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Pulmonary dirofilariasis in man
Pulmonary dirofilariasis in man A case report and review of the literature Pulmonary dirofilariasis in man is becoming a well-recognized entity. Its pathogenesis and histopathological picture have been well characterized but the preoperative diagnosis still remains a challenge. The roentgenographic picture, usually described as a "coin lesion," is nonspecific and easily mistaken for other inflammatory and neoplastic nodules . Forty-seven clinical instances of pulmonary dirofilariais have. been reported in the literature, with most of them in the last two decades. Considering the entire clinical picture, a strong suspicion can be based on serological studies, thus improving the possibilities of a correct preoperative diagnosis.
Newell B. Robinson, M.D., Carlos M. Chavez, M.D., and J. Harold Conn, M.D., Jackson, Miss.
PUlmOnary dirofilariasis in man has been recognized in recent years as an emerging zoonosis. The ravages of the canine heart worm have been familar to the veterinarian and researcher, but only since the late 1940' s and early 1950's has the incidence of this parasite in man become evident. Subcutaneous dirofilariasis, usually caused by Dirofilaria tenuis (formerly D. conjunctivae), is the most common manifestation in man.' The second most common manifestation is as a pulmonary nodule, discovered in routine x-ray films of asymptomatic individuals or, in some cases, those with mild respiratory symptoms (cough, chest pain, hemoptysis). Pulmonary dirofilariasis dates back to 1887, when delvlagalhaes" reported the discovery of a single male and single female filaria in the left ventricle of a male child from Rio de Janeiro. In 1940 Faust, Thomas, and Jones" reported the first confirmed case involving D. immitis found in the inferior vena cava of a 73-year-old cadaver. Involvement of the pulmonary artery by the parasite was reported in 1965 by Abadie, Swartzwelder, and Holman" but the first documented infection resulting in pulmonary infarction in man was described by Dashiell" in 1961. Since that time a total of 46 cases From the Department of Surgery, Veterans Administration and University Medical Centers, Jackson, Miss. Received for publication March 11, 1977. Accepted for publication April 14, 1977. Address for reprint: Dr. Carlos M. Chavez, 440 E. Woodrow Wilson, Suite 601, Jackson, Miss. 39216.
of pulmonary dirofilariasis in man manifested as pulmonary infarctions have been reported in the English literature. Mosquito vectors act as the mode of transmission for the microfilariae shed by the adult female parasite. The symptomatology is characteristically mild, if present at all. Symptoms include cough, chest pain, fever, malaise, anorexia, hemoptysis, chills, and dyspnea. Eosinophilia is a common sign. The following case is the forty-seventh reported to date.
Case report A 66-year-old white man was referred to the Veterans Administration Hospital, Jackson, Miss., for evaluation of symptoms which included productive cough, chest tightness, malaise, and weakness on two occasions - the first 3 months and the second 2 weeks prior to admission. Except for a history of hypertension, gout, and pneumonia with hemoptysis 30 years prior to admission, the patient's past history was unremarkable. At the time of admission he was living in Sartartia, Mississippi. Physical examination was essentially unremarkable. Chest roentgenograms revealed a 2 cm., relatively well-defined, uncalcified nodule located in the posterior apical segment of the left upper lobe (Fig. 1). Tomograms at 13 em. confirmed a 2 cm., well-defined, left apical mass (Fig. 2). Bronchoscopy, including biopsy and washings for cytology, sputums stained and cultured for acid-fast bacillus, fungus, and bacteria were all negative. Results of pulmonary function studies and the remainder of the laboratory studies were within normal limits. No eosinophilia was reported on either occasion. Operation. A left thoracotomy was performed on Feb. 9, 1976. Exploration of the lung revealed two nodules measuring 4 by 2 by 2.5 cm. and 2.5 by 1.5 by 1.5 cm., located in 403
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Fig. 1. Preoperative chest roentgenogram showing the "coin" lesion in the left upper lobe (arrow). the left upper lobe. These were removed by wedge resection. The postoperative course and recovery of the patient were uneventful. Gross examination revealed two well-circumscribed nodules that on cut surface appeared grayish white to yellowish tan and of a somewhat honeycombed appearance. Their consistency was firm, and both nodules were surrounded entirely by lung tissue described as reddish tan and somewhat rubbery. Microscopically both nodules were similar and characterized by an area of coagulation necrosis surroundedby a rim of fibrosis containing scattered lymphocytes, monocytes, and infrequent eosinophils. A trace of multinucleated giant cells were present within the rim. Each nodule contained a centrally located, medium-size artery that was thrombosed and had undergone coagulation necrosis. The lumen of each artery contained an autolyzed, wormlike structure, cut in longitudinal, transverse, and diagonal sections. One transverse section had undergone calcification. The parasite itself was 150 f.Lm in diameter, with characteristic broad lateral chords and thick cuticle. There were lateral chords, somatic muscle, and only one identifiable reproductive duct. The cuticle was marked with transverse striations 4 f.Lm apart. One calcified segment was noted. Discussion In 1975, Dayal and Neafie" reviewed 41 cases of human pulmonary dirofi1ariasis. In our review, five additional cases surfaced, which, in addition to the present case report, brings the total reported since 1961 to 47 (Table I). Mode of transmission. Most cases have occurred in areas that correspond to the distribution of the canine heart worm in a coastal belt that extends from central New Jersey, south along the eastern seaboard, and across the gulf states to Texas, inland for 50 to 75 miles. It has been estimated that close to 40 percent of
Fig. 2. Tomogram of the left upper lobe area outlining the lesion. The borders are sharp and no evidence of gross calcification is seen. the outdoor canine population of the coastal cities in this enzootic area are infected with D. immitis, and infection is more prevalent near mosquito-breeding waters. 7 In Australia, 12 percent of 761 dogs in the Brisbane RSPCA shelter, 20 percent of 296 dogs presenting to the Veterinarian Clinic at the University of Queensland, and 37 percent of 94 dogs tested in Townsville, Queensland, were found to harbor the parasite." This distribution has long been recognized by veterinarians in the past, but only in recent years has a new rise in both prevalence and incidence been recognized in the canine population." This corresponds with the relative novelty of human heart worm infections. The life cycle of D. immitis consists primarily of a vector-intermediate host, the mosquito (Culex, Aedes, Myzorhynchus, Anopheles) and a host, the dog, with the possibility of some species of fleas, ticks, and lice acting as vectors."?' 11 The adult female worm residing in the right ventricle of the dog may attain a size several millimeters in diameter and up to 24 cm. in length. These worms are larviparous, shedding several thousand microfilariae per day. The microfilariae are approximately 315 f.t in length, exhibit an incomplete nocturnal periodicity, and in hearts of infected dogs it is not unusual to find several hundred microfilariae per cubic milliliter of blood. These microfilariae are ingested by the mosquito during a blood meal and subsequently undergo two molts within the malpighian tubules.
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Table I. Review of recently reported cases of human pulmonary dirofilariasis Ref. No. 34
I
Age
I
Sex
I
Site
45
M
Baltimore, Md.
7
48
M
7
59
M
Sitka, Alaska: Houston x 4 yr. Texas
35
48
F
36 Present case
57 61
F M
I
Massachusetts, Maryland, Florida Miami, Fla. Sartartia, Miss.
Within 10 to 17 days, they have reached the infective third stage and have come to rest within the labium of the mosquito vector. During the next blood meal these larvae escape through the labella and are deposited on the skin of the next host, whereupon they actively progress toward the puncture wound provided by the mosquito fascicle. 12 They then migrate into the subcutaneous tissues and muscle sheaths, where they reside, molt, and mature for 80 to 120 days. After one additional molt, they migrate into venous capillary channels, are transported to the right heart chambers, and within 6 months are sexually mature and ready to mate and repeat the cycle. Man is a dead-end host. Should the cycle be arrested in the subcutaneous tissues, as is usually the case, subcutaneous nodules are the result. Due perhaps to altered immunological patterns of the host, vector, or parasite, an occasional larva may reach the right ventricle in man, implant, and develop into a sexually immature form before death and embolization to the lungs. This is the apparent fate of the parasites in the cases reviewed. To date, no microfilaremia has been documented in man, supporting the conclusion that D. immitis larvae do not reach sexual maturity in man. Signs and symptoms. The symptomatology associated with human pulmonary dirofilariasis is summarized in Table II. The most common presentation is that of the asymptomatic nodule discovered in routine roentgenographic examination. The symptomatic patient most commonly presents with cough, chest pain, and hemoptysis. Eosinophilia is a common finding. A less common presentation is that of a "flulike" syndrome. Roentgenographic examination usually reveals a
Symptoms Dry, nonprod. cough x 2 mo. Asymptomatic, 5 percent eosinophilia Malaise, anorexia, sputum prod., 4 percent eosinophilia 69 percent eosinophilia, hemoptysis Cough x I mo. Cough, malaise, weakness, chest pain x 3 mo.
I
Location Unknown
Coin, RLL 1.5 em. LUL 3 em.; RUL 2 em. LLL
M 275 p,m
Ill-defined LUL. 3 by 3 cm. RLL 3 cm. 2 coin, LUL 2 em.
Table II. Signs and symptoms in order offrequency _ _ _ _ _ _ _ _1
No. of cases
I
Percent
Asymptomatic Cough Chest pain Eosinophilia Hemoptysis Fever
27 II 8 7 4 3
57.4 23.4 17.0 14.9 8.5 6.4
Total
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lOa
relatively well-circumscribed "coin" lesion without calcification; this will occasionally present as a more diffuse image, suggesting carcinoma. There are no distinct characteristic findings, and usually at this point the differential diagnosis includes carcinoma, caseous granulomas, eosinophilic granulomas (histiocytosis), Wegener's granulomatosis, and thromboembolism among others. The fact that this finding on roentgenogram indeed does represent embolic phenomenon with subsequent coagulation necrosis and inflammatory reaction is rather interesting in contradistinction to the classic x-ray description of a "wedge-shaped" defect. We feel that this is due to two factors; (1) the level of thrombotic occlusion and (2) subsequent exotoxic reaction following parasite autolysis. Of the 47 patients with pulmonary dirofilariasis, 18 (38.3 percent) were female and 29 (61.7 percent) were male. This perhaps reflects differences in exposure to the parasite, although intrinsic immunological and hormonal characteristics could be factors. The average age of the patients was 50 years, with a range from 28 to 75 years. Younger patients are less commonly seen, and this has been attributed to the fact that children are
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Fig. 3. Pulmonary artery branch containing the parasite . Oblique and transverse sections of the dirofilaria show the parasite in autolysis .
examined less often roentgenographically than are adults. Another theory involves immunological differences and acquired immunity . Diagnosis and treatment. Correct preoperative diagnosis has not been made in any of the cases reported to date. Various attempts have been made at serological detection in patients postoperatively and indeed one case with positive intradermal protein testing!" and two cases with positive hamagglutination have been reported.':' A recent study in Australia investigated the prevalence of antibodies to D . immitis in aborigines and Caucasians as well as in the canine population. Prevalence among dogs parallels the estimated infection among the Australian canine population (85 percent in some locations). Twenty percent of the aboriginal sera were positive as compared to 2.6 percent in Caucasians in a random selection. However, Caucasians with eosinophilia were found to have positive sera in 22.1 percent of cases . Five cases of Caucasian Australians with pulmonary dirofilariasis have been reported as compared to none in aborigines, suggesting acquired immunity or at least implicating immunological factors. IS From these data several conclusions are suggested: (I) early exposure results in acquired immunit y; (2) eosinophilia coupled with coin lesions and nonspecific symptoms raises the index of suspicion in favor of parasitic embolic etiology. The ultimate diagnosis and definitive treatment involve wedge resection of the affected lobe .
Pathological findings. The combination of infarction, endarteritis, eosinophilic pneumonitis, and granulomatous response should alert the pathologist to a diagnosis of dirofilariasis. The lesion is well known to veterinary pathologists and has been implicated in the etiolog y of cardiac complications, including congestive heart failure, in the canine population. A granulomatous response was present only around the branches of the pulmonary artery containing dead adult
worms." In man the findings are consistent with a rounded infarction with subsequent granulomatous response. The gross appearance has been described variously as well-circumscribed, grayish-yellow nodule, approximately 2 to 3 em . in diameter, surrounded by normal lung parenchyma. Microscopically , the involved parenchyma has undergone coagulation necrosis surrounded by a rim of fibrosis and scattered lymphocytes, monocyte s, occasional eosinophils, and multinucleated giant cells . In the center of the lesion is located a necrotic thrombosed artery containing the dead autolyzed and occasionally calcified parasite (Figs. 3 and 4). Occasionally the artery has been found to be only partially occluded, leading to the postulation that the inflammatory response and subsequent pathology actually result from toxin released by the autolyzing worm. Peripheral endarteritis may be noted. Dirofilaria have a multilayered cuticle 4 to 6 110m thick , consisting of an outer smooth layer, a thicker
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Fig. 4. Extensive coagulation necrosis surround two segments of the parasite in autolysis. One segment has undergone calcification (arrow). fibrous middle layer, and a thin lamellar inner layer. Transverse striations 4 to 7 JLm apart are characteristic. Two internal cuticular ridges support lateral chords and a thick somatic muscle bundle . The female has two reproductive ducts and the male has one. The diameter varies from 100 to 330 JLm.
3
Summary Human pulmonary dirofilariasis affects individuals living near coastal mosquito-breeding areas . This condition is rare but increasing in recognition and should be included in the differential diagnosis of pulmonary nodules. Although commonly asymptomatic , cough, chest pain, and hemoptysis may be the first indication of its presence in the lung, particularly if associated with eosinophilia. The diagnosis has been made in all cases at operations. Serological studies have correlated well with the incidence of infection and may be of value in the future for the preoperative recognition of this entity. There seems to be a prevalence among males and older individuals. An updated review of the literature is made with description of a case personally treated by the authors . REFERENCES Schlotthauer, J. C.; Harrison, E. G., Jr., and Thompson, J. H. , Jr.: Dirofilariasis-An Emerging Zoonosis? Arch Environ. Health 19: 887, 1969. 2 de Magalhaes, P. S.: Descripcao de uma especie de
4 5 6 7
8 9 10 II
filariasencantradas no coraciiohumano, predidida de uma contribuicao para 0 estudo de filariose de Wucherer e do respectivo parasito adulto, a Filaria bancrofti (Cobbold) on Filaria sanguis hominis (Lewis), Rev. dos cursos praticos e teoricos da Faculd. de Med. do Rio de Janeiro, 3 ann., 3: 4193 , 1887. Faust, E. C., Thomas, E. P., and Jones, J.: Discovery of Human Heart Worm Infection in New Orleans, 1. Parasito!. 27: 115, 1941. Abadie, S. H., Swartzwelder, J. C., and Holman, R. L.: A Human Case of Dirofilaria immitis Infection, Am. J. Trop. Med 14: 117, 1965. Dashiell, G. F.: A Case of Dirofilariasis Involving the Lung, Am. J. Trop. Med. 10: 37, 1961. Dayal, Y., and Neafie, R. c.: Human Pulmonary Dirofilariasis: A Case Report and Review of the Literature, Am. Rev. Respir. Dis. 112: 437, 1975. Awe, R. 1. , Mattox, K. L., Alvarez, B. A. , Stork, W. J., Estrada, R., and Greenberg, D. S.: Solitary and Bilateral Nodules Due to Dirofilaria immitis, Am. Rev. Respir. Dis. 122: 445, 1975. Carlisle, L. H.: The Incidence of Dirofilaria immitis (Heart Worm) in Dogs in Queensland, Aust. Vet. 1. 45: 535, 1969. Altman, L. K.: Heart Worm in Pet Dogs is Found Spreading, New York Times, Sept. 3, p. 26, 1972. Ludlow, K. W., Jackowski, L. A., and OUo, G. F.: Potential Vectors of Dirofilaria immitis, J. Am. Vet. Med. Assoc. 157: 1354, 1970. Otto, G. F.: Geographical Distribution, Vectors, and Life Cycle of Dirofilaria immitis, J. Am. Vet. Med. Assoc. 154: 370, 1969.
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12 Southgate, B. A., and Bryan, H.: Human Pulmonary Dirofilariasis: Entry Methods of Infective Larvae, Chest 68: 274, 1975. 13 Navarette-Reyna, A., and Noon, G.: Pulmonary Dirofilariasis Manifested as a Coin Lesion. Report of a Case and Review of the Literature, Arch. Patho!. 85: 266, 1968. 14 Yoshimura, H., and Yokogawa, M.: Dirofilaria Causing Infarct in Human Lung, Am. J. Trop. Med. Hyg. 19: 63, 1970. 15 Welch, J. S., and Dobson, C.: The Prevalence of Antibodies to Dirofilaria immitis in Aboriginal and Caucasian Australians, Trans. R. Soc. Trop. Med. Hyg. 68: 466, 1974. 16 Adcock, L.: Pulmonary Arterial Lesions in Canine Dirofilariasis, Am. 1. Vet. Res. 22: 655, 1961. 17 Goodman, M. L., and Gore, I.: Pulmonary Infarct Secondary to Dirofilaria Larva, Arch. Intern. Med. 113: 702, 1964. 18 Beaver, P. c., and Oribel, T. C.: Human Infection With Filariae of Animals in the United States, Am. 1. Trop. Med. Hyg. 14: 1010, 1965. 19 Moore, M. P., Jr.: The Pathologic Aspects of Ascariasis, South Med. J. 47: 825, 1954. 20 Osborne, D. P., Brown, R. c., and Dimmette, R. S.: Solitary Pulmonary Nodule Due to Ascaris lumbricoides, Dis. Chest 40: 308, 1961. 21 Harrison, E. G., Jr., and Thompson, J. H., Jr.: Dirofilariasis of Human Lung, Am. J. Clin. Patho!. 43: 224, 1965. 22 Beskin, C. A., Colvin, S. H., and Beaver, P. c.: Pulmonary Dirofilariasis. Cause of Pulmonary Nodular Disease, J. A. M. A. 198: 665, 1966. 23 Tuazon, R. A., Firestone, F., and Blaustein, A. U.: Human Pulmonary Dirofilariasis Manifested as a "Coin" Lesion. A Case Report, J. A. M. A. 199: 45,1967.
Thoracic and Cardiovascular Surgery
24 Spear, H. c., Daughtry, D. c.. Chesney, J. D., Gentsch, T. 0., and Larsen, P. B.: Solitary Pulmonary Lesion Due to Dirofilaria, N. Eng!. 1. Med 278: 832, 1968. 25 Tannehill, A. W., and Hatch, H. B.: Coin Lesions of the Lung Due to Dirofilaria immitis, Dis. Chest 53: 369, 1968. 26 Lewis, J. F., Williams, R. W., and Tinsley, E. A.: Pulmonary "Coin" Lesion Due to Dirofilaria immitis, Arch. Surg. 98: 388, 1969. 27 Neafie, R. C.; and Piggott, J.: Human Pulmonary Dirofilariasis, Arch. Patho!' 92: 342, 1971. 28 Moorhouse, D. E., Abrahams, E. W., and Stephens, B. J.: Human Pulmonary Dirofilariasis in Queensland, Med. J. Aust. 2: 1230, 1971. 29 Brine, J. A. S., Finlay-Jones, L. R., and Charters, A. D.: Pulmonary Dirofilariasis. A Case in Western Australia, Med. J. Aust. 2: 1238, 1971. 30 Navarrette, A. R.: Pulmonary Dirofilariasis, Chest 61: 51, 1972. 31 Feld, H.: Dirofilaria immitis (Dog Heartworm) as a Cause of a Pulmonary Lesion in Man, Radiology 108: 311, 1973. 32 Hendricks, G. L., Jr., Barnes, W. T., and Lerman, D. S.: Dirofilaria immitis. A Cause of Pulmonary Coin Lesion in Human Beings, Ann. Thorac. Surg. 16: 526, 1973. 33 Hoch, W. S., Wershba, M. E., and Patchefsky, A. S.: Pulmonary Dirofilariasis. J. THORAC. CARDIOVASC. SURG. 67: 159, 1974. 34 Martire, R., Liberman, I. I., and Goldman, S. M.: Dirofilaria immitis (Dog Heartworm) as a Cause of Pulmonary Infarction in Man, Md. State Med. J. 24: 62, 1975. 35 Gershwin, L. J., Gershwin, M. E., and Kritzman, J.: Human Pulmonary Dirofilariasis, Chest 66: 92, 1974. 36 Robinson, M. J., Viamonte, M., and Viarmonte, M.: Dirofilariasis: Diagnostic Consideration for Pulmonary Coin Lesions, South. Med. 1. 67: 461, 1974.
Newell B. Robinson, M.D., Carlos M. Chavez, M.D., and J. Harold Conn, M.D., Jackson, Miss.
PUlmOnary dirofilariasis in man has been recognized in recent years as an emerging zoonosis. The ravages of the canine heart worm have been familar to the veterinarian and researcher, but only since the late 1940' s and early 1950's has the incidence of this parasite in man become evident. Subcutaneous dirofilariasis, usually caused by Dirofilaria tenuis (formerly D. conjunctivae), is the most common manifestation in man.' The second most common manifestation is as a pulmonary nodule, discovered in routine x-ray films of asymptomatic individuals or, in some cases, those with mild respiratory symptoms (cough, chest pain, hemoptysis). Pulmonary dirofilariasis dates back to 1887, when delvlagalhaes" reported the discovery of a single male and single female filaria in the left ventricle of a male child from Rio de Janeiro. In 1940 Faust, Thomas, and Jones" reported the first confirmed case involving D. immitis found in the inferior vena cava of a 73-year-old cadaver. Involvement of the pulmonary artery by the parasite was reported in 1965 by Abadie, Swartzwelder, and Holman" but the first documented infection resulting in pulmonary infarction in man was described by Dashiell" in 1961. Since that time a total of 46 cases From the Department of Surgery, Veterans Administration and University Medical Centers, Jackson, Miss. Received for publication March 11, 1977. Accepted for publication April 14, 1977. Address for reprint: Dr. Carlos M. Chavez, 440 E. Woodrow Wilson, Suite 601, Jackson, Miss. 39216.
of pulmonary dirofilariasis in man manifested as pulmonary infarctions have been reported in the English literature. Mosquito vectors act as the mode of transmission for the microfilariae shed by the adult female parasite. The symptomatology is characteristically mild, if present at all. Symptoms include cough, chest pain, fever, malaise, anorexia, hemoptysis, chills, and dyspnea. Eosinophilia is a common sign. The following case is the forty-seventh reported to date.
Case report A 66-year-old white man was referred to the Veterans Administration Hospital, Jackson, Miss., for evaluation of symptoms which included productive cough, chest tightness, malaise, and weakness on two occasions - the first 3 months and the second 2 weeks prior to admission. Except for a history of hypertension, gout, and pneumonia with hemoptysis 30 years prior to admission, the patient's past history was unremarkable. At the time of admission he was living in Sartartia, Mississippi. Physical examination was essentially unremarkable. Chest roentgenograms revealed a 2 cm., relatively well-defined, uncalcified nodule located in the posterior apical segment of the left upper lobe (Fig. 1). Tomograms at 13 em. confirmed a 2 cm., well-defined, left apical mass (Fig. 2). Bronchoscopy, including biopsy and washings for cytology, sputums stained and cultured for acid-fast bacillus, fungus, and bacteria were all negative. Results of pulmonary function studies and the remainder of the laboratory studies were within normal limits. No eosinophilia was reported on either occasion. Operation. A left thoracotomy was performed on Feb. 9, 1976. Exploration of the lung revealed two nodules measuring 4 by 2 by 2.5 cm. and 2.5 by 1.5 by 1.5 cm., located in 403
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Fig. 1. Preoperative chest roentgenogram showing the "coin" lesion in the left upper lobe (arrow). the left upper lobe. These were removed by wedge resection. The postoperative course and recovery of the patient were uneventful. Gross examination revealed two well-circumscribed nodules that on cut surface appeared grayish white to yellowish tan and of a somewhat honeycombed appearance. Their consistency was firm, and both nodules were surrounded entirely by lung tissue described as reddish tan and somewhat rubbery. Microscopically both nodules were similar and characterized by an area of coagulation necrosis surroundedby a rim of fibrosis containing scattered lymphocytes, monocytes, and infrequent eosinophils. A trace of multinucleated giant cells were present within the rim. Each nodule contained a centrally located, medium-size artery that was thrombosed and had undergone coagulation necrosis. The lumen of each artery contained an autolyzed, wormlike structure, cut in longitudinal, transverse, and diagonal sections. One transverse section had undergone calcification. The parasite itself was 150 f.Lm in diameter, with characteristic broad lateral chords and thick cuticle. There were lateral chords, somatic muscle, and only one identifiable reproductive duct. The cuticle was marked with transverse striations 4 f.Lm apart. One calcified segment was noted. Discussion In 1975, Dayal and Neafie" reviewed 41 cases of human pulmonary dirofi1ariasis. In our review, five additional cases surfaced, which, in addition to the present case report, brings the total reported since 1961 to 47 (Table I). Mode of transmission. Most cases have occurred in areas that correspond to the distribution of the canine heart worm in a coastal belt that extends from central New Jersey, south along the eastern seaboard, and across the gulf states to Texas, inland for 50 to 75 miles. It has been estimated that close to 40 percent of
Fig. 2. Tomogram of the left upper lobe area outlining the lesion. The borders are sharp and no evidence of gross calcification is seen. the outdoor canine population of the coastal cities in this enzootic area are infected with D. immitis, and infection is more prevalent near mosquito-breeding waters. 7 In Australia, 12 percent of 761 dogs in the Brisbane RSPCA shelter, 20 percent of 296 dogs presenting to the Veterinarian Clinic at the University of Queensland, and 37 percent of 94 dogs tested in Townsville, Queensland, were found to harbor the parasite." This distribution has long been recognized by veterinarians in the past, but only in recent years has a new rise in both prevalence and incidence been recognized in the canine population." This corresponds with the relative novelty of human heart worm infections. The life cycle of D. immitis consists primarily of a vector-intermediate host, the mosquito (Culex, Aedes, Myzorhynchus, Anopheles) and a host, the dog, with the possibility of some species of fleas, ticks, and lice acting as vectors."?' 11 The adult female worm residing in the right ventricle of the dog may attain a size several millimeters in diameter and up to 24 cm. in length. These worms are larviparous, shedding several thousand microfilariae per day. The microfilariae are approximately 315 f.t in length, exhibit an incomplete nocturnal periodicity, and in hearts of infected dogs it is not unusual to find several hundred microfilariae per cubic milliliter of blood. These microfilariae are ingested by the mosquito during a blood meal and subsequently undergo two molts within the malpighian tubules.
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September. 1977
Table I. Review of recently reported cases of human pulmonary dirofilariasis Ref. No. 34
I
Age
I
Sex
I
Site
45
M
Baltimore, Md.
7
48
M
7
59
M
Sitka, Alaska: Houston x 4 yr. Texas
35
48
F
36 Present case
57 61
F M
I
Massachusetts, Maryland, Florida Miami, Fla. Sartartia, Miss.
Within 10 to 17 days, they have reached the infective third stage and have come to rest within the labium of the mosquito vector. During the next blood meal these larvae escape through the labella and are deposited on the skin of the next host, whereupon they actively progress toward the puncture wound provided by the mosquito fascicle. 12 They then migrate into the subcutaneous tissues and muscle sheaths, where they reside, molt, and mature for 80 to 120 days. After one additional molt, they migrate into venous capillary channels, are transported to the right heart chambers, and within 6 months are sexually mature and ready to mate and repeat the cycle. Man is a dead-end host. Should the cycle be arrested in the subcutaneous tissues, as is usually the case, subcutaneous nodules are the result. Due perhaps to altered immunological patterns of the host, vector, or parasite, an occasional larva may reach the right ventricle in man, implant, and develop into a sexually immature form before death and embolization to the lungs. This is the apparent fate of the parasites in the cases reviewed. To date, no microfilaremia has been documented in man, supporting the conclusion that D. immitis larvae do not reach sexual maturity in man. Signs and symptoms. The symptomatology associated with human pulmonary dirofilariasis is summarized in Table II. The most common presentation is that of the asymptomatic nodule discovered in routine roentgenographic examination. The symptomatic patient most commonly presents with cough, chest pain, and hemoptysis. Eosinophilia is a common finding. A less common presentation is that of a "flulike" syndrome. Roentgenographic examination usually reveals a
Symptoms Dry, nonprod. cough x 2 mo. Asymptomatic, 5 percent eosinophilia Malaise, anorexia, sputum prod., 4 percent eosinophilia 69 percent eosinophilia, hemoptysis Cough x I mo. Cough, malaise, weakness, chest pain x 3 mo.
I
Location Unknown
Coin, RLL 1.5 em. LUL 3 em.; RUL 2 em. LLL
M 275 p,m
Ill-defined LUL. 3 by 3 cm. RLL 3 cm. 2 coin, LUL 2 em.
Table II. Signs and symptoms in order offrequency _ _ _ _ _ _ _ _1
No. of cases
I
Percent
Asymptomatic Cough Chest pain Eosinophilia Hemoptysis Fever
27 II 8 7 4 3
57.4 23.4 17.0 14.9 8.5 6.4
Total
47
lOa
relatively well-circumscribed "coin" lesion without calcification; this will occasionally present as a more diffuse image, suggesting carcinoma. There are no distinct characteristic findings, and usually at this point the differential diagnosis includes carcinoma, caseous granulomas, eosinophilic granulomas (histiocytosis), Wegener's granulomatosis, and thromboembolism among others. The fact that this finding on roentgenogram indeed does represent embolic phenomenon with subsequent coagulation necrosis and inflammatory reaction is rather interesting in contradistinction to the classic x-ray description of a "wedge-shaped" defect. We feel that this is due to two factors; (1) the level of thrombotic occlusion and (2) subsequent exotoxic reaction following parasite autolysis. Of the 47 patients with pulmonary dirofilariasis, 18 (38.3 percent) were female and 29 (61.7 percent) were male. This perhaps reflects differences in exposure to the parasite, although intrinsic immunological and hormonal characteristics could be factors. The average age of the patients was 50 years, with a range from 28 to 75 years. Younger patients are less commonly seen, and this has been attributed to the fact that children are
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Thoracic and Cardiovascular Surgery
Fig. 3. Pulmonary artery branch containing the parasite . Oblique and transverse sections of the dirofilaria show the parasite in autolysis .
examined less often roentgenographically than are adults. Another theory involves immunological differences and acquired immunity . Diagnosis and treatment. Correct preoperative diagnosis has not been made in any of the cases reported to date. Various attempts have been made at serological detection in patients postoperatively and indeed one case with positive intradermal protein testing!" and two cases with positive hamagglutination have been reported.':' A recent study in Australia investigated the prevalence of antibodies to D . immitis in aborigines and Caucasians as well as in the canine population. Prevalence among dogs parallels the estimated infection among the Australian canine population (85 percent in some locations). Twenty percent of the aboriginal sera were positive as compared to 2.6 percent in Caucasians in a random selection. However, Caucasians with eosinophilia were found to have positive sera in 22.1 percent of cases . Five cases of Caucasian Australians with pulmonary dirofilariasis have been reported as compared to none in aborigines, suggesting acquired immunity or at least implicating immunological factors. IS From these data several conclusions are suggested: (I) early exposure results in acquired immunit y; (2) eosinophilia coupled with coin lesions and nonspecific symptoms raises the index of suspicion in favor of parasitic embolic etiology. The ultimate diagnosis and definitive treatment involve wedge resection of the affected lobe .
Pathological findings. The combination of infarction, endarteritis, eosinophilic pneumonitis, and granulomatous response should alert the pathologist to a diagnosis of dirofilariasis. The lesion is well known to veterinary pathologists and has been implicated in the etiolog y of cardiac complications, including congestive heart failure, in the canine population. A granulomatous response was present only around the branches of the pulmonary artery containing dead adult
worms." In man the findings are consistent with a rounded infarction with subsequent granulomatous response. The gross appearance has been described variously as well-circumscribed, grayish-yellow nodule, approximately 2 to 3 em . in diameter, surrounded by normal lung parenchyma. Microscopically , the involved parenchyma has undergone coagulation necrosis surrounded by a rim of fibrosis and scattered lymphocytes, monocyte s, occasional eosinophils, and multinucleated giant cells . In the center of the lesion is located a necrotic thrombosed artery containing the dead autolyzed and occasionally calcified parasite (Figs. 3 and 4). Occasionally the artery has been found to be only partially occluded, leading to the postulation that the inflammatory response and subsequent pathology actually result from toxin released by the autolyzing worm. Peripheral endarteritis may be noted. Dirofilaria have a multilayered cuticle 4 to 6 110m thick , consisting of an outer smooth layer, a thicker
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Pulmonary dirofilariasis
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Fig. 4. Extensive coagulation necrosis surround two segments of the parasite in autolysis. One segment has undergone calcification (arrow). fibrous middle layer, and a thin lamellar inner layer. Transverse striations 4 to 7 JLm apart are characteristic. Two internal cuticular ridges support lateral chords and a thick somatic muscle bundle . The female has two reproductive ducts and the male has one. The diameter varies from 100 to 330 JLm.
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Summary Human pulmonary dirofilariasis affects individuals living near coastal mosquito-breeding areas . This condition is rare but increasing in recognition and should be included in the differential diagnosis of pulmonary nodules. Although commonly asymptomatic , cough, chest pain, and hemoptysis may be the first indication of its presence in the lung, particularly if associated with eosinophilia. The diagnosis has been made in all cases at operations. Serological studies have correlated well with the incidence of infection and may be of value in the future for the preoperative recognition of this entity. There seems to be a prevalence among males and older individuals. An updated review of the literature is made with description of a case personally treated by the authors . REFERENCES Schlotthauer, J. C.; Harrison, E. G., Jr., and Thompson, J. H. , Jr.: Dirofilariasis-An Emerging Zoonosis? Arch Environ. Health 19: 887, 1969. 2 de Magalhaes, P. S.: Descripcao de uma especie de
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filariasencantradas no coraciiohumano, predidida de uma contribuicao para 0 estudo de filariose de Wucherer e do respectivo parasito adulto, a Filaria bancrofti (Cobbold) on Filaria sanguis hominis (Lewis), Rev. dos cursos praticos e teoricos da Faculd. de Med. do Rio de Janeiro, 3 ann., 3: 4193 , 1887. Faust, E. C., Thomas, E. P., and Jones, J.: Discovery of Human Heart Worm Infection in New Orleans, 1. Parasito!. 27: 115, 1941. Abadie, S. H., Swartzwelder, J. C., and Holman, R. L.: A Human Case of Dirofilaria immitis Infection, Am. J. Trop. Med 14: 117, 1965. Dashiell, G. F.: A Case of Dirofilariasis Involving the Lung, Am. J. Trop. Med. 10: 37, 1961. Dayal, Y., and Neafie, R. c.: Human Pulmonary Dirofilariasis: A Case Report and Review of the Literature, Am. Rev. Respir. Dis. 112: 437, 1975. Awe, R. 1. , Mattox, K. L., Alvarez, B. A. , Stork, W. J., Estrada, R., and Greenberg, D. S.: Solitary and Bilateral Nodules Due to Dirofilaria immitis, Am. Rev. Respir. Dis. 122: 445, 1975. Carlisle, L. H.: The Incidence of Dirofilaria immitis (Heart Worm) in Dogs in Queensland, Aust. Vet. 1. 45: 535, 1969. Altman, L. K.: Heart Worm in Pet Dogs is Found Spreading, New York Times, Sept. 3, p. 26, 1972. Ludlow, K. W., Jackowski, L. A., and OUo, G. F.: Potential Vectors of Dirofilaria immitis, J. Am. Vet. Med. Assoc. 157: 1354, 1970. Otto, G. F.: Geographical Distribution, Vectors, and Life Cycle of Dirofilaria immitis, J. Am. Vet. Med. Assoc. 154: 370, 1969.
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12 Southgate, B. A., and Bryan, H.: Human Pulmonary Dirofilariasis: Entry Methods of Infective Larvae, Chest 68: 274, 1975. 13 Navarette-Reyna, A., and Noon, G.: Pulmonary Dirofilariasis Manifested as a Coin Lesion. Report of a Case and Review of the Literature, Arch. Patho!. 85: 266, 1968. 14 Yoshimura, H., and Yokogawa, M.: Dirofilaria Causing Infarct in Human Lung, Am. J. Trop. Med. Hyg. 19: 63, 1970. 15 Welch, J. S., and Dobson, C.: The Prevalence of Antibodies to Dirofilaria immitis in Aboriginal and Caucasian Australians, Trans. R. Soc. Trop. Med. Hyg. 68: 466, 1974. 16 Adcock, L.: Pulmonary Arterial Lesions in Canine Dirofilariasis, Am. 1. Vet. Res. 22: 655, 1961. 17 Goodman, M. L., and Gore, I.: Pulmonary Infarct Secondary to Dirofilaria Larva, Arch. Intern. Med. 113: 702, 1964. 18 Beaver, P. c., and Oribel, T. C.: Human Infection With Filariae of Animals in the United States, Am. 1. Trop. Med. Hyg. 14: 1010, 1965. 19 Moore, M. P., Jr.: The Pathologic Aspects of Ascariasis, South Med. J. 47: 825, 1954. 20 Osborne, D. P., Brown, R. c., and Dimmette, R. S.: Solitary Pulmonary Nodule Due to Ascaris lumbricoides, Dis. Chest 40: 308, 1961. 21 Harrison, E. G., Jr., and Thompson, J. H., Jr.: Dirofilariasis of Human Lung, Am. J. Clin. Patho!. 43: 224, 1965. 22 Beskin, C. A., Colvin, S. H., and Beaver, P. c.: Pulmonary Dirofilariasis. Cause of Pulmonary Nodular Disease, J. A. M. A. 198: 665, 1966. 23 Tuazon, R. A., Firestone, F., and Blaustein, A. U.: Human Pulmonary Dirofilariasis Manifested as a "Coin" Lesion. A Case Report, J. A. M. A. 199: 45,1967.
Thoracic and Cardiovascular Surgery
24 Spear, H. c., Daughtry, D. c.. Chesney, J. D., Gentsch, T. 0., and Larsen, P. B.: Solitary Pulmonary Lesion Due to Dirofilaria, N. Eng!. 1. Med 278: 832, 1968. 25 Tannehill, A. W., and Hatch, H. B.: Coin Lesions of the Lung Due to Dirofilaria immitis, Dis. Chest 53: 369, 1968. 26 Lewis, J. F., Williams, R. W., and Tinsley, E. A.: Pulmonary "Coin" Lesion Due to Dirofilaria immitis, Arch. Surg. 98: 388, 1969. 27 Neafie, R. C.; and Piggott, J.: Human Pulmonary Dirofilariasis, Arch. Patho!' 92: 342, 1971. 28 Moorhouse, D. E., Abrahams, E. W., and Stephens, B. J.: Human Pulmonary Dirofilariasis in Queensland, Med. J. Aust. 2: 1230, 1971. 29 Brine, J. A. S., Finlay-Jones, L. R., and Charters, A. D.: Pulmonary Dirofilariasis. A Case in Western Australia, Med. J. Aust. 2: 1238, 1971. 30 Navarrette, A. R.: Pulmonary Dirofilariasis, Chest 61: 51, 1972. 31 Feld, H.: Dirofilaria immitis (Dog Heartworm) as a Cause of a Pulmonary Lesion in Man, Radiology 108: 311, 1973. 32 Hendricks, G. L., Jr., Barnes, W. T., and Lerman, D. S.: Dirofilaria immitis. A Cause of Pulmonary Coin Lesion in Human Beings, Ann. Thorac. Surg. 16: 526, 1973. 33 Hoch, W. S., Wershba, M. E., and Patchefsky, A. S.: Pulmonary Dirofilariasis. J. THORAC. CARDIOVASC. SURG. 67: 159, 1974. 34 Martire, R., Liberman, I. I., and Goldman, S. M.: Dirofilaria immitis (Dog Heartworm) as a Cause of Pulmonary Infarction in Man, Md. State Med. J. 24: 62, 1975. 35 Gershwin, L. J., Gershwin, M. E., and Kritzman, J.: Human Pulmonary Dirofilariasis, Chest 66: 92, 1974. 36 Robinson, M. J., Viamonte, M., and Viarmonte, M.: Dirofilariasis: Diagnostic Consideration for Pulmonary Coin Lesions, South. Med. 1. 67: 461, 1974.