akari () 187 Pierre-Edouard Fournier and Didier Raoult

SHORT VIEW SUMMARY

Definition Microbiology Therapy } Vesicular fever with eschar caused by } Infection caused by the intracellular bacterium } Doxycycline, 100 mg twice daily for 7 days. mite bites; may be confused with Rickettsia akari. Prevention anthrax. Diagnosis } Mouse eradication from buildings will prevent Epidemiology } Based on serology and polymerase chain transmission to humans. } Found worldwide but is particularly common reaction assay of swab from a vesicle or in New York City. eschar.

Rickettsialpox is a worldwide mite-borne presenting as a is approximately 7 to 14 days. Eschar is the clinical hallmark of the febrile and vesicular eruption. It is caused by Rickettsia akari, associated disease.12 It starts as a primary papule; a vesicle then appears in the with mice, and transmitted by its ectoparasite, the mite Liponyssoides center and, when it dries, it leaves a brown or dark eschar (Fig. 187.1). sanguineus. Palpable regional lymph nodes draining this eschar are common and are usually tender.11 The rash usually appears on the third or fourth day. ETIOLOGY It is papular at the beginning and becomes vesicular in many patients. Rickettsia akari isis classified among group rickettsiae based The vesicles dry, and each leaves a black crust. Patients typically have on antigenic and genetic data. Its genome has a size (1.23 Mb) similar 20 to 40 skin lesions. In contrast with other spotted fever group rick- to those of other Rickettsia species but its plasmid content varies, possibly ettsioses, palms and soles are not involved. The disease is benign, and according to the strain and/or culture passage, as described for other patients usually recover. A transient leukopenia can be documented, closely related species such as .1,2 as can thrombocytopenia and elevated aminotransferases.13 A case was It differs from other Rickettsia species in that its target cell in humans described of a human immunodeficiency virus–positive patient who is the macrophage and not the endothelial cell,3 and it is transmitted recovered.14 by the bite of Liponyssoides sanguineus, the mouse mite. DIAGNOSIS EPIDEMIOLOGY SerologySerology has beebeenn the easiest tool that can be used for diagnosis. Cross- The ep epidemiologyidemiology ooff ririckettsialpoxc is linked to house mice. Another reactions have been noted between R. akari and . vector (perhaps the tick or ) is suspected in that the seroprevalence Assay of homologous antigens is more sensitive and is preferable. of R. akari is high in New York City dogs.4 In Korea, a sylvatic cycle of Immunoglobulin M and immunoglobulin G are detected 7 to 15 days R. akari in voles is suspected.5 Rickettsialpox was initially described in after onset. Immunohistochemistry is of value with skin biopsies and New York City in 19466 and has since been reported in Europe, Ukraine, was considered the most efficient tool in the New York City series. A Korea, and South Africa.7,8 The 2001 bioterrorist attack with anthrax polymerase chain reaction (PCR) assay targeting DNA sequences coding directed the attention of physicians to skin eschars and rash and allowed for a 17-kDa antigen was used on fresh tissues.7 Recently, it was found the identification of 34 cases of rickettsialpox in New York City7 from that swabbing eschar or vesicles of patients with rickettsioses allows February 2001 to August 2002. The patients were suspected of suffering DNA detection by PCR15,16 and should be the preferred sample. Isolation cutaneous anthrax or smallpox. The usual yearly incidence in New York from skin biopsy may be performed on Vero cells in specialized labo- City is 5 cases. A surprisingly high seroprevalence of R. akari has been ratories. Consideration of R. akari in the differential diagnosis is critical reported in intravenous drug users from Baltimore9 and in patients in that its eschar can be misdiagnosed as inoculation anthrax. Moreover, using a free clinic in Los Angeles County.10 Because this disease is not it is one of the few infections that causes vesicular rashes, along with actively tracked, its overall prevalence is completely unknown. smallpox, varicella, herpes zoster, herpes simplex, and some other rickettsioses (e.g., Queensland tick and African tick-bite fever). CLINICAL MANIFESTATIONS The typ typicalical ttriadriad ooff tthehe ddisease,isease, wwhichhich inincludesclu fever, vesicular rash, THERAPY and eschar,11 was found in 92% of patients investigated in New York TreatmentTreatment17 forfor rickettsialpox is doxycycline, 200 mg per day, given as City (Table 187.1). Indeed, the disease is recognized by only a few 100 mg twice daily, for 7 days. The alternative treatment is chloram- physicians; in the New York City cases, half of patients were identi- phenicol. Although clinical efficacy is unknown, R. akari is susceptible fied by a single physician and 75% by three. The incubation period to many antibiotics, including azithromycin. 2358 2359

TABLE 187.1 Clinical and Epidemiologic Findings in Rickettsialpox Cha PADDOCK GREENBERG KASS 7 6 11 SERIES ET AL. ET AL. ET AL. p ter 18 Number of cases 34 144 13

Year of study 2003 1947 1994 7

Fever 97% 100% 100% Ric k Mice at residence or work 67% — — ettsia akari (Rickettsialpox) Eschars 90% 99.8% 100% Any rash 100% 100% 100% Vesicular rash — — 92% Fever plus eschars plus rash 92% — 100% Hospitalization 32% — — FIG. 187.1 Patient with eschar of rickettsialpox in 2002. (Courtesy C. Paddock.) Headache NA 90% 100% NA, Not available.

References 6. Greenberg M, Pellitteri O, Klein IF, et al. 12. Brettman LR, Lewin S, Holzman RS, et al. Rickettsialpox: Rickettsialpox—a newly recognized rickettsial disease, II. report of an outbreak and a contemporary review. 1. Baldridge GD, Burkhardt NY, Labruna MB, et al. Wide Clinical observations. JAMA. 1947;133:901–906. Medicine (Baltimore). 1981;60:363–372. dispersal and possible multiple origins of low-copy- 7. Paddock CD, Zaki SR, Koss T, et al. Rickettsialpox in 13. Madison G, Kim-Schluger L, Braverman S, et al. Hepatitis number plasmids in rickettsia species associated with New York City: a persistent urban zoonosis. Ann N Y in association with rickettsialpox. Vector Borne Zoonotic blood-feeding arthropods. Appl Environ Microbiol. Acad Sci. 2003;990:36–44. Dis. 2008;8:111–115. 2010;76:1718–1731. 8. Paddock CD, Koss T, Eremeeva ME, et al. Isolation of 14. Sanders S, Di Costanzo D, Leach J, et al. Rickettsialpox in 2. Fournier PE, Belghazi L, Robert C, et al. Variations of Rickettsia akari from eschars of patients with a patient with HIV infection. J Am Acad Dermatol. plasmid content in Rickettsia felis. PLoS ONE. rickettsialpox. Am J Trop Med Hyg. 2006;75:732–738. 2003;48:286–289. 2008;3:e2289. 9. Comer JA, Tzianabos T, Flynn C, et al. Serologic evidence 15. Bechah Y, Socolovschi C, Raoult D. Identification of 3. Walker DH, Hudnall SD, Szaniawski WK, et al. of rickettsialpox (Rickettsia akari) infection among rickettsial infections by using cutaneous swab specimens Monoclonal antibody-based immunohistochemical intravenous drug users in inner-city Baltimore, Maryland. and PCR. Emerg Infect Dis. 2011;17:83–86. diagnosis of rickettsialpox: the macrophage is the Am J Trop Med Hyg. 1999;60:894–898. 16. Denison AM, Amin BD, Nicholson WL, et al. Detection principal target. Mod Pathol. 1999;12:529–533. 10. Bennett SG, Comer JA, Smith HM, et al. Serologic of Rickettsia rickettsii, , and Rickettsia 4. Comer JA, Vargas MC, Poshni I, et al. Serologic evidence evidence of a Rickettsia akari-like infection among akari in skin biopsy specimens using a multiplex of Rickettsia akari infection among dogs in a wild-caught rodents in Orange County and humans in real-time PCR assay. Clin Infect Dis. 2014;59:635–642. metropolitan city. J Am Vet Med Assoc. Los Angeles County, California. J Vector Ecol. 17. Raoult D, Maurin M. Rickettsia akari (rickettsialpox). In: 2001;218:1780–1782. 2007;32:198–201. Yu VL, Weber R, Raoult D, eds. Antimicrobial Therapy 5. Jackson EB, Danauskas JX, Coale MC, et al. Recovery of 11. Kass EM, Szaniawski WK, Levy H, et al. Rickettsialpox in and Vaccine. 2nd ed. New York: Apple Trees Production; Rickettsia akari from the Korean vole Microtus fortis a New York City hospital, 1980 to 1989. N Engl J Med. 2002:889–892. pelliceus. Am J Hyg. 1957;66:301–308. 1994;15:1612–1617.