Category Archives: Plague

The Case for Louse-Transmitted Plague

800px-louse_diagram-_micrographia-_robert_hooke-_1667
Louse illustration by Robert Hooke, Micrographia, 1667. (Public domain)

by Michelle Ziegler

The key to understanding plague — past, present, and future — has always been understanding its vector dynamics. By the latest tally, there are 269 known flea species, plus a small collection of ticks and lice, that can be infected with Yersinia pestis. With this many infected parasites, it’s not a surprise that 344 hosts have been identified (Dubyanskiy & Yeszhanov, 2016), but this list is still incomplete. (It does not include all of the minor hosts in North America.) Regardless, this is not a description of a picky pathogen! Unfortunately, it is far easier to identify infected hosts and potential vectors than to determine which of these insects are effective vectors and their transmission dynamics.

Numerous species of fleas have been identified as plague vectors in specific localities. However, only five infected potential human vectors are possibly involved in a wide distribution of human plague cases — the rat flea Xenopsylla cheopis, the cat flea Ctenocephalides felis, the human flea Pulex irritans,  the human body louse Pediculus humanus humanus, and the human head louse Pediculus humanus capitis. The rat flea and the cat flea are known vectors, but  they are unlikely to account for the full transmission of the massive first and second pandemics.  I recently discussed the possible role of the human flea. Given the worldwide distribution of human lice, they are attractive vectors but there is still work to do before they can be considered likely primary vectors for human to human transmission during the first two pandemics.

Raoult Makes his Case…again

Didier Raoult and his team have been working on plague and their louse transmission hypothesis for a long time.  It has already been ten years since they had enough information to write their first review article putting forth their human ectoparasite theory of plague transmission (Drancourt, Houhamdi, & Raoult, 2006).

At this point, their primary supporting evidence was some experiments with human louse plague transmission in rabbits (Houhamdi et al, 2006) and they thought they could associate louse transmission with an “Orientalis-like” biovar of Yersinia pestis they identified in the first two pandemics (Drancourt et al, 2004).  However, later ancient DNA work showed that the first two pandemics were caused by strains of Yersinia pestis that emerged before the Orientalis biovar. Genetic reclassification of Yersinia pestis has also made the biovars largely obsolete.  Tensions between groups working on ancient plague DNA developed quickly, and have been documented by historians Lester Little (2011) and Jim Bolton (2013).

This summer Didier Raoult (2016) restated his “personal view” on the role of lice in plague transmission. This essay is unusual not only as a first person narrative in science, including individual claims of discovery, but also for being so vindictive in its attack on his rivals. Again, see Little (2011) and Bolton (2013) for less biased accounts.  His team has done very impressive work.

His team has continued to assemble much of the work needed to argue that human lice were instrumental in at least some of the major human outbreaks of plague during the first two pandemics. Combing primarily French medical reports in North Africa, they were able to identify observations that suggest that lice were involved in some mid-twentieth century outbreaks (Raoult, 2016; Malak, Bitam, & Drancourt, 2016).  One of their most interesting findings in 2011 was the discovery of co-infection with Yersinia pestis and Bartonella quintana (trench fever) in late medieval French remains (Tran et al, 2011).  Trench fever is well known to be transmitted by the human louse. Both B. quintana and Y. pestis have been found in contemporary lice taken from plague patients in regions of endemic plague in the Congo (Piarroux et al, 2013; Drali et al, 2015). Unfortunately, neither of these studies mention the presence or absence of fleas.  That blood feeding lice would be infected is not a surprise, but the question of transmission stubbornly remains. There has yet to be a contemporary outbreak where all potential vectors, fleas and lice, were investigated. On a side note, the finding of widespread B. quintana is interesting, and perhaps a proxy for heavy lice infestation.

Modeling Transmission

In the meantime, while Raoult’s latest summary was in press, additional evidence was beginning to be revealed. Graduate student Katharine Dean of the MedPlag project in Oslo was modeling past epidemics for transmission by rat fleas, human lice, and pneumonic transmission. In her master’s thesis, she showed that lice transmission fits the second pandemic epidemics at Givry in 1348, London in 1563-64, and Florence in 1630-31 better than rat fleas or pneumonic transmission (Dean 2015). At the most recent Yersinia meeting in October, Dean presented a poster with expanded data finding outbreaks that fit each of these three modes of transmission (pneumonic in Manchuria, rat fleas in Sydney and Hong Kong, and lice in many locations) (Dean et al, 2016). Their work is still in progress and I’m sure many will be eager to see their results in due course.

Almost there

There are still a few lingering things to nail down. A modern outbreak investigation that looks at all ectoparasites, fleas and lice,  in the region that suggests lice are involved. It would be good to find lice (or fleas for that matter) in a plague burial that yields Y pestis aDNA. Alternatively, detection of more coinfection of Y. pestis with a louse-transmitted infection like B. quintana would lend additional support.  These findings will will require some good fortune. To differentiate between the human flea and lice, a better understanding of the pathology of a Y. pestis infection in the potential vector and its transmission dynamics is really needed. The models can’t differentiate human ectoparasites without more information.

Human ectoparasites are beginning to look much more likely especially for northern epidemics (Hufthammer & Walløe, 2013). More information is still needed to distinguish between human fleas and lice, although they may be both involved in different outbreaks.  We need to be ready for yet another paradigm change in plague history. Looking at the overall plague vector dynamics of the great pandemics, from sylvatic reservoir to distant human populations, is going to get a whole lot more complicated but also more interesting.


Reference:

Bolton, J. L. (2013). Looking for Yersinia pestis: Scientists, Historians, and the Black Death. The Fifteenth Century, XII, 15–38.

Dean, K. R. (2015, June 1). Modeling plague transmission in Medieval European cities. (B. V. Schmid, Supervisor). Oslo. [Master’s Thesis]

Dean, K. R., Stenseth, N. C., Walløe, L., Lingærde, O. C., Bramanti, B., & Schmid, B. V. (2016, October). Human ectoparasites spread plague during the Black Death and Second Pandemic. Yersinia 12th International Symposium. Tbilisi, Georgia.

Drali, R., Shako, J. C., Davoust, B., Diatta, G., & Raoult, D. (2015). A New Clade of African Body and Head Lice Infected by Bartonella quintana and Yersinia pestis–Democratic Republic of the Congo. American Journal of Tropical Medicine and Hygiene, 93(5), 990–993. http://doi.org/10.4269/ajtmh.14-0686

Drancourt, M., Houhamdi, L., & Raoult, D. (2006). Yersinia pestis as a telluric, human ectoparasite-borne organism. The Lancet Infectious Diseases, 6(4), 234–241. http://doi.org/10.1016/S1473-3099(06)70438-8

Drancourt, M., Roux, V., Dang, L. V., Tran-Hung, L., Castex, D., Chenal-Francisque, V., Ogata, H., Fournier, P-E., Crubezy, E, and  Raoult, D. (2004). Genotyping, Orientalis-like Yersinia pestis, and plague pandemics. Emerging Infectious Diseases, 10(9), 1585–1592. http://doi.org/10.3201/eid1009.030933

Dubyanskiy, V. M., & Yeszhanov, A. B. (2016). Ecology of Yersinia pestis and the Epidemiology of Plague. Yersinia Pestis: Retrospective and Perspective, 918(Chapter 5), 101–170. http://doi.org/10.1007/978-94-024-0890-4_5

Houhamdi, L., Lepidi, H., Drancourt, M., & Raoult, D. (2006). Experimental model to evaluate the human body louse as a vector of plague. The Journal of Infectious Diseases, 194(11), 1589–1596. http://doi.org/10.1086/508995

Hufthammer, A. K., & Walløe, L. (2013). Rats cannot have been intermediate hosts for Yersinia pestis during medieval plague epidemics in Northern Europe. Journal of Archaeological Science, 40(4), 1752–1759. http://doi.org/10.1016/j.jas.2012.12.007

Little, L. K. (2011). Plague Historians in Lab Coats. Past & Present, 213(1), 267–290. http://doi.org/10.1093/pastj/gtr014

Malek, M. A., Bitam, I., & Drancourt, M. (2016). Plague in Arab Maghreb, 1940–2015: A Review. Frontiers in Public Health, 4, 18–6. http://doi.org/10.3389/fpubh.2016.00112

Piarroux, R., Abedi, A. A., Shako, J. C., Kebela, B., Karhemere, S., Diatta, G., et al. (2013). Plague epidemics and lice, Democratic Republic of the Congo. Emerging Infectious Diseases, 19(3), 505–506. http://doi.org/10.3201/eid1903.121329

Raoult, D. (2016). A Personal View of How Paleomicrobiology Aids Our Understanding of the Role of Lice in Plague Pandemics. Microbiology Spectrum, 4(4). http://doi.org/10.1128/microbiolspec.PoH-0001-2014

Drali, R., Mumcuoglu, K., & Raoult, D. (2016). Human Lice in Paleoentomology and Paleomicrobiology. Microbiology Spectrum, 4(4). http://doi.org/10.1128/microbiolspec.PoH-0005-2014

Tran, T.-N.-N., Forestier, C. L., Drancourt, M., Raoult, D., & Aboudharam, G. (2011). Brief communication: co-detection of Bartonella quintana and Yersinia pestis in an 11th-15th burial site in Bondy, France. American Journal of Physical Anthropology, 145(3), 489–494. http://doi.org/10.1002/ajpa.21510

Rivers in European Plague Outbreak Patterns, 1347-1760

by Michelle Ziegler

The era of big data is coming to historic epidemiology. A new study published this month in Scientific Reports took a database of 5559 European outbreak reports (81.9% from UK, France and Germany) between 1347 and 1760 to analyze the role of rivers in the incidence and spread of plague. Their hypothesis was that river trade played a similar role as maritime trade in disseminating the plague but that the correlation would grow weaker over time as movement of goods over land became less expensive. In the 14th century, water transport was approximately ten times cheaper than land transport; the cost ratio diminishes to two to four times as expensive by the 18th century.  While it is not surprising that rivers had a role in disseminating the plague, the high correlation Yue, Lee, and Wu (2016) found between not only the proximity of the river but also its size and elevation is striking. Over 95% of the outbreaks occurred within 10 km of a ‘navigable’ river, defined as 5 m or greater in modern width and to differentiate maritime from riverine trade, excluded outbreak sites within 5 km of the maritime coastline. To ensure that rivers were suitable as trade routes, they only included rivers that linked two cities and excluded rivers that flowed into a lake without an outlet.

srep34867-f1
“Figure 1. Temporal and spatial distribution of plague outbreak in Europe in AD 1347–1760 (modifed from Büntgen et al 2012).” Yue, Lee, & Wu, 2016.http://www.nature.com/articles/srep34867/figures/1

If we drill down into their results more directly, then we find that 84% of the city centers were less than 1 km from a river with 79.5% of those being on a river at least 20 meters wide. By their calculations, the average river width was 84.6 m. This correlates well with increased traffic and goods following to and through cities on substantial rivers. It is worth nothing here that the specific examples they give in England, Fossdyke, River Great Ouse, and the River Derwent are either canals or fit into an extensive canal system.

Looking at relationships between the outbreak sites and geography also favors high traffic river routes. When they included a “spatial lag in the regression models” they showed that there is a “highly significantly correlation with the spatial lag (p <0.01), indicating that plague outbreaks were spatially dependent upon previous outbreaks in adjacent cities” (Yu, Lee & Wu, p. 2). There was also a negative correlation between elevation and plague incidence, which they attribute to a lack of navigable rivers at higher elevations noting that only 20 incidents were recorded above 1000 m over sea level.  They also tested their results with controls for population density and economic status which did not effect their results for the likelihood of plague incidence or the association between outbreaks and river width. This will have to be evaluated by those with more modeling experience than I have.

There are a few caveats. First, such studies are only as good as their database. Yue, Lee and Wu used the digitized database constructed by Büntgen et al (2012) that was itself based on  a 35 year old archive published in French. I’ll leave its scrutiny to historians. They also do not address potential biases in all such databases, such as the likelihood that urban sites are recorded at a higher frequency than rural sites or that the political climate can effect the survival of records. Indeed, economic records are likely to note pestilence as a factor effecting commerce. While the environmental destruction of an enduring war could increase plague incidence, the high level of records from the ’30 years war’ needs a historians eye to evaluate. They also note that they are using measurements of modern rivers and canals that may have been significantly different in the past, modified by both natural processes such as silting or flooding and man-made changes such as straightening, dredging, or canal development.

They  also assume there were no European reservoirs, which we now know is not true. Ancient DNA studies have indicated that there were at least two strains descended from the Black Death circulating within late medieval Europe (Bos et al, 2016;  Spyrou et al, 2016). The European reservoir(s) have not yet been located. However, relatively few of the incidents reported in the database are likely to be actual zoonotic events linked directly to a local sylvatic (wild) reservoir, plus many known reservoirs outside of Europe are found at high elevation (for example in Tibet or Madagascar) and so are unlikely to be in this particular database given the absence of sites at higher elevations. Once a new outbreak emerges from a high elevation reservoir and comes off the mountain so to speak, then its transmissions by rivers is as likely as a strain entering from outside of Europe. On the other hand, if cities or even river networks are the actual reservoir, it would significantly effect their results.

River and canal networks or large river ports could function as reservoirs. River ports are similar to coastal maritime ports in that they have warfs, warehouses and nearby markets that would support large rodent populations. Barge traffic would specialize in transport of grain and other foodstuffs attractive to rodents.  Yue, Lee and Wu  (2016) state that they did not query their database for the effect of flooding because they could not accurately predict where floods would occur, that flooding is not predictable based solely on river width. Flooding along these river and canal systems is something that needs to be investigated because it would force rodents out of their normal shelter and could be related to human outbreaks (as the plague of 589 in Rome probably was). Floods could also carry infected rodents or fleas downstream on floating debris.

This study is a interesting jumping off point for future work. The database needs to be evaluated by historians and perhaps subdivided into smaller time periods. Division of the database into regional studies would also allow local archaeology and ecology to be more informative on precise outbreaks. I’m looking forward to all of questions big data studies like this one open up!


Reference:

Yue, R. P. H., Lee, H. F., & Wu, C. Y. H. (2016). Navigable rivers facilitated the spread and recurrence of plague in pre-industrial Europe. Scientific Reports, 1–8. http://doi.org/10.1038/srep34867

Büntgen, U., Ginzler, C., Esperf, J., Tegel, W., & McMichael, A. J. (2012). Digitizing historical plague. Clinical Infectious Diseases, 55(11), 1586–1588. http://doi.org/10.1093/cid/cis723

Bos, K. I., Herbig, A., Sahl, J., Waglechner, N., Fourment, M., Forrest, S. A., et al. (2016). Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus. eLife, 5, 17837. http://doi.org/10.7554/eLife.12994

Spyrou, M. A., Tukhbatova, R. I., Feldman, M., Drath, J., Kacki, S., de Heredia, J. B., et al. (2016). Historical Y. pestis Genomes Reveal the European Black Death as the Source of Ancient and Modern Plague Pandemics. Cell Host and Microbe, 19(6), 874–881. http://doi.org/10.1016/j.chom.2016.05.012

The Promiscuous Human Flea

Female Pulex irritans, the human flea, from the Katja ZSM collection (CC3.0)
Female Pulex irritans, the human flea, from the Katja ZSM collection (CC3.0)

by Michelle Ziegler

The human flea seems like a misnomer today. We are not its current primary host, but that doesn’t mean that it once wasn’t our primary flea.  Pulex irritans  was first described by Carl Linnaeus as the “house flea” in 1758 (Krasnov 2012:4) and it is still found in homes in many parts of the world.

For the most part, the human flea is a nuisance, an irritant as its name implies. Except when it isn’t, when it occasionally transmits Yersinia pestis, the plague, to people. Pulex irritans has been  in homes with human plague cases from Arizona to Madagascar (Archibald & Kunitz, 1971; Ratovonjato et al, 2014). In 2006, Drancourt, Houhamdi, and Raoult argued that either the human flea or louse played a major role in human plague epidemics.

Human fleas have been found in the homes in several areas where plague occurs. P. irritans infected with Y. pestis were found on a dog in a home of a plague victim on Navajo land in Arizona in 1968. They also report knowledge  Y. pestis being isolated from  P. irritans fleas on dogs in the home of an infected child in Kayneta in 1968 (Archibald & Kunitz, 1971).   A recent survey of plague regions in Tanzania found 50% of the fleas in homes were P. irritans (Haule et al, 2013). A recent survey of fleas in Madagascar found that 98% of the fleas found inside control homes  in the control region of the study were Pulex irritans (Miarinjara et al, 2016). The fact that they did not find them in the homes within the area of the plague outbreak a month earlier may be due to extensive spraying of insecticide to end the epidemic. Human fleas are suspected of being the vectors for a variety of zoonotic diseases in Iran today (Rahbari, Nabian, & Nourolahi, 2008).

The human flea, Pulex irritans, has had a very interesting and convoluted history. All of the Pulex fleas are thought to have evolved in South America, perhaps on guinea pigs or piccary . P. irritans is the only member of its genus  that has left the Americas.  It made it to Eurasia long before the “Columbian Exchange”.  So it crossed a land bridge at some point to begin spreading in Eurasia, and it need not have crossed on a human.  Ötzi the 5000 year old ice mummy from the Italian Alps yielded two human fleas from his  artifacts (Schedl, 2000). P. irritans has also been found Egypt from 3500 BC  (Bain 2004) and 1350-1323 BC (Panagiotakopulu, 2001) showing that it does well in warm, dry climates also. So not only where they present for the entire known period of plague but they have been specifically found in warm and cold regions. Pulex irritans has been found in floor debris of uncovered sites from Roman Britain (Kenward, 1998). They were common inhabitants of early medieval Irish homes (O’Sullivan, 2008).  They are fairly common finds in Norse Greenland settlements. Unfortunately flea surveys have not been done on most continental archaeological sites (or at least I haven’t found them).

So why is P. irritans called a promiscuous flea? It has nothing to do with sex! In this case promiscuous means that it will feed off of a wide variety of host species. It has a truly impressive host range beyond humans including pigs, dogs, cats, goats and sheep, cattle, chickens, porcupines, multiple species of foxes, wolves, coyotes,  golden jackel of Iran,  badgers, prairie dogs,  rabbits, wild cats,  and mice. There are undoubtably more species that could be added. It seems to be very common on foxes in North America and Europe. These are, of course, primarily predators of rodents.  Given its wide range of hosts, its distribution and frequency among hosts has probably fluctuated wildly due to environmental and biodiversity changes over the last millennia.

Such a wide host range also makes it a potential bridging vector, one that can move disease between a wild reservoir to a domestic space transmitting it to domestic rodents, pets, and humans. Importantly, bridging vectors work in both directions, meaning that it could be instrumental in developing a wildlife reservoir after a human epidemic in a new region.

fleaslifecycle
General flea life cycle (CDC). Adults are only 5% of flea biomass.

flea-pyramid-1P. irritans has a life cycle that is well suited to thriving in buildings like houses, barns, sheds, and animal nests or dens. Most of their biomass is in the egg stage. Small white eggs are often laid on the host but almost always fall off on to the floor. They do particularly well on the floor of stables and animal sheds where fermenting manure and debris keeps the eggs warm and moist.  They also do well in human homes where it is usually warmer and more humid than outdoors. They breed all year around. The eggs will hatch into larvae that resemble maggots within 4-6 days. The very active larvae will feed on organic debris including feces of the adult flea and other animals. After three molts it will develop a cocooned pupae where it will undergo a metamorphosis to the adult flea. It can remain in the pupa for several months if necessary until the conditions are suitable. So although human fleas are usually not present in stables or sheds during the coldest months the pupa can easily span the winter to emerge as adults in the early spring. This may explain why they are often the most abundant in the spring when all of the pupae from the late fall and winter emerge. It is unclear if the lifecycle pauses inside a heated human home. A well fed adult can live up to 513 days and even starved can last 135 days (Krasnov, 2012: 54). It is unclear how long they live after being infected by Yersinia pestis (or other pathogens). Fleas only feed on blood as adults so this is their only phase that can be infected by Yersinia pestis.

Modern infestations of P. irritans in Greece and Iran can give a few insights into its disease ecology. Sheep and goats are consistently the most heavily infested animals with P. irritans in modern Iran and Greece. In parts of Iran, P. irritans is the most common flea captured from humans or domestic livestock: goats, sheep, cattle and chickens (Moemenbellah-Fard et al, 2014; Rahbari,  Nabian, & Nourolahi, 2008;  Rafinejad et al, 2013). In some modern surveys, P. irritans is over 90% of the fleas collected in rural areas, found on sheep, goats, cattle, humans and chickens — “wherever the animal infestation was high the fleas easily transmitted to humans” (Rahbari et al, 2008:44). In Greece, Christodoulopoulos et al. (2006) made a very important observation:

“fleas accumulated in the goat environment with each successive generation leading to an increase in their number. This conclusion could be corroborated by the observation that the most successful flea control measure was the change of barn location with movement of the goats to another far away new-constructed barn.” (p. 142-143)

So even with modern insecticides, sheep dips, and building techniques available, the infestation of the building could not be controlled. This has implications for human housing. Observations of flea ecology in Iran back this up, albeit without addressing methods of eliminating infestations.

The Iranian reports discuss human flea bites more. Noting that men who worked with animals had a higher bite rate. Bites are primarily around the ankles and lower legs, often multiple bites in a row.  In Iran they noted that human reactions to the flea bites varied from highly allergic to no sensitivity at all (Rahbari, Nabian, & Nourolahi, 2008). This is a difference in human immunology to the fleas and sensitivity is likely to alter the immune response to not only the bite but also bacteria in the bite. There is also likely to be heterogeneity in which humans and animals are bitten.

As we begin to take Pulex irritans more seriously as a plague vector, there is a lot of basic biology that needs to be done yet. How long can they survive infected? How does it effect their feeding behavior? Some studies showed that a small percentage of P. irritans can block, so what effect does that have on transmission in that small percent of fleas?


References

Archibald, W. S., & Kunitz, S. J. (1971). Detection of plague by testing serums of dogs on the Navajo Reservation. HSMHA Health Reports, 86(4), 377–380.

Bain, A. (2004). Irritating intimates: the archaeoentomology of lice, fleas, and bedbugs. Northeast Historical Archaeology, 33(1), 81–90.

Barnes, Jefferey. (22 April 2014)  Human flea, Arthropod Museum Notes, Number 108. University of Arkansas.

Buckland, P. C., & Sadler, J. P. (1989). A biogeography of the human flea, Pulex irritans L.(Siphonaptera: Pulicidae). Journal of Biogeography (UK).

Christodoulopoulos, G., Theodoropoulos, G., Kominakis, A., & Theis, J. H. (2006). Biological, seasonal and environmental factors associated with Pulex irritans infestation of dairy goats in Greece. Veterinary Parasitology, 137(1-2), 137–143. http://doi.org/10.1016/j.vetpar.2005.12.012

Dobler, G., & Pfeffer, M. (2011). Fleas as parasites of the family Canidae. Parasites & Vectors, 4, 139–139. http://doi.org/10.1186/1756-3305-4-139

Drancourt, M., Houhamdi, L., & Raoult, D. (2006). Yersinia pestis as a telluric, human ectoparasite-borne organism. The Lancet Infectious Diseases, 6(4), 234–241. http://doi.org/10.1016/S1473-3099(06)70438-8

Eisen, Rebecca J., David T. Dennis, and Kenneth L. Gage. “The Role of Early-Phase Transmission in the Spread of Yersinia pestis.” Journal of medical entomology 52.6 (2015): 1183-1192.

Haule, M., Lyamuya, E. E., Kilonzo, B. S., Matee, M. I., & Hangombe, B. M. (2013). Investigation of fleas as vectors in the transmission of plague during a quiescent period in North-Eastern, Tanzania. Journal of Entomology and Nematology, 5(7). http://doi.org/10.5897/JEN2013.0083

Hufthammer, Anne Karin, and Lars Walløe. “Rats cannot have been intermediate hosts for Yersinia pestis during medieval plague epidemics in Northern Europe.” Journal of Archaeological Science 40.4 (2013): 1752-1759.

Kenward, H. (1999). Insect remains as indicators of zonation of land use and activity in Roman Carlisle, England. Reports from the Environmental Archaeology Unit (Vol. 99, pp. 1–30).

Kotti, B. K. (2015). Fleas (Siphonaptera) of mammals and birds in the Great Caucasus. Entomological Review, 95(6), 728–738. http://doi.org/10.1134/S0013873815060068

Krasnov, Boris (2012) Functional and Ecological Ecology of Fleas: A Model for Ecological Parasitology. Cambridge University Press.

Laudisoit, A., Leirs, H., Makundi, R. H., Van Dongen, S., Davis, S., Neerinckx, S., et al. (2007). Plague and the human flea, Tanzania. Emerging Infectious Diseases, 13(5), 687–693. http://doi.org/10.3201/eid1305.061084

Miarinjara A, Rogier C, Harimalala M, Ramihangihajason TR, Boyer S. Xenopsylla brasiliensis fleas in plague focus areas, Madagascar. Emerg Infect Dis. 2016 Dec [3 Sept 2016]. http://dx.doi.org/10.3201/eid2212.160318

Moemenbellah-Fard, M. D., Shahriari, B., Azizi, K., Fakoorziba, M. R., Mohammadi, J., & Amin, M. (2014). Faunal distribution of fleas and their blood-feeding preferences using enzyme-linked immunosorbent assays from farm animals and human shelters in a new rural region of southern Iran. Journal of Parasitic Diseases, 40(1), 169–175. http://doi.org/10.1007/s12639-014-0471-1

O’Sullivan, A. (2008). Early medieval houses in Ireland: social identity and dwelling spaces. Peritia, 20, 225–256.

Panagiotakopulu, E. (2001). Fleas from pharaonic Amarna. Antiquity, 75, 499–500.

Pulex irritans, Animal Diversity Web, accessed 18 June 2016.

Rahbari, S., Nabian, S., & Nourolahi, F. (2008). Flea infestation in farm animals and its health implication. Iranian Journal of Parasitology, 3(2), 43–47.

Rafinejad, J., Piazak, N., Dehghan, A., Shemshad, K., & Basseri, H. R. (2013). Affect of some environmental parameters on fleas density in human and animal shelters. American Journal of Research Communication.

Ratovonjato, J., Rajerison, M., Rahelinirina, S., & Boyer, S. (2014). Yersinia pestis in Pulex irritans Fleas during Plague Outbreak, Madagascar. Emerging Infectious Disease, 20(8), 1414–1415. http://doi.org/10.3201/eid1509.090442

Reilly, E. (2003). The contribution of insect remains to an understanding of the environment of Viking-age and medieval Dublin.  pp. 40-61 In: Medieval Dublin IV. Four Courts Press.

Schedl, W. (2000). “Contribution to insect remains from the accompanying equipment of the Iceman”. pp. 151-155 In S. Bortenschlager & K. Oeggl (Eds.), The Iceman and his Natural Environment. Springer.

Yakhchali, M., & Bahramnejad, K. (2015). A survey of Pulex irritans (Linnaeus 1758, Siphonaptera: Pulicidae) infestation in sheep and residential areas in Kurdistan Province, Iran. The Iranian Journal of Veterinary Science and Technology, 7(1), 40–47.