### Microbiology A little gram-negative rod (aka coccobacillus) that can have bipolar staining. *Y*. *enterocolitica*, *Y*. *frederiksenii*, *Y*. *intermedia*, *Y*. *kristensenii*, *Y*. *pestis*, *Y*. *pseudotuberculosis* and others. It may be misidentified by some automated systems and delay the diagnosis. [^1] ### Epidemiologic Risks *Y*. *pestis* is found in burrowing rodents. > "In North America, plague is found from the Pacific Coast eastward to the western Great Plains and from British Columbia and Alberta, Canada southward to Mexico. Most of the human cases occur in two regions; one in northern New Mexico, northern Arizona, and southern Colorado, another in California, southern Oregon, and far western Nevada. > > It came to the US from Asia with the advent of the steamship. The first outbreak was in San Francisco where the city fathers tried to cover up the problem." Plague is classically spread by fleas. The physiology is interesting. The organism multiplies in the gut of the flea causing obstruction and hunger in the flea. So when it feeds on a human, the flea vomits *Yersinia* into the bite along with a bit of iron to perpetuate the infection. So it is death by flea-bite-us. In the US over 50% of cases are from animal exposure, [^2] often the *infected* pet dog or cat. Occasionally found in chipmunk fleas in the Sierra Nevada Mountains of California. [^3] Not so cute now, are they? Also found in SE Asia, Africa (especially Madagascar) and China. In Africa, increased rainfall presages plague. Rain means plants means food for rodents means a booming rodent population and with it comes death from plague. And Hanta. There was a cluster of pneumonic plague in China when a dog gave it to its master, who then gave it to 12 others. In Madagascar the Asian house shrew *Suncus* *murinus* is the reservoir, [^4] so Petruchio was just trying to keep Padua from getting plague from Kate ([explanation for the Shakespeare impaired](https://en.wikipedia.org/wiki/The_Taming_of_the_Shrew)). Dogs and cats are common vectors in the US. They kill a rodent, or just sniff the prairie dog [^5], get plague and pass it on to their owners. Cats are more likely to get and give pneumonic plague. [^6] So avoid the coughing cat, it may be hacking up more than a hairball. In modern Uganda, history repeats itself with an unusual number of dead rats a harbinger of plague outbreaks where 1 in 4 dies. [^7] [Nice historical review](http://wwwnc.cdc.gov/eid/article/21/1/14-0564_intro). This organism has been plaguing humans for millennia. Get it? Plaguing? I am soooooo clever. *Y*. *enterocolitica*, *Y*. *pseudotuberculosis* are found in a wide variety of domestic and wild animals. ### Syndromes *Y*. *pestis*: bubonic plague. There are three clinical presentations: 1) Bubonic plague: enlarged, tender lymph nodes, fever, chills, and prostration. 2) Septicemic plague: fever, chills, prostration, abdominal pain, shock and bleeding into skin and other organs, a purpura fulminans syndrome, a similar presentation can also be caused by *Capnocytophagia* *canimorsis*, *N*. *meningitis*, and *S*. *pneumoniae* (especially in the asplenic). 3) Pneumonic plague: fever, chills, cough, and difficulty breathing; rapid shock and 100% fatal in 72 hours if antibiotics are delayed more than 18 hours after the onset of respiratory symptoms. Infectious: put in respiratory isolation. Recent data suggests 'only' a 17% mortality rate. [^8] *Y*. *enterocolitica*, *Y*. pseudotuberculosis: Diarrhea, sepsis in compromised hosts and those with iron overload states, and Pharyngitis. *Y*. *enterocolitica* can cause transfusion sepsis, usually from old pints (blood, not beer). It multiplies nicely in cold and needs iron, which is plentiful after a couple of weeks as the red cells start to break down. [^9] *Y*. pseudotuberculosis: mesenteric adenitis; can mimic acute appendicitis. And in the Far East a Scarlet-Like Fever syndrome. [^10] ### Treatment *Y*. *pestis*: for historical reasons, in order of preference, gentamicin, streptomycin, doxycycline/tetracycline, OR chloramphenicol are the recommended agents, however, I bet all aminoglycosides, piperacillin, quinolones and third-generation cephalosporins will work (although not suggested), one of which most people will get for empiric sepsis anyway. Oral ciprofloxacin was effective in Africa, but I would start with iv in the US. [^11] There was a naturally occurring strain with multiple resistance (chloramphenicol, streptomycin, and tetracycline, sulfonamides and tetracycline) in Madagascar, [^12] and bioterrorism strains will likely be resistant as well. *Y*. *enterocolitica*, *Y*. pseudotuberculosis: aminoglycosides, doxycycline, piperacillin, and quinolones should all be effective. ### Notes Familial Mediterranean Fever carriers are immune to plague, so another human disease selected for by infection and evolution. There is an interesting book "The Biology of Plagues" that makes a compelling argument that the black death of the middle ages was NOT due to *Y*. *pestis*. However, when they have dug up patients from plague pits, it is the DNA of *Y*. *pestis* they find in the pulp of teeth. On the basis of dental pulp, it was responsible for Plague of Justinian and > "Y *pestis* lineages that caused the Plague of Justinian and the Black Death 800 years later were independent emergences from rodents into human beings." [^13] *Y*. *pestis* may be used for bioterrorism.  Back in the 16th century, there was a plan to use "a liquid made from the spleens and buboes of plague victims" (aka Mountain Dew) as a weapon to end a siege. [^14] An agent of bioterrorism, the Soviets probably bioengineered a strain to be resistant to antibiotics, which has also occurred naturally in Madagascar. Using genetic analysis, plague may have started in Europe a century earlier than supposed. [^15] ### Puswhisperers [Wrong. Again. And again. And again](http://www.pusware.com/PW1/WrongAgainAndagainAndagain.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop36.mp3) [Grand Rounds Part 1: Where is Ra's al Ghul when we need him?](http://www.pusware.com/PW1/GrandRounds1.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop107.mp3) [Peripatetic Pastimes](http://www.pusware.com/PW4/PeripateticPastimes.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop547.mp3) [I am now to be called the Chief Morber](http://www.pusware.com/PW6/ChiefMorber.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop712.mp3) [Vague Unease](http://www.pusware.com/PW9/VagueUnease.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1089.mp3) ### Rationalizations [^1]: Tourdjman M, Ibraheem M, Brett M, Debess E, Progulske B, Ettestad P, McGivern T, Petersen J, Mead P. Misidentification of Yersinia pestis by automated systems, resulting in delayed diagnoses of human plague infections--Oregon and New Mexico, 2010-2011. Clin Infect Dis. 2012 Oct;55(7):e58-60. doi: 10.1093/cid/cis578. Epub 2012 Jun 19. PMID: 22715170. [^2]: Campbell SB, Nelson CA, Hinckley AF, et al. Animal Exposure and Human Plague, United States, 1970–2017. _Emerging Infectious Diseases_. 2019;25(12):2270-2273. doi:10.3201/eid2512.191081. [^3]: Hammond TT, Liebman KA, Payne R, et al. Plague Epizootic Dynamics in Chipmunk Fleas, Sierra Nevada Mountains, California, USA, 2013–2015. _Emerging Infectious Diseases_. 2020;26(4):801-804. doi:10.3201/eid2604.190733. [^4]: Rahelinirina S, Rajerison M, Telfer S, Savin C, Carniel E, Duplantier JM. The Asian house shrew Suncus murinus as a reservoir and source of human outbreaks of plague in Madagascar. PLoS Negl Trop Dis. 2017 Nov 20;11(11):e0006072. doi: 10.1371/journal.pntd.0006072. PMID: 29155827; PMCID: PMC5714386. [^5]: Schaffer PA, Brault SA, Hershkowitz C, et al. Pneumonic Plague in a Dog and Widespread Potential Human Exposure in a Veterinary Hospital, United States. _Emerging Infectious Diseases_. 2019;25(4):800-803. doi:10.3201/eid2504.181195. [^6]: Kassem AM, Tengelsen L, Atkins B, Link K, Taylor M, Peterson E, Machado A, Carter K, Hutton S, Turner K, Hahn C. Notes from the Field: Plague in Domestic Cats - Idaho, 2016. MMWR Morb Mortal Wkly Rep. 2016 Dec 9;65(48):1378-1379. doi: 10.15585/mmwr.mm6548a5. PMID: 27932783. [^7]: Forrester JD, Apangu T, Griffith K, et al. Patterns of Human Plague in Uganda, 2008–2016. _Emerging Infectious Diseases_. 2017;23(9):1517-1521. doi:10.3201/eid2309.170789. [^8]: Salam AP, Rojek A, Cai E, et al. Deaths Associated with Pneumonic Plague, 1946–2017. _Emerging Infectious Diseases_. 2020;26(10):2432-2434. doi:10.3201/eid2610.191270. [^9]: Guinet F, Carniel E, Leclercq A. Transfusion-transmitted Yersinia enterocolitica sepsis. Clin Infect Dis. 2011 Sep;53(6):583-91. doi: 10.1093/cid/cir452. PMID: 21865196. [^10]: Amphlett A. Far East Scarlet-Like Fever: A Review of the Epidemiology, Symptomatology, and Role of Superantigenic Toxin: Yersinia pseudotuberculosis-Derived Mitogen A. Open Forum Infect Dis. 2015 Dec 17;3(1):ofv202. doi: 10.1093/ofid/ofv202. PMID: 26819960; PMCID: PMC4728291. [^11]: Apangu T, Griffith K, Abaru J, et al. Successful Treatment of Human Plague with Oral Ciprofloxacin. _Emerging Infectious Diseases_. 2017;23(3):553-555. doi:10.3201/eid2303.161212. [^12]: Galimand M, Guiyoule A, Gerbaud G, Rasoamanana B, Chanteau S, Carniel E, Courvalin P. Multidrug resistance in Yersinia pestis mediated by a transferable plasmid. N Engl J Med. 1997 Sep 4;337(10):677-80. doi: 10.1056/NEJM199709043371004. PMID: 9278464. [^13]: Wagner DM, Klunk J, Harbeck M, Devault A, Waglechner N, Sahl JW, Enk J, Birdsell DN, Kuch M, Lumibao C, Poinar D, Pearson T, Fourment M, Golding B, Riehm JM, Earn DJ, Dewitte S, Rouillard JM, Grupe G, Wiechmann I, Bliska JB, Keim PS, Scholz HC, Holmes EC, Poinar H. Yersinia pestis and the plague of Justinian 541-543 AD: a genomic analysis. Lancet Infect Dis. 2014 Apr;14(4):319-26. doi: 10.1016/S1473-3099(13)70323-2. Epub 2014 Jan 28. PMID: 24480148. [^14]: Thalassinou E, Tsiamis C, Poulakou-Rebelakou E, et al. Biological Warfare Plan in the 17th Century—the Siege of Candia, 1648–1669. _Emerging Infectious Diseases_. 2015;21(12):2148-2153. doi:10.3201/eid2112.130822. [^15]: https://www.smithsonianmag.com/history/did-black-death-rampage-across-world-more-century-previously-thought-180977331/