Category Archives: ecology

Grandes Chroniques de France The Death of Saint Louis.

The Schistosoma in the Reliquary

The 800th anniversary of the birth of Saint Louis, King of France, in 2014 provided an opportunity to obtain a sample of his relics for “scientific identification”. With all relics the chain of custody and its backstory are critical for evaluation. Most of Louis’ relics held in the Basilica of Saint-Denis  were destroyed during the religious violence of  sixteenth century Paris. Fortunately the process of preserving and transferring Louis home to France from the site of death on crusade in Tunis, North Africa left bits of him in several locations.  Part of the preservation process used at the time removed his intestines and other internal organs to be embalmed separately while the remainder of the body was boiled to clean the bones to return to Paris. The bones were enshrined in Paris, while the heart and some viscera were enshrined at the abbey of Monreale near Palermo by his brother Charles, King of Sicily, who oversaw the preparation of the body and its transport back to France.

San_Domenico47
13th century Reliquary of Saint Louis, Basicilla of St. Dominic, Bologna Italy. (Source: Photo of Georges Jansoone, public domain on Wikipedia)

During a stop over at Bologna en route to Lyon and then Paris, some of his viscera were removed and interned in the Basilica of Saint Dominic. In 1297 Louis, who had died on 25 August 1270, was officially canonized as Saint Louis of France.  A portion of these visceral relics were given for the consecration of the cathedral of Turin in 1895, and these were transferred to the cathedral of Versailles in 1985. It is from this visceral relic that the 2 g specimen was obtained for scientific evaluation.

Microscopic Examination

The plan is to do a full “medical and forensic anthropological analysis” of the remains. The first result released by Phillipe Charlier’s team is the discovery of a semicircular parasite viewed by Scanning Electron Microscope (SEM) analysis, identified as a male Schistosoma based on its size and morphology.  Schistomsoma are a sexually dimorphic flat worm, also known as a blood fluke, that inhabit the capillaries of the abdomen (mesentery or bladder plexus depending on species) and release their eggs into either feces or urine. The eggs hatch in fresh water and must pass through a fresh water snail before emerging as larvae that can inhabit a mammalian host. Only about 50% of the eggs produced actually exit the body.  The adult worms and eggs that do not reach the feces or urine can cause extensive inflammation resulting in granulomas and fibrosis (scar tissue) to the abdominal organs (liver, spleen, intestines, bladder) and the blood vessels of the abdomen causing an accumulation of fluid in the peritoneal cavity.  Eggs that do breach into the lumen of the intestine cause chronic blood loss into the lumen producing chronic bloody stools. In the worst cases the blood loss can cause anemia.

Saint Louis
Source: Charlier, Bouchet, Weil & Bonnet, 2015.

Compare to a SEM preparation of a modern (non-mummified) male Schistosoma:

800px-Schistosoma_20041-300
A C-shaped male schistosoma; the smaller female resides in the canal. (Source: David Williams, Illinois State University made public domain, Wikipedia)

King Louis had not been in Tunis long enough for him to contracted schistosomiasis upon his arrival only a month before his death. When and where he contracted the flat worm infestation is open to more speculation.  Schistosoma have been observed in archaeological remains of one individual from 9th century France, but have not yet been commonly observed. Charlier et al. (2015) suggest that Louis’ previous crusade in North Africa between 1250 and 1254, spending some time imprisoned in Damietta, Egypt, is the most likely period for start of the infection. If this is true, then Louis would have had a chronic infection for about 20 years at the time of his death. Charlier’s team do not believe that Schistosomiasis contributed to his death.

So far they have not observed any other parasites in the sample. This is not necessarily surprising considering that they have not yet identified the anatomic source of the specimen. It is not possible to even guess at the anatomic source from the crumbling, blackened specimen pictured in their study (fig. 1). Their analysis is continuing.

Debating Saint Louis’ Cause of Death

As soon as the schistosoma report was published, the debate on the cause of Louis’ death began in the letters of Forensic Science, Medicine and Pathology (where the report was published). So lets begin with the best account of Louis’ death, and go from there.

Beyond skirmishing and entrenching the camp nothing was done, as King Louis was awaiting the arrival of his brother Charles of Anjou (now King of Sicily). Whilst they were waiting encamped, John Tristan fell sick, and died on board one of the ships on August 3rd. A few days later the Legate also died and many other persons, some of fever, some of dysentery. Philip, the King’s eldest son, fell sick with fever; and the King was taken with dysentery (the complaint to which he nearly succumbed in his first Crusade) and died on August 25th. (Guillaume de Nangis account in the Memoirs of Lord Joinville, Book 4, Ch. 4)

Strangely, the plague has traditionally been claimed as Louis’ cause of death. This is completely unfounded since the Black Death will not bring epidemic Yersinia pestis back to the Mediterranean for another 77 years! There is nothing in the account above to suggest plague. This has rightly been dismissed as Louis’ cause of death.

Eric Faure wrote a letter arguing that malaria was a possible cause based on reports of Louis’ history of tertian fevers dating back to the 1242. Faure suggests that Louis went on his first crusade in thanksgiving for surviving “cerebral malaria with a coma” after a relapse in 1244. Cerebral malaria is usually caused by Plasmodium falciparum, which is not a chronic (relapse causing) infection. If Louis suffered relapses of malaria contracted in France then it was most likely Plasmodium vivax, which rarely causes cerebral malaria. Whether or not Louis had cerebral malaria in the 1240s, this doesn’t really inform of his his health in 1270.  Faure also notes that some of the men on Louis’ last crusade had intermittent fevers suggestive of malaria. Faure reaches too far suggesting that the dysentery was a symptom of malaria. Gastrointestinal symptoms are possible but rare in malaria and usually then in children. Philippe Charlier responded with a letter dismissing Faure’s suggestion to look for Plasmodium in the remains, because they would not have caused Louis’ death. Following the report in Lord Joinville’s memoir (quoted above), Charlier reports in his letter that his team is now looking for evidence of bacteria, viruses or amoeba in the embalmed “intestines” that are more likely to be the cause of the “dysenteric syndrome” reported in “Louis and his court”.

I will be watching for the final report, but the idea of a single enteric pathogen being the cause of death may not really represent reality. Based on Joinville’s memoir is appears that the “court” was suffering from a variety of camp diseases found in most medieval armies on prolonged campaigns. In such a situation, co-infection is highly likely particularly with chronic parasites. Indeed, Louis was probably not the only one in camp with schistosomiasis lingering from previous travels.  Although I doubt malaria caused Louis’ dysentery, it is quite possible he was suffering from chronic malaria and that it contributed to weakening his health, making him more susceptible to other pathogens. Indeed co-infection with Schistosoma and Plasmosdium could have made him quite anemic.  It would still be worth knowing if Louis had an active malaria infection, even if Shigella or another enteric pathogen was the primary cause of death.

References:

Charlier, P., Bouchet, F., Weil, R., & Bonnet, B. (Oct. 2015). Schistosomiasis in the mummified viscera of Saint-Louis (1270 AD). Forensic Science, Medicine, and Pathology, 1–2. http://doi.org/10.1007/s12024-015-9722-4

Faure, E. (Dec. 2015). The infections of Saint-Louis: possible involvement of malaria.[Letter]  Forensic Science, Medicine, and Pathology, 1–1. http://doi.org/10.1007/s12024-015-9732-2

Charlier, P. (2016). Neither plague nor malaria, but dysentery as a cause of death for St. Louis. [Letter]  Forensic Science, Medicine, and Pathology, 1–1. http://doi.org/10.1007/s12024-015-9738-9

The Memoirs of Lord Joinvilletranslated by Ethel Wedgwood, E-text. University of Virginia library

Louis IV of France, Wikipedia.

WHO fact sheet: Schistosomiasis

Schistosoma, Wikipedia

Michael Walsh, Schistosomiasis on the Infection Landscapes blog. See this page for the best description of the medical effects of schistosomiasis.

Reading in August

august

Just a little update on my reading in August. I’ve been jumping around a bit reading on the history of malaria and wetlands.  Lots of interesting bits and pieces!

Books

  • John Aberth. An Environmental History of the Middle Ages: The Crucible of Nature, 2013.
  • Gregory of Tours (d. 594): Glory of the Confessors 
  • Gregory of Tours (d. 594): The Life of the Fathers
    • Looking at what diseases people are seeking cures for primarily at the shrines of the saints.
  • William McNeill, Plagues and Peoples. 1976.
    • I reread this book about every ten years, so I’m working my way through it over lunch at work at the present. Odd to reread a book I first read in the late 1980s as a student.  Its surprising how well it holds up, but it is now out of date in biology, history and anthropology. It really can’t be used to represent modern views on either infectious disease biology or history. We really need a new, updated edition!  Just to give a few examples, HIV hadn’t even been identified in 1976 (as McNeill mentions in the preface of the 1998 edition) and antibiotic resistance and ‘(re)emerging infectious diseases’ were not considered critical problems (although both had begun to appear).
  • Robert Sallares, Malaria and Rome: A History of Malaria in Ancient Italy. 2002 (in progress)
 Standout Papers – (more or less in order they were read)
  • Couser, J. (2010). The Changing Fortunes of Early Medieval Bavaria to 907 ad. History Compass, 8(4), 330–344. doi:10.1111/j.1478-0542.2009.00671.x
  • King, G., & Henderson, C. (2013). Living cheek by jowl: The pathoecology of medieval York. Quaternary International, xxx, 1–12. doi:10.1016/j.quaint.2013.07.032
  • Förster, F., Großmann, R., Hinz, M., Iwe, K., Kinkel, H., Larsen, A., et al. (2013). Towards mutual understanding within interdisciplinary palaeoenvironmental research: An exemplary analysis of the term landscape. Quaternary International, 312(C), 4–11. doi:10.1016/j.quaint.2013.07.045
  • Rippon, S. (2009). ‘Uncommonly rich and fertile’ or “not very salubrious?” The Perception and Value of Wetland Landscapes. Landscapes, 10(1), 39–60.
  • Bankoff, G. (2013). The“English Lowlands” and the North Sea Basin System: A History of Shared Risk. Environment and History, 19(1), 3–37.
  • Justin T. Noetzel. Monster, Demon, Warrior: St Guthlac and the Cultural Landscape of the Anglo-Saxon Fens. Comitatus: A Journal of Medieval and Renaissance Studies, Volume 45, 2014, pp. 105-131.
  • O’Sullivan, L., Jardine, A., Cook, A., & Weinstein, P. (2008). Deforestation, mosquitoes, and ancient Rome: Lessons for today. BioScience, 58(8), 756–760.

General Principles of Zoonotic Landscape Epidemiology

Zoonoses, pathogens with animal reservoirs, exist as part of a complex system of interactions between animal reservoirs, vectors, ecological factors and human interaction. Landscape epidemiology has existed as a field of study since Russian epidemiologist E.N. Pavlovsky coined the term and laid the groundwork in the 1960s. Landscape epidemiology is in essence the study of environmental foci of zoonotic disease, what Pavlovsky called a nidas. Many of the variables have been identified and studied in individual pathogen systems.

Each system seems so complex and unique that it can be easy to think that they each exist as separate entities with little to do with each other. It is necessary to develop some general principles to both see the bigger picture, and guide research and response to less studied and newly discovered pathogens. Lambin et al. set out to do just that by doing a meta-analysis of eight regional case studies of zoonotic diseases in Europe and East Africa: West Nile Virus in Senegal, Tick-borne Encephalitis in Latvia, Sandfly abundance (leishmaniasis vector) in the French Pyrenees, Rift Valley Fever in Senegal, West Nile Virus hosts in Camargue, Rodent-borne Puumala hantavirus in Belgium, human cases of Lyme borreliosis in Belgium, and risk of malaria re-emergence in Camargue. Obviously, as indicated, not all of these studies look at all factors involved in landscape epidemiology so validation is not solely based on the number of case studies that support each principle.

The ten proposed principles by Lambin et al are shown graphically below where they fit into the system of variables.

Graphical representation of the landscape determinants of disease transmission. The numbers refer to the ten propositions formulated in this paper. Lambin et al. International Journal of Health Geographics 2010 9:54   doi:10.1186/1476-072X-9-54
Graphical representation of the landscape determinants of disease transmission. The numbers refer to the ten propositions formulated in this paper.
Lambin et al. International Journal of Health Geographics 2010 9:54 doi:10.1186/1476-072X-9-54

Proposed general principles (Lambin et al, 2010):

  1. Landscape attributes may influence the level of transmission of an infection” This proposal is found in all case species. Features of the landscape influence vector and host distribution across the region of study. Distribution and type of water (fresh, brackish, or salt water) is a common landscape feature that influences density of insect vectors.
  2. Spatial variations in disease risk depend not only on the presence and area of critical habitats but also on their spatial configuration“.   The sheer size of the critical area is not the only or necessarily the most important characteristic to determine risk in an area. Some vectors like ticks thrive along border zones between ecosystems, like edges between woodland and grasslands.
  3. Disease risk depends on the connectivity of habitats for vectors and hosts” Creating contact zones or contiguous zones that create linked areas are also important. The spatial configuration can create corridors for disease persistence in harsh landscapes. Type and connectivity of  vegetation is as important as terrain for vector habitats. Connectivity between suitable habitat for rodents and insects allows the disease to spread from one patch to the next amplifying the pathogen to a level that increases risks of human transmission. Connections between patches of critical habitats allows for recolonization after local extinction.
  4. The landscape is a proxy for specific associations of reservoir hosts and vectors linked with the emergence of multi-host disease.” Their principle could be better fleshed out; their primary evidence coming from West Nile Virus (WNV). Like other multi-host pathogens, WNV has some hosts that are much more important than others for transmission across wide regions. In WNV migratory birds are a key to understanding its spread and epidemic dynamics. WNV is also an example of a disease with different proxies and amplification hosts in different regions of the world.
  5. To understand ecological factors influencing spatial variations of disease risk, one needs to take into account the pathways of pathogen transmission between vectors, hosts, and the physical environment.” Vector-borne diseases require direct contact between humans and the vector. For other zoonoses like hantavirus contact between humans and animal hosts can be via aerosols of material with rodent feces or dust containing rodent remains. For example, people have contracted hantavirus by vacuuming up rodent remains in homes. When estimating risk of transmission to humans, abiotic (non-living) environmental conditions that can preserve or transmit to humans have to be considered. Climate and moisture content of the soil are common abiotic factors to be concerned about. Additional support for this principle comes from the role of the rodent burrow system on plague (Yersinia pestis) hosts and vectors.
  6. The emergence and distribution of infection through time and space is controlled by different factors acting at multiple scales” In their discussion of this principle, they focus on human interaction with the environment and particularly urbanization altering disease risk. They note that climate change and natural environmental change do not account for all emerging and re-emerging disease but the activities of humans including urbanization and ecological change like deforestation. Ben-Ari et al‘s study on plague and climate change also looks at the many factors at all levels from micro to macro scales effect the abundance and likelihood of transmission of the plague.

    Plague cycle including hosts and vectors with abiotic influences
    Plague cycle including hosts and vectors with abiotic influences (Ben-Ari et al, 2011).
  7. Landscape and meteorological factors control not just the emergence but also the spatial concentration and spatial diffusion of infection risk” This principle just adjusts the previous principles to take account of primarily rainfall by looking at temporary ponds or wetlands. This particularly affects mosquito abundance, but as the graphic above demonstrates also effects soil moisture.
  8. Spatial variation in disease risk depends not only on land cover but also on land use, via the probability of contact between, on one hand, human hosts and, on the other hand, infectious vectors, animal hosts or their infected habitats” Land use has been long known to affect mosquito abundance and disease transmission. Clearing land for settlements or agriculture always increases standing water in ditches, tire ruts, railroad ditches, animal troughs, incomplete building projects, and due to loss of water absorbing vegetation. A century of malaria research and management has focused on land use and the elimination of standing water.  Mature water management programs for cultivation or flood control can also alter vector abundance and human contact rates. For example flooding fields to grow rice not only provides habitat for mosquito production but also brings people into the fields to cultivate increasing contact rates. Irrigation canals would have a similar effect.
  9. The relationship between land use and the probability of contact between vectors and animal hosts and human hosts is influenced by land ownership” In Lambin et al, they looked at the contact rates between public (state) land and private ownership. In these studies state ownership increased access to forestland over private ownership.By the same token, state ownership could also prevent deforestation and urbanization by preserving the wilderness or reserving the land for other uses. Forest age and maturity also varies significantly between state forests and private land.
  10. Human behaviour is a crucial controlling factor of vector-human contacts, and of infection.”  Humans bring themselves into contact with vectors by risky behavior and can control exposure vectors and infections. Obviously, vaccination is one of the controlling factors of infection, although many zoonotic infections have either no or poor vaccines. Occupational and recreational exposure to vectors often explains gender difference in infection rates.

In conclusion these principles begin to mark out the three sides of a zoonotic triangle: biology of pathogen, vector and host; ecological system where they exist; and human behavior and ecological interaction. Human behavior including land use and constructed environments is as important as the other two sides of the triangle. Humans are not passive victims or collateral damage.

Reference:

Lambin, E. F., Tran, A., Vanwambeke, S. O., Linard, C., & Soti, V. (2010). Pathogenic landscapes: Interactions between land, people, disease vectors, and their animal hosts. International Journal of Health Geographics, 9(1), 54. doi:10.1186/1476-072X-9-54 [open access]

Ben-Ari T, Neerinckx S, Gage KL, Kreppel K, Laudisoit A, et al. (2011) Plague and Climate: Scales Matter. PLoS Pathog 7(9): e1002160. doi:10.1371/journal.ppat.1002160