CLOSE ENCOUNTERS WITH THE ENVIRONMENT

What’s Eating You? Oriental ( cheopis)

Lauren E. Krug, BS; Dirk M. Elston, MD

he (Xenopsylla cheopis) is important for (murine) in best known for its ability to spread 2 poten- South Texas. The has been shown to be T tially lethal to humans: and a competent vector but has low efficiency and a endemic (murine) typhus. Plague has caused 3 great decreased bacterial load when compared with the rat that killed almost a third of the population flea.4 Although X cheopis remains the most impor- in Europe.1 Similar to other , X cheopis has a lat- tant plague vector in endemic zoonotic , erally compressed body and large hind legs (Figure). P irritans and pulmonary of pneumonic Female fleas have a more rounded body; males have a plague were more important means of spread during flatter back, rounded ventral surface, and a prominent the great pandemics. retroverted genital apparatus approximately half the The method of acquiring the 2 (R typhi length of the entire flea. and Y pestis) is the same: takes a meal Unlike cat and fleas, XenopsyllaCUTIS fleas are comb- from an infected such as a rat, mouse, or less, that is they lack the prominent combs resembling opossum, and then transmits the organism through a mustache and mane of on cat and dog fleas. a bite or defecation. The consumed bacteria must Additional identifying features for X cheopis include survive long enough in the flea’s gut to be transmitted. a rounded frons (forehead). The flea that is closest in survives by forming cohesive aggregates appearance is irritans (the ). Unlike that protect the bacteria from being lysed, allowing P irritans, X cheopis has several setae () posterior for further propagation. The aggregate of bacteria to theDo antennae as well as a pleuralNot rod visible within can becomeCopy so large that it can block the flea’s the mesopleuron above the second pair of legs. In midgut, resulting in starvation.5,6 The source of the contrast, Pulex fleas lack the pleural rod and have only blood (eg, rat, mouse, opossum) impacts the flea’s 1 hair on the postantennal head. ability to maintain Y pestis in an adequate bacterial load. The rat is the most infectious source of blood, 'LVHDVH9HFWRU possibly due to nutrient content, passage time, Xenopsylla cheopis serves as an important arthro- and decreased complement content in the blood.7 pod vector for Yersinia pestis and typhi, , an obligate intracellular organism, the organisms that cause the plague and endemic survives by entering the flea’s midgut epithelial cells. (murine) typhus, respectively. Additionally, the flea Within 3 to 5 days, the entire midgut has been shown to harbor (cat flea is infected.8 Despite the potential for starvation )2 and 2 of : Bartonella with massive propagation of Y pestis, the flea’s tribocorum and Bartonella vinsonii subsp vinsonii.3 It overall fitness usually is not affected by the presence should be noted that the cat flea is now the most of either of the bacteria, which is a marked difference from the ancestor of Y pestis, Yersinia pseudotuberculosis, whose toxins detrimentally Ms. Krug is from Temple University School of Medicine, Philadelphia, affect the flea, inflicting diarrhea and immobility.9 Pennsylvania. Dr. Elston is from the Departments of Dermatology and Temperature-regulated expression plays a role Medicine, Geisinger Medical Center, Danville, Pennsylvania. in the -vector relationship. Certain key in The authors report no conflict of interest. each species of bacteria are turned on or off due to Correspondence: Dirk M. Elston, MD, Department of Dermatology and Laboratory Medicine, Geisinger Medical Center, 100 N Academy Ave, the relatively low body temperature of the flea. If the Danville, PA 17822-5206 ([email protected]). bacteria are introduced to a warmer environment,

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Multiple hairs No pronotal comb

Pleural rod No genal comb

Xenopsylla cheopis.

such as a human, the gene expression changes and as well as gangrene of acral areas including the ensues.10,11 nose and digits, which prompted the historical Humans become a target when the infected flea is nickname “.”16 The disease persists at in search of a blood meal, oftenCUTIS due to the death a low-level enzootic state in the western United of its prior host. When rat are treated States. From 1947-1996, 390 cases of endemic through extermination, there may be a transient plague were reported in the United States with increase in bites, as the fleas look for alterna- the majority of cases occurring in New Mexico, tive hosts. The bacteria can be transmitted in Arizona, Colorado, and California.17 Because of several ways. Small pieces of the Y pestis bacterial the severity of the disease and its ability to be aggregate, which have blocked the flea’s midgut, weaponized, Y pestis is considered a potential agent can Dobe regurgitated during feeding.Not Alternatively, of . Copy The bacteria could be spread by the Y pestis can enter the skin through infected mouth- mass release of fleas but is more likely to be released parts or flea feces.12 Unblocked fleas have been as aerosolized droplets leading to pneumonic plague. shown to be as efficient as blocked fleas at transmit- In the latter case, lymphadenitis and buboes would ting Y pestis and are able to infect another mammal not be present. only 1 day after acquiring the bacteria themselves.13 Endemic (Murine) Typhus—Rickettsia typhi is Without a blocked gut, fleas can survive longer, manifested as endemic (murine) typhus, with the allowing for more opportunity to spread the bacte- majority of US cases reported in Texas and south- ria.14 Rickettsia typhi is mainly transmitted to humans ern California. After an of 7 to when the flea feeds and its infected feces come in 14 days, the most common symptoms include , contact with the bite site. The feces are inoculated headache, rash, arthralgia, and gastrointestinal with bacteria that have been released from the gut’s tract and respiratory symptoms. Thus the presenta- epithelial cells into the lumen via binary .15 tion can mimic and often be confused with more Plague—After X cheopis transmits Y pestis to common viral illnesses. The rash has been reported the human, of in only 54% of patients, varying greatly in presenta- typically begin after a 2- to 6-day incubation period, tion but most commonly presenting on the trunk; it including fever, painful lymphadenitis, and buboes is nonpruritic and is usually macular or morbilliform (fluctuant necrotic lymph nodes). If left untreated, in appearance.18,19 Severe manifestations may occur the disease can enter the bloodstream, leading to in patients who have received a sulfa drug dur- shock, disseminated intravascular coagulation, and ing the course of their illness. These patients may death. Patients with septicemic plague may present present with multiorgan failure, coma, and stellate with large ecchymoses similar to meningococcemia purpuric infarcts.18

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3UHYHQWLRQDQG7UHDWPHQW 8. Houhamdi L, Fournier PE, Fang R, et al. An experimen- Keeping and other that potentially tal model of human body infection with Rickettsia harbor infected fleas away from humans can decrease typhi. Ann N Y Acad Sci. 2003;990:617-627. the incidence of disease transmission. It also has 9. Erickson DL, Waterfield NR, Vadyvaloo V, et al. Acute been suggested to use to exterminate fleas. oral toxicity of Yersinia pseudotuberculosis to fleas: impli- However, fleas may develop resistance and tolerance cations for the evolution of vector-borne transmission of to commonly used pesticides, such as DDT, mala- plague. Cell Microbiol. 2007;9:2658-2666. thion, and permathion, which may limit the efficacy 10. Robinson JB, Telepnev MV, Zudina IV, et al. Evaluation of these products.20 of a Yersinia pestis mutant impaired in a thermoregulated If either of these is suspected, treat- type VI-like secretion system in flea, macrophage and ment should be immediately started, even before murine models. Microb Pathog. 2009;47:243-251. diagnosis is confirmed, to avoid further complica- 11. Dreher-Lesnick SM, Ceraul SM, Rahman MS, et al. tions. Bubonic plague can be treated with strepto- -wide screen for temperature-regulated genes mycin. Alternatively, gentamicin has been suggested of the obligate intracellular bacterium, Rickettsia typhi. as a treatment option. Tetracycline and BMC Microbiol. 2008;8:61. can be used as prophylaxis.18 Endemic (murine) 12. Perry RD, Fatherston JD. Yersina pestis—etiologic agent typhus can be treated with either tetracycline or of plague. Clin Microbiol Rev. 1997;10:35-66. doxycycline, which have been shown to decrease the 13. Eisen RJ, Wilder AP, Bearden SW, et al. Early-phase trans- length of the febrile illness.19 mission of Yersinia pestis by unblocked Xenopsylla cheopis (Siphonaptera: ) is as efficient as transmission by 5()(5(1&(6 blocked fleas. J Med Entomol. 2007;44:678-682. 1. Prentice MB, Rahalison L. Plague. Lancet. 2007;369: 14. Eisen RJ, Eisen L, Gage KL. Studies of vector competency 1196-1207. and efficiency of North American fleas for Yersinia pestis: 2. Eremeeva ME, Warashina WR, Sturgeon MM, et al. state of the field and future research needs. J Med Rickettsia typhi and R. felis in rat fleas (Xenopsylla cheopis), Entomol. 2009;46:737-744. Oahu, Hawaii. Emerg Infect Dis. 2008;14:1613-1615. 15. Azad AF. Epidemiology of . Annu Rev 3. Reeves WK, Rogers TE, DurdenCUTIS LA, et al. Association Entomol. 1990;35:553-569. of Bartonella with the fleas (Siphonaptera) of 16. McGovern TW, Christopher GW, Eziten EM. Cutaneous and using molecular techniques. J Vector Ecol. manifestations of biological warfare and related threat 2007;32:118-122. agents. Arch Dermatol. 1999;135:311-322. 4. Eisen RJ, Borchert JN, Holmes JL, et al. Early- 17. Inglesby TV, Dennis DT, Henderson DA, et al. Plague as phase transmission of Yersinia pestis by cat fleas a biological weapon: medical and manage- ( felis) and their potential role as vectors ment. Working Group on Civilian Biodefense. JAMA. Doin a plague-endemic region of NotUganda. Am J Trop Med 2000;283:2281-2290.Copy Hyg. 2008;78:949-956. 18. Dumler JS, Taylor JP, Walker DH. Clinical and labora- 5. Hinnebusch BJ, Rudolph, AE, Cherepanov P, et al. Role tory features of murine typhus in south Texas, from 1980 of Yersinia murine toxin in survival of Yersinia pestis in the through 1987. JAMA. 1991;266:1365-1370. midgut of the flea vector. Science. 2002;296:733-735. 19. Civen R, Ngo V. Murine typhus: an unrecognized subur- 6. Forman S, Bobrov AG, Kirillina O, et al. Identification ban vectorborne disease. Clin Infect Dis. 2008;46:913-918. of critical amino acid residues in the plague biofilm Hms 20. Shyamal B, Ravi Kumar R, Sohan L, et al. Pres- proteins. Microbiology. 2006;152(pt 11):3399-3410. ent susceptibility status of rat flea Xenopsylla cheopis 7. Eisen RJ, Vetter SM, Holmes JL, et al. Source of host (Siphonaptera: Pulicidae), vector of plague against organo- blood affects prevalence of infection and bacterial chlorine, organophosphate and synthetic pyrethroids 1. loads of Yersinia pestis in fleas. J Med Entomol. 2008;45: the Nilgiris District, Tamil Nadu, India. J Commun Dis. 933-938. 2008;40:41-45.

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