Heartworm infection in dogs has been diagnosed in all 50 US states, but not yet in Alaska, even though the climatic and mosquito populations in central Alaska are conducive to the further dissemination of this parasite.
Environmental climate changes with global warming, along with animal movements and urban development, have increased the heartworm infection potential. Urban-dwelling mosquitoes of the relevant species are able to reproduce in small containers such as flowerpots, and urban sprawl has allowed buildings and parking lots to retain heat during the day creating microclimates that support development of heartworm larvae in mosquitoes during colder months, thereby lengthening the transmission season.
It has been shown that maturation of larvae, within three mosquito species, ceases at temperatures below 57°F (14°C). Thus, heartworm transmission does decrease in winter months, although the risk of transmission never reaches zero. The length of the heartworm transmission season in the temperate latitudes is critically dependent on the accumulation of sufficient heat to incubate larvae to the infective stage in the mosquito. The peak months for heartworm transmission in the Northern Hemisphere are typically July and August. But, variations in time of larval development and mosquito life expectancy, year-to-year temperature fluctuations, and global climate change have extended the transmission period to up to 8 months in the northern states.
Survey studies of trapped mosquitoes randomly collected at various locations have demonstrated heartworm infection rates in mosquitoes ranging from 2-19% in known endemic areas. When mosquito sampling was restricted to kennel structures where known positive dogs were being housed, the infection rates of the mosquitoes was much higher 30-74% in and around them.
Biology and Life Cycle
The domestic dog and some wild canids are the normal definitive hosts for heartworms and thus serve as the main reservoir of infection. Even less suitable hosts, such as cats and ferrets, occasionally have low-level, transient microfilaremia and therefore, theoretically, may serve as a limited source of infection.
The life cycle of Dirofilaria immitis is relatively long (usually 7–9 months) compared with most parasites. The susceptible mosquito becomes infected when taking a blood meal from a microfilaremic host. Microfilariae cannot develop into adult heartworms without first developing into 3 larval stages. The third-stage larvae then migrate via the body cavity to the head and mouthparts of the mosquito, where they become infective. The time required for the development of microfilariae to the infective stage in the mosquito is temperature-dependent. At 80°F (27°C) and 80% relative humidity, development takes about 10-14 days; with cooler temperatures, maturation takes longer.
When the mosquito takes a blood meal, the infected larvae enter the animal’s body via the puncture wound. Immature adult (fifth stage) worms then reach the pulmonary circulation vasculature as early as day 67 and all have arrived by day 90-120. Thereafter, adult worms increase in length, with females increasing by almost tenfold, becoming sexually mature about day 120 post-infection. Dogs develop patent infections (i.e., have circulating microfilariae) as early as 6 months but usually by 7 – 9 months after infection.
A clear understanding of heartworm transmission, development, pre-patent period, and the susceptibility of the different life stages of the parasite to available drug therapy is critical. This knowledge is needed to effectively select the most appropriate treatment option and time, and to develop realistic expectations for the outcome of therapy.
Heartworm preventive medication requires a prescription from a licensed veterinarian having a valid relationship with the client and patient. Options for effective chemoprophylaxis include several drugs administered monthly either orally or topically, or even systemically at 6-month intervals.
Heartworm infection is preventable with this therapy. Puppies should be started on preventives as early as possible, but no later than 8 weeks of age. Puppies started on a heartworm preventive after 8 weeks of age, or housed unprotected outdoors in heavily endemic areas, should be tested 6 months after the initial dose and annually thereafter. Before initiating a preventive regimen in older dogs (7 months of age or greater), heartworm antigen and microfilariae testing should be performed.
Evidence strongly suggests that by reducing the reservoir population through increasing the number of dogs receiving prevention, a large decrease in the prevalence of infection among unprotected dogs may also occur as a collateral benefit from the “herd health” effect.
Macrocyclic Lactone Drugs
The heartworm preventives currently marketed (ivermectin, milbemycin oxime, moxidectin, and selamectin) belong to the macrocyclic lactone class of drugs. These drugs affect microfilariae, third- and fourth-stage larvae, and with continuous use, may affect adult heartworms. Macrocyclic lactones, when given according to label instructions, are highly effective and are among the safest medications used in veterinary medicine.
All orally and topically administered macrocyclic lactone are labeled for a 30-day dosing interval. Beyond this interval efficacy against late fourth-stage larvae declines and is unpredictable. Continuous, year-round administration of heartworm preventive is important in most, if not all, areas of the United States.
Oral administration: Ivermectin (Heartgard®) and milbemycin oxime (Interceptor®) are available for monthly oral administration. Some formulations are flavored and chewable to increase patient acceptance and facilitate administration. Dose units are packaged for dogs within prescribed weight ranges. To be maximally effective, heartworm prophylaxis should be given year-round, but if seasonal treatment is chosen, administration should begin at least one month prior to the anticipated start of heartworm transmission and should continue for at least 3 months after transmission typically ceases. The latter 3-month recommendation emanates from new knowledge regarding resistant strains, which showed that extended treatment after exposure is required to prevent infection. Current data demonstrate that not all compounds and formulations necessitate this extension.
Topical administration: Moxidectin (Advantage Multi®) and selamectin (Revolution®) are available as topically applied liquid formulations. Treatment parameters are the same as for the monthly oral drugs. [Note: This author prefers the single oral heartworm preventives, rather than any combination products.]
Parenteral administration: A single dose of slow-release subcutaneously injected moxidectin-impregnated lipid microspheres provides continuous protection for 6 months, with the potential to enhance compliance. Treatment every 6 months is recommended for maximal protection.
Reports of Lack of Efficacy
Lack of efficacy of a heartworm preventive product is considered by the Center for Veterinary Medicine (CVM) of the FDA as a dog testing heartworm positive regardless of appropriateness of dosage or administration consistency. There are many possible reasons for such reports, including failure to administer sufficient preventive, when it should be given; failure of a dog to retain the drug, and failure of absorption of the active ingredient. There is also biological variation between hosts in drug metabolism and immune response, and in parasite susceptibility to the drug. Thus, the exact cause of a reported failures can be difficult or impossible to determine. Fortunately most claims are explained by compliance failure.
It is now generally accepted that pockets of resistant heartworms exist, especially in the Mississippi River Valley. The extent, the degree of spread, and the reasons for resistance are not understood and are controversial, and genetically resistant strains may have developed. However, pet owner compliance is the biggest factor in the “failure” of preventives. There is general agreement that resistance to heavy experimental infections is worrisome, and that the products now available are effective well over 95% of the time and should continue to be used as the manufacturers suggest.
Whether screening a population of asymptomatic dogs or seeking verification of a suspected heartworm infection, antigen testing is the most sensitive diagnostic method.
Microfilaria testing should be done in tandem with antigen testing to determine whether this life-cycle stage is also present in dogs.
Heartworm Antigen Tests
Enzyme-linked immunosorbent assay (ELISA) is commonly used for detecting circulating heartworm antigen. It detects infections of at least one mature female worm and are nearly 100% specific. Differences in sensitivity exist especially in cases with low worm burdens and/or low antigen levels in the blood. Currently there are no verified tests capable of detecting infections consisting of only adult male worms.
Heartworm Microfilaria Tests
In areas where the prevalence of heartworm infection is high, many (~20%) heartworm-infected dogs may not have filaria in the blood (microfilaremia). Most microfilaremic dogs can be detected by microscopically examining fresh blood for microfilariae or cell movement created by the motility of the microfilariae. Movement beneath the buffy coat in a microhematocrit tube also may be visible. But, these are insensitive methods for examining blood in which low numbers (50–100/mL) of microfilariae are present. Therefore, at least 1.0 mL of blood should be examined using a concentration technique (modified Knott test or filtration test) to determine the absence or presence of microfilariae. The modified Knott test remains the preferred method for observing morphology and measuring body dimensions to differentiate D immitis from non-pathogenic filarial species such as Acanthocheilonema (formerly called Dipetalonema) reconditum.
The modified Knott test is performed by mixing 1.0 mL of blood with 9.0 mL of 2% formalin in a test tube. The tube is inverted several times to mix the blood with the formalin solution, lysing the red blood cells, which causes the mixture to become a clear, red-wine color. Next the tube is placed in a centrifuge, spun for 5 minutes, and the liquid is poured off leaving the sediment. A drop of methylene blue is added to the tube and then a drop of the stained sediment is placed on a glass slide and a cover slip applied. The slide is examined under 100 X for the presence of microfilariae. To observe the characteristics of the microfilariae, the slide can be examined under 400X. The microfilariae of Dirofilaria immitis are 295 to 325 microns (μm) long and have tapered heads. The microfilariae of Acanthocheilonema reconditum are 250 to 288 μm with blunt heads and curve tails.
Testing Following Noncompliance and When Changing Preventives
In these situations, it is important to determine the heartworm status of the dog. The dog should be antigen and microfilaria-tested prior to starting or changing products.
Principles of Treatment
Treating heartworm infections in asymptomatic patients or those exhibiting signs of mild disease usually is not problematic if exercise is curtailed. Infections associated with moderate or severe heartworm disease or in patients with concurrent disease often are challenging.
The goals of any heartworm treatment are to improve the clinical condition of the animal and to eliminate all life stages of the heartworms (microfilariae, larval stages, juveniles, and adults) with minimal post-treatment complications. Dogs exhibiting significant clinical signs of heartworm disease should be stabilized before administering a heartworm adulticid, such as arsenicals. This may require administration of glucocorticosteroids, diuretics, vasodilators, positive inotropic cardiac agents, and fluid therapy.
Heartworm Diagnostics: The American Heartworm Society recommends annual antigen and microfilariae testing.
Heartworm Preventives: The American Heartworm Society recommends year-round administration of heartworm preventive (chemoprophylactic) drugs to prevent heartworm disease, control other pathogenic and/or zoonotic parasites, and enhance compliance, the latter being particularly important in light of the documented presence of resistant sub-populations.
Therapy to Kill Adult Heartworms: The American Heartworm Society recommends use of doxycycline and a macrocyclic lactone prior to the three-dose regimen of melarsomine (arsenic; 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 (e.g. milbemycin oxime) as a slow-kill adulticide is not recommended.
* Excerpted from: “Current Canine Guidelines for the Prevention, Diagnosis, and Management of Heartworm (Dirofilaria immitis) Infection in Dogs”, American
Heartworm Society, 2014, 20 pp.