Category Archives: Geography

Yersinia pestis found in human fleas, Madagascar 2013

Madagascar is consistently one of the top two countries in Africa (and usually the world) in cases of plague, caused by Yersinia pestis. For five years prior to January 2013, Madagascar registered 312 to 648 cases per year, with a majority being laboratory confirmed of which >80% were bubonic plague. Of the multiple reservoir species in Madagascar, the black rat (Rattus rattus) is the primary reservoir with Xenopsylla choepus being the main urban vector and Synopsyllus fonquerniei in rural areas.

After a nine case bubonic outbreak in the rural area of Soavina in the district of Ambatofinandrana (shown below), fleas were collected within and outside of five houses over three nights.


The team from the Institut Pasteur de Madagascar collected 319 fleas representing five genera; the most common being the human flea Pulex irritans (73.3%).  In this study, X. cheopis and S. fonquerniei were only collected outside of the houses. Pulex irritans was found only indoors where it made up 95.5% of flea species. Of the 274 fleas tested for Yersinia pestis, 9 pulex irritans were positive. These positive human fleas came from three homes, one of which had a confirmed case of human plague. None of the other flea species tested positive for plague.

Previous observations of pulex irritans in Madagascar suggest this flea may be responsible for domestic human-to-human transmission. High densities of human fleas were reported in plague outbreak villages in 2012-2013. Flea surveys on rats in Madagascar conducted over the last three quarters of a century show that pulex irritans are very rare on rats, suggesting it is not transmitting plague from rats to humans at least in Madagascar. Although pulex irritans are commonly called the human flea, they will feed on dogs and pigs  in addition to humans.  They have also been sporadically found on a variety of other mammals and birds, including rats.

Coping with human fleas as plague vectors will be a significant extra burden on the public health services of Madagascar. Ridding homes of human fleas can be a difficult task. It will however give plague researchers an opportunity to study pulex irritans as a vector in one of the top human plague producing countries in the world.

Within the last ten years, Madagascar has produced human plague cases from three different fleas and pneumonic transmission. With its diversity of plague reservoirs and now flea vectors, Madagascar is illustrating how deeply Yersinia pestis can penetrate and become entrenched in the environment.

Reference:

Ratovonjato J, Rajerison M, Rahelinirina S, Boyer S. “Yersinia pestis in Pulex irritans fleas during plague outbreak, Madagascar” [letter]. Emerging Infectious Disease. 2014 Aug [30 June 2014].http://dx.doi.org/10.3201/eid2008.130629

Wyrwa, J. 2011. “Pulex irritans” (On-line), Animal Diversity Web. Accessed July 01, 2014 at http://animaldiversity.ummz.umich.edu/accounts/Pulex_irritans/

Microbial Forensics of a Natural Pneumonic Plague Outbreak

For bioterrorism agents like Yersinia pestis it is necessary to identify the strain and its source specifically enough for forensic use. Categorizing an epidemic isolate and tracing its source is always important for public health measures, but the level of precision is far higher for legal uses. Developing forensic techniques to characterize and parse very similar strains of a species and trace it to a specific location robs terrorists (and states) of the ability to deny responsibility for an attack (Koblentz & Tucker, 2010). The ability to launch a secret and deniable attack on an enemy has been viewed as one of attractive advantages of biological warfare.

A Chinese group led by Ruifu Yang and Yujun Cui recognized that only whole genome sequencing could adequately parse the strains of the monomorphic species Yersinia pestis but that the computing power necessary to compare entire genomic sequences as the database enlarges is impractical (Yan et al, 2014). Unlike most pathogens, typing only specific regions of the genome are just not enough to get a unique genetic fingerprint for low genetic variability pathogens like Yersinia pestis. This is yet another indication of the genomic similarity of all Yersinia pestis strains.

The Chinese group developed a two stage method of classification detailed enough for forensic work.  They took a twelve person outbreak of pneumonic plague contracted from a dog in 2009 in the Qinghai area of Tibet / western China, specifically at Xinghai as their test case (Wang et al, 2010). In the first step they took six cases including the two dogs who died in the outbreak and compared them to 24 strains representing the 23 phylogroups of the phylogenetic tree. This comparison selected which branch of the phylogenetic tree the outbreak belonged. There were no SNP (single nucleotide polymorphisms) different between the seven isolates confirming a common source, one of the dogs based on outbreak narratives. The seven isolates were all the same strain belonging to branch 1.IN2 of the tree. The second step was to then compare the isolates to all known strains of 1.IN2 shown below. Since these strains all come from the Qinghai-Tibetan plateau, they were able to add other strains historically isolated from this region.

Distribution of 1.IN in Qinghai  (site source)
Distribution of 1.IN2 in Qinghai (Yan et al, 2014, click to enlarge)

The results localized the new isolates (r) as being from the same focus as strains g, r, s, t. u plus, interestingly, the 0.PE7 strain (green b) that is over 300 SNPs different from the 1.IN2 strains. All of these other strains from this branch are scattered around the Qinghai region near Lake Qinghai. The polysomy (branch point) that produced all of the 1.IN2 in Xinghai (g,r,s,t,u) is located closer to the eastern end of Lake Qinghai, where the Chinese team hypothesizes this these strains began. The new outbreak isolates did not match any previous isolates from Xinghai which is testimony to the degree of movement of these strains around the region. Without the case narrative, they would not have been able to identify the specific foci at Xinghai, but would have got it to the region of east Qinghai lake. This illustrates how important sampling all of these foci are because a biological attack is likely to be far from its site of environmental isolation. Characterization of all laboratory strains, obviously, needs to happen as well for forensic tracing.

Reconstructing the historical epidemiology of this region will be an area of continuing research. The location of 0.PE7, the most genetically ancestral strain ever found — the closest the common ancestor of all Yersinia pestis, plus the likelihood that the ‘big bang’ epidemic (or epizootic), that produced the third pandemic, represented by node 12, was also in this region. (Each of the nodes represents a bang of evolutionary diversity, with all major branch points in the lineage probably representing large epidemics or epizootics.) The full diversity of strains in this region (unrelated to the outbreak isolates) are not shown in the figure above. This same group lead by Ruifu Yang  produced the primary phylogenetic tree of Yersinia pestis in China that noted that the molecular clock is not constant (Cui et al, 2012), here calculates that N12 is about 212 years old (95% confidence being 116 to 336 years ago) (Yan et al, 2014).  They note that in the history of Qinghai, there was a major human outbreak in the year 1754 CE linked to a Buddhist missionary working in Qinghai and Gansu provinces (Yan et al, 2014). Its is unclear if we can trust this narrative at all; scapegoats are common in plague narratives. Linking the 1.IN2 strains from Qinghai to four of the five o.IN2 isolates from Tibet suggest that the epidemic moved from Qinghai to Tibet in one ancient epidemic, though remaining isolate from Tibet looks like a more recent transmission from Qinghai. Regardless of the movements of 1.IN2, this area is believed to have been a site of long-term survival of Yersinia pestis, potentially over a thousand years, so that it has a lot to teach us about enduring foci.

Microbial forensics has already been used in criminal investigations, court cases and intelligence operations, such as the ‘Amerithrax’ (anthrax) attacks of 2001, anthrax spores sprayed over Japan by a cult, and suspicious plague cases in New York City (Yan et al, 2014). Phylogenetic microbial forensics was successfully used to show the intentional transmission of HIV from Dr Richard Schmidt to his girlfriend in his 1998 trial. This was the first successful use of microbial forensics in a court case (Koblentz & Tucker, 2010). In these cases, isolates are taken from the accused, the victim, other sexual partners, and the local population so show phylogenetic linkage between the accused and victim in the context of the local epidemiology.  The United States, United Kingdom, Sweden, the Netherlands, Japan, Canada, Germany, Australia, Singapore, and now China are involved in the development of microbial forensics (Koblentz & Tucker, 2010; Yan et al, 2014).

Reference

Koblentz, G. D., & Tucker, J. B. (2010). Tracing an Attack: The Promise and Pitfalls of Microbial Forensics. Survival, 52(1), 159–186. doi:10.1080/00396331003612521

Yan Y, Wang H, Li D, Yang X, Wang Z, et al. (2014) Two-Step Source Tracing Strategy of Yersinia pestis and Its Historical Epidemiology in a Specific Region. PLoS ONE 9(1): e85374. doi:10.1371/journal.pone.0085374

Wang, H., Cui, Y., Wang, Z., Wang, X., Guo, Z., Yan, Y., et al. (2010). A Dog-Associated Primary Pneumonic Plague in Qinghai Province, China. Clinical Infectious Diseases, 52(2), 185–190. doi:10.1093/cid/ciq107

Cui, Y., Yu, C., Yan, Y., Li, D., Li, Y., Jombart, T., et al. (2012). Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis. Proceedings of the National Academy of Sciences, 110(2), 577–582. doi:10.1073/pnas.1205750110/-/DCSupplemental/sd01.xls

Personal ties to Cholera, 1833

Tanner-Cholera1832
Map created by Henry S Tanner of the 1832 Cholera pandemic

What a strange feeling looking at this map of the 1832 cholera pandemic.  It looks like a blotchy bruise on the country. A little surprise at how restricted the pandemic was in America. As it turns out this map is incomplete, ending in October 1832;  cholera eventually traveled down the Mississippi to reach New Orleans and stops along the way.  One of my first experiences with history of medicine discovered in my own research occurred while doing some family genealogy. Cholera is often depicted among the poor in crowded, old cities like London. For me though, cholera is a disease of the American frontier.

My ancestor John Biggs Moore died of cholera on July 4th, 1833. John Moore was the patriarch of a large family in frontier Illinois on the Mississippi River. He came to Kaskaskia Illinois with his parents in 1781 in the last years of the Revolutionary war. His father James Moore had first seen the Illinois country in the militia of George Rogers Clark when they took the area from English control during the Revolution. John Moore was teenager listed among the men on the first census of Americans in the Illinois country in 1787 used in part to prove that Americans were settled as far west as the Mississippi River to Congress. When American territorial boundaries were established, the Mississippi River was set as the western border, putting them on the furthest edge of the American frontier. (The Louisiana Purchase would extend the frontier in 1804.) The Moore family started the American settlement at Bellefontaine (present city of Waterloo), at the site of a big well-known spring,  on the trail between Kaskaskia and Cahokia in 1782.

John Moore’s death on July 4th tells us something about its circumstances. July 4th was the biggest community celebration held on the frontier. John Moore was the son, son-in-law, and nephew of Revolutionary war soldiers and a former War of 1812 soldier. There is little doubt that he would have been part of the independence day celebrations. Cholera came to Illinois the previous summer with Gen. Scott’s arrival with federal soldiers to take charge of the Black Hawk War.  They arrived at Fort Dearborn (modern Chicago) on the shore of Lake Michigan and the disease traveled with the troops down the Illinois and Mississippi rivers fading out in the fall. When cholera re-emerged the following summer it is recorded in Belleville in July of 1833 it claimed the life of former Governor Ninian Edwards on July 20, 1833. John Moore died of it over two weeks earlier 20 miles from Belleville. Most of the men in John Moore’s extended family where in the Illinois militia on campaign under his step-brother Gen. Samuel Whiteside during the Black Hawk War. So the community gathering for independence day celebrations the summer after the war, that could have went on for days, is the context of his death.

The arrival of the first steamship in Illinois brought with it the double-edged sword of connection with ‘civilization’. Most of the early Illinois pioneers did not come with grand visions of living in an isolated primitive wilderness.  They were very focused on land ‘improvements’ and recreating a Virginia-style plantation landscape. Steam ships would have been heralded as a sign of progress since river trade was vital to their economy until the railroad arrived. The cholera brought to the frontier by the federal troops killed more people than the Black Hawk War.