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A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS



                                                                          SEPTEMBER 2006 VOLUME 4, NUMBER 3




                                                 Wolbachia and
                                                 Heartworm Disease
                                                 Laura H. Kramer, DVM, PhD, DEVPC
                                                 College of Veterinary Medicine
                                                 University of Parma, Parma, Italy




    Dirofilaria immitis is the causative agent       developing embryonic stages within the            Wolbachia increases its own fitness by
of canine and feline heartworm disease.              uteri. This suggests that the bacterium is        increasing the fitness of the host
Adult worms live in the pulmonary                    vertically transmitted through the                involved in its transmission.
arteries, and females produce first-stage            cytoplasm of the egg.1                        s   Removal of Wolbachia (via antibiotics
larvae (microfilariae), which are taken up                                                             or radiation) leads to sterility of female
by mosquitoes that then transmit the                 ROLE OF WOLBACHIA IN                              worms and eventual death of adults.
infection to other animals. In dogs, an              ITS FILARIAL HOST
untreated infection leads to congestive                 Human research has revealed several        It is still unclear, however, exactly what
heart failure (Figures 1 and 2). D. immitis,         reasons why the presence of Wolbachia is      Wolbachia does to make it so important
like most filarial worms studied to date,            thought to be essential for a filarial        for its filarial host. It has been suggested
harbor bacteria called Wolbachia, which are          worm’s survival:                              that, while the filarial worm likely supplies
thought to play an essential role in the             s                                             the bacteria with amino acids necessary
                                                         In those species of filarial worms that
biology and reproductive functions of their                                                        for growth and replication, Wolbachia may
                                                         have been identified as harboring
filarial hosts. Wolbachia pipientis, the only                                                      produce several important molecules that
                                                         Wolbachia, all of the individuals are
species thus far identified in the genus,                                                          are essential for heartworms, such as
                                                         infected (i.e., 100% prevalence).
are gram-negative bacteria belonging to                                                            glutathione and heme.2 It is indeed a “one
                                                     s   The evolution of the bacteria matches
the order Rickettsiales (just like Ehrlichia                                                       hand washing the other” situation that
spp and Anaplasma spp).1 In adult D.                     that of the filarial worms, and
immitis, Wolbachia is predominantly found                phylogenic studies have shown that
throughout cells in the hypodermis, which                the two organisms have been “walking
is directly under the worm’s cuticle (Figure             hand-in-hand” for millions of years.            ALSO IN THIS ISSUE:
3). In female D. immitis, Wolbachia is also          s   The bacteria are transmitted from               Deworming Demystified............     4
present in the ovaries, oocytes, and                     female to offspring and, in this way,
A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS



                                                                                                                    SEPTEMBER 2006 VOLUME 4, NUMBER 3



                                                                                                                Consulting Editors
                                                                                                                Albert Ahn, DVM
                                                                                                                 Vice President of Corporate
                                                                                                                 Communications and Consumer
                                                                                                                 Relations
                                                                                                                 The Hartz Mountain Corporation
                                                           Figure 2.         Radiograph of the dog              Bruce Truman
                                                           in Figure 1. Note the enlarged cardiac
                                                                                                                 Senior Director
  Figure 1.      A 6-year-old Great Dane                   chambers (white arrows), thickened
                                                                                                                 Animal Health and Nutrition
  with chronic heartworm disease. Note the                 pulmonary arteries (yellow arrow), and
  weight loss (apparent by the noticeable                  interstitial inflammation. (Photo by Dr. Luigi        The Hartz Mountain Corporation
  spine and rib cage) and dilated abdomen                  Venco)
  (due to ascites). (Photo by Dr. Luigi Venco)
                                                                                                                Associate Editors
                                                          disease. Bacteria were observed in the                Jill A. Richardson, DVM
  may, however, be the key to novel                       lungs and particularly in organs where                 Director
  strategies for the control/treatment of                 microfilariae normally circulate, such as the          Consumer Relations
  filarial infection, including canine and                kidney and liver. Furthermore, when we                 The Hartz Mountain Corporation
  feline heartworm disease.                               looked at specific antibody responses to              David Levy
                                                          Wolbachia, we observed a stronger response             Assistant Manager
  ROLE OF WOLBACHIA IN                                    in dogs with circulating microfilariae                 Animal Health and Nutrition
  THE INFLAMMATORY AND                                    compared with dogs with occult infection,              The Hartz Mountain Corporation
  IMMUNE RESPONSE IN D.                                   supporting the hypothesis that microfilarial
                                                                                                                HARTZ® COMPANION ANIMAL                                      SM

  IMMITIS–INFECTED ANIMALS                                turnover is an important source of
                                                          Wolbachia in dogs with heartworm disease.             is produced for The Hartz Mountain
      As gram-negative bacteria, Wolbachia
                                                                                                                Corporation by Veterinary Learning
  have the potential to play an important role            Furthermore, Wolbachia from D. immitis
                                                                                                                Systems, 780 Township Line Rd.,
  in the pathogenesis and immune response                 have been shown to provoke chemokinesis               Yardley, PA 19067.
  to filarial infection. The possible                     and proinflammatory cytokine production
  consequences of the massive release of                  in canine neutrophils. Cats with                      Copyright © 2006 The Hartz Mountain
  Wolbachia in the filaria-infected host have             heartworm disease also produce antibodies             Corporation. All rights reserved.
  been evaluated. Wolbachia are released both             to Wolbachia. Interestingly, it has recently          Hartz® and other marks are owned by
  by living worms and after worm death                    been reported that the development of a               The Hartz Mountain Corporation.
  through natural attrition, microfilarial                strong antibody response against D. immitis
                                                          occurs after 1 to 2 months of infection,              Printed in U.S.A. No part of this
  turnover, and pharmacologic intervention.3
                                                                                                                publication may be reproduced in any
  In human and murine models of infection,                which has important implications for early
                                                                                                                form without the express written
  the release of bacteria has been shown to               diagnosis.5                                           permission of the publisher.
  be associated with the up-regulation of                     Areas of future research should include
  proinflammatory cytokines, neutrophil                   the possible diagnostic use of specific               For more information on The Hartz
  recruitment, and an increase in specific                immune responses to Wolbachia, its                    Mountain Corporation, visit
                                                          potential immunomodulatory activity                   www.hartz.com.
  immunoglobulins. Ongoing studies in dogs
  with heartworm disease may shed light on                (prevention), and the effects of antibiotic
  what happens when infected animals come                 treatment in infected animals.                    synthetic derivatives appear to be the
  into contact with the bacteria. For example,                                                              most effective) are able to drastically
  my colleagues and I recently tested the                 EFFECT OF ANTIBIOTIC                              reduce if not completely remove the
  hypothesis that D. immitis–infected dogs                TREATMENT ON FILARIAL                             endosymbiont from the worm host. Such
  come into contact with Wolbachia either                 WORMS                                             depletion of Wolbachia is then followed by
  through microfilarial turnover or natural                   Wolbachia can be eliminated from              clear antifilarial effects, including:
  death of adult worms.4 In our study,                    filarial worms through antibiotic therapy
  positive staining for Wolbachia was                     of the infected host. Numerous studies            s   Inhibition of larval development:
  observed in various tissues from dogs that              have shown that various treatment                     It has been shown that antibiotic
  had died because of natural heartworm                   protocols and dosages (tetracycline and               treatment of filaria-infected hosts can

2 HARTZ COMPANION ANIMAL
        ®                   SM
                                 • SEPTEMBER 2006 • VOL. 4, NO. 3
ADDITIONAL CONSIDERATIONS FOR ADULTICIDE
                                                   THERAPY—WOLBACHIA
                                                         Most filarial nematodes, including D. immitis, harbor obligate, intracellular, gram-
                                                   negative bacteria belonging to the genus Wolbachia (Rickettsiales). In infections with other
                                                   filarial parasites, treatment with tetracyclines during the first month of infection was lethal
                                                   to some Wolbachia-harboring filariae but not to a filariae that did not harbor Wolbachia,
                                                   and treatment of Wolbachia-harboring filariae suppressed microfilaremia. Similar
                                                   prophylaxis studies with D. immitis have not been reported, but in one study, tetracycline
                                                   treatment of heartworm-infected dogs resulted in infertility in the female worms. These
                                                   bacteria also have been implicated in the pathogenesis of filarial diseases, possibly through
Figure 3. Cross–section of an adult
female Dirofilaria immitis stained with a          their endotoxins. Recent studies have shown that a major surface protein of Wolbachia
polyclonal antibody against the Wolbachia          (WSP) induces a specific IgG response in hosts infected by D. immitis. It is hypothesized
surface protein. Note the numerous                 that Wolbachia contribute to pulmonary and renal inflammation through the surface
bacteria (arrows) that almost entirely fill        protein WSP independent of its endotoxin component. Studies to determine the effects
the cell of the lateral hypodermal cord.
                                                   of suppressing Wolbachia populations with doxycyline prior to adulticide therapy will be
(Original magnification x40)
                                                   required to determine the clinical utility of this therapeutic approach.
    inhibit molting, an essential process          From: Guidelines for the Diagnosis, Prevention and Management of Heartworm ( Dirofilaria immi-
                                                   tis) Infection in Dogs; reprinted with permission of the American Heartworm Society. Available
    in the maturation of worms from                at www.heartwormsociety.org; accessed August 2006.
    larvae to adult.
s   Female worm sterility: Antibiotic
    treatment leads first to a reduction              ultrasonography in 21 of 27 patients.            worm. There are little data concerning the
    and then to the complete and                      In the other patients, the number of             effects of antibiotic treatment in dogs with
    sustained absence of microfilariae.               scrotal worm nests declined. This was            natural heartworm disease; what is known,
    Researchers at the University of                  significantly different from placebo             however, is that such treatment drastically
    Milan, Italy, have reported that D.               patients in which lack of worm nests             reduces Wolbachia loads in D. immitis.
    immitis adults taken from naturally               was only observed in three of 27                 Preliminary trials8 in naturally infected
    infected dogs that had been treated               patients. This is the first report of            dogs have shown that doxycycline treatment
    with doxycycline at 20 mg/kg/day                  antibiotic-induced adulticide activity           before adulticide therapy with melarsomine
    for 30 days showed morphologic                    in a human filarial worm. Could                  may help reduce proinflammatory reactions
    alterations of uterine content with a             antibiotic treatment have the same               due to the death of adult worms (as seen
    dramatic decrease in the number of                effect on D. immitis? Several research           by lower antibody levels against Wolbachia
    mature microfilariae, indicating that             groups, including our laboratory, are            and lower levels of interleukin-8, an
    bacteriostatic antibiotic treatment               curently attempting to answer this very          inflammatory cytokine involved in
    was able to block embryogenesis.6                 important question.                              neutrophil recruitment). These results have
s   Adulticide effects: This is a particularly                                                         encouraged our laboratory to continue to
    intriguing aspect of antibiotic treatment     EFFECTS OF ANTIBIOTIC                                evaluate the clinical benefits of antibiotic
    of the filarial worm–infected host and        TREATMENT ON THE FILARIAL                            treatment in naturally infected dogs.
    one that merits strict attention. Clinical    WORM–INFECTED HOST                                       Given the recent and very promising
    trials in human filariasis have reported          It is very likely that antibiotic treatment      developments in the use of tetracyclines
    extremely promising results: A recent         will have some beneficial effects on subjects        for micro- and macrofilaricidal therapy in
    placebo-controlled trial in humans            with filariasis. First, the effects on the           human filariasis, it is hoped that similar
    infected with Wuchereria bancrofti has        worm (described above) will themselves               attention will be given to canine and
    demonstrated a clear macrofilaricidal         lead to improved clinical presentation,              feline heartworm disease, which could
    (i.e., adulticidal) effect of doxycycline.7   such as a reduction in the circulating               greatly benefit from alternative
    When administered for 8 weeks at 200          microfilariae that have been implicated in           therapeutic strategies.
    mg/day, doxycycline treatment resulted        immune complex formation during
    in complete amicrofilaremia in 28 of 32       infections.4 However, if Wolbachia is
                                                                                                       REFERENCES
                                                                                                        1. Bandi C, Trees AJ, Brattig NW: Wolbachia in filarial
    patients assessed and a lack of worm          considered a potential cause of                          nematodes: Evolutionary aspects and implications for
    nests in the scrotum (where adult             inflammation in the course of filarial                   the pathogenesis and treatment of filarial diseases. Vet
                                                                                                           Parasitol 98:215–238, 2001.
    worms reside) at 14 months after              disease, depletion of the bacteria may be             2. Foster J, Ganatra M, Kamal I, et al: The Wolbachia
    treatment, as determined by                   beneficial independent of its effect on the              genome of Brugia malayi: Endosymbiont evolution
                                                                                                                                         (continues on page 8)

                                                                                          HARTZ® COMPANION ANIMALSM • SEPTEMBER 2006 • VOL. 4, NO. 3                  3
Deworming Demystified:
                                                    Update on Deworming Protocols
                                                   Byron L. Blagburn, MS, PhD
                                                   Distinguished University Professor
                                                   Department of Pathobiology
                                                   College of Veterinary Medicine
                                                   Auburn University




      Parasites are important causes of                  that can eliminate many parasites, often      Discretionary Deworming
  disease in dogs and cats of all ages (Table            including both internal and external             Discretionary deworming is based on a
  1) but can be particularly important in                parasites) (Table 2). The language becomes    perceived need to deworm, such as results
  puppies and kittens because of their small             even more confusing when one considers        of fecal examination or other diagnostic
  size, developing immunity, and other                   that some single-entity products have         tests (e.g., elevated eosinophil count,
  stresses associated with growth and                    broad-spectrum activity (e.g., pyrantel       radiographic evidence of pulmonary
  maturation. Young pets are often exposed               pamoate, milbemycin oxime) and that           parasitism). As the name implies,
  to and acquire parasites differently than              combining products may or may not             discretionary deworming is performed at
  older pets. Because of their increased                 increase the spectrum of internal parasites   the discretion of the veterinarian. In my
  exposure and susceptibility, they often                eliminated (e.g., ivermectin–pyrantel         view, discretionary deworming should be
  harbor greater numbers of parasites than               pamoate versus milbemycin oxime–              performed only based on knowledge
  mature animals. Heavier parasite burdens               lufenuron).                                   gained from history or presenting signs,
  place puppies and kittens at greater risk of                                                         appropriate diagnostic procedures, or
  disease and also lead to higher shedding               Strategic Deworming                           other information sufficient to warrant
  rates of fecal stages into the environment.                Strategic deworming is the application    the use of parasiticides.
  Increased environmental contamination                  of a specific parasite-control strategy
  also increases the risk of human exposure              based on an individual pet’s age,             Targeted Deworming
  to zoonotic roundworms and hookworms.                  environment, and likelihood of exposure           Targeted deworming, in my opinion,
  This article reviews strategies for                    to parasites, prevalence of the parasite in   is just another term for strategic
  deworming dogs and cats. Available                     question, and geographic region. An           deworming. The intent is to “target”
  parasiticides now allow important                      example of strategic deworming would be       particular time points based on criteria
  parasites to be eliminated safely and                  deworming puppies at 2, 4, 6, and 8           mentioned above for strategic deworming
  pets to be maintained free of parasites                weeks of age to control migrating stages      (i.e., age, environment, history of prior
  throughout their lives.                                of roundworms and hookworms                   parasitism or exposure to parasites, and
                                                         (discussed below). Additional examples        geographic region).
  SOME DEWORMING                                         include strategically placed intervals
  DEFINITIONS                                            between dewormings throughout the year,       Interval Deworming
      Several terms have been used to define             such as every 6 months or every 3 months          Interval deworming is deworming
  the various approaches to internal parasite            for pets with a seasonal likelihood of        pets at specific intervals. The approach
  control and the available parasiticides.               exposure to parasites or if control of a      is similar to strategic or targeted
  Deworming terms include “strategic,”                   specific parasite, such as whipworm, is       deworming, but with less attention given
  “discretionary,” “targeted,” and “interval,”           needed. Strategic deworming may also          to specific reasons for selecting time
  and parasite control products are identified           include a strategy of monthly, year-round,    points. Interval deworming is usually
  as single entity (one active ingredient),              broad-spectrum internal parasite control      intended to provide a “safety net,” based
  combination (more than one active                      to improve compliance and take                on the presumption that pets are likely
  ingredient), narrow spectrum (products that            advantage of heartworm preventives            to be exposed to parasites but without
  are capable of removing one or two                     or flea-control products with activity        specific knowledge of when that exposure
  parasites), and broad spectrum (products               against important internal parasites.         is likely to occur.

4 HARTZ COMPANION ANIMAL
        ®                  SM
                                • SEPTEMBER 2006 • VOL. 4, NO. 3
TABLE 1: Common Nematode Parasites of Dogs and Cats
                                Prevalence/          Site of
 Parasite                       Geographic        Development                                           Developmental    Diagnostic Procedure/   Zoonotic
 (Common Name)      Host(s)      Location        (Adult Worms)                Life Cycle                   Period           Stage in Feces       Potential
 Toxocara canis     Dogs           High/             Small       Infection by embryonated eggs          28–35 days       Fecal flotation/non-     Very
 (canine                        throughout         intestine     and transplacental transmission;                        embryonated eggs         high
 roundworm)                       the US                         larvae undergo liver–lung                                are 90 × 75 µm,
                                                                 migration; rodents may serve as                          subglobular, with
                                                                 transport hosts; transmammary                            thick pitted shells
                                                                 transmission is uncommon

 Toxocara cati      Cats           High/             Small       Direct infection by embyronated        38–56 days       Fecal flotation/non-     Very
 (feline                        throughout         intestine     eggs and transmammary                                   embryonated eggs         high
 roundworm)                       the US                         transmission; rodents may serve                           are 65–75 µm;
                                                                 as transport hosts; larvae may                           similar to T. canis
                                                                 undergo liver–lung migration;                            eggs but smaller
                                                                 transplacental transmission
                                                                 apparently does not occur

 Toxascaris         Dogs            Low/             Small       Direct infection by embryonated          74 days        Fecal flotation/non-     None
 leonina            and         throughout         intestine     eggs; rodents may serve as                              embryonated eggs
 (nonmigratory      cats          the US;                        transport hosts; development is                          are 80 × 70 µm,
 roundworm)                     distribution                     restricted to small intestine; no                       slightly oval with a
                                   spotty                        extraintestinal, transplacental, or                         smooth shell
                                                                 transmammary transmission

 Ancylostoma        Dogs          High/              Small       Direct infection by ingestion or       15–18 days       Fecal flotation/non-     High
 caninum (canine               throughout          intestine     skin penetration; may undergo                           embryonated eggs
 hookworm)                    the US; more                       lung migration; ingested larvae                          are 70 × 40 µm
                               common in                         may mature without lung
                                 warmer                          migration; rodents may serve as
                                 climates                        transport hosts; the principal route
                                                                 of infection is transmammary

 Ancylostoma        Cats          High/          Middle small    Direct infection by ingestion or       16–25 days       Fecal flotation/non-      Low
 tubaeforme                    throughout         intestine      skin penetration; larvae may                            embryonated eggs
 (feline                      the US; more                       undergo lung migration; rodents                          are 61 × 40 µm
 hookworm)                     common in                         may serve as transport hosts; no
                                 warmer                          transmammary or transplacental
                                 climates                        transmission

 Ancylostoma        Dogs      High in tropical     Anterior      Direct infection by ingestion or       14–27 days       Fecal flotation/non-     High
 braziliense        and       and subtropical        small       skin penetration; larvae may                             embryonated eggs
 (subtropical       cats      regions/limited      intestine     undergo lung migration; rodents                        are 55 × 34 µm; not
 hookworm)                     to Florida and                    may serve as transport hosts; no                        easily differentiated
                                 Golf Coast                      information on transmammary                             from A. tubaeforme
                                                                 or transplacental transmission

 Trichuris vulpis   Dogs           High/           Cecum         Direct infection by ingestion of       77–84 days       Fecal flotation/non-       Not
 (whipworm)                     throughout                       embryonated eggs                                        embryonated eggs        thought
                                  the US                                                                                are brownish, bipolar,     to be
                                                                                                                          and 80 × 30 µm         zoonotic



SPECIFIC                                             and by ingestion of paratenic (transport)               puppies and kittens requires a strategy to
RECOMMENDATIONS                                      hosts (Table 1). Both roundworms and                    eliminate parasites as they mature. Both
Puppies and Kittens                                  hookworms may undergo multisystem                       the Companion Animal Parasite Council
   Parasite control in puppies and kittens           migrations in puppies and kittens.                      (CAPC; www.capcvet.org) and the Centers
presents several unique challenges; some             Continual infection via multiple routes                 for Disease Control and Prevention (CDC;
are the result of parasite behavior, whereas         and multisystemic migration lead to the                 www.cdc.gov) recommend deworming
others are the result of host factors and            presence of parasites in different stages in            puppies beginning at 2 weeks of age and
parasiticidal efficacy. Roundworms and               different organ systems during their                    continuing every 2 weeks through 8 weeks
hookworms, the most common parasites                 migrations. Because current parasiticides               of age; thereafter, puppies can be placed
of young pets, are acquired through                  are most effective in eliminating the adult             on monthly broad-spectrum agents that
several routes: embryonated eggs, milk or            stages of roundworms and hookworms in                   include heartworm and/or flea control and
colostrum, via the uterus and placenta,              the intestine, control of these parasites in            also possess activity against roundworms

                                                                                                HARTZ® COMPANION ANIMALSM • SEPTEMBER 2006 • VOL. 4, NO. 3   5
TABLE 2: Selected Broad-Spectrum Canine and Feline Internal Parasiticides
                                                                            Host Species:
    Chemical Name          Product Name                                     Parasites Removed                          Dosage/Regimen                           Minimum Age
    Pyrantel                      ®
                           Hartz Advanced Care™ Rid Worm™                   Dog: TC, TL, AC, US                        5 mg/kg                                  No minimum age
    pamoate                Chewable Flavored Wormer Tablets;                                                           Discretionary treatment
                           Nemex™, Nemex™-2 (Pfizer Animal
                           Health); many others

    Pyrantel               Drontal® (Bayer Animal Health)                   Cat: Tca, AT, DC, TT                       5 mg/kg praziquantel and                 4 wk and >1.5 lb
    pamoate–                                                                                                           20 mg/kg pyrantel pamoate
    praziquantel                                                                                                       Discretionary treatment

    Fenbendazole           Panacur® C Canine Dewormer                       Dog: TC, TL, AC, US, TV                    50 mg/kg/day for 3 days                  6 wk
                           (Intervet)                                                                                  Discretionary treatment

    Febantel–              Drontal® Plus (Bayer Animal Health)              Dog: TC, TL, AC, US, TV,                   10 mg/kg febantel, 5 mg/kg               3 wk and >2 lb
    pyrantel                                                                DC, TP, EG, EM                             pyrantel pamoate, and 5
    pamoate–                                                                                                           mg/kg praziquantel
    praziquantel                                                                                                       Discretionary treatment

    Ivermectin             Heartgard® Chewables for Cats                    Cat: DI (L3/L4), AT, AB                    24 µg/kg q30d                            6 wk

    Ivermectin–            Heartgard® Plus Chewables for Dogs;              Dog: DI (L3/L4), TC, TL, AC,               6 µg/kg ivermectin and                   6 wk
    pyrantel               Iverhart™ Plus Flavored Chewables                AB, US                                     5 mg/kg pyrantel pamoate
    pamoate                (Virbac); Triheart® Plus Chewable                                                           q30d
                           Tablets (Schering-Plough Animal Health)

    Milbemycin             Interceptor® Flavor Tabs® for Dogs               Cat: DI (L3/L4), Tca, AT                   Cat: 2.0 mg/kg q30d                      Cat: 6 wk or >1.5 lb
    oxime                  and Cats (Novartis)                              Dog: DI (L3/L4), TC, TL, AC, TV            Dog: 0.5 mg/kg q30d                      Dog: 4 wk or >2 lb

    Milbemycin             Sentinel® Flavor Tabs® (Novartis)                Dog: DI (L3/L4), TC, TL, AC,               0.5 mg/kg milbemycin oxime               4 wk or >2 lb
    oxime–lufenuron                                                         TV, eggs of CF                             and 10 mg/kg lufenuron q30d

    Selamectin             Revolution® (Pfizer Animal Health)               Cat: DI (L3/L4), Tca, AT                   6 mg/kg q30d                             Cat: >8 wk
                                                                            Dog: DI (L3/L4), CF, SS, OC, DV                                                     Dog: >6 wk

    AB = Ancylostoma braziliense; AC = Ancylostoma caninum; AT = Ancylostoma tubaeforme; CF = Ctenocephalides felis; DC = Dipylidium caninum; DI = Dirofilaria immitis; DV =
    Dermacentor variabilis; EG = Echinococcus granulosus; EM = Echinococcus multilocularis; L3 = third-stage larvae; L4 = fourth-stage larvae; OC = Otodectes cynotis; SS = Sarcoptes sca-
    biei; TC = Toxocara canis; Tca = Toxocara cati; TL = Toxascaris leonina; TP = Taenia pisiformis; TT = Taenia taeniaeformis; TV = Trichuris vulpis; US = Uncinaria stenocephala.



  and hookworms (Table 2). This monthly                            described for puppies. If pets are not                           Adult Dogs and Cats
  strategy serves two purposes—it helps                            maintained on monthly broad-spectrum                                Surveys indicate that dogs and
  improve pet owner compliance and                                 agents, annual or semiannual fecal                               cats remain susceptible to parasites
  provides continuous roundworm and                                examinations using centrifugal flotation                         throughout their lives, although the risk
  hookworm control. It should be noted                             should be performed. Appropriate                                 of disease diminishes somewhat as pets
  that only pyrantel pamoate can be used                           treatments should then be administered                           age. Adult dogs and cats are also less
  in puppies as young as 2 weeks; other                            based on results of fecal examinations                           likely to harbor burdens of intestinal
  available agents can be used in puppies                          (discretionary deworming).                                       roundworms and hookworms that are
  and kittens starting at 3 to 4 weeks of age.                        It is important to remember that pets                         as large as is seen in puppies or kittens.
     If monthly broad-spectrum control                             are susceptible to and may harbor parasites                      A number of strategies have been
  strategies are not used, an alternative                          that are not eliminated by broad-spectrum                        employed to control parasitic infections
  strategy of biweekly deworming from 2                            heartworm preventives. Examples include                          in adult pets. Among them are continual
  to 8 weeks of age followed by monthly                            tapeworms, coccidia, and Giardia. These                          monthly administration of broad-
  deworming through 6 months of age can                            and other parasites drive the need for                           spectrum heartworm preventives; annual,
  be employed. Because of the differences                          accurate fecal examinations conducted at                         semiannual, or quarterly use of broad-
  in the life cycles of canine and feline                          regular intervals. The frequency of                              spectrum dewormers; and discretionary
  roundworms, kittens can be treated                               fecal examinations (e.g., one to four                            deworming based on results of fecal
  biweekly between 3 and 9 weeks and                               times/year) varies based on the age of                           examinations. The strategy of
  then placed on broad-spectrum agents                             the pet, prior infection status, and                             continuous monthly use of broad-
  or treated monthly for 6 months as                               potential exposure.                                              spectrum heartworm products is often

6 HARTZ COMPANION ANIMAL
         ®                         SM
                                        • SEPTEMBER 2006 • VOL. 4, NO. 3
HARTZ
                                                                                                                ®


IMPORTA                      N T NEWS FROM                                                                                              e nation, introdu
                                                                                                                                                          ced
                                                                                                                     k products in th
                   ian:                                                           ing provider   s of flea and tic            t is registe red by the US
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                                          n Corporation, ®                                                                          be available in
    is spring, The     Hartz Mountai               d Hartz U       ltraGuardplus              er 12 weeks of
                                                                                                                 age, and it will
Th                                         t calle                               kittens ov
                      secticide produc                       use on cats and
a new topical in                         ncy (EPA) for                                                                                                    d
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                                  14 for answers to
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                              , DVM                       Services
              Jill Richardson               and Technical
                             umer Relations
              Director, Cons                                                                                  33231
                                                                                            l.jsp?Rec_Id=PC
                                                                          /Detail_Chemica                                                                   et_igr.htm
                                                         esticideinfo.org              ents/press.asp?
                                                                                                       prm_id=568                          ctsheets/factshe
                                          . http://www.p                     /news_ev                                     s/ingredients/fa
               1 PAN Pesticides Database                   w.sergeants.com                               pd1/biopesticide
                                          Available at ww                              w.epa.gov/oppbp
               2 Sergeant’s news release.                 fact sheet. Availa
                                                                             ble at ww
                                         tection Agency
               3 U.S. Environmental Pro
WOLBACHIA AND HEARTWORM DISEASE (continued from page 3)
    within a human pathogenic nematode. PLoS Biology           Immunol Immunopathol 106(3–4):303–308, 2005.             endosymbionts Wolbachia. Int J Parasitol 29:
    3:e121–129, 2005.                                       5. Morchon R, Ferreira AC, Martin-Pacho J, et al:           357–364, 1999.
 3. Taylor MJ, Cross HF, Ford L: Wolbachia bacteria            Specific IgG antibody response against antigens of    7. Taylor MJ, Makunde WH, McGarry HF, et al:
    in filarial immunity and disease. Parasite Immunol         Dirofilaria immitis and its Wolbachia endosymbiont       Macrofilaricidal activity after doxycycline treatment
    23:401–409, 2001.                                          bacterium in cats with natural and experimental          of Wuchereria bancrofti: A double-blind, randomised
 4. Kramer LH, Tamarozzi F, Morchon R, et al:                  infections. Vet Parasitol 125:313–321, 2004.             placebo-controlled trial. Lancet 365:2116–2121,
    Immune response to and tissue localization of the       6. Bandi C, McCall JW, Genchi C, et al: Effects of          2005.
    Wolbachia surface protein (WSP) in dogs with natural       tetracycline on the filarial worms Brugia pahangi     8. Kramer L: Treating canine heartworm infection.
    heartworm (Dirofilaria immitis) infection. Vet             and Dirofilaria immitis and their bacterial              NAVC Clin Brief May:17–18, 2006.



DEWORMING DEMYSTIFIED (continued from page 6)
implemented in regions where                               of ascarids and hookworms from breeding                  parasiticides can then be administered
heartworm prevention is necessary for all                  bitches. These strategies require intense                as necessary. Annual fecal examinations
or most of the year. Veterinarians must                    use of available parasiticides during the                and discretionary use of parasiticides are
still conduct fecal examinations to assure                 gestation period and should be used only                 especially important in senior pets that
that selected parasiticides are effectively                after consulting with qualified experts.                 are not receiving monthly broad-spectrum
controlling parasites. It is sometimes                                                                              agents.
necessary to supplement monthly broad-                     Senior Pets
spectrum heartworm preventives with                            Modern parasiticides are safe and                    SUGGESTED READING
other control strategies using additional                  effective for use in older pets, including               Blagburn BL: Prevalence of canine parasites based on
                                                                                                                        fecal flotation. Compend Contin Educ Vet 18:483–509,
parasiticides based on results of fecal                    those with other illnesses. In regions                       1996.
examinations.                                              where heartworms remain prevalent                        Blagburn BL, Butler J: Optimize intestinal parasite
    Pregnant bitches and queens are also                   throughout most of the year, continuous                      detection with centrifugal fecal flotation. Vet Med
                                                                                                                        July:455–464, 2006.
more susceptible to certain parasites                      use of broad-spectrum agents remains
                                                                                                                    Fisher M: Toxocara cati: An underestimated zoonotic
during the periparturient period. These                    a popular strategy. Periodic fecal                           agent. Trends Parasitol 19:167–170, 2003.
pets should either remain on broad-                        examinations are necessary in senior pets                Kalkofen UP: Hookworms of dogs and cats. Vet Clin
spectrum preventives throughout                            not only because they remain susceptible                     North Am Small Anim Pract 7(6):1341–1354, 1987.
pregnancy and lactation or they should be                  to parasites but also because other health               Marty AM: Toxocariasis, in Meyers WM, Neafie RC,
                                                                                                                       Marty AM, Wear DJ (eds): Pathology of Infectious
dewormed at the same time their offspring                  conditions may make them more                               Diseases. Washington, DC, American Registry of
are dewormed during the postparturient                     vulnerable to the effects of parasites.                     Pathology, 2000, pp 411–421.
period. Veterinarians can consult with                     Senior pets should be examined at least                  Nolan TJ, Smith G: Time series analysis of the
                                                                                                                       prevalence of endoparasitic infections in cats and
academic parasitologists regarding                         annually using a sensitive centrifugal fecal                dogs presented to a veterinary teaching hospital. Vet
strategies for eliminating tissue reservoirs               flotation procedure. Appropriate                            Parasitol 59:87–96, 1995.




Veterinary Learning Systems                                                                                                                               PRST STD
780 Township Line Road                                                                                                                                  U.S. POSTAGE
Yardley, PA 19067
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Hartz Companion Animal - Wolbachia and Heartworm Disease

  • 1. A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS SEPTEMBER 2006 VOLUME 4, NUMBER 3 Wolbachia and Heartworm Disease Laura H. Kramer, DVM, PhD, DEVPC College of Veterinary Medicine University of Parma, Parma, Italy Dirofilaria immitis is the causative agent developing embryonic stages within the Wolbachia increases its own fitness by of canine and feline heartworm disease. uteri. This suggests that the bacterium is increasing the fitness of the host Adult worms live in the pulmonary vertically transmitted through the involved in its transmission. arteries, and females produce first-stage cytoplasm of the egg.1 s Removal of Wolbachia (via antibiotics larvae (microfilariae), which are taken up or radiation) leads to sterility of female by mosquitoes that then transmit the ROLE OF WOLBACHIA IN worms and eventual death of adults. infection to other animals. In dogs, an ITS FILARIAL HOST untreated infection leads to congestive Human research has revealed several It is still unclear, however, exactly what heart failure (Figures 1 and 2). D. immitis, reasons why the presence of Wolbachia is Wolbachia does to make it so important like most filarial worms studied to date, thought to be essential for a filarial for its filarial host. It has been suggested harbor bacteria called Wolbachia, which are worm’s survival: that, while the filarial worm likely supplies thought to play an essential role in the s the bacteria with amino acids necessary In those species of filarial worms that biology and reproductive functions of their for growth and replication, Wolbachia may have been identified as harboring filarial hosts. Wolbachia pipientis, the only produce several important molecules that Wolbachia, all of the individuals are species thus far identified in the genus, are essential for heartworms, such as infected (i.e., 100% prevalence). are gram-negative bacteria belonging to glutathione and heme.2 It is indeed a “one s The evolution of the bacteria matches the order Rickettsiales (just like Ehrlichia hand washing the other” situation that spp and Anaplasma spp).1 In adult D. that of the filarial worms, and immitis, Wolbachia is predominantly found phylogenic studies have shown that throughout cells in the hypodermis, which the two organisms have been “walking is directly under the worm’s cuticle (Figure hand-in-hand” for millions of years. ALSO IN THIS ISSUE: 3). In female D. immitis, Wolbachia is also s The bacteria are transmitted from Deworming Demystified............ 4 present in the ovaries, oocytes, and female to offspring and, in this way,
  • 2. A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS SEPTEMBER 2006 VOLUME 4, NUMBER 3 Consulting Editors Albert Ahn, DVM Vice President of Corporate Communications and Consumer Relations The Hartz Mountain Corporation Figure 2. Radiograph of the dog Bruce Truman in Figure 1. Note the enlarged cardiac Senior Director Figure 1. A 6-year-old Great Dane chambers (white arrows), thickened Animal Health and Nutrition with chronic heartworm disease. Note the pulmonary arteries (yellow arrow), and weight loss (apparent by the noticeable interstitial inflammation. (Photo by Dr. Luigi The Hartz Mountain Corporation spine and rib cage) and dilated abdomen Venco) (due to ascites). (Photo by Dr. Luigi Venco) Associate Editors disease. Bacteria were observed in the Jill A. Richardson, DVM may, however, be the key to novel lungs and particularly in organs where Director strategies for the control/treatment of microfilariae normally circulate, such as the Consumer Relations filarial infection, including canine and kidney and liver. Furthermore, when we The Hartz Mountain Corporation feline heartworm disease. looked at specific antibody responses to David Levy Wolbachia, we observed a stronger response Assistant Manager ROLE OF WOLBACHIA IN in dogs with circulating microfilariae Animal Health and Nutrition THE INFLAMMATORY AND compared with dogs with occult infection, The Hartz Mountain Corporation IMMUNE RESPONSE IN D. supporting the hypothesis that microfilarial HARTZ® COMPANION ANIMAL SM IMMITIS–INFECTED ANIMALS turnover is an important source of Wolbachia in dogs with heartworm disease. is produced for The Hartz Mountain As gram-negative bacteria, Wolbachia Corporation by Veterinary Learning have the potential to play an important role Furthermore, Wolbachia from D. immitis Systems, 780 Township Line Rd., in the pathogenesis and immune response have been shown to provoke chemokinesis Yardley, PA 19067. to filarial infection. The possible and proinflammatory cytokine production consequences of the massive release of in canine neutrophils. Cats with Copyright © 2006 The Hartz Mountain Wolbachia in the filaria-infected host have heartworm disease also produce antibodies Corporation. All rights reserved. been evaluated. Wolbachia are released both to Wolbachia. Interestingly, it has recently Hartz® and other marks are owned by by living worms and after worm death been reported that the development of a The Hartz Mountain Corporation. through natural attrition, microfilarial strong antibody response against D. immitis occurs after 1 to 2 months of infection, Printed in U.S.A. No part of this turnover, and pharmacologic intervention.3 publication may be reproduced in any In human and murine models of infection, which has important implications for early form without the express written the release of bacteria has been shown to diagnosis.5 permission of the publisher. be associated with the up-regulation of Areas of future research should include proinflammatory cytokines, neutrophil the possible diagnostic use of specific For more information on The Hartz recruitment, and an increase in specific immune responses to Wolbachia, its Mountain Corporation, visit potential immunomodulatory activity www.hartz.com. immunoglobulins. Ongoing studies in dogs with heartworm disease may shed light on (prevention), and the effects of antibiotic what happens when infected animals come treatment in infected animals. synthetic derivatives appear to be the into contact with the bacteria. For example, most effective) are able to drastically my colleagues and I recently tested the EFFECT OF ANTIBIOTIC reduce if not completely remove the hypothesis that D. immitis–infected dogs TREATMENT ON FILARIAL endosymbiont from the worm host. Such come into contact with Wolbachia either WORMS depletion of Wolbachia is then followed by through microfilarial turnover or natural Wolbachia can be eliminated from clear antifilarial effects, including: death of adult worms.4 In our study, filarial worms through antibiotic therapy positive staining for Wolbachia was of the infected host. Numerous studies s Inhibition of larval development: observed in various tissues from dogs that have shown that various treatment It has been shown that antibiotic had died because of natural heartworm protocols and dosages (tetracycline and treatment of filaria-infected hosts can 2 HARTZ COMPANION ANIMAL ® SM • SEPTEMBER 2006 • VOL. 4, NO. 3
  • 3. ADDITIONAL CONSIDERATIONS FOR ADULTICIDE THERAPY—WOLBACHIA Most filarial nematodes, including D. immitis, harbor obligate, intracellular, gram- negative bacteria belonging to the genus Wolbachia (Rickettsiales). In infections with other filarial parasites, treatment with tetracyclines during the first month of infection was lethal to some Wolbachia-harboring filariae but not to a filariae that did not harbor Wolbachia, and treatment of Wolbachia-harboring filariae suppressed microfilaremia. Similar prophylaxis studies with D. immitis have not been reported, but in one study, tetracycline treatment of heartworm-infected dogs resulted in infertility in the female worms. These bacteria also have been implicated in the pathogenesis of filarial diseases, possibly through Figure 3. Cross–section of an adult female Dirofilaria immitis stained with a their endotoxins. Recent studies have shown that a major surface protein of Wolbachia polyclonal antibody against the Wolbachia (WSP) induces a specific IgG response in hosts infected by D. immitis. It is hypothesized surface protein. Note the numerous that Wolbachia contribute to pulmonary and renal inflammation through the surface bacteria (arrows) that almost entirely fill protein WSP independent of its endotoxin component. Studies to determine the effects the cell of the lateral hypodermal cord. of suppressing Wolbachia populations with doxycyline prior to adulticide therapy will be (Original magnification x40) required to determine the clinical utility of this therapeutic approach. inhibit molting, an essential process From: Guidelines for the Diagnosis, Prevention and Management of Heartworm ( Dirofilaria immi- tis) Infection in Dogs; reprinted with permission of the American Heartworm Society. Available in the maturation of worms from at www.heartwormsociety.org; accessed August 2006. larvae to adult. s Female worm sterility: Antibiotic treatment leads first to a reduction ultrasonography in 21 of 27 patients. worm. There are little data concerning the and then to the complete and In the other patients, the number of effects of antibiotic treatment in dogs with sustained absence of microfilariae. scrotal worm nests declined. This was natural heartworm disease; what is known, Researchers at the University of significantly different from placebo however, is that such treatment drastically Milan, Italy, have reported that D. patients in which lack of worm nests reduces Wolbachia loads in D. immitis. immitis adults taken from naturally was only observed in three of 27 Preliminary trials8 in naturally infected infected dogs that had been treated patients. This is the first report of dogs have shown that doxycycline treatment with doxycycline at 20 mg/kg/day antibiotic-induced adulticide activity before adulticide therapy with melarsomine for 30 days showed morphologic in a human filarial worm. Could may help reduce proinflammatory reactions alterations of uterine content with a antibiotic treatment have the same due to the death of adult worms (as seen dramatic decrease in the number of effect on D. immitis? Several research by lower antibody levels against Wolbachia mature microfilariae, indicating that groups, including our laboratory, are and lower levels of interleukin-8, an bacteriostatic antibiotic treatment curently attempting to answer this very inflammatory cytokine involved in was able to block embryogenesis.6 important question. neutrophil recruitment). These results have s Adulticide effects: This is a particularly encouraged our laboratory to continue to intriguing aspect of antibiotic treatment EFFECTS OF ANTIBIOTIC evaluate the clinical benefits of antibiotic of the filarial worm–infected host and TREATMENT ON THE FILARIAL treatment in naturally infected dogs. one that merits strict attention. Clinical WORM–INFECTED HOST Given the recent and very promising trials in human filariasis have reported It is very likely that antibiotic treatment developments in the use of tetracyclines extremely promising results: A recent will have some beneficial effects on subjects for micro- and macrofilaricidal therapy in placebo-controlled trial in humans with filariasis. First, the effects on the human filariasis, it is hoped that similar infected with Wuchereria bancrofti has worm (described above) will themselves attention will be given to canine and demonstrated a clear macrofilaricidal lead to improved clinical presentation, feline heartworm disease, which could (i.e., adulticidal) effect of doxycycline.7 such as a reduction in the circulating greatly benefit from alternative When administered for 8 weeks at 200 microfilariae that have been implicated in therapeutic strategies. mg/day, doxycycline treatment resulted immune complex formation during in complete amicrofilaremia in 28 of 32 infections.4 However, if Wolbachia is REFERENCES 1. Bandi C, Trees AJ, Brattig NW: Wolbachia in filarial patients assessed and a lack of worm considered a potential cause of nematodes: Evolutionary aspects and implications for nests in the scrotum (where adult inflammation in the course of filarial the pathogenesis and treatment of filarial diseases. Vet Parasitol 98:215–238, 2001. worms reside) at 14 months after disease, depletion of the bacteria may be 2. Foster J, Ganatra M, Kamal I, et al: The Wolbachia treatment, as determined by beneficial independent of its effect on the genome of Brugia malayi: Endosymbiont evolution (continues on page 8) HARTZ® COMPANION ANIMALSM • SEPTEMBER 2006 • VOL. 4, NO. 3 3
  • 4. Deworming Demystified: Update on Deworming Protocols Byron L. Blagburn, MS, PhD Distinguished University Professor Department of Pathobiology College of Veterinary Medicine Auburn University Parasites are important causes of that can eliminate many parasites, often Discretionary Deworming disease in dogs and cats of all ages (Table including both internal and external Discretionary deworming is based on a 1) but can be particularly important in parasites) (Table 2). The language becomes perceived need to deworm, such as results puppies and kittens because of their small even more confusing when one considers of fecal examination or other diagnostic size, developing immunity, and other that some single-entity products have tests (e.g., elevated eosinophil count, stresses associated with growth and broad-spectrum activity (e.g., pyrantel radiographic evidence of pulmonary maturation. Young pets are often exposed pamoate, milbemycin oxime) and that parasitism). As the name implies, to and acquire parasites differently than combining products may or may not discretionary deworming is performed at older pets. Because of their increased increase the spectrum of internal parasites the discretion of the veterinarian. In my exposure and susceptibility, they often eliminated (e.g., ivermectin–pyrantel view, discretionary deworming should be harbor greater numbers of parasites than pamoate versus milbemycin oxime– performed only based on knowledge mature animals. Heavier parasite burdens lufenuron). gained from history or presenting signs, place puppies and kittens at greater risk of appropriate diagnostic procedures, or disease and also lead to higher shedding Strategic Deworming other information sufficient to warrant rates of fecal stages into the environment. Strategic deworming is the application the use of parasiticides. Increased environmental contamination of a specific parasite-control strategy also increases the risk of human exposure based on an individual pet’s age, Targeted Deworming to zoonotic roundworms and hookworms. environment, and likelihood of exposure Targeted deworming, in my opinion, This article reviews strategies for to parasites, prevalence of the parasite in is just another term for strategic deworming dogs and cats. Available question, and geographic region. An deworming. The intent is to “target” parasiticides now allow important example of strategic deworming would be particular time points based on criteria parasites to be eliminated safely and deworming puppies at 2, 4, 6, and 8 mentioned above for strategic deworming pets to be maintained free of parasites weeks of age to control migrating stages (i.e., age, environment, history of prior throughout their lives. of roundworms and hookworms parasitism or exposure to parasites, and (discussed below). Additional examples geographic region). SOME DEWORMING include strategically placed intervals DEFINITIONS between dewormings throughout the year, Interval Deworming Several terms have been used to define such as every 6 months or every 3 months Interval deworming is deworming the various approaches to internal parasite for pets with a seasonal likelihood of pets at specific intervals. The approach control and the available parasiticides. exposure to parasites or if control of a is similar to strategic or targeted Deworming terms include “strategic,” specific parasite, such as whipworm, is deworming, but with less attention given “discretionary,” “targeted,” and “interval,” needed. Strategic deworming may also to specific reasons for selecting time and parasite control products are identified include a strategy of monthly, year-round, points. Interval deworming is usually as single entity (one active ingredient), broad-spectrum internal parasite control intended to provide a “safety net,” based combination (more than one active to improve compliance and take on the presumption that pets are likely ingredient), narrow spectrum (products that advantage of heartworm preventives to be exposed to parasites but without are capable of removing one or two or flea-control products with activity specific knowledge of when that exposure parasites), and broad spectrum (products against important internal parasites. is likely to occur. 4 HARTZ COMPANION ANIMAL ® SM • SEPTEMBER 2006 • VOL. 4, NO. 3
  • 5. TABLE 1: Common Nematode Parasites of Dogs and Cats Prevalence/ Site of Parasite Geographic Development Developmental Diagnostic Procedure/ Zoonotic (Common Name) Host(s) Location (Adult Worms) Life Cycle Period Stage in Feces Potential Toxocara canis Dogs High/ Small Infection by embryonated eggs 28–35 days Fecal flotation/non- Very (canine throughout intestine and transplacental transmission; embryonated eggs high roundworm) the US larvae undergo liver–lung are 90 × 75 µm, migration; rodents may serve as subglobular, with transport hosts; transmammary thick pitted shells transmission is uncommon Toxocara cati Cats High/ Small Direct infection by embyronated 38–56 days Fecal flotation/non- Very (feline throughout intestine eggs and transmammary embryonated eggs high roundworm) the US transmission; rodents may serve are 65–75 µm; as transport hosts; larvae may similar to T. canis undergo liver–lung migration; eggs but smaller transplacental transmission apparently does not occur Toxascaris Dogs Low/ Small Direct infection by embryonated 74 days Fecal flotation/non- None leonina and throughout intestine eggs; rodents may serve as embryonated eggs (nonmigratory cats the US; transport hosts; development is are 80 × 70 µm, roundworm) distribution restricted to small intestine; no slightly oval with a spotty extraintestinal, transplacental, or smooth shell transmammary transmission Ancylostoma Dogs High/ Small Direct infection by ingestion or 15–18 days Fecal flotation/non- High caninum (canine throughout intestine skin penetration; may undergo embryonated eggs hookworm) the US; more lung migration; ingested larvae are 70 × 40 µm common in may mature without lung warmer migration; rodents may serve as climates transport hosts; the principal route of infection is transmammary Ancylostoma Cats High/ Middle small Direct infection by ingestion or 16–25 days Fecal flotation/non- Low tubaeforme throughout intestine skin penetration; larvae may embryonated eggs (feline the US; more undergo lung migration; rodents are 61 × 40 µm hookworm) common in may serve as transport hosts; no warmer transmammary or transplacental climates transmission Ancylostoma Dogs High in tropical Anterior Direct infection by ingestion or 14–27 days Fecal flotation/non- High braziliense and and subtropical small skin penetration; larvae may embryonated eggs (subtropical cats regions/limited intestine undergo lung migration; rodents are 55 × 34 µm; not hookworm) to Florida and may serve as transport hosts; no easily differentiated Golf Coast information on transmammary from A. tubaeforme or transplacental transmission Trichuris vulpis Dogs High/ Cecum Direct infection by ingestion of 77–84 days Fecal flotation/non- Not (whipworm) throughout embryonated eggs embryonated eggs thought the US are brownish, bipolar, to be and 80 × 30 µm zoonotic SPECIFIC and by ingestion of paratenic (transport) puppies and kittens requires a strategy to RECOMMENDATIONS hosts (Table 1). Both roundworms and eliminate parasites as they mature. Both Puppies and Kittens hookworms may undergo multisystem the Companion Animal Parasite Council Parasite control in puppies and kittens migrations in puppies and kittens. (CAPC; www.capcvet.org) and the Centers presents several unique challenges; some Continual infection via multiple routes for Disease Control and Prevention (CDC; are the result of parasite behavior, whereas and multisystemic migration lead to the www.cdc.gov) recommend deworming others are the result of host factors and presence of parasites in different stages in puppies beginning at 2 weeks of age and parasiticidal efficacy. Roundworms and different organ systems during their continuing every 2 weeks through 8 weeks hookworms, the most common parasites migrations. Because current parasiticides of age; thereafter, puppies can be placed of young pets, are acquired through are most effective in eliminating the adult on monthly broad-spectrum agents that several routes: embryonated eggs, milk or stages of roundworms and hookworms in include heartworm and/or flea control and colostrum, via the uterus and placenta, the intestine, control of these parasites in also possess activity against roundworms HARTZ® COMPANION ANIMALSM • SEPTEMBER 2006 • VOL. 4, NO. 3 5
  • 6. TABLE 2: Selected Broad-Spectrum Canine and Feline Internal Parasiticides Host Species: Chemical Name Product Name Parasites Removed Dosage/Regimen Minimum Age Pyrantel ® Hartz Advanced Care™ Rid Worm™ Dog: TC, TL, AC, US 5 mg/kg No minimum age pamoate Chewable Flavored Wormer Tablets; Discretionary treatment Nemex™, Nemex™-2 (Pfizer Animal Health); many others Pyrantel Drontal® (Bayer Animal Health) Cat: Tca, AT, DC, TT 5 mg/kg praziquantel and 4 wk and >1.5 lb pamoate– 20 mg/kg pyrantel pamoate praziquantel Discretionary treatment Fenbendazole Panacur® C Canine Dewormer Dog: TC, TL, AC, US, TV 50 mg/kg/day for 3 days 6 wk (Intervet) Discretionary treatment Febantel– Drontal® Plus (Bayer Animal Health) Dog: TC, TL, AC, US, TV, 10 mg/kg febantel, 5 mg/kg 3 wk and >2 lb pyrantel DC, TP, EG, EM pyrantel pamoate, and 5 pamoate– mg/kg praziquantel praziquantel Discretionary treatment Ivermectin Heartgard® Chewables for Cats Cat: DI (L3/L4), AT, AB 24 µg/kg q30d 6 wk Ivermectin– Heartgard® Plus Chewables for Dogs; Dog: DI (L3/L4), TC, TL, AC, 6 µg/kg ivermectin and 6 wk pyrantel Iverhart™ Plus Flavored Chewables AB, US 5 mg/kg pyrantel pamoate pamoate (Virbac); Triheart® Plus Chewable q30d Tablets (Schering-Plough Animal Health) Milbemycin Interceptor® Flavor Tabs® for Dogs Cat: DI (L3/L4), Tca, AT Cat: 2.0 mg/kg q30d Cat: 6 wk or >1.5 lb oxime and Cats (Novartis) Dog: DI (L3/L4), TC, TL, AC, TV Dog: 0.5 mg/kg q30d Dog: 4 wk or >2 lb Milbemycin Sentinel® Flavor Tabs® (Novartis) Dog: DI (L3/L4), TC, TL, AC, 0.5 mg/kg milbemycin oxime 4 wk or >2 lb oxime–lufenuron TV, eggs of CF and 10 mg/kg lufenuron q30d Selamectin Revolution® (Pfizer Animal Health) Cat: DI (L3/L4), Tca, AT 6 mg/kg q30d Cat: >8 wk Dog: DI (L3/L4), CF, SS, OC, DV Dog: >6 wk AB = Ancylostoma braziliense; AC = Ancylostoma caninum; AT = Ancylostoma tubaeforme; CF = Ctenocephalides felis; DC = Dipylidium caninum; DI = Dirofilaria immitis; DV = Dermacentor variabilis; EG = Echinococcus granulosus; EM = Echinococcus multilocularis; L3 = third-stage larvae; L4 = fourth-stage larvae; OC = Otodectes cynotis; SS = Sarcoptes sca- biei; TC = Toxocara canis; Tca = Toxocara cati; TL = Toxascaris leonina; TP = Taenia pisiformis; TT = Taenia taeniaeformis; TV = Trichuris vulpis; US = Uncinaria stenocephala. and hookworms (Table 2). This monthly described for puppies. If pets are not Adult Dogs and Cats strategy serves two purposes—it helps maintained on monthly broad-spectrum Surveys indicate that dogs and improve pet owner compliance and agents, annual or semiannual fecal cats remain susceptible to parasites provides continuous roundworm and examinations using centrifugal flotation throughout their lives, although the risk hookworm control. It should be noted should be performed. Appropriate of disease diminishes somewhat as pets that only pyrantel pamoate can be used treatments should then be administered age. Adult dogs and cats are also less in puppies as young as 2 weeks; other based on results of fecal examinations likely to harbor burdens of intestinal available agents can be used in puppies (discretionary deworming). roundworms and hookworms that are and kittens starting at 3 to 4 weeks of age. It is important to remember that pets as large as is seen in puppies or kittens. If monthly broad-spectrum control are susceptible to and may harbor parasites A number of strategies have been strategies are not used, an alternative that are not eliminated by broad-spectrum employed to control parasitic infections strategy of biweekly deworming from 2 heartworm preventives. Examples include in adult pets. Among them are continual to 8 weeks of age followed by monthly tapeworms, coccidia, and Giardia. These monthly administration of broad- deworming through 6 months of age can and other parasites drive the need for spectrum heartworm preventives; annual, be employed. Because of the differences accurate fecal examinations conducted at semiannual, or quarterly use of broad- in the life cycles of canine and feline regular intervals. The frequency of spectrum dewormers; and discretionary roundworms, kittens can be treated fecal examinations (e.g., one to four deworming based on results of fecal biweekly between 3 and 9 weeks and times/year) varies based on the age of examinations. The strategy of then placed on broad-spectrum agents the pet, prior infection status, and continuous monthly use of broad- or treated monthly for 6 months as potential exposure. spectrum heartworm products is often 6 HARTZ COMPANION ANIMAL ® SM • SEPTEMBER 2006 • VOL. 4, NO. 3
  • 7. HARTZ ® IMPORTA N T NEWS FROM e nation, introdu ced k products in th ian: ing provider s of flea and tic t is registe red by the US Dear Veterinar one of the lead ™ Drops for Cats. The produc retail n Corporation, ® be available in is spring, The Hartz Mountai d Hartz U ltraGuardplus er 12 weeks of age, and it will Th t calle kittens ov secticide produc use on cats and a new topical in ncy (EPA) for d l Protection Age harmful fleas an Environmenta d. protected from in the weeks ahea make sure that all pets are ent the ca re provided by stores nationally community – to ort and supplem tz® the veterinary ts that can supp their pets. Har ur goal is the same as that of effective, wel l-tested produc no flea and tic k protection on the number of O mmitted to offe ring icans use lp expand ticks. We are co illions of Amer ners and may he ely show that m ative for pet ow veterinarians . Surveys routin ec onomical altern Cats offers an us™ Drops for m ectoparasites . UltraGuardpl are protected fro companion animals that enprox, adulticide, Etof s s a well-tested l tive ingredient ula that combine -a-month topica Well-tested ac ats contains an all-new form consumers an ef fective, once ps for C t offers uardplus™ Dro ene. This produc Hartz® UltraG R), (S)-Methopr er ticks, and mosquitoes. e insecticide ow th regulator (IG as, flea eggs, de 1 insect pests . Th e feline and an insect gr ickly to kill fle food crops from treatment that works qu to protect ntly availabl ound the world in another, curre by governments ar d is an ac tive ingredient er Hartz ® feline topicals been registered pets in 2004 an one used in form Etofenprox has ation for use on icide from the first EPA registr different insect received its is a completely e use. t2. Etofenprox story of effectiv topical produc ch has a long hi other insects . 3 rin). ethoprene, whi flies, ants, and (phenoth r Cats is (S)-M , mosquitoes, plus™ Drops fo fight infestatio ns of fleas e same series tz® UltraGuard than 20 years to n underwent th The IGR in Har used for more Cats formulatio y flea (S)-Methopren e has been aGuardplus ™ Drops for uding veterinar the Hartz Ultr ® on animals, incl west acute toxi city products used the EPA’s lo A registration, required for all insecticidal rmined to be in In orde r to receive EP xicity tests n was dete ty, and acute to , the formulatio of efficacy, safe ute toxicity tests ve felines. An ts. Through the ac events in sensiti and tick produc 40 CFR 156.62 ). oduce adverse ese category (Categ ory IV - oduct can pr owners about th y insecticide pr to educate pet sages in study results, an otection is an ongoing effort important mes ith excellent flea and tick pr blicizes these u know, even w tely. Hartz pu ® As yo mitment to appropria ent of our com d tick products important elem of using flea an efforts. ians to report d the importance ebsites and other outreach e urge veterinar health issues an ochures, our w ld they occur, w a week advertising, co nsumer br pets, shou day, seven days adverse event in nsumer Relations 24 hours a e th e chance of any t Hartz ® Co eks to minimiz ners can contac While Hartz se ® ians and pet ow pport. any incident to us. Veterinar their questio ns and other su 14 for answers to at 1-800-275-14 Sincerely, , DVM Services Jill Richardson and Technical umer Relations Director, Cons 33231 l.jsp?Rec_Id=PC /Detail_Chemica et_igr.htm esticideinfo.org ents/press.asp? prm_id=568 ctsheets/factshe . http://www.p /news_ev s/ingredients/fa 1 PAN Pesticides Database w.sergeants.com pd1/biopesticide Available at ww w.epa.gov/oppbp 2 Sergeant’s news release. fact sheet. Availa ble at ww tection Agency 3 U.S. Environmental Pro
  • 8. WOLBACHIA AND HEARTWORM DISEASE (continued from page 3) within a human pathogenic nematode. PLoS Biology Immunol Immunopathol 106(3–4):303–308, 2005. endosymbionts Wolbachia. Int J Parasitol 29: 3:e121–129, 2005. 5. Morchon R, Ferreira AC, Martin-Pacho J, et al: 357–364, 1999. 3. Taylor MJ, Cross HF, Ford L: Wolbachia bacteria Specific IgG antibody response against antigens of 7. Taylor MJ, Makunde WH, McGarry HF, et al: in filarial immunity and disease. Parasite Immunol Dirofilaria immitis and its Wolbachia endosymbiont Macrofilaricidal activity after doxycycline treatment 23:401–409, 2001. bacterium in cats with natural and experimental of Wuchereria bancrofti: A double-blind, randomised 4. Kramer LH, Tamarozzi F, Morchon R, et al: infections. Vet Parasitol 125:313–321, 2004. placebo-controlled trial. Lancet 365:2116–2121, Immune response to and tissue localization of the 6. Bandi C, McCall JW, Genchi C, et al: Effects of 2005. Wolbachia surface protein (WSP) in dogs with natural tetracycline on the filarial worms Brugia pahangi 8. Kramer L: Treating canine heartworm infection. heartworm (Dirofilaria immitis) infection. Vet and Dirofilaria immitis and their bacterial NAVC Clin Brief May:17–18, 2006. DEWORMING DEMYSTIFIED (continued from page 6) implemented in regions where of ascarids and hookworms from breeding parasiticides can then be administered heartworm prevention is necessary for all bitches. These strategies require intense as necessary. Annual fecal examinations or most of the year. Veterinarians must use of available parasiticides during the and discretionary use of parasiticides are still conduct fecal examinations to assure gestation period and should be used only especially important in senior pets that that selected parasiticides are effectively after consulting with qualified experts. are not receiving monthly broad-spectrum controlling parasites. It is sometimes agents. necessary to supplement monthly broad- Senior Pets spectrum heartworm preventives with Modern parasiticides are safe and SUGGESTED READING other control strategies using additional effective for use in older pets, including Blagburn BL: Prevalence of canine parasites based on fecal flotation. Compend Contin Educ Vet 18:483–509, parasiticides based on results of fecal those with other illnesses. In regions 1996. examinations. where heartworms remain prevalent Blagburn BL, Butler J: Optimize intestinal parasite Pregnant bitches and queens are also throughout most of the year, continuous detection with centrifugal fecal flotation. Vet Med July:455–464, 2006. more susceptible to certain parasites use of broad-spectrum agents remains Fisher M: Toxocara cati: An underestimated zoonotic during the periparturient period. These a popular strategy. Periodic fecal agent. Trends Parasitol 19:167–170, 2003. pets should either remain on broad- examinations are necessary in senior pets Kalkofen UP: Hookworms of dogs and cats. Vet Clin spectrum preventives throughout not only because they remain susceptible North Am Small Anim Pract 7(6):1341–1354, 1987. pregnancy and lactation or they should be to parasites but also because other health Marty AM: Toxocariasis, in Meyers WM, Neafie RC, Marty AM, Wear DJ (eds): Pathology of Infectious dewormed at the same time their offspring conditions may make them more Diseases. Washington, DC, American Registry of are dewormed during the postparturient vulnerable to the effects of parasites. Pathology, 2000, pp 411–421. period. Veterinarians can consult with Senior pets should be examined at least Nolan TJ, Smith G: Time series analysis of the prevalence of endoparasitic infections in cats and academic parasitologists regarding annually using a sensitive centrifugal fecal dogs presented to a veterinary teaching hospital. Vet strategies for eliminating tissue reservoirs flotation procedure. Appropriate Parasitol 59:87–96, 1995. Veterinary Learning Systems PRST STD 780 Township Line Road U.S. POSTAGE Yardley, PA 19067 PAID YORK, PA PERMIT #200 402344