sign in sign up
<<
Home , Bartonellosis, Ehrlichia ewingii, Proteobacteria

Spotlight on

Ehrlichia ewingii

Sponsored by: By Leah A. Cohn, dvm, phd, dacvim and Edward B. Breitschwerdt, dvm, dacvim Spotlight on ewingii

In many parts of the United States, of dogs with the is far more common than infection with the better-known . Although these two ehrlichial share a phyloge- netic similarity, there are many important differences, including vectors, host- tropisms, disease mani- festations, geographic restrictions, and zoonotic potential. In fact, E. ewingii produces morulae in granulocytes rather than monocytes, is transmitted by a highly prevalent environmental tick (, the lone star tick) as compared with the localized kennel tick (, the brown dog tick), and often causes lameness or polyarthritis as a primary component of the dog’s clinical presentation. It is important for veterinarians practicing in E. ewingii-endemic regions of the south central and southeast- ern United States to be familiar with tick transmission, disease consequences, diagnosis, treatment, and the zoonotic implications that are particular to E. ewingii.

Transmission and states.9 Lone star are aggressive ticks central nervous system signs (e.g., head geographic distribution that commonly feed on dogs, people, and tilt, tremors, and anisocoria) may also The only proven competent vector for numerous wildlife .10,11 As a result, be present.19,20 Rarely reported findings the transmission of canine granulocytic serologic evidence supporting exposure to have included hemorrhage, weight loss, is Amblyomma americanum, E. ewingii is very common in A. america- organomegaly, uveitis, pruritus, vomiting, the lone star tick. Although E. ewingii in- num-endemic states. against E. and diarrhea.12,19-21 Onset of clinical signs fection has also been documented in dogs ewingii have been detected in 26% to 44.8% generally occurs within 7 to 14 days fol- from both South America and Africa, of randomly sampled dogs in Oklahoma, lowing infection. the tick species responsible for natural Missouri, and Arkansas, with 9% to 20% It is quite likely that many dogs infected transmission in those regions remains to testing positive for E. ewingii DNA by with E. ewingii either remain clinically be determined.1,2 Transstadial transmis- polymerase chain reaction (PCR).9,12,13 healthy or develop a brief, self-limiting sion in the lone star tick assures that ticks illness, as has been reported in experi- can be infected during all three stages of Pathogenesis mentally infected dogs.15,16 The often mild the cycle (larva, nymph, and adult) and and clinical disease pathogenicity following infection is further remain competent to transmit E. ewingii at Ehrlichia ewingii is a small, obligate intra- supported by the high seropositive rates their next blood meal.3,4 cellular bacterium, and, following the bite among dogs lacking historical evidence White-tailed deer, the major host species of an infected tick, it invades granulocytes of clinical disease attributable to canine for A. americanum, apparently serve as forming membrane-bound, intracyto- granulocytic ehrlichiosis, and the lack the major reservoir for E. ewingii. Not plasmic colonies of known as of reported mortality due to E. ewingii surprisingly, E. ewingii occur morulae.14 The time required from tick infection.3,9,15 Immunosuppression may most often in the southeastern and south attachment to pathogen transmission exacerbate or potentiate disease manifes- central United States where both white- is unknown. Morulae can be observed tations in infected dogs, as it apparently tailed deer and lone star ticks are plentiful within granulocytes in as little as 12 days does in E. ewingii-infected people.22-24 (Figure 1).5-8 In fact, dogs are more likely to after experimental inoculation.3,15,16 Experimental infection with E. ewingii be seropositive for E. ewingii than for either Clinical illness associated with canine has been more successfully attained in E. canis or in Missouri, granulocytic ehrlichiosis is most often an dogs receiving either cyclophosphamide or acute febrile glucocorticoids.3,16,25 Similarly, co-infection Canine granulocytic ehrlichiosis caused by condition with other tick-transmitted pathogens occurs most often in the southeastern associated may worsen disease manifestations in E. ewingii with musculo- infected dogs.26 and south central United States where both skeletal signs. Evidence to date suggests that canine white-tailed deer and lone star ticks are plentiful. Reluctance and human granulocytic ehrlichiosis to stand or causes only an acute illness in dogs and Oklahoma, Arkansas, Kansas, Georgia, walk, lameness, a stiff or stilted gait, and people. This association is in contrast to Alabama, Mississippi, Tennessee, Florida, joint effusion are common findings inE. the pathogenesis of canine monocytic Virginia, and New Jersey.9 The average se- ewingii-infected dogs and may be quite ehrlichiosis, caused by E. canis, where the roprevalence for E. ewingii is 8.5% in these severe.12,17-19 Lethargy, anorexia, and acute illness typically resolves spontane- 2 ously, after which the dog enters a period of subclinical infection, followed in some cases by the development of chronic disease manifestations that can be quite challenging to treat.27-29 Due to the acute nature of canine granulocytic ehrlichiosis, disease manifestations have only been identified when vector lone star ticks are active, predominantly during the late spring and summer.19,30 At the University of Missouri Veterinary Medical Teaching Hospital, from 32 dogs with granulocytic morulae and clinical illness compatible Figure 1. This map shows with E. ewingii infection, only two were the distribution of Amblyomma identified outside of the months May to americanum (the lone star tick; August (in September and November) inset) in the United States. (Cohn, L: Unpublished data). Despite the fact that illness documented to result ehrlichiosis.31,32 Arthrocentesis from joints or summer. However, there is substantial from E. ewingii infection is acute in nature, of affected dogs with polyarthritis reveals overlap in the clinical presentation for dogs actual infections can be persistent.15,19 It is neutrophilic inflammation.19 On occasion, infected with other tick-borne pathogens, possible that chronic E. ewingii infections morulae are identified in granulocytes from including rickettsii and may contribute to as-of-yet unrecognized peripheral blood (Figure 2), cerebrospinal species. Examination of a peripheral blood disease manifestations or pathophysiologic fluid, joint fluid, consequences. prostatic fluid It is possible that chronic E. ewingii infections (Cohn L.: Person- may contribute to as-of-yet unrecognized disease Clinicopathologic al observation), or findings and diagnosis potentially other manifestations or pathophysiologic consequences. As with most ehrlichial infections, bodily fluids.18-20 Unfortunately, observa- smear to identify and thrombocytopenia is the most consistent tion of morulae is neither sensitive nor allow visual inspection of granulocytes for clinicopathologic abnormality associated specific; microscopic differentiation ofA. morulae is often the only diagnostic test with E. ewingii infection.3,15,18-20 Neverthe- phagocytophilum from E. ewingii morulae performed before treatment is initiated. less, a normal platelet count does not rule is impossible, therefore PCR confirmation Culture of the pathogen from the blood out the possibility of active infection, and of the infecting is recommended, has thus far been unsuccessful in a research thrombocytopenia has been found to be particularly when morulae are found in setting, so disease diagnosis via pathogen cyclical in some experimentally infected dogs in non-endemic regions. isolation is not possible. Instead, identifica- dogs over a period of weeks.15 Occasionally, A presumptive clinical diagnosis can be tion of E. ewingii nucleic acid via PCR has mild anemia and reactive are made based on compatible signs in dogs been used. PCR testing not only detects E. identified.12,19 Similar to other rickettsial from endemic regions during the spring ewingii, but also can be used to distinguish infections, short-lived leukopenia was recognized during the early acute phase of Figure 2. A morula in a experimental infection in dogs.15 Serum neutrophil. These morulae biochemical abnormalities are mild and caused by infection with nonspecific but may include increases in either Ehrlichia ewingii or hepatic enzyme concentrations, hyperglob- phagocytophilum appear identical. While micro- ulinemia, hypokalemia, and hyperphospha- scopic recognition of morulae 15,20,21 temia or hypophosphatemia. Protein- is extremely useful, it is an uria, which has been associated with both insensitive diagnostic tool for E. canis and Anaplasma phagocytophilum disease confirmation. (Courtesy of Dr. Linda Berent, infections, has thus far not been identified University of Missouri Veterinary as a component of canine granulocytic Medical Diagnostic Laboratory.) 3 Spotlight on Ehrlichia ewingii

not detect E. ewingii antibodies in most infected dogs, whereas these peptides do Ehrlichia ewingii infection in dogs cross-react with E. chaffeensisantibod - CLINICAL SIGNS ies.34,36 For the SNAP® 4Dx® Plus Test kit, • Clinical signs include , musculoskeletal signs (reluctance to stand or walk, addition of an E. ewingii peptide allows, lameness, stiff or stilted gait, joint effusion), lethargy, anorexia, and central nervous for the first time, serologic detection ofE. system signs (head tilt, tremors, anisocoria) • Signs may be worse if there is co-infection with other tick-transmitted pathogens ewingii-specific antibodies. Thus, a single • Some E. ewingii-infected dogs remain clinically healthy; some develop brief, “positive blue dot” on a SNAP 4Dx Plus self-limiting illness Test will reflect serologic evidence of exposure to , , LABORATORY ABNORMALITIES E. canis E. ewingii E. chaffeen- • E. ewingii infects predominantly neutrophils (granulocytes) forming membrane- sis, or any combination of these three bound colonies of organisms known as morulae that are sometimes identified on Ehrlichia species. Importantly, serologic review of a stained blood smear testing can be used not only to diagnose a • Thrombocytopenia is the most consistent laboratory finding, but normal platelet count does not rule out active infection specific infection, but can also be used to rule out infections with other pathogens DIAGNOSTIC PROCEDURES that might cause similar clinical signs or Serologic Testing • E. canis IFA — May detect cross-reactive antibodies from a dog infected with pathologic abnormalities (e.g., anaplas- E. ewingii. mosis, , , canine ® ® • ELISA (SNAP 4Dx Plus Test) — Uses species-specific peptides for detection of monocytic ehrlichiosis, Rocky Mountain antibodies to E. canis, E. ewingii, and E. chaffeensis; indicates exposure to one or a combination of Ehrlichia species ) or to characterize atypical • Lack of response during acute illness does not rule out infection; retest in or more severe disease manifestation that 2 to 3 weeks occurs during co-infections.37,38 PCR Testing • Can identify active E. ewingii infection; PCR detects E. ewingii, and can distin- guish it from related Ehrlichia species and Anaplasma phagocytophilum Treatment and prevention Treatment should not be withheld pend- this pathogen from related Ehrlichia species transmitted infection, positive documenta- ing disease confirmation from dogs with and from A. phagocytophilum. In addition, tion of antibody titers against E. ewingii clinical signs compatible with canine gran- PCR testing may be helpful in identifying can only confirm prior exposure, but does ulocytic ehrlichiosis in endemic regions. those dogs with subclinical, persistent E. not confirm disease causation or active Although mortality has not been reported, ewingii infections.12,19,22,33 infection at the time of sample collection. dogs with illness attributable to canine Serologic tests are often used in epide- Based upon experimental studies, some granulocytic ehrlichiosis often seem to be miologic studies of ehrlichial prevalence, dogs may be persistently infected, yet PCR in marked pain. Fortunately, the clinical and can also be used as a tool when negative, potentially because the organism and hematologic manifestations of illness diagnosing canine ehrlichiosis. Depending is sequestered outside of the vasculature or usually respond rapidly, within 24 to 48 on the route of exposure, experimentally persists in the blood at levels undetectable hours after treatment with tetracycline infected dogs develop E. ewingii antibod- by PCR. or begins. Although a 14-day ies between 7 and 21 days after infection Multiple serologic methodologies are course of oral doxycycline and remain seroreactive for at least 10 available for antibody detection, including (5 mg/kg every 12 hours or 10 mg/kg months.15 As with any acute infection, the E. canis assay (IFA) once daily) is thought to clear E. ewingii, absence of an antibody response during and ELISA (SNAP® 4Dx® Plus Test — E. canis is generally treated for 28 days.19,20 the acute illness does not rule out infec- IDEXX Laboratories, Inc.). Detection Therefore, unless granulocytic morulae tion. If an initial serologic test finding is of cross-reactive antibodies from dogs are observed or serologic or PCR evidence negative, convalescent titers acquired 2 infected with E. ewingii on E. canis IFA confirms the ehrlichial species responsible to 3 weeks later are required to confirm a can be variable; on the other hand, anti- for infection is E. ewingii, the longer course clinical diagnosis through seroconversion bodies to E. ewingii are not serologically of therapy is justified. Supportive care, or to rule out exposure to E. ewingii. Sero- cross-reactive with A. phagocytophilum including analgesia for polyarthropathy, negative infection has not been reported. by any serologic methodology.18,19,21,33-35 may be necessary. Clinical, hematologic, Just as importantly, because antibody titers TheE. canis peptides in the commercially and PCR evidence suggests that dogs persist for months after an acute, tick- available, in-clinic SNAP® 3Dx® Test do may clear E. ewingii spontaneously within 4 weeks to several months, even if treatment ingii, E. canis, and E. chaffeensis). Healthy clinical infection, or might be chronically is withheld.15,16 dogs with a positive serologic response to infected. In each case, further diagnostic Healthy dogs that are seroreactive to any any Ehrlichia spe- Ehrlichia species do not require immediate cies antigen might Healthy dogs with a positive serologic re- treatment. Considerations for diagnostic have been infected sponse to any Ehrlichia species antigen might evaluation and the potential initiation of without evidence have been infected without evidence of treatment will become even more impor- of obvious clinical obvious clinical illness, might have recovered tant as veterinarians use screening tests illness, might have that recognize antibodies to any of these recovered spontane- spontaneously from a mild clinical infection, three important ehrlichial species (E. ew- ously from a mild or might be chronically infected.

Acute onset of canine granulocytic ehrlichiosis in a young dog On May 31, 2010, a urinalysis, and a SNAP® 2-year-old 27-kg (59.4-lb) 3Dx® Test (IDEXX Labora- neutered male mixed-breed tories). The hematocrit was dog was presented to normal at 42% with total the University of Missouri protein of 6.5, but the plate- Veterinary Medical Teach- lets were decreased at 80.2 ing Hospital’s Community x 103/μl. The white blood Practice clinic for progres- cell count was 8.8 x 103/μl sive lethargy and difficulty with a mild lymphopenia of walking of about 4 days’ 0.880 x 103/μl. On blood duration. The morning smear examination, platelet of presentation, the dog clumps were not identified, refused to get up to go out- but several granulocytic side. It was up-to-date on inclusions compatible with its core vaccinations (i.e., Ehrlichia ewingii or Ana- rabies, DA2LPP) and re- plasma phagocytophilum ceived monthly heartworm were seen. No abnormali- preventive medication but ties were identified on the it is now possible to detect dog was discharged from no routine ectopic parasite serum biochemical profile. antibodies to E. ewingii. In the hospital with instructions control therapy. The urine specific gravity this case, however, antibody to continue a 14-day course On arrival at the clinic, was well concentrated at results may still have been of doxycycline. Addition- the dog had to be brought 1.067 with a 1+ protein negative even had the new ally, 50-mg tramadol tablets into the building on a and an inactive urine SNAP 4DX Plus Test been (x10) were prescribed with gurney. It would stand sediment. The SNAP 3Dx used given that this dog instructions to administer 1 with reluctance and would Test result was negative for had an acute onset illness to 2 tablets by mouth twice walk a short distance with antibodies to Dirofilaria im- and might not have yet daily as needed for pain coaxing but appeared mitis, burgdorferi, seroconverted. control. Telephone follow- ataxic. On examination, and Ehrlichia canis. Treatment was initiated up about 2 weeks after the temperature was Neither the morulae nor with doxycycline at a dose discharge revealed that the 39.5 C (103.2 F), the heart clinical presentation can be of 10 mg/kg once daily by dog’s clinical improvement rate was 130 beats/min., used to distinguish between mouth. The dog was placed continued, with a return to and the respiratory rate canine granulocytic ehrlichi- on intravenous fluids at clinical normalcy within 2 was 32 breaths/min. Joint osis and canine anaplas- twice maintenance rates; days of hospital discharge. effusion was identified in mosis. However, because buprenorphine was given The owner had discontinued the right carpus and stifle. Missouri is considered a for analgesia (0.02 mg/kg tramadol after the first dose. It was difficult to evaluate highly endemic region for subcutaneously every 8 Clinical signs did not recur conscious proprioception E. ewingii but not A. phago- hours). By the next morning, after discontinuation of since the dog was unwilling cytophilum, a presumptive the temperature had normal- treatment. The owner did not to stand. diagnosis of canine granulo- ized, and the dog was will- return the dog for a recom- Initial evaluation includ- cytic ehrlichiosis was made. ing to stand and walk and mended repeat complete ed a complete blood count, With the introduction of eat canned . Fluids blood count to re-evaluate serum biochemical profile, the SNAP® 4Dx® Plus Test, were discontinued, and the the platelet count.

5 Spotlight on Ehrlichia ewingii

Ehrlichia ewingiiinfection: infection: Treatment Treatment and prevention and prevention strategies strategies

Dog exhibiting clinical signs Healthy dog, annual screening consistent with ehrlichiosis

Serology: SNAP® 4Dx® Plus or IFA SNAP® 4Dx® Plus

Ehrlichia antibody Ehrlichia antibody Ehrlichia antibody Ehrlichia antibody positive negative positive negative

CBC with blood smear CBC with blood smear No further and serum protein and serum protein evaluation or treatment required Normal CBC and Normal CBC and serum protein serum protein

Anemia, thrombocytopenia, pancytopenia, hyper- Doxycycline, 5 mg/kg every globulinemia, or morulae 12 hours or 10 mg/kg once daily; 14 days for E. ewingii; Consider alternative diagnostic +/– 28 days for E. canis tests and other differential diagnoses. Additional testing: • PCR to confirm active infection with E. canis, As needed, supportive care, includ- E. ewingii, or E. chaffeensis ing analgesia for polyarthropathy • (E. canis IFA) Begin treatment while awaiting results

Owner education: • Reduce tick exposure • Apply topical acaricides • Conduct regular tick checks  • Discuss zoonotic implications with lone star tick exposure

investigation is warranted, beginning some veterinarians will simply opt to treat recommendations.) Rapid manual removal with a complete blood count and blood seroreactive dogs with a 28-day course of ticks may be helpful, but the length smear evaluation. For healthy dogs with a of doxycycline, which is adequate to treat of time necessary for transmission of E. normal platelet count and the absence of either an acute infection with E. ewingii or ewingii following vector tick attachment is leukocytic morulae, anemia, or hyper- a chronic infection with E. canis.39,40 unknown. globulinemia, no further evaluation or There are no vaccines for canine treatment may be required. If morulae granulocytic ehrlichiosis or for any canine Public health are identified in neutrophils, monocytes, or human ehrlichial infection, so preven- considerations or (rarely) other circulating cell types or a tion consists of reducing exposure to tick Human infection with E. ewingii occurs dog is found to have thrombocytopenia, bites. Year-round topical acaricides are most often in immunocompromised anemia, or hyperglobulinemia, PCR is recommended for all dogs in tick-endemic people, and reported cases are relatively recommended to confirm active infection regions.41 (This is in accordance with the uncommon.22,24,42,43 Ehrlichia chaffeensis and treatment is warranted. Alternatively, Companion Parasite Council’s causes a more severe and potentially life- 6 threatening illness in humans (monocytic 7. Varela-Stokes AS. Transmission of bacterial agents from lone tors in naturally occurring canine monocytic ehrlichiosis. J Vet star ticks to white-tailed deer. J Med Entomol 2007;44:478-483. Intern Med 2011. ehrlichiosis), is carried by the same tick 8. Yabsley MJ, Varela AS, Tate CM, et al. Ehrlichia ewingii infec- 30. Kollars TM, Jr., Oliver JH, Jr., Masters EJ, et al. Host tion in white-tailed deer (Odocoileus virginianus). Emerg Infect utilization and seasonal occurrence of Dermacentor spe- vector as is E. ewingii, and can also infect Dis 2002;8:668-671. cies (Acari:Ixodidae) in Missouri, USA. Exp Appl Acarol dogs.5,9,10,33,44-46 Although experimental 9. Beall MJ, Breitschwerdt EB, Cohn LA, et al. Seroprevalence 2000;24:631-643. of three Ehrlichia species in dogs — A multi-institutional study. 31. Ravnik U, Tozon N, Smrdel KS, et al. in infection of dogs with E. chaffeensis has J Vet Intern Med 2011;25.25(3):748 (Abstract). dogs: The relation of haematological, biochemical and clinical 10. Castellaw AH, Showers J, Goddard J, et al. Detec- alterations to antibody titre and PCR confirmed infection.Vet produced only clinically inapparent tion of vector-borne agents in lone star ticks, Amblyomma Microbiol 2011;149:172-176. americanum (Acari: Ixodidae), from Mississippi. J Med Entomol 32. Mylonakis ME, Koutinas AF, Breitschwerdt EB, et al. infection or mild thrombocytopenia, co- 2010;47:473-476. Chronic canine ehrlichiosis (Ehrlichia canis): a retrospective infection with other pathogens or concur- 11. Merten HA, Durden LA. A state-by-state survey of ticks study of 19 natural cases. J Am Anim Hosp Assoc 2004;40:174- recorded from humans in the United States. J Vector Ecol 184. rent immunosuppression might result in 2000;25:102-113. 33. Breitschwerdt EB, Hegarty BC, Hancock SI. Sequential 33,45,46 12. Liddell AM, Stockham SL, Scott MA, et al. Predomi- evaluation of dogs naturally infected with Ehrlichia canis, Ehrlichia more severe disease manifestations. nance of Ehrlichia ewingii in Missouri dogs. J Clin Microbiol chaffeensis, Ehrlichia equi, Ehrlichia ewingii, or . J Certainly, both human granulocytic and 2003;41:4617-4622. Clin Microbiol 1998;36:2645-2651. 13. Little SE, O’Connor TP, Hempstead J, et al. Ehrlichia ewin- 34. O’Connor TP, Hanscom JL, Hegarty BC, et al. Comparison human monocytic ehrlichiosis can result gii infection and exposure rates in dogs from the southcentral of an indirect immunofluorescence assay, western blot analysis, United States. Vet Parasitol 2010;172:355-360. and a commercially available ELISA for detection of Ehrlichia in serious morbidity and, in the case of 14. Anderson BE, Greene CE, Jones DC, et al. Ehrlichia ewingii canis antibodies in canine sera. Am J Vet Res 2006;67:206-210. 47,48 sp. nov., the etiologic agent of canine granulocytic ehrlichiosis. 35. Greig B, Breitschwerdt EB, Armstrong PJ. Canine E. chaffeensisinfection, mortality. Int J Syst Bacteriol 1992;42:299-302. granulocytic ehrlichiosis. In: Greene CE, ed. Infectious diseases While there are no reports of direct 15. Yabsley MJ, Adams DS, O’Connor TP, et al. Experimental of the dog and cat, 3rd ed. St. Louis, Mo.: Saunders Elsevier, primary and secondary infections of domestic dogs with 2006;217-219. dog-to-human transmission of either E. Ehrlichia ewingii. Vet Microbiol 2011; 150:315-321. 36. O’Connor TP, Saucier JM, Daniluk D, et al. Evaluation of 16. Stockham SL, Tyler JW, Schmidt DA, et al. Experimental peptide- and recombinant protein-based assays for detection of ewingii or E. chaffeensis, identification of an transmission of granulocytic ehrlichial organisms in dogs. Vet anti-Ehrlichia ewingii antibodies in experimentally and naturally infected pet would suggest that the pet’s Clin Pathol 1990;19:99-104. infected dogs. Am J Vet Res 2010; 71:1195-200. 17. Bellah JR, Shull RM, Selcer EV. Ehrlichia canis-related 37. Gaunt S, Beall M, Stillman B, et al. Experimental infection owner may also come into contact with polyarthritis in a dog. J Am Vet Med Assoc 1986;189:922-923. and co-infection of dogs with and Ehrlichia 18. Stockham SL, Schmidt DA, Curtis KS, et al. Evaluation of canis: hematologic, serologic and molecular findings ticks carrying these pathogens. In endemic granulocytic ehrlichiosis in dogs of Missouri, including serologic Parasit Vectors 2010;3:33-43. status to Ehrlichia canis, Ehrlichia equi and . 38. Beall MJ, Chandrashekar R, Eberts MD, et al. Serological and regions, veterinarians should educate Am J Vet Res 1992;53:63-68. molecular prevalence of Borrelia burgdorferi, Anaplasma phagocyto- their clientele about the importance of 19. Goodman RA, Hawkins EC, Olby NJ, et al. Molecular philum, and Ehrlichia species in dogs from Minnesota. Vector Borne identification ofEhrlichia ewingii infection in dogs: 15 cases Zoonotic Dis 2008;8:455-464. tick control and the possibility of human (1997-2001). J Am Vet Med Assoc 2003;222:1102-1107. 39. Hegarty BC, de Paiva Diniz PP, Bradley JM, et al. Clinical 20. Gieg J, Rikihisa Y, Wellman M. Diagnosis of Ehrlichia relevance of annual screening using a commercial enzyme-linked ehrlichial infections. Veterinarians play ewingii infection by PCR in a puppy from Ohio. Vet Clin Pathol immunosorbent assay (SNAP 3Dx) for canine ehrlichiosis. J a critically important role in the national 2009;38:406-410. Am Anim Hosp Assoc 2009;45:118-124. 21. Goldman EE, Breitschwerdt EB, Grindem CB, et al. Granu- 40. Baneth G, Harrus S, Ohnona FS, et al. Longitudinal public health infrastructure relative to the locytic ehrlichiosis in dogs from North Carolina and Virginia. J quantification ofEhrlichia canis in experimental infection with Vet Intern Med 1998;12:61-70. comparison to natural infection. Vet Microbiol 2009;136:321- prevention of human tick-borne illness. 22. Buller RS, Arens M, Hmiel SP, et al. Ehrlichia ewingii, a 325. newly recognized agent of human ehrlichiosis. N Engl J Med 41. Otranto D. Assessment of the efficacy of parasiticides for 1999;341:148-155. the control of tick infection in dogs under field conditions: 23. Dumler JS, Madigan JE, Pusterla N, et al. Ehrlichioses in what’s new? Parassitologia 2006;48:141-144. References humans: epidemiology, clinical presentation, diagnosis, and 42. Thomas LD, Hongo I, Bloch KC, et al. Human ehrlichiosis treatment. Clin Infect Dis 2007;45 Suppl 1:S45-51. in transplant recipients. 2007;7:1641-1647. 1. Oliveira LS, Oliveira KA, Mourao LC, et al. First report of Am J Transplant 24. Paddock CD, Folk SM, Shore GM, et al. Infections 43. Ganguly S, Mukhopadhayay SK. Tick-borne ehrlichiosis Ehrlichia ewingii detected by molecular investigation in dogs with Ehrlichia chaffeensis and Ehrlichia ewingii in persons infection in human beings. J Vector Borne Dis 2008;45:273-280. from Brazil. Clin Microbiol Infect 2009. coinfected with human immunodeficiency virus.Clin Infect Dis 44. Nicholson WL, Allen KE, McQuiston JH, et al. The in- 2. Ndip LM, Ndip RN, Esemu SN, et al. Ehrlichial infection 2001;33:1586-1594. creasing recognition of rickettsial pathogens in dogs and people. in Cameroonian canines by Ehrlichia canis and Ehrlichia ewingii. 25. Xiong Q, Bao W, Ge Y, et al. Ehrlichia ewingii infection Trends Parasitol 2010;26:205-212. 2005;111:59-66. Vet Microbiol delays spontaneous neutrophil apoptosis through stabilization 45. Dawson JE, Ewing SA. Susceptibility of dogs to infection 3. Anziani OS, Ewing SA, Barker RW. Experimental of mitochondria. J Infect Dis 2008;197:1110-1118. with Ehrlichia chaffeensis, causative agent of human ehrlichiosis. transmission of a granulocytic form of the tribe Ehrlichieae by 26. Kordick SK, Breitschwerdt EB, Hegarty BC, et al. Coinfec- Am J Vet Res 1992;53:1322-1327. and to dogs. Dermacentor variabilis Amblyomma americanum tion with multiple tick-borne pathogens in a Walker Hound 46. Zhang XF, Zhang JZ, Long SW, et al. Experimental Am J Vet Res 1990;51:929-931. kennel in North Carolina. J Clin Microbiol 1999;37:2631-2638. Ehrlichia chaffeensis infection in beagles. J Med Microbiol 4. Varela AS, Moore VA, Little SE. Disease agents in Ambly- 27. Harrus S, Waner T. Diagnosis of canine monocytotropic 2003;52:1021-1026. omma americanum from northeastern Georgia. J Med Entomol ehrlichiosis (Ehrlichia canis): An overview. Vet J 2011;187:292- 47. Doudier B, Olano J, Parola P, et al. Factors contributing to 2004;41:753-759. 296. emergence of Ehrlichia and Anaplasma spp. as human patho- 5. Childs JE, Paddock CD. The ascendancy ofAmblyomma 28. McClure JC, Crothers ML, Schaefer JJ, et al. Efficacy of a gens. Vet Parasitol 2010;167:149-154. as a vector of pathogens affecting humans in the americanum doxycycline treatment regimen initiated during three different 48. Thomas RJ, Dumler JS, Carlyon JA. Current management United States. Annu Rev Entomol 2003;48:307-337. phases of experimental ehrlichiosis. Antimicrob Agents Che- of human granulocytic anaplasmosis, human monocytic 6. Paddock CD, Yabsley MJ. Ecological havoc, the rise of white- mother 2010;54:5012-5020. ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Rev Anti tailed deer, and the emergence of Amblyomma americanum- 29. Mylonakis ME, Ceron JJ, Leontides L, et al. Serum acute Infect Ther 2009;7:709-722. associated zoonoses in the United States. Curr Top Microbiol phase proteins as clinical phase indicators and outcome predic- Immunol 2007;315:289-324.

ABOUT THE AUTHORS Leah A. Cohn, DVM, PhD, DACVIM Edward B. Breitschwerdt, DVM, DACVIM Department of Veterinary Medicine and Surgery Department of Clinical Sciences College of Veterinary Medicine College of Veterinary Medicine University of Missouri North Carolina State University Columbia, MO Raleigh, NC

Dr. Cohn is a professor of veterinary medicine. She is Dr. Breitschwerdt is a professor of internal medicine at a specialist in small animal internal medicine and is a NCSU’s College of Veterinary Medicine and an adjunct diplomate of the American College of Veterinary Internal Medicine. She holds professor of medicine at Duke University Medical Center. He is a diplomate a PhD in veterinary immunology and infectious diseases. She has been a of the American College of Veterinary Internal Medicine. He has published faculty member at University of Missouri since 1995, where she serves as the more than 250 articles in scientific journals. His research areas include infec- director of graduate studies and associate department chair. She is currently tious diseases and immunology, with a particular emphasis on vector-transmit- the president of the American College of Veterinary Internal Medicine. Her re- ted, intracellular pathogens. Since 1984, he has supervised the Intracellular search emphasis is infectious and respiratory disease. Current projects include Pathogens Research Laboratory and co-supervised the NCSU Vector-Borne treatment of Cytauxzoon felis infection and immunotherapy for feline asthma. Disease Diagnostic Laboratory.

7 Spotlight on Ehrlichia ewingii

Ehrlichia ewingiiQ&A

What is Ehrlichia ewingii? A. americanum transmits E. ewingii and E. chaffeensis to dogs Ehrlichia ewingii is a tick-transmitted member of the alpha and people and Cytauxazoon felis to domestic and wild cats. that can induce intra-neutrophilic infection in The lone star tick also carriesBorrelia lonestari and Rickettsia dogs and acute febrile illness in people. amblyommii, but the pathogenic potential for each of these organisms for dogs and people remains unclear. What are the clinical presentations of the disease that it causes? What do you do with a dog that tests Clinical signs can be highly variable among dogs. Following positive for Ehrlichia ewingii? tick-transmission of E. ewingii, clinical signs will most often With the advent of the SNAP® 4Dx® Plus Test (IDEXX develop within 7 to 14 days. Clinical manifestations include Laboratories), veterinarians practicing in regions of the country fever, lethargy, lameness, polyarthropathy, and neurologic with high numbers of A. americanum should anticipate an manifestations including ataxia, paresis, proprioceptive increase in the number of Ehrlichia positive SNAP results they deficits, and vestibular dysfunction. see in both healthy and sick dogs. With the addition of an E. ewingii-specific peptide to the SNAP platform, antibodies to How is Ehrlichia ewingii different from all three Ehrlichia species will now be detectable. Because the other species of Ehrlichia, and what SNAP platform is designed as a screening test, it is important problems does that present? to realize that antibody levels may not be detectable during the In North America, dogs can be infected with E. ewingii, acute phase of infection (i.e., the first 7 to 14 days following tick Ehrlichia canis, and Ehrlichia chaffeensis. Although the clinical transmission). However, the SNAP Test can be used to confirm presentations associated with infection with each Ehrlichia seroconversion following an acute infection in dogs. Optimally, species can be similar with overlapping disease manifesta- when a dog tests positive for Ehrlichia antibodies using the tions, E. ewingii appears to be somewhat unique in its ability SNAP 4Dx Plus Test, the veterinarian should recommend a to cause a neutrophilic polyarthritis. Historically the world complete blood count and a serum protein measurement. If literature relative to canine ehrlichial disease is biased to- abnormalities are noted (anemia, thrombocytopenia, neutro- ward E. canis; only recently, with the advent of PCR testing, penia, pancytopenia, hyperglobulinemia) a PCR test can be have clinicians been able to definitively determine which performed to confirm active infection with anEhrlichia species Ehrlichia species is causing disease in their patients. or the dog can be treated with doxycycline (5 mg/kg every 12 hours or 10 mg/kg once daily for 4 weeks). Western blot testing What role does the lone star tick play as is not available for E. ewingii testing because the organism has a vector of Ehrlichia ewingii, and what never been cultured. Immunofluorescence assay (IFA) testing other diseases (particularly human diseases) is less specific to differentiate among species, but can be used to does it carry? detect and quantify antibodies or to confirm seroconversion, if Although the most prevalent tick species to infest cats, dogs, acute and convalescent sera are tested. To document serocon- people, and many wild animal species in the southern and version by SNAP Test or IFA, an acute serum sample should central United States, Amblyomma americanum (the lone star be collected and the dog should be retested in about 3 weeks. tick) has been the least studied as a vector for canine and Seroconversion requires a fourfold increase in the IFA titer or a human disease. It is important to realize that the distribu- change from a negative to positive Ehrlichia SNAP Test result. tion of this tick species continues to move northward, with increasing sightings as far north as New York and Maine.

© 2012 IDEXX Laboratories, Inc. The views expressed in this article are solely those of the authors. Dr. Cohn and Sponsored by: Dr. Breitschwerdt occasionally collaborate with and receive compensation from IDEXX Laboratories, Inc. SNAP, 4Dx and 3Dx are trademarks or registered trademarks of IDEXX Laboratories, Inc. and/or its affiliates in the United States and other countries. 09-69356-00 8