Category Archives: microbiology

Syndemics and Historic Diseases

I’ve been looking for a model or framework to bring together interdisciplinary evidence on diseases of the past. There are a variety of disciplinary approaches but few that can readily incorporate very different types of evidence well.

Apart from past discussions of discrete co-morbidities, the most common framework for understanding historic disease ecology has been pathocoenosis or ‘disease pools’ originated by M. D. Grmek in 1969 and popularized as ‘disease pools’ through McNeill’s Plagues and Peoples (1976). While this concept has proven popular among historians of medicine in high level overviews of human history, the concept begins to break down when practically applied to specific problems, as outlined by Robert Sallares (2004). It is hard enough to identify all of disease-causing microbes in a modern environment, much less a historic environment or population. It is often the minor or chronic disease-causing agents that make the most difference during a co-infection; malaria being a prime contender for the most important.  Pathocoenosis doesn’t adequately take into account the dynamic complexity of microbes in any population (however defined) and the idea that epidemics are disruptions in the equilibrium of pathogens in the population caused by new entrants to the population often doesn’t hold up.

Syndemics is a related concept emerging among biologists and medical anthropologists as a way to understand the diverse complex outcomes of diseases in populations. Syndemic comes from the terms synergistic and epidemic; it is a synergistic epidemic. A synergism exists when two conditions together produce a much greater effect than either individually added together ( ex. 1 +1 = 5 not 2).

A syndemic, in short, involves a set of enmeshed and mutually enhancing health problems that, working together in a context of deleterious social and physical conditions that increase vulnerability, significantly affect the overall disease status of a population (Singer, 2014).

The theory of syndemics is still evolving. The CDC’s definition refers specifically to two epidemics in the same population that produce a synergistic adverse outcome in human health. Consequently biology and medicine focus primarily on coinfections with an occasional look at nutrition. So far they are beginning to find some fascinating insights into how the immune system copes with two or more disease-causing microbes at once. We have to really take in that we are all coinfected all of the time. It comes down to if there is a significant interaction between multiple microbial species and the immune system. (It should be also said that coinfection can occasionally be protective as well.) Not surprisingly medical anthropologists insist on there always being a social component like malnutrition causing events, human behaviors like drug abuse and sexual practices,  or social disorder and inequality. So far from what I’ve read, these different focuses are complementing each other pretty well.

Some of the well-recognized syndemics include:

  • malaria + malnutrition
  • influenza + bacterial pneumonia
  • HIV + TB
  • HIV + HCV
  • HIV + HCV + IV drug use
  • Lyme disease + other Tick Borne Diseases
  • malnutrition + war (social disruption) + infectious disease (mostly diarrhea)

HIV has had a critical role in recognizing syndemics. Not unexpectedly, HIV coinfection with multiple organisms causes recognized synergetically worse outcomes. In many parts of the world, liver disease is a leading cause of HIV+ patient deaths due to Hepatitis C (HCV). It has also highlighted social conditions and behaviors that increase risk and vulnerability. The massive size, duration and amount of research done on AIDS is what has really allowed syndemic theory to become established.

Syndemics is just beginning to look at zoonotic disease but the future is already promising. As has already been suggested by work on pathocoenosis, malaria is a leading candidate to understand the syndemics of zoonoses. Syndemic effects have been suggested for malaria plus malnutrition, HIV and influenza.  Patients with long-term and serious health outcomes from Lyme disease are often coinfected with other less common tick born infectious diseases that are often undiagnosed (Singer & Bulled, 2014).

From what I have read so far, syndemics appears to take the best parts of the pathocoenosis paradigm, while jettisoning the unsupportable, over-reaching baggage. As we can already see for HIV and malaria, the syndemics approach has the potential to build up a foundation to understand the multifaceted outcomes of disease causing agents in different environments and provide insights into how the human microbiome and immune system interact. While its not perfect and doesn’t incorporate all of the disciplines needed to understand historic disease, it may provide a basis to build upon.

References and further reading:

Sallares, R. (2005). Pathocoenoses ancient and modern. History and Philosophy of the Life Sciences, 27 (2): 201–220. [Malaria]

Singer, M. (2014). Pathogen-pathogen interaction.Virulence, 1(1), 10–18. doi:10.4161/viru.1.1.9933

Singer, M., & Clair, S. (2003). Syndemics and public health: reconceptualizing disease in bio-social context. Medical Anthropology Quarterly, 17(4), 423–441.

Rock, M., Buntain, B. J.,Hatfield, J. M., & HallgrImsson, B. (2009). Animal–human connections, “‘one health,’” and the syndemic approach to prevention. Social Science & Medicine (1982), 68(6), 991–995. doi:10.1016/j.socscimed.2008.12.047

Singer, M. C. (2009). Doorways in nature: Syndemics, zoonotics, and public health. A commentary on Rock, Buntain, Hatfield & Hallgrı ́msson. Social Science & Medicine (1982), 68(6), 996–999. doi:10.1016/j.socscimed.2008.12.041

Ostrach, B., & Singer, M. (2013). Syndemics of War: Malnutrition-Infectious Disease Interactions and the Unintended Health Consequences of International War Policies.  Annals of Anthropological Practice, 36(2), 257–273. doi:10.1111/napa.12003

Morano, J. P., Gibson, B. A., & Altice, F. L. (2013). The Burgeoning HIV/HCV Syndemic in the Urban Northeast: HCV, HIV, and HIV/HCV Coinfection in an Urban Setting. PLoS ONE, 8(5), e64321. doi:10.1371/journal.pone.0064321.t003

Kwan, C. K., & Ernst, J. D. (2011). HIV and Tuberculosis: a Deadly Human Syndemic. Clinical Microbiology Reviews, 24(2), 351–376. doi:10.1128/CMR.00042-10

Conant, K. L., Marinelli, A., & Kaleeba, J. A. R. (2013). Dangerous liaisons: molecular basis for a syndemic relationship between Kaposi’s sarcoma and P. falciparum malaria. Frontiers in Microbiology, 4(article 35), 1–14. doi:10.3389/fmicb.2013.00035/abstract

Faure, E. (2014). Malarial pathocoenosis: beneficial and deleterious interactions between malaria and other human diseases. Frontiers in Physiology, 5. doi:10.3389/fphys.2014.00441/abstract

Herring, D. Ann, & Sattenspiel, L. (2007). Social contexts, syndemics, and infectious disease in northern Aboriginal populations. American Journal of Human Biology, 19(2), 190–202. doi:10.1002/ajhb.20618   [1918 influenza]

Singer, M., & Bulled, N. (2014). Ectoparasitic Syndemics: Polymicrobial Tick-borne Disease Interactions in a Changing Anthropogenic Landscape.Medical Anthropology Quarterly, n/a–n/a. doi:10.1111/maq.12163

Contagion and Pestilence in Isidore of Seville’s Etymologies

Saint Isidore of Seville (c. 560–636). Bishop, confessor and Doctor of the Church. Altarpiece of Saint Isidore. 15th century. Diocesan Museum of Calatayud. Spain.

Before Isidore of Seville became the patron saint of the internet, he was known for over a thousand years as a font of knowledge.  Isidore was not an innovator; he was a master of synthesis. It is through Isidore that we have an orderly account of the learned knowledge of the Late Roman world.  He was conscious of the fact that he was saving information at risk of being lost.  His Etymologies, written in twenty sections between 621 and 636, was both the Latin dictionary and encyclopedia of the entire medieval period. Isidore is not always correct — there is a lot of sounds-like etymology– but his explanations were accepted throughout the medieval period. So, Isidore is an ideal source to gain an understanding of how modern terms like contagion and pestilence were defined from the early seventh century in the midst of the first plague pandemic.

From Book IV: On Acute Illnesses:

17. Pestilence is a contagion that as soon as it seizes on one person quickly spreads to many. It arises from corrupt air and maintains itself by penetrating the internal organs. Although this is generally caused by powers in air, it never occurs without the consent of God. 18. It is called pestilence (pestilentia) as if it were pastulentia, because it consumes (depascere, ppl. depastus) like fire, as Vergil, Aen. 5.683): The pestilence descends on the whole body*. Likewise contagion (contagium) is from ‘touching’ (contingere), because it contaminates anyone it touches. 19. The swellings (inguen) (ie. bubonic plague) are so called from their striking the groin (inguen). Pestilence is also called plague (lues), so called from destruction (labes) and distress (luctus), and is so violent that there is no time to anticipate life or death, but weakness comes suddenly together with death. (p. 110-111).

The general definition of both pestilence and contagion, along with their spellings in Latin, are recognizable to us today. The modern editors note that Vergil is using pestilence as a metaphor for the burning of a Trojan ship. It is on the origin or mechanism of pestilence where we differ. Isidore’s world understood medicine as a function of airs and humors, a topic for another time. He also writes of plague again in his On the Nature of Things, which was less influential than the Etymologies. In a later post I will look at what the Venerable Bede does with both the works of Isidore and Pliny in his own On the Nature of Things.

Inguen as the term for a swelling in the groin is the what draws my attention. Inguen is the root for the modern word inguinal; as in inguinal bubo.  Two of the most important European historians of the first pandemic, Gregory of Tours and Paul the Deacon, used the term inguinaria for the pandemic. Unfortunately, inguinaria is usually literally lost in translation. Rather than leaving inguinaria as the early medieval term for bubonic plague, it is usually translated as the less specific ‘plague’ or a little better ‘inguinal plague’. Even in the translation above, it is translated as swelling with the original word in parenthesis.

Bubo is likewise said to come from the Greek word for groin, boubon (βουβών), but I have not found a source to discuss its earliest use. Isidore does not discuss the term bubo or the Greek term boubon, presumably using inguen instead. Greek boubon translates into Latin as inguen, both meaning groin or swelling the groin. Ironically “inguinal bubo” then duplicates the same meaning. It would be interesting to know if boubon or bubonic is a word used for the first pandemic (541-c. 750) in the Eastern Roman empire.

One of the important inferences from the derivation of inguen/boubon is that it supports the groin as the primary site of early infection. So while buboes can be found in the axilla and neck, and there are other transmission routes, it was recognized from the beginning as a disease of the groin. This in turn supports fleas as the primary transmission vector, since as insects found on the floor most of the time, they usually bite on the legs resulting in an inguinal bubo.

Reference: Barney, SA, Lewis, WI, Beach, JA, and Berghof, O. (trans and ed). The Etymologies of Isidore of Seville. Cambridge, 2006.

Plague in Surat: 20 Years Later

I can’t let 2014 pass in a few weeks without mentioning that this fall was the twentieth anniversary of the plague outbreak in Surat, India — a major turning point in modern plague history and in the development of the (re)emerging infectious disease paradigm.

In the final accounting, 53 people died of plague, mostly pneumonic, but there are over 5000 cases classified as suspected and at least half a million people fled across India. Compared to other pneumonic plague outbreaks in Africa within the last twenty years, the number of deaths was small and the mortality rate tiny (1% of suspected cases). The government response was not only woefully inadequate but also exacerbated the damage within India and scared the rest of the world.

The lessons learned from Surat are really what is important.

  • The need for a national database to keep track of seemingly isolated cases and the need for surveillance of rodents, even when there haven’t been any human cases in many years. Better surveillance established since 1994 has identified several more plague outbreaks in India and enough evidence of enduring plague foci in the country.
  • The need for transparency, willingness to accept foreign help and the futility of trying to hide the epidemic from the press.
  • The costs of unsupported allegations of biological warfare or terrorism are too high to make unless there is certainty. It ultimately does not deflect responsibility away from the government for the response. The political costs for governments who make official erroneous allegations are greater than accepting responsibility for the outbreak.

In this month’s issue of the Indian Journal of Microbiology, the full genomic sequence of Yersinia pestis collected at Surat in 1994 and at a 2002 outbreak in India was released. Four samples were sequenced and they are all four different strains. Unfortunately, they did not do a phylogenetic analysis to indicate where they fit on the Y. pestis tree.

Twenty years ago it was the double hit of plague in Surat in 1994 and the discovery of antibiotic resistant plague in Madagascar in 1995 that raised concern about re-emerging infection diseases. Antibiotic resistant strains of Yersinia pestis have continued to appear in Madagascar and now insecticide resistant fleas are a problem as well. While public health processes and surveillance are better than in 1994, there has been no improvement plague incidence or concerning resistant strains.

Ebola is currently extracting the toll that was feared of plague in Surat two decades ago. If Surat was the warning that acute pandemics are still possible, Ebola is showing how far we still have to go 20 years later. Both plague in Surat and Ebola in 2014 are also reminding us that knowing what to do to stop an epidemic is not enough, execution is everything.

Further reading on Surat:

Barrett, Ron. (2008) “The 1994 Plague in Western India: Human Ecology and the Risks of Misattribution” p. 49-71 in Terrorism, War, or Disease? Unraveling the Use of Biological Weapons. Edited by A.L. Clunan, P.B. Lavoy, and S. B. Martin. Stanford Security Studies. Stanford University Press. This is the best analysis of the Surat outbreak that I have found.

Ziegler, Michelle (2014) The Black Death and the Future of the Plague. The Medieval Globe, 1: 183-199 for an overview of plague since 1994.

Mahale, K. N., Paranjape, P. S., Marathe, N. P., Dhotre, D. P., Chowdhury, S., Shetty, S. A., et al. (2014). Draft Genome Sequences of Yersinia pestis Strains from the 1994 Plague Epidemic of Surat and 2002 Shimla Outbreak in India. Indian Journal of Microbiology, 54(4), 480–482. doi:10.1007/s12088-014-0475-7

For more on antibiotic resistant plague, see this past post and on the most recent reported pneumonic plague outbreak in Madagascar.