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As of March 22, 1995, an addendum has been appended to this article.

After having a malignant skin tumor removed, a 47-year-old woman from a heartworm endemic area underwent routine follow-up thoracic radiography. On the anterior-posterior view, a rounded 2.5-cm soft tissue density was observed in the right lower lung field. The nodule could not be identified on the lateral view. Assuming the mass represented metastasis from her skin tumor, a right thoracotomy with wedge resection of the pulmonary nodule was performed. Microscopic examination of the specimen revealed lung tissue with granulomatous vasculitis and infarction secondary to a parasite that was later identified in tissue sections as Dirofilaria immitis.¹ The woman recovered from surgery without complication.

The physician called a veterinarian with the following questions concerning dirofilariasis.

Q: What type of parasite is Dirofilaria immitis?

A: Members of the genus Dirofilaria are long, thin, filarial parasites that inhabit the blood vasculature or connective tissues of several varieties of definitive hosts indigenous to North America. Dirofilaria immitis is found in the right ventricle and pulmonary arteries of canids and felids.² It has also been reported in aberrant locations in many incidental hosts, including foxes and California sea lions.³ Dirofilaria tenuis has been found in the subcutaneous tissues of raccoons in the southern part of the United States.² Dirofilaria ursi has been found in subcutaneous tissues around brachial and cervical lymph nodes of black bears.⁴ Dirofilaria subdermata is found in the subcutaneous tissues of porcupines.⁴ Dogs in the Mediterranean area are parasitized frequently with Dirofilaria repens, and the worm is found subcutaneously.²

Q: Do other species of Dirofilaria have zoonotic potential?

A: Only Dirofilaria immitis, the canine heartworm, causes pulmonary dirofilariasis in human beings; however, several other species of Dirofilaria also are zoonotic.^5-7 Filarial nematodes from raccoons (D tenuis), bears (D ursi), and porcupines (D subdermata) can cause subcutaneous dirofilariasis in human beings.^8,9 Another parasite of this genus, D repens, is found in dogs and causes ocular dirofilariasis in human beings.¹⁰

Q: What is the current distribution pattern of dirofilariasis in domestic and wild animals in North America?

A: The distribution of Dirofilaria spp is related to the population dynamics of the definitive hosts and the availability of vectors involved in transmission.¹¹ Before 1960, D immitis was reported only in the coastal areas of the United States. The disease is now recognized in every state, with the highest prevalence along the East Coast and the Mississippi River Valley.³ Dirofilaria tenuis is reported in the southern United States from Texas to Florida.¹² Both D ursi and D subdermata have been found only in the northern United States and Canada.^12-14 Few recent studies have been conducted on the geographic distribution of D ursi, D tenuis, and D subdermata; therefore, their ranges are likely to be more extensive than previously reported. This is particularly true of Dirofilaria tenuis, because raccoons adapt easily to living in an urban environment. Dirofilaria repens has been detected only in the Mediterranean area.²

Q: How are these parasites transmitted to dogs or cats?

A: These parasites are transmitted to dogs or cats through the bites of infected mosquitoes. Adult D immitis have a life span of approximately 7 years and microfilariae live approximately 5 years.^a Adult parasites copulate in the right ventricle and pulmonary arteries of the host, and the females produce microfilariae.² The microfilaria has been described as an embryonic stage.¹⁵ Microfilariae are in circulation at all times. The concentration of microfilariae in the blood varies over a 24-hour period, and may reach as high as 10³ to 10⁵ microfilariae/ml of blood.¹⁶ The microfilariae exhibit an incomplete nocturnal periodicity. Microfilariae are ingested by female mosquitoes during blood feeding.²

Over 72 species of mosquitoes have been documented as potential intermediate hosts for D immitis.¹⁷ In mosquitoes, the microfilariae develop to the third larval stage in the Malpighian tubules.¹⁵ They then migrate from the tubules through the body cavity to the proboscis of the mosquito. Dogs and cats are infected through wounds inflicted by mosquitoes. Successful transmission involves the emergence of infective larvae from the proboscis of the mosquito. Larvae are contained in a small drop of mosquito body fluid. The moist larvae must be close to the puncture wound, which they must enter before the fluid dries.¹⁸ After passage through the wound, the larvae continue to develop in the subcutaneous tissues. Third-stage larvae molt to the fourth stage as early as 24 hours after infection. Fourth-stage larvae molt to the fifth stage between 50 and 70 days after infection. Most larvae migrate to the cranial portion of the abdomen and the thorax and then to the head, neck, and forelimb regions before migrating to the heart. Adult worms are found in the heart and pulmonary arteries within 70 days of infection.¹⁹ In this site, they mature in 2 months, copulate, and the females begin to produce microfilariae.²

Q: Are mosquitoes the only vectors involved in the transmission of these diseases to human beings and has human being to human being transmission ever been reported?

A: Mosquitoes are the intermediate hosts for all Dirofilaria spp, with the exception of D ursi and D subdermata.^7,11 These species are transmitted from wild animals to human beings through bites of infected blackflies (Simuliidae).⁸ Transmission to human beings is dependent on vector availability and the presence of the definitive host.¹¹ Mosquito species involved in transmission may vary from one region to another. Human beings are accidental hosts for these parasites, and infected mosquitoes must readily attack both the definitive hosts and human beings for transmission to occur. Opportunistic feeders such as Culex salinarius, Aedes taeniorhynchus, and A vexans are ideal vectors for transmission of dirofilariasis between dogs and human beings.^20,21

In most human cases of dirofilariasis, only a single adult worm is found and it is often dead. Microfilariae have been found in a small number of cases; however, they are associated with the local lesion and a notable microfilaremia does not develop.¹¹ Because development of Dirofilaria spp is arrested in the human host, human being to human being transmission does not occur.^7,22

Q: How does Dirofilaria induce disease in human beings, and what are the clinical manifestations of human dirofilariasis?

A: Based on the hypothesized life cycle of Dirofilaria spp in human beings, there are 3 clinical manifestations: intravascular dirofilariasis, pulmonary dirofilariasis, and cutaneous dirofilariasis.^6,7,23-27 Intravascular and pulmonary dirofilariases are the result of infection with D immitis, whereas subcutaneous manifestations may be caused by D tenuis, D ursi, or D subdermata.^6,8,12,26

In intravascular dirofilariasis, adult D immitis are located in the chambers of the heart and its associated great vessels. Intravascular infections are typically single sex infections; therefore, microfilaremia is not a consistent finding.²⁶ The original report of this condition, however, did cite a mixed-sex infection (1 male and 1 female worm) but it did not mention whether microfilariae were detected in the blood.²⁴ All reported cases of intravascular dirofilariasis were incidental findings at autopsy.

In sharp contrast, pulmonary dirofilariasis caused by D immitis has been reported in more than 20 instances outside the United States and more than 60 instances in the United States.^6,25 Rather than residing in the right ventricle or pulmonary arteries, young adult D immitis are carried to the lung and produce a solitary pulmonary nodule.⁷ The infarction in pulmonary dirofilariasis is probably caused by occlusion of an arteriole when a thrombus forms around an impacted worm. The spherical shape results from the secondary granulomatous and fibrotic reaction when antigen from the degenerating worm diffuses into the surrounding tissues.²⁷ The presence of symptoms has followed a random distribution pattern and has not been associated with nodule location in the lungs, or with the age and sex of the patients. The nodule distribution pattern in the lungs has also been random and unrelated to the age and sex of the patient. Of the reported patients, 95% (56 of 59) had a single nodule, whereas 5% (3 of 59) had 2 nodules in separate lobes. Ninety percent (56 of 62) of the nodules contained a single worm. As with intravascular dirofilariasis, microfilaremia is seldom observed.⁶ One case of microfilaremia in a human being has been reported; however, the predilection site of adult worms was not determined.²⁸

Subcutaneous dirofilariasis in North America may be caused by 3 members of the genus Dirofilaria: D tenuis, D ursi, or D subdermata.^8,12 Most infected human beings have a single, subcutaneous nodule that may arise in any area of the body, but especially the conjunctiva, eyelid, scrotum, breast, arms, and legs. The lesion may be tender, painful, erythematous, and, in some instances, migratory. There may be single or multiple worms within the nodule.⁷

Dirofilaria ursi-like parasites have been diagnosed in 10 women from the northeastern United States and Canada.⁸ Nodules were located on or near the scalp, face, breast, or arm. In 4 of 8 cases for which clinical data were available, the nodule was described as painless; in 1, the area of the nodule was pruritic. In 2 cases, eosinophilia was pronounced, whereas in 3 cases, the eosinophil count was normal. In the remaining cases, leukograms were not reported. In 4 cases, live worms were recovered, and in 6 cases, dead necrotic worms were embedded in dense granulomatous tissue. Live worms or worms that had recently died lay coiled in a cavity surrounded by dense fibrous tissue with numerous eosinophils at the periphery. Worms were well preserved in some portions and necrotic in others. The authors noted the possibility that these nematodes might also be D subdermata, a subcutaneous filariid of porcupines. Dirofilaria subdermata has not been widely studied, and details of its life cycle are not known.⁸

Q: Are there any other diagnostic tests available for human dirofilariasis other than biopsy?

A: Presently, the only means of diagnosing human dirofilariasis is through biopsy and histologic examination of the tissue.¹ This is unfortunate, particularly in cases of pulmonary dirofilariasis, because complications can develop during thoracotomy.²⁸ The parasite can also be missed easily in the biopsy material unless special staining, such as the Movat stain, is used.^7,22

A limited amount of data are available on the use of serologic tests for the diagnosis of human dirofilariasis. Glickman et al²⁹ evaluated indirect hemagglutination (IHA) and ELISA in 8 human beings with pulmonary dirofilariasis. Of the 8 patients, 5 had antibodies to D immitis by the IHA test, and 6 were determined to be infected by the ELISA test. The specificity of these tests was also determined in human beings with other parasitic infections and neoplasms. The greatest amount of cross-reactivity was detected in human beings with filarial infections acquired outside the United States. Results of ELISA and IHA tests were negative in 7 human beings with neoplasms.

Studies of other possible means for diagnosing pulmonary dirofilariasis have been unsuccessful. The location of the lesion is not helpful in differentiating pulmonary dirofilariasis from other conditions. A study of 60 human beings with solitary pulmonary nodules from D immitis indicated that lesions developed in every lobe of the lung.⁶ Eosinophil counts vary considerably among people with pulmonary dirofilariasis, and are consequently of little value.

Diagnosis of cutaneous dirofilariasis may also be difficult.⁷ The subcutaneous nodule may or may not be tender, and develops over a period of several weeks.^7,8 Lesions usually contain a single worm that has begun to degenerate.⁷ Older lesions are characterized by a chronic granulomatous inflammation.

In all forms of dirofilariasis, determination of the species of worm is important epidemiologically. Worm species may be determined by examination of transverse sections.^1,8 Tissue samples from suspected cases should be sent to a pathologist who is familiar with the appearance of these parasites in the tissues.

Q: How common is human diroflariasis and who is most likely to become infected?

A: Human dirofilariasis rarely is reported; however, recently there have been more cases reported in the United States.⁵ Subcutaneous dirofilariasis was first reported in 1952, and an additional 23 cases were reported between 1952 and 1965.^5,30 Most of these cases were in the southeastern United States. Beaver et al⁵ summarized reports of an additional 10 cases of subcutaneous dirofilariasis caused by D ursi. All of these cases were in the northern United States and Canada.

Approximately 60 cases of D immitis from 15 states have been documented in human beings.^3,6,26 Eleven cases were reported before 1965 and 49 were reported between 1965 and 1985.⁵ The geographic distribution of these cases coincided with the distribution of canine dirofilariasis. Males were infected twice as often as females and 56% of all infections were identified in men and women 40 to 59 years old.⁶ The increase in reported cases may be related to the increased use of radiography for the early detection of cancer. Frances and Zimmerman³¹ studied intrapulmonary coin lesions identified at an Australian hospital and found that 54 of 71 (76%) were caused by carcinoma and only 1 (1%) was caused by dirofilariasis. Because pulmonary carcinoma is common in the United States, a similar pattern is likely to exist in this country.

Risk factors for dirofilariasis in human beings have not been clearly defined. The size of the dog population and the prevalence of canine dirofilariasis play a role in transmission of D immitis to human beings.⁶ However, dog ownership alone may not be an important risk factor.¹¹ The reason for the high rate of dirofilariasis in male human beings is not known; however, it may relate to preferential feeding of the mosquitoes.⁶ Of the 60 patients, 7 (12%) were immunocompromised; therefore, immunosuppression may play a role in human infection. People who are more likely to be outside when mosquitoes feed are at higher risk for infection.

Q: Are pet owners or veterinarians at high risk of acquiring human dirofilariasis?

A: Dog ownership was specifically mentioned in 20 patients with pulmonary dirofilariasis reported by Ciferri.⁶ Of these patients, 11 (55%) owned one or more dogs. These results do not provide enough information to evaluate the effect of dog ownership on the risk of human dirofilariasis. The chances of an individual becoming infected are directly related to his or her personal behavior or habits. Pet owners who walk their dogs at night in areas with trees, long grass, ponds, lakes, and open drainage ditches where mosquitoes breed are likely to be heavily exposed. Because transmission is only through contact with the vector, veterinarians are not at increased risk for infection with Dirofilaria spp.

Q: How can transmission of infections from pets or wild animals to human beings be prevented?

A: The transmission cycle of dirofilariasis can be interrupted in several different ways. Veterinarians play an important role in the prevention of dirofilariasis in human beings by encouraging pet owners to give their dogs preventive medicine.²⁸ The regular administration of larvicidal drugs to dogs is an effective means for controlling this disease.³² The drugs available are safe and effective. In general, larvicides should be administered beginning 1 month before the mosquito season, and continuing for 1 month after the first killing frost. Because the weather in many southern states is mild, preventive medication should be given throughout the year. Control of stray and feral dogs is also an important consideration for the control of dirofilariasis.¹¹ These animals represent a major reservoir for this disease.

Control of mosquitoes can also reduce exposure of man and animals to these parasites. The removal of breeding sites and proper drainage of low-lying areas can be helpful.³³ Mosquito larvicides may be used in some cases; however, resistance to these compounds can occur, and such compounds also disrupt the normal ecologic balance in an area.³⁴ Recently, the biological control of mosquitoes has been attempted in some areas, and the use of various species of fish to reduce larvae populations has been successful.^34,35

A final line of defense for dirofilariasis is the prevention of mosquito bites in both human beings and animals. Human beings can help prevent mosquito bites by the application of repellants and by wearing protective clothing.^33,34 All effective mosquito repellants contain deet (N, N,-diethyl-3-methylbenzamide). Walking dogs in the early evening hours when mosquitoes are most abundant should be avoided to reduce exposure in both human beings and animals.¹¹ Mosquitoes are not attracted to light, thus electrocution devices are not helpful for their control; their use may actually be detrimental because they destroy insects that may feed on mosquitoes.³³

Q: What drugs are most efficacious for eliminating all stages of heartworms from dogs and cats? What drugs are most efficacious for eliminating all stages of Dirofilaria spp from wild animals?

A: The treatment presently recommended by the American Heartworm Society for the various Dirofilaria life cycle stages in the dog are as follows: ¹ thiacetarsamide as an adulticide; ² dithiazanine as a microfilaricide; and ³ ivermectin, diethylcarbamazine (DEC), or styrylpyridinimdiethylcarbamazine as a larvicide.³² Benzimidazoles also are available in combination with DEC as a larvicide. Thiacetarsamide also may be used as an adulticide in cats. However, after treatment, the formation of thrombi is more frequent and severe than in dogs. Because D tenuis and D ursi are in wild animals and usually are diagnosed during postmortem examination, there are no approved recommendations for treatment.

Q: Is it possible to eliminate heartworms from an ecosystem once nidi of infection have become established?

A: The complete elimination of Dirofilaria immitis from an ecosystem would be difficult. The prevention of this infection in the canine reservoir requires the diligent administration of DEC by pet owners. In some areas, approximately half of the pet owners do not seek veterinary medical care³⁶ and they probably would not give their dogs preventive medication. Wild canids also may play an important role in transmission of D immitis. In foxes, the disease is similar to that in dogs, and even the California sea lion develops a parasitemia.^3,37 Stray and feral dogs also represent a major reservoir for D immitis, and these dogs are at high risk for infection with the parasite. These factors indicate that canine heartworms can be controlled; however, elimination of this parasite would be impossible.

Footnote

(a) Schlotthauer JC, Department of Veterinary Pathobiology, University of Minnesota, St Paul: Personal communication, 1988.

References

1. Gutierrez Y. Diagnostic features of zoonotic filariae in tissue sections. Hum Pathol 1984; 15:514-525.

2. Soulsby EJL. Filaroidea: Filariidae: Dirofilaria. In: Helminths, arthropods and protozoa of domesticated animals. 7th ed. Philadelphia: Lea & Febiger, 1982; 306-312.

3. Otto GF. Occurrence of heartworm in unusual locations and in unusual hosts, in Proceedings. Heartworm Symp 1974; 6-13.

4. Dau J, Barrett R. Dirolilaria. In: Dieterich RA, ed. Alaskan wildlife diseases. Fairbanks, Alaska: Fairbanks Institute of Arctic Biology, University of Alaska. 1981; 146-148.

5. Beaver PC, Orihel TC. Human infection with filariae of animals in the United States. Am J Trop Med Hyg 1965; 14:1010-1029.

6. Ciferri F. Human pulmonary dirofilariasis in the United States: a critical review. Am J Trop Med Hyg 1982; 31:302-308.

7. Neafie RC, Connor DH, Meyers WM. Dirofilariasis. In: Binford CH, Connor DH, eds. Pathology of tropical and extraordinary diseases. Washington, DC: Armed Forces Institute of Pathology 1976; 2:391-396.

8. Beaver PC, Wolfson JS, Waldron MA, et al. Dirofilaria ursi-like parasites acquired by humans in the northern United States and Canada: report of two cases and brief review. Am J Trop Med Hyg 1987; 37:357-362.

9. Payan M. Human infection with Dirofilaria. Arch Dermatol 1978; 114:593-594.

10. Bruijning CFA. Human dirofilariasis: a report of the first case of ocular dirofilariasis in the Netherlands and a review of the literature. Trop J Med 1981; 33:295-305.

11. Grieve RB, Lok JB, Glickman LT. Epidemiology of canine heartworm infection. Epidemiol Rev 1983; 5:220-246.

12. Orihel TC, Beaver BC. Morphology and relationship of Dirofilaria tenuis and Dirofilaria conjunctivae. Am J Trop Med Hgy 1965; 14:1030-1043.

13. Crum JM, Nettles VF, Davidson WR. Studies on endoparasites of the black bear (Ursus americanus) in the Southeastern United States. J Wildl Dis 1978; 14:178-186.

14. Jellison WL. Parasites of porcupines of the genus Erethizon. Trans Am Microsc Soc 1933; 52:42-47.

15. Taylor AER.The development of Dirofilaria immitis in the mosquito Aedes aegypti. J Helminthol 1960; 34:27-38.

16. Church EM, Georgi JR, Robson DS. Analysis of the microfilarial periodicity of Dirofilaria immitis. Cornell Vet 1976; 66:333-346.

17. Hendrix CM, Brunner CJ, Bellamy LK. Natural transmission of Dirofilaria immitis by Aedes aegypti. J Am Mosq Control Assoc 1986; 2:48-51.

18. Hendrix CM, Schlotthauer JC, Bemrick WJ. Dirofilaria immitis in the mosquito intermediate host. Canine Pract 1985; 12:32-38.

19. Kotani T, Powers KG. Developmental stages of Dirofilaria immitis in the dog. Am J Vet Res 1982; 43:2199-2206.

20. Cupp EW, Stokes GM. Feeding patterns of Culex salinarius Coquillett in Jefferson Parish, Louisiana. Mosq News 1976; 36:332-335.

21. Edman JD. Host-feeding patterns of Florida mosquitoes I. Aedes, Anopheles, Coquillettidia, Mansonia and Psorophora. J Med Entomol 1971; 8:687-695.

22. Merrill JR, Otis J, Logan WD, et al. The dog heartworm (Dirofilaria immitis) in man. An epidemic pending or in progress? JAMA 1980; 243:1066-1068.

23. Abadie SH, Swartzwelder JC, Holman RL. A human case of Dirofilaria immitis infection. Am J Trop Med Hyg 1965; 14:117-118.

24. Faust EC, Thomas EP, Jones J. Discovery of human heartworm infection in New Orleans. J Parasitol 1941; 27:115-122.

25. Takeuchi T, Asami K, Kobayashi S, et al. Dirofilaria immitis infection in man: report of a case of the infection in heart and inferior vena cava from Japan. Am J Trop Med Hyg 1981; 30:966-969.

26. Goldstein JD, Smith DR. Dirofilaria immitis in a portacaval shunt. Hum Pathol 1985; 16:1172-1173.

27. Dayal Y, Neafie RC. Human pulmonary dirofilariasis. Am Rev Respir Dis 1975; 112:437-443.

28. Human dirofilariasis: An emerging zoonosis. Norden News 1983; Winter/Spring:4-8.

29. Glickman LT, Grieve RB, Schantz PM. Serologic diagnosis of zoonotic pulmonary dirofilariasis. Am J Med 1986; 80:161-164.

30. Faust EC, Agosin M, Garcia-Laverde A, et al. Unusual findings of filarial infections in man. Am J Trop Med Hyg 1952; 1:239-247.

31. Francis DB, Zimmerman PU. Intrapulmonary coin lesions: the changing pattern. Med J Aust 1986; 144:122-123.

32. American Heartworm Society. Recommended procedures for the management of canine and feline heartworm disease, in Proceedings. Heartworm Symp 1986; 2103-2106.

33. Schreck CE. Protection from blood-feeding arthropods. In: Auerbach P, Geehr E, eds. Management of wilderness and environmental emergencies. St Louis, Mo: CV Mosby Co; in press.

34. Rice PL, Pratt HD. Epidemiology and control of vector-borne diseases. US Department of Health, Education, and Welfare, 1976.

35. Bay EC. Adaptation studies with the Argentinian pearl fish, Cynolebias bellotti for its introduction into California. Copeia 1966; 4:839-846.

36. Dorn CR. Veterinary medical services: utilization by cat and dog owners. J Am Vet Med Assoc 1970; 156:321-327.

37. Hirth RS, Nielsen SE. Vascular lesions of Dirofilaria immitis in the red fox. J Am Vet Med Assoc 1966; 149:915-919.

Addendum (1995)

An additional 37 human cases of Dirofilaria immitis have been reported in the United States since publication of the initial report. A total of 97 human cases in the United States now have been reported in literature, including 10 cases over a 19-year period from a single hospital.¹ Human cases of D immitis have been confirmed in 16 states and, with the exception of Texas and Louisiana, all cases have been reported from states east of the Mississippi river. Reduction in incidence of human infections is best achieved by diagnosis, treatment, and prevention of D immitis infections in dogs. Seven antigen test kits (3 membrane ELISA, 2 microwell, 1 wand, and 1 hemagglutination) now are available for use in private veterinary practices, and all have good sensitivity and specificity.² Levamisole, ivermectin, and milbemycin oxime recently have been used as microfilaricides in infected dogs.³ Prevention of D immitis infection in dogs also has been made easier by monthly administered doses of either ivermectin^a,b or milbemycin oxime.^4c

Both IgM and IgG ELISA for D immitis antibodies have been used in studies of human populations. An investigation of 395 people in an endemic region of Spain indicated a 9.3% seropositivity rate, with IgG antibodies being more frequent in older people and IgM antibodies being more frequent in younger people.⁵ Titer of IgM antibodies peaked in summer, whereas IgG antibody titer peaked in winter.⁶ An ELISA also has been used to detect D immitis-specific IgE in human sera. This test was reported to have good sensitivity and specificity for detection of early infections; however, false-negative results were obtained in individuals with lung lesions.⁷

Even with improvements in detection of antibodies to D immitis in human beings, diagnosis remains difficult and often must be achieved, using immediate thoracotomy and wedge resection.¹ Stains, such as Tinopol CBS-X and Calcufluor white, have been used for identification of D immitis parasites on deparaffinized rehydrated tissue slides⁸; in that study, worm fragments stained green and background tissue stained red. Electrophoresis patterns also have been used to identify species of Dirofilaria in lesions.⁹

Some recently described human cases of D immitis are of interest. Three cases of transient solitary pulmonary nodules have been described.¹⁰ The authors concluded that these cases could be managed conservatively by use of repeat radiography and serologic testing. A gravid adult worm was found in the lungs of a patient with lymphoid leukemia in Columbia.¹¹ This rare finding likely resulted from the simultaneous presence of leukemia and dirofilariasis.

Footnotes

(a) Heartguard-30, Merck Agvet, Rahway, NJ.
(b) Heartguard-30 Plus, Merck Agvet, Rahway, NJ.
(c) Interceptor, Ciba-Geigy Corp, Greensboro, NC.

References

1. Asimacopoulos PJ, Katras A, Christie B. Pulmonary dirofilariasis. The largest single-hospital experience. Chest 1992;102:851-855.

2. McTier TL. A guide to selecting adult heartworm antigen test kits. Vet Med 1994;88:529-544.

3. Blagburn BL. Microfilaricidal therapy: Review and update. Vet Med 1994;88:630-638.

4. Dzimianski MT. Developing a heartworm prevention program. Vet Med 1994;88:545-550.

5. Simon F, Muro A, Cordero M, et al. A seroepidemiologic survey of human dirofilariasis in Western Spain. Trop Med Parasitol 1991;42:106-108.

6. Muro A, Cordero M, Ramos A, et al. Seasonal changes in the levels of anti-Dirofilaria immitis antibodies in an exposed human population. Trop Med Parasitol 1991;42:371-374.

7. Green LK, Ansari MQ, Schwartz MR, et al. Non-specific fluorescent whitener stains in the rapid recognition of pulmonary dirofilariasis: A report of 20 cases. Thorax 1994;49:590-593.

8. Espinoza E, Cordero M, Muro A, et al. Anti-Dirofilaria immitis IgE: Seroepidemiology and seasonal variation in an exposed human population. Trop Med Parasitol 1993;44:172-176.

9. Cancrini G, D'Amelio S, Mattiucci S, et al. Identification of Dirofilaria in man by multilocus electrophoretic analysis. Ann Trop Med Parasitol 1991;85:529-532.

10. Cordero M, Muro A, Simon F, et al. Are transient pulmonary solitary nodules a common event in human dirofilariasis? Clin Invest 1992;70:437-440.

11. Beaver PC, Orihel TC, Leonard G. Pulmonary dirofilariasis: Restudy of worms reported gravid. Am J Trop Med Hyg 1990;43:167-169.