December 2008

Infectious Diseases

Stephen C. Barr BVSc MVS PhD DACVIM
Cornell University


Leptospirosis: Serology and Vaccine Concerns

INTRODUCTION
  • A systemic bacterial infection of dogs (and very rarely, cats) causing mainly acute nephritis and hepatitis, vasculitis, and chronic carrier states.

    CAUSE/PATHOGENESIS
  • Pathogenic members of the genus Leptospira - main serovars causing disease in dogs include L. pomona, L. grippotyphosa (about the same incidence although perhaps more cases of L. pomona in Northeast, more L. grippotyphosa in mid-west), occasionally L. autumnalis and L. bratislava, and rarely, L. canicola, L. hardjo, and L. icterohaemorrhagiae - these results mainly based on serologic data.
  • In fact, if you try to infect young beagle puppies with L. bratislava, none become infected raising the issue as to whether this serovar is pathogenic or merely a serologic phenomenon.
  • Direct transmission - host-to-host contact via infected urine, postabortion discharge, infected fetus/discharge, and sexual contact (semen).
  • Indirect transmission - exposure (via urine) to a contaminated environment (vegetation, soil, food, water, and bedding) under conditions in which Leptospira can survive.
  • Wildlife reservoirs in Northeast - about a third of raccoons (mainly L. icterohaemorrhagiae), 15% of skunks (virtually all L. grippotyphosa) show exposure to serovars that infect dogs.
  • Leptospira - penetrate intact or cut skin or mucous membranes; rapidly invade bloodstream (4-7 days); spread to all parts of the body (2-4 days).
  • Invasion leads to transient fever, leukocytosis, transitory anemia (hemolysis), mild hemoglobinuria, and albuminuria; capillary and endothelial cell damage (occasionally results in petechial hemorrhages); liver necrosis and jaundice; acute nephritis with leptospiruria (organism replicates readily in tubular epithelial cell).
  • Vasculitis - may cause interstitial pneumonia, anterior uveitis, myocardial damage and meningitis (rare), abortions.
  • Death - usually a result of interstitial nephritis, vascular damage, and renal failure; may result from acute septicemia or DIC.
  • Usually one or more serovars account for endemic disease in a geographic area - overall reported incidence probably falsely low as most infections are inapparent (undiagnosed).
  • Worldwide distribution - especially in warm, wet climates or seasons.
  • Standing water and neutral or slightly alkaline soil - promote presence in environment.
  • Most cases occur during late summer/fall in Northeastern USA.

    SIGNALMENT
  • Dogs in rural habitat, more males affected, 4 to 7 yr-olds more at risk than dogs < 1 yr.
  • Dogs in that walk or swim in a rural area, or drinking outdoor water are 8 and 12 times, respectively, more likely to get infected.
  • Young dogs - without passive maternal antibody-more likely to exhibit severe disease.
  • Old dogs - with adequate antibody titer levels-seldom exhibit clinical disease unless exposed to a serovar not in the vaccine.
  • Dense animal population (kennels and urban settings) - increases chances of urine exposure, exposure to rodents, and other wildlife (hunting dogs).

    CLINICAL SIGNS
  • Lethargy, depression, anorexia and vomiting are the most common clinical signs.
  • Peracute/Acute - fever, sore muscles, stiffness, weakness, anorexia, depression, acute onset of vomiting, rapid dehydration, diarrhea (occasional bloody), occasionally iceterus, cough with mild respiratory distress if respiratory component severe, Pu/Pd progressing to anuria.
  • Chronic - usually no apparent illness, Pu/Pd if chronic renal failure, hepatic signs.

    DIFFERENTIAL DIAGNOSIS
  • Subacute/acute disease - any severe systemic disease involving mainly the liver or kidneys alone, or together:- heartworm disease; immune mediated hemolytic anemia; bacteremia/septicemia (bite wound, prostatitis, endocarditis, dental disease); infectious canine hepatitis virus; canine herpesvirus; hepatic neoplasia; trauma; lupus; Rocky Mountain spotted fever; ehrlichiosis; toxoplasmosis; acute nephritis, renal neoplasia; renal calculi.
  • Reproductive failure - brucellosis; distemper; herpes.

    DIAGNOSIS
  • CBC - signs of dehydration (PCV and total plasma solids elevated); anemia, and thrombocytopenia are the main findings. Leukocytosis with left shift also.
  • Serum biochemistry profile - Elevated BUN, creatine, phosphate, liver enzymes are main changes.
  • Other changes due to dehydration, renal failure (electrolyte changes include hyponatremia, hypochloremia, hyperkalemia, hyperphosphatemia, hypoalbuminemia).
  • Although Dogs infected with L. pomona are more likely to suffer from vomiting, thrombocytopenia, severe azotemia, and hyperphosphatemia (i.e, the most severe cause of renal disease), and are less likely to survive infection, there are few differences in clinical signs and lab data from dogs infected with different serovars.
  • Urinalysis - proteinuria, isosthenuria usually, casts.
  • In chronic carrier states - may only see isosthenuria with few granular casts in urine.
  • Serology - MAT; test in acute stage and 3-4 weeks later (convalescent serum); in unvaccinated patients, titers may be low initially (1:100-1:200), then rise during convalescents (1:800 - 1:1600 or higher); several serovars usually show elevated titer but make serovars diagnosis based on highest titer.
  • MAT titers in vaccinated dogs - vaccination causes elevation of MAT titer in most cases but usually only to serovars vaccinated against (no cross reactivity); do get MAT titer elevations to L. autumnalis after vaccination with subunit vaccines against L. grippotyphosa and L. pomona (Fort Dodge).
  • Dogs vaccinated with whole cell bacteria - usually develop higher MAT titers (up to 1:800) than subunit vaccines (negative to 1:400).
  • MAT titers induced by vaccination - usually only last up to 4 months.
  • MAT titers induced by infection - usually last over 12 months.
  • Darkfield Microscopy of Urine - often inconclusive as difficult to read and requires fresh urine.
  • Fluorescent Antibody Test of Urine - more conclusive as leptospires do not need to be viable; submit urine to laboratory on ice by overnight courier; pretreatment with furosemide (2 mg/kg, SC) 15 min before urine collection will increase success rate.
  • PCR on urine - offered by some commercial laboratories; shown in 1 dog out of 8 to detect organisms in urine before development of serologic titer; needs more work in experimentally infected dogs before being well validated.
  • Culture - usually unrewarding.
  • Tissue diagnosis (kidney biopsy) - FA, immunohistochemistry, Warthin-Starry silver stain, PCR, all effective.

    TREATMENT/PREVENTION
  • Inpatient for acute severe disease - extent of supportive therapy depends on severity; renal failure requires closely monitored diuresis, attention to DIC development; care must be taken not to over-hydrate as vasculitis of respiratory endothelium can lead to pulmonary edema during diuresis.
  • Vaccines - bacterin and subunit vaccines available against L. canicola and L. icterohaemorrhagiae, and subunit vaccine available against L. pomona, L. grippotyphosa; most claim year efficacy except those subunit vaccines covering L. pomona and L. grippotyphosa (protect for 2 to 2½ weeks post-booster); no cross-protection outside of the serovars used in vaccine serogroup); revaccination at least yearly; Data suggests to vaccinate at-risk groups (middle aged dogs actively visiting /muddy areas, ponds, low-lying areas with stagnant surface water, heavily irrigated pastures, and access to wildlife) every 4-6 months, or at least yearly just before at-risk period of infection (late summer - fall); reports on earlier bacterin vaccines suggested there was no protection against carrier state but some studies do show that urine shedding is prevented in dogs infected 2 - 3 weeks post vaccination with most vaccines, and up to a year in certain vaccines (not available in the US); vaccination is associated with a high incidence of anaphylaxis (particularly bacterin vaccines) after booster doses occurring within 1 hour of booster.
  • There is still considerable controversy about the efficacy of some vaccines with little data. Some vaccines show efficacy out to a year post-booster; others are ineffective after 7 weeks post-booster (shed organisms in urine when challenged). Kennels - strict sanitation to avoid contact with infected urine; control rodents; monitor and remove carrier dogs until treated; isolate affected animals during treatment; disinfection of premises, use iodine-based disinfectant or stabilized bleach solutions.

    DRUGS USED IN TREATMENT
  • Doxycycline - use alone to clear leptospiremia and leptospiruria, as well as carrier state. [Dose: 5 mg/kg, PO or IV, q12h, for 2 weeks. IV doxycycline may induce vomiting].
  • If doxycycline to be used, unnecessary to use penicillin.
  • Penicillin compounds - may be used during acute leptospiremic phase if unable to administer doxycycline.
  • Streptomycin - will clear organisms from kidneys but difficult to obtain and may potentiate renal insufficiency.

    PUBLIC HEALTH CONCERNS
  • Inform client of zoonotic potential from contaminated urine of affected dogs and their environment; after doxycycline, risk of shedding is greatly reduced.

    REFERENCES
    1. Ghneim GS, Viers JH, Chomel BB, et al. Use of a case-control study and geographic information systems to determine environmental demographic risk factors for canine leptospirosis. Vet Res 38:37-50, 2007.
    2. Greenlee JJ, Alt DP, Bolin CA, et al. Experimental canine leptospirosis caused by Leptospira interrogans serovars pomona and bratislava. Am J Vet Res 66:1816-1822, 2005.
    3. Andre-Fontaine G, Branger C, Gray AW, et al. Comparison of the efficacy of three commercial bacterins in preventing canine leptospirosis. Vet Rec 153:165-169, 2003.
    4. Greene GE, Sykes JE, Brown CA, et al. Leptospirosis. In: Greene GE (ed) Infectious diseases of the dog and cat. 3rd ed. Philadelphia, Saunders. 402-417, 2006.

    Lyme Disease: Treatment, Vaccination, and Control Controversies

    INTRODUCTION
  • In the USA, caused by spirochete Borrelia burgdorferi - it is the most common tick-transmitted zoonotic diseases in North America.
  • Although 95% of exposed dogs remain asymptomatic, the main clinical features in dogs include recurrent lameness due to arthritis (sometimes accompanied fever, anorexia and depression).
  • Rarely, renal failure (due to immune mediated glomerulonephritis) can occur.
  • Cardiac, neurologic, and dermatologic disease has also been attributed to Lyme disease but not shown in experimental models.
  • Horses, cattle, and cats can be infected - clinical disease in cats has not been reported.

    EPIZOOTIOLOGY
  • Transmission - by Ixodes ticks: I. scapularis in the Northeast and Midwest; I. pacificus in the West.
  • In particularly the coastal regions of Northeastern states (CT, NY, RI), the infection rate of I. scapularis ticks with Borrelia can be 50-90%.
  • Tick larvae and nymphs feed on small mammals (mice); adult ticks feed on deer and larger mammals.
  • Infected nymphs and adult ticks attach to dogs and pass on Borrelia while feeding.
  • Because the bacteria lives in the mid-gut of the tick, and must migrate to the salivary glands of the tick for transfer to the skin of a host , transmission does not occur at least for the first 24 hours after attachment - some suggest this is as long as 36-48 hours.
  • The presence of small, flat, non-engorged Ixodes ticks on a dog suggests a very low risk of infection.

    INCIDENCE/PREVALENCE/GEOGRAPHIC DISTRIBUTION
  • Seroprevalence in dogs varies greatly with exposure to infected ticks in endemic areas.
  • 70-90% of dogs in highly endemic areas may be sero-positive but less than 5% of these dogs will show clinical signs of Lyme disease (lameness) over nearly a 2 year period.
  • Distribution - Northeast (Maine to Maryland - >90% of cases occur here), the upper Midwest (Wisconsin, Minnesota) and the far west (mainly northern California).

    SIGNALMENT/BREEDS/AGE
  • Dogs, occasionally horses and cattle, show signs; cats are exposed but signs not reported.
  • Any dog breed exposed may become infected but Shetland Sheepdogs, Labrador and Golden Retrievers have been more likely than other breeds to develop Lyme nephritis.
  • Adult dogs experimentally infected with B. burgdorferi did not develop clinical signs; 6-26 week-old-puppies were more likely to develop disease experimentally. Any age dog may be infected after natural exposure. No gender differences have been reported.

    PATHOPHYSIOLOGY
  • Arthritis - although not completely clear, the immune (both cellular and humoral) response to the migrating spirochetes is involved.
  • After a tick bite, the organism migrates over weeks and months to produce a generalized infection mainly of connective tissue in joints, tendons, muscles, and lymph nodes.
  • Immune-complexes to Borrelia-specific antigens may be deposited in the kidneys but living organisms are not found in the kidneys.
  • Incubation period in experimentally infected does: 2-5 months.

    SIGNS
  • Important to remember that 95% of exposed dogs remain asymptomatic.
  • Acute form - transient fever (103 - 105F), anorexia, depression, and acute lameness lasting for only 3-4 days; reoccurs days to weeks later in the same or in other limbs (shifting lameness); one or more joints may be swollen and warm; a pain response is elicited on joint manipulation; responds well to antibiotic treatment.
  • Chronic non-erosive polyarthritis found in animals with prolonged infection without adequate treatment; may persist despite antimicrobial therapy.
  • Superficial lymph nodes close to the infecting tick bite may be enlarged.
  • Kidneys - reported glomerulonephritis with immune-complex deposition in the glomeruli leading to fatal renal disease; patients may present with renal failure (vomiting, diarrhea, anorexia, weight loss, polyuria/polydipsia, peripheral edema or ascites); unknown why some dogs develop nephropathy while others do not.
  • Cardiac and neurologic complication - rare clinical reports.

    DIFFERENTIAL DIAGNOSIS/COINFECTIONS
  • Fever, lameness, or proteinuria can have many other causes - infectious (bacterial, tick-borne such as ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, leishmaniasis, and fungal; histoplasmosis, blastomycosis), immune-mediated (idiopathic, lupus, rheumatoid), degenerative, trauma, neoplasia, breed specific (Akita arthritis, Shar Pei fever).
  • Ixodes ticks can also be infected with Anaplasma phagocytophilum, Babesia microti, Bartonella spp., and tick borne encephalitis virus (about 40% of dogs sero-positive for Lyme disease are also sero-positive for A. phagocytophilum).
  • Dogs infected with both Borrelia and A. phagocytophilum have slightly less than twice the frequency of lameness than dogs infected with Borrelia alone (53% compared to 29%).

    DIAGNOSIS
  • Although no individual test result proves that a dogs clinical signs are due to Borrelia infection, a presumptive diagnosis can be made based on: 1) evidence of exposure, 2) consistent clinical signs with infection, 3) ruling out other differentials, 4) response to appropriate treatment.
  • Evidence of exposure - presence of an engorged Ixodes tick, dog lives or visited an endemic area, or positive test result.
  • Routine CBC and serum biochemistry are usually unremarkable unless protein-losing glomerulopathy is present (uremia, proteinuria, hypercholesterolemia, hyperphosphatemia, and hypoalbuminemia).
  • Culture of the organism (from the skin site of tick attachment, collagen-rich connective tissues such as muscle fascia and synovium, blood or plasma, CSF, and synovial fluid) requires special media and long incubation times (2-4 weeks); limited by low sensitivity (especially after antibiotic therapy), expense, delayed results, and invasive nature of tissue sampling.
  • PCR on similar samples as above - sensitivity depends on the samples (varies from 10 to 80% in human studies); techniques have not been standardized among laboratories: not a widely accepted as a diagnostic tool as not reliable, practical, cost effective, or sensitive.
  • ELISA and Western blotting - positive serology indicates previous exposure to B. burgdorferi antigens; may indicate disease; regular ELISA cannot be used to differentiate between vaccination and infection, but Western blotting allows differentiation; cross-reaction with antibodies induced by other bacterial infections (e.g. Leptospira spp., Anaplasma spp.) is minimal.
  • Point-of-care tests - SNAP 3Dx or 4Dx, (IDEXX Laboratories, Westbrook, ME) - membrane ELISA test detects a subgroup of antibodies against the outer surface protein VlsE using the C6 peptide; convenient test that only detects infection and does not respond to Lyme vaccine-induced antibodies; in dogs, a positive antibody response occurs 3-5 weeks after infection and normally drops or may even disappear about 2-6 months after antibiotic therapy.
  • A quantitative version of the IDEXX SNAP test exists - Lyme Quant C6 Test (IDEXX Laboratories, Westbrook, ME) - correlates well with Western blotting; test remains positive for at least 69 weeks.
  • C6 antibody titers also correlate with Lyme-specific circulating immune complexes, and the level of these immune complexes correlates with the severity of clinical illness of dogs.
  • Because serology becomes positive well before the development of disease in infected dogs, paired titers are redundant; also, titer magnitude is not associated with the presence or absence of clinical signs, thus serology is not an accurate indicator of disease status or response to treatment.

    TREATMENT
  • The most commonly used antibiotic in dogs to treat Lyme disease is doxycycline (10 mg/kg, PO, q24h for at least 4 weeks); also addresses most co-infections.
  • Others - amoxicillin (20 mg/kg, PO, q8h), azithromycin (25 mg/kg, PO, q12h), ceftriaxone (25 mg/kg, IV, q24h) for 4 weeks; amoxicillin is indicated in young puppies to avoid teeth staining from doxycycline.
  • NOTE: all these therapeutic regimes have failed to clear organisms from the tissues of some dogs.
  • The clinical signs of acute arthritis and fever should improve within 1-2 days of starting therapy; titers can remain for months or years although C6 titers may disappear.
  • C6 antibody titers and Lyme-specific circulating immune complexes are both decreased 5 months after Lyme-infected dogs (both clinically affected and asymptomatic) are treated for 1 month with doxycycline - implications of this are still unknown.
  • Lyme positive but asymptomatic dog - is some studies, neither sero-positivity nor the titer magnitude were correlated with whether the dog would show clinical signs during a 20 month period. Thus, currently, there seems little data to support the treatment of asymptomatic dogs with antibiotics.

    MONITORING
  • Dogs with Lyme disease should be monitored for proteinuria (complete urinalysis, in-house E.R.D.-HealthScreen Urine Test [Heska Corp, Fribourg, Switzerland], urine protein:creatinine ratio).
  • ACVIM consensus statement - monitoring C6 antibody concentrations can not be routinely recommended at this time as there is not enough field data correlating titers with the subsequent development of disease.

    PREVENTION

    Vaccination
  • ACVIM consensus statement - Dogs in non-endemic areas should not need vaccination. The majority of ACVIM diplomats do NOT recommend vaccination in endemic areas also. Such decisions should be made between each owner and vet based on individual case basis.
  • 4 vaccines are currently available in the US
  • Monovalent bacterin - Lymevax, Fort Dodge Animal Health, Fort Dodge, IA.
  • Bivalent bacterin - Galaxy Lyme, Schering-Plough Animal Health, Union, NJ.
  • Non-adjuvanted rOsp A vaccine - Recombitek, Merial, Duluth, GA.
  • Adjuvanted rOsp A vaccine - ProLyme, Intervet, Millsborough, DE.
  • Bacterin and rOsp A vaccines all work by generating anti-Osp A antibodies in the dog which when ingested by ticks, kill the Borrelia bacteria in the mid-gut of the ticks.
  • Protocols of use: - ideally administer before exposure at 9 to 12 weeks, booster 2-4 weeks later, followed by annual boosters, preferably in the spring before tick exposure. Duration of immunity is short because there is no natural booster effect.
  • Efficacy studies: - Lymevax bacterin resulted in a 78% efficacy against illness. Recombitek has been reported to produce a 100% protection against illness or infection to a 1 year of challenge.
  • Bacterins have been suggested to also stimulate anti-Osp C antibodies but few bands to Osp C are seen on Western blots in bacterin-vaccinated dogs. Further, there is no evidence to suggest that anti-Osp C antibodies protect dogs against infection or disease (they don't appear to in mice).
  • Some have suggested that because bacterins contain more types of antigens, there might be more risk for immune-mediated reactions and adverse effects (ACVIM consensus statement).
  • Adverse vaccine effects:- estimated to be < 2% overall. There are concerns that vaccination may contribute to the immunopathogenesis of disease in dogs (certainly, Lyme-nephropathy is a immune complex disease). Currently, there is no clear data implicating vaccine antigens in the potentiation of Lyme disease.
  • Vaccination of seropositive dogs:- although some have advocated treating Lyme-positive dogs with a month of doxycycline and vaccination with Lymevax at 0 and 14 days, there is no data supporting this recommendation. In fact, there might be untoward immunologic consequences to this approach; further, the indiscriminate use of doxycycline could well lead to resistance developing in Borrelia and other organisms. However, some have suggested that vaccinating a seropositive asymptomatic dog with a non-adjuvanted rOsp A vaccine will prevent further infection from ticks (not supported by the ACVIM consensus statement) - perhaps one alternative to this would be to concentrate on tick control on the dog.

    Tick control
  • Essential not only to prevent Lyme disease but also RMSF, ehrlichiosis, anaplasmosis, babesiosis, bartonellosis etc.
  • Avoid tick habitats by careful landscaping - ticks love leaf litter, low-lying vegetation, overhanging branches, wooded areas, and overgrown lawns; consult State health websites.
  • Recommended tick control products:
  • Fipronil - Frontline Top Spot, Merial, Duluth, GA. Also provides effective flea control. Not washed off with swimming/bathing. 7 to 28 days protection after application.
  • Amitraz collar - Preventic collar, Virbac, Forth Worth, TX. Not active against fleas. Washed off easily. Toxic if eaten (antidote - yohimbine)
  • Permethrin/imidacloprid - Advantix, Bayer, Shawnee Mission, KS. Also repels fleas. Not washed off with swimming or mild bathing.
  • Permethrin-containing products - Defend EXspot or Proticall, Schering-Plough Animal Health, Union, NJ. Also repels fleas. Not washed off with swimming or mild bathing.
  • Often recommended to use Fripronil together with Amitraz collar if infestations are heavy.
  • Products that prevent tick attachment (Amitraz) or repel ticks (permethrin-containing products) are needed to decrease transmission of other tick-borne disease.

    ZOONOSIS
  • Dogs can transport unattached ticks, which later attach to humans - however, Ixodid ticks are not intermittent feeders and attach quickly; once tick starts feeding on a dog, it feeds to repletion and does not change hosts.
  • Although it has been speculated that Borrelia in the saliva or urine of affected dogs might be transmissible to humans, experiments have failed to prove this.

    REFERENCES
    1. Eschner AK. Effect of passive immunoglobulin transfer on results of diagnostic tests for antibodies against Borrelia burgdorferi in pups born to a seropositive dam. Vet Ther, 9:184-191, 2008.
    2. Littman, MP, Goldstein, RE, Labato, MA, et al. ACVIM small animal consensus statement on Lyme disease in dogs: diagnosis, treatment, and prevention. J Vet Intern Med 20;422-434, 2006.
    3. National Lyme disease risk map. Centers for Disease Control and Prevention, 2004. http://www.cdc.gov/ncidod/dvbid/lyme/riskmap.htm

    Anaplasma and Ehrlichia in the Northeast: Diagnostic Challenges?

    INTRODUCTION
  • Tick-borne diseases of dogs and cats causing vasculitis leading to multisystemic dysfunction often characterized by thrombocytopenia and hyperglobulinemia.
  • Recently reclassified - moved from the family Rickettsiaceae to the Anaplasmataceae.

    OVERVIEW OF ETIOLOGIC AGENTS
  • 3 pathogenic genera: Ehrlichia, Anaplasma, and Neorickettsia; we are concerned here with the first 2.
  • Ehrlichia spp. - divided into 3 groups:-
  • E. canis - intracyctoplasmic morulae found in circulating leukocytes.
  • E. chaffeensis - like E. canis, found in mononuclear cells; mainly a human pathogen but can causes disease in dog.
  • E. ewingii - canine granulocytic ehrlichiosis; like A. phagocytophila, infects granulocytic cells in dogs, but differs in geographic distribution (mainly found in southeastern and south-central USA).
  • Anaplasma spp. - 2 organisms of importance:-
  • A. phagocytophila - previously E. equi, E. phagocytophila, and HGE; infects mainly horses; infects granulocytic cells of dogs; serologic cross reactivity occurs with other Anaplasma spp. but uncommon with Ehrlichia spp.; same distribution as Lyme dz (same tick vector) - northeastern and upper Midwestern states, and California. No serologic cross reactivity with Borrelia, Bartonella or Rickettsia rickettsii.
  • A. platys - previously E. platys; tropism for platelets; does not share serologic cross reactivity with E. canis.

    In this presentation, we will focus on E. canis and A. phagocytophilum.

    PATHOGENESIS
    Ehrlichia canis - Canine monocytotrophic ehrlichiosis.
  • Rhipicephalus sanguineus (brown dog tick) and occasionally Dermacentor variabilis transmits disease to dogs in saliva.
  • Incubation period - 1 to 3 weeks.
  • Severity and outcome of disease depends on infecting strain and dose of inoculum; German shepherd dogs seem more clinically affected
  • After infection - organisms multiply in macrophages then spread throughout hose:-
  • 3 stages of disease:-
  • Acute - spreads from bite site to the spleen, liver, and lymph nodes (causes organomegaly); then subclinical with mild thrombocytopenia; mainly endothelial cells affected; vasculitis; anti-platelet antibodies exacerbates thrombocytopenia; variable leukopenia; mild anemia; severity depends on organism.
  • Subclinical - organism persists; antibody response increases (hyperglobulinemia); thrombocytopenia persists.
  • Chronic - impaired bone marrow production (platelets, erythroid suppression); marrow hypercellular with plasma cells.
  • Multisystemic disease - including bleeding tendencies (thrombocytopenia and vasculitis), lymphadenopathy, splenomegaly, CNS, ocular (anterior uveitis), and lung.

    Anaplasma phagocytophilum - Canine granulocytic anaplasmosis.
  • Ixodes spp (I. scapularis in northeast, I. pacificus in California). transmit Dz in saliva
  • Incubation period - 1to 2 weeks (much shorter than for Lyme disease).
  • Reservoir hosts - white-footed mouse, chipmunks, wood rats, voles, and white-tailed deer; various bird species are also implicated in spread of disease.
  • After infection, organism binds and enters mainly neutrophils - multiply (morula) - rupture cell to release more organisms which infect more cells.
  • How organisms cause disease is not known; after ~ 10 days of infection, cellular and humoral immune mechanisms control infection.
  • Clinical findings are virtually always associated with acute disease period during the bacteremic phase - chronic disease has not been reported.
  • Mild illness typified by fever, lethargy and thrombocytopenia; polyarthritis occurs but rare in comparison to infection with E. ewingii; most dogs present in the spring, early summer and again in the fall.

    CLINICAL SIGNS
    Ehrlichia canis
  • Duration of clinical signs from initial acute illness to presentation - usually > 2 months.

    Acute
  • Bleeding diatheses - resulting in the development of petechia on mucous membranes (conjunctiva, skin), epistaxis, retinal hemorrhage due to thrombocytopenia and vasculitis
  • Fever - with depression, anorexia, weight loss.
  • Generalized lymphadenopathy/splenomegaly (in about 25% of cases).
  • Ticks - found in 40% of cases.
  • Respiratory - dyspnea (even cyanosis) and increased bronchovesicular sounds.
  • Diffuse CNS disease - meningitis (seizures, stupor, ataxia, vestibular dysfunction, cerebellar dysfunction, anisocoria).
  • Generalized or local hyperesthesia.
  • Polyarthritis can occur but is rare in E. canis infections - much more common in E. ewingii and A. phagocytophilum.
  • Most dogs recover without treatment - then enter a subclinical state.

    Chronic
  • Spontaneous bleeding, anemia, and generalized lymphadenopathy.
  • Scrotal and limb edema.
  • Splenomegaly, hepatomegaly.
  • Uveitis, hyphema, retinal hemorrhages and detachment with blindness, corneal edema.
  • Seizures - rare.

    Anaplasma phagocytophilum
  • Middle aged to older dogs are more likely diagnosed with the disease.
  • Most dogs present in the spring, early summer and again in the fall.
  • Mild illness typified by fever, lethargy, depression, anorexia.
  • Generalized musculoskeletal pain (reluctance to move, stiff, lameness) - 50% of dogs.
  • Actual joint pain is found in fewer than 10% of cases.
  • Very rarely - lymphadenopathy, splenomegaly, hepatomegaly, or CNS signs.
  • Although thrombocytopenia occurs, bleeding diatheses do not (clinically inapparent).
  • Dogs are susceptible to reinfection (with 5 mths or more between infections).
  • Serum antibody levels revert to negative levels by 7 to 8 mths post-treatment.
  • Chronic carrier state may exist although asymptomatic - none to date show chronic Dz.
  • Unknown if treatment removes carrier status.
  • Dogs co-infected with A. phagocytophilum and Borrelia (Lyme disease) will have more severe disease.

    DIAGNOSIS

    Ehrlichia canis

    Acute
  • CBC - thrombocytopenia (before onset of clinical signs), anemia, leukopenia (due to lymphopenia and eosinopenia), leukocytosis and monocytosis (as disease becomes more chronic); morulae (intracytoplasmic inclusions in leukocytes) are rare.
  • Mild increases in ALT, ALP, BUN, creatinine, and total bilirubin (rare).
  • Hyperglobulinemia - progressively increases 1-3 weeks post-infection.
  • Hypoalbuminemia - usually from renal loss.
  • Proteinuria - with or without azotemia.

    Chronic
  • CBC - Pancytopenia typical; monocytosis and lymphocytosis may be present.
  • Hyperglobulinemia - size of globulin increase correlates with duration of infection; usually polyclonal gammopathy, but monoclonal (IgG) gammopathies occur.
  • Hypoalbuminemia.
  • Elevated BUN and creatinine - glomerulonephritis and renal interstitial plasmacytosis.

    Serology
  • Indirect FA - positive by 7 days post-infection (some not until 4 wks PI); most clinically useful and reliable method; highly sensitive - poor specificity with cross-reactivity with E. chaffeensis and E. ewingii (not problems in the northeast) but not A. phagocytophilum (in A. phagocytophilum IFA, slight cross-reactivity with E. canis serum).
  • Titers usually 1:80 are diagnostic; paired titers recommended as single titer can reflect past infection; titer progressively declines over 6 to 9 months after treatment. high seroprevalence compared to disease prevalence.
  • Canine Snap® 3 and 4Dx Diagnostic Test (IDEXX Laboratories, Westbrook, ME) - an in-house snap test which tests for antibodies against Lyme disease and E. canis, and heartworm antigen (4D included A. phagocytophilum); detects positive titers to E. canis at an equivalent IFA titer of > 1:500; sensitivity of 95%; specificity of 100% (according to manufacturer); also detects antibodies against E. chaffeensis but not E. ewingii; as with any serologic test, predictive value also depends not only on sensitivity and specificity but also prevalence; in low prevalence areas, likely to get a high false positive rate; could get false positives by reactions to non-pathogenics; confirm +ve test with IFA.
  • Western Blotting - may be used to differentiate mixed infection.
  • PCR - proving to be very sensitive in early detection of experimental infections (positive as early as 4 to 10 days PI) but sensitivity (using whole blood samples) in naturally infected cases not as clear cut; poor correlation with IFA in some studies; should be used in conjunction with serology to detect early cases; analysis of samples other than blood (joint fluid, CSF, aqueous humor, splenic aspirates) may be more clinically applicable.

    Anaplasma phagocytophilum
  • Most reported cases have been found by finding morulae in neutrophils on the CBC; however, more and more cases are being diagnosed in asymptomatic dogs using the Snap® 4Dx Diagnostic Test (IDEXX Laboratories, Westbrook, ME).
  • Up to ~40% of neutrophils can contain morulae (are present for 5 to 9 days experimentally); about 80% have mild thrombocytopenia and lymphopenia, and most have eosinopenia (but not neutrophilia); some have mild anemia and hypoalbuminemia.

    Serology
  • Sero-conversion (using indirect IFA) occurs about 2 to 5 days after appearance of morulae in blood, and titers remain detectable for about 8 months after acute infection.
  • Need paired samples 2 to 3 weeks apart to show 4 fold increase in titer because 40% of acutely ill morulae-positive dogs can be sero-negative at presentation; low titers may be because of a previous infection.
  • Serologic cross-reaction does occur with other Anaplasma spp. and E. canis (although mild) but becomes less cross-reactive during convalescences; no cross-reactions with Borrelia or Rickettesia. A positive Snap® 4Dx Diagnostic Test in southeast US is most likely due to A. platys; in the northeast US, it is most likely A. phagocytophilum.
  • Also, by using the Snap® 4Dx Diagnostic Test, if there is a positive E. canis and A. phagocytophilum reaction, the dog could have both infections, or Anaplasma with a cross reaction with E. canis (and likely an acute active infection and not convalescent), but unlikely to have E. canis alone because there is little cross-reactivity between E.canis antigen and A. phagocytophilum-positive serum.
  • PCR - more sensitive than finding morulae and provides a very species-specific test in the right hands - not well reported in diagnosing naturally-infected cases.

    TREATMENT
  • Only E. canis cases might need hospitalization; stabilize medical for anemia and hemorrhagic tendency (due to thrombocytopenia) - fluids, blood transfusion, platelet-rich plasma (in emergency), or treat for the results of pancytopenia (sepsis) with broad spectrum antibiotics if necessary.
  • Short-term therapy of glucocorticoids (2 to 5 days of 2mg/kg/day of prednisone) may be beneficial early in acute disease when life-threatening thrombocytopenia is present, and may help other immune mediated associations of the disease (polyarthritis, vasculitis, meningitis).
  • Androgenic steroids (oxymetholone or nandrolone decanoate) or granulocyte colony-stimulating factor (Neupogen®, Amgen) - to stimulate bone marrow production in chronically E. canis-affected dogs with hypoplastic marrows may be indicated.
  • Doxycycline is the drug of choice for both E. canis and A. phagocytophilum (5 mg/kg, PO, q12h for 3 to 4 weeks) - see rapid (within 72 hrs of onset of treatment) improvement of platelet count in acute cases; recovered dogs still able to become re-infected.
  • Imidocarb dipropionate (Imazol®, Schering-Plough Animal Health - 5mg/kg, IM, once then repeat in 2 to 3 weeks); reasonable alternative to doxycycline; pretreatment with atropine may lessen anticholinergic adverse effects (salivation, serous nasal discharge, diarrhea).
  • Both doxycycline and imidocarb give ~ 95% cure rate - not improved if used together.
  • Other effective antibiotics include: minocycline, tetracycline, oxytetracycline, and chloramphenicol; enrofloxacin is not effective.
  • A seropositive (by the 4Dx test) asymptomatic dog for A. phagocytophilum - could treat with doxycycline with hope (unknown if it does) that it removes carrier state, but as carriers seem to remain subclinical, this practice is controversial.
  • Prognosis in acute E. canis and A. phagocytophilum infections is excellent; response may take months in chronic ehrlichiosis.
  • Control tick infestations with dips or sprays containing dichlorvos, chlorfenvinphos, dioxathion, propoxur, or carbaryl; flea and tick collars may reduce reinfestation but reliability unproven; selamectin topically (Revolution®, Pfizer) monthly; a combination of imidacloprid and permethrin is effective; avoid tick-infested areas.
  • Examine dogs for concurrent infections that exist in the region frequented by the pet.
  • Zoonotic potential - serologic evidence indicates that E. canis (or possibly a related species) occurs in people; probably not directly infected from dogs; tick exposure thought to be necessary; R. sanguineus probably not the vector in humans.

    REFERENCES
    1. Eddleston SM, Diniz PP, Neer TM et al: Doxycycline clearance of experimentally induced chronic Ehrlichia canis infection in dogs. J Vet Int Med 21:1237-42, 2007.
    2. Neer TM and Harrus S. Canine monocytotrophic Ehrlichiosis and Neorickettsiosis. In:Greene GE (ed) Infectious diseases of the dog and cat. 3rd ed. Philadelphia, Saunders. 203-216, 2006.
    3. Greig B and Armstrong PJ. Canine granulocytotrophic anaplasmosis. In:Greene GE (ed) Infectious diseases of the dog and cat. 3rd ed. Philadelphia, Saunders. 21-224, 2006.

    Giardiasis: Confusion with Diagnosis and Treatment?

    INTRODUCTION
  • Flagellated protozoan parasite found in the GIT of animals including man.
  • Prevalence: General population cats; <1% to 13.6% with most reports around 10%. Shelter cats: Can be as high as 80% in cats housed in high density rooms. [Worth noting that prevalence data may depend on the sensitivity of the test used: IFA - 14%, IDEXX SNAP Giardia test - 11%]
  • Although prevalence can be high, clinical disease is rare, and often not dependent on prevalence - more often dependent on age (young cats, higher incidence of signs).

    LIFE CYCLE
  • Direct with infection via oral route. Entire development occurs in the GIT. Cysts in feces.
  • 2 forms: 1) teardrop-shaped trophozoite (active motile form found in GIT), 2) cyst or dormant resistant stage responsible for transmission.
  • Cyst capable of surviving for several months outside host in wet cold condition. Can also survive chlorinated water. Very susceptible to desiccation under dry hot conditions.

    CLINICAL FINDINGS
  • Most infections are asymptomatic.
  • Diarrhea is main sign. May be acute, short-lived, intermittent, or chronic. Feces pale, malodorous, and steatorrheic. May see weight loss (diarrhea) but rarely inappetence.

    DIAGNOSIS
  • Clinical signs and tests (CBC, serum chemistry, radiology etc) are non-specific.
  • Unequivocal diagnosis relies on finding cysts or trophozoites (or products of these) feces or samples taken from the GIT.

    Fecal smear
  • Easy, non-invasive, and very specific but low sensitivity. Trophozoites more likely passed in loose feces, especially in cats.
  • Drop of fecal material mixed with a drop of normal saline, cover slipped, examine at 40X. Trophozoites easily identified by rapid forward motion, and concave ventral disc. Trichomonads (the only other organism that looks like Giardia has a rolling motion, no concave disc, single nucleus, and an undulating membrane. Stain organisms with Lugols iodine to confirm.

    Zinc sulfate concentration technique (ZSCT)
  • Use a 1.18 SG ZnSO4 solution with centrifugation. Needs trained personal to conduct test as cyst shedding (particularly in dogs) is highly variable (from a few to 50,000/gm of feces within 3 days)
  • Unfortunately, the 1.18 SG ZnSO4 solution may not float heavier eggs (such as Taenia spp.) so can use a modified 1.27 SG Sheather sugar solution which will also get Giardia. [Dryden's Modified Sheather's Solution (SG 1.27): 454 gm granulated sugar, 355 ml tap water, 6 ml formaldehyde. Dissolve sugar over gentle heat, check SG with hydrometer, filter thru course filter paper if not clear.]
  • Performing 3 tests on fresh fecal samples collected over a 3 to 5 day period (because cysts are shed intermittently) is considered the gold standard. One test is about 70% efficacious, 2 tests are about 93% efficacious, and 3 tests are about between 95 and 100% efficacious.
  • Problem is, not very practical in a private practice situation.
  • May ship samples refrigerated (cysts live for 2 days at 4C, but will not survive formalin). ZSCT also excellent for nematode eggs.
  • Cysts may be confused with yeast.

    Fecal ELISA kits
  • ELISA microplate tests - usually conducted in diagnostic laboratories as can run multiple tests at a time. Developed for use in man originally (96% specific, 100% sensitive).
  • IDEXX - SNAP® Giardia test - for cats and dogs - in-house - 8 minute test. Compared to ELISA microplate test, this SNAP test is 92% sensitive, and 99.8% specific). Detects a trophozoite protein in feces. Can use frozen samples or feces fixed in formulin. [Worth noting that while 6 of 27 veterinary practices can identify a known positive Giardia sample using flotation techniques, 27 or 27 correctly diagnosed the sample using the IDEXX SNAP Giardia test.] May remain positive for up to 3 weeks post-treatment (according to IDEXX).

    Direct Immunofluorescent test
  • Uses fluorescent labeled monoclonal antibodies to detect cysts. As effective as the ZSCT in man.
  • Used in both cats and dogs: some studies suggest that it is more sensitive than ZSCT as picks up lower numbers of cysts/gm of feces (certainly the case in cattle).
  • Needs to be performed in a diagnostic laboratory (needs a fluorescent microscope).
  • Use fresh feces or fix in formulin.

    Duodenal aspirates
  • Impractical to perform endoscopy and duodenal aspirates under general anesthesia to rule out Giardia. However, reasonable to collect a sample during endoscopy for examination.
  • Method: flush 10ml of saline through polyethylene tube passed down endoscope channel, then aspirate immediately. Centrifuge sample (150g, 10min), examine sediment (wet mount, or stain with Giemsa).

    Peroral string test
  • Method for collecting duodenal contents from people using a commercially available peroral technique (Entero-Test, HDC Corp, San Jose, Ca). Used in third world countries.
  • In 21 tests performed in dogs with Giardia infections, none were positive and one dog developed a string foreign body. Extremely insensitive, impractical, risks string foreign body - don't use!

    TREATMENT
  • Determine why treatment is important: 1) Zoonotic considerations although no clinical signs [NIH web page states: "an infected family dog with diarrhea may pass the parasite to human family members" - presumably same for cat!] 2) Clinical signs consistent with giardiasis, 3) Prevent spread to naive population, 4) As part of a colony "clean up" policy.
  • Determine if the drug to be used is appropriate and safe for use in the patient.
  • Consider other intercurrent diseases the patient may have which may benefit from drugs used to treat Giardia, or may prevent the use of certain drugs.
  • Consider re-infection after treatment, and how this affects interpretation of drug efficacy results.

    SPECIFIC DRUGS

    1. Fenbendazole [Dose: 50mg/kg, PO, q24h for 5 consecutive days].
  • Benzimidazole derivative. Works by inhibition of microtubule assembly by inhibiting tubulin polymerization.
  • In dogs, 3 consecutive doses were found to be over 95% efficacy [in some studies, up to 100% efficacious).
  • However, in cats (also infected with cryptosporidium) treated with above dose, 4 of 8 (50%) became completely negative, and others showed improvement in cyst shedding but not all become negative.
  • May not be ideal drug in cats but probably is in dogs.
  • Also used to remove whipworms, roundworms, hookworms, and the tapeworm, Taenia pisiformis. No side effects, not teratogenic, and safe in cats.

    2. Febantel, praziquantel, pyrantel pamoate combination Drontal-Plus (Bayer Corp, Shawnee, Kan). [Dose: 5.4-7mg/kg praziquantel, 26.8-35.2mg/kg pyrantel, 26.8-35.2mg/kg febantel in combination (label dose for Drontal-Plus ), q24h, for 3 consecutive doses].
  • Febantel is metabolized in the liver to fenbendazole and oxfendazole; most anti-Giardia activity is ascribed to the fenbendazole although a synergistic activity of the other drugs can not be discounted.
  • Close to 100% efficacy. No side effects reported at above doses by vomiting and non-formed feces reported in dogs receiving 5 times label dose for 3 consecutive days.
  • Cats: ½ a Drontal Plus tablet (for small dogs)/kg, PO, q24h, for 5 days is close to 100% effective in cats.

    3. Albendazole [Dose: 25mg/kg, PO, q12h for 4 doses].
  • Benzimidazole derivative (same mechanism as fenbendazole). > 90% efficacy.
  • Suspect of being teratogenic. Effective in cats when used for 5 days.
  • No side effects reported in beagles treated with 30mg/kg q24h for 13 weeks. Reported to cause bone marrow toxicosis with pancytopenia in a dog and cat.

    4. Metronidazole: Dogs: Dose of 25mg/kg, PO, q12h for 5 days reported to be 67% effective.
  • Cats: Dose of 25 mg/kg, PO, q12h for 7 days reported to be 100% effective.
  • Associated with anorexia, vomiting progressing to neurologic signs of ataxia and nystagmus, but usually only at higher doses than those above.

    5. Oxfendazole: Dogs: Dose: 11.3 mg/kg, PO, q24h for 3 days. Not used in cats.
  • In a European study, found to be very effective in dogs when used in association with cleaning procedures.
  • In the US, only available as a cattle dewormer (Synanthic Bovine Dewormer Suspension® 9.06%, Fort Dodge, Fort Dodge, Ia).

    6. Quinacrine hydrochloride: [Dose: 6.6 mg/kg, PO, q12h for 5 days].
  • 100% effective at this dose but complicated with a 50% side effect rate (lethargy, fever which stop 2 to 3 days after treatment stops).

    7. Furazolidine: [Dose - Cats: 4mg/kg, PO, q12h for 5 to 10 days].
  • High efficacy but side effects include diarrhea and vomiting. Teratogenic.

    VACCINATION
  • Released by Fort Dodge early in 2000.
  • Made of inactivated trophozoites
  • Young pups and kittens immune to giardia challenge 6 mts and 12mths after 1 injection and booster.
  • Reduces cyst excretion on older dogs (non-immune).
  • Has been used to treat dogs - given to dogs with chronic infection to reduce load.
  • Some studies show that vaccination fails to prevent infection
  • Not efficacious in cats already infected.
  • Probably little utility for its use except for odd case that does not respond to drugs.

    CONTROL: Drugs may not remove organisms for GIT but only inhibit cyst production.
  • In wet cold environments, cysts survive for long periods. These, as well as cysts on the hair coat of pet are a source of infection.
  • 4 approaches to control:
    1. Decontaminate environment by creating "clean areas".
    2. Treat animals with highly efficacious drugs, and rotate drugs used.
    3. Clean cysts from coats of animals.
    4. Prevent re-introduction of infection.
  • If only a few animals are involved, move them all out of the facility while it is cleaned. In large facility, create a "clean area" a few cages at a time on a rotation basis once animals are moved out to a holding facility.
  • Treat animals with efficacious agents (3 - 5 day course of fenbendazole or Drontal Plus for dogs; a 7 day course of metronidazole for cats) prior to moving: move on the last day of treatment.
  • Remove all solid fecal material
  • Steam clean facility or clean with quaternary ammonium-containing disinfectants (use at manufacturers recommended concentration - cysts are very susceptible).
  • Allow facility to dry thoroughly - facility is now considered "clean".
  • Prior to moving animals back in to "clean area", bath with all-purpose pet shampoo, rinse shampoo off coat, then wash coat (especially perianal area) with quaternary ammonium compound, then rinse thoroughly from coat (can irritate mucus membranes if left on for long periods of time - leave on only for 1 minute). Dry hair coat thoroughly, preferably blow dry.
  • When return animals to "clean area," treat with a second course of drugs.
  • Prevent re-infection of "clean area" by treating and bathing animals prior to introduction.
  • Prevent fomite transmission by physically cleaning boots of people entering facility.

    ZOONOSIS

    Assemblage Susceptible Species
    A Humans, Dogs, Cats
    B Humans, Dogs
    C Dogs, Cats
    D Dogs, Cats
    E Large animals, possibly cats?
    F Cats


  • Assemblage A and F have been identified in cats from the USA and Europe, but only D in Australia. Little specific information on dogs but only D to date!!

    REFERENCES
    1. Vasilopulos RJ, Mackin AJ, Rickard LG, et al. Prevalence and factors associated with fecal shedding of giardia spp. in domestic cats. J Am An Hosp Assoc 42:424-429, 2006.
    2. Calin EP, Bowman DD, Scarlett JM, et al. Prevalence of Giardia in symptomatic dogs and cats throughout the United States as determined by the IDEXX SNAP Giardia test. Vet Therapeut. 7:199-206, 2006.
    3. Scorza AV, Radecki SV, Lappin MR. Efficacy of a combination of febantel, pyrantel, praziquantel for the treatment of kittens experimentally infected with Giardia spp. J Fel Med Surg 8:7-13, 2006.
    4. Dryden MW, Payne PA, Smith V. Accurate diagnosis of Giardia spp. and proper fecal examination procedures. Vet Therapeut 7:4-14, 2006.
    5. Barr SC. Giardiasis. In: Infectious diseases of the Dog and Cat. Greene CE (ed) 3rd ed. Saunders, Philidelphia. Pp 736-742, 2006.
    6. Barr SC. Giardiasis. In: Canine and Feline Infectious Diseases and Parasitology. Barr SC and Bowman DD (ed). Blackwell, Ames. Pp 259-264, 2006.
    7. Vasilopulos RJ, Rickard LG, Mackin AJ et al. Genotypic analysis of Giardia duodenalis in domestic cats. J Vet Intern Med 21:352-355, 2007.

    Canine Parvovirus: Treatment Revisited

    ETIOLOGY
    The parvoviruses are small nonenveloped single stranded DNA virus. 3 known to infect dogs:
    1. CPV-1 (minute virus of canines) - uncertain pathogenicity - has been associated with "fading pups" - lethargy, loose stools, respiratory distress, sudden death.
    2. Canine adeno-associated virus - apparently non-pathogenic.
    3. CPV-2 replicates in dividing cells especially intestinal, lymphoid, bone marrow and fetal tissues and is severely pathogenic. This virus is known simply as canine parvovirus or CPV, and is closely related to feline panleukopenia virus and mink enteritis virus. CPV-2 is a new canine virus appearing about 1977. Current isolates (CPV-2a,b first observed in 1980, 2c reported in Italy in 2000, and widespread in USA and world by 2007) have different antigenic structures, increased pathogenicity, and a shorter incubation period (4-5 days vs 5-8) than CPV-2. These variants also replicate efficiently in cats. MLV vaccines of 2 and 2b protect against 2c.
    Of clinical importance are a few features of the virus:
  • Parvoviruses- resistant to inactivation; can remain infectious outside the host > 5 months.
  • Most common detergents and disinfectants fail to inactivate these viruses.
  • CPV-2 hemagglutinates RBCs from a number of species so hemagglutination assays are useful for diagnosis.

    HOST RANGE AND PREDISPOSING FACTORS
  • Probably all Canidae are susceptible. Within domestic dog populations, Dobermans pinschers, Rottweilers, English Springer Spaniels, and in some studies, American Pit bull terriers and German Shepherds are at higher risk of severe illness.
  • Intact male dogs seem more predisposed to infection than intact females.
  • Unvaccinated dogs - about 13 X more likely to become infected than vaccinated dogs.
  • Concurrent infection with other gastrointestinal pathogens (Giardia, hookworms and roundworms, coronavirus) may exacerbate the severity of CPV infection. Stress of overcrowding, poor nutrition, and age at infection can dictate the outcome of infection.

    TRANSMISSION
  • Fecal-oral route. A vast amount of virus is shed in the feces of clinically infected dogs. However, the persistence of virus in the environment is thought to be more important than chronic carriers in perpetuating disease - not clear if carrier state exists?
  • Active shedding of virus occurs up to the first 2 weeks post inoculation. Generally, dogs that recover from infection do not transmit disease to susceptible kennel mates.

    PATHOGENESIS
  • After oronasal exposure - primary replication occurs in regional lymph nodes of the pharynx/tonsils followed by plasma-associated viremia (develops even as early as the 1st or 2nd day post-infection (PI) although becomes high 3 to 4 days PI); other lymphoid tissue (thymus, mesenteric nodes, bone marrow) becomes infected by the 3rd day PI; virus can be detected in intestinal epithelial cells by day 4 PI (it is suspected that the virus initially arrives in the GIT by way of plasma or in infected lymphocytes).
  • Active excretion of virus in the feces occurs as early as day 3 PI before clinical signs occur.
  • Viral fecal shedding increases rapidly to peak at day 4 to 7 PI - coincides with the onset of clinical signs; virus can rarely be found in the feces by 12 to 14 days PI.
  • CPV-2 depends on dividing cells for replication and cells that become infected die. Thus, cell loss is present in tissues of high multiplication rates - small intestinal crypt cells, lymphatic tissue and bone marrow, and myocardial cells in very young pups.

    Myocardial disease
  • Age and immunity determine whether CPV infection results in myocardial disease or enteritis.
  • Cardiac myocyte replication is sufficient enough only to support virus until 2 weeks of age. Although myocarditis is seen in pups at 6 to 8 weeks of age, it is the result of infection several weeks earlier.
  • Myocardial disease is exceptionally rare in the US these days because most bitches (greater than 85% in one census in 1991 in the USA) are immune and the pups are protected by passive immunity in-utero or during the first weeks of life.

    Enteritis
  • Commonly seen in pups 6 to 16 weeks of age.
  • In the intestine, dividing crypts cells are primarily affected, as opposed to the cells at the tip of the villus (as seen in corona virus and rotavirus).
  • As the enteric cells move up the villus to be lost at the tip they are not replaced from below resulting in the lesion seen in CPV-2 infection.
  • In severely clinically affected dogs, the crypt cells and lymphoid cells in Peyer's patches are destroyed faster than they can be replaced.
  • Nearly all signs occur because of crypt cell and lymphoid/bone marrow destruction.
  • It will take 2 weeks before this damage can be repaired.

    Bone Marrow effects
  • Of major clinical importance is the effect CPV-2 infection has on bone marrow. CPV-2 infection causes necrolysis of the myeloid and erythroid stem cells in marrow.
  • Because of the long half-life of RBCs, few effects are seen on RBC indices although anemia may be seen from blood loss from the bowel.
  • Leukocyte counts reflect both peripheral consumption and myeloid destruction. In severe disease there is progressive reduction in leukocyte numbers from day 3 to 5 PI.
  • Neutropenia, toxic changes in neutrophils, degenerative left shift and often absolute lymphopenia occurs concurrently with the onset of clinical signs (6 days PI).
  • In recovery, leukocytosis + left shift often predict a successful treatment outcome.
  • Recently reported that WBC count > 4.5, lymphocyte count > 1, monocyte count > 0.15, eosinophil count > 0.1 with a left shit are accurate predictors of a good outcome.
  • Neutrophils: Survivors develop a left shift (usually degenerative): non-survivors don't.
  • vLymphocytes: Get marked rise in lymphocyte in 1st 24 hrs post-admission in survivors.
  • [more significant than total WBC count]
  • Monocytes: Quicker production time (3 days compared to 6 days for PMN). So increases
  • in monocytes usually precede those of PMNs.
  • Eosinophils: Good prognostic indicator when appear especially after 48hrs post-admit.

    Neurologic effects
  • Cerebellar hypoplasia (common in kittens infected with feline panleukopenia virus) occurs in dogs (also due to neonatal infection) but is very rare.

    CLINICAL SIGNS
  • Can be extremely variable dependent on age (under 3 months), immunity, co-pathogens (parasites, enteric bacteria, viruses), and infective dose.
  • Crowding, poor sanitation reduces the chances of successful immunization in kennels but do not enhance disease in individuals.
  • Signs can vary even within single litters.
  • Viral dose and antigenic type can influence intensity of illness. Pups infected with CPV-2a or 2b can die acutely even before diarrhea has developed.

    Classically:
  • Depression, anorexia, vomiting, with or without pyrexia are initial signs.
  • Dogs vomit repeatedly, sometimes with roundworms in vomitus.
  • Then mucoid to then bloody diarrhea develops. Although many clinicians claim they can "smell" a parvovirus case walk in the door, the character of the vomitus and diarrhea do not distinguish it from other enteritides.
  • Severe lymphopenia even to absolute lymphopenia is common and helps distinguish the disease from other causes of severe diarrhea (Hemorrhagic Gastroenteritis, Salmonellosis).
  • Neutropenia may also be present.
  • With diarrhea, severe dehydration, weight loss, abdominal discomfort and pain are consistent features.
  • Dogs may present in endotoxic shock or disseminated intravascular coagulation. These are extremely difficult to save and require 24-hour intensive care.

    DIAGNOSIS
  • Young pups under 16 weeks old, particular breeds affected (Rottweilers, Dobermans, English Springer Spaniels), kennels, acute onset of typical signs with lympho/neutropenia (sometimes absolute).
  • The progression of leukopenia can help to set a prognosis. When band cells appear in the blood smear, prognosis improves markedly.
  • Blood chemistry reflects dehydration and electrolyte disturbances (hypokalemia, hypoglycemia).
  • Virus can be detected in stools for 2-4 days after onset of disease by commercial fecal ELISA tests that appear to be highly specific and sensitive. Blood in the stool may give false negatives due to antibody binding virus in stool.
  • Again, remember that virus shedding in feces occurs 3-4 days PI, reaching a peak about the time clinical signs first occur, and stops 8-12 days PI.

    MANAGEMENT AND TREATMENT
  • The most important principle of therapy is to address the tremendous fluid loss associated with diarrhea and vomiting, and prevent secondary bacterial infections.
  • Replace fluid loss. First, assess dehydration. Dehydration less than 5% is difficult to appreciate clinically. Most dogs with diarrhea and vomiting from CPV infection are 8 to 10% dehydrated as indicated by sunken eyes in orbits, prolonged capillary refill time, dry mucous membranes, signs of shock (increased heart rate, weak pulses), skin tenting. Simple laboratory tests help: A PCV and Total Plasma Protein are useful but will be also affected by blood loss (diarrhea). Urinalysis should show markedly concentrated urine (> 1.030). It is essential to realize that little or no change can occur in laboratory values in severely dehydrated animals. Estimate fluid volume to be replaced (% dehydration X body weight in Kg = liters of fluid to replace). Also add in estimated ongoing losses (diarrhea and vomiting) as well as "normal" (insensible and sensible) losses (about 15ml/kg/day). Use a balanced fluid, such as Lactated ringers, Plasma-Lyte, Normosol, or 0.9% sodium chloride supplemented with dextrose and potassium. Fluids containing dextrose is usually indicated especially in small puppies (Chihuahuas), and may need to be preceded by a bolus in some cases.
  • Route of administration. If can, always administer fluids to CPV-infected dogs by the IV route. Avoid the subcutaneous route especially in leukopenia animals as can introduce infections. Avoid oral route at least until 24 hours after vomiting has stopped and preferably after diarrhea has stopped.
  • Replace electrolytes - hypokalemia is not always present but whole body depletion of potassium will occur during the illness due to no oral intake, increased loss in feces, and renal loss. Put in IV fluids not to exceed 0.5 mEq/kg/hr. Use Scott's table to calculate how much K to add. However, generally 20 to 30 mEq/L can be added to fluids. Dogs with severe and persistent diarrhea can suffer from hyponatremia and hypochloremia which will be replaced with balanced fluids.
  • Correct acid-based abnormalities. Dogs may be acidemic (due to dehydration and bicarbonate loss and diarrhea if not much vomiting) or alkalotic (loss of gastric acid from vomiting), but rapid IV fluids will usually replace deficit. There is no need to use bicarbonate or ammonium chloride to off set acid-base abnormalities.
  • Prevent secondary bacterial infection. Use broad spectrum antibiotics against enteric bacteria, especially in leukopenic animals. Enteric Clostridium perfringens frequently proliferates in dogs with CPV. Cephalosporins, enrofloxicins, or combinations such as IV ampicillin and gentamicin (NOTE: probably best combination but do not give gentamicin to dehydrated dogs unless can monitor urine and BUN). In less severe cases, oral metronidazole has been used. Be aware however that CPV-infected dogs with CPV on extended antibiotic therapy have developed oral and intestinal candidiasis.
  • Prevent further fluid loss. Antiemetics (not anticholinergic drugs) - metoclopramide and prochlorperazine are most effective in the recovering dog that persists in vomiting. Do not use too early as mask clinical signs. Serotonin receptor antagonists (ondansetron and dolastron) are also very effective. Gut motility modifiers (dephenoxylate or loperamide) are rarely ever needed.
  • Oral gastric protectants. Once vomiting has stopped carafate and famotidine and even Peptibismol may be indicated.
  • Withhold food? In fact, the earlier dogs with clinical parvovirus are fed (even by using enteral feeding tubes), the quicker is their recovery and the better they maintain their body weight.
  • Parenteral nutrition - intravenously. Risk of systemic infection is very high. Only give during the recovery stage when the leukogram is normalizing.
  • Corticosteroids? Only in severe shock and only one dose. Use is highly questionable.
  • Non-steroid anti-inflammatory agents (flunixin meglumine) - rarely indicated. Some advocate giving with fluids at 1mg/kg.
  • Granulocyte colony-stimulating factor. When administered to neutropenic pups with CPV enteritis, it did not change any aspect of clinical outcome.
  • Recombinant feline interferon-omega. When given (1 mega units/kg/day, IV, for 3 days) to 3-4 mth-old beagles 4 days after experimental infection, the severity of enteritis was improved in some of the dogs.
  • BPI protein. A recombinant bactericidal-permeability-increasing protein which counteracts endotoxin - not shown to alter the clinical outcome or survival at all, even when plasma endotoxin levels increase in treated animals.
  • Blood/plasma. Indicated if severe hypoproteinemia. Usually short-lived but may save the dogs life. The administration of antiendotoxin hyperimmune plasma has been shown in one study to decrease both mortality and the length of hospitalization in dogs with CPV enteritis. Hyperimmune serum or immunoglobulin has been tried but few controlled studies have been conducted. In these studies, it has been difficult to separate the beneficial effects of protein as opposed to immunoglobin that binds virus or endotoxins.
  • Monitor closely: clinical signs (palpate the abdomen daily), dehydration (PCV, TP, urine SpG, body weight), electrolytes (K, Na), renal function (BUN/creatinine), glucose, blood smear for WBC numbers.
  • Try to avoid doing surgery on recovering dogs as they are at great risk of post-operative wound break down and infections.

    CLIENT EDUCATION
  • Disinfect premises (1:30 solution of 5% sodium hypochlorite is effective in a few minutes). Strict sanitation, isolate pups till reach 3 months of age.
  • Carrier state has not been demonstrated in the dog. CPV-2 is shed for less than 2 weeks after infection.
  • Vaccination schedule is essential in at-risk populations.
  • Even though apparent break down in vaccine efficacy against CPV-2c virus has been reported in a kennel of dogs from Italy, experimental evidence suggests that current vaccines against CPV-2b (MLV vaccine Galaxy DA2PPv; Schering-Plough Animal Health), and CPV-2 (MLV vaccine Continuum DAP, Intervet) protect against CPV-2c. Similar findings from UK.

    REFERENCES
    1. Larson LJ, Schultz RD. Do two current canine parvovirus type 2 and 2b vaccines provide protection against the new type 2c variant? Vet Therapy, 9(2):94-101, 2008.
    2. Goddard A, Leisewitz AL, Christopher MM et al. Prognostic usefulness of blood leukocyte changes in canine parvoviral enteritis. J Vet Intern Med, 22:309-316, 2008.

    Heartworm Disease: How Treatment is Changing

    OVERVIEW
  • Filarial nematode infection of dogs and cats - Dirofilaria immitis - adults (female worms up to 30 cm in length) live in pulmonary arteries causing respiratory, cardiac, and in some cases, renal disease.
  • Adults living in pulmonary artery cause lobar arterial enlargement, obstruction, and tortuosity causing pulmonary hypertension and thrombosis.
  • Severity of disease - directly related to the number of worms, host response, and duration of infection.
  • Female adult worms release L1 microfilaria into circulation where they can live for up to 2 years; L1 infective stage for the vector, mosquitoes, in which they develop to L3; mosquitoes inject L3 back into dog where they mature and migrate to the heart. PPP = 6 to 7 months (dogs) - longer in cats.
  • Prevalence - widespread throughout North America (even Alaska) but much more common in southern States - along the Atlantic and Gulf coasts and Ohio and Mississippi River basins.
  • 100% in of dogs not on prophylaxis may be infected in highly endemic regions.
  • Low prevalence areas (Northern States) - pockets of infection usually where mosquito vector is common.
  • Although D. immitis can infect man, infected dogs represent no direct zoonotic potential.

    SIGNALMENT
  • Mainly affects dogs 3 to 8 yrs old; all breeds but medium to large-breed dogs (those that spend a lot of time outdoors) are most susceptible.
  • Most infected dogs are asymptomatic (Class I or perhaps display an occasional cough) so most infections are picked up during routine heartworm antigen screening during wellness checks.

    CLINICAL SIGNS
  • Class I - dogs show no abnormal findings.
  • Class II - exercise intolerance; cough; weight loss; pulmonary changes on thoracic radiography; blood worm might show a mildly reduced PCV (20 - 25).
  • Class III - exercise intolerance; cachexia; syncope; tachycardia; perhaps ascites due to right sides heart failure; hepatomegaly; pulmonary and cardiac changes on thoracic radiography; hemoptysis may occur (suggests severe pulmonary thromboembolic); blood work shows a PCV < 20.
  • Vena cava syndrome (occurs when vena cava is obstructed by adult worms) can result in hemoglobinuria due to acute hemolytic crisis.

    HEMATOLOGY/SERUM BIOCHEMISTRY/URINALYSIS
  • CBC: anemia (Class II - mild; Class III - severe); eosinophilia and basophilia are a sensitive indicator of heartworm disease when they occur together; leukocytosis and thrombocytopenia are often associated with severe thromboembolism.
  • Serum biochemical profile and urinalysis: Hyperglobulinemia is not a consistent finding; proteinuria (immune complex glomerulonephritis) is common in dogs with severe chronic infection; hemoglobinuria can occur during an acute hemolytic crisis (vena cava syndrome).

    SPECIFIC HEARTWORM TESTING
  • Heartworm antigen tests are highly specific, sensitive tests that identify adult female D. immitis antigen in serum; now the standard screening test in dogs.
  • Antigen tests should not be used in pups under 7 months (can take 7 months after infection to develop a positive); test 7 months after the end of the previous transmission season.
  • Annual testing is probably unnecessary if dog receiving monthly macrolide chemoprophylaxis; a 3 year testing interval is probably adequate.
  • In cats, antigen tests are more specific (positive test result is strong evidence of heartworm disease) than antibody tests; low worm burdens (fewer than 5 worms) and single-sex infections often result in false-negative results; because > 40% of cats with adult infection are antigen-negative, a negative result does not rule out heartworm disease; risk of false-positive results increases with low prevalence (most of USA) so positive results in low prevalence areas should be confirmed by other diagnostic criteria or second test.
  • Antibody Tests detect serum antibodies to immature and adult heartworms; the most sensitive tests for feline heartworm disease; a positive result documents exposure but does not always indicate mature or current infection (positive predictive value = 25%); in cats, can detect male-only and immature infections; this test is the most logical screening test for asymptomatic cats.
  • Microfilaria identification tests (Modified Knott's test, filter tests, and direct smear); about 25% of infected dogs will be missed if use only these tests.

    IMAGING
  • Thoracic radiology should always be performed to determine the Class of infection and the degree of thromboembolism; pre-treatment radiographs allow determination of amount of thromboembolism occurring as a result of therapy.
  • Thoracic radiographic signs: Enlargement of the main pulmonary artery, lobar arterial enlargement and tortuosity (absent in Class I, severe in Class III); parenchymal lung infiltrates of variable severity can help predict degree of thromboembolism; allergic reactions to microfilaria represented by diffuse, symmetrical, alveolar, and interstitial infiltrates.
  • Echocardiography is usually unremarkable and not a cost-effective test, but may show dilation of the right ventricle with wall hypertrophy, and the presence of heartworms (parallel linear lines) especially in cats (rarely found in dogs) most commonly in the right pulmonary artery (cats) but also in right ventricle and atria; expertise and high index of suspicion increases sensitivity of test.
  • None-selective angiography is best in cats if used at all - of little practical clinical application.
  • Electrocardiography may show RV hypertrophy and atrial fibrillation in dogs with Class III infection.

    THERAPEUTICS
  • Need to assess justification of adulticide treatment in certain patients. e.g. in very old dogs, the outcome of treatment may be worse than the benefit of treating.
  • Dogs with thromboembolic complications especially during adulticide administration should be hospitalized.
  • Activity should be severely restriction for at least 4 weeks (6 better) after adulticide treatment; confine dogs treated for Class III disease to a cage for 4 weeks, and 1 week for dogs suffering from pulmonary thromboembolic events.
  • Pulmonary failure should be stabilized with antithrombotic agents (e.g., aspirin or heparin) and anti-inflammatory doses of corticosteroid; monitor using clinical and radiographic parameters.
  • For dogs with Class III disease, treat CHF (with cage rest, diuretics) until stable before adulticide.
  • Vena cava syndrome: remove adult worms from right heart and PA via jugular vein by use of fluoroscopy and a long, flexible, alligator forceps; requires an experienced operator but this surgery is really the only effective method of treating dogs with very high worm burdens.

    TREATMENT REGIMENS
  • Melarsomine dihydrochloride (Immiticide®, Merial) is the drug of choice. It is highly efficacious against both male, female worms and L5 (>90%), but is thought not to be effective against heartworms less than 4 months of age; has low toxicity; treatment can still result in pulmonary thromboembolism (usually 7-30 days after therapy); anorexia (13% incidence); injection site reaction (myosytis - 32% incidence but mild and only lasts 1-2 days); lethargy or depression (15% incidence); elevations of hepatic enzymes rare; neurologic damage as a result of local nerve root inflammation from the drug reaching nerve roots close to the injection site (essential to make sure the injection is deep within a muscle body).
  • Prior to initiating melarsomine treatment, it is often beneficial to give ivermectin (at prophylactic doses of 6 ug/kg orally) for 1 to 6 months (3 months most often recommended) especially when dogs are clinically stable; this should allow older larvae and immature adults time to develop to an age at which they can be killed by melarsomine (over 4 months at least); it will also greatly reduce circulating microfilaria and migrating larvae, stunt immature worms, and reduce female worm mass, which should reduce the risk of thromboembolism at the time of melarsomine treatment.
  • Class I infection:- Give 2 injections 24 hrs apart are given into the epaxial muscles (1st on one side, 2nd on opposite side, using 22-gauge needles); apply pressure over the injection site during and after needle withdrawal; antigen test may be checked 7 to 8 months later and if positive, repeat treatment.
  • Class II and Class III infections:- Give 1 injection (kills approximately 40% of worms), then 1 month later, give 2 injections 24 hrs apart (as per for Class I infections); this spreads the worm killing effect of the drug over 2 treatments and reduces the severity of thromboembolism; many veterinarians and teaching hospitals use this schedule for treating Class I infections also.
  • Dogs that develop thromboembolism usually present with anorexia, low grade fever, cough, occasionally hemoptysis, which usually becomes evident within 7 to 10 days (occasionally as late as four weeks) after completion of adulticide administration - treat with corticosteroids and rest.
  • Ivermectin (at 6 ug/kg orally) has been suggested for use as a treatment for adult heartworms: given monthly for a year, it is about 98% and 95% effective against 3 and 4-month old heartworms (larvae), respectively. Against worms that are 5 months old, ivermectin is over 98% effective if given for 30 months. Against 8 month-old worms (full adults), ivermectin is 56% effective if given for 16 months, and 95% effective if given for 30 months; the older the adult heartworms, the more resistant they are to the effects of ivermectin.
  • Long-term administration of ivermectin (at 6 ug/kg orally) or any other prophylactic drug, should NOT be a substitute for melarsomine adulticide therapy because such treated infected dogs often develop worsening clinical, radiographic, and echocardiographic changes.
  • The other macrocyclic lactones (milbemycin, salemectin, moxidectin) all are very effective (like ivermectin, close to 100%) 2 to 3 months after infection - good "reach-back" activity so provide a good safety net if prophylactic dosing has been missed - but are NOT effective as adulticides.
  • In dogs that still have microfilaria after melarsomine treatment (and pretreatment with ivermectin), attempts should be made to treat these about 4 weeks after giving adulticide.
  • Regimen: admit dog to the hospital during the morning, check for the presence of microfilaria, then (if present) give milbemycin (Interceptor®, 0.5 mg/kg) or ivermectin (multiple preparation, 50 µg/kg) orally and watch the patient for signs of microfilarial anaphylaxis (shock; vomiting, diarrhea, circulatory collapse) for the day; discharged in the evening on regular monthly preventative.
  • If shock occurs, give shock dose of corticosteroids and IV fluids; prognosis excellent; shock is more likely to occur in those dogs with high circulating microfilaria burdens.
  • Ivermectin (at 6 ug/kg orally) will also remove microfilaria from circulation of most dogs but will take 8 months; there is a concern that use of these drugs at doses that allow microfilaria to survive for several months will lead to the development of resistance.
  • Begin monthly microfilaricide prophylaxis 4 weeks later - re-infection can occur in treated dogs.
  • Antigen test 6 months after adulticide treatment; if positive, reassess the patient to determine the degree of improvement as a result of the first treatment (chest radiographs, strength of positive antigen test, age of patient) and only repeat adulticide treatment if necessary.
  • Heparin and aspirin use before and during treatment may not provide any advantages (prevent or lessen thromboembolic events).
  • Strict cage rest after melarsomine treatment or during pre-treatment ivermectin can not be over-emphasized.
  • The Wolbachia story - Adult D. immitis are capable of harboring obligate, intracellular, gram-negative bacteria (genus Wolbachia (Rickettsiales); these bacteria can be treated with tetracyclines (doxycycline is drug of choice) - by killing the bacteria, could be lethal to the filarial worms (in one study, tetracycline treatment of heartworm-infected dogs resulted in infertility in the female worms); Wolbachia in the adult heartworms might contribute to the pulmonary disease (and even the renal disease) seen in heartworm disease; infected dogs do develop immune responses to the bacteria and bacterial antigens have been found in several organs (lung, liver, kidney).
  • Pre-treat with Doxycycline? As yet, not enough data. However, recent paper:
  • Di positive dogs with microfilaremia: Tx with ivermectin (6ug/kg weekly) and Doxycycline
  • (10mg/kg/day from weeks 0-6, 10-12, 16-18, 22-26, and 28-34) resulted in faster
  • decrease in microfilaremia, and higher adulticide acitivity compared with ivermectin or
  • doxy alone.
  • Implications for treatment. If use doxycycline pretreatment with Immiticide, could get a more rapid adult kill off and therefore increase side effects.
  • Could initiate doxycycline at time of 2nd Immiticide dose when less adults around.
  • Prognosis:
  • Class I and II - excellent.
  • Class III - guarded with a higher risk of complications.
  • Old dogs may not require treatment, since heartworm infection may not be the life-limiting factor.
  • Adulticide treatment - delay in pregnant animals; transplacental infection (microfilaria) can occur.

    PROPHYLAXIS
  • In spite of excellent prophylactic drugs on the market, many dogs (nearly a quarter of a million in one survey of over 18,000 vet clinics) still get infected; prophylaxis should be provided for all dogs at risk.
  • In new patients starting on prophylaxis for the first time; use the antigen test as a screening test prior to starting preventive treatment (rule out possible adult infection and antigen test has a much higher predictive value than looking for microfilaria); all antigen-positive dogs should be also tested for microfilariemia as some macrolide endectocides (milbemycin) may induce a shock syndrome within 24 hours of the first dose; (if positive, consider adulticide treatment options but start prophylaxis treatment immediately).
  • Start pups on prophylaxis no later than 8 months of age.

    DRUG OPTIONS
  • Ivermectin (Heartgard®, Merial) - highly effective monthly preventive; retroactive efficacy as long as 4 months after infection when monthly administration is continued for 12 months; when combined with pyrantel pamoate (Heartgard® Plus), also controls hookworms and roundworms.
  • Milbemycin oxime (Interceptor®, Novartis); highly effective monthly preventive; also controls hookworms, roundworms, and whipworms; the preventive dosage is microfilaricidal - acute reactions may occur when given to microfilaremic dogs.
  • Moxidectin (ProHeart® tablets, Fort Dodge) monthly preventive; can give to microfilaremic dogs
  • Moxidectin (ProHeart®6 injectable, Fort Dodge); prophylactic effective for at least 6 months after injection; currently not available in the USA.
  • Selamectin (Revolution , Pfizer); monthly topical preventive; also controls fleas, ear mites, sarcoptic mange, and some tick infestations.
  • Macrocide endectocide preventives (milbemycin oxime, ivermectin, selamactin, and moxidectin) - provide retroactive efficacy of 100% for 1 month and close to 100% for 2 months (see above)
  • Diethylcarbamazine citrate (Filaribits®, Pfizer; Nemacide®, Boehringer Ingelheim) - daily administration (6.6 mg/kg) is required to ensure prophylaxis; cheaper than macrolides; need to continue dosing 2 months beyond the end of transmission season; if miss a few doses (which voids protection), administer one dose of a macrolide endectocide (ivermectin, milbemycin etc) at prophylaxis doses.
  • All of the prophylactic drugs can be administered safely to collies or collie-like breeds at the appropriate preventive dosages.

    REFERENCES
    1. Kramer L, Simon F, Tamarozzi F, et al. Is Wolbachia complicating the pathological effects of Dirofilaria immitis infections? Vet Parasitol 133:133-136, 2005.
    2. Bazzocchi C et al. Combined invermectin and doxycycline treatment has microfilaricidal and adulticidal activity against Dirofilaria immitis in experimentally infected dogs. Int J for Parasitol 38:1401-1410, 2008.
    3. http://www.heartwormsociety.org/heart.htm


    • © 2008 - Stephen C. Barr BVSc MVS PhD DACVIM - All rights reserved