Category Archives: immunology

Medieval Historians Taking Genomics into Account

At the International Congress on Medieval Studies at Kalamazoo (Kzoo) last month, I couldn’t help feeling that we have reached a turning point. I went to four sessions that engaged in genomics, human and/or bacterial, in some way. Granted, these are a tiny proportion of the 500+ sessions offered, but I have learned that if you can string together so many sessions on any topic related to your work, it’s a really good Congress.

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Before and After 1348: Prelude and Consequences of the Black Death session, Kalamazoo, 2017. Pictured: Monica Green and Robert Hymes (Photo: Nukhet Varlik, used with permission)

The tone was set in the very first session when Philip Slavin brought up human epigenetics in his discussion of 14th-century famine. This was followed the next day with three sessions on the Black Death and 14th-century crisis. The two Contagions society sessions went very well. Carenza Lewis talked about her ceramics landscape survey that showed how deep the 14th-century demographic loss actually was. Fabian Crespo introduced the audience to the human immune landscape and how it can be fruitfully approached (including by epigenetics).  I will post on the roundtable on Bruce Campbell’s The Great Transition later this summer. The third plague session, Before and After 1348,  organized by Monica Green focused on Asia and generated a vigorous discussion.   I also attended a fifth session that focused on more traditional biological anthropology, ie. mostly osteology.

This turn hasn’t come all of a sudden. Historians began paying more attention to bacterial genomics a little over a decade ago when plague aDNA first hit the news. Michael McCormick, Lester Little, and Monica Green have all been instrumental in bringing science to the attention of historians. Three edited volumes stand out for putting genomics in front of historians: Lester Little’s Plague and the End of Antiquity: The Pandemic of 541-750 (2007), Linda Clark and Carol Rawcliffe’s Society in the Age of Plague (2013), and Monica Green’s Pandemic Disease in the Medieval World: Rethinking the Black Death* (2015).

On the other hand, scientists have also edited collections of papers that should make the science more accessible to historians. Didier Raoult and Michel Drancourt have edited two volumes, Paleomicrobiology (2008) and Paleomicrobiology of Humans (2017). Ruifu Yang and Andrey Anisimov edited a more technical volume, Yersinia pestis: Retrospective and Perspective (2016) that should summarize the state of the science  (as of 2016) for more advanced readers in the humanities.

Of the monographs, the historian’s usual primary venue,  books addressing genomics or using genomics as a springboard are limited. With at least three appearing in 2016 by Nükhet Varlik, Ole Benedictow, and Bruce Campbell, this should change soon. At this point, I should mention that genomics is already becoming useful to historians of other diseases, especially leprosy and tuberculosis. Historians are also becoming reinvigorated to provide context for plague and other diseases that may be of interest to geneticists and biological anthropologists. Varlik’s edited collected Plague and Contagion in the Islamic Mediterranean  (2017) is the most recent to provide context for a variety of diseases in an understudied area.


*Green’s volume was first published as a double inaugural issue of the journal The Medieval Globe and then published as a hardback book by ARC Medieval Press.

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An Unnatural History of Emerging Infections

Unnatural HistoryRon Barrett and George Armelagos. An Unnatural History of Emerging Infections. Oxford University Press, 2013 (e-book)

This is not a traditional review. In keeping with this blog’s function as my shared file cabinet, this post will be something like a précis /notes with a few of  my comments in italics.

Medical anthropologists Ron Barrett and George Aremelagos argue that there have been common factors in the disease ecology that has governed all three main epidemiological transitions in human health. They argue that there is nothing fundamentally new about the driving factors of the current ecology of emerging and re-emerging infectious diseases. In all three transitions, human factors have created the ecology for acute infectious disease to thrive.

Concept: “syndemics: interactions between multiple diseases that exacerbate the negative effects of one or more diseases” (p. 10). Examples: co-infections of HIV, and combinations of infection and chronic respiratory disease (asthma etc).

Metaphor: “seed and soil” where the microbe is the seed and the ecology is the soil. Historically used by physicians who accepted Germ theory but practiced environmental medicine (sanitarians) especially in the gap between the beginning of germ theory and the availability of antibiotics. I really like this metaphor; it still works today. 

Prehistoric baseline

  • Important as our evolutionary context, first 100,000 years of human history. (that’s about 90% of total human history). At its peak only 8 million people globally; small, nomadic groups  rarely in contact.
  • Temporary shelter and carried little with them to carry vectors (or fomites?). Hunter gatherers maintained near zero population growth. More diverse nutrition but could not support large groups. Little hierarchy within the group so few inequalities (at least not consistently detectable in the osteological record.)
  • Nutrition is closely tied to immunological competence.  Protein deficiencies reduces competence to the level of AIDS patients. Nomads can move to find better nutrition, avoiding ‘famine foods’. Diets higher in lean meats and  fiber, but low in carbohydrates.
  • Too small to support acute epidemics (ran out of hosts too soon) but at an increased risk for parasites. Heirloom parasites like pin worms and lice; souvenir parasites picked up while foraging like ticks and tapeworms. Mostly chronic infections that could remain with the nomads until they could be transmitted to new groups.  New zoonoses that can be passed human to human contracted from hunting would ‘flash out’ in a small group. Groups too small for diseases like measles, smallpox or influenza.

First epidemiological transition – Agricultural revolution

  • The first transition comes with people settle down and form villages.  Settlement and agriculture allow populations to grow large enough to support acute epidemic disease and animal domestication brings humans in prolonged contact with animals sparking some important zoonotic diseases.
  • They note that agriculture and settlement begin in multiple parts of the world independently but not at the same time. It took about 9000 years for 99.99 % of the population to shift to farming and domestic animals as their primary nutrition source. Once the shift to agriculture comes, there is no going back.  They debate which comes first, settlement or agriculture, but they note that in the end for heath it doesn’t matter. (The length of time here has important implications for the incomplete nature of the second transition.)
  • Decrease in overall health seen in all societies that shifted to agriculture. Correlations between more/better grave goods and better health; ie. social inequity was bad for health as early as the neolithic. Very high childhood mortalities bring the overall lifespan down considerably. Settlement increased densities of humans and newly domestic animals making conditions ripe for the first acute epidemics and zoonotic transfers. Most zoonotic transfers in this period come from domestic animals.
  •  Nutrition suffers with settlement. Reliance on a monoculture makes them vulnerable to bad years and nutritional deficiencies of essential nutrients not found in the monoculture.  There is a general reduction in stature, increase in signs of anemia, and increase in osteological signs of infection. Examples: Nubia and Dickson Mounds, IL, USA. Correlation of age with skeletal pathologies shows that is health declines are not due to the ‘osteological paradox’ (more pathologies in stronger people because they survive what would have killed others).

Second epidemiological transition – Industrial revolution

  • Transition marked by decreasing deaths due to infectious disease and an increase in chronic diseases. Increasing life expectancy due in large part to decreasing childhood mortality. Total human population soars.
  • Germ theory vs. Sanitation reform: Germ theory is associated with quarantine tied to power of the church and state. (??) Sanitary reform has greater success in controlling diseases like cholera and food-bourne diseases. Sanitary reformers focused on building infrastructure, improving living conditions and personal hygiene. “Germ theorists had begun a revolution in medical thinking, but in the realm of medical practice, they could do little more than agree with existing recommendations of the miasmists.” “with the exception of a few vaccines and surgical asepsis, Germ Theory offered little…until well into the 20th century”. Not surprising that germ theory didn’t make much difference until antibiotics came along. 
  • McKeown Thesis: “identifies nutrition as the primary determinant in the decline of infection-related mortality” Improved nutrition best explains increasing population growth in different countries in a short time period; improved agricultural methods and transport of food. Urban growth with industrialization increased crowding and decreasing sanitation leaving nutrition as the cause for decreasing infectious disease. Correlation between increasing height and decreasing infant mortality, increasing maternal height (indicating good nutrition) increased indicators of infant health so that improving nutrition improved health from generation to generation.
  • McKeown’s critics: error rates in bills of mortality obscure particularly respiratory infections in the elderly. They also believe that he underestimates the significance of smallpox vaccination in decreasing death rates. Greatest criticism is that McKeown places too much emphasis on nutrition over non-medicinal factors.
  • “Comparing the Agricultural Revolution with the Industrial Revolution, we find the same human determinants of infectious disease: a) subsistence, via its affects on nutritional status and immunity; b) settlement, via its effects on population densisty, living conditions, and sanitation; and c) social organization, via distributions of these resources and their differences within and between groups…. As such, the First and Second Transition could be seen as two sides of the same epidemiological coin with human actions as the basic currency.” (p. 61)
  • Second transition is incomplete in many countries. Only seven nations began the transition before 1850 and 17 more by 1900 with most transitioning after World War II. “The ‘low mortality club’ consisted of richer nations whose life expectancies converged at around 75 years old at the turn of the millennium. The ‘high mortality club’ consisted of poorer nations whose life expectancies converged at the same time around 50 years of age.” (p. 66)  The poorer nations have relied more heavily on vaccines and drugs as a buffer against living conditions to achieve the transition. Drug resistant pathogens removes this buffer for poorer nations. High childhood moralities continued in the poorer countries for the same reasons as in the first transition.
  • Chronic diseases make people susceptible to different infections. example: diabetes + TB, infectious diseases causing cancer: HPV, H. pylori, EBV (lymphoma).
  • Developed world vulnerable to “reimportation epidemics” from poorer nations with agents like smallpox (prior to eradication). Increased speed of air travel allows people to travel between high and low disease areas during the incubation period through entry ports without detection.

Third epidemiological transition (current)

  • Convergence of chronic and infectious diseases in a global human disease ecology marks the Third epidemiological transition.
  • Human health determinants remain subsistence, settlement and social organization.
  • 335 novel pathogens discovered 1940-2004, mostly after 1980, 60% of which are zoonoses and 70% of those come from wild animals. With long exposure to zoonoses from domestic animals it makes sense for most new pathogens today to come from wild animals; also due to encroachment and habitat destruction.
  • Challenges of new zoonotic pathogens: establishing animal to human  transmission, then human to human transmission, and finally human population to population. Chatter is a pathogen trying to establishing the animal to human transmission but not yet getting the human to human. Chatter is often viral but can be other microbes as well. Viral chatter is a transitional moment in evolution; purely biological for the pathogen but primarily cultural for humans (human practices that help the pathogen make the transition by our behavior).
  • Attenuation hypothesis: evolutionary interests favor microbes not killing their hosts too soon. Works for the first transition when population groups were widely scattered.
  • Virulence hypothesis: Ewald’s concluded that evolution favors virulence for pathogens with multiple hosts. (ex. plague). We can’t take either hypothesis too far as both have contradicting examples.
  • We need to shift from just looking for drugs to combat pathogens and spend more time on factors of human ecology.
  • An interesting chapter on antibiotics and evolution.

Concluding focus: To dispel three myths

  1. Emerging infections are a new phenomenon. They are not. This is why the emerging infections page on this blog begins with emergences in Antiquity / Prehistoric. 
  2. Emerging and re-emerging infections are a natural or spontaneous phenomena. We have a part to play in microbial co-evolution. Epidemiological transitions are intended to balance microbiology in understanding these infections.
  3. Determinants of disease are different today than in the past. They are not.

“The purpose of this Unnatural History is to reveal the macroscopic determinants of human infection just as the germ theorists once revealed their microscopic determinants…. our approach has been one of both seed and soil, acknowledging the importance of pathogens while stressing their evolution in response to human activities: the ways we feed ourselves, the ways we populate and live together, and the ways we relate to each other for better or worse.” (p. 111)

 

I’m not an anthropologist so I’m not really going to look at this like an anthropologist.  Demographics shifts are what they are, facts. The underlying factors / variables  – subsistence (nutrition), settlement (living conditions/infrastructure), and social inequalities –are the same under all three transitions. As these conditions vary, so do the demographics. This is very useful; a reminder of the importance of human disease ecology. The Unnatural History of the title is reference to human manipulation of the environment creating the conditions for emerging infections. Epidemics are not ‘acts of god’, or simply a natural process that we are helpless to stop. We play our part. Often drugs are the easy way out of the problem, far easier and cheaper than building infrastructure or improving living conditions. 

The paradigm of epidemiological transitions is an anthropological tool. I don’t really have a practical use for labeling ‘transitions’.  As both the second and third transitions are incomplete, they are not of much use to me as concepts. The shortness of these transitions makes me wonder if we are not really looking at just one transition since ca. 1800 that is yet incomplete. It is more important to me to look at these underlying variables and their outcomes at specific times and places. From my point of view, taking generalizations about epidemiological transitions as more than a guide for research or a teaching paradigm can be problematic.

This is a short book and yet I probably highlighted more than any other e-book that I’ve read. The focus here is more theory than details. Some of their plague information is a little out of date but it doesn’t really detract from their main points. It’s a valuable resource for thinking about microbe-human co-evolution. 

Western Iranian Plague Foci Still Active, 2011-2012

In a letter in this month’s Emerging Infectious Diseases, an Iranian and French team of epidemiologists report that the old plague focus in western Iran bordering Kurdistan is still active. Between 1947 and 1966 there were nine human plague epidemics causing 156 human deaths.  The last recorded human case occurred in 1966 and in animals in 1978. No surveys for plague were conducted for the following 30 years. It is unlikely to be a coincidence that the Iranian Revolution also began in 1978.

During the summers of 2011 and 2012, the team captured and tested for the plague F1 antibody 98 rodents and counted their fleas, finding only one rodent with antibodies (1.08%). They also tested 117 sheepdogs finding 4 positive dogs or 3.42%.  In dogs, plague antibodies only last about six months suggesting that these sheepdogs must have had recent infections.  This is enough to suggest that the plague foci is still present in western Iran. Moreover, they believe the number of reservoir rodents and fleas per rodent (Xenopsylla species index 4.10) is “most favorable” circumstances for an epizootic. With plague antibodies found in the only area surveyed in 30 years, it is clear that surveillance needs to not only continue but expand extensively.

Reference:

Esamaeili S, Azadmanesh K, Naddaf SR, Rajerison M, Carniel E, & Mostafavi E (2013). Serologic survey of plague in animals, Western Iran. Emerging infectious diseases, 19 (9) PMID: 23968721