the increasingly complicated story of ehrlichia

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The IncreasinglyComplicated Story of EhrlichiaUniversity of Missouri-Columbia

Diane E. Preziosi, DVM, DABVP* Leah A. Cohn, DVM, PhD, DACVIM

ABSTRACT: Ehrlichiosis, once viewed as a rare disease in the United States, has become anincreasingly common diagnosis in many regions of the country. Although Ehrlichia canis wasthe first species described and remains the best understood, many other species of Ehrlichiaare now known to infect dogs. The recognition of new types of ehrlichial infections has addedcomplexity to the diagnosis of ehrlichiosis. The importance of these pathogens has increasedwith the recognition of human ehrlichiosis.

Ehrlichial infection was first recognized as a cause of canine disease in Alge-ria circa 1935.1 Veterinarians in the United States did not become familiarwith this disease until the Vietnam War era when military working dogs,

including many that had never left the country, developed what was then knownas tropical pancytopenia caused by Ehrlichia canis.2,3 Since then, other species ofEhrlichia that cause disease in dogs have been identified. Classification of theseehrlichial species has been reorganized, diagnostic testing options have increased,and additional manifestations of ehrlichiosis have been recognized in a widergeographic area. In the mid-1980s, an ehrlichial species was recognized as acause of disease in humans in the United States; since then, various other specieshave been found to infect humans as well. Some ehrlichial species that infectdogs can also infect humans (through tick bites), leading to concerns about therole of dogs in harboring a disease that may be transmitted to humans. This arti-cle addresses these developments and their importance in the understanding,diagnosis, and treatment of ehrlichiosis primarily in dogs.

CLASSIFICATIONEhrlichia are gram-negative obligate intracellular bacteria that lack

lipopolysaccharide endotoxins and rely on arthropod vectors for transmission.For many years, E. canis was the only ehrlichial species known to cause disease indogs, and it is by far the best described veterinary ehrlichial pathogen. Severaladditional Ehrlichia species that infect dogs as either primary or incidental hostsare now recognized. Previous classification schemes have made use of the cell

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n Ehrlichial infection can result in a wide range of manifestations(from inapparent infection to fatal illness).

n Diagnosis can be problematicbecause not all species ofEhrlichia produce cross-reactiveantibody titers and positive titersmay reflect either inactiveinfection or past exposure.

n Dogs and other domestic specieshave the potential to harbor ticksthat can transmit certain types ofehrlichiosis to humans.

*Dr. Preziosi is currently affiliated with the University of Pennsylvania.

type infected by the ehrlichial organism. Although thishas proven useful, several species, such as Ehrlichiaewingii, Ehrlichia chaffeensis, Ehrlichia risticii, andEhrlichia phagocytophila, may infect more than one celltype.4,5 Current classification schemes are based ongenetic analysis of the organism’s 16S rRNA genesequence. This method produces three speciesgenogroups, with the members of any one genogroupcommonly producing cross-reactive antibody titers.5–8

Despite close genetic relatedness, the individual specieswithin a genogroup may infect different cells withindifferent hosts, use different vectors, and have differentgeographic distributions (Table 1).

EPIDEMIOLOGYMost ehrlichial species rely on arthropod vectors for

transmission, although the specific vectors are not welldescribed for every species of Ehrlichia. The geographicdistribution pattern of various ehrlichial species isrelated to the distribution of the relevant vector(s). Thepredominant vector for E. canis is the brown dog tick(Rhipicephalus sanguineus), which is found worldwide.9,10

Accordingly, E. canis has been reported in dogs fromAfrica, Europe, Asia, the Middle East, and the UnitedStates. In contrast to E. canis, E. ewingii is known to useat least three different vectors. In addition to R. san-guineus, both Dermacentor variabilis (American dogtick) and Amblyomma americanum (lone star tick) arecapable of transmitting E. ewingii infection.10 The pri-mary distribution of the lone star tick in the midwesternand southeastern United States may account for theincreased incidence of E. ewingii infection in theseregions.5,6,10 Ehrlichia equi infection, which is transmit-ted by Ixodes ticks, is most often reported in the upper

midwestern and northeastern United States.7,11,12

In addition to ticks, other known vectors of ehrlichialinfection include snails and flukes. E. risticii, thecausative agent of Potomac horse fever, is transmittedthrough the ingestion of snails and can cause infectionin dogs as well as horses.13 Although not often thoughtof as an ehrlichial species, Neorickettsia helminthoeca,the causative agent of salmon poisoning disease,belongs to the same genogroup as E. risticii. During acomplex life cycle, it is transmitted to dogs through theingestion of flukes harbored in certain types of fish.14

The vectors of some ehrlichial species that affect dogsremain incompletely defined.

Concurrent infection with multiple arthropod-bornepathogens is possible and may contribute to illnessesdescribed in some Ehrlichia-positive dogs. Dogs thatharbor one tick are likely to harbor several (of either thesame or different species). In addition, the same arthro-pod may serve as transmission vector for several generaand species of infectious agents. For instance, R. san-guineus is capable of transmitting not only E. canis andE. ewingii, but Babesia canis and Babesia gibsoni aswell.2,10,15–17 Ixodes ticks, competent vectors for transmis-sion of E. equi and the agent of human granulocyticehrlichiosis (HGE), can also transmit infection withBorrelia burgdorferi and Babesia microti.18–21 In additionto many case reports in the literature describing suchconcurrent infections, serologic surveys have docu-mented these cases on a larger scale. In one such study,6

almost 50% of dogs diagnosed with Ehrlichia also har-bored Bartonella vinsonii. Concurrent seropositivity hasalso been documented for B. burgdorferi and E. canis.18

Such simultaneous infections may worsen the severity ofobserved disease and impact the outcome of treatment.

278 Small Animal/Exotics Compendium April 2002

Table 1. Ehrlichial Agents Known to Infect Dogs

Type Target Cells Major Host Known Vector(s)

Genogroup IEhrlichia canis Mononuclear cells Dogs Rhipicephalus sanguineusEhrlichia chaffeensis Mononuclear cells Humans Amblyomma americanum, Dermacentor variabilisEhrlichia ewingii Granulocytes Dogs R. sanguineus, A. americanum, D. variabilis

Genogroup IIEhrlichia phagocytophila Granulocytes Ruminants Ixodes ricinusEhrlichia equi Granulocytes Equidae I. ricinus, Ixodes pacificusAgent of human Granulocytes Humans Ixodes scapularis, I. ricinus, I. pacificus

granulocytic ehrlichiosisEhrlichia platys Platelets Dogs R. sanguineus

Genogroup IIIEhrlichia risticii Monocytes, enterocytes Equidae ArthropodsNeorickettsia helminthoeca Monocytes Dogs Flukes

TRANSMISSION AND PATHOGENESISThe transmission and pathogenesis of canine ehr-

lichiosis are best understood for E. canis infection. E.canis organisms gain entry via salivary secretions duringthe bite of an infected tick.4 Ticks acquire the organismduring their larval or nymph stage when they feed onan infected canid. Infection is spread when the tickfeeds again on a new host. Because transovarial trans-mission does not occur, the tick vector cannot serve as areservoir of disease.4 Ticks can remain infected for longperiods, however, allowing for disease transmission inearly spring after the infected tick has overwintered.

The course of clinical infection with E. canis is tra-ditionally divided into three stages, which vary inlength. These stages may be difficult to differentiatein natural infections.4,22,23

Acute PhaseThe acute phase occurs 1 to 3 weeks after the

infected tick bites a dog.9 During this phase, the organ-ism invades leukocytes and divides to form morulae,which are colonies bound by a vacuolar membrane.Usually a specific ehrlichial species preferentiallyinvades either mononuclear or granulocytic leukocytes.E. canis, E. chaffeensis, and E. risticii invade mononu-clear cells, whereas E. ewingii, E. phagocytophila, and E.equi invade granulocytic neutrophils or eosinophils(Table 1). During acute infection, the most consistenthematologic change is the development of thrombocy-topenia.24 This multifactorial change results from vas-cular endothelial inflammation with resulting plateletconsumption, immunologically mediated destructionof platelets, and splenic sequestration of platelets.9,24,25

Interestingly, thrombocytopenia seems to be a commonfinding during infection with all species of Ehrlichiadescribed thus far. In addition to thrombocytopenia,thrombocytopathia may accompany E. canis infec-tion.26 Hyperglobulinemia during acute E. canis infec-tion is usually the result of a polyclonal gammopathy,but the gammopathy does not seem to be caused byehrlichial-specific antibody production.9,27 Few dogssuccumb to the acute disease; most either clear theorganism (likely via cell-mediated immunity) or enterthe subclinical stage of infection.4,9

Subclinical PhaseThe subclinical phase of E. canis infection is charac-

terized by persistence of the organism in the host in theabsence of clinical illness. It appears likely that organ-isms are retained at low numbers in splenic mononu-clear cells during subclinical infection.28 The length ofthe subclinical phase may range from weeks to years; infact, it is not known what percentage of subclinically

infected dogs will ever develop clinical illness. In a sin-gle study of naturally infected dogs, 53% demonstratedpositive E. canis antibody titers 4 years after the pre-sumed time of infection but remained clinically asymp-tomatic. Many of these dogs did, however, demonstrateabnormalities suggestive of ehrlichial disease on com-plete blood cell counts (e.g., hyperglobulinemia,thrombocytopenia).29 Although subclinical infection iswell documented for E. canis, it is less clear whetherother Ehrlichia species also induce persistent but sub-clinical infections. In at least one case,12 E. ewingiimorulae were observed in an asymptomatic dog.

Chronic StageThe pathogenesis of the chronic stage of E. canis infec-

tion is poorly understood because adequate models arenot available. Not all infected animals progress to thechronic stage, and the factors that influence progressionare still unknown. Persistent E. canis infection results inpersistent antibody formation (both nonspecific andehrlichial directed).9,30,31 Unfortunately, humoral immu-nity to E. canis provides no protection.4,32 In fact, many ofthe manifestations of chronic ehrlichial disease may resultfrom an exuberant but nonprotective humoral immuneresponse.4,9 As in the acute stage, hemorrhagic tendenciesmay be related to either thrombocytopenia or thrombo-cytopathia. In addition to the mechanisms mentionedpreviously, hyperglobulinemia associated with chronicinfection is often more pronounced, and hyperviscositysyndrome with resultant thrombocytopathy may result.26

Glomerulonephritis may result from the deposit of anti-gen–antibody complexes with resultant inflammatorydamage.23 Bone marrow hypoplasia has been a classicfinding associated with chronic E. canis infection andmay result in pancytopenia.3,22,23 Nonregenerative anemiacommonly associated with chronic E. canis infection maybe caused by either anemia of inflammatory disease or bypancytopenia due to bone marrow hypoplasia.22,23,33 Con-current infectious diseases documented in dogs with E.canis have been attributed to immunosuppressive effectsof chronic infection.23

CLINICAL FINDINGSEhrlichia canis

Clinical findings associated with E. canis infectionvary tremendously and are likely influenced by thestrain of organism, host immune status, and breed ofanimal.4,34 German shepherds are classically thought tobe more susceptible to infection and to have a more ful-minant course of infection than dogs of otherbreeds.34–36 By definition, no clinical signs are apparentduring the subclinical phase of infection, althoughhematologic abnormalities may be identified.29 Often,

Compendium April 2002 Ehrlichiosis 279

either the acute stage of infection goes unnoticed orsigns are mild enough that owners do not seek veteri-nary care for their pets. When dogs are evaluated duringthe acute stage of infection, signs are largely nonspecificand include lethargy, fever, anorexia, weight loss,splenomegaly, and generalized lymphadenopathy.4,37

Most diagnoses of E. canis infection occur during thechronic stage of infection. As occurs with dogs pre-sented during the acute stage, the owners of dogs withchronic ehrlichiosis most commonly report nonspecificsigns, such as lethargy, anorexia, and weight loss.23,34

Signs attributable to bleeding tendencies, includingepistaxis, melena, petechial and/or ecchymotic hemor-rhages, hyphema, retinal hemorrhage, and hematuria,occur in 25% to 60% of cases.22,23,33,34 Additional physi-cal examination findings include lymphadenopathy,fever, pale mucous membranes, and splenomegaly.22,23,33,34

Anterior uveitis, retinal changes, or neurologic abnor-malities are noted occasionally.23,38 Ataxia, paraparesis,conscious proprioceptive deficits, head tilt, nystagmus,and seizures have all been reported as neurologic mani-festations of infection.23 The importance of lameness asa clinical sign of E. canis infection is debatable.Although lameness is often listed as a clinical sign ofinfection in the older literature, many of the animalsdisplaying lameness were found to have granulocyticmorulae, suggesting that the infection may have beencaused by E. ewingii rather than E. canis.39–41 Other clin-ical signs of chronic E. canis infection relate to compli-cations, including glomerulonephritis with nephroticsyndrome, or pancytopenia resulting in secondary infec-tions and severe anemia.

Clinicopathologic abnormalities are also nonspecific.Although normal platelet concentrations do not rule outchronic ehrlichiosis, most cases display some degree ofthrombocytopenia.22,23,33,34 Nonregenerative anemia(often mild to moderate) is also identified in mostcases.22,23 White blood cell counts may fall below, within,or above reference ranges in dogs with ehrlichiosis.22,23,33

Although hyperglobulinemia has not been reported con-sistently, it is observed in most cases.22,23,34 Albeit usuallydue to polyclonal gammopathy, hyperglobulinemia maypresent as a monoclonal gammopathy that can be easilymistaken for multiple myeloma.27,42 Other serum bio-chemistry abnormalities noted with some regularityinclude hypoalbuminemia, elevated alkaline phos-phatase, and elevated alanine transaminase concentra-tions.22,23,33 Proteinuria may occur independently or con-currently with glomerulonephritis.22,23,33,43,44 Althoughearly descriptions of E. canis infection were of a tropicalpancytopenia, the pancytopenic manifestations nowappear to account for a small minority of cases in theUnited States. Cytologic evaluation of bone marrow

aspirates often displays increased numbers of plasmacells, with either hypoplasia (suggesting chronic infec-tion) or hyperplasia (suggesting acute or chronic infec-tion) of the other marrow elements.3,22,23,37

Ehrlichia ewingiiE. ewingii is one of two ehrlichial agents known to

result in granulocytic infection in dogs, with the otheragent being E. equi.12 Unfortunately, identification ofgranulocytic morulae does not differentiate E. equi infec-tion from E. ewingii infection, which likely predomi-nates in the southern and lower midwestern UnitedStates. Because E. ewingii belongs to the same genogroupas E. canis, E. canis titers should be positive during infec-tion.12 Many descriptions of granulocytic ehrlichial infec-tion are of dogs with acute-onset polyarthritis, and thesecases have more often than not been ascribed to E.ewingii infection.5,39–41,45 The lameness may involve morethan one leg or appear to shift from limb to limb. Jointstiffness and occasional joint swelling due to effusionmay be noted, and dogs are often febrile. Splenomegalyand hepatomegaly have been reported. Bleeding tenden-cies may be noted, and many infected dogs have mild tomoderate thrombocytopenia.12 Central nervous systeminvolvement, particularly meningitis, has beenreported.46 Dual infection with both E. canis and E.ewingii has also been reported in association with pro-found ataxia and epistaxis.47 Polyarthritis resolves quicklywith appropriate therapy. Fatal granulocytic ehrlichialinfections seem to be extremely rare in dogs.

Ehrlichia equiAs with E. ewingii, the true incidence of E. equi infec-

tions in dogs is unknown, but E. equi may account for asignificant proportion of granulocytic ehrlichiosis in thenortheastern and upper midwestern United States andCalifornia, where equine infections are endemic.7,11,12

Experimental infection with E. equi in dogs producedonly mild to inapparent clinical signs, but naturallyinfected dogs have presented with nonspecific illness,including fever, lethargy, and thrombocytopenia.11,48

There are no unique clinical findings attributed to infec-tion with E. equi, but polyarthritis is described less fre-quently than for E. ewingii.11 Without an index of suspi-cion, veterinarians may not request the specific diagnostictesting required to differentiate this ehrlichial infectionfrom others, and E. canis titers may be negative.11,12

Ehrlichia risticiiE. risticii, the causative agent of Potomac horse fever, can

infect dogs and cats as well as horses. This agent is trans-mitted not by a tick bite but rather by ingestion of snails,perhaps explaining why canine infection is not commonly


described. When dogs are infected, lethargy, vomiting,bleeding disorders, and arthralgia have been reported.13

Because E. risticii belongs to a different genogroup than E.canis, antibody cross-reactivity may be lacking. Unlessgenogroup-specific titers are requested, dogs with E. risticiiinfection may display negative ehrlichial titers.13

Ehrlichia chaffeensisAlthough E. chaffeensis is primarily notable as a

human pathogen, dogs are also susceptible to infectionwith this organism. Experimentally infected dogs seemto have mild or inapparent disease.49 However, a reportof three dogs infected naturally with E. chaffeensis doc-umented more serious signs, including vomiting, epis-taxis, lymphadenopathy, and anterior uveitis.6 BecauseE. chaffeensis shares genogrouping with E. canis, routinetiters should prove positive in infected dogs.6

Ehrlichia platysE. platys is unique among the Ehrlichia species because

of its predisposition for platelets rather than leukocytes.E. platys does not share serologic cross-reactivity with E.canis, but co-infections have been documented.8,15,50,51

Although infection with E. platys results in cyclic throm-bocytopenia in dogs, it is seldom the cause of clinical

bleeding unless trauma or surgery is performed duringthe thrombocytopenic cycle.52,53 The disease manifesta-tions associated with E. platys may be more severe instrains found outside the United States.54–56 Veterinariansshould consider specific testing for E. platys infection indogs with recurring evidence of thrombocytopenia forwhich another cause (including the more commonehrlichial infections) cannot be documented.

Feline EhrlichiosisThe topic of feline ehrlichiosis deserves separate men-

tion from canine ehrlichiosis.57 Cats have been experi-mentally infected with both E. risticii and E. equi, pro-ducing either subclinical infection or mild illness.48,58 Todate, experimental infection with E. canis or E. ewingiihas not been attempted. Naturally occurring feline ehrli-chiosis has been documented in only 31 cats worldwide.These cats presented with various clinical signs, includ-ing fever, anorexia, arthropathy, gastrointestinal signs,and general malaise.57,59–62 Until a clearer picture of theimportance and clinical presentation of feline ehrlichiosisis developed, ehrlichiosis should remain a considerationin cats with various unexplained clinical illnesses. Diag-nosis relies on ruling out other causes for the describedclinical illness in combination with either identification


of morulae within the peripheral blood cells or serologicevidence of exposure to an ehrlichial agent as well as res-olution of clinical signs after appropriate antibiotic ther-apy.57 Both granulocytic and monocytic infections havebeen described, with the expected variations in serologicreactivity to different ehrlichial agents.57,60,62

DIAGNOSISEhrlichiosis is usually diagnosed based on clinical

signs, consistent laboratory abnormalities, andEhrlichia-specific testing. Although observation ofintracellular morulae is diagnostic, the search for moru-lae is most often unrewarding.35 The use of concentra-tion techniques, such as buffy coat examination with aRomanovsky-type stain, maximizes the chance of iden-tifying morulae.3 Morulae may be observed in whiteblood cells from peripheral blood or other fluids,including cerebrospinal and joint fluids.39,40,46,47 In gen-eral, morulae are more readily apparent during theacute phase of monocytic E. canis infection or duringinfection with the granulocytic species E. ewingii andE. equi (Figure 1).5,11,23,35

The most commonly employed diagnostic test forsuspected ehrlichial infection is indirect fluorescentantibody (IFA) serology. This form of testing does notdetect the actual ehrlichial organism but ratherehrlichial-reactive antibody in the serum. Veterinariansemploying IFA testing must understand that a positivetiter in a dog from an endemic area does not confirmthat the disease under investigation is caused byehrlichial infection. Rather, a positive titer confirmsexposure to the organism but may be observed afterexposure and clearance of the organism, during thesubclinical stage, or after successful treatment, as well asduring active infection. Likewise, a negative titer doesnot rule out infection. Moribund animals may cease to

produce antibody, resulting in a diminished or negativetiter, and acutely infected dogs require 7 to 21 days forseroconversion, potentially resulting in negative titersin infected dogs.63 Depending on the particular IFA testused, serology can be more or less specific for a speciesof Ehrlichia. Antibody generated to one species ofEhrlichia may cross-react with other species. Speciesthat fall within the same genogroup are likely to possessserologic cross-reactivity. Likewise, titers to onegenogroup may be negative during infection withmembers of a different genogroup (i.e., E. canis titersmay be negative during infection with E. equi). Cur-rently, titers are commercially available for members ofeach genogroup, including E. canis, E. equi, E. risticii,and E. platys.a

Polymerase chain reaction (PCR) detects actual DNAfrom the ehrlichial organism. Primers are chosen toamplify a portion of the bacterial DNA, allowing detec-tion of that genetic material. The use of genericehrlichial primers allows detection of any of severalspecies of Ehrlichia using one test. Alternatively, byusing primers directed at a specific, highly variable por-tion of the bacterial gene, PCR can identify the specificspecies of Ehrlichia in an affected animal. Such primersare currently available for E. canis, E. ewingii, E. equi,E. chaffeensis, E. risticii, and E. platys.6 Many commer-cial laboratories use generic primers and then may ormay not speciate positive samples.b,c Although PCR canbe a sensitive test, the choice of sample will influenceresults. Most commercial laboratories that performPCR request whole blood samples, but organismsmight at times be sequestered in low numbers in suchtissues as the spleen or bone marrow.64 PCR may beused occasionally in conjunction with IFA to differenti-ate between exposure to Ehrlichia and true infection(such as after completion of treatment and in the pres-ence of continued clinical signs and persistent ehrlichialtiters).65 The laboratory’s quality control is crucial forreliable PCR results.

A commercial in-house screening kit that tests for B.burgdorferi antibodyd has been marketed. ScreeningELISA tests of this kind are designed to produce a posi-tive response in animals with an antibody titer corre-sponding to an IFA titer of greater than 1:500.Reported sensitivity and specificity of these test kits are98.9% and greater than 99%, respectively. As with anytest, predictive value is more important than either sen-sitivity or specificity, but it depends on both as well as


aProtaTek International, Inc., Chandler, AZ.bAntech Diagnostics, Irvine, CA. cTick-borne disease testing facility, College of Veterinary Medi-cine, North Carolina State University, Raleigh, NC.dSnap® 3Dx™ Test, IDEXX Laboratories, Inc., Westbrook, ME.

Figure 1—A round, basophilic morula of E. ewingii is seen inthe cytoplasm of the neutrophil. (Courtesy of Steve Stock-ham, DVM, MS, Kansas State University.)

on the prevalence of the disease in question. Thus apositive screening test in an endemic area is more likelyto be a true positive than is the same result in an areawith a lesser disease prevalence. As is true of the IFAtest, a positive titer must be interpreted with cautionbecause it may represent current or resolved infectionor merely exposure.

TREATMENTTetracycline-related antibiotics have been the treat-

ment of choice for ehrlichial infections for years.3

Excellent absorption and an infrequent dosing intervalmake doxycycline the preferred drug.32,66 Although a 7-to 14-day course of doxycycline at 10 mg/kg/day hasbeen previously recommended,4,6,32 this length of treat-ment may be inadequate.66,67 In fact, in a study of sub-clinically infected dogs treated with doxycycline for 6weeks, ehrlichial organisms could still be identified byPCR in one of four dogs.67 Although the appropriatelength of treatment has not been clearly determined,treatment for dogs with chronic infection may be quitelong in duration and titers may remain elevated formonths to years, regardless of the treatment length.Even long courses of treatment (average, 210 days) didnot produce negative titers in a significant proportion

of naturally infected dogs.30 Although most studies havebeen directed at E. canis infections, doxycycline hasproven effective for E. equi and E. ewingii infectionsbut less effective for E. chaffeensis.6,12,32

Imidocarb dipropionate, only recently available inthe United States, has also been used successfully totreat canine ehrlichiosis. Although a study in 1980found that imidocarb produced more effective clear-ance of E. canis than did a 2-week course of tetracy-cline, recent studies using doxycycline have docu-mented no difference in the clinical response of dogstreated with either drug alone or with both drugssimultaneously.68,69 Imidocarb is administered at 5mg/kg IM, with a second injection 2 weeks after thefirst.4,69 Pretreatment with atropine may lessen theoccurrence of unpleasant anticholinergic side effects,including salivation, serous nasal discharge, diarrhea,and dyspnea.

Other antibacterial agents have also been evaluatedfor the treatment of ehrlichial infections. Chloram-phenicol may be used in puppies to avoid the discol-oration of erupting teeth associated with tetracycline.4

Quinolones cannot be recommended currently as atreatment for ehrlichiosis. Although enrofloxacin hasbeen used successfully to treat experimental Rickettsia


rickettsii infection in dogs, it does not seem an effectivetreatment for E. canis. Most dogs with experimental E.canis infections that were administered dosages of 10mg/kg PO q12h for 21 days remained thrombocy-topenic and blood culture positive.32 Similarly,ciprofloxacin was unsuccessful in eliminating infectionwith E. chaffeensis in humans.70

In addition to antibiotics, other supportive therapiesmay be required during ehrlichial infection. Glucocor-ticosteroids can attenuate the immune-mediateddestruction of platelets associated with infection, andthus a short course (2 to 7 days) of prednisone may beindicated if thrombocytopenia is severe or pendingdiagnostic testing to differentiate ehrlichiosis fromimmune-mediated thrombocytopenia.4,23 Steroids mayalso be indicated for the treatment of polyarthritis, vas-culitis, or meningitis associated with certain types ofehrlichial infections.4,46,47 Other supportive treatmentsmight include the administration of parenteral crystal-loid or colloidal fluids or blood transfusion, as indi-cated.3,4 Complications of chronic E. canis infection(e.g., glomerulonephritis, pancytopenia) may likewiserequire specific supportive therapy.

EVALUATING TREATMENTEvaluation of treatment remains problematic. Reso-

lution of clinical signs and normalization of plateletcounts are usually noted within days of initiatingproper treatment for acute cases and often for mildchronic cases as well.4,23,69 Even after rapid clinicalimprovement, studies have found that platelet countsmay again decrease after completion of doxycyclinetherapy, titers remain elevated, organisms can still becultured, and PCR results remain positive.64,69 Serumantibody titers can remain elevated for months to yearsafter appropriate treatment in dogs that remain clini-cally and hematologically normal.30,31,64,69 These persis-tently positive titers, which tend to correlate with thehighest initial titers, may indicate continued infectionor re-infection or may be indicative of a past infectiononly.23,30 PCR may offer the best option for document-ing clearance of the organisms after therapy, but evenPCR evaluation can be problematic. PCR detects bac-terial DNA but cannot distinguish between living andnonliving organisms. However, it is unlikely that killedehrlichial organisms would persist in the body formore than several weeks, rendering a positive PCRresult strongly suggestive of active infection. Thegreater problem is related to false-negative results whensampling tissues that contain low levels of organisms(e.g., blood, bone marrow).64,65 Practically speaking,treated dogs for which the clinical and laboratory evi-dence of disease is resolved need not be further evalu-

ated for the presence of organisms. In animals treatedappropriately for infection but in which evidence ofdisease remains, a positive PCR would warrant contin-uation or alteration of therapy, while a negative PCRshould prompt consideration that the observed diseasemay not be due to ehrlichiosis.

PREVENTION AND CONTROLUnfortunately, exposure to E. canis does not confer

protective immunity. Effective tick control is the mostimportant preventive measure for infection or re-infec-tion. Several highly efficacious products are availablefor direct application to dogs, including Frontline® TopSpot™ (Merial Ltd, Iselin, NJ), Preventic® collars (Vir-bac, Inc., Fort Worth, TX), and Kiltix® Topical TickControl for Dogs (Bayer Animal Health, Shawnee Mis-sion, KS). In addition, many premise sprays are avail-able to decrease tick populations in the dog’s local envi-ronment. The prophylactic use of tetracyclineantibiotics during tick season has also been advocatedfor prevention of infection, but this option is not freefrom either the cost or risk associated with antibioticuse.4 To prevent disease associated with chronic E. canisinfection, it has been suggested that dogs in endemicareas be serologically monitored and positive animalstreated regardless of the presence of clinical signs.4 Wesuggest that a positive screening test (e.g., ELISA) beused as evidence that further evaluation is needed. At aminimum, such evaluation should include a thoroughphysical examination, quantitative platelet count, andmeasurement of serum globulin. Positive screening testsmight also prompt confirmatory tests, including eitherIFA or PCR, prior to initiation of antibiotic therapy.

ZOONOTIC POTENTIALSince the first description of human monocytic ehr-

lichiosis (HME) in the United States in 1986,71 the dis-ease has garnered both scientific and public attention.The agent of HME, which shares a penchant formonocytic cell infection and produces antibodies cross-reactive to E. canis, was named E. chaffeensis.72 E. chaf-feensis infection in dogs has been identified in bothexperimental and natural settings, with the organismpersisting for months.6,49 These long-lasting infectionsraise the concern that dogs may serve as a reservoir ofinfection for human disease.72 Adding to those con-cerns, it seems that doxycycline may not easily clear theorganism from naturally infected dogs.6 In addition toHME, HGE has been recognized as well. The causativeagent of HGE, which differs from that of HME, hasproven to be nearly identical to E. phagocytophila andE. equi. Although these agents are most commonlyassociated with infection in small ruminants and/or


horses, respectively, both organisms have been isolatedfrom dogs, again raising the possibility that dogs mayserve as a reservoir for human infection.8,11,73,74 Addi-tionally, the common agents of canine ehrilichiosis, E.canis, and E. ewingii can occasionally cause clinical dis-ease in humans.75 The symptoms of HME and HGEare quite similar and include fever, headache, and myal-gia. Left untreated, either infection may prove fatal tohumans.8,71,72,76

CONCLUSIONEhrlichiosis is a bacterial infection transmitted largely

through the bite of infected ticks. Dogs with ehrlichiosiscan no longer be assumed to have an E. canis infectionalone. Veterinarians should be aware of the similaritiesand differences between E. canis and other arthropod-borne infections. Dogs with suggestive clinical signs andlaboratory abnormalities may be started on doxycyclinepending specific diagnostic testing. Veterinarians prac-ticing in endemic areas are confronted with the oftendifficult task of sorting out ehrlichial infection frommere exposure. Once a diagnosis is established, treat-ment should continue for at least 3 weeks. Tick preven-tion for animals in endemic areas should be maintainedthroughout tick season, not only to prevent disease but

also to lessen the potential for dogs to become carriers ofdisease for their human companions.

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1. Ehrlichial organisms are best classified by thea. type of tick involved in transmission.b. type of host cell infected.c. genetic analysis of the 16S rRNA segment.d. species of host animal infected.

2. Which is the primary transmission vector for E. canis?a. D. variabilis c. A. americanumb. R. sanguineus d. Ixodes scapularis

3. Which statement regarding transmission of ehrlichiosis by ticks is true?a. Ticks can infect dogs only in the fall.b. Ticks serve as the reservoir for ehrlichial organisms.c. The ehrlichial organism is passed transovarially prior to infection of dogs.d. Ticks transmit the infection through salivary secretions released during a bite.

4. What are the most common presenting complaints in ehrlichiosis?a. lethargy, fever, and weight lossb. epistaxis and feverc. lameness and lethargyd. secondary infections

5. Which Ehrlichia species most commonly causes lameness?a. E. canis c. E. equib. E. chaffeensis d. E. ewingii


CEARTICLE #1 CE TEST

The article you have read qualifies for 1.5 contact hours of ContinuingEducation Credit from the Auburn University College of VeterinaryMedicine. Choose the best answer to each of the following questions; thenmark your answers on the postage-paid envelope inserted in Copendium.

6. A positive E. canis titer in an asymptomatic dog in anendemic area indicates that the dog hasa. been exposed and has produced antibodies.b. entered the subclinical phase of infection.c. been infected in the past but has cleared the organisms.d. any of the above

7. Infection with _________ is the most likely explana-tion for observed granulocytic morulae and a negativeE. canis titer.a. E. ewingii c. E. equib. E. platys d. E. chaffeensis

8. Six months after treating an infected dog with doxycy-cline, a positive E. canis IFA titer can reveal

a. persistence of the titer despite elimination of theorganisms.

b. persistence of the organism.c. re-infection with organisms.d. any of the above

9. Administration of ______________ for _______ daysis the recommended treatment protocol for chronicehrlichiosis.a. doxycycline; 21 c. doxycycline; 7 to 10b. tetracycline; 7 to 10 d. enrofloxacin; 21

10. ___________ has not been reported to infect humans.a. E. chaffeensis c. E. equib. E. ewingii d. E. platys


the increasingly complicated story of ehrlichia

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