Consultant on Call

Parasitology

Peer Reviewed

Canine Heartworm Infection

Wendy Mandese, DVM
Amara Estrada, DVM, DACVIM (Cardiology)
University of Florida

Profile

Definition
n Disease of the pulmonary vasculature
caused by the parasite Dirofilaria immitis
(Figure 1)

Gross photo of
Dirofilaria immitis
in the pulmonary
artery of a dog.
Courtesy Dr. Julia A. Conway

Geographic Distribution
n D immitis is found in all 50 states, with
increased prevalence in warmer climates.
Transmission
n Mosquitoes extract the L1 microfilarial
stage of D immitis from an infected dog.
o L1-L3 molting occurs within the
mosquito.
o The L3 larval stage enters the bloodstream of another dog when the
mosquito bites.
o L3-L5 (adult) molting occurs within
the dog.

Risk Factors
n Any dog that does not receive preventive
medication is at risk for heartworm
disease.
n In endemic areas, up to 45% of dogs that
do not receive preventive medication can
be expected to have heartworm disease.1
Pathophysiology
n Adult heartworms lodge in the pulmonary artery and reproduce.
n The direct endothelial contact of adult
worms induces an inflammatory response

n
n
n

(ie, arteritis) that causes endothelial

thickening.
o The degree of host immune response
directly influences the extent of the
disease process.
Blood flow obstruction (by the presence
of worms) and endothelial thickening
can lead to pulmonary hypertension and
fibrosis.
Antigenantibody complexes can cause
microvascular and glomerular damage.
Embolism of dead worm fragments and
fibrin clots can lead to hypoxemia.
Larger worm burdens can cause caval
syndrome.
o Worms back up into the right ventricle

Heartworm disease is the

most easily preventable
cause of canine pulmonary
disease.

MORE
June 2014 Clinicians Brief

83

Consultant on Call

and atrium and become entangled

in the tricuspid apparatus.
o Shear force of RBCs against the
worms creates intravascular
hemolysis, hemoglobinemia, and
hemoglobinuria.
o Volume overload because of tricuspid and/or pulmonary insufficiency and right ventricular
systolic dysfunction can lead to
signs of right-sided heart failure.
o Volume underload of the left side
of the heart can cause hypovolemia and shock.

Clinical Signs
n Many dogs with D immitis infection
have no signs, but cough, exercise
intolerance, and lethargy may be
seen.
n Caval syndrome is the most severe
form of heartworm disease.
o Patients may present with pale
mucous membranes, pronounced
right-sided heart murmur, shock,
hemoglobinuria, hemoglobinemia,
and jugular pulsations.
o Sudden death may occur.

Treatment Schedule

84

Day 0 (diagnosis)

E
 xecute staging (examination, laboratory
studies, thoracic radiography).

Begin doxycycline at 10 mg/kg q12h for 3

weeks.

Begin oral macrocyclic lactone once monthly.

Recommend moderate rest and/or corticosteroid if signs are present.

Day 60

Administer diphenhydramine at 2.2 mg/kg

PO or parenterally.

Administer melarsomine at 2.5 mg/kg via

deep lumbar epaxial injection.

Administer NSAID or corticosteroids as

indicated.

Enforce strict cage rest.

Day 90

A
 dminister diphenhydramine at 2.2 mg/kg
PO or parenterally.

Administer melarsomine at 2.5 mg/kg via deep

lumbar epaxial injection twice 24 hours apart.

Administer NSAIDs or corticosteroids as

indicated.

Enforce strict cage rest.

Days 120-150

Begin gradual return to activity.

Continue monthly macrocyclic lactone.

On day 120, test for microfilariae, and, if

positive, retest in 4 weeks

Day 240

Perform antigen testing to confirm elimination of adult worms.

cliniciansbrief.com June 2014

Diagnosis
Laboratory Findings
n Serum chemistry panel is often
within reference ranges.
o In more severe cases, increased
liver enzyme activity may be present because of hepatic congestion
from right-sided heart failure.
n Caval syndrome
o Azotemia
o Hemoglobinemia
o Hemoglobinuria
n CBC may show eosinophilia.

Imaging
Radiography
n Enlarged right side of heart (reverse-D
appearance on VD view)
n Prominent main pulmonary artery
bulge
n Blunted, tortuous vessels are noted
most often in the caudal lung lobes.
o Dorsoventral projection is best for
evaluation of pulmonary
vasculature.
Echocardiography
n In general, abnormal findings will
not be noted with uncomplicated
heartworm disease.
n Right ventricular dilation or hypertrophy and tricuspid or pulmonic
valve insufficiency may be present
with more severe disease.
n Worms may be visualized in the pulmonary arteries, but quantification
of worm burden is difficult.
n Echocardiography results may provide good confirmation for caval
syndrome.
o Worms can be visualized in the
right atrium/right ventricle.

Additional Diagnostics
n Antibody testing is not often
performed.
n Antigen testing is preferred.
o Tests for the presence of mature
adult female worms; heartworm
larvae must have been present 6
months for a positive test result.
o The test is very sensitive and
nearly 100% specific.
n Microfilariae testing is confirmatory,
but differentiation from microfilariae
of Acanthocheilonema reconditum
(formerly Dipetalonema reconditum)
is important.
o Confirms that the dog is contagious via mosquito vector
o Negative results may occur if a dog
receives macrocyclic lactone preventive medication.
o Helps predict protocol for possible
adverse reaction to treatment

Treatment
n

To determine severity of disease and

help predict therapy response and
potential posttreatment complications, pretreatment evaluation (ie,
staging) should be performed.
o Thoracic radiography (2 lateral
views and 1 DV view)
o CBC and serum chemistry panel
to evaluate for underlying systemic
disease and ensure patient is
healthy enough for adulticide
therapy
o Urinalysis to evaluate for proteinuria and bilirubinuria
o Confirmatory heartworm test (eg,
microfilariae or repeat antigen
testing)
o Thorough physical examination
o History, including time patient
was without heartworm prevention, prevalence, and severity of
clinical signs at home

Heartworm at a Glance: Cats vs Dogs

Cats

Dogs

1%10% of third-stage infective

larvae (L3) survive

75% of third-stage infective L3

survive

Low maturation rate

High maturation rate

Microfilariae uncommon

Microfilariae common

Worms survive 24 years

Worms survive 5 years

15 worms present

Many worms present

Smaller adult worms

Larger adult worms

Adulticide Therapy
n Melarsomine dihydrochloride
(Immiticide, merial.com) is approved
for use by the FDA.
n Treatment with macrocyclic lactone
immediately following diagnosis may
decrease or eliminate microfilariae
and eliminate L3 and early L4 larval
stages.2
o These stages are not proven to be
eliminated by melarsomine
dihydrochloride.
Adjunct Therapy
n Doxycycline is used to eliminate
Wolbachia pipientis, a symbiotic
bacterium harbored by D immitis.3
o Doxycycline is often difficult
and/or expensive to obtain; minocycline is a common replacement.
o This therapy weakens adult worms
and makes them less fertile.
o Doxycycline may improve pulmonary pathology, as Wolbachia spp
have been shown to contribute to
pulmonary inflammation.3
n Corticosteroids are often recommended if the dog shows clinical
signs (eg, coughing).
n Diphenhydramine can be

administered before melarsomine

administration.

Alternative Therapy
n A slow-kill method of placing a dog
on macrocyclic lactone and/or doxycycline and waiting for worms to die
is not recommended.1
o The potential exists for irreversible
heart damage while waiting up to
5 years for all worms to die.
o R isk for thromboembolism exists
until all worms have died and are
absorbed.
o It selects for macrocyclic lactone
resistance.
Client Education
n Strict cage rest throughout the duration of treatment is crucial to prevent
life-threatening pulmonary embolism
caused by dead worms.
n Gradual return to activity can take
place 68 weeks after final administration of melarsomine.
MORE

June 2014 Clinicians Brief

85

Consultant on Call

Medications
Melarsomine
n 2.5 mg/kg via deep lumbar epaxial IM
injection
o After 1 month, 2 additional injections should be administered 24
hours apart.
n Adverse effects include pain at
injection site, lethargy, and allergic
reaction.

o If the patient is not receiving corti-

costeroids, discomfort can be alleviated with NSAIDs for several

days following injection.

Doxycycline
n 10 mg/kg q12h for 3 weeks starting
at time of diagnosis
n Minocycline can be used at the same
dose if doxycycline is unavailable.

Heartworm Prevention
Options for Dogs

86

Monthly Oral

Ivermectin

Heartgard (heartgard.com)

Heartgard Plus (heartgard.com)

Iverhart Max (virbacvet.com)

Iverhart Plus (virbacvet.com)

Pet Trust Plus (pettrust.com)

Tri-Heart Plus (triheartplus.com)

Milbemycin oxime

Interceptor (interceptor.novartis.us)

Sentinel (sentinelpet.com)

Sentinel Spectrum (ah.novartis.com)

Trifexis (trifexis.com)

Monthly Topical

Selamectin

Revolution (zoetis.com)

Moxidectin

Advantage Multi (bayerdvm.com)

6-Month Injectable

Moxidectin

ProHeart 6 (proheart6.com)

cliniciansbrief.com June 2014

Macrocyclic Lactone
n Preventive medications can be started
at diagnosis and continued for life.
Prednisolone
n Often used to decrease pulmonary
inflammation in patients with clinical signs
n 12 mg/kg q12h
Diphenhydramine
n Often used to help prevent or
decrease allergic reactions associated
with adulticide therapy
n Should be used before administration
of melarsomine therapy
o 2.2 mg/kg PO or parenterally 12
hours before melarsomine
injection

Follow-up

All adult heartworms should be eliminated within 12 months of final

melarsomine injection.
o Six months after completion of
melarsomine therapy, results of
antigen testing should be negative.
n If results are positive, adult
infection is most likely still
present, and adulticide therapy
should be restarted.
n Testing may also be performed
after 6 additional months to
determine whether all worms
have died.

In General

Prognosis
n Prognosis is good to excellent with
treatment.
o If untreated, prognosis is variable.

Relative Cost
n Depending on size of dog and relative
cost for melarsomine therapy and

UNLEASH

associated medication: $$$$$

Heartworm disease staging: $$$$$
n Relative cost for preventive medication, yearly: $$
n

your potential

Cost Key
$ = up to $100
$$ = $101$250
$$$ = $251$500
$$$$ = $501$1000
$$$$$ = more than $1000

Prevention
n Heartworm disease is preventable with administration of
macrocyclic lactones (see Heartworm Prevention
Options for Dogs).
o Monthly oral
n Ivermectin
n Milbemycin oxime
o Monthly topical
n Selamectin
n Moxidectin
o 6-Month injectable
n Moxidectin
n Prevention should be started at 8 weeks of age and continued for life.
o These medications also have efficacy against some
internal and external parasites. ncb
See Aids & Resources, back page, for references & suggested
reading.

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For More
See the companion article, Feline Heartworm Infection,
on page 69 of the April 2014 issue of Clinicians Brief or
online at cliniciansbrief.com/feline-heartworminfection.

Help Your Patients. Help Your Bottom Line.

TM

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T E C H N O L O G I E S

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www.celasers.com/veterinary

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