Prevention, Diagnosis, and Management of - Heartworm (Dirofilaria immitis) - Revised 2018 - American Heartworm Society
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Current Canine Guidelines for the
Prevention, Diagnosis,
and Management of
Heartworm (Dirofilaria immitis)
Infection in Dogs
Revised 2018
Thank You to Our Generous Sponsors: © 2018 American Heartworm Society | PO Box 8266 | Wilmington, DE 19803-8266 | E-mail: info@heartwormsociety.org
Current Canine Guidelines for the Prevention, Diagnosis, and Management of Heartworm (Dirofilaria immitis) Infection in Dogs (Revised 2018) CONTENTS Click on the links below to navigate to each section. Preamble......................................................................................................................................................................3 HIGHLIGHTS.................................................................................................................................................................3 EPIDEMIOLOGY...........................................................................................................................................................4 Key Points Minimizing Heartworm Transmission in Relocated Dogs (box) Figure 1. Urban heat island profile. BIOLOGY AND LIFE CYCLE.........................................................................................................................................7 Key Points Figure 2. The heartworm life cycle. Figure 3. Images of a feeding mosquito. HEARTWORM PREVENTION......................................................................................................................................9 Key Points Macrocyclic Lactones Reports of Lack of Efficacy Vector Control Measures to Reduce Heartworm Transmission (box) Use of Repellents and Ectoparasiticides Multimodal Risk Management PRIMARY DIAGNOSTIC SCREENING.......................................................................................................................14 Key Points Test Timing for Optimal Results Microfilaria and Antigen Testing Antigen Tests When Should Heat Treatment of Samples Be Considered? (box) Microfilaria Tests How to Perform the Knott Test (box) Testing Considerations Following Noncompliance and When Changing Products Figure 4. Acanthocheilonema reconditum and Dirofilaria immitis. Figure 5. The testing protocol following known noncompliance. 2018 Canine Heartworm Guidelines 1
Other Diagnostic Aids ..............................................................................................................................................17
Radiography
Echocardiography
Figure 6. Moderate heartworm disease (radiographs).
Figure 7. Severe heartworm disease (radiographs).
Figure 8. Echocardiogram.
Diagnostics For Pre-Adulticide Evaluation In An Infected Dog.............................................................................18
PRINCIPLES OF TREATMENT...................................................................................................................................20
Key Points
Table 1. Summary of Clinical Signs of Canine Heartworm Disease
Figure 9. Image of the main trunk of the right pulmonary artery.
Figure 10. Image of a dead adult heartworm lodged in a distal pulmonary artery.
Adulticide Therapy....................................................................................................................................................21
Melarsomine Dihydrochloride
Pulmonary Thromboembolism
Adjunct Therapy........................................................................................................................................................22
Steroids
NSAIDs and Aspirin
Doxycycline
Macrocyclic Lactones
Macrocyclic Lactones/Doxycycline
Figure 11. Pulmonary pathology associated with death of heartworms.
AHS-Recommended Protocol...................................................................................................................................24
Table 2. AHS-Recommended Protocol
Elimination of Microfilariae.......................................................................................................................................26
Surgical Extraction of Adult Heartworms................................................................................................................26
Caval Syndrome (Dirofilarial Hemoglobinuria)
Pulmonary Arterial Infections
Figure 12. Photographic Image of a heart from a dog suffering from caval syndrome.
Figure 13. Echocardiogram image.
Figure 14. Surgical removal of worms.
Alternative Therapies.................................................................................................................................................28
Long-term Macrocyclic Lactone Administration
Herbal Therapies
Compounded Medications........................................................................................................................................28
Confirmation of Adulticide Efficacy..........................................................................................................................28
Elective Surgeries in Dogs with Heartworms..........................................................................................................29
REFERENCES..............................................................................................................................................................29
2 American Heartworm SocietyPrepared by Dr. C. Thomas Nelson, Dr. John
W. McCall, Dr. Stephen Jones, and Dr. Andrew HIGHLIGHTS
Moorhead, and approved by the Executive Board of • Diagnostics
the American Heartworm Society: Officers: Dr. Chris AHS recommends annual antigen and
Rehm, President; Dr. Stephen Jones, Past President; microfilaria testing. (As the interpretation
Dr. Tony Rumschlag, Vice President; Dr. Bianca of diagnostics has become more complex,
Zaffarano, Secretary-Treasurer; Dr. Patricia Payne, please see the “Microfilaria and Antigen
Editor; Dr. Doug Carithers, Symposium Program Testing” section for more complete
Chair; Board Members: Dr. Elizabeth Clyde, Dr. Brian information.)
DiGangi, Dr. Chris Duke, Dr. Andrew Moorhead, Dr.
Charles Thomas Nelson, and Dr. Jennifer Rizzo; and • Prevention
Ex Officio Members: Dr. Marisa Ames, Symposium AHS recommends year-round
Program Co-Chair; Dr. John W. McCall, Associate administration of preventive drugs
Editor; Dr. Chris Adolph and Dr. Edward Wakem. approved by the US Food and Drug
Administration (FDA) to prevent heartworm
References by Christopher Evans, MS, Research infection and enhance compliance, the
Professional II, Department of Infectious Diseases, latter being particularly important in
College of Veterinary Medicine, University of light of the documented presence of
Georgia. resistant subpopulations. Application
Preamble of an Environmental Protection Agency
(EPA) registered mosquito repellent/
These recommendations supersede previous ectoparasiticide has been shown to
editions and are based on the information increase the overall efficacy of a heartworm
presented at the 2016 Triennial Symposium of prevention program in laboratory
the American Heartworm Society (AHS), new studies involving known resistant
research, and additional clinical experience. The heartworm isolates by providing control
recommendations for the prevention, diagnosis, of the arthropod vector of heartworm. In
and management of heartworm infection in cats addition, AHS recommends reduction of
are contained in a companion feline document exposure to mosquitoes through standard
(available on the AHS website). environmental control of mosquitoes and
their breeding environments, and when
possible, reducing outdoor exposure during
key mosquito feeding periods.
• Adulticide Therapy
AHS recommends use of doxycycline and a
macrocyclic lactone prior to the three-dose
regimen of melarsomine (one injection of
2.5 mg/kg body weight followed at least
one month later by two injections of the
same dose 24 hours apart) for treatment of
heartworm disease in both symptomatic
and asymptomatic dogs. Any method
utilizing only macrocyclic lactones as a
slow-kill adulticide is not recommended.
2018 Canine Heartworm Guidelines 3EPIDEMIOLOGY
Heartworm infection in dogs has been diagnosed
around the globe. In the United States, its territories,
and protectorates, heartworm is considered at
least regionally endemic in each of the contiguous
48 states, Hawaii, Puerto Rico, US Virgin Islands,
and Guam (Bowman et al, 2009; Kozek et al, 1995;
Ludlam et al, 1970). Heartworm transmission has
not been documented in Alaska; however, there are
regions in central Alaska that have mosquito vectors
KEY POINTS: and climate conditions to support the transmission
EPIDEMIOLOGY of heartworms for brief periods (Darsie and Ward,
• Heartworm infection has been diagnosed 2005; Slocombe et al, 1995; Terrell, 1998). Thus,
in all 50 states and around the globe. the introduction of microfilaremic dogs or wild
• Environmental and climatic changes, canids could set up a nidus of infection for local
both natural and those created by transmission of heartworm in this state (see box on
humans, relocation of microfilaremic page 5 for more on the role of transport of infected
dogs, and expansion of the territories of dogs). Such relocation of microfilaremic dogs
microfilaremic wild canids continue to be and expansion of the territories of microfilaremic
important factors contributing to further wild canids in other areas of the United States
spread of the parasite. continue to be important factors contributing
to further dissemination of the parasite, as the
• A pivotal prerequisite for heartworm
ubiquitous presence of one or more species of
transmission is a climate that provides
vector-competent mosquitoes makes transmission
adequate temperature and humidity to
possible wherever a reservoir of infection and
support a viable mosquito population, and
favorable climatic conditions co-exist. Change in
can also sustain sufficient heat to allow
any of these factors can have a significant effect on
maturation of ingested microfilariae into
the transmission potential in a specific geographic
infective, third-stage larvae (L3) within the
location.
intermediate host.
• The length of the heartworm transmission Environmental and climatic changes, both
season in the temperate latitudes also natural and those created by humans, and animal
depends on factors such as the influence movement have increased heartworm infection
of microclimates, unique biological habits potential. Commercial and residential real estate
and adaptations of the mosquito vector, development of non-endemic areas and areas of
variations in time of larval development, low incidence has led to the resultant spread and
mosquito life expectancy, and temperature increased prevalence of heartworms by altering
fluctuations. drainage of undeveloped land and by providing
water sources in new urban home sites. In the
• Heartworm transmission does decrease
western United States, irrigation and planting of
in winter months, but the presence
trees has expanded the habitat for Aedes sierrensis
of microenvironments in urban areas
(western treehole mosquito), the primary vector for
suggests that the risk of heartworm
transmission of heartworms in those states (Scoles
transmission never reaches zero.
et al, 1993, 1995).
Aedes albopictus (Asian tiger mosquito), which was
introduced into the Port of Houston in 1985, has
now spread northward and eastward, approaching
Canada, and isolated populations have been
identified in areas in the western states. This urban-
dwelling mosquito is able to reproduce in small
containers, such as flowerpots (Benedict et al, 2007).
4 American Heartworm SocietyFigure 1. Urban heat island profile showing the elevation in urban air temperature compared
with rural air temperature. (Image courtesy of Heat Island Group, Lawrence Berkeley National
Laboratory).
Urban sprawl has led to the formation of The length of the heartworm transmission season in
“heat islands,” as buildings and parking lots the temperate latitudes is critically dependent on the
retain heat during the day (Figure 1), creating accumulation of sufficient heat to incubate larvae to
microenvironments with potential to support the the infective stage in the mosquito (Knight and Lok,
development of heartworm larvae in mosquito 1998 ; Lok and Knight, 1998). The peak months for
vectors during colder months, thereby lengthening heartworm transmission in the Northern Hemisphere
the transmission season (Morchón et al, 2012, are typically July and August. Models predict that
Nelson, 2016). heartworm transmission in the continental United
States is limited to 6 months or less above the 37th
As mosquito vectors expand their territory and parallel at approximately the Virginia–North Carolina
new non-native vectors are introduced (e.g., Aedes
notoscriptus introduction to California; Peterson
and Campbell, 2015) the number of animals infected Minimizing Heartworm Transmission in
will continue to increase. A pivotal prerequisite for Relocated Dogs
heartworm transmission is a climate that provides
Transporting and relocating dogs is an
adequate temperature and humidity to support a
increasingly common practice. Whether the
viable mosquito population, and can also sustain
situation is an owned pet accompanying
sufficient heat to allow maturation of ingested
emigrating or traveling caretakers, the relocation
microfilariae into the infective, third-stage larvae
of homeless animals for adoption, or the
(L3) within this intermediate host. It has been
movement of dogs for competition, exhibition,
shown in three mosquito species that maturation
research or sale, this process carries the risk of
of larvae ceases at temperatures below 57˚F (14˚C)
spreading infectious diseases. This includes the
(Christensen and Hollander, 1978; Fortin and
transmission of Dirofilaria immitis when infected
Slocombe, 1981). Heartworm transmission does
dogs are microfilaremic.
decrease in winter months, but the presence of
microenvironments in urban areas suggests that The American Heartworm Society, in
the risk of heartworm transmission never reaches collaboration with the Association of Shelter
zero (Nelson, 2016). Furthermore, some species of Veterinarians, has developed a protocol to help
mosquitoes overwinter as adults. While heartworm minimize the risk of heartworm transmission
larval development in these mosquitoes may cease associated with transportation and relocation
in cool temperatures, development quickly resumes of dogs. The document, which includes an
with subsequent warming (Christensen and algorithm outlining testing and treatment
Hollander, 1978; Ernst and Slocombe, 1983). recommendations, is available on the AHS
website.
2018 Canine Heartworm Guidelines 5state line (Guerrero et al, 2004). Anopheles quadrimaculatus surviving for 4 to 5
months (Hinman and Hurlbut, 1940), so the predictive
While model-based predictions of transmission risk maps likely reflect a shorter transmission season
using climatic data are academically appealing, they than actually exists in some areas.
typically fail to consider several potentially important
factors, such as influence of microclimate, unique Survey studies of trapped mosquitoes randomly
biological habits and adaptations of the mosquito collected at various locations have demonstrated
vector, variations in time of larval development, heartworm infection rates in mosquitoes ranging
mosquito life expectancy, and temperature from 2% to 19.4% in known endemic areas. When
fluctuations. Predictive risk maps assume that mosquito sampling was restricted to kennel
mosquito vectors live for only one month; however, structures where known positive dogs were being
several significant mosquito vectors live and breed housed, the infection rates of the mosquitoes in
for much longer periods, including: these restricted samplings resulted in rates of 30%
• Aedes albopictus (3 months) (Löwenberg-Neto and adjacent to and 74% inside the facilities (McKay
Navarro-Silva, 2004), et al, 2013). Based upon these data, it is important
to protect pets from mosquito exposure (see
• Aedes sticticus (3 months) (Gjullin et al, 1950), Vector Control starting on page 11) in addition to
• Ochlerotatus (formerly Aedes) trivittatus (2 months) administering year-round heartworm preventive.
(Christensen and Rowley, 1978),
Once a reservoir of microfilaremic domestic and
• Aedes vexans (2 months) (Gjullin et al, 1950), and wild canids is established beyond the reach of
• Ochlerotatus (formerly Aedes) canadensis (several veterinary care, the ubiquitous presence of one
months) (Pratt and Moore, 1960). or more species of vector-competent mosquitoes
makes transmission possible and eradication
There are also documented cases of hibernating improbable.
Heartworm-infected Dog
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American Heartworm Society
Wilmington, DE
Figure 2. The heartworm life cycle.
6 American Heartworm SocietyBIOLOGY AND LIFE CYCLE
The life cycle of Dirofilaria immitis is relatively
long (usually 7 to 9 months) compared with most
parasitic nematodes (Kotani and Powers, 1982)
(Figure 2). This protracted life cycle requires
a reservoir of infection, a vector capable of
transmitting infection, and a susceptible host.
The domestic dog and some wild canids are the KEY POINTS:
normal definitive hosts for heartworms and are BIOLOGY AND LIFE CYCLE
inclined to develop high microfilaria counts, thus • The relatively long life cycle of D. immitis
allowing them to serve as the main reservoir of (7 to 9 months) requires a reservoir of
infection. Less suitable hosts, such as cats and infection, a vector capable of transmitting
ferrets, occasionally have low-level, transient infection, and a susceptible host.
microfilaremia and theoretically may serve as a
• The mosquito, the required vector for
limited source of infection for mosquitoes during
transmission of D. immitis, becomes
their short periods of microfilaremia (McCall et al,
infected as she takes a blood meal from a
2008b).
microfilaremic host.
The mosquito, the required vector for transmission • The D. immitis microfilariae mature within
of D. immitis, becomes infected as she takes the malpighian tubules of the mosquito,
a blood meal from a microfilaremic host. It is developing into larval stage 1 (L1) , then
important to note that microfilariae cannot develop molting into larval stage 2 (L2), and finally
into adult heartworms without first developing molting into the infective third-stage larvae
into larval stage 1 (L1) in the malpighian tubules (L3), which are transmitted to the dog when
of the mosquito, then molting into larval stage bitten by the mosquito.
2 (L2), and finally molting into third-stage larvae
• Once the infective L3 enter the dog’s body,
(L3) (Taylor, 1960). The third-stage larvae, the
they molt into fourth-stage larvae (L4).
infective stage, then migrate via the body cavity to
the head and mouthparts of the mosquito, where • A final molt into juvenile/immature adults
they are positioned for transmission. The time occurs between days 50 and 70, while they
required for the development of microfilariae to the are migrating through the body; and they
infective stage within the mosquito is temperature eventually reach the smallest pulmonary
dependent. At 27°C (80.6°F) and 80% relative arteries as early as day 67 after transmission.
humidity, development takes about 10 to 14 days; • Sexual maturity occurs about day 120
with cooler temperatures maturation takes longer post infection with dogs developing
(Kartman, 1953; Slocombe et al, 1989). patent infections (i.e., having circulating
microfilariae) as early as 6 months but
Once in the mouth parts, transmission of the
usually by 7 to 9 months after infection.
infective L3 is accomplished when an infected
mosquito again takes a blood meal. As the • A clear understanding of heartworm
mosquito’s stylet penetrates an animal’s skin, the transmission, development, prepatent
labium (lower lip) is forced to fold back at a dramatic period, and the susceptibility of the different
angle (Figure 3). When this occurs, the tip of the life stages of the parasite to available
labium ruptures expelling a droplet of hemolymph pharmaceutical drugs is critical to the
containing infective larvae onto the surface of the successful management of infected dogs.
host’s skin (McGreevy et al, 1974).
Immediately after the blood meal, these sexually
differentiated larvae enter the animal’s body via
the puncture wound made by the mosquito. As
early as day 3, and by days 9 to 12, the L3 molt
into fourth-stage larvae (L4) where they appear to
travel between subcutaneous tissues and muscle
2018 Canine Heartworm Guidelines 7Figure 3. Left, Image of a feeding mosquito indicating how deeply the stylet
(S) penetrates the skin and the dramatic folding (black arrow) of the labium
(L). Right, Magnified image of a feeding mosquito indicating the release of
a hemolymph pool (white arrows) containing infective heartworm larvae
(L3). Photographic images courtesy of Stephen Jones, DVM.
fibers during migration within the infected animal. heartworms ultimately grow tenfold to reach 10 to
A final molt into juvenile/immature adults occurs 12 inches in length. Sexual maturity occurs about
between days 50 and 70, while they migrate through day 120 post infection with dogs developing patent
the body, eventually enter the circulatory system, infections (i.e., having circulating microfilariae) as
and are transported toward the heart and lungs early as 6 months but usually by 7 to 9 months after
(Kotani and Powers, 1982; Kume and Itagaki, 1955; infection (Kotani and Powers, 1982; Orihel, 1961).
Lichtenfels et al, 1985). These immature adults reach
the pulmonary vasculature as early as day 67 and all When juvenile heartworms first arrive in the
have arrived by days 90 to 120. lungs the flow of blood forces them into the small
pulmonary arteries (Rawlings, 1980). As the worms
At the time of arrival in the pulmonary arteries, increase in size, they progressively occupy larger
these immature heartworms measure between 1 and larger arteries until they become fully mature.
and 1.5 inches in length. As they mature, female The eventual location of the mature adult worm
appears to depend mainly on the size of the dog
and the worm burden. A medium-sized dog (e.g.,
Beagle) with a low worm burden (≤5) usually
A clear understanding of has worms mainly in the lobar arteries and main
pulmonary artery. As the worm burden increases,
heartworm transmission,
worms also can be located in the right ventricle.
development, prepatent Dogs with more than 40 worms are more likely
period, and the susceptibility to develop caval syndrome, where the worms
maneuver into the right ventricle, right atrium, and
of the different life stages
the vena cava, thus interfering with valvular function
of the parasite to available and blood flow and producing hemolysis, liver and
pharmaceutical drugs is critical kidney dysfunction, and heart failure (Atwell and
Buoro, 1988; Ishihara et al, 1978; Jackson, 1975).
to be able to effectively select
the most appropriate adulticidal A clear understanding of heartworm transmission,
development, prepatent period, and the
treatment option and treatment
susceptibility of the different life stages of the
time, and to convey realistic parasite to available pharmaceutical drugs is critical
expectations to the client for the to be able to effectively select the most appropriate
adulticidal treatment option and treatment time, and
outcome of therapy.
to convey realistic expectations to the client for the
outcome of therapy.
8 American Heartworm SocietyHEARTWORM PREVENTION
The prescription and administration of heartworm
preventive medication requires authorization by
a licensed veterinarian having a valid relationship
with the client and patient. To establish this
relationship, heartworm prevention must be
discussed with the client. If records of past
treatment and testing do not exist, it is necessary KEY POINTS:
to test the patient before dispensing or prescribing HEARTWORM PREVENTION
preventive. Options for effective preventive include • The FDA-approved heartworm preventives
several drugs administered monthly either orally or currently marketed (ivermectin, milbemycin
topically, or parenterally at 6-month intervals. oxime, moxidectin, and selamectin) belong
to the macrocyclic lactone (ML) class of
Heartworm disease is preventable despite the
drugs.
dog’s inherently high susceptibility. Because all
dogs living in heartworm-endemic areas are at risk, • Macrocyclic lactones, when given according
preventive medications are a high priority. Puppies to label instructions, are highly effective and
should be started on prevention consisting of a are among the safest medications used in
macrocyclic lactone as early as possible, no later veterinary medicine.
than 8 weeks of age. In highly endemic regions the • It is possible for an animal to become
addition of a mosquito repellent/ectoparasiticide infected because of skipped or delayed
is warranted. Puppies started on a heartworm administration of just one preventive dose,
preventive after 8 weeks of age should be tested particularly in highly endemic areas.
6 months after the initial dose and annually
• While the vast majority of reported
thereafter. Before initiating a preventive regimen
claims of lack of efficacy of macrocyclic
in older dogs (7 months of age or older), antigen
lactones can be linked to poor compliance,
and microfilaria testing should be performed (see
isolated pockets of resistant heartworm
PRIMARY DIAGNOSTIC SCREENING). This practice
subpopulations have been documented,
avoids delays in detecting subclinical infections and
mainly in the southeastern US.
the potential confusion concerning effectiveness of
the prevention program if a pre-existing infection • AHS and the FDA recommend year-round
becomes evident after beginning preventive (e.g., administration of FDA-approved preventive
preventive initiated during the prepatent period). drugs to prevent heartworm infection and
enhance compliance.
Even though continuous, year-round transmission
• Application of an EPA-registered mosquito
may not occur throughout the country, the
repellent/ectoparasiticide has been shown to
administration of broad-spectrum preventive
increase the overall efficacy of a heartworm
products with endoparasitic and/or ectoparasitic
prevention program by controlling the
activity for 12 months each year likely enhances
mosquito vector in laboratory studies.
compliance and may assist in preventing other
pathogenic and/or zoonotic parasitic infections. • In addition, reduction of exposure to
mosquitoes through standard environmental
Macrocyclic Lactones control of mosquitoes and their breeding
environments, and when possible, reducing
The FDA-approved heartworm preventives outdoor exposure during key mosquito
currently marketed (ivermectin, milbemycin feeding periods is recommended.
oxime, moxidectin, and selamectin) belong to the
macrocyclic lactone (ML) class of drugs and likely
work in concert with the dog’s immune system
to kill susceptible larval stages (Campbell 1989,
Moreno et al 2010, Vatta et al, 2014). These drugs
affect microfilariae, third- and fourth-stage larvae,
and in some instances of continuous use, juvenile
2018 Canine Heartworm Guidelines 9and adult heartworms (McCall et al, 2001a, 2008b). or overdosed because of human error in dosage
Because their filaricidal effect on precardiac calculation. This practice is an unjustified extra-
(migrating) larvae can be achieved by brief pulsing label drug use and is discouraged. The standard
at very low doses (e.g., monthly) or continuous preventive dosages of all macrocyclic lactones have
release of small amounts over long periods (e.g., been shown to be safe in all breeds.
six months), they have excellent therapeutic/toxic
ratios. Macrocyclic lactones, when given according Macrocyclic lactones can be administered by three
to label instructions, are highly effective and are routes:
among the safest medications used in veterinary • Oral administration: Ivermectin and milbemycin
medicine. oxime are available for monthly oral
All orally and topically administered macrocyclic administration. Some formulations are flavored
lactone preventive products are labeled for a and chewable to increase patient acceptance and
30-day dosing interval. Beyond this interval facilitate administration. Dose units are packaged
efficacy against late fourth-stage larvae declines for dogs within prescribed weight ranges. To
be maximally effective, heartworm prophylaxis
and is unpredictable (Paul et al, 1986). Juvenile
should be given year-round, but if seasonal
worms, which can be found as early as 52 days
treatment is chosen, administration should begin
post infection, are even less susceptible to the
at least one month prior to the anticipated start of
effects of preventives. As worms age, they require
heartworm transmission and, depending on the
progressively longer-term administration to achieve
product used, may need to be continued for up
a high level of protection (McCall, 2005; McCall
to 6 months after transmission typically ceases to
et al, 2001). Therefore, continuous, year-round
meet label requirements for some products (see
administration of heartworm preventive is a partial
section on Lack of Efficacy).
safeguard in the event of inadvertent delay or
omission of regularly scheduled doses. • Topical administration: Moxidectin and selamectin
are available as topically applied liquid
formulations. The parameters for treatment with
Macrocyclic lactones, when topical products are the same as for monthly oral
given according to label preventive.
instructions, are highly effective • Parenteral administration: A single dose of the
and are among the safest slow-release (SR) formulation of subcutaneously
injected moxidectin-impregnated lipid
medications used in veterinary microspheres provides continuous protection for 6
medicine. months, with the potential to enhance compliance.
Administration every 6 months is necessary for
maximal protection.
Reports of Lack of Efficacy
Some Collies and other P glycoprotein–deficient Lack of efficacy (LOE) of a heartworm preventive
dogs that have the MDR 1 mutation are unusually product is considered by the FDA’s Center for
sensitive to a variety of commonly used Veterinary Medicine (CVM) to be a treated dog
veterinary drugs, including some antidepressants, testing positive for heartworm regardless of
antimicrobial agents, opioids, immunosuppressants, appropriateness of dosage or administration
and cardiac drugs (Mealey, 2008). (For more consistency. Possible reasons for reports of LOE
information on drugs that cause problems in dogs include:
with the MDR 1 mutation visit http://vcpl.vetmed.
wsu.edu/problem-drugs.) The macrocyclic lactones • Failure to administer sufficient preventive,
are also included in this list with toxicities being • Failure to administer the preventive at the
reported with overdosing or in combination with proper time,
other P-glycoprotein–inhibiting drugs (Pulliam et
• Failure of a dog to retain a dose and failure of
al, 1985). These intoxications have occurred most
expected absorption of the active ingredient,
often when concentrated livestock preparations of
macrocyclic lactones are either accidentally ingested • Biological variation between hosts in drug
10 American Heartworm Societymetabolism and immune response, and in preventing heartworm infection and efforts need
parasite susceptibility to the drug. to be intensified to increase the number of dogs
receiving preventive and to increase the number
Thus, the exact cause of a specific reported LOE can of doses administered per year. Reminder systems
be difficult or impossible to determine. should be implemented to assist pet owners in
Fortunately, most LOE claims can be explained purchasing and administering products in a timely
by compliance failure, either between the clinic manner.
and the client or the client and the pet, rather It is now generally accepted that isolated instances
than product failure. It is possible for an animal to of resistant heartworms have been identified.
become infected because of skipped or delayed The extent, the degree of spread, and the reasons
administration of just one preventive dose, for resistance are not well understood and are
particularly in highly endemic areas. Such areas controversial. Although an algorithm utilizing
typically have warm temperatures most of the year, the microfilarial suppression test (MFST) to help
an abundance of standing water, and substantial clinicians evaluate cases of suspected resistance
mosquito populations. These endemic areas also to macrocyclic lactones was recently developed
have large populations of infected dogs and wild (Moorhead et al, 2017), no definitive test for
canids providing a reservoir of infection. resistance exists, making determination of its
Research is ongoing to determine the reasons for distribution difficult. The data suggest that owner
LOE. Every new study adds to our knowledge base compliance is the biggest factor in the “failure” of
and increases our understanding but also produces preventives (Atkins et al, 2014). There is general
new questions. The complex biology of the parasite, agreement that resistance to experimental infections
the effect of changing environmental conditions that is concerning, and that the products now available
affect vector populations, the dynamics of host (wild are highly effective and should continue to be used
and domestic) populations, and even the dynamics as the manufacturers suggest.
of human interactions with pets are also relevant.
In the face of the many variable factors, it is critical
Vector Control
that all members of the veterinary practice ensure Heartworm disease has the greatest morbidity and
that clients understand the risk and implications mortality of any vector-borne disease affecting
of heartworm infection in their area, and that they dogs in the United States, and despite the excellent
are providing appropriate year-round heartworm products available to prevent heartworm disease
prevention for their pets. The macrocyclic lactones in dogs, the range and number of cases grows
continue to be the only FDA-approved option for annually. Because the mosquito is an obligate
intermediate host and vector for heartworms, the
opportunity to interrupt the chain of transmission
at the level of the vector should not be ignored
It is possible for an animal by the pet owner, the veterinarian, or the local
municipalities responsible for environmental health-
to become infected because mosquito abatement. A multimodal approach to
of skipped or delayed address both heartworm transmission and infection
administration of just one needs to be considered as an important opportunity
to improve outcomes for both individual dogs and
preventive dose, particularly the population at large. There are many examples
in highly endemic areas. Such both in veterinary and human medicine where
areas typically have warm individual and community based multimodal
approaches to vector-borne disease control are
temperatures most of the year, strongly advocated, if not the standard of care.
an abundance of standing Examples are Lyme borreliosis in dogs and malaria
water, and substantial mosquito in humans.
populations. Several tactical approaches can be employed to
support the overall strategy of vector control.
Vector biology has been addressed elsewhere
2018 Canine Heartworm Guidelines 11in these guidelines. The first community-based laying, and ultimately reducing the local mosquito
approach should be elimination of mosquito population with further reduction in heartworm
larval habitats like standing water sources transmission in the area.
wherever possible or treatment of these habitats
with chemical and biological tools such as, but While repellents and ectoparasiticides alone or
not limited to, insect growth regulators, Bacillus together are helpful, they are not completely
species, and mosquitofish. Local application of effective as monotherapy for heartworm prevention
insecticidal sprays and fogs and deployment of in highly endemic areas. In a recent study using a
adult mosquito traps are other approaches. Low repellent-ectoparasiticide along with a macrocyclic
winds greatly disturb internally directed flight lactone, however, dogs challenged with mosquitoes
patterns of mosquitoes, and fan-generated wind carrying a highly ML resistant strain of heartworm
has been shown to dilute attractants like carbon were 100% protected from infection (McCall et al,
dioxide and is a practical approach to protecting 2017b). Thus, a macrocyclic lactone preventive,
people and pets in back yard settings (Hoffman et concurrent with the use of a topical mosquito
al, 2003). Public municipal organizations as well as repellent-ectoparasiticide, may provide more
private professional businesses can provide expert complete protection from resistant as well as
guidance and tools for these efforts. susceptible heartworms.
Direct protective measures that can be Multimodal Risk Management
recommended to the dog owner include risk-
behavior modification such as limiting outdoor The risk management approach for heartworm
activities during peak mosquito feeding times and disease in dogs is a process of qualitatively and
avoidance of known mosquito habitats. A highly quantitatively evaluating the threat of infection and
effective direct protective measure is the use of disease followed by coordinated and reasonable
topically applied ectoparasiticide products with application of countermeasures to mitigate each
demonstrated mosquito repellency and insecticidal of those threats. The threat of heartworm infection
claims. can be readily assessed from the AHS Incidence
Maps (heartwormsociety.org) and from information
Use of Repellents and Ectoparasiticides provided elsewhere in these Guidelines.
Repellents work by inhibiting blood-feeding by
Veterinarians should be encouraged to make
vector mosquitoes and the associated transmission
recommendations for heartworm infection and
of infective heartworm larvae to the treated dog
disease countermeasures that are commensurate
or microfilariae to mosquitoes. This decreases the
likelihood of an uninfected dog becoming infected,
or a microfilaremic dog from serving as a reservoir Vector Control Measures to
for infecting mosquitoes and subsequently infecting Reduce Heartworm Transmission
other pets. A repellent was demonstrated to be • Eliminate sources of standing water where
highly effective (>95%) in preventing mosquito mosquitoes can breed.
feeding in two well-controlled laboratory studies.
• If standing water cannot be eliminated,
When treated microfilaremic dogs were challenged
it should be treated with chemical and/
with uninfected mosquitoes, a repellent was 95%
or biological tools such as insect growth
effective in preventing heartworm infection in the
regulators, Bacillus species, and mosquitofish.
mosquito as compared with the control group
(McCall et al, 2017a). These initial study results are • Utilize local application of insecticidal sprays/
encouraging but additional studies are needed to fogs and adult mosquito traps.
determine outcomes under field conditions. • Reduce exposure of dogs by limiting outdoor
activities during peak mosquito feeding
Ectoparasiticides work by killing mosquitoes that
times (dusk and dawn) and avoiding known
have contacted or fed on a treated animal. Because
mosquito habitats.
mosquitoes die within 3 days following exposure
to treated dogs, they are incapable of transmitting • Use topical ectoparasiticide products with
heartworms. This, in essence, renders the treated demonstrated mosquito repellency and
dog a non-reservoir, and as an added benefit kills insecticidal claims.
the female mosquito, therefore preventing egg
12 American Heartworm Societywith the known level of threat. For example, a
The risk management approach dog residing in an area of low incidence may be
for heartworm disease in dogs administered a macrocyclic lactone product as
a reasonable year-round countermeasure. As
is a process of qualitatively and the threat increases, the application of a topical
quantitatively evaluating the ectoparasiticide product having demonstrated
threat of infection and disease mosquito repellency and insecticidal claims during
the months of highest mosquito activity is a
followed by coordinated and reasonable addition to the year-round macrocyclic
reasonable application of lactone. For dogs residing in areas of the country
countermeasures to mitigate where the threat is highest and sustained, the best
recommendation to counter the threat of heartworm
each of those threats. The infection is year-round use of both a macrocyclic
threat of heartworm infection lactone and a topical ectoparasiticide product with
can be readily assessed from demonstrated mosquito repellency and insecticidal
claims, in addition to ensuring environmental
the AHS Incidence Maps mosquito abatement measures are taken.
(heartwormsociety.org).
Using a multimodal risk-management approach
to address the threat of heartworm infection and
disease enhances the potential to break the cycle of
heartworm transmission, addresses the challenges
of resistant phenotypes in the heartworm
population, and benefits both the individual dog as
well as the population at risk.
2018 Canine Heartworm Guidelines 13PRIMARY DIAGNOSTIC
SCREENING
Annual testing is an integral part of ensuring that
KEY POINTS: prophylaxis is achieved and maintained. Should an
infection be diagnosed, more timely treatment can
PRIMARY DIAGNOSTIC SCREENING
be provided to minimize pathology
• The American Heartworm Society recom-
mends annual screening for all dogs over 7 Test Timing for Optimal Results
months of age with both an antigen and a
Currently available heartworm antigen tests
microfilaria test.
detect protein secreted mainly by adult female
• The current generation of heartworm an- Dirofilaria immitis (Courtney and Cornell, 1990),
tigen tests identifies most “occult” (adult and the most useful microfilaria tests concentrate
worms present but no circulating microfi- microfilariae (modified Knott or filtration test) and
lariae) infections consisting of at least one allow for greater sensitivity (Georgi and Georgi,
mature female worm and are nearly 100% 1992; Knott, 1939). The earliest that heartworm
specific. Differences in sensitivity exist espe- antigen and microfilariae can be detected is
cially in cases with low worm burdens and/ about 5 and 6 months post infection, respectively.
or low antigenemia. Currently there are no Antigenemia usually precedes but sometimes lags
verified tests capable of detecting infections the appearance of microfilariae by a few weeks.
consisting of only adult male worms. Antigen may never be detected or may only be
• All positive antigen tests should be con- sporadically detected in dogs with very low female
firmed through additional testing prior to the worm burdens (Atkins, 2003; McCall, 1992). In
administration of any therapy. Confirmation addition, antigenemia may be suppressed until
is accomplished upon the identification of about 9 months post infection in infected dogs
circulating microfilariae, or when another receiving macrocyclic lactone preventive (McCall et
positive result is obtained utilizing a differ- al, 2001b). To determine when testing might become
ent type of antigen test. useful, a pre-detection period should be added to
the approximate date on which infection may have
• A negative antigen test result does not con-
been possible. A reasonable interval is 7 months.
firm that a dog is free of heartworm infec-
Thus, there is no need or justification for testing a
tion; it simply indicates that no antigen can
dog for antigen and microfilariae prior to 7 months
be detected by that particular testing meth-
of age.
od.
• All dogs should be tested for microfilariae. Microfilaria and Antigen Testing
Microfilaremia validates serologic results,
Whether screening a population of asymptomatic
identifies the patient as a reservoir of infec-
dogs or seeking verification of a suspected
tion, and alerts the veterinarian to a high
heartworm infection, antigen testing is the
microfilariae burden.
most sensitive diagnostic method. It is now
• Heat treatment of serum samples prior to recommended, however, that microfilaria testing
heartworm antigen tests to release blocked be done in tandem with antigen testing. This is
antigen is currently available through refer- especially important if there is a high degree of
ence laboratories. However the routine heat- suspicion or if the heartworm prevention history
ing of blood samples IS NOT PRESENTLY is unknown (e.g., dogs adopted from shelters).
RECOMMENDED for heartworm screening. It has come to light that in some dogs infected
• In cases of noncompliance or changing the with heartworms, antigen blocking, presumably
brand or type of heartworm preventive, the from antigen–antibody complexes, may lead to
dog should be antigen and microfilaria test- false-negative antigen test results. These dogs
ed prior to starting or changing products. will be antigen negative and possibly microfilariae
positive; a study conducted on shelter dogs in the
southeastern United States reported this occurred
at a rate of 7.1% (Velasquez et al, 2014). It is
important that these dogs are identified and treated
14 American Heartworm Societyto decrease the potential for selection of resistant disease. In general, it is better to trust rather than
subpopulations of heartworms. There will be reject positive antigen test results.
instances where an infected dog is both antigen and
microfilaria negative. The amount of antigen in circulation bears a direct,
but imprecise, relationship to the number of mature
Antigen Tests female heartworms (Courtney, 1987). A graded
Enzyme-linked immunosorbent assay (ELISA) and test reaction can be recognized by ELISA test
immunochromatographic test systems are available systems, but quantitative results are not displayed
for detecting circulating heartworm antigen. Each by immunochromatographic tests. The utility of the
testing format has proven to be clinically useful. ELISA tests for assessing the degree of parasitism
The current generation of heartworm antigen tests is limited by confounding complications such as
identifies most “occult” (adult worms present but the transient increase in antigenemia associated
no circulating microfilariae) infections consisting with recent worm death, low antigen levels from
of at least one mature female worm and are infections with young adult female worms and/or
nearly 100% specific (Atkins, 2003; Courtney and only a few adult females (Grieve and Knight, 1985;
Zeng, 2001; Lee et al, 2011; McCall et al, 2001b). Wang, 1998), and the presence of antigen-antibody
Differences in sensitivity exist especially in cases complexes which can reduce or completely block
with low worm burdens and/or low antigenemia. antigen detection. Therefore, quantitative analysis
Currently there are no verified tests capable of of antigen results is highly speculative and requires
detecting infections consisting of only adult male correlation with other relevant information. In as
worms. much, the color intensity of a positive antigen test
result cannot reliably be used to determine the level
To obtain reliable and reproducible results, antigen of heartworm burden, and the use of antigen testing
tests must be performed in strict compliance in this manner should be largely discouraged.
with the manufacturer’s instructions. Accuracy
of all heartworm tests under field conditions is False-negative test results occur most commonly
influenced by adherence to the instructions and when infections are light, female worms are
storage and handling of the test kit and sample. immature, only male worms are present, and/or
This process has been simplified for several test the test kit instructions have not been followed.
kits that use devices that minimize the number of There are also suspected cases of antigen blocking
steps and partially automate the procedure. Both from antigen–antibody complexes interfering with
false-positive and false-negative results can occur. antigen testing, resulting in false-negative tests.
When a test result is unexpected, either positive or Laboratory studies have shown that heating serum
negative, the test should be repeated. If the result will release blocked antigen, and result in more
remains ambiguous, independent confirmation by a positive test results (Velasquez et al, 2014). (For
reference laboratory is recommended to confirm or more on heat treatment, see the box on page 16).
refute the result. A negative antigen test result does not verify an
While a positive heartworm antigen test indicates animal to be free of heartworm infection; it simply
the presence of specific heartworm antigen, there indicates that no antigen can be detected by that
are factors that can initiate a false-positive result. particular testing methodology. As such, a negative
Currently, it is recommended that all positive test result should be interpreted (and perhaps
antigen tests be confirmed through additional documented) more accurately as no antigen
testing prior to the administration of any therapy detected (NAD) rather than “negative.”
including the use of macrocyclic lactones, Microfilaria Tests
doxycycline, or melarsomine. Confirmation is
accomplished upon the identification of circulating In areas where the prevalence of heartworm
microfilariae, or when a positive result is obtained infection is high, many (~20%) heartworm-infected
utilizing a different manufacturer’s antigen test. dogs may not be microfilaremic, and this figure
Ultrasonographic visualization of adult heartworms is even higher for dogs on a macrocyclic lactone
within the heart or pulmonary artery is also prevention program (McCall, 2005). Considering
confirmatory. Thoracic radiography depicting signs this, most microfilaremic dogs can be detected
of heartworm disease, while not diagnostic of by microscopically examining a drop of fresh
current infection, can be supportive of heartworm blood under a cover slip for microfilariae or cell
2018 Canine Heartworm Guidelines 15When Should Heat Treatment of Serum Samples Be Considered?
Heat treatment of serum samples prior to heartworm antigen tests as well as other non-heat methods
to release blocked antigen is currently available through reference laboratories. This process should
be considered when a negative antigen test result does not correlate with the presence of circulating
microfilariae, or when there is suspicion of active clinical disease. However, the routine heating of blood
samples IS NOT PRESENTLY RECOMMENDED for routine heartworm screening.
While heat treatment of samples has been shown to release blocked antigen that can cause false-
negative test results, it is contrary to the label instructions for commonly used in-house tests and may
interfere with the accuracy of results of not only heartworm testing but also the results of combination
tests that include antibody detection of other infectious agents. Further studies on the possible cross-
reactivity of heartworms with other helminths are needed to more accurately interpret the conversion
from “no antigen detected” to “antigen positive” after heat treatment.
movement caused by the motile microfilariae
How to Perform the Modified Knott Test (Rawlings, 1986). A stationary rather than a
The modified Knott test is performed by mixing migratory pattern of movement is indicative of a
1.0 mL of EDTA blood with 9.0 mL of 2% for- Dirofilaria species, nearly always D. immitis in the
malin in a centrifuge tube. The tube is inverted United States. Movement above the buffy coat in
several times to mix the blood with the formalin a microhematocrit tube also may be visible. These
solution, lysing the red blood cells. The tube is are insensitive testing methods when low numbers
then placed in a centrifuge, spun at 1100 to 1500 (50–100/mL) of microfilariae are present; however,
rpm for 5 to 8 minutes, and the liquid is poured such patients are at a lower risk for severe reaction
off leaving the sediment. A drop of methylene after the administration of a microfilaricide and are
blue is added to the sediment and then the less likely to pose a threat as a reservoir of infection.
stained sediment is placed on a glass slide and a
cover slip applied. The slide is examined under For more accurate results a concentration technique
low power (100X) for the presence of micro- (modified Knott test) should be used to determine
filariae. To observe the characteristics of the the absence or presence of microfilariae (Georgi
microfilariae, the slide can be examined under and Georgi, 1992; Knott, 1939). The modified
high-dry (400X). The microfilariae of Dirofilaria Knott test (see box on left) remains the preferred
immitis are 295 to 325 microns (μm) long and method for observing morphology and measuring
have tapered heads. The microfilariae of Acan- body dimensions to differentiate D. immitis
thocheilonema reconditumare 250 to 288 μm from non-pathogenic filarial species, such as
long with blunt heads and curved tails (Figure 4) Acanthocheilonema (formerly Dipetalonema)
(Rawlings, 1986). reconditum.
All dogs should be tested for microfilariae.
Microfilaremia validates serologic results, identifies
the patient as a reservoir of infection, and alerts
the veterinarian to a high microfilariae burden,
which may precipitate a severe reaction following
administration of a microfilaricide.
Testing Considerations Following
Figure 4. Acanthocheilonema reconditum (top) and Noncompliance and When Changing
Dirofilaria immitis (below). Photograph courtesy of Products
Byron Blagburn, PhD.
In instances of noncompliance or changing the
brand or type of heartworm preventive, it is
important to determine the heartworm status of the
16 American Heartworm SocietyFigure 5. The testing protocol following known noncompliance includes three tests in the first year, with annual testing
thereafter.
dog. The dog should be antigen and microfilaria
tested prior to starting or changing products. A
positive test indicates preexisting infection. The dog
should always be retested 6 months later (Figure 5).
A positive test at this time would most likely be due
to an infection acquired before starting or resuming
preventive therapy; however, in rare instances,
an existing infection might be missed (i.e., false-
negative test due mainly to young or low worm
burden infection). Antigen and microfilaria testing
should be performed on the one-year anniversary
date of the initial test and annually thereafter.
Other Diagnostic Aids
Additional testing methods, such as radiography
and echocardiography, are useful for confirming the
diagnosis and staging the severity of heartworm
disease.
Radiography
Assessment of cardiopulmonary status may
be useful for evaluating a patient’s prognosis.
Radiography provides the most objective
method of assessing the severity of heartworm
cardiopulmonary disease secondary to heartworm
infection. Typical (nearly pathognomonic) signs
of heartworm vascular disease are enlarged,
tortuous, and often truncated peripheral intralobar
and interlobar branches of the pulmonary arteries,
particularly in the diaphragmatic (caudal) lobes
(Figure 6). These findings are accompanied by
variable degrees of pulmonary parenchymal
disease. The earliest and most subtle pulmonary Figure 6. Moderate heartworm disease. Right heart
arterial changes are most commonly found in the enlargement (reverse “D” shape) is seen in heartworm
disease. Radiographic images courtesy of C. Thomas
dorsal caudal wedge of the diaphragmatic lung
Nelson, DVM.
lobes. As the severity of infection and chronicity of
disease progress, the pulmonary arterial signs are
seen in successively larger branches (Figure 7). In
the worst cases, the right heart eventually enlarges
(Bowman and Atkins, 2009; Calvert and Rawlings,
1988; Rawlings, 1986).
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