The Spotty History of Chicken Pox

For its extreme antiquity the virus that causes chicken pox, it has a surprising sparse documented history.  The earliest clear reference to the virus is actually to an emergence of its latent form as shingles, also called zoster. The ancient Greeks called it zoster after word for girdle, while shingles comes from the latin word cingulus (belt) both referring to the most common site of emergence along peripheral nerves of the back that wrap around the abdomen. There are many theories, but as far as I know, no one has successfully explained how it got the name chicken pox. It was not until histological and immunological investigations in the early twentieth century that the relationship between the primary phase infection, chicken pox (varicella), and the emergence of the latent virus as shingles (zoster) was confirmed.

Into the 18th century, chicken pox and smallpox were commonly confused as a severe and mild form of the same disease. There are subtle differences between the rashes than can distinguish them. Chicken pox produces watery pustules that concentrate on the head and trunk of the body, while smallpox lesions become hard and dimpled and are concentrated on the appendages.  Chicken pox lesions are sparse or absent from the palms of the hands and soles of the feet, while these areas are often heavily covered by smallpox lesions. But, both diseases can cause lesions anywhere in the body including internal cavities and both can leave deep scars.

Chicken Pox 1

They are also, of course, distinguished by their mortality rates. Smallpox has a mortality rate of around 30%, while chicken pox  has a mortality rate of less than 1%. However, pregnant women and immune compromised patients are at high risk for life threatening complications from chicken pox. The blisters can also develop secondary bacterial infections that can become life threatening. Unlike chicken pox, smallpox requires a constant supply of non-immune hosts to persist in a community.

 

Viral Lifecycle

The lifecycle of the varicella virus is ideal to persist in small communities over many generations without outside introduction. It is primarily transmitted as a respiratory virus, but it can also be transmitted by contact with fluid from the blisters. Both routes are critical. Respiratory transmission allows it to spread rapidly while contact with blisters transmission allows it to persist in the community (more on this below).

As the virus enters the body it replicates for 10 to 21 days before the chicken pox rash of virus filled blisters appears. Meanwhile, some of the virons are infecting the peripheral nerves where the virus becomes dormant (latent). A couple days before the rash appears people feel unwell with fatigue, headache and potentially a fever, and they become contagious by coughing or sneezing. By spreading the virus before the rash appears, they spread the virus far and wide before the disease is recognized and isolated. The blisters usually appear first on the scalp and on the trunk of the body with the number of blisters increasing with increasing age of the person. Young children can have as few as a dozen or less, while adults can have thousands of blisters. Over one to two weeks,  the immune system gains the upper hand and the pustules scab over. Once the rash is scabbed over, the person is no longer contagious. The length of time it takes for the rash to stop depends completely on the strength of the immune system.

The virus can remain dormant in the peripheral nerves for 50 years or more emerging when either the peripheral nerves become inflamed (often by injury) or immune suppression develops. It reemerges as shingles (zoster), a highly painful, high density group of blisters that break out along the line of the peripheral nerve they come from, usually spinal peripheral nerves. It will looks something like a whip mark of blisters wrapping around the body from the back to the front. Fluid from these blisters can cause chicken pox in non-immune people. This is a generational persistence strategy. In small communities, the virus persists by being transmitted from an elder’s shingles to children born after the last epidemic.

life long immunity usually follows recovery from chicken pox.  Young children who only have a few lesions in their first infection can contract chicken pox a second time. It is also possible for vaccinated people to develop a usually mild case of chicken pox. In the United States vaccine acceptance is high enough that many people under age 25 have never seen a case of chicken pox. There is little doubt that if vaccination coverage wains, chicken pox will quickly become endemic again.

Origins and Evolution

The ancestral  Varicella-Zoster Virus (VZV), that causes chicken pox and shingles, co-evolved with apes, hominids and humans. Along with VZV, its closest alphaherpesvirus relatives herpes simplex 1 (HSV1, ‘cold sores’) and herpes simplex 2 (HSV2, genital herpes) have a common ancestor that is approximately 120 million years old. If the age estimates for the herpes phylogenetic tree are accurate, the evolution of the alphaherpesviruses  (VZV, HSV1, HSV2) coincides with the split of Africa from the supercontinent Godwanaland.

VZV has the ideal lifecycle to persist in small, isolated groups of humans, allowing to easily survive through all three human epidemiological transitions. Latency and re-emergence in elders allowed the virus to survive in small hunter-gatherer groups, and continues to remain an advantage today. This process was observed in action on the small mid-Atlantic island of Tristan de Cunha where the population of about 200 people only experienced chicken pox outbreaks after an elder first exhibited shingles (Grose, 2012).

Phylogeny of VSV supports its origin in Africa before humans left the continent and subsequent spread through the world. Regionalism has likely occurred because VZV viruses undergo few replications per infection before they become latent so there is little chance for mutation or recombination between the clades (though it does occur).  Once many more sequences are available correlations between VZV evolution and human migration should become more clear.

The history of the chicken pox virus still has a long way to go. As a DNA virus, it is possible that it may be found in ancient DNA but as a virus with a low mortality rate, it will be extremely difficult to find specimens with a high enough viral copy number to detect. Those rare mummies found with pox scars should be tested for both the smallpox virus and varicella-zoster virus. Regardless we must be careful distinguishing smallpox and chicken pox in the historic record.

 

References:

Grose, C. (2012). Pangaea and the Out-of-Africa Model of Varicella-Zoster Virus Evolution and Phylogeography. Journal of Virology, 86(18), 9558–9565. doi:10.1128/JVI.00357-12

Schmidt-Chanasit, J., & Sauerbrei, A. (2011). Evolution and world-wide distribution of varicella–zoster virus clades. Infection, Genetics and Evolution, 11(1), 1–10. doi:10.1016/j.meegid.2010.08.014

Wood, M. J. (2000). History of Varicella Zoster Virus. Herpes : the Journal of the IHMF, 7(3), 60–65.

Centers for Disease Control and Prevention (CDC): Chicken Pox (Varicella) Information portal. Last updated February 26, 2014.

CDC, Varicella: People at High Risk for complications. Nov. 16, 2011.

Conger, Cristen.  “How Chicken Pox Works”  11 March 2008.  HowStuffWorks.com. <http://health.howstuffworks.com/skin-care/problems/medical/chicken-pox.htm&gt;  24 May 2014.

‘Seed and Soil’: an epidemiological parable

I’ve been thinking about the ‘seed and soil’ metaphor used by turn of the century by physicians who accepted germ theory but only had environmental medicine to combat infections. All classically trained physicians, whether religious or not, would have been familiar with the biblical parable of the sower. It also works well as an epidemiological parable of ‘seed and soil’, microbe and environment.  For this parable, imagine that the seeds are genetically identical microbes, only the environment varies.

Then he told them many things in parables, saying: “A farmer went out to sow his seed.  As he was scattering the seed, some fell along the path, and the birds came and ate it up.  Some fell on rocky places, where it did not have much soil. It sprang up quickly, because the soil was shallow.  But when the sun came up, the plants were scorched, and they withered because they had no root.  Other seed fell among thorns, which grew up and choked the plants.  Still other seed fell on good soil, where it produced a crop—a hundred, sixty or thirty times what was sown.” (Matt 13:3-8)

 

The seed that falls upon the path and is devoured by birds are the microbes that are deposited in a completely hostile environment, where they can not sprout (thrive) at all and are prey primarily for other microbes. Their presence is invisible to the non-microscopic world.

The seeds in rocky places that sprout only to wither are the microbes that quickly deplete their resources: viruses that run out of susceptible hosts or a zoonotic disease without sufficient vectors. There is an an initial outbreak, but it is self-limiting and does not become endemic.

Typical ‘food poisoning’ infections are a great example of a seeds that initial thrive only to be choked out by the thorns. The bacteria land in our intestines, initially thriving causing typical nausea, vomiting, and diarrhea, but within about a day our normal flora begin to out compete the foreigner. Hardly thorns, these microbes that normally reside in our intestines protect us from most pathogens. The infection usually ends without medical treatment.  Just as a pesticide can cut back the weeds (thorns), antibiotic treatment can depress the normal flora growth and give an opportunistic microbe the chance to flourish.

The seeds that fall on good moist soil are the microbes that thrive in an ideal environment , often becoming endemic. When the conditions are perfect, a super spreading event can occur with the potential to spark a regional outbreak.

No matter what tools the microbe possesses, interaction with the environment determines  its success. The environment must be permissive for any epidemic to flourish.

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.