Public health aspects of dirofilariasis in the United States

doi:10.1016/j.vetpar.2005.04.007

Veterinary Parasitology

Volume 133, Issues 2–3, 24 October 2005, Pages 157-180

https://doi.org/10.1016/j.vetpar.2005.04.007 Get rights and content

Abstract

Coin lesions in the human lung present significant differential diagnostic problems to the physician. There are at least 20 known causes of such lesions, including neoplastic lesions, infectious diseases, and granulomas. The human medical literature contains many misconceptions about the life cycle of Dirofilaria immitis, including the method of entry of the infective-stage larvae and the development of the young adult worm. These misconceptions have obscured the recognition of the clinical presentation of pulmonary dirofilariasis and the potential for D. immitis to lodge in many other areas of the human body besides the lung. Exposure to infective larvae of D. immitis is more common in humans than is currently recognized. Reported cases in humans reflect the prevalence in the canine population in areas of the United States. The veterinary literature provides compelling evidence that D. immitis is a vascular parasite, not an intracardiac one. Its presence in the right ventricle is a post-mortem artifact, because it has never been shown to be there by echocardiography or angiography in a living dog, even though these techniques have demonstrated adult D. immitis in the pulmonary, femoral, and hepatic arteries; posterior vena cava; and right atrium of live dogs. Physicians have taken the name “heartworm” literally, believing that the worm lives in the heart and only after it dies does it embolize to the pulmonary artery. However, the coin lesion is spherical in shape, not pyramidal, as embolic infarcts to the lung in humans are known to be. The coin lesion is an end-stage result of the parasite's death in the vascular bed of the lungs and the stimulation of a pneumonitis followed by granuloma formation. This pneumonitis phase of human pulmonary dirofilariasis is often not recognized by the radiologist because of the way pneumonitis is diagnosed and treated and because the developing nodule is obscured by the lung inflammation. Serologic methods for use in humans are needed for clinical evaluations of patients with pneumonitis living in highly enzootic D. immitis regions. As well, epidemiological surveys are needed to determine the real extent of this zoonotic infection.

Introduction

Zoonotic filarial nematode infections, other than those due to Dirofilaria spp. in humans, have been reported in the United States in both those with a travel history out of the country and those without such a history (Beaver et al., 1974, Scully and McNeely, 1974). By far, however, the majority of reported cases of zoonotic filariasis in the United States have involved Dirofilaria species, either Dirofilaria tenuis, a subcutaneous parasite of the raccoon (Procyon lotor), or Dirofilaria immitis, the pulmonary artery parasite of canids (Orihel and Beaver, 1965, Beaver and Orihel, 1965, Neafie and Piggott, 1971, Ro et al., 1989).

From a human and veterinary medical point of view, D. immitis is the most important of the two recognized zoonotic species of the genus Dirofilaria in the United States. The public health significance of D. immitis is not associated with the overt clinical disease it produces in humans, but rather with the seriousness of the diseases that the radiographic findings of a coin lesion suggest might be present (Navarrete-Reyna and Noon, 1968, Schlotthauer et al., 1969, Toomes et al., 1983). The diagnostic differentials of a coin lesion include primary or metastatic neoplasia, fungal infections, hamartomas, and tuberculosis (Trunk et al., 1974, Toomes et al., 1983, Allison et al., 2004). This lesion requires an extensive clinical work-up, which, not infrequently, culminates in a thoracotomy. The cost of health-care delivery in evaluating a coin lesion may exceed $80,000 per patient and will have subjected the patient to unnecessary stress and invasive procedures if the lesion is discovered to be pulmonary dirofilariasis.

There are numerous misconceptions in the human medical literature regarding the parasitologic and pathologic aspects of pulmonary dirofilariasis. This paper will address these misconceptions, and based upon the evaluation of reports in the human and veterinary medical literature, will present an alternative hypothesis to explain the pathological sequence of events in human infections.

Section snippets

Infection process

Among the many misconceptions in the human medical literature is that the infective larvae are injected into the dermis as the female mosquito feeds (Harrison and Thompson, 1965, Gershwin et al., 1974, Hoch et al., 1974, Riskin and Toppell, 1977, Robinson et al., 1977, Darrow and Lack, 1981, Kahn et al., 1983, Kochar, 1985, Lum, 1985, Ro et al., 1989, Bradham et al., 1990). In reality, however, the larvae infective to the vertebrate host are known to break out of those components of the

Dirofilariasis in extrapulmonary sites in humans

Although the vast majority of human cases of D. immitis infection have been detected in the lung, as with dogs, this may be due to the ease with which the lung can be surveyed. Involvement of other areas of the human, however, are reported, including the same regions that have been reported in dogs and cats.

Dobson and Welch (1974) reported that six of seven children with acute dirofilariasis showed cranial involvement manifested by epileptiform seizures and/or eosinophilic meningitis. One of

Development of Dirofilaria immitis in its vertebrate host

The development and migration of D. immitis following natural and experimental infections has been reported in detail in at least two papers (Kume and Itagaki, 1955, Orihel, 1961). These studies indicate that neither the location of the migrating larvae nor their size supports an exclusive intracardiac destination. The studies also support the hypothesis that the pulmonary arteries are the site of development because the worms are too small at the time they enter the right ventricle to maintain

Differential diagnosis of the coin lesion in humans

As mentioned above, the significance of pulmonary dirofilariasis in humans is not due to its production of overt disease. As reported by several reviews, fewer than 50% of the patients with pulmonary dirofilariasis have symptoms at the time the coin lesion is discovered (Moorehouse et al., 1971, Neafie and Piggott, 1971, Neafie et al., 1976, Robinson et al., 1977, Ciferri, 1982, Kochar, 1985, Ro et al., 1989, Asimacopoulos et al., 1992) (Table 1).

Coin lesions pose a considerable problem to the

The vascular reaction to Dirofilaria immitis

The lesions in the pulmonary arterial branches in dogs supports this sequence of events (Schaub and Rawlings, 1980). Adcock (1961) reported pulmonary arteritis to be present in 42 dogs infected with D. immitis and, in all cases, the worms were still alive, whereas in the arteries with granuloma formation, all the worms were dead. Atwell et al. (1986) inserted one dead adult female D. immitis into each of 10 puppies. Although all worms were inserted into the anterior vena cava at necropsy 1, 3,

The need for serologic tests to diagnose Dirofilaria immitis in humans

If a more accurate evaluation of human D. immitis infection is to be achieved, indirect tests must be developed and applied to people living in highly enzootic areas of canine D. immitis infections. These tests should be used to evaluate patients with pneumonitis as well as those with coin lesions.

Currently, there are no commercially available serologic tests for this purpose. However, experimental indirect hemagglutination and ELISA tests have been used on sera from human patients with

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Dirofilaria spp. are vector-borne filarial nematodes that affect a variety of animal species, including humans. Dirofilaria immitis and Dirofilaria repens are the two main zoonotic species, but also other wildlife-associated Dirofilaria species are occasionally reported as causative agents of human dirofilariasis, including Dirofilaria striata, Dirofilaria tenuis, Dirofilaria ursi, Dirofilaria spectans, and Dirofilaria magnilarvata. Since the etiological identity of most of the species mentioned here is arguable, we summarized and critically discussed data concerning infections in humans, focusing on the reliability of Dirofilaria species identification. We advocate the importance of combined morphological and genomic approaches to provide unequivocal evidence for their zoonotic potential and pathogenicity.
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Dirofilaria repens is a nematode affecting domestic and wild canids, transmitted by several species of mosquitoes of different genera. It usually causes a non-pathogenic subcutaneous infection in dogs and is the principal agent of human dirofilariasis in the Old World. The geographic distribution of D. repens is changing rapidly, and several factors contribute to the spread of the infection to non-endemic areas. A mathematical model for transmission of Dirofilaria spp. was built, using a system of ordinary differential equations that consider the interactions between reservoirs, vectors, and humans. The transmission simulations of D. repens were carried out considering a projection in time, with intervals of 15 and 100 years. For the dynamics of the vector, seasonal variations were presented as series with quarter periodicity during the year. The results of the simulations highlight the peak of contagions in the reservoir and in humans, a product of the action of the vector when it remains active throughout the year. A 300 $%$ infection increase in the reservoir was observed during the first decade and remains present in the population with a representative number of cases. When the vector maintains its density and infectivity during the year, the incidence of the infection in humans increases. Accumulated cases amount to 45 per 100,000 inhabitants, which corresponds to a cumulative incidence of 0.05 $%$ , in 85 years. This indicates that early prevention of infection in canids would significantly reduce the disease, also reducing the number of accumulated cases of human dirofilariasis by D. repens. The interaction between the simulations generated by the model highlights the sensitivity of the epidemiological curve to the periodicity of seasonality, reaffirming the hypothesis of the probability of movement of the zoonotic disease to non-endemic areas, due to climate change.
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  First Described: Heartworm was first described in dogs in Italy in 1626¹ and in the United States in 1847.²
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  Cause: Dirofilaria immitis, belonging to the superfamily Filarioidea and family Onchocercidae. A related nematode, Dirofilaria repens, is found in southern and central Europe, Africa, and Asia but is not currently endemic in North America.
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  Affected Hosts: Although canids (domestic dogs, coyotes, foxes, wolves, and other wild canids) are the definitive hosts for heartworms, the parasite has been found in more than 30 species of animals, including domestic cats and wild felids, bears, ferrets, seals, sea lions, and humans.
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  Intermediate Hosts: There are multiple mosquito vectors in every region of the United States. More than 70 species of mosquitoes have been shown to be capable of transmitting heartworms; 25 species have been proven to be significant vectors.
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  Geographic Distribution: Heartworms are endemic in North, Central, and South America; the Caribbean Islands; the coastal regions of Africa, southern Europe, and Asia; Japan; Indonesia; and Australia.
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  Route of Transmission: Female mosquitoes feeding on a microfilaremic canine host ingest microfilariae. The ingested microfilariae undergo a transformation and two molts over a 2- to 4-week period to become infective third-stage larvae (L₃). The L₃ are then deposited on a dog’s skin in a droplet of hemolymph by a feeding female mosquito. The L₃ enter through the bite wound into the subcutaneous tissue.
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  Major Clinical Signs: Signs of heartworm disease can range from a cough and exercise intolerance to dyspnea, abnormal heart and lung sounds, hepatomegaly, syncope, ascites, and death.
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  Differential Diagnoses: These include primary pulmonary diseases (pneumonia, chronic bronchitis, allergic lung disease), pulmonary thromboembolism, pulmonary hypertension, and right-sided heart failure.
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  Human Health Significance: Dirofilaria immitis is of public health concern even though the number of reports of infection in humans is relatively small. The most common clinical syndrome reported in human infections is the formation of a pulmonary nodule or nodules within the lung parenchyma.
Human Pulmonary Dirofilariasis: A Review for the Clinicians
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In addition to the supplementary diagnostic role, serologic and molecular diagnostic testing can serve other important purposes. For example, evaluation and management of a solitary pulmonary nodule, including surgical removal, is expensive (approximately 80,000 dollars or more per patient).22 In patients with low risk of lung cancer, who reside in a Dirofilaria endemic area, and test positive for D. immitis by serologic or molecular testing, the workup of an incidentally identified lung nodule could be more conservative.
Human pulmonary dirofilariasis (HPD) is a rare zoonotic disease caused by Dirofilaria immitis, the nematode responsible for canine cardiopulmonary dirofilariasis (dog heartworm). The incidence of HPD is on the rise throughout the world due to increased awareness and factors affecting the vector (mosquito). Humans are accidental hosts for D. immitis. Most patients are asymptomatic and present with an incidental pulmonary nodule that mimics primary or metastatic pulmonary malignancy. Some patients suffer from pulmonary and systemic symptoms in the acute phase of pneumonitis caused by pulmonary arterial occlusion by the preadult worms resulting in pulmonary infarction and intense inflammation. These patients may have ill-defined pulmonary infiltrate on chest radiology. Pulmonary nodules represent the end result of initial pneumonitis. There are no specific clinical, laboratory, or radiologic findings that differentiate HPD from other causes of a pulmonary nodule. Although serologic tests exist, they are usually not commercially available. The majority of patients are diagnosed by histopathologic identification of the decomposing worm following surgical resection of the lesion.
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This descriptive study was carried out as a cross-sectional investigation. A questionnaire was completed for 100 domestic dogs from May 2017 to February 2018 and recorded their age, sex, and clinical features. Also, we used enzyme-linked immunosorbent assay (ELISA) to identify antigens of heartworms in the bloodstream, with 98% sensitivity and 100% specificity, and parasitological techniques (Knott's test) to detect microfilariae in canine blood in Jiroft district, south of Kerman province, Iran.
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Public health aspects of dirofilariasis in the United States

Abstract

Introduction

Section snippets

Infection process

Dirofilariasis in extrapulmonary sites in humans

Development of Dirofilaria immitis in its vertebrate host

Differential diagnosis of the coin lesion in humans

The vascular reaction to Dirofilaria immitis

The need for serologic tests to diagnose Dirofilaria immitis in humans

Chest

Ann. Thorac. Surg.

Res. Vet. Sci.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Chest

Am. J. Med.

Chest

Exp. Parasitol.

Lancet

J. Thorac. Cardiovasc. Surg.

J. Thorac. Cardiovasc. Surg.

Br. Vet. J.

Lancet

Chest

Chest

Ann. Thorac. Surg.

A human case of Dirofilaria immitis infection

Am. J. Trop. Med. Hyg.

Pulmonary arterial lesions in canine dirofilariasis

Am. J. Vet. Res.

Heartworm (Dirofilaria immitis) in the brain of a cat – Review and case report

California Veterinarian

Infectious pulmonary nodules mimicking lung carcinoma

Infect. Med.

Seroepidemiological studies on human pulmonary dirofilariasis in Spain

Ann. Trop. Med. Parasitol.

Application of the indirect fluorescent antibody test on sections of adult filariae to the serodiagnosis, epidemiology, and post-therapeutic surveillance of human filariasis

Ann. Trop. Med. Parasitol.

Experimental production of lesions in canine pulmonary arteries similar to those produced by Dirofilaria immitis infection

Vet. Rec.

Early pulmonary lesions caused by dead Dirofilaria immitis in dogs exposed to homologous antigens

Br. J. Exp. Pathol.

Solitary and bilateral pulmonary nodules due to Dirofilaria immitis

Am. Rev. Respir. Dis.

Zoonotic onchocercosis in a resident of Illinois and observations on the identification of Onchocerca species

Am. J. Trop. Med. Hyg.

Human infection with filariae of animals in the United States

Am. J. Trop. Med. Hyg.

Parasite in eye of a dog

Sm. An. Clin.

Removal of intraocular Dirofilaria immitis with subsequent corneal scarring

Am. Anim. Hosp. Assoc. J.

Pulmonary dirofilariasis cause of pulmonary nodular disease

J. Am. Med. Assoc.

Aberrant location of Dirofilaria immitis

Vet. Med./SAC

Recurring tetraparesis attributable to a heartworm in the epidural space of a dog

J. Am. Vet. Med. Assoc.

Observations on the dog heartworm Dirofilaria immitis

North Am. Vet.

Femoral artery occlusion by Dirofilaria immitis in a dog

J. Am. Vet. Radiol. Soc.

Intraocular dirofilariasis in dogs

Compend. Contin. Educ. Pract. Vet.

Human pulmonary dirofilariasis in the west

West. J. Med.

Diagnosis of human pulmonary dirofilariasis

West. J. Med.

Human pulmonary dirofilariasis in the United States: A critical review

Am. J. Trop. Med. Hyg.

Heartworm disease manifested by encephalomyelitis and myositis in a dog

J. Am. Vet. Med. Assoc.

Managing solitary pulmonary nodules: The choice of strategy is a “close call”

Am. Rev. Respir. Dis.

Dirofilaria immitis in the brain and heart of a cat from Massachusetts

Am. Anim. Hosp. Assoc. J.

Solitary lung nodule due to Dirofilaria immitis (dog “heartworm”)

J. Surg. Oncol.