EPIDEMIOLOGY

Heartworm infection in dogs has been diagnosed around the globe, including all 50 of the United States of America (USA). In the USA, its territories and protectorates, heartworm is considered at least regionally endemic in each of the contiguous 48 states, Hawaii, Puerto Rico, U.S. Virgin Islands and Guam. Heartworm transmission has not been documented in Alaska; however there are regions in central Alaska that have mosquito vectors and climate conditions to support the transmission of heartworms for brief periods. Thus, the introduction of microfilaremic dogs or wild canids could set up a nidus of infection for autochthonous transmission of heartworm in this State. Such re-location of microfilaremic dogs and expansion of the territories of microfilaremic wild canids in other areas of the USA continue to be important factors contributing to further dissemination of the parasite, as the ubiquitous presence of one or more species of vector competent mosquitoes makes transmission possible wherever a reservoir of infection and favorable climatic conditions co-exist.

Environmental changes created by humans, changes in natural climatic conditions, and animal movement have increased heartworm infection potential. Commercial and residential real estate development of non-endemic and low incidence areas has led to the spread and increased prevalence of heartworms by altering drainage of undeveloped land and by providing water sources in new urban home sites. In the western USA, irrigation and planting of trees have expanded the habitat for Aedes sierrensis (western knot hole mosquito), the primary vector for transmission of heartworms in those states. Aedes albopictus (Asian tiger mosquito), which was introduced into the southeastern United States in 1987, has now spread north approaching Canada and has extended past the Rocky Mountains to the west coast. This urban-dwelling mosquito is able to reproduce in small containers such as flower pots. In the northern half of the United States, urban sprawl has led to the formation of “heat islands”, as buildings and parking lots retain heat during the day and subsequently radiate it during the night. This can potentially create microenvironments that support development of heartworm larvae in mosquito vectors during colder months, thus lengthening the transmission season.

As these vectors expand their territory the number of unprotected animals infected will continue to increase. A pivotal prerequisite for heartworm transmission is a climate that provides adequate temperature and humidity to support a viable mosquito population, and sustains sufficient heat to allow maturation of ingested microfilariae to infective, third-stage larvae (L3) within this intermediate host. It has been shown under laboratory conditions in three mosquito species that maturation of larvae within mosquitoes ceases at temperatures below 57ºF (14ºC) and similar activity is expected in other mosquitoes capable of transmitting heartworms. Heartworm transmission does decrease in winter months but micro-environments commonly present in urban areas virtually ensure that the risk of heartworm transmission never reaches zero. Some species of mosquitoes overwinter as adults. While heartworm larval development in mosquitoes may cease in cool temperatures, development quickly resumes with subsequent warming.

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 usually July and August. Models predict that heartworm transmission in the continental USA is limited to six months or less above the 37th parallel, i.e., Virginia-North Carolina State line. Furthermore, predictive risk maps have been produced coupling these basic models with Geographic Information Systems (GIS) based on a thermal regimen and information about mosquito vectors. While these model-based predictions are academically appealing, they do not yet consider several potentially important factors, such as the influence of microclimate and the unique biological habits and adaptations of the numerous mosquito vectors on larval development. Once a reservoir of microfilaremic domestic and wild canids is established beyond the reach of veterinary care, the ubiquitous presence of one or more species of vector competent mosquitoes makes transmission possible and eradication becomes improbable.

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. However, even less suitable hosts such as cats and ferrets occasionally have low-level, transient microfilaremias and therefore may serve as a source of infection for mosquitoes during these short periods of microfilaremia. The life cycle of D. immitis is relatively long (usually 7-9 months) compared with most parasitic nematodes. The susceptible mosquito becomes infected when taking a blood meal needed for egg development from a microfilaremic host. The microfilariae develop to the third stage in the mosquito’s malpighian tubules and 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 27° C and 80% relative humidity, development takes about 10-14 days.

Infective, third-stage larvae (L3) are deposited in a droplet of hemolymph (mosquito blood) on the host while the mosquito is taking a blood meal. Immediately after the blood meal, these sexually differentiated L3 enter the animal’s body via the puncture wound in the skin made by the mosquito’s mouthparts. Three days after experimental subcutaneous injection of the L3 in the inguinal region of the dog, most of the larvae are found in the subcutaneous tissues near their entry site. By day 21, most of the larvae have migrated to the abdominal tissues of the dog, and by day 41, they may be recovered from either the abdominal or thoracic tissues. Apparently L3 and L4 travel between muscle fibers during migration, whereas juveniles (immature adults) penetrate muscle and eventually veins, transporting them toward the heart and lungs. The molt from L3 to L4 begins as early as day 3 and ends as late as day 9-12. L4 molt to the final stage at day 50-70. Worms reach the pulmonary vasculature as early as day 70 and all have arrived by day 90-120. The first worms entering the pulmonary vasculature on day 70-85 are 1-1.5 inches in length. Thereafter the female worms will increase in length by almost tenfold. They become sexually mature about day 120 post infection. Dogs develop patent infections (i.e., have microfilariae circulating in their blood) as early as 6 months but usually by 7-9 months post-infection.

When juvenile heartworms first reach the lungs, the blood pressure forces them into the small pulmonary arteries. As they grow and increase in size, they progressively occupy larger and larger arteries until they become fully mature. The eventual location of the mature adult worms 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 (i.e., 10) usually has worms mainly in the lobar arteries and main pulmonary artery. As the worm burden increases, worms are also located in the right ventricle. Dogs with more than 40 worms are more likely to have caval syndrome, where most of the worms migrate into the right ventricle, right atrium and the caudal vena cava, thus interfering with valvular function and/or blood flow.

A clear understanding of heartworm transmission, development, prepatent period, and the susceptibility of the different life stages to the parasite to available pharmaceutical drugs is critical. This knowledge base is necessary to effectively select the most appropriate adulticide treatment option and treatment time, and to develop realistic expectations for the veterinarian and client for the outcome of therapy.