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==Life Cycle==
==Life Cycle==
Mosquito vector species acquire the first stage larvae (microfilariae) while feeding on an infected host. Development of microfilariae to the second larval stage (L2) and to the infective third stage (L3) occurs within the mosquito in ~1-4 wk, depending on environmental temperatures. This development phase requires the shortest time when the ambient temperature is >86°F (30°C). When mature, the infective larvae migrate to the labium of the mosquito. As the mosquito feeds, the infective larvae erupt through the tip of the labium with a small amount of hemolymph onto the host’s skin. The larvae migrate into the bite wound, beginning the mammalian portion of their life cycle. A typical Aedes mosquito is only capable of surviving the developmental phase of small numbers of HW larvae, usually <10 larvae per mosquito.
In canids and other susceptible hosts, infective larvae (L3) molt into a fourth stage (L4) in 2-3 days. After remaining in the subcutaneous tissue for close to 2 mo, they molt into young adults (L5) that migrate through host tissue, arriving in the pulmonary arteries ~50 days later. Adult worms (males ~15 cm in length, females ~25 cm) develop primarily in the pulmonary arteries of the caudal lung lobes over the next 2-3 mo. They reside primarily in the pulmonary arteries but can move into the right ventricle when the worm burden is high. Microfilariae are produced by gravid females ~6-7 mo postinfection.
Microfilariae are usually detectable in infected canids not receiving macrolide prophylaxis. However, 25% to >50% of infected canids may not have circulating microfilariae. Thus, the number of circulating microfilariae does not necessarily correlate strongly to adult female HW burden. Adults typically live 3-5 yr, while microfilariae may survive for 1-2 yr while awaiting a mosquito intermediate host.
Most dogs are highly susceptible to HW infection, and the majority of infective larvae (L3) develop into adults. Ferrets are susceptible hosts, and cats are somewhat resistant. A lower percentage of exposed cats develop adult infections and the burden is often only 1-3 worms. Further evidence of relative resistance in cats is the short survival time of many L5 in the pulmonary arteries; adult worms probably survive no longer than 2 yr. Aberrant migration into different organs, including the CNS, has been described in cats.
==Pathogenesis==
==Pathogenesis==