Dirofilaria immitis

Dirofilaria immitis Jennie Xiong Senait Gebrehiwot

Kingdom: Animalia Phylum: Nemathelminthes Class: Nematoda Subclass: Spiruria Order: Spirurida Family: Filariidae Genus:Dirofilaria Species:immitis Penial spicules Taxonomy

Information • Parasitic in the right side of the heart and pulmonary artery of dogs and other mammals throughout most of the world • Found in humans including in US but do not mature in humans • Neither mature worms nor eggs have been detected in humans

The Wolbachia factor • Wolbachia is a bacterium that lives in endosymbiosis within adult heartworms • They are beneficial to worms reproduction in embryogenesis. • When a dog is treated with antibiotic to kill the Wolbachia, the adult worm either dies or becomes sterile • Wolbachia can be killed by mild antibiotics like tetracycline. • The large part of pathogenesis during filarial infections comes from the immune response to the bacteria Wolbachia • In humans inflammatory responses may show symptom of infection when the worms die and the body’s immune system tries to get rid of the bacteria. • When heartworms die, Wolbachia bacteria can still cause embolism and shock to the host organism

Question #1 • In what way would treating heartworm infected dogs with antibiotics like tetracycline be beneficial? It kills the Wolbachia that lives in the worm and helps either by killing the worm or at least sterilizing it.

Geographic Distribution • World wide • Prefers mild and warm climates • United States, Italy, Japan, Canada, Australia, France, Armenia, Brazil, Venezuela, Philippines, Malaysia, New Guinea, Tahiti, Sierra Leone and China

U.S. Distribution Most common along Atlantic and Gulf Coasts

Morphology • Adult female • 25-31 cm long and 1-1.3 mm wide • Obtuse posterior end • Adult Male • 12-20 cm long and 0.7-0.9 mm wide • Tapering, spirally-coiled posterior end

Intermediate Host Mosquitoes (many—over to 60 species of mosquitoes) Culex pipiens aka house mosquito – worldwide night feeder plain, brown insect that breeds freely around human habitation, laying egg rafts in tin cans, tires, cisterns, clogged rain gutters, and any other receptacle of water Aedes species - US Definitive Host Dogs, Cats, Foxes, Wolves, Coyotes, Ferrets, Seals Humans (accidental host) Culex pipiens Host

Question #2 • How many species of mosquitoes are capable of transmitting D. immitis? Which ones are common? Over 60 species. Culex pipiens and Aedes species.

Life Cycle • Adult parasites in chambers of right side of heart and pulmonary artery • Eggs developing in uterus are enclosed in a thin vitelline membrane • As embryo elongates, surrounding membrane stretches to conform as an enclosing sheath • At birth membrane is lost and embryo appears in blood as a sheath less microfilariae • Microfilariae deposited in blood of chambers of right side of the heart and pulmonary artery then carried through the lungs into a left chambers of heart and into circulation • Mosquito takes blood meal and ingest microfilariae • Microfilariae migrate from intestine within 24 to 36 hours into the Malpighian tubules where further development and molt form the first to the second stage juvenile occurs • After 9 days they enter the abdominal hemocoel where second molt occurs • Third stage larvae are about 900 um long and appear 10-20 days after entering mosquito • Third stage larvae migrate to mouthparts of mosquito • Infection of dogs occurs while mosquito goes for blood meal • Third stage juveniles escape onto the skin and enter through feeding site • 80 days juveniles are in subcutaneous tissues and muscles where third molt takes place 9-12 days after entry • In tissue, fourth stage juveniles attain lengths up to 25 mm and begin entering right side of heat shortly after the fourth molt 60-70 days after entering the dog • Development to maturity takes 174-223 days at which time microfilariae appear in the blood • Reproductive period exceeds 2 years and may extend to 5 years

Question #3 What is the circulation route for microfilariae from the adult to the blood system? From the right heart (ventricle) to the pulmonary artery to the lung and to the heart via pulmonary vein and then out to the peripheral circulation.

Question #4 • Where do microfilariae come from (what stage)? From the adult female heartworm at birth in either right side of the heart or the pulmonary artery.

Epidemiology • Highest prevalence in US corresponds with the highest mosquito density, along the Mississippi River throughout the Midwestern states, prevalence among dogs is up to 45%, prevalence is much lower in western US but can range to 5% in some areas of California and Oregon • Transmission may occur whenever daily temperature regularly exceeds 57°F (14°C), the threshold for development of juveniles in mosquitoes • Usually in humans, the worms migrate to the lungs instead of the heart. Here they form a lesion that can be seen on X-rays. There are normally few symptoms noticed with human heartworm infestation. Surgical removal of the lung lesion may be performed, if necessary (cysts in lungs or eyes) • The parasite is spread by mosquitoes and while most of us have immune systems that successfully fight off the disease, the disease is sometimes the winner. Immune suppressed people, especially AIDS and other cancer patients are most susceptible. • Human infection and inflammation is usually related to Wolbachia.

Question #5 • Why is D. immitis prevalence high along the Mississippi River? Because of high density of mosquito.

Pathogenesis • Ig-cleaving protease on surface that cleaves adherent antibodies that are produced from humans • Can synthesize all classes of complex lipids, including cholesterol • Dangerous pathogen for dogs and although prevalence and worm load are usually lower in cats, even a few worms can cause serious disease in cats • Clinical signs include respiratory insufficiency, vomiting, chronic cough and exercise intolerance • Larger worms extending through the openings of the tricuspid and semilunar valves will prevent efficient operation of those heart valves • Pulmonary arteries show thickening and inflammation of their inner walls • Death may occur from cardiopulmonary failure • In humans symptoms are vague and unpredictable and may include chest pain, cough, coughing up blood, fever and depression • Dying adult worms passing from the heart into the lungs clog arteries, lead to granuloma formation and become life threatening in severe cases

Diagnosis • Routine diagnosis is finding microfilariae in blood smear, X-ray or ultrasound and immunodiagnostic (ELISA) • Dogs and other susceptible animals should be given prophylactic doses of Ivermectin or Milbemycin once a month or DEC once each day, these drugs do not affect adults, which must be killed with other drugs

Diagnosis cont. Microfilariae in blood Heartworm can affect humans through mosquito bites. This X-Ray image of a person with heartworm was in a human medical journal

Microfilaria picture

Treatment and prevention • Surgery to remove worms • To treat Microfilariawe can use Chemoprophylaxis drugs such as • Macrocyclic lactones • Ivermectin (Heartgard) • Milbemycin oxime (Interceptor) • Moxidectin (ProHeart) • Selamectin (Revolution) • Diethycarnamazine Citrate (DCE)—(Filaribits) (None of microfilaricides are approved by FDA but licensed veterinarians are permitted to use it)

Treatment & Prevention cont. • Foradulticidetherapy • Melarsomine Dihydrochloride (Immiticide) • For Larvae therapy Ivermectin in combination with pyrantel pamoate—this prevents development and infection of larvae Treatment should be sequential—adult, microfilaria, and precardiac larvae

Treatment controversy • Most heartworm drugs are not FDA approved yet are sold over-the-counter • Veterinarians can use “extra labels” i.e. design treatment procedure that individual vet thinks is right. Sometimes preventive treatments are given to dogs without testing for presence of adult worms. • Even if dogs with patent infection are given microfilaria treatment, most remain being microfilaremic for as long as a year

Question #6 • In the article you read, what was mentioned as a solution for this problem? • Verifying if dogs are heartworm negative • If they are infected, treat them with Immiticide to kill the adult heartworms and start the macrocyclic lactones • Stop over-the-counter sale

Public Health Concerns • It can cause death in highly infected dogs • Direct cost to pet owners providing treatment • Heartworm dies shortly after arriving in the human lung and form granuloma which might look like lung cancer during X-ray exam. • The only medical consequence they might have is misdiagnosis of granuloma in lungs for lung cancer. • It was believed heartworm infected the human eye but was found being caused by closely related parasite of raccoons Dirofilaria tenuis.

Control • Pet owners should provided chemoprophylaxis during mosquito season • Mosquito control in residential areas • Treating dogs with antibiotics to make sure there is no more production of microfilariae.

Reference • http://cal.vet.upenn.edu/dxendopar/parasitepages/filariidsandspirurids/d_immitis.html#lifecycle • http://www.heartwormsociety.org/MediaLetter.htm • http://en.wikipedia.org/wiki/Wolbachia • http://ucdnema.ucdavis.edu/imagemap/nemap/ENT156HTML/nemas/dirofilariaimmitis • Schmidt, G. and Robert, L. Foundations of Parasitology. 7th edition

Dirofilaria immitis