensive biomolecular research, which has allowed the confirmation of possible tuberculous skeletons.81,82 In Sweden, an extensive study of more than 3000 skeletons from Lund dated between ad 990 and 1536 showed TB of the spine in one individual (ad 1050–1100), although more than 40 had possible TB in one or more joints.83 The Czech Republic also provides its first evidence of TB during the later medieval period.84

ASIA AND THE PACIFIC ISLANDS

Asia and the Pacific islands reveal TB in skeletal remains much later than the Mediterranean and Northern European areas. China has evidence from a mummy dated between 206 bc and the seventh century ad,85 although the first written description of TB treatment is dated to 2700 bc,86 with the first accepted description of the disease dated to 2200 bc.85 Japan has skeletal evidence dated from 454 bc to ad 124; Korea has evidence from the first century bc87,88 and Thailand has evidence dated to the first two centuries ad.89 Papua New Guinea and Hawaii90–92 produce data much later (pre-Euro- pean, i.e., pre−late-fifteenth century ad), with possible TB being recorded in human remains from Tonga and the Solomon Islands.

Summary of data from the Old World

Although the Old World data for skeletal TB appear quite plentiful, there are many areas where there is no evidence (Figures 1.5 and 1.6).

This may be because:

●●It really does not exist even though extensive skeletal analysis has been undertaken.

●●Skeletal remains are not traditionally studied in a particular country.

●●Management of the burial of the dead at a specific time may not preserve them well enough for the evidence to be observed (e.g., cremation in Bronze Age Britain).

●●Skeletal remains do not survive burial because of the climate or environment in a specific geographic area, for example, the acidic soils of Wales or Scotland.

●●For some time periods in certain countries, no skeletal remains have been excavated (e.g., the Roman period in Poland).

On the basis of the evidence published to date, TB has an early focus in the Mediterranean and Northern European areas. There are later appearances in Asia and other parts of Northern Europe and also in parts of the Mediterranean. However, it is not until the hazards of urban living and the increase in population size

Figure 1.6  Distribution map of occurrences of skeletal tuberculosis in Europe (light stars = early evidence).

and density of the later medieval period that we see a rise in the frequency of the disease in most places. In addition, at this time, a practice known as “Touching for the King’s Evil” was developing—a monarch could apparently cure somebody with TB by touching them on the head and giving them a gold piece.95 Whether all people “touched” were tuberculous is debatable.

Skeletal remains from the New World

In the New World, particularly in North America, skeletal remains have been studied for a considerable time. For example, the first reported human remains with TB were found in 1886,96 although they have since been critically reviewed.9 By the mid-twentieth century, evidence for the disease had increased considerably in Eastern North America,97 the North American Southwest,98 and South America.99 Some have raised doubts concerning the presence of TB in the New World prior to the sixteenth century,100 but current evidence, both skeletal and biomolecular, confirms that TB was present in the prehistoric Americas. A major argument for its absence in prehistoric populations was the suggestion that sufficiently large population aggregates did not exist. However, the existence of very large prehistoric communities effectively counters this argument.4,101 For example, estimates of population size at Cahokia in the Central Mississippi Valley, circa ad 1100, have ranged from 3500102 to 35,000,103 with a population density of 21–27 individuals per square kilometer.102 Although there have been doubts about the need for large populations in order for TB to flourish,104 there were certainly wild and domesticated animals that could have provided a reservoir for the infection.

The evidence from the Americas can be divided into northern, central, and southern areas. Most of the evidence comes from North and South America.

NORTH AMERICA

There are two areas of North America where the skeletal evidence for TB derives—Eastern North America, especially the mid-­ continent, and the Southwest.101 Both these areas were large population centers in late prehistory, that is, before ad 1492. However, Eastern North America provides most of the data, with four sites producing more than 10 individuals with TB: Uxbridge,105 Norris Farms,106 Schild,107 and Averbuch.108 This may reflect not only the intensity of skeletal analysis there, but also the frequency of destructive burial practices along with casual disposal of the dead in the Southwest. However, the earliest evidence of TB in North America does derive from the Southwest during the same time that there were major population concentrations in large pueblos (permanent agricultural settlements).109 For example, the site of Pueblo Bonito had more than 800 rooms, with some of the sites having buildings up to five stories high.110 All the evidence in North America thus post-dates ad 900 and is more recent than that in South America.

MESOAMERICA

Despite large numbers of people living in Mesoamerica before European contact, along with considerable skeletal analysis, there is a virtual absence of TB until very late prehistory.4 This may be explained by poor preservation in some areas of Mesoamerica, but there have also been excavations and analysis of very large well-preserved cemeteries with no evidence of TB forthcoming.111 One explanation for the absence of TB is that people were dying in Mesoamerica before bone changes occurred. However, similar stresses are also identified in North America where evidence of TB exists.109 One could also argue that those with TB, manifested by Pott’s disease of the spine, were buried away from the main cemetery or laid to rest in a different way from those without the disease. In Mesoamerica, we also know that people with “hunchbacks” (the deformity seen in spinal TB) appear to have been awarded special status, as depicted on painted ceramics,112 and that their treatment in society may have been very different from that of the rest of the population, including their final resting place.105

SOUTH AMERICA

The earliest evidence for TB in the New World is seen in South America in Peru,113 Venezuela,114 Chile,114 and Colombia,115 with the oldest evidence recovered from the Caserones site in northern Chile’s Atacama Desert.116 Three individuals with TB were recorded and dated originally to around ad 290 by Allison et al.,115 but Buikstra,101 in considering radiocarbon dating problems in coastal environments, dates them to no earlier than ad 700. Within the larger South American sites, it is interesting to note that more males than females are affected (as is seen generally today), whereas in North American sites the sexes are equally affected.4 Although men and women herded, caravans—groups of travelers—were composed of men; a possible reason for the South American asymmetry would be that males were placed more at risk due to their proximity to camelids while engaged in long-­ distance trade.4 Stead et al.117 also suggest that prehistoric TB in the Americas is likely due more to the bovis organism from infected animal products. M. bovis, compared with M. tuberculosis, is also

10 times more likely to produce skeletal damage. Thus, in North and South America, we see TB increasing after about ad 1000 and into the early historic period.118,119

Summary of the data from the New World

The earliest evidence of skeletal TB in the New World is in South America by ad 700, with later appearances in North America. This suggests a transmission route of south to north, although Mesoamerica generally does miss the encounter until relatively late prehistory. One model suggests transmission by sea, coincident with material evidence of trade between western Mexico and Ecuador.4 The only relatively early Mesoamerican sites with multiple skeletons with Pott’s disease being found in western Mexico. However, the south to north transmission is now compatible with the molecular evidence. One of the lessons we learn from the New World data is the degree to which TB can and did move between mammalian hosts, including human.

HISTORICAL AND PICTORIAL DATA

Although we would argue that the presence of TB in past communities should rely primarily on evidence from skeletal or mummified remains, including that from biomolecular studies, there are large bodies of written and illustrative evidence that have contributed to tracing the origin, evolution, and history of this infectious disease. However, these data are less convincing than those derived from human remains. Unfortunately, the clinical expression of pulmonary TB may mimic other lung diseases such as cancer and pneumonia, and kyphotic deformities of the spine could be caused by spinal conditions other than TB. We also have to remember that authors and artists often wrote about and depicted the most disturbing diseases (especially those that were visually dramatic), and therefore they may not always include TB in their renderings. Thus, using historical sources as an indicator of the presence and frequency of TB remains challenging, and what is represented in these sources may provide a biased portrayal of what diseases were present at any point in time.

Historical data

In the Old World, a Chinese text (2700 bc) provides a description of possible TB in the neck’s lymph nodes and in expectoration of blood,120 while the Ebers Papyrus (1500 bc) also describes TB of the lymph glands. In India, the Rig Veda, of the same date, describes “phthisis,” and a possible example of TB in a skeleton from Mesopotamia (675 bc) has also been described.86 Numerous references are encountered in Classical Antiquity ranging from Homer (800 bc) through Hippocrates (460–377 bc) to Pliny (first century ad); Arabian writers during the ninth to eleventh centuries ad also suggested that animals may be affected by the disease.

The late medieval period in Europe produced considerable written evidence. For example, Fracastorius (1483–1553), in De Contagione, was the first to suggest that TB was due to invisible