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A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS



                                                                        AUGUST 2005 VOLUME 3, NUMBER 3




                                              Tickborne Diseases
                                              of Cats
                                                         Edward B. Breitschwerdt, DVM
                                                         Professor of Medicine and Infectious Diseases
                                                         College of Veterinary Medicine
                                                         North Carolina State University




    In general, our knowledge of tickborne     states, cytauxzoonosis is now reported      disease transmission. Most tick-transmitted
diseases in cats is substantially less than    throughout the southeastern, south          pathogens require a 24- to 48-hour
our knowledge of the comparable disease        central, and mid-Atlantic states. As        period of attachment to the host before
in dogs or human patients. One exception       such, cytauxzoonosis is an important        successful transmission of an infectious
to this generality is cytauxzoonosis, a        emerging tickborne disease of cats with     organism is possible. Fastidious grooming
protozoal disease of cats caused by            an expanding geographic distribution.       may result in the early removal of most
Cytauxzoon felis. The organism is              In C. felis–endemic regions, acaracides     ticks from cats and, thereby, the
supposedly transmitted from bobcats,           should be recommended routinely for cats    prevention of disease transmission.
the primary reservoir host, to domestic        in an effort to prevent this highly fatal   Alternatively, serologic testing in cats
cats via a tick vector (the ixodid tick        infection.                                  has led to confusing and somewhat
Dermacentor variabilis). Because of the           Recent molecular evidence indicates      discordant data. Therefore, as described
rapidly fatal nature of C. felis–induced       that cats can also be infected with         below, polymerase chain reaction (PCR)
illness, the domestic cat has usually been     Anaplasma phagocytophilum and an            testing should be used more frequently in
considered an accidental dead-end host         Ehrlichia canis–like organism. The          the future to clarify the role of tickborne
for this infectious agent. Typical clinical    infrequent diagnosis of anaplasmosis        organisms as a cause of disease in cats.
manifestations include depression,             and ehrlichiosis in cats may be related
lethargy, anorexia, fever, and jaundice.       to a number of factors, including a
Cats often die less than a week from the       general underrecognition of tickborne             IN THIS ISSUE:
initial onset of clinical signs. Some cats,    diseases in cats, potentially decreased           Tickborne Diseases of Cats ........            1
however, survive C. felis infections and       pathogenicity of tickborne organisms in
after recovery may remain asymptomatic         cats as compared with dogs or people,             Tickborne Diseases of Dogs.......              4
carriers for months to years. Initially        and the rapid removal of ticks from cats          Ask the Vet ................................   7
reported in Missouri and surrounding           resulting in decreased opportunity for
Although various Ehrlichia, Anaplasma,            comparable E. canis DNA sequences                               A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS

  and Neorickettsia spp have been reported              obtained from canine E. canis isolates.
                                                                                                                 AUGUST 2005 VOLUME 3, NUMBER
  to cause disease in cows, sheep, dogs,                Because no isolates were made from                                                  3


  horses, and humans, the role of any                   these cats, a more complete genetic               Consulting Editors
  specific species as a pathogen in cats                characterization was not possible;                Albert Ahn, DVM
  remains less clearly defined. The first               therefore, we are currently describing             Vice President of Corporate
  evidence for naturally occurring feline               these feline infections as E. canis–like.          Communications and Veterinary
  ehrlichiosis was provided by Charpentier              Antibodies could not be detected in                Operations
  and Groulade in France. Feline                        these cats by immunofluorescent assay              The Hartz Mountain Corporation
  ehrlichiosis was subsequently reported in             using E. canis antigens. Serum from all           Bruce Truman
  1989 by Buoro and colleagues when they                three cats from Canada and the United              Senior Director
  described intracytoplasmic inclusions in              States contained antinuclear antibodies.           Animal Health and Nutrition
                                                                                                           The Hartz Mountain Corporation
  monocytes and lymphocytes derived from                The predominant disease manifestations
  three cats in Kenya. By both light and                included polyarthritis accompanied                Associate Editors
  electron microscopy, the inclusions were              by fever in one cat, bone marrow                  Jill A. Richardson, DVM
  morphologically similar to Ehrlichia sp               hypoplasia or dysplasia accompanied                Director—Consumer Relations
  morulae, as observed on blood smears                  by pancytopenia in one cat, and anemia             The Hartz Mountain Corporation
  obtained from other animals. Subsequently,            and thrombocytopenia in one cat. In               David Levy
  morulae were described in stained blood               dogs, neutrophilic polyarthritis has               Assistant Manager
  smears obtained from cats in the United               been most frequently associated with               Animal Health and Nutrition
                                                                                                           The Hartz Mountain Corporation
  States, France, Brazil, and Sweden. To                E. ewingii infection. Neutrophilic
  date, no Anaplasma or Ehrlichia spp have              polyarthritis in the one cat was confirmed
                                                                                                          HARTZ® COMPANION ANIMAL                                      SM


  been cultured from the blood of a cat;                by cytologic analysis of joint fluid at           is produced for The Hartz Mountain
  however, Bjoersdorff and colleagues                   1 and 3 years of age, suggesting the              Corporation by Veterinary Learning
  amplified and sequenced 16S rDNA                      possibility of chronic E. canis–like              Systems, 780 Township Line Rd.,
  (from an EDTA blood sample obtained                   infection. Previous serologic studies             Yardley, PA 19067.
  from a 14-month-old shorthaired cat                   have reported an association between              Copyright © 2005 The Hartz Mountain
  from Sweden) that was 100% similar to                 thrombocytopenia, hyperglobulinemia,              Corporation. All rights reserved.
  canine and equine A. phagocytophilum                  and polyarthritis in cats that had E. canis       Hartz® and other marks are owned by
  strains from the same region.                         antibodies. Other nonspecific clinical            The Hartz Mountain Corporation.
  Experimentally, inoculation of cats with              abnormalities, including lethargy,
                                                                                                          Printed in U.S.A. No part of this
  A. phagocytophilum resulted in                        anorexia, conjunctivitis, swelling in the         publication may be reproduced in any
  asymptomatic infection or mild fever                  ventral neck region, and mild interstitial        form without the express written
  and depression, and the development                   lung disease, were reported in these cats         permission of the publisher.
  of neutrophilic and eosinophilic                      and can be observed in association with           For more information on The Hartz
  morulae. Recently, several laboratories,              canine ehrlichiosis.                              Mountain Corporation, visit
  including the North Carolina State                        There is increasing evidence that ticks,      www.hartz.com.
  University Vector Borne Diseases                      as well as fleas, can transmit Bartonella
  Diagnostic Laboratory, have amplified                 spp. The extent to which various tick          perpetuating future generations of
  A. phagocytophilum DNA from the blood                 species are vector competent to transmit       tickborne organisms.
  of acutely ill cats with fever, lethargy,             various Bartonella spp to cats, dogs, or           To further define the spectrum of
  inappetence and thrombocytopenia.                     humans is unknown. There are numerous          feline tickborne infections and until such
  These feline cases have been identified in            recent reviews of bartonellosis that           time as serologic testing is thoroughly
  geographic regions that are endemic for               provide veterinarians with an excellent        validated in experimentally or naturally
  canine, equine, or human anaplasmosis.                background for these emerging zoonotic         infected cats, PCR testing will be
      Our research group has also described             infectious organisms. Two reviews are          necessary. In addition, until E. canis and
  E. canis–like infection in young cats from            cited in the suggested readings. Similar to    other tickborne pathogens have been
  the southeastern United States, eastern               Ehrlichia spp, Bartonella spp can cause        isolated from cats and several isolates are
  Canada, and France. Based on PCR                      long-lasting intravascular infections in       available from disparate geographic
  amplification and DNA sequencing, the                 cats and dogs. As with other vectorborne       regions for detailed comparative genetic
  Ehrlichia DNA amplified from the blood                organisms, blood serves as a food source       study, the molecular evidence supporting
  of these cats was 100% similar to the                 for fleas and ticks and as a means of          E. canis infection in cats must be

2 HARTZ COMPANION ANIMAL
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                               • AUGUST 2005 • VOL. 3, NO. 3
interpreted with caution. Because tick            should be avoided because it denatures         ■ If the PCR test is properly designed
exposure has not been clearly established         DNA with prolonged exposure.                        and performed, a false-positive result
in cats with E. canis–like infection, it is                                                           should not occur. PCR contamination
                                               ■ After completion of treatment to
possible that an Ehrlichia genotype, with                                                             can result in a false-positive result.
                                                  confirm therapeutic elimination of
complete or partial 16S rDNA homology                                                                 However, good molecular diagnostic
                                                  the infection (i.e., failure to detect
with E. canis, is capable of infecting cats                                                           laboratories run several controls to help
                                                  DNA supports treatment success):
and may have evolved with a different                                                                 avoid or detect PCR contamination.
                                                  Conceptually, veterinarians can think
mode of transmission as compared with                                                                 Newer PCR approaches such as
                                                  of PCR testing as using the same
tick transmission of E. canis to dogs.                                                                real-time PCR greatly decrease the
                                                  logic and approach as when culturing
   To facilitate the generation of                                                                    possibility of PCR contamination as
                                                  urine. It is best to perform PCR
new information related to tickborne                                                                  compared to older, conventional PCR
                                                  before antibiotic administration or
infections in cats, veterinarians will                                                                assays.
                                                  after treatment has been stopped. If
have to become more knowledgeable
                                                  treatment has not eliminated the               ■ PCR assays performed by different
about molecular versus serologic testing
                                                  infection, waiting 2 to 3 weeks after               laboratories can vary substantially in
modalities. I will briefly review some
                                                  treatment should allow the number of                the quality of the assay and test
considerations when requesting molecular-
                                                  organisms to increase in the blood or               results. Always know your laboratory.
based diagnostic testing on a cat with
                                                  tissue sample to a level that can be
suspected tickborne infection.
                                                  detected by PCR.
                                                                                                 SUGGESTED READING
                                                                                                 Bjoersdorff A, Svendenius L, Owens JH, Massung RF:
               PCR testing should be used                                                            Feline granulocytic ehrlichiosis—A report of a new
                                                                                                     clinical entity and characterisation of the infectious
      more frequently to clarify the role of tickborne                                               agent. J Small Anim Pract 40:20–24, 1999.
                                                                                                 Bondy PJ, Cohn LA, Kerl ME: Feline cytauxzoonosis.
             organisms as a cause of disease.                                                       Compend Contin Educ Pract Vet 27:69–75, 2005.
                                                                                                 Bouloy RP, Lappin MR, Holland CH, et al: Clinical
                                                                                                    ehrlichiosis in a cat. JAVMA 204:1475–1478, 1994.
MOLECULAR DIAGNOSTICS                          ■ When the species of an infectious
                                                                                                 Breitschwerdt EB, Abrams-Ogg ACG, Lappin M, et al:
AND PCR TESTING:                                  agent is important for determination               Molecular evidence supporting Ehrlichia canis-like
DO’S AND DON’TS                                   of the appropriate type of drug to use             infection in cats. J Vet Intern Med 16:642–649, 2002.
   PCR is a highly sensitive diagnostic           for treatment: For example, different          Breitschwerdt EB, Kordick DL: Bartonella infection in
                                                  drugs would be used to treat Babesia               animals: Carriership, reservoir potential,
technique that can be used to detect small                                                           pathogenicity, and zoonotic potential for human
quantities of bacterial, viral, or protozoal      canis and Babesia gibsoni infections in            infection. Clin Microbiol Rev 13:428–438, 2000.
DNA or RNA in a patient’s blood, fluid,           dogs. Species-specific PCR allows              Buoro IBJ, Atwell RB, Kiptoon J, et al: Feline anemia
or tissue specimens. PCR does not                 differentiation of the infecting species.         associated with Ehrlichia-like bodies in three domestic
                                                                                                    shorthaired cats. Vet Rec 125:434–436, 1989.
amplify or detect antibodies or antigens,
                                                                                                 Charpentier F, Groulade P: Probable case of ehrlichiosis
only DNA or RNA. Therefore, the                PCR: Points to Ponder                                in a cat. Bull Acad Vet Fr 59:287–290, 1986.
targeted organism must be in the sample        ■ Although this is a very sensitive test,         Chomel B, Kasten RW, Sykes JE, et al: Clinical impact
for its DNA or RNA to be detected.               a negative PCR result will never                   of persistent Bartonella bacteremia in humans and
                                                 definitively eliminate the possibility             animals. Ann N Y Acad Sci 990:1–12, 2003.
When to Use PCR Testing                          of an infectious agent.                         Kidd L, Breitschwerdt EB: Transmission times and
                                                                                                    prevention of tick-borne diseases in dogs. Compend
■ Before administration of an antibiotic
                                               ■ Repeated negative PCR results from                 Contin Educ Pract Vet 25:742–750, 2003.
  or antiprotozoal drug to confirm                                                               Lappin MR, Breitschwerdt EB, Jensen WA, et al:
                                                  the same patient would strongly
  active infection (i.e., presence of                                                               Molecular and serologic evidence of Anaplasma
                                                  support therapeutic elimination of the
  DNA equals presence of the organism):                                                             phagocytophilum infection in cats in North America.
                                                  infectious agent.                                 JAVMA 225(6):893–896, 2004.
  Antibody tests confirm exposure to
                                                                                                 Luria BJ, Levy JK, Lappin MR, et al: Prevalence of
  the organism and may or may not be           ■ In most instances, the use of                       infectious diseases in feral cats in northern Florida.
  reflective of active infection. When in         glucocorticoids will increase the                  J Feline Med Surg 6:287–296, 2004.
  doubt, store an EDTA-anticoagulated             number of infectious particles in              Meinkoth J, Kocan AA: Feline cytauxzoonosis. Vet Clin
  blood sample in the refrigerator                the blood. Therefore, corticosteroid              North Am Small Anim Pract 35:89–101, 2005.
  before administering treatments. It is          administration, particularly at                Stubbs CJ, Holland CJ, Reif JS, et al: Feline ehrlichiosis:
                                                                                                     Literature review and serologic survey. Compend
  better to have a pretreatment sample            immunosuppressive doses, can                       Contin Educ Pract Vet 22:307–317, 2000.
  and not need it than to need the                enhance PCR detection of an                    Wagner JE: A fatal cytauxzoonosis-like disease in cats.
  sample and not have it. Formalin                infectious agent.                                JAVMA 168:585–588, 1976.



                                                                                       HARTZ® COMPANION ANIMALSM • AUGUST 2005 • VOL. 3, NO. 3                 3
Tickborne Diseases
                                                        of Dogs
                                                        Edward B. Breitschwerdt, DVM
                                                        Professor of Medicine and Infectious Diseases
                                                        College of Veterinary Medicine
                                                        North Carolina State University



      Despite substantial progress in                    and tick-transmitted organisms need            the comparative medical understanding
  our understanding of the disease                       a “home” for the maintenance and               of these seemingly elusive infectious
  manifestations caused by several tick-                 perpetuation of future generations.            agents.
  transmitted pathogens, numerous                        Therefore, on a daily basis, veterinarians
  challenges continue to confront the                    and pet owners are confronted with an          CASE EXAMPLE
  veterinary profession. This is particularly            evolutionary cycle that has been ongoing           To highlight the clinical complexity
  true in the context of canine tickborne                for millions of years.                         and the challenges to our current
  infections. Depending on their geographic                  Without question, veterinarians play       understanding of tick-transmitted
  location, local environmental exposure                 a central role in the diagnosis, treatment,    infectious diseases, I would like to use the
  to brush and high grass (well confined                 and prevention of tick-transmitted             following example from a consultation
  or allowed to roam), utility (hunting,                 infectious diseases of companion animals.      with a practice owner in Iowa. The
  search and rescue, herding, household                  They also play an important role in            veterinarian contacted me because one of
  companion), and individual personalities,              advising the public as to the zoonotic         his “associates” had evaluated a dog that
  dogs will experience highly variable                   potential of pathogens that are transmitted    initially presented with acute onset of
  degrees of tick infestation. For example, it           by ticks to cats, dogs, and humans.            weakness and mild anemia (hematocrit
  is uncommon for a golden retriever or                  Based on scientific evidence that has          27%). Following “symptomatic therapy,”
  Labrador retriever to stay on the sidewalk             been generated during the past several         the hematocrit normalized for several
  and not run through high grass and low                 decades, tick-transmitted pathogens can        weeks (rechecked at least four times);
  brush, the favorite habitats of most ticks.            induce clinical manifestations ranging         however, on a subsequent recheck,
  In addition, management practices,                     from acute fatal illnesses (e.g., Rocky        the hematocrit was 12%, immune-
  particularly for kennel dogs, will greatly             Mountain spotted fever, ehrlichiosis, and      mediated hemolytic anemia (IMHA)
  influence the frequency and severity of                babesiosis) to chronic debilitating disease    was diagnosed, and the dog was
  tick infestations. For these reasons, tick             states (e.g., ehrlichiosis, babesiosis,        immediately referred to the University
  exposure and tickborne infections, although            borreliosis, bartonellosis). The family dog    of Iowa College of Veterinary Medicine.
  more frequent in medium- to large-breed                is an exceptional environmental sentinel       In conjunction with the medical
  dogs or hunting and herding breeds, can                for establishing the potential for             management of IMHA, serum was sent
  be found in all dog breeds and in most                 infection with tickborne organisms in a        to the North Carolina State University
  parts of the world. Clearly, the routine use           given locality. Although controversial,        Vector Borne Diseases Diagnostic
  of acaracide products plays an important               exposure surveillance for a spectrum of        Laboratory (VBDDL) for a tickborne
  role in killing ticks before pathogens can             tickborne organisms in dogs can be used        pathogen serology panel. Unfortunately,
  be effectively transmitted; however,                   to educate clients and physicians as to        the dog died before test results were
  veterinarians should not assume that                   the potential for human infection.             available, which is not surprising. Several
  any available product or combination                   Clearly, minimizing or eliminating tick        recent studies indicate that approximately
  of products will be 100% effective in                  infestations in companion animals is           50% of IMHA referrals to tertiary care
  preventing transmission of tickborne                   perhaps of greater importance to the           centers die because of their disease. In
  pathogens. Tick transmission of a                      pet-owning public today than during any        our laboratory, immunofluorescent assay
  spectrum of microorganisms constitutes                 previous time in history. In addition to       detected Babesia canis antibodies (titer
  a highly complex process that on an                    facilitating improvements in health care       1:64), and additional review of the dog’s
  evolutionary basis seems to favor the tick             for companion animals, veterinarians are       history determined that the dog had
  and the microorganism. Ticks need blood,               contributing in a substantial manner to        traveled to Arkansas during the previous

4 HARTZ COMPANION ANIMAL
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                                • AUGUST 2005 • VOL. 3, NO. 3
year. Conclusions we can draw from this       COMPLICATING FACTORS IN                           When multiple factors simultaneously
example are as follows:                       CLINICAL CONFIRMATION                             induce chronic changes in structural,
                                                 I believe that the above example               biochemical, and physiologic processes
1. A diagnosis of IMHA secondary to
                                              of vectorborne infection is repeated              over a protracted period of time, disease
   babesiosis was made (perhaps), but
                                              on a daily basis in veterinary practices          expression can be highly variable,
   too late to benefit the dog or the
                                              throughout the United States, only                even among a specific dog population.
   owner.
                                              with different organisms, different dogs,         Because the factors that influence disease
2. Serologic evidence of B. canis exposure    different owners, and different attending         expression can differ significantly among
   does not confirm active Babesia            clinicians. The same evolutionary                 individuals within a given population,
   infection. Polymerase chain reaction       adaptations that facilitate the persistence       clinicians should anticipate a broad
   (PCR) testing would have documented        of many tickborne infections in dogs              spectrum of clinical, hematologic, or
   active infection by detecting B. canis–    also complicate clinical confirmation of          biochemical abnormalities when focusing
   specific DNA sequences in the dog’s        disease causation. This is particularly true      diagnostic emphasis on a single factor
   blood sample. EDTA-anticoagulated          when assessing diagnostic test results for        or test result. For example, diverse
   blood was not submitted to the             an individual dog residing in a highly            disease manifestations, including
   VBDDL at the same time the serum           endemic area for vectorborne infections.          epistaxis, IMHA, immune-mediated
   sample was submitted, so PCR testing       For example, our research group has               thrombocytopenia, glomerulonephritis,
   was not a possibility. Because Babesia     generated PCR evidence (i.e., finding             polyarthritis, and myelofibrosis, have
   spp are intraerythrocytic organisms,       organism-specific DNA) for the presence           been historically attributed to Ehrlichia
   DNA must be extracted from the             of six different tickborne pathogens in a         canis infection in dogs. For a variety of
   erythrocytes for PCR amplification.        single EDTA blood sample, obtained                reasons, it is increasingly clear that
3. Arkansas is highly endemic for B.          from a Walker hound with extensive tick           canine ehrlichiosis is a disease complex
   canis. Iowa is not endemic for B. canis.   exposure. Most dogs in this kennel also           that is influenced by the infecting
   The dog most likely acquired the
   infection from a brown dog tick
   (Rhipicephalus sanguineus) while in           The same evolutionary adaptations that facilitate
   Arkansas.                                        the persistence of tickborne infections also
Other considerations include:
                                               complicate clinical confirmation of disease causation.
1. Because of research by Dr. Adam
   Birkenheuer at NCSU (and others            had antibodies to nearly every tickborne          Ehrlichia sp, the host immune response,
   around the country), babesiosis is         organism for which we tested. Therefore,          coinfection with other vectorborne or
   becoming recognized as an emerging         clinicians need to recognize that the             nonvectorborne pathogens, and perhaps
   canine and human infectious disease        mammalian body functions as a component           numerous other factors yet to be
   in the United States.                      of numerous complex ecosystems, which             clarified. In addition to E. canis, other
                                              facilitates the evolutionary perpetuation         species (Ehrlichia chaffeensis, Ehrlichia
2. Babesiosis is a definitive cause of
                                              of vectorborne bacteria, protozoa, and            ruminatum, and Ehrlichia ewingii) can
   IMHA in dogs.
                                              viruses. In practical terms, this means           cause ehrlichiosis in dogs and people. In
3. Based on recent studies, both              that the detection of antibodies,                 conjunction with numerous highly
   visualization of Babesia organisms on      antigens, DNA, RNA, or the culture                variable host factors, the infecting
   blood smears and serologic testing are     of microorganisms from a sick dog in a            Ehrlichia sp can influence disease
   insensitive diagnostic tests as compared   highly endemic tick environment does              expression. For instance, polyarthritis in
   with PCR.                                  not directly support a cause and effect           dogs is more frequently associated with
4. Dogs, owners, and other animals travel     relationship between detection of the             E. ewingii infection than with E. canis or
   farther and more frequently than at        microorganism and those disease                   E. chaffeensis infection. It is also possible
   any other time in history. Recent          manifestations found in an individual             that genetic variation in organism
   examples of infectious agents that         patient.                                          virulence can influence disease severity.
   “travel” include SARS, monkeypox,             It is also increasingly obvious                For instance, dogs infected with E. canis
   West Nile virus, and canine                that disease expression is frequently             in Greece are likely to develop severe
   leishmaniasis.                             multifactorial, particularly in those             bone marrow suppression that is
5. It takes only one brown dog tick to        instances in which vectorborne organisms          frequently not therapeutically responsive
   transmit B. canis.                         use blood or the vasculature as a reservoir.      to doxycycline. Both of these


                                                                                      HARTZ® COMPANION ANIMALSM • AUGUST 2005 • VOL. 3, NO. 3   5
observations are in direct contrast to the             E. chaffeensis, Rickettsia rickettsii, and     the potential for the transmission of these
  overall experience with E. canis infections            other less pathogenic spotted fever group      pathogens. Also useful would be a means
  in the United States (i.e., pancytopenia               rickettsiae, such as Rickettsia montana and    of tracking companion animal infectious
  is rare and most dogs, despite chronic                 Rickettsia rhipicephalus. These geographic     diseases maintained by an organization
  illness, respond hematologically after                 differences can be problematic when            such as the Centers for Disease Control
  doxycycline administration). In addition,              determining the causative pathogen,            and Prevention or the Infectious Diseases
  recent data indicate that the common                   particularly because many tick-transmitted     Society of America. Currently, no
  evolutionary history of Anaplasma,                     infections result in a prolonged subclinical   database exists to address local, regional,
  Babesia, Bartonella, Borrelia, Ehrlichia,              course. Therefore, a dog or cat might be       or national concerns about these diseases
  and Rickettsia spp has resulted in                     infected in an endemic area where              in companion animals.
  complex polymicrobial interactions that                veterinarians are very familiar with the
  influence the pathophysiology of disease               disease manifestations but become ill          SUGGESTED READING
  expression in dogs and human patients.                 months to years later after moving to an       Adelson ME, Rao RV, Tilton RC, et al: Prevalence
                                                                                                            of Borrelia burgdorferi, Bartonella spp., Babesia microti,
  For clinicians and diagnostic laboratories,            area where the disease is not endemic and          and Anaplasma phagocytophila in Ixodes scapularis ticks
  confirming active infection caused by                  veterinarians are far less familiar with the       collected in northern New Jersey. J Clin Microbiol
                                                                                                            42:2799–2801, 2004.
  a single tickborne pathogen can be                     disease manifestations. This emphasizes
                                                                                                        Birkenheuer AJ, Breitschwerdt EB: Canine babesiosis.
  challenging, particularly when evaluating              the importance of obtaining a travel               Stand Care Emerg Crit Care Med 6(2):1–4, 2004.
  chronic rather than acute illness.                     history for all sick animals when a vector-    Birkenheuer AJ, Levy MG, Breitschwerdt EB:
                                                                                                            Development and evaluation of a seminested PCR
                                                                                                            for detection and differentiation of Babesia gibsoni
                                                                                                            (Asian genotype) and B. canis DNA in canine blood
            Development of a “tick vaccine” that would                                                      samples. J Clin Microbiol 41:4172–4177, 2003.
                                                                                                        Breitschwerdt EB, Atkins CE, Brown TT, et al:
            prevent transmission of tickborne pathogens                                                     Bartonella vinsonii supsp. berkhoffi and related
             would seem to have great medical utility.                                                      members of the alpha subdivision of the Proteobacteria
                                                                                                            in dogs with cardiac arrhythmias, endocarditis, or
                                                                                                            myocarditis. J Clin Microbiol 37:3618–3626, 1999.
                                                                                                        Breitschwerdt EB, Blann KR, Stebbins ME, et al:
  Seroconversion, culture, and PCR can                   transmitted infectious disease is a                Clinicopathologic abnormalities and treatment
                                                                                                            response in 24 dogs seroreactive to Bartonella vinsonii
  all be used to support causation in an                 diagnostic consideration.                          (berkhoffii) antigens. JAAHA 40:92–101, 2004.
  acutely infected individual. However,                                                                 Breitschwerdt EB, Hegarty BC, Hancock SI: Sequential
  the microbiologic confirmation of                      CONCLUSIONS                                        evaluation of dogs naturally infected with Ehrlichia
                                                                                                            canis, Ehrlichia chaffeensis, Ehrlichia equi, Ehrlichia
  polymicrobial tickborne infections in a                   Tick-transmitted infectious diseases            ewingii or Bartonella vinsonii. J Clin Microbiol
  chronically ill patient using these same               will continue to challenge the creativity          36:2645–2651, 1998.
                                                                                                        Daszak P, Cunningham AA, Hayatt AD: Emerging
  diagnostic modalities can be extremely                 of the medical professions. Future                 infectious diseases of wildlife—Threats to biodiversity
  difficult or in certain instances                      research efforts must substantially                and human health. Science 287:443–449, 2000.
  impossible to achieve.                                 improve our ability to detect the presence     Goodman RA, Hawkins EC, Olby NJ, et al: Molecular
                                                                                                            identification of Ehrlichia ewingii infection in dogs:
      Geographic variation in the prevalence             of tick-transmitted pathogens in our               15 cases (1997–2001). JAVMA 222:1102–1107, 2003.
  of tick-transmitted pathogens also presents            patients. For several tick-transmitted         Kidd L, Breitschwerdt EB: Transmission times and
  an important challenge for veterinary                  diseases, there is a serious need for better       prevention of tick-borne diseases in dogs. Compend
                                                                                                            Contin Educ Pract Vet 25:742–750, 2003.
  clinicians. It has become increasingly                 treatment modalities. The currently            Kordick SK, Breitschwerdt EB, Hegarty BC, et al:
  obvious that ticks in different geographic             available treatments for diseases such             Coinfection with multiple tick-borne pathogens in a
                                                                                                            Walker Hound kennel in North Carolina. J Clin
  regions or localities can transmit                     as babesiosis, bartonellosis, ehrlichiosis,        Microbiol 37:2631–2638, 1999.
  different pathogens. For example, in                   and borreliosis may only induce a state        Lappin MR, Breitschwerdt EB, Jensen WA, et al:
  the northeastern United States, Ixodes                 of remission, rather than eliciting a              Molecular and serologic evidence of Anaplasma
                                                                                                            phagocytophilum infection in cats in North America.
  scapularis can transmit Anaplasma                      therapeutic cure. Because the diagnosis            JAVMA 225(6):893–896, 2004.
  phagocytophilum, Borrelia burgdorferi,                 and treatment of these diseases will           Mylonakis ME, Koutinas AF, Breitschwerdt EB, et al:
  Babesia microti, and Bartonella vinsonii               remain challenging for the clinician and           Chronic canine ehrlichiosis (Ehrlichia canis): A
                                                                                                            retrospective study of 19 natural cases. JAAHA
  (arupensis). In the southeastern United                expensive for the client, development              40:174–184, 2004.
  States, dogs are more frequently exposed               of a “tick vaccine” that would prevent         Tuttle AD, Birkenheuer AJ, Juopperi T, et al: Concurrent
  to Dermacentor variabilis, Amblyomma                   transmission of all or most tickborne              bartonellosis and babesiosis in a dog with persistent
                                                                                                            thrombocytopenia. JAVMA 233:1306–1310, 2003.
  americanum, and Rumex sanguineus,                      pathogens would seem to have great             Weinkle TK, Center SA, Randolph JF, et al: Evaluation
  which could result in infection with                   medical utility. In the interim, the use of        of prognostic factors, survival rates, and treatment
                                                                                                            protocols for immune-mediated hemolytic anemia in
  Anaplasma platys, B. canis, Bartonella                 products that kill ticks before or shortly         dogs: 151 cases (1993–2000). JAVMA 226:1869–
  vinsonii (berkhoffii), E. canis, E. ewingii,           after attachment to the pet will minimize          1880, 2005.


6 HARTZ COMPANION ANIMAL
        ®                  SM
                                • AUGUST 2005 • VOL. 3, NO. 3
Albert Ahn, DVM, is Vice President of Corporate Communications
                   and Veterinary Operations at The Hartz Mountain Corporation.




                                              ASK TH E VET
Q    A client of mine mentioned that she saw
     something on the news regarding the
     discontinuation of the Hartz Advanced
                                                                 Q    What is the dose of grapes and raisins
                                                                      that can cause poisoning in dogs?

     Care Flea and Tick drops for cats. Could
     you explain what is going on with this
     situation?
                                                                 A    According to current information,1 the lowest
                                                                      documented toxic grape and raisin doses are 0.7
                                                                      oz/kg and 0.11 oz/kg, respectively. The mechanism of
                                                                      action and toxic principal are unknown at this

A    Hartz has decided to voluntarily discontinue sales of
     our Hartz® ADVANCED CARE® 4 in 1® Flea and Tick
     Drops Plus+ for Cats and Hartz® ADVANCED CARE®
                                                                      time but are currently being studied. Reported
                                                                      histopathologic lesions seen with raisin and/or
                                                                      grape poisoning include proximal renal tubular
                                                                      degeneration and necrosis.
     3 in 1® Flea and Tick Drops for Cats as of March 31,
     2006. In addition, Hartz has implemented label
     changes to these products this summer.                           REFERENCE
                                                                      1. Gwaltney-Brant S, Holding JK, Donaldson CW, et al: Renal failure
                                                                         associated with ingestion of grapes or raisins in dogs [letter]. JAVMA
                                                                         218(10):1555–1556, 2001.
     This move is being made following discussions
     with the Environmental Protection Agency, which
     regulates topical insecticides. Those discussions were
     prompted by concerns over the number of adverse
     reactions that have been reported by cat owners. If
     you or your clients have any questions about this
     situation, please contact the Hartz Consumer
     Relations Department at 800-275-1414. Please be
     assured that Hartz will offer you any support needed
     to address customer concerns.



Articles found in the Hartz Companion Animal SM newsletter can be copied and distributed to your colleagues, staff, and clients.
     Additional newsletters may also be obtained by contacting us at feedback@hartz.com or by phone at 800-275-1414.


 WE WANT TO HEAR FROM YOU!
 • Have questions or comments? Call our Consumer Relations Department at 800-275-1414 and ask to speak to a Hartz staff
   veterinarian or email us at feedback@hartz.com.
 • To obtain a Hartz Veterinary Catalog of products, please call 800-999-3000 x5118 or email us at feedback@hartz.com.



                                                                                 HARTZ® COMPANION ANIMALSM • AUGUST 2005 • VOL. 3, NO. 3          7
For more than 10 years, the American
These Pals are                                   Veterinary Medical Foundation (AVMF) has
                                                 helped thousands of animals in emergency
                                                 situations, like earthquakes, hurricanes, fires,

  Life Savers!
  life savers
       Savers                                    floods and even terrorist attacks.
                                                 In honor of their dedicated service, Hartz® is
                                                 pleased to announce the new Vet PalsTM plush
                                                 toy line. Hartz® Vet PalsTM tell the stories of
                                                 animals helped during times of emergency.
                                                 But that’s not all. For each Hartz® Vet Pal™
                                     ™
                                                 sold, Hartz® donates a portion of the proceeds

             VETPALS                             to the AVMF to help in future aid efforts.
                                                 We need your help. Offer Hartz® Vet PalsTM
 Plush pet toys designed to make a difference!   to your clients, and together we can make a
                                                 difference in the lives of so many more animals.

                                                 Together, we can save lives.
                                                 To order,
                                                 visit www.
                                                 Vetpals.org
                                                 or call
                                                 1-888-281-6400.
                                                                             only
                                                                                    $     30             00
                                                                                                         for the
                                                                                                 entire 6 piece
                                                                                                     collection
                                                                                          R




                                                 American Veterinary Medical Foundation                            AD-347




Veterinary Learning Systems
780 Township Line Road
                                                                                              PRESORTED STANDARD

Yardley, PA 19067
                                                                                                  U.S. POSTAGE
                                                                                                  PAID
                                                                                                 BENSALEM, PA
                                                                                                 PERMIT #118




                                                                                                            401303

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Hartz Companion Animal - Tickborne Diseases of Cats

  • 1. A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS AUGUST 2005 VOLUME 3, NUMBER 3 Tickborne Diseases of Cats Edward B. Breitschwerdt, DVM Professor of Medicine and Infectious Diseases College of Veterinary Medicine North Carolina State University In general, our knowledge of tickborne states, cytauxzoonosis is now reported disease transmission. Most tick-transmitted diseases in cats is substantially less than throughout the southeastern, south pathogens require a 24- to 48-hour our knowledge of the comparable disease central, and mid-Atlantic states. As period of attachment to the host before in dogs or human patients. One exception such, cytauxzoonosis is an important successful transmission of an infectious to this generality is cytauxzoonosis, a emerging tickborne disease of cats with organism is possible. Fastidious grooming protozoal disease of cats caused by an expanding geographic distribution. may result in the early removal of most Cytauxzoon felis. The organism is In C. felis–endemic regions, acaracides ticks from cats and, thereby, the supposedly transmitted from bobcats, should be recommended routinely for cats prevention of disease transmission. the primary reservoir host, to domestic in an effort to prevent this highly fatal Alternatively, serologic testing in cats cats via a tick vector (the ixodid tick infection. has led to confusing and somewhat Dermacentor variabilis). Because of the Recent molecular evidence indicates discordant data. Therefore, as described rapidly fatal nature of C. felis–induced that cats can also be infected with below, polymerase chain reaction (PCR) illness, the domestic cat has usually been Anaplasma phagocytophilum and an testing should be used more frequently in considered an accidental dead-end host Ehrlichia canis–like organism. The the future to clarify the role of tickborne for this infectious agent. Typical clinical infrequent diagnosis of anaplasmosis organisms as a cause of disease in cats. manifestations include depression, and ehrlichiosis in cats may be related lethargy, anorexia, fever, and jaundice. to a number of factors, including a Cats often die less than a week from the general underrecognition of tickborne IN THIS ISSUE: initial onset of clinical signs. Some cats, diseases in cats, potentially decreased Tickborne Diseases of Cats ........ 1 however, survive C. felis infections and pathogenicity of tickborne organisms in after recovery may remain asymptomatic cats as compared with dogs or people, Tickborne Diseases of Dogs....... 4 carriers for months to years. Initially and the rapid removal of ticks from cats Ask the Vet ................................ 7 reported in Missouri and surrounding resulting in decreased opportunity for
  • 2. Although various Ehrlichia, Anaplasma, comparable E. canis DNA sequences A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS and Neorickettsia spp have been reported obtained from canine E. canis isolates. AUGUST 2005 VOLUME 3, NUMBER to cause disease in cows, sheep, dogs, Because no isolates were made from 3 horses, and humans, the role of any these cats, a more complete genetic Consulting Editors specific species as a pathogen in cats characterization was not possible; Albert Ahn, DVM remains less clearly defined. The first therefore, we are currently describing Vice President of Corporate evidence for naturally occurring feline these feline infections as E. canis–like. Communications and Veterinary ehrlichiosis was provided by Charpentier Antibodies could not be detected in Operations and Groulade in France. Feline these cats by immunofluorescent assay The Hartz Mountain Corporation ehrlichiosis was subsequently reported in using E. canis antigens. Serum from all Bruce Truman 1989 by Buoro and colleagues when they three cats from Canada and the United Senior Director described intracytoplasmic inclusions in States contained antinuclear antibodies. Animal Health and Nutrition The Hartz Mountain Corporation monocytes and lymphocytes derived from The predominant disease manifestations three cats in Kenya. By both light and included polyarthritis accompanied Associate Editors electron microscopy, the inclusions were by fever in one cat, bone marrow Jill A. Richardson, DVM morphologically similar to Ehrlichia sp hypoplasia or dysplasia accompanied Director—Consumer Relations morulae, as observed on blood smears by pancytopenia in one cat, and anemia The Hartz Mountain Corporation obtained from other animals. Subsequently, and thrombocytopenia in one cat. In David Levy morulae were described in stained blood dogs, neutrophilic polyarthritis has Assistant Manager smears obtained from cats in the United been most frequently associated with Animal Health and Nutrition The Hartz Mountain Corporation States, France, Brazil, and Sweden. To E. ewingii infection. Neutrophilic date, no Anaplasma or Ehrlichia spp have polyarthritis in the one cat was confirmed HARTZ® COMPANION ANIMAL SM been cultured from the blood of a cat; by cytologic analysis of joint fluid at is produced for The Hartz Mountain however, Bjoersdorff and colleagues 1 and 3 years of age, suggesting the Corporation by Veterinary Learning amplified and sequenced 16S rDNA possibility of chronic E. canis–like Systems, 780 Township Line Rd., (from an EDTA blood sample obtained infection. Previous serologic studies Yardley, PA 19067. from a 14-month-old shorthaired cat have reported an association between Copyright © 2005 The Hartz Mountain from Sweden) that was 100% similar to thrombocytopenia, hyperglobulinemia, Corporation. All rights reserved. canine and equine A. phagocytophilum and polyarthritis in cats that had E. canis Hartz® and other marks are owned by strains from the same region. antibodies. Other nonspecific clinical The Hartz Mountain Corporation. Experimentally, inoculation of cats with abnormalities, including lethargy, Printed in U.S.A. No part of this A. phagocytophilum resulted in anorexia, conjunctivitis, swelling in the publication may be reproduced in any asymptomatic infection or mild fever ventral neck region, and mild interstitial form without the express written and depression, and the development lung disease, were reported in these cats permission of the publisher. of neutrophilic and eosinophilic and can be observed in association with For more information on The Hartz morulae. Recently, several laboratories, canine ehrlichiosis. Mountain Corporation, visit including the North Carolina State There is increasing evidence that ticks, www.hartz.com. University Vector Borne Diseases as well as fleas, can transmit Bartonella Diagnostic Laboratory, have amplified spp. The extent to which various tick perpetuating future generations of A. phagocytophilum DNA from the blood species are vector competent to transmit tickborne organisms. of acutely ill cats with fever, lethargy, various Bartonella spp to cats, dogs, or To further define the spectrum of inappetence and thrombocytopenia. humans is unknown. There are numerous feline tickborne infections and until such These feline cases have been identified in recent reviews of bartonellosis that time as serologic testing is thoroughly geographic regions that are endemic for provide veterinarians with an excellent validated in experimentally or naturally canine, equine, or human anaplasmosis. background for these emerging zoonotic infected cats, PCR testing will be Our research group has also described infectious organisms. Two reviews are necessary. In addition, until E. canis and E. canis–like infection in young cats from cited in the suggested readings. Similar to other tickborne pathogens have been the southeastern United States, eastern Ehrlichia spp, Bartonella spp can cause isolated from cats and several isolates are Canada, and France. Based on PCR long-lasting intravascular infections in available from disparate geographic amplification and DNA sequencing, the cats and dogs. As with other vectorborne regions for detailed comparative genetic Ehrlichia DNA amplified from the blood organisms, blood serves as a food source study, the molecular evidence supporting of these cats was 100% similar to the for fleas and ticks and as a means of E. canis infection in cats must be 2 HARTZ COMPANION ANIMAL ® SM • AUGUST 2005 • VOL. 3, NO. 3
  • 3. interpreted with caution. Because tick should be avoided because it denatures ■ If the PCR test is properly designed exposure has not been clearly established DNA with prolonged exposure. and performed, a false-positive result in cats with E. canis–like infection, it is should not occur. PCR contamination ■ After completion of treatment to possible that an Ehrlichia genotype, with can result in a false-positive result. confirm therapeutic elimination of complete or partial 16S rDNA homology However, good molecular diagnostic the infection (i.e., failure to detect with E. canis, is capable of infecting cats laboratories run several controls to help DNA supports treatment success): and may have evolved with a different avoid or detect PCR contamination. Conceptually, veterinarians can think mode of transmission as compared with Newer PCR approaches such as of PCR testing as using the same tick transmission of E. canis to dogs. real-time PCR greatly decrease the logic and approach as when culturing To facilitate the generation of possibility of PCR contamination as urine. It is best to perform PCR new information related to tickborne compared to older, conventional PCR before antibiotic administration or infections in cats, veterinarians will assays. after treatment has been stopped. If have to become more knowledgeable treatment has not eliminated the ■ PCR assays performed by different about molecular versus serologic testing infection, waiting 2 to 3 weeks after laboratories can vary substantially in modalities. I will briefly review some treatment should allow the number of the quality of the assay and test considerations when requesting molecular- organisms to increase in the blood or results. Always know your laboratory. based diagnostic testing on a cat with tissue sample to a level that can be suspected tickborne infection. detected by PCR. SUGGESTED READING Bjoersdorff A, Svendenius L, Owens JH, Massung RF: PCR testing should be used Feline granulocytic ehrlichiosis—A report of a new clinical entity and characterisation of the infectious more frequently to clarify the role of tickborne agent. J Small Anim Pract 40:20–24, 1999. Bondy PJ, Cohn LA, Kerl ME: Feline cytauxzoonosis. organisms as a cause of disease. Compend Contin Educ Pract Vet 27:69–75, 2005. Bouloy RP, Lappin MR, Holland CH, et al: Clinical ehrlichiosis in a cat. JAVMA 204:1475–1478, 1994. MOLECULAR DIAGNOSTICS ■ When the species of an infectious Breitschwerdt EB, Abrams-Ogg ACG, Lappin M, et al: AND PCR TESTING: agent is important for determination Molecular evidence supporting Ehrlichia canis-like DO’S AND DON’TS of the appropriate type of drug to use infection in cats. J Vet Intern Med 16:642–649, 2002. PCR is a highly sensitive diagnostic for treatment: For example, different Breitschwerdt EB, Kordick DL: Bartonella infection in drugs would be used to treat Babesia animals: Carriership, reservoir potential, technique that can be used to detect small pathogenicity, and zoonotic potential for human quantities of bacterial, viral, or protozoal canis and Babesia gibsoni infections in infection. Clin Microbiol Rev 13:428–438, 2000. DNA or RNA in a patient’s blood, fluid, dogs. Species-specific PCR allows Buoro IBJ, Atwell RB, Kiptoon J, et al: Feline anemia or tissue specimens. PCR does not differentiation of the infecting species. associated with Ehrlichia-like bodies in three domestic shorthaired cats. Vet Rec 125:434–436, 1989. amplify or detect antibodies or antigens, Charpentier F, Groulade P: Probable case of ehrlichiosis only DNA or RNA. Therefore, the PCR: Points to Ponder in a cat. Bull Acad Vet Fr 59:287–290, 1986. targeted organism must be in the sample ■ Although this is a very sensitive test, Chomel B, Kasten RW, Sykes JE, et al: Clinical impact for its DNA or RNA to be detected. a negative PCR result will never of persistent Bartonella bacteremia in humans and definitively eliminate the possibility animals. Ann N Y Acad Sci 990:1–12, 2003. When to Use PCR Testing of an infectious agent. Kidd L, Breitschwerdt EB: Transmission times and prevention of tick-borne diseases in dogs. Compend ■ Before administration of an antibiotic ■ Repeated negative PCR results from Contin Educ Pract Vet 25:742–750, 2003. or antiprotozoal drug to confirm Lappin MR, Breitschwerdt EB, Jensen WA, et al: the same patient would strongly active infection (i.e., presence of Molecular and serologic evidence of Anaplasma support therapeutic elimination of the DNA equals presence of the organism): phagocytophilum infection in cats in North America. infectious agent. JAVMA 225(6):893–896, 2004. Antibody tests confirm exposure to Luria BJ, Levy JK, Lappin MR, et al: Prevalence of the organism and may or may not be ■ In most instances, the use of infectious diseases in feral cats in northern Florida. reflective of active infection. When in glucocorticoids will increase the J Feline Med Surg 6:287–296, 2004. doubt, store an EDTA-anticoagulated number of infectious particles in Meinkoth J, Kocan AA: Feline cytauxzoonosis. Vet Clin blood sample in the refrigerator the blood. Therefore, corticosteroid North Am Small Anim Pract 35:89–101, 2005. before administering treatments. It is administration, particularly at Stubbs CJ, Holland CJ, Reif JS, et al: Feline ehrlichiosis: Literature review and serologic survey. Compend better to have a pretreatment sample immunosuppressive doses, can Contin Educ Pract Vet 22:307–317, 2000. and not need it than to need the enhance PCR detection of an Wagner JE: A fatal cytauxzoonosis-like disease in cats. sample and not have it. Formalin infectious agent. JAVMA 168:585–588, 1976. HARTZ® COMPANION ANIMALSM • AUGUST 2005 • VOL. 3, NO. 3 3
  • 4. Tickborne Diseases of Dogs Edward B. Breitschwerdt, DVM Professor of Medicine and Infectious Diseases College of Veterinary Medicine North Carolina State University Despite substantial progress in and tick-transmitted organisms need the comparative medical understanding our understanding of the disease a “home” for the maintenance and of these seemingly elusive infectious manifestations caused by several tick- perpetuation of future generations. agents. transmitted pathogens, numerous Therefore, on a daily basis, veterinarians challenges continue to confront the and pet owners are confronted with an CASE EXAMPLE veterinary profession. This is particularly evolutionary cycle that has been ongoing To highlight the clinical complexity true in the context of canine tickborne for millions of years. and the challenges to our current infections. Depending on their geographic Without question, veterinarians play understanding of tick-transmitted location, local environmental exposure a central role in the diagnosis, treatment, infectious diseases, I would like to use the to brush and high grass (well confined and prevention of tick-transmitted following example from a consultation or allowed to roam), utility (hunting, infectious diseases of companion animals. with a practice owner in Iowa. The search and rescue, herding, household They also play an important role in veterinarian contacted me because one of companion), and individual personalities, advising the public as to the zoonotic his “associates” had evaluated a dog that dogs will experience highly variable potential of pathogens that are transmitted initially presented with acute onset of degrees of tick infestation. For example, it by ticks to cats, dogs, and humans. weakness and mild anemia (hematocrit is uncommon for a golden retriever or Based on scientific evidence that has 27%). Following “symptomatic therapy,” Labrador retriever to stay on the sidewalk been generated during the past several the hematocrit normalized for several and not run through high grass and low decades, tick-transmitted pathogens can weeks (rechecked at least four times); brush, the favorite habitats of most ticks. induce clinical manifestations ranging however, on a subsequent recheck, In addition, management practices, from acute fatal illnesses (e.g., Rocky the hematocrit was 12%, immune- particularly for kennel dogs, will greatly Mountain spotted fever, ehrlichiosis, and mediated hemolytic anemia (IMHA) influence the frequency and severity of babesiosis) to chronic debilitating disease was diagnosed, and the dog was tick infestations. For these reasons, tick states (e.g., ehrlichiosis, babesiosis, immediately referred to the University exposure and tickborne infections, although borreliosis, bartonellosis). The family dog of Iowa College of Veterinary Medicine. more frequent in medium- to large-breed is an exceptional environmental sentinel In conjunction with the medical dogs or hunting and herding breeds, can for establishing the potential for management of IMHA, serum was sent be found in all dog breeds and in most infection with tickborne organisms in a to the North Carolina State University parts of the world. Clearly, the routine use given locality. Although controversial, Vector Borne Diseases Diagnostic of acaracide products plays an important exposure surveillance for a spectrum of Laboratory (VBDDL) for a tickborne role in killing ticks before pathogens can tickborne organisms in dogs can be used pathogen serology panel. Unfortunately, be effectively transmitted; however, to educate clients and physicians as to the dog died before test results were veterinarians should not assume that the potential for human infection. available, which is not surprising. Several any available product or combination Clearly, minimizing or eliminating tick recent studies indicate that approximately of products will be 100% effective in infestations in companion animals is 50% of IMHA referrals to tertiary care preventing transmission of tickborne perhaps of greater importance to the centers die because of their disease. In pathogens. Tick transmission of a pet-owning public today than during any our laboratory, immunofluorescent assay spectrum of microorganisms constitutes previous time in history. In addition to detected Babesia canis antibodies (titer a highly complex process that on an facilitating improvements in health care 1:64), and additional review of the dog’s evolutionary basis seems to favor the tick for companion animals, veterinarians are history determined that the dog had and the microorganism. Ticks need blood, contributing in a substantial manner to traveled to Arkansas during the previous 4 HARTZ COMPANION ANIMAL ® SM • AUGUST 2005 • VOL. 3, NO. 3
  • 5. year. Conclusions we can draw from this COMPLICATING FACTORS IN When multiple factors simultaneously example are as follows: CLINICAL CONFIRMATION induce chronic changes in structural, I believe that the above example biochemical, and physiologic processes 1. A diagnosis of IMHA secondary to of vectorborne infection is repeated over a protracted period of time, disease babesiosis was made (perhaps), but on a daily basis in veterinary practices expression can be highly variable, too late to benefit the dog or the throughout the United States, only even among a specific dog population. owner. with different organisms, different dogs, Because the factors that influence disease 2. Serologic evidence of B. canis exposure different owners, and different attending expression can differ significantly among does not confirm active Babesia clinicians. The same evolutionary individuals within a given population, infection. Polymerase chain reaction adaptations that facilitate the persistence clinicians should anticipate a broad (PCR) testing would have documented of many tickborne infections in dogs spectrum of clinical, hematologic, or active infection by detecting B. canis– also complicate clinical confirmation of biochemical abnormalities when focusing specific DNA sequences in the dog’s disease causation. This is particularly true diagnostic emphasis on a single factor blood sample. EDTA-anticoagulated when assessing diagnostic test results for or test result. For example, diverse blood was not submitted to the an individual dog residing in a highly disease manifestations, including VBDDL at the same time the serum endemic area for vectorborne infections. epistaxis, IMHA, immune-mediated sample was submitted, so PCR testing For example, our research group has thrombocytopenia, glomerulonephritis, was not a possibility. Because Babesia generated PCR evidence (i.e., finding polyarthritis, and myelofibrosis, have spp are intraerythrocytic organisms, organism-specific DNA) for the presence been historically attributed to Ehrlichia DNA must be extracted from the of six different tickborne pathogens in a canis infection in dogs. For a variety of erythrocytes for PCR amplification. single EDTA blood sample, obtained reasons, it is increasingly clear that 3. Arkansas is highly endemic for B. from a Walker hound with extensive tick canine ehrlichiosis is a disease complex canis. Iowa is not endemic for B. canis. exposure. Most dogs in this kennel also that is influenced by the infecting The dog most likely acquired the infection from a brown dog tick (Rhipicephalus sanguineus) while in The same evolutionary adaptations that facilitate Arkansas. the persistence of tickborne infections also Other considerations include: complicate clinical confirmation of disease causation. 1. Because of research by Dr. Adam Birkenheuer at NCSU (and others had antibodies to nearly every tickborne Ehrlichia sp, the host immune response, around the country), babesiosis is organism for which we tested. Therefore, coinfection with other vectorborne or becoming recognized as an emerging clinicians need to recognize that the nonvectorborne pathogens, and perhaps canine and human infectious disease mammalian body functions as a component numerous other factors yet to be in the United States. of numerous complex ecosystems, which clarified. In addition to E. canis, other facilitates the evolutionary perpetuation species (Ehrlichia chaffeensis, Ehrlichia 2. Babesiosis is a definitive cause of of vectorborne bacteria, protozoa, and ruminatum, and Ehrlichia ewingii) can IMHA in dogs. viruses. In practical terms, this means cause ehrlichiosis in dogs and people. In 3. Based on recent studies, both that the detection of antibodies, conjunction with numerous highly visualization of Babesia organisms on antigens, DNA, RNA, or the culture variable host factors, the infecting blood smears and serologic testing are of microorganisms from a sick dog in a Ehrlichia sp can influence disease insensitive diagnostic tests as compared highly endemic tick environment does expression. For instance, polyarthritis in with PCR. not directly support a cause and effect dogs is more frequently associated with 4. Dogs, owners, and other animals travel relationship between detection of the E. ewingii infection than with E. canis or farther and more frequently than at microorganism and those disease E. chaffeensis infection. It is also possible any other time in history. Recent manifestations found in an individual that genetic variation in organism examples of infectious agents that patient. virulence can influence disease severity. “travel” include SARS, monkeypox, It is also increasingly obvious For instance, dogs infected with E. canis West Nile virus, and canine that disease expression is frequently in Greece are likely to develop severe leishmaniasis. multifactorial, particularly in those bone marrow suppression that is 5. It takes only one brown dog tick to instances in which vectorborne organisms frequently not therapeutically responsive transmit B. canis. use blood or the vasculature as a reservoir. to doxycycline. Both of these HARTZ® COMPANION ANIMALSM • AUGUST 2005 • VOL. 3, NO. 3 5
  • 6. observations are in direct contrast to the E. chaffeensis, Rickettsia rickettsii, and the potential for the transmission of these overall experience with E. canis infections other less pathogenic spotted fever group pathogens. Also useful would be a means in the United States (i.e., pancytopenia rickettsiae, such as Rickettsia montana and of tracking companion animal infectious is rare and most dogs, despite chronic Rickettsia rhipicephalus. These geographic diseases maintained by an organization illness, respond hematologically after differences can be problematic when such as the Centers for Disease Control doxycycline administration). In addition, determining the causative pathogen, and Prevention or the Infectious Diseases recent data indicate that the common particularly because many tick-transmitted Society of America. Currently, no evolutionary history of Anaplasma, infections result in a prolonged subclinical database exists to address local, regional, Babesia, Bartonella, Borrelia, Ehrlichia, course. Therefore, a dog or cat might be or national concerns about these diseases and Rickettsia spp has resulted in infected in an endemic area where in companion animals. complex polymicrobial interactions that veterinarians are very familiar with the influence the pathophysiology of disease disease manifestations but become ill SUGGESTED READING expression in dogs and human patients. months to years later after moving to an Adelson ME, Rao RV, Tilton RC, et al: Prevalence of Borrelia burgdorferi, Bartonella spp., Babesia microti, For clinicians and diagnostic laboratories, area where the disease is not endemic and and Anaplasma phagocytophila in Ixodes scapularis ticks confirming active infection caused by veterinarians are far less familiar with the collected in northern New Jersey. J Clin Microbiol 42:2799–2801, 2004. a single tickborne pathogen can be disease manifestations. This emphasizes Birkenheuer AJ, Breitschwerdt EB: Canine babesiosis. challenging, particularly when evaluating the importance of obtaining a travel Stand Care Emerg Crit Care Med 6(2):1–4, 2004. chronic rather than acute illness. history for all sick animals when a vector- Birkenheuer AJ, Levy MG, Breitschwerdt EB: Development and evaluation of a seminested PCR for detection and differentiation of Babesia gibsoni (Asian genotype) and B. canis DNA in canine blood Development of a “tick vaccine” that would samples. J Clin Microbiol 41:4172–4177, 2003. Breitschwerdt EB, Atkins CE, Brown TT, et al: prevent transmission of tickborne pathogens Bartonella vinsonii supsp. berkhoffi and related would seem to have great medical utility. members of the alpha subdivision of the Proteobacteria in dogs with cardiac arrhythmias, endocarditis, or myocarditis. J Clin Microbiol 37:3618–3626, 1999. Breitschwerdt EB, Blann KR, Stebbins ME, et al: Seroconversion, culture, and PCR can transmitted infectious disease is a Clinicopathologic abnormalities and treatment response in 24 dogs seroreactive to Bartonella vinsonii all be used to support causation in an diagnostic consideration. (berkhoffii) antigens. JAAHA 40:92–101, 2004. acutely infected individual. However, Breitschwerdt EB, Hegarty BC, Hancock SI: Sequential the microbiologic confirmation of CONCLUSIONS evaluation of dogs naturally infected with Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia equi, Ehrlichia polymicrobial tickborne infections in a Tick-transmitted infectious diseases ewingii or Bartonella vinsonii. J Clin Microbiol chronically ill patient using these same will continue to challenge the creativity 36:2645–2651, 1998. Daszak P, Cunningham AA, Hayatt AD: Emerging diagnostic modalities can be extremely of the medical professions. Future infectious diseases of wildlife—Threats to biodiversity difficult or in certain instances research efforts must substantially and human health. Science 287:443–449, 2000. impossible to achieve. improve our ability to detect the presence Goodman RA, Hawkins EC, Olby NJ, et al: Molecular identification of Ehrlichia ewingii infection in dogs: Geographic variation in the prevalence of tick-transmitted pathogens in our 15 cases (1997–2001). JAVMA 222:1102–1107, 2003. of tick-transmitted pathogens also presents patients. For several tick-transmitted Kidd L, Breitschwerdt EB: Transmission times and an important challenge for veterinary diseases, there is a serious need for better prevention of tick-borne diseases in dogs. Compend Contin Educ Pract Vet 25:742–750, 2003. clinicians. It has become increasingly treatment modalities. The currently Kordick SK, Breitschwerdt EB, Hegarty BC, et al: obvious that ticks in different geographic available treatments for diseases such Coinfection with multiple tick-borne pathogens in a Walker Hound kennel in North Carolina. J Clin regions or localities can transmit as babesiosis, bartonellosis, ehrlichiosis, Microbiol 37:2631–2638, 1999. different pathogens. For example, in and borreliosis may only induce a state Lappin MR, Breitschwerdt EB, Jensen WA, et al: the northeastern United States, Ixodes of remission, rather than eliciting a Molecular and serologic evidence of Anaplasma phagocytophilum infection in cats in North America. scapularis can transmit Anaplasma therapeutic cure. Because the diagnosis JAVMA 225(6):893–896, 2004. phagocytophilum, Borrelia burgdorferi, and treatment of these diseases will Mylonakis ME, Koutinas AF, Breitschwerdt EB, et al: Babesia microti, and Bartonella vinsonii remain challenging for the clinician and Chronic canine ehrlichiosis (Ehrlichia canis): A retrospective study of 19 natural cases. JAAHA (arupensis). In the southeastern United expensive for the client, development 40:174–184, 2004. States, dogs are more frequently exposed of a “tick vaccine” that would prevent Tuttle AD, Birkenheuer AJ, Juopperi T, et al: Concurrent to Dermacentor variabilis, Amblyomma transmission of all or most tickborne bartonellosis and babesiosis in a dog with persistent thrombocytopenia. JAVMA 233:1306–1310, 2003. americanum, and Rumex sanguineus, pathogens would seem to have great Weinkle TK, Center SA, Randolph JF, et al: Evaluation which could result in infection with medical utility. In the interim, the use of of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in Anaplasma platys, B. canis, Bartonella products that kill ticks before or shortly dogs: 151 cases (1993–2000). JAVMA 226:1869– vinsonii (berkhoffii), E. canis, E. ewingii, after attachment to the pet will minimize 1880, 2005. 6 HARTZ COMPANION ANIMAL ® SM • AUGUST 2005 • VOL. 3, NO. 3
  • 7. Albert Ahn, DVM, is Vice President of Corporate Communications and Veterinary Operations at The Hartz Mountain Corporation. ASK TH E VET Q A client of mine mentioned that she saw something on the news regarding the discontinuation of the Hartz Advanced Q What is the dose of grapes and raisins that can cause poisoning in dogs? Care Flea and Tick drops for cats. Could you explain what is going on with this situation? A According to current information,1 the lowest documented toxic grape and raisin doses are 0.7 oz/kg and 0.11 oz/kg, respectively. The mechanism of action and toxic principal are unknown at this A Hartz has decided to voluntarily discontinue sales of our Hartz® ADVANCED CARE® 4 in 1® Flea and Tick Drops Plus+ for Cats and Hartz® ADVANCED CARE® time but are currently being studied. Reported histopathologic lesions seen with raisin and/or grape poisoning include proximal renal tubular degeneration and necrosis. 3 in 1® Flea and Tick Drops for Cats as of March 31, 2006. In addition, Hartz has implemented label changes to these products this summer. REFERENCE 1. Gwaltney-Brant S, Holding JK, Donaldson CW, et al: Renal failure associated with ingestion of grapes or raisins in dogs [letter]. JAVMA 218(10):1555–1556, 2001. This move is being made following discussions with the Environmental Protection Agency, which regulates topical insecticides. Those discussions were prompted by concerns over the number of adverse reactions that have been reported by cat owners. If you or your clients have any questions about this situation, please contact the Hartz Consumer Relations Department at 800-275-1414. Please be assured that Hartz will offer you any support needed to address customer concerns. Articles found in the Hartz Companion Animal SM newsletter can be copied and distributed to your colleagues, staff, and clients. Additional newsletters may also be obtained by contacting us at feedback@hartz.com or by phone at 800-275-1414. WE WANT TO HEAR FROM YOU! • Have questions or comments? Call our Consumer Relations Department at 800-275-1414 and ask to speak to a Hartz staff veterinarian or email us at feedback@hartz.com. • To obtain a Hartz Veterinary Catalog of products, please call 800-999-3000 x5118 or email us at feedback@hartz.com. HARTZ® COMPANION ANIMALSM • AUGUST 2005 • VOL. 3, NO. 3 7
  • 8. For more than 10 years, the American These Pals are Veterinary Medical Foundation (AVMF) has helped thousands of animals in emergency situations, like earthquakes, hurricanes, fires, Life Savers! life savers Savers floods and even terrorist attacks. In honor of their dedicated service, Hartz® is pleased to announce the new Vet PalsTM plush toy line. Hartz® Vet PalsTM tell the stories of animals helped during times of emergency. But that’s not all. For each Hartz® Vet Pal™ ™ sold, Hartz® donates a portion of the proceeds VETPALS to the AVMF to help in future aid efforts. We need your help. Offer Hartz® Vet PalsTM Plush pet toys designed to make a difference! to your clients, and together we can make a difference in the lives of so many more animals. Together, we can save lives. To order, visit www. Vetpals.org or call 1-888-281-6400. only $ 30 00 for the entire 6 piece collection R American Veterinary Medical Foundation AD-347 Veterinary Learning Systems 780 Township Line Road PRESORTED STANDARD Yardley, PA 19067 U.S. POSTAGE PAID BENSALEM, PA PERMIT #118 401303