Asymptomatic Plague: Qinghai, China, 2005

Now that we know the Tibet-Qinghai plateau region is where Yersinia pestis originated and the region where subsequent pandemics arose, I think its time to look more closely at regional outbreaks and case studies.

In this region, the marmot (Marmota himalayana) is the primary reservoir for Yersinia pestis. This large communal burrowing rodent is hunted by local Tibetan tribesmen for both meat and pelts. Butchering marmots has long been considered a risk factor for contracting plague via their fleas, aerosols or skin abrasions. To investigate the exposure of marmot hunters to plague, Chinese epidemiologists collected serum from 120 Qinghai villagers, 68 male hunters and 52 female family members, along with 120 negative controls from the non-endemic area of Beijing. None of the villagers or controls reported having a fever within the last two years.

The results are eye-opening and illustrates the importance of occupational exposure. Over a third of the male villagers had an antibody response to Yersinia pestis. Only 2% of their female family members produced an antibody response. Wether two fever-free years are enough time to determine if they had symptomatic plague in the past is an open question. Their letter to Emerging Infectious Diseases does not provide much information on the test subject’s histories or oral reports.

Table 1: Plague antibody assays (Li et al, 2005)

The epidemiologists explained this high level of immune protection to the use of prophylactic antibiotics by marmot hunters. They suggest the presence of tetracycline or sulfamethaoxazole, common prophylactic antibiotics in Tibet, in  their system at the time of exposure would be enough to prevent a symptomatic infection while still giving them an immunizing dose of bacteria.

The use of prophylactic antibiotics is, of course, a double-edged sword. It is clearly preventing symptomatic infections and probably outbreaks. The Chinese epidemiologists credit  most outbreaks in Qinghai to marmot hunters who either a lack of prophylactic antibiotics or have ineffective antibiotics.  On the other hand, the use of antibiotics is possibly encouraging them to harvest the easier to catch, sicker marmots. The use of prophylactic antibiotics also promotes antibiotic resistance in Yersinia pestis.

Li, M., Song, Y., Li, B., Wang, Z., Yang, R, Jaing, L., and Yang, R. Asymptomatic Yersinia pestis, China. Emerging Infectious Disease, 2005, 11 (9): 1494-1496.

The Great Pneumonic Plague of 1910-1911

The Great Manchurian Plague of 1910-1911: Geopolitics of an Epidemic Disease

by William C. Summers
Yale U Press, 2012

Manchuria was a political mess at the turn of the 20th century. Although it was the homeland of the Qing dynasty, the Chinese considered it a backwater. Japan and Russia on the other hand saw it as potential colonial territory, a beachhead for Japan’s mainland ambitions or access to a valuable ice-free Pacific port for Russia. By 1910 an uneasy truce held giving Russia and Japan corridors to build railroads with stations and towns to support them while technically still in Chinese sovereign territory. The importance of Manchuria to global politics and trade was underscored by the presence of European and American diplomatic representatives in these upstart towns and ports. Into this delicate situation, the discovery that marmot fur could be dyed to pass as ermine brought a flood of primarily Chinese hunters into the region. The drive for furs (and marmot oil) led many to cast aside traditional hunting practices and safeguards, setting the stage for the plague to come.

The beginning of the plague was sparsely recorded. Starting in October 1910 scattered reports were sent that plague had appeared at sites along the railway, but concern was slow in coming. Summers credits the nearly annual outbreaks of plague, low concern for locals, and the temporary camps of hunters for the lack of information on beginning of the plague. Deaths quickly jumped into the thousands in towns along the rail line but never spread very far from the lines. Summers notes that of the over 43,000 recorded cases during the outbreak only one single person survived (p. 19). Some estimates place the mortality closer to 60,000 when early cases and locals away from the rail line are included. Summers notes that this puts the death toll in the range of the great London plague of 1665. By February 1911, the plague was over; blatant proof the plague outbreaks can flourish in winter (as it sometimes did in medieval European winters).

This plague has some unique features. First, there is no report of bubonic plague at all; it was exclusively pneumonic. Most plagues are primarily bubonic with flair ups of pneumonic transmission. Etiology was confirmed by autopsy and the then new bacteriological techniques including culture. American doctor Richard Strong, working with the Chinese under Wu Lien-Teh, did 25 autopsies before the International Plague Conference called by the Chinese in Mukden. There is no doubt the Yersinia pestis caused this epidemic.

Without antibiotics, quarantine and isolation were the only effective means of control. The means were brutal but effective. In the Russian zone the Chinese were crowded into train cars and not let out until there were several days with no one displaying any symptoms. If a case of pneumonic plague was locked in the car with others, the prognosis for the others was predictably terrible. Within this relatively small region, we can also see three different national approaches (China, Russia, and Japan) to controlling the epidemic each always subordinated to their respective political anxieties.

The chapter on origins of the plague begins to move toward was Edmund Russell envisioned as evolutionary history in his book of the same name (2011). The most useful information here is the history of marmot activity and traditional hunting. Summers hypothesizes that traditional shaman-like practices may have aided hunters in only taking healthy animals. Concern for the health of the animal was one of the early traditions abandoned by hunters eager for furs. Following the reports of the time, Summers believes the plague originated in the marmots, and was distinct from the third pandemic lineage. In accordance with modern strain maps, Summers predicts that the 1910-1911 Manchurian outbreak strain will belong to either the antiqua or medievalis biovars (p. 128-9). If this is true, as is likely, it’s a relatively modern challenge to our notion that plague during pandemics has a single lineage and origin. It should be possible to type this outbreak from graves of the epidemic (which should be relatively easy to locate at barely a century old) or even tissue archived from the autopsies (if it was saved and can be located).

Summers is clearly in his element when he discusses the politics of turn of the 20th century politics. This is a region and time period that most Americans know very little about but is still critically important for Asian politics today with the still uneasy relationship between China, Korea, Japan, and Russia. Summers account lays out the different approaches to healthcare and attitudes toward the epidemic as a national and economic threat. This carried over to the International Plague Conference that nevertheless managed to focus on science and medicine. While the scientific politics was interesting I would have liked to hear more about the contents of the wide-ranging Conference report.

Summers does a good job of being very diplomatic will all parties concerned. In doing so, he does overlook a major legacy of the Manchurian plague. There seems little doubt that this plague, witnessed and closely reported on by Russia, the United States and Japan, played a role in plague being developed as a biological weapon. This plague illustrated the deadly efficiency and sustained transmission of pneumonic plague. This book should be read as a prologue to Japan’s biological ‘experiments’ during World War II beginning in Manchuria (see Sheldon Harris’ Factories of Death) and the continuing programs of the United States and Russia during the Cold War.

This book makes a valuable contribution to plague studies, and early 20th century public health practices. Yet there are still unanswered questions on genetics, epidemiology, and ecology. I hope this book along with Myron Eschenberg’s Plague Ports(2007) and others are ushering in a new period of focus on the plague in the 19th-20th century.

Leprosy in Medieval Scandinavia

Medieval leper’s bell from Denmark.

Leprosy is an ancient disease. References to leprosy and the social stigma attached to it go back to 600 BC from India and in the Old Testament. However, like the plague, it was not until relatively late (1873) that the term leprosy became attached to a particular microbe, Mycobacterium leprae. Although some medieval descriptions suggest M. leprae,  it can be very difficult to sort true leprosy from other skin conditions in medieval texts. This is where paleomicrobiology and biological anthropology come in.

Bioarchaeologists have been able to identify skeletal changes suggestive of M. leprae for some time. These changes only occur in the most severe cases making it unclear how common true leprosy was in ancient and medieval times.  It takes many years, if not decades, for leprosy to cause skeletal changes. As with many chronic infectious diseases, it is likely that more people died with the disease than from it. Another way to assess the level and origins of ancient and medieval leprosy is by looking at ancient DNA.

Like the plague, leprosy is considered a monomorphic pathogen that has very little genetic diversity. Four single nucleotide polymorphism (SNP)* types have been characterized for M. leprae. These SNP types are defined by three sites in each type. SNP typing can be technologically challenging with degraded ancient DNA (aDNA) because the typing is based on a single base position at each site. These four SNP types define regional types of M. leprae with type 2 found in Asia and type 3 found in Europe and the Mediterranean today.

A Swedish group led by Christos Economou investigated the M. leprae aDNA of ten skeletons, eight with osteological signs of leprosy,  from Sigtuna, Sweden, dating from the 10th to 14th centuries. DNA analysis revealed that nine of the ten were positive for M. leprae aDNA, including all eight with osteological signs. Leprosy often does not have a high bacterial load so they took nine samples from each skeleton. For each skeleton ruled positive for leprosy DNA, there are two to nine positive samples. However, only three of these nine produced readable results at all three SNP sites: two SNP type 2 (G) and one SNP type 3 (I). This is the first discovery of SNP type 2 in Europe. SNP subtype 2G had previously only been found in Nepal near Uzbekistan. The SNP subtype 3I found in one skeleton is consistent with other samples found in Europe of similar date, according to Economou et al (2013).

Map showing the M. leprae SNP types in Europe and Asia. Purple lines show trade routes. Economou et al, 2013.

Although this is the first discovery of SNP type 2 in Europe, it is not terribly surprising. Sweden borders Asia and was tied to Eastern and Central Asia through trade routes from the early medieval period. Economou et al (2013) note that Sigtuna was an economic and administrative center in 10th-14th Sweden producing artifacts from the Middle East. Missing data from Poland and Russia is a significant gap in the map above.

We are left to hypothesize how an Asian strain of M. leprae got to Sweden. Ultimately we can never know for sure. Leprosy takes so many years to manifest disability or outwards signs that infected individuals could travel from the Middle East or Central Asia to Sweden at least once without sign of infection. These two individuals were unlikely traders: a 20-30 year old female and a 11-12 year old child. It is possible that they either traveled with traders or were slaves, but it is more likely that they contracted leprosy in Sweden. (There is no indication that they were related or died even in the same century.) Economou et al (2013) indicate that grave goods and practices from this cemetery suggest a multi-ethnic population.

Studies like this from Economou et al (2013) are just the first step in our understanding of the rise and fall of leprosy in Europe and Asia. Like plague, it is hard to imagine an environment where leprosy flourished in Europe or Asia, but we know it did. These ancient DNA studies offer some of the best evidence of a pathogenic landscape that seems so foreign to us.

__________________________

Note and Reference:

*The difference between a SNP and a point mutation is the functional effect on the gene. A mutation causes an observable or measurable change in the function of a gene product. Most mutations are harmful, but not all. A polymorphism is a neutral change, as far as can be determined at the time of identification. Polymorphisms are usually found in a significant percentage of individuals or strains. It is not uncommon for human polymorphisms to be found in 10% or more of the populations. SNP typing can be thought of as a type of micro-genetic fingerprinting, based on the smallest possible change between people (or organisms).

Economou, C., Kjellström, A., Lidén, K., & Panagopoulos, I. (2013). Ancient-DNA reveals an Asian type of Mycobacterium leprae in medieval Scandinavia Journal of Archaeological Science, 40 (1), 465-470 DOI: 10.1016/j.jas.2012.07.005

Enzootic Plague and the Great Gerbil of Central Asia

The Great Gerbil, Rhombomys opimus. Range from Afghanistan to China. (photo source: Wikipedia Commons)

Meet the Great Gerbil

The Great Gerbil of Central Asia is not much like the little gerbils found in American pet stores. This bad boy can get as long as 13 inches head to tail, about the size of a  prairie dog or large black rat. It holds a similar ecological niche as the prairie dog as well.

Great gerbils live in family units within large burrow systems across the Central Asian arid and semi-arid regions.Their burrows go 1.5-2 meters deep to take advantage of the warmth and moisture in deep soil. Although they live in semi-arid regions, they also survive winters under snow pack without hibernation. Great gerbils are found from the Caspian Sea to north-eastern China and have been observed in Pakistan, Afghanistan, Iran, Mongolia, and southern Russia [1, 2]. The great gerbil and its fleas are a major reservoir for Yersinia pestis in the natural foci of plague across central Asia [1]. It has long been hypothesized that coevolution of the great gerbil and Yersinia pestis has shaped both species [1]

Immunology of a Plague Reservoir

Junggar Basin, NW China (click to enlarge)

A Chinese group led by Ruifu Yang and Hanli Cao are the first to examine the immunological response of great gerbils from natural plague foci to a Yersinia pestis challenge [1]. They isolated Y. pestis and collected great gerbils from the Junggar basin of northern western China [1]. The Junggar basin (Dzungaria) area was once part of West Mongolia. Previous studies have shown that great gerbils from this region have an average plague antibody incidence of 10% with pockets reaching 30-70% [1]. They collected great gerbils from the Junggar Basin that were proven to be free of Y. pestis by a six month quarantine  in the lab and repeated negative antibody and antigen screening [1].

To mimic a flea bite, the gerbils were challenged with Y. pestis through subcutaneous injections in the groin. The infections were monitored by anal temperature, body posture, animal weight, and changes in diet, fur and respiration. Y. pestis was isolated from dead animals and all animals were assessed for liver and spleen abscesses.  They used 90 great gerbils to determine effects of Y. pestis dosage and time; guinea pigs were used as controls at a lower dosage for the liver and spleen assessment.

Anatomical assessment of the liver and spleen of the great gerbil [A] and a control guinea pig [B]. Y. pestis abscesses are clearly visible on the liver and spleen of the guinea pig [B]. Zhang et al (2012) doi:10.1371/journal.pone.0046820.g002

Infection was only observed in the great gerbil at higher infection dosages (>7.4 x 10(9) CFU), with no difference observed based on gender or age [1]. Their temperatures climbed for three days, returning to normal within seven days and their body weight returning to normal within fifteen days. Blood work showed only an elevated white blood cell count but otherwise remained stable [1]. As shown in the photos above, the great gerbil did not develop visible abscesses on the liver and spleen as the control guinea pig did or as other studies have indicated in mice.

Most of the great gerbils were used for a 21 day Y. pestis challenge. The results were remarkable, an infection rate of 81% but a mortality rate of only 12.7% [1].  Differences in susceptibility is an important factor in the great gerbil’s role in the natural plague focus. Not surprisingly the bacterial load in the liver and spleen of infected animals correlated with survival outcomes. Y. pestis was isolated from spleen and liver as early as one to two days post infection suggesting that it does become systemic early, as indicated previously in mice.  Anti-F1 antibodies (to the F1 capsule protein of Y. pestis) were detected between the second and third week producing an seroconversion rate of 85.7% [1]

What these high percentages don’t show clearly is the observed high variability between individuals in both infection rate in each time cohort and antibody response [1] . In a couple of live gerbils, a low bacterial load of Y. pestis was isolated on day 14 and 15 post infection [1].  It is possible that low-level infections can persist for longer than imagined.  Variability in reservoir host susceptibility is necessary to keep Y. pestis viable in the environment for years. This study increases the evidence that the great gerbil is the key enzootic reservoir for natural plague foci across central Asia.

References

1. Zhang Y, Dai X, Wang X, Maituohuti A, Cui Y, Rehemu A, Wang Q, Meng W, Luo T, Guo R, Li B, Abudurexiti A, Song Y, Yang R, & Cao H (2012). Dynamics of Yersinia pestis and Its Antibody Response in Great Gerbils (Rhombomys opimus) by Subcutaneous Infection. PloS one, 7 (10) PMID: 23071647
2. Nannizzi, M. 2002. “Rhombomys opimus” (On-line), Animal Diversity Web.  University of Michigan Museum of Zoology. Accessed October 20, 2012 at http://animaldiversity.ummz.umich.edu/accounts/Rhombomys_opimus/

Japanese Use of Plague during World War II

I’ve been reading Sheldon Harris’ Factories of Death: Japanese Biological Warfare, 1932-1945, and the American Cover-up. (Rev. ed, 2002), considered the definitive book on biological warfare in the Pacific theater during WWII. My primary interest is in Japanese research and use of plague in their biological warfare program.  Since this blog is, in part, a research tool, this post is a collection of notes taken specifically on plague, though the book covers a much wider program. If you ever wondered why plague is a category A bioterrorism agent, what follows will go a long way in explaining.

Lt. Gen. Shiro Ishii (1892-1959) of Unit 731, the biological warfare unit of Imperial Japan.

Lt. Gen. Shiro Ishii was the primary organizer, promoter and director of the Japanese biological warfare (BW) program. He was involved at all levels from pitch-man to the Japanese military and academia to personally supervising research on human subjects. He began his work research in the potential of biological weapons in the late 1920s.

One of Ishii’s first facilities was called the Zhong Ma Castle in Beiyinhe northern Manchuria. Initially their test subjects were trouble makers among the Chinese population: criminals, communists, and other suspicious persons. Ishii began by focusing on plague, glanders and anthrax. Subjects were injected with the pathogen and the course of their disease was monitored; all were extensively autopsied. (p. 33-34) There are numerous reports of autopsies being carried out on the unconscious, as in  not yet dead.

In 1939 the stressed Japanese military allowed Ishii to send several BW attacks  against Soviet forces in the Nomonhan region. Details of the mission refer to the contamination of water supplies with typhoid but plague, cholera and dysentery effected both Japanese and Soviet troops during the campaign. Harris is unclear whether these were effects of biological weapons operations or naturally occurring outbreaks. (p. 97-98) In 1942 a Soviet defector to Germany claimed that Soviet biological weapons were field tested during combat in Mongolia (/Manchuria) and that a there was a major plague epidemic at that time. (p. 98) With both sides attempting biological warfare and with the level of technology at the time, it is unlikely that it will be possible to unravel outcome of either the Japanese or Soviet efforts.  The Japanese BW program was developed primarily with a future war against the Soviets in mind, as Japan planned to take land north of Manchuria. The intent of the BW program was to give Japan an advantage over the vast population and natural resources of China and the Soviet Union.

Shiro Ishii built an extensive network of facilities in China for the purposes of research and testing. Some details of these units in respect to plague activity follows:

• Unit 731 was the primary unit under Ishii’s command based at his specially built facility at Ping Fan outside of Harbin, Manchuria. The scale of Ping Fan was enormous. Here Ishii built his dream facility complete with four boilers capable of producing one ton of  culture media each sterilized in fourteen autoclaves, ‘Ishii cultivators’ each capable of producing 30 kilograms of bacterial cell mass, and the capacity to maintain  plague, cholera, typhoid and paratyphoid, dysentery, anthrax, gas gangrene, tetnus, and glanders. Ping Fan was also equipped with the capacity to mass produce fleas and its own fleet of airplanes for experiments. (p. 69) After the war Maj. Gen. Kawaashima Kiyochi boasted that Ping Fan could produce 300 kg of plague monthly in addition to other pathogens. (p. 69)

Manchuria, today split between Russia and China. (Public domain image from the CIA’s World Fact Book via Wikipedia Commons.)

• Unit 731 conducted ‘field tests’ throughout northern and eastern China from late 1939 to 1942. They specialized in spreading pathogens by contaminated water and food. They tested cholera, typhoid, paratyphoid, and especially anthrax and plague. They were reported to start epidemics and then enter villages claiming to vaccinate against the epidemic, except that they would inject the pathogen instead. Their experiments involved introducing pathogens by unusual routes such as ‘vaccine’ injections including cholera bacteria. In a Soviet war crimes trial, testimony was given that Ishii’s forces handed out special chocolate bars laced with anthrax to Chinese school children “with unavoidable side effects”‘. (p. 99)

• Unit 731  gave special attention to plague, spreading plague infected rats widely throughout China and experimenting with spreading plague through fomites like contaminated fountain pens or canes. When a full scale epidemic broke out, Japanese soldiers would force an evacuation of the village and burn it to the ground. An American missionary Archie Crouch reported seeing Japanese plains drop odd bombs that spread what looked like wheat over the city of Ningbo and plague erupted just days later. Chinese officials tried to combat the plague with isolation, quarantine and burning the most infected part of the city but over 500 people died of plague and other agents spread by Ishii’s forces. Outbreaks of plague continued in the region of Ningbo until as late as 1959 (p. 101-103).  The city of Quzhou was also subjected to bombs that scattered, soy beans and rags contaminated with plague, cholera, typhoid and possibly anthrax. Bacteriologist Qui Mingxuan lived in the city as a child, and put the death toll for the six years after the first plague outbreak in 1940 at 50,000. Qui noted that there was no history of plague in Quzhou before 1940. (p. 102) In August 1942 plague was sprayed over the village of Congshan in the Zhejiang Province.  Rats began to die in droves two weeks later and over the next two months 392 out of 1200 residents died of bubonic plague. (p. 103) For unexplained reasons, after 1942 Unit 731 stopped large field tests and began to concentrate on more direct human experimentation in controlled environments. Harris estimates that by the end of 1942, “the casualty count in the open tests surely fell into the six figure range” (p. 104).

• Enough credible reports made their way out of China to convince the Allies that Japan was conducting biological warfare. (p. 100-103) In addition to reports coming out of China, American investigators found ampoules of cholera in Burma that locals reported where dropped from planes by the Japanese. In September 1944, Thailand also experienced a plague although there had been no recent plague activity in the area. The Thais and Americans both concluded that these outbreaks in Burma and Thailand were acts of biological warfare by Japan. (p. 226)

• The facility at Nanking, operated by Unit Ei 1644 under the direction of Tomosada Masuda, was a mass production site for bacteria (cholera, typhus, and plague), rodents and vectors. Nanking specialized in flea production for plague experiments. It was also a training site for bacteriologists to conduct biological warfare, producing about  900  from 1941-1943 (p. 142-143)

• Unit 100 in Changchun region worked on plague among other pathogens from 1940 to 1945. Although plague outbreaks had occurred in the region previously, several large suspicious outbreaks that took thousands of lives occurred from 1940 to the end of the war. Unit 100 used these outbreaks as cover for widespread experimentation on villagers.  Injecting slum dwellers with plague under the guise of vaccines against the plague was one of their notable practices. They then relocated about 5000 survivors and burned the slum to the ground. As the war was coming to a close, the order came to destroy all evidence, buildings and people. None of the test subjects or Chinese workers escaped. Some of the infected animals were released into the countryside after the official surrender possibly triggering outbreaks of plague, anthrax and glanders in 1946, 1947 and 1951. (p. 126-133)

• At the Anda test facility in northern Manchuria, Chinese test subjects were tied to open air stakes and bombs containing either an anthrax slurry or plague infected fleas were exploded around them in an attempt to infect them. There is some evidence that anthrax worked slightly better than the plague because the fleas did not handle the exploding bomb well (!). By 1944 they were working on developing means for spreading pneumonic plague and other respiratory pathogens. Fortunately, they were still unsuccessful by the end of the war. (p. 88-90) Ishii would later brag to US war dept. interrogators that he developed a porcelain bomb that successfully disseminated plague (p. 247).

At the beginning of the war, the American biological weapons program was the least developed of all the major combatants. The US military was eager to repair this deficit. American offensive and defensive biological warfare research began at Fort Detrick, Maryland, in 1942. Plague was one of many different pathogens worked on during the war. (p. 210) After the Japanese surrender, American officials were much more interested in extracting intelligence from cooperative Japanese researchers, including Shiro Ishii, than in pursuing justice for the Chinese or even American POWs that were victims of their experiments. To insure cooperation Shiro Ishii was given immunity from prosecution and no one was ever brought to the war crimes trials in Tokyo for biological warfare.  I will leave issues of justice and the cover-up to journalists and political historians.

I do have to take issue with Harris’ assertion that Shiro Ishii was a good microbiologist. He may have been a good pitch-man, organizer and military man but not necessarily a good biologist or physician.  First, I can’t accept that anyone racist enough to mentally justify this work was a competent biologist, much less a physician. Designing and carrying out these ‘experiments’ are the sign of an unstable mind. Methodologically,  ‘try absolutely everything you can think of and something might work’ is not good science, not even in wartime. Even if allied programs did similar things, it is still not good science. He thought more like an engineer than a biologist. The innovation that started his career and gained military attention was the development of a water filtration system to prevent cholera for the military. From a strategic point of view, biological weapons were incredibly risky in the 1940s before the discovery of penicillin and other effective antibiotics. The Japanese military actually had to reign them in out of fears of blow-back. Considering what the Japanese military was willing to do during World War II, this says a great deal.

Plague at the Siege of Caffa, 1346

The first stage of the Black Death among Europeans was said to begin with the whoosh of a Mongol trebuchet. Gabriele De’ Mussi, a lawyer from near Genoa writing in about 1348, is believed to have recorded the account of the earliest use of plague as  weapon of war at Caffa in 1346.

Mongol siege with trebuchet. Edinburgh University Library via Wikipedia Commons.

“The dying Tartars, stunned and stupefied by the immensity of the disaster brought about by the disease, and realizing that they had no hope of escape, lost interest in the siege. But they ordered corpses to be placed in catapults and lobbed into the city in the hope that the intolerable stench would kill everyone inside. What seemed like mountains of dead were thrown into the city, and the Christians could not hide or flee or escape from them, although they dumped as many bodies as they could into the sea. As soon as the rotting corpses tainted the air and poisoned the water supply, and the stench was so overwhelming that hardly one in several thousand was in a position to flee the remains of the Tartar army. Moreover one infected man could carry the poison to others, and infect people and places with the disease by look alone. No one knew, or could discover, a means of defense.” (Horrox, p. 17).

As Mark Wheelis observes in his 2002 article, infected corpses flung into the fortress by trebuchet are a plausible means of infecting the inhabitants. It is not unlikely that corpses would be flung into fortresses, as a terror tactic, with or without disease. Imagine being besieged for months and then having rotting corpses flung at you. By choosing the strongest smelling corpses, it is likely that when they were hurled they came down hard and very sticky. Body fluids can certainly spread Yersinia pestis to people with abrasions and the mess these would have caused upon landing would draw rats from within the fortress. Rats will feed on dead corpses. Direct contact may account for more medieval cases of plague that it is generally credited; in the United States, direct contact is the likely form of transmission for 20% of cases between 1970 and 1995 (Wheelis, 2002).  Wheelis suggests that this had an additional bonus,  helping the Mongols (Tartars)  deal with the mortuary problem that plague always causes. While it is possible that rat transmission brought the plague into the fortress, there is no reason to doubt Gabriele De’ Mussi’s association between the flung corpses and the beginning of the outbreak.

Gabriele De’ Mussi is also revealing his own thoughts about contagion and transmission. Following the miasma theory of contagion, infection is passed through the contamination of the air and water/food. According to Gabriele De’ Mussi, “intolerable stench would kill everyone inside”; the contagion is in the foul-smelling air that can also permeate and therefore contaminate food or water. Although he recognized that it could be transmitted person to person, it was done “by look alone”. Without understanding germ theory, they could not understand what was actually being passed but did recognize respiratory and oral routes of transmission.

Using corpses to foul land or water is a method of biological warfare that is probably as old as warfare itself. If you read all of Gabriele De’ Mussi’s account, he is not really condemning the Tartars (Mongols) as doing anything out-of-bounds or evil. To Gabriele, God was striking down both the Tartars and the Christians. It is unclear if the Tartars were using the corpses as a tactic of biological warfare  or as an act of terrorism and desperation, a ‘share the pain’ or revenge tactic.   Gabriele De’ Mussi says “realizing that they had no hope of escape, lost interest in the siege” and then began to fling the corpses. At this point the Tartars had nothing more to lose. Unlike virtually every other biological warfare strategy, the Tartars did not have to be concerned with the greatest risk of biological warfare, blow-back, that is, the infection of your own army. Although many Italians fled the fortress, it remained under Italian control and the Tartars did abandon their siege (Wheelis, 2002).

Far from blaming the Tartars, Gabriele De’ Mussi places the responsibility for bringing the plague to the Mediterranean squarely on his own people, the Genoese and Venetians.

“among those who escaped from Caffa by boat were a few sailors who had been infected with the poisonous disease. Some boats were bound for Genoa, others for Venice, and to other Christian areas. When sailors reached these places and mixed with people there, it was as if they had brought evil spirits with them: every city, every settlement, and their inhabitants, both men and women, died suddenly. … We Genoese and Venetians bear responsibility for revealing the judgements of God. Alas, once our ships had brought us to port we went to our homes. And because we had long been delayed by tragic events, and because among us there were scarcely ten survivors from a thousand sailors, relations, kinsmen and neighbors flocked to us from all sides. But, to our anguish, we were carrying darts of death. While they hugged and kissed us we were spreading poison from our lips even as we spoke.” (Horrox, p. 18-19)

Wheelis argues that Gabriele De’ Mussi must be mistaken that a single or few ships fleeing from Caffa brought the plague to Europe.  He notes that the spread into the Mediterranean shown in the figure below took too long for a direct voyage from Caffa to Italy. Wheelis points out that this is probably the work of multiple streams of infected ships. He also suggests that caravan routes over land did spread plague to the south of Caffa, though as his maps shows, not nearly as effectively as by sea. Wheelis concludes that “the siege of Caffa, for all its dramatic appeal, probably had no more than anecdotal importance in the spread of the plague, a macabre incident in terrifying times.” Perhaps, but Gabriele De’ Mussi’s rhetoric may be read in other ways.

Transmission from Caffa. (Wheelis, 2002)

Gabriele De’ Mussi deploys a dizzying array of rhetorical devices to express the trauma and tragedy of the plague. He is inconsistent in his point of view, sometimes writing as through he were at Caffa or on the fleeing ship, other times writing from  a distance. As Wheelis notes, Gabriele De’ Mussi did not leave Italy during this years. The entire treatise is wailing to God over the tragedy, and at times talking directly or even conversing with God. When Gabriele De’ Mussi writes that “we Genoese and Venetians bear responsibility for revealing the judgements of God”, he is not referring to a few refugees. This seems to be an indictment of an entire people and could reflect transmission of the plague through the Italian trading network. It should also be considered that ships carrying refugees from the East had a powerful symbolic importance to Italians. Mythologically, the Romans claimed descent from Aeneas who led refugees from Troy to Italy where they won a home. Just as refugees from the East founded the Roman people, Italians fleeing from the East have now brought destruction to Italy and all of Europe. Gabriele De’ Mussi does not mention Aeneas, Troy or the founding of Rome but simplifying his story of plague transmission to a few refugees fleeing from the East makes his story more powerful.

Although refugees from Caffa may have only been one stream of disease transmission, ships from Caffa could have been important for two reasons. First, ships from Caffa could have been a primary disease stream even if they didn’t directly reach Genoa or Venice. Following what we now know about super-spreading phenomena a few ships stopping at multiple ports could radically effect transmission dynamics as plague entered Europe. Additionally, at least in Genoa and possibly Venice, the events at Caffa and its refugees formed a foundation narrative for a tragedy of biblical proportions. A few survivors from Caffa who eventually made their way home, possibly changing ships multiple times, may have arrived about the same time as the plague with horror stories of the plague in ships and ports along their route.

References:

Wheelis M (2002). Biological warfare at the 1346 siege of Caffa. Emerging infectious diseases, 8 (9), 971-5 PMID: 12194776

Horrox, R. ed & trans. (1994) The Black Death. Manchester Medieval Sources series. Manchester and New York: Manchester University Press.

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Did India and China Escape the Black Death?

One of the few things everyone studying the plague can, I think, agree on is the importance of plague dynamics in Asia. Genetic diversity and biogeography suggest that Yersinia pestis evolved in East Central Asia (S. Russia, Mongolia, N. China) and spread along the Eurasian steppe from the Caspian Sea in Kazakstan to the Mongolia very early, perhaps even before it became a human pathogen [1]. The orange labeled clones in the diagram below represent Y. pestis clones that branched off of the main stem before Y. pestis was a human pathogen. These clones only infect voles [2]. They are spread in a wide belt along the Asian steppe but as these are modern clones, we can’t be sure how early this spread occurred. Pandemic Yersinia pestis, ‘the plague’, could have emerged anywhere along this wide Asian belt. Note the red clones (the “Medievalis biovar”) shadow the Silk Road.

Yersinia pestis isolates across modern Asia. (Li et al, 2009) Click to enlarge

The three main pandemics probably arose from different localities  as clones were slowly spread along the Silk Road and endemic foci emerged and expanded [1,2]. The Plague of Justinian is first recorded in Pelusium Egypt, but it probably arrived via canals linking it to the Red Sea and ultimately the Indian Ocean. The Black Death is first recorded at Caffa on the Black Sea. The third (modern) pandemic began in southern China (purple clones on the figure). Not unsurprisingly it is difficult to trace these pandemics back to an endemic site since as a primarily rodent pathogen, Yersinia pestis can move without effecting humans.

The Black Death (1347-1352) draws all the attention because of its scope and scale, the amount of evidence, and the intensity of its legend. In some parts of the world, legend is nearly all we have (or have so far). Although the scientific evidence points toward an Asian origin for Yersinia pestis, there is precious little documentary evidence of it in Asia before modern times (17th century onwards).

George Sussman set out to examine the evidence of the Black Death in India and China in the current edition of the Bulletin of the History of Medicine. What he found in both enlightening and yet mystifying.

Western legends of the Black Death in the Far East go back to contemporary 14th century accounts of the plague in Europe and the Middle East [3]. Witnesses of the Black Death fueled by traveler’s stories imagined that all the known world was stricken, embellishing their writing accordingly. For the most part, modern historians have accepted their accounts of plague in China and India without scientific or historical evidence from China and India themselves. Sussman notes that McNeill’s influential Plagues and Peoples argues that plague foci in the Indian Himalayas and in central Africa are much earlier and more likely to be the source of the first plague pandemic (6th century) than the endemic strip along the Eurasian Steppe that McNeill dated to the 14th century [3]. Modern genetic diversity and biogeography points toward just the opposite with the eastern Asian steppe (Mongolia/N. China) being the original focus and the African focus dating to about the 14th-15th century [1]. There isn’t much evidence that the Indian Himalayan site is very old at all. We clearly need to learn a lot more about the Indian Ocean trade routes in Antique and Medieval periods to understand how the plague reached Pelusium in the 6th century and southern Africa by the 14th century.

So what evidence is there for plague in India before the third pandemic? During the 14th century northern and central India was ruled by Islamic sultans based in Delhi who kept close ties with the Central Asian peoples they came from and with the Middle Eastern centers of Islam [3]. They were well-connected diplomatically, economically and culturally with both Central Asia and the Middle East, areas that were both devastated by the Black Death and its successive waves. Yet there is no evidence of the plague in 14th century India [3]. Origins aside, this is strange, for there to be no record of plague even at ports makes me suspicious of the completeness of the written records. I would expect small local epidemics in ports, even if it couldn’t get traction in the countryside.  Sussman argues that the Indian subcontinent may have been the only area of Eurasia to have population growth during the 14th century [3].

Plague is unambiguously described in the Deccan of India in the early 17th century. It first came to the attention of Emperor Jahangir in Hindustan in 1616 [3]. The annals of the Emperor Jahangir record the third year of the winter plague with mad and dying rodents in January 1619 [3]. The annals include an interesting story of a cat contracting the plague from a mouse and passing it on to a girl who triggered a larger outbreak.

“After this the grain (dana) of the plague (a bubo) appeared in the girl, and from excess of temperature and increase of pain she had no rest. Her colour became changed—it was yellow inclining to black—and the fever was high (tap muhriq gardid). The next day she vomited and had motions, and died. Seven or eight people in that household died in the same way, and so many were ill that I went to the garden from that lodging. Those who were ill died in the garden, but in that place there were no buboes. In brief, in the space of eight or nine days seventeen people became travellers on the road of annihilation”.(Sussman, p. 337-338)

He is describing a case of secondary pneumonic plague that then spread throughout the household. The development of secondary pneumonic plague in a child can be especially damaging because more people will come to care for a child than an adult. In this case, mouse to cat to child to family doesn’t require any fleas at all. The cat got the plague from biting the sick mouse, the child got the plague from playing with the cat and passed it on to her family. The lack of buboes in the last people to die suggest that at some point in the transmission bubonic plague became pneumonic, probably in the child.

So plague is firmly established in 17th century India, but not in the 14th century during the Black Death pandemic. While I expect that we may yet find evidence of small outbreaks, there not does appear to have been a large epidemic. Why that was is unknown. Perhaps a combination of geographic isolation, climate, vector availability and sheer luck.  Turning to neighboring China, the picture becomes more complicated.

As I’ve already mentioned, Yersinia pestis genetic diversity and biogeography suggests that it has been in northern China long before any of the pandemics. With the wide-spread of early clones, the pandemic does not necessarily have to begin where there is the greatest genetic diversity.

Sussman notes that in the third pandemic the large northern outbreak was marmot-derived pneumonic plague while the southern outbreak was rat-derived bubonic plague [3]. This is still the case today. A marmot derived outbreak of pneumonic plague occurred in northern China as recently as 2009. If plague in northern China is usually pneumonic plague from marmots, I’m not surprised that they did not have a specific name for the disease. Pneumonic plague does not produce unique enough symptoms to differentiate from other rapidly lethal respiratory diseases.

The Yuan dynasty controlled China and Mongolia during the first half of the 14th century. This period coincided with a concerted withdrawal from the greater Mongolian world most of whom had by this time converted to Islam [3]. It was a time of great turbulence: famines, epidemics, natural disasters, political unrest, as the last remnants of the Mongol empire in China devolved to regional warlords and the Ming Dynasty began to develop [3]. Record keeping during this devolution is sporadic and uneven, but it does show three rounds of massive epidemic in 1330- 1350 each taking over 60% of at least regional populations. Unfortunately medical descriptions of the disease(s) have not survived [3]. Sussman’s analysis of the overall Chinese population during the early to mid 14th century is that the losses are comparable to the 25-30% loss in Europe that is directly credited to the Black Death [3]. Given the ancient foci of plague in northern China, this is where we should expect it to come from in the 14th century, and so it does appear to. On the other hand, Sussman notes that the first obvious medical description of plague in China dates to 1644.

Sussman questions whether the 14th century epidemics were plague based on some questionable criteria. He is bothered by the apparent lack of spread of the epidemic to the southwest (where the third pandemic began). He thinks a ‘virgin territory’ epidemic in densely populated China should have easily spread throughout China as it spread throughout Europe.  The European pandemic was the unusual behavior for the plague, not a regional epidemic in China where plague was more ancient than in Europe. In other words, I don’t think that Europe and China were equally ‘virgin territory’ epidemics. The importance of ‘virgin territory’ is probably also being over estimated for Yersinia pestis. Also the terrain in southwestern China is unlike northern China or Europe; it is more tropical. We need to let go of the idea that the second and third pandemic must behave the same. With a sample set of only three pandemics, we surely can not say that there must be one pattern that they will all conform. The lack of medical description also makes Sussman question if it was the plague. However, there is apparently no medical description at all to rule plague out or in. He also finds it unlikely that the plague could have traveled the length of the Eurasian steppe because much of it is so sparsely populated. Yet the first epidemic in northern China occurs in the early 1330s, surely enough time to travel the Silk Road west by caravan or Mongol horsemen. It is also possible that this clone spread along the steppe over several decades or even a century before it erupted at multiple points into large epidemics where the conditions were right and into a pandemic in the west.

Noticeably absent in this discussion is archeological evidence in either India or China. Now that we can identify Yersinia pestis aDNA in remains, hopefully this could be investigated in at least northern China. Unfortunately, I rarely hear about any medieval archaeology from India or China.

World Biomes (click to enlarge)

Plague’s normal biome is semi-arid grassland, shown on this simplified biome map as brown and yellow. From Sussman’s information it appears that the Black Death avoided tropical rainforest biomes (light green). This is not really surprising given its endemic regions. It is the opposite of the third and weakest pandemic. The endemic foci produced by the third pandemic are the usual semi-arid grasslands in the American south-west, Madagascar (which has some savanna), and Brazil.

So in conclusion, what are we left with? First, western reports of plague in the east may be more rhetoric than reality. Even if there were small unrecorded outbreaks in India, there doesn’t seem to be much evidence of population decline. For China, it would help to have more evidence of the nature of the northern epidemic. However, the coincidence and lethality of the epidemic support it being the plague. There is still a lot of work to be done on plague history in southern Asia.

References:

[1] Morelli G, Song Y, Mazzoni CJ, Eppinger M, Roumagnac P, Wagner DM, Feldkamp M, Kusecek B, Vogler AJ, Li Y, Cui Y, Thomson NR, Jombart T, Leblois R, Lichtner P, Rahalison L, Petersen JM, Balloux F, Keim P, Wirth T, Ravel J, Yang R, Carniel E, & Achtman M (2010). Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nature genetics PMID:21037571

[2] Li Y, Cui Y, Hauck Y, Platonov ME, Dai E, Song Y, Guo Z, Pourcel C, Dentovskaya SV, Anisimov AP, Yang R, & Vergnaud G (2009). Genotyping and phylogenetic analysis of Yersinia pestis by MLVA: insights into the worldwide expansion of Central Asia plague foci. PloS one, 4 (6) PMID: 19543392

[3] Sussman GD (2011). Was the black death in India and China? Bulletin of the history of medicine, 85 (3), 319-55 PMID: 22080795