Category Archives: ecology

Dogs as Plague Sentinels and Vectors

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Marmot fighting a wild dog in northern Tibet (Source: China Tibet Online/ Xinhua)

I’ve been a little obsessed with thinking about dogs and the plague lately. Dogs are often overlooked in historic plague discussions because they usually survive plague and dog-specific fleas are not associated with transmitting plague. Yet, dogs can host many of the fleas common among rodents and others that do transmit the plague including the cat flea (Ctenocephalidis felis) and the human flea (Pulex irritans) (Gage, Montenieri, & Thomas 1994). In a case controlled study of nine US cases of bubonic and septicemic plague in 2006, having dogs in the home and particularly sleeping with a dog was a significant risk factor, probably by flea transfer (Gould et al, 2008).  There is also a growing awareness that dogs can also transmit pneumonic plague directly to humans. Like other aspects of plague biology, there is a lot going on under a veneer of normalcy.

Dogs do readily contract the plague; it’s just not apparent to casual observation. In the American state of New Mexico, 62 domestic dogs were diagnosed with plague just between the years 2003 and 2011 — 97% survived (Nichols et al, 2014).  The dogs were diagnosed by an increase of Yersinia pestis F1 antibody greater than four times greater than the recovered level, by isolation of Yersinia pestis from a body fluid or by direct flourescent antibody assay of a tissue specimen. All of them had some physical sign of infection with fever and lethargy being found in 100% of cases, but buboes or lymphadenopathy (enlarged lymph nodes) were found in only 23% and these were all in the jaw and neck region. The mean time for recovery was two days, although all but one did receive at least one dose of antibiotics. Potential sources of plague exposure are from prairie dogs, ground squirrels, chipmunks, and rabbits. Only three of the dogs had any fleas at all, but as these dogs were pets, most had received anti-flea treatment.

Monitoring plague in working dogs and other carnivores is the most efficient method of doing plague surveillance in the vast semi-arid grasslands that harbor some of the most enduring plague reservoirs. Dogs are especially useful because their immunity only lasts about six months, so a detectable level (titre) of plague antibody indicates recent contact with an infected animal. Gage, Montenieri, and Thomas (1994:6) estimated that  “sampling even a few rodent consuming carnivores, such as coyotes, can be roughly equivalent to sampling hundreds of rodents for evidence of plague infection”. The earliest serologic survey that I have found was done in Navajo lands in 1966-1968. In this same survey  in 1968, “the plague organism was isolated from a pool of fleas (Pulex irritans) taken from the household dogs of a person with plague” (Archibald & Kunitz 1971). Carnivores are now routinely monitored in the US.  Surveying herding dogs in Iran was able to show that the long unmonitored plague foci is still active (Esamaeili et al., 2013). Recent Chinese F1 antibody surveys in the Gansu province are more ominous: in 2012 4.55% of dogs were positive, but it had jumped to 10% of dogs by 2014 (Ge et al, 2014). Another  2014 survey of multiple Yersinia species in dogs found 25% of dogs in Gansu province and 18% of dogs in Qinghai province to be positive for Yersinia pestis F1 antibody, while no plague-free provinces had a single dog that had a positive antibody titre (Wang et al, 2014).

Consumption is the likely primary route of infection for dogs.  The 62 dogs from New Mexico are believed to have been primarily infected by consumption of a plague infected rodent or rabbit (Nichols et al, 2014). In a 2014 case study from China, an infected marmot was taken from a dog, butchered and divided among five dogs. All five dogs developed positive antibody titers for  plague and the shepherd who took the marmot from the dog developed pneumonic plague (but not his brother who butchered the marmot). Aerosol transmission was supported by  the isolation of Y. pestis from sputum and throat samples (Ge et al, 2014). One dog not fed the marmot was negative for the F1 antigen. Three of the 151 human contacts given prophylactic antibiotics developed an antibody titre but did not manifest disease. According to Chinese policy, the five positive dogs were euthanized and the local marmots were depopulated (Ge et al., 2014).

Dogs can transmit plague to humans through fleas that feed on the dog, fleas carried by the dog from the rodent source of the infection,  through bites or scratches, or by aerosols from dogs that develop a systemic infection. While dogs are usually thought of transmitting infected fleas to people, the  number of pneumonic cases linked to dogs is increasing. The first confirmed transmission of pneumonic plague from a dog to a person occurred in China in 2009 (Wang et al, 2015). The index case in turn transmitted pneumonic plague to eleven people. Three of these twelve cases died with the other nine cases confirmed by Y. pestis F1 antibody titres. All of the Y. pestis isolates were later typed to “biovar antiqua” — a reminder that older strains are still very virulent (Wang et al, 2009). In June 2104, in Colorado, a dog transmitted pneumonic plague to three caregivers, one of whom transmitted it to another person. All of four of these cases survived and 88 additional people were given prophylactic antibiotics (Runfola et al, 2015). Three of China’s 2014 plague cases in Gansu province within the Qinghai-Tibet plague focus area  were pneumonic plague in herders.  All three arrived at the medical center too late for effective antibiotic treatment and died (Li et al, 2016). Chinese authorities believe that two of these men may have contracted plague from infected dogs and the third directly from a marmot (Lie et al, 2016).

Dog transmitted plague seems to usually result in family or small settlement size outbreaks. I do wonder about the potential role of dogs in the Bronze Age cases of plague (Rasmussen et al, 2015). Dogs contracting plague by consumption of infected rodents and passing it on to human contacts seems possible with the tools of the Bronze Age strains. It might also be worth investigating the potential role of dogs in the beginning of the Great Manchurian Plague of 1910-1911, which focused on hunters who likely used dogs extensively. Indeed hunters in this region would feed sick marmots to their dogs believing that they could not contract the disease. Outbreaks of 100% lethal plague were not unknown among hunting families in Manchuria (Summers 2012: 122-124). Such a high mortality rate would suggest pneumonic plague.

References:

Archibald, W. S., & Kunitz, S. J. (1971). Detection of plague by testing serums of dogs on the Navajo Reservation. HSMHA Health Reports.

Esamaeili, S., Azadmanesh, K., Naddaf, S. R., Rajerison, M., Carniel, E., & Mostafavi, E. (2013). Serologic Survey of Plague in Animals, Western Iran. Emerging Infectious Diseases, 19(9). http://doi.org/10.3201/eid1909.121829

Gage, K. L., Montenieri, J. A., & Thomas, R. E. (1994). The role of predators in the ecology, epidemiology, and surveillance of plague in the United States, 20.Proceedings of the 16th Vertebrate. Pest Conference (W.S. Halverson& A.C. Crabb, Eds.) Published at Univ. of Calif., Davis. 1994.

Ge P, Xi J, Ding J, Jin F, Zhang H, Guo L, Zhang J, Li J, Gan Z, Wu B, Liang J, Wang X, Wang X, Primary Case of Pneumonic Plague in Marmata himalayana natural focus area Gansu Province, China, International Journal of Infectious Diseases (2014), http://dx.doi.org/10.1016/j.ijid.2014.12.044

Gould, L. H., Pape, J., Ettestad, P., Griffith, K. S., & Mead, P. S. (2008). Dog-Associated Risk Factors for Human Plague. Zoonoses and Public Health, 55(0), 448–454. http://doi.org/10.1111/j.1863-2378.2008.01132.x

Li, Y., Li, D, Shao, H., Li, H and Han, Y. (2016) Plague in China 2014 — All sporadic case report of pneumonic plague. BMC Infectious Disease. 16: 85.

Lin, Karen. (2014-07-02) Photo: Himalaya marmot eaten by wild dogs in N. Tibet. China Tibet Online. http://www.vtibet.com/en/news_1746/focus/201407/t20140703_209395.html

Nichols, M. C., Ettestad, P. J., Vinhatton, E. S., Melman, S. D., Onischuk, L., Pierce, E. A., & Aragon, A. S. (2014). Yersinia pestis infection in dogs: 62 cases (2003-2011). Journal of the American Veterinary Medical Association, 244(10), 1176–1180. doi:10.2460/javma.244.10.1176

Rasmussen, S., Allentoft, M. E., Nielsen, K., Orlando, L., Sikora, M., Sjögren, K.-G., et al. (2015). Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago. Cell, 163(3), 571–582. http://doi.org/10.1016/j.cell.2015.10.009 [Bronze Age cases]

Runfola, J. K., House, J., Miller, L., Coltron, L., Hite, D., Hawley, A., et al. (2015). Outbreak of Human Pneumonic Plague with Dog-to-Human and Possible Human-to-Human Transmission — Colorado, June–July 2014. MMWR. Morbidity and Mortality Weekly Report, 64(16), 429–434.

Salkeld, D. J., & Stapp, P. (2006). Seroprevalence Rates and Transmission of Plague (Yersinia pestis) in Mammalian Carnivores. Vector-Borne and Zoonotic Diseases, 6(3), 231–239. http://doi.org/10.1089/vbz.2006.6.231

Summers, William C. (2012) The Great Manchurian Plague of 1910-1911: The Geopolitics of an Epidemic Disease. Yale University Press.

Wang, H., Cui, Y., Wang, Z., Wang, X., Guo, Z., Yan, Y., et al. (2015). A Dog-Associated Primary Pneumonic Plague in Qinghai Province, China. Clinical Infectious Diseases, 52(2), 185–190. doi:10.1093/cid/ciq107

Wang, X., Liang, J., Xi, J., Yang, J., Wang, M., Tian, K., et al. (2014). Canis lupus familiaris involved in the transmission of pathogenic Yersinia spp. in China. Veterinary Microbiology, 172(1-2), 339–344. doi:10.1016/j.vetmic.2014.04.015

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.

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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:

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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.