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Author: Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA, Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital

Michael D Nissen is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Pediatric Infectious Diseases Society, Royal Australasian College of Physicians, and Royal College of Pathologists of Australasia

Coauthor(s): John Charles Walker, MSc, PhD, Head, Department of Parasitology, Center for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, Australia; Senior Lecturer, Department of Medicine, University of Sydney, Australia

Editors: Charles S Levy, MD, Associate Professor, Department of Medicine, Section of Infectious Disease, George Washington University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Thomas M Kerkering, MD, Professor of Medicine and Microbiology, Department of Internal Medicine, Division of Infectious Disease, Brody School of Medicine at East Carolina University; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Author and Editor Disclosure

Synonyms and related keywords: dirofilariasis, human pulmonary dirofilariasis, HPD, dog heartworm infection, Dirofilaria immitis, D immitis, Dirofilaria (Nochtiella) repens, D repens, Aedes, Anopheles, Culex

Background

The zoonotic filariae, Dirofilaria immitis and Dirofilaria (Nochtiella) repens, have become increasingly recognized worldwide as inadvertent human pathogens. The usual hosts of these infective nematodes are domestic and wild carnivores.

Human infection presents with either subcutaneous nodules or lung parenchymal disease that may be asymptomatic. The significance of infection in humans is that pulmonary lesions and some subcutaneous lesions are commonly labeled malignant tumors, requiring invasive investigation and surgery before a correct diagnosis is made. The pathology of the condition is associated with aberrant localization of immature worms that fail to reach adulthood; therefore, microfilaria almost always is absent.

Pathophysiology

The dirofilarial life cycle, like all filarial and helminthic nematodes, consists of 5 developmental or larval stages in a vertebral host and an arthropod (mosquito) intermediate host and vector. Adult female worms produce thousands of first-stage larvae or microfilariae that are ingested by a feeding insect vector. Some microfilariae have a unique circadian periodicity in the peripheral circulation over a 24-hour period. The arthropod vectors, mosquitoes and flies, also have a circadian rhythm when they obtain blood meals. The highest concentration of microfilariae usually occurs when the local vector is feeding most actively. Microfilariae undergo 2 developmental changes in the insect. For the final 2 stages of development, third-stage larvae are inoculated back into the vertebral host during the act of feeding.

The usual definitive host of D immitis and D repens is the domestic dog, although cats, wolves, coyotes, foxes, muskrats, and sea lions may act as suitable hosts and reservoirs of the disease. Mosquitoes of the genera Aedes, Anopheles, and Culex all are suitable intermediate hosts and vectors. Some species of fleas, lice, and ticks also may act as vectors.

In the dog, adult D immitis resides in the right ventricle and pulmonary arteries of the lung. Female worms produce and release thousands of microfilariae larvae into the circulation daily, which are ingested by mosquitoes in a blood meal. Larvae develop into infective larvae over the next 10-16 days, depending on environmental conditions, before being reintroduced back into the dog. These larvae reside and mature in the subcutaneous tissues and along muscle sheaths for the next several months before migrating to the heart, where the nematode matures for 6-7 months. Adult worms are 1-2 mm in diameter, with females being 25-30 cm in length and males generally being shorter. The adults of D repens, in contrast, reside in the subcutaneous tissues of dogs and cats, although the life cycle and release of microfilaria in the peripheral circulation remain the same as for D immitis.

Humans are accidental and dead-end hosts of dirofilariae because adult worms do not reach maturity in the heart or skin. Most infective larvae injected into humans are thought to perish; therefore, infected individuals usually are not microfilaremic. Only one report of circulating diromicrofilaremia in a human exists in the medical literature (Nozais, 1994). One would predict that, in general, human disease is amicrofilaremic, although, because human disease is an accidental event, only one degenerate immature (fourth-stage) larva or adult worm (fifth-stage larva) usually is isolated from an ectopic position of the body, and dirofilariae, like other nematodes, rely on sexual reproduction before microfilariae are produced.

Frequency

United States

The epidemiology of human dirofilariasis is related to the prevalence of canine dirofilariasis, the presence of suitable mosquito vectors, and human activities that lead to vector exposure.

Human disease tends to be independent of dog ownership. In most cases, D immitis causes human dirofilariasis in the United States, and Dirofilaria tenuis only causes human dirofilariasis occasionally. The prevalence of canine dirofilariasis has been increasing over the last 3 decades. Traditionally, human pulmonary dirofilariasis (HPD) has been localized predominantly to the states adjacent to the Gulf of Mexico and the southern Atlantic states, where the prevalence of canine D immitis infection has been documented to be as high as 40%. The range of canine D immitis infection now extends along the Mississippi River Valley and into southern Canada. Canine dirofilariasis has been described in all the lower 48 states except Nevada. The geographic spread of human disease has paralleled that of the dog population.

The first human case of dirofilariasis in the United States was reported in a female cadaver in New Orleans in 1941. The first description in the medical literature of HPD causing pulmonary infarction was in 1961. Since then, at least 197 cases of HPD have been reported, presumably caused by D immitis. Ten cases of Dirofilaria ursi infection, 3 cases of D tenuis subcutaneous infection, and isolated cases of Dirofilaria striata and possible Dirofilaria lutrae infection have been reported.

International

The most commonly reported manifestation of human dirofilariasis worldwide is subcutaneous nodular disease caused by D repens, with over 400 case reports in the medical literature. D repens is an Old World parasite and has not been described as endemic in the Americas, Japan, or Australia. Endemic foci for D repens exist in southern and Eastern Europe, Asia Minor, Central Asia, and Sri Lanka. Italy is the European country with the highest prevalence of human dirofilariasis (66%), followed by France (22%), Greece (8%), and Spain (4%). Cases of canine and human disease have been described in northern European countries, although they have been traced back to exposure during a visit to southern Europe.

HPD has been described in many other countries on virtually all continents, including South America (Brazil), Europe (France, Italy, Spain), Asia (Ukraine, Japan, India), Africa, and Australia, although D repens apparently induces subcutaneous disease less commonly. Human exposure to D immitis larvae has also been reported in isolated communities of Colombian Indian tribes of the Amazon rain forest.

Mortality/Morbidity

The dog and cat parasites, D immitis (heartworm) and D repens, are the most commonly described etiologic agents of human infection. Occasional reports exist in the medical literature of the Dirofilaria species that affect other animals, including D tenuis (raccoon worm), D ursi (bear), D subdermata (porcupine), D lutrae (North American otter), D striata (wild American felines), and D spectans (Brazilian otter) causing human disease.

No recorded fatalities directly due to dirofilariasis have been reported in the medical literature. HPD infection is symptomatic in 38-45% of cases. The infection rarely is reported in children, although the initial description of human dirofilariasis was noted in 1887 in a Brazilian child.

The primary significance of HPD infection in adults is the confusion and invariable radiological misdiagnosis of a primary or metastatic lung tumor, which usually leads to thoracotomy with open lung biopsy or wedge resection of the lung to obtain the correct diagnosis.

  • D immitis infection
    • The true prevalence of human D immitis exposure and disease may be underestimated because canine infection is widespread throughout the world, and most infected people are asymptomatic.
    • A seroprevalence study in Spain (Simon, 1991) where 33% of dogs are infected with D immitis, revealed that 22% of humans developed antibodies of immunoglobulin G ([IgG] 5.8%), immunoglobulin M ([IgM] 3.5%), or immunoglobulin E ([IgE] 12.6%) isotype. IgG seroconversion was most prevalent in people older than 60 years, while IgM seropositivity was most commonly observed in those younger than 19 years. The level of IgE also decreased with age. The authors concluded that repeated contacts with D immitis in this endemic population was common and began at an early age.
    • D immitis usually is associated with pulmonary lesions or radiological coin lesions of the lung.
    • Isolated reports exist of D immitis or D immitis–like worms causing cutaneous or abdominal nodular disease and conjunctival disease.
  • D repens infection
    • D repens infection is the most frequent and widespread form of dirofilariasis in the world.
    • The most common localization is a subcutaneous or submucosal nodule.
    • Ophthalmic involvement also is described, and direct visualization of the worm can be made in the bulbar conjunctiva.
    • Breast nodules resulting from D repens infection also commonly are misdiagnosed as potential tumorous masses and are observed in hyperendemic areas for the parasite, usually Italy and Sri Lanka. Imported cases of D repens affecting the breast have been reported in the United States, Canada, Japan, and Australia.
    • Pulmonary and abdominal lesions resulting from D repens infection have also been reported in endemic areas of Italy, France, and Greece.
  • Other dirofilarial infections
    • D tenuis has been described as a cause of subcutaneous facial nodules and ophthalmic dirofilariasis in Florida, United States.
    • A living adult female D striata was removed from the orbit of a 6-year-old boy living in North Carolina, United States.
    • D spectans has been extracted from a digital artery lesion of a Brazilian man.

Race

All studies of HPD from the United States have reported a predominance of infection in people of European descent (as high as 95%) compared to African American people. This figure probably indicates a selection bias, with more white Americans presenting for radiological screening investigations than African Americans.

Sex

The incidence and prevalence of human dirofilariasis shows a human sexual preference dependent on the infecting species.

  • D immitis infection: The reported male-to-female ratio of HPD is 2:1 in patients in the United States.
  • D repens infection: Women represent 55% of worldwide infections.

Age

The incidence and prevalence of human dirofilariasis favors middle-aged adults.

  • D immitis infection: All reviews of HPD cases report that most affected adults are aged 50-60 years. A selection bias is probably occurring in adults because of the use of chest radiographs for screening, a history of cigarette smoking, and a heightened concern for malignancy with any chest symptoms. HPD has been described in children as young as 8 years.
  • D repens infection: D repens also occurs more commonly in adults, peaking in individuals aged 40-49 years. The only exception is in Sri Lanka, where children younger than 9 years are most likely to be infected. The youngest individual reported was aged 4 months. This pediatric predominance is attributed to the custom of allowing male toddlers to completely eschew clothing or to only wear upper garments. The theory is supported by the observation that most pediatric cases in Sri Lanka are localized to the scrotum, penis, and perineal regions of the body.



History

Symptoms of dirofilariasis depend on the species of the causative organism and body site involved.

Patients rarely, if ever, remember being bitten by mosquitoes in the months preceding the appearance of symptoms. However, confirming the patient's place of residence and recording a travel history of the previous couple of years to confirm possible exposure to suitable mosquito vectors is useful.

Coincidentally, some adult patients report a history of heavy tobacco use, which increases the suspicion of a malignant pulmonary process when a coin lesion is observed on chest radiograph.

  • D immitis infection
    • Most patients with pulmonary D immitis infection (HPD) are asymptomatic (approximately 56-62% of cases).
    • Symptoms of HPD, when present, include localized retrosternal chest pain, cough, hemoptysis, wheezing, low-grade fever, chills, and malaise.
    • One patient also reported loss of consciousness following chest pain.
    • Another patient experienced acute bilateral knee pain and swelling with fever.
    • One reference exists of an 8-year-old girl from the United States with HPD who presented with chest pains and wheezing.
    • Aberrant cutaneous sites may be involved (eg, conjunctiva), and the most common symptom is eye pain.
  • D repens and other dirofilarial infections
    • Usually, patients notice a single painful subcutaneous lump in the affected area.
    • The areas most commonly affected include the face and eyelids, chest wall, upper arms, thighs, abdominal wall, and male genitalia.

Physical

Signs of dirofilariasis depend on the species of the causative organism and body site involved.

  • D immitis infection
    • Physical examination of patients with HPD usually is noncontributory, whether patients are symptomatic or not.
    • A subcutaneous or subconjunctival lesion caused by D immitis infection is rare but easily detectable, in contrast to HPD.
  • D repens and other dirofilarial infections
    • Superficial infections (subcutaneous or subconjunctival lesions) are detected easily. A single nodule is the usual presentation.
    • A review of all reported cases of D repens dirofilariasis emphasizes a predilection for upper body site infection (76%) compared to lower body site infection (24%). This is thought to reflect the biting patterns of the mosquito vector.
    • Upper body sites, in order of involvement, are the head (46%), which includes eyelids and/or conjunctiva (31%) and face (15%); chest wall and/or breast (15%); upper limbs (12%); and neck (3%).
    • The lower body sites affected include lower limbs (11%), abdominal wall (5%), and male genitalia (6%).
    • A minority of D repens infections have been isolated from deep internal body sites, including lung-associated sites with subpleural infarction, gastrosplenic ligament, omentum, peritoneal cavity, mesocolon, pancreas, and a perirectal nodule.
    • A predilection for male genitalia infection with D repens (21%) occurs in Sri Lanka. In Sri Lanka, infection of the male genitalia outnumbers infection in other separate sites, such as conjunctiva (19%), eye adnexa (16%), upper limbs (11%), face and/or cheek (9%), chest wall and/or breast (7%), neck (6%), lower limbs (4%), abdominal wall (3%), and the peritoneal cavity (1%).

Causes

Infection with dirofilariae is independent of dog ownership, although residence in or travel to an area where canine dirofilariasis is endemic is almost universal among clinical cases of human dirofilariasis.

  • Prevalence of canine and feline dirofilariasis
    • The prevalence of dirofilariasis in domestic dogs and cats varies by state and geographical region throughout the United States. All states, except Nevada, have reported D immitis infection in dogs, with the prevalence varying from low levels in some states (0.3%, 0.5%, and 1.2% in Colorado, Washington, and Montana, respectively) to as high as 40% in Florida and South Carolina. Of stray cats in Michigan, 3% were found to have adult D immitis worms upon autopsy following euthanasia. In general, the infection is more prevalent in dogs compared to cats, in which prophylaxis is not routinely recommended.
    • A similar variation in prevalence for D immitis in dogs and cats occurs elsewhere in the world, except Japan, where as many as 10% of stray cats are infected. In Europe, the recorded prevalence rate of D immitis in dogs is 5-11% in Greece; 13% in Barcelona, Spain; 44-55% in northeastern Italy; and 59% in the Canary Islands, Spain (highest). In Australia, rates in stray dogs vary among states, from 1-15%, with only approximately 1% of cats affected. Rates that are 3 times higher were found in dogs older than 2 years compared with dogs younger than 2 years. Approximately 2% of dogs in Recife, Brazil are infected with D immitis. A prevalence of 55% was recorded in dogs in northern Taiwan.
    • The prevalence of D repens in endemic areas of southern Europe, in comparison to D immitis, is more marked. The known rates are 7-22% in Greece; 20% in France; 29% in Sicily, Italy; and as high as 37-85% in areas of Spain.
    • The rate of dirofilariasis in dogs in Sri Lanka, another area endemic for D repens, also is high, with rates of 30-60%.
  • Human immunodeficiency predisposing to dirofilariasis
    • Initial theories suggested that the increased incidence of HPD among elderly individuals, with a correspondingly low incidence of the condition in children, was the result of failing immunity.
    • This theory has been disputed because only 14% of adults diagnosed with HPD have a coexistent immune defect.
  • Dirofilariasis in wildlife
    • The prevalence of D immitis is becoming increasingly recognized in North American wildlife (ie, coyotes, foxes, wolves, black bears) that may share environments with human activity.
    • This may become increasingly relevant in the future control of dirofilariasis, because prophylactic antifilarials can be administered to domestic canines to eradicate and control dirofilariae in urban areas.
  • Dirofilariasis in wild canids
    • The prevalence of D immitis in coyotes varies from 7% (Missouri, United States) to 75% (Georgia, United States) to 91% (northern California, United States).
    • D immitis was detected in 14% of red wolves released into the wild in the Alligator River National Wildlife Refuge in North Carolina in the United States 2-24 months after testing negative for microfilariae during the captive stage.
    • Fifty-six percent of dingoes (Australian wild dog or Canis familiaris dingo) in a tropical region of the Northern Territory, Australia were infected with adult worms of D immitis.
  • Dirofilariasis in foxes
    • In the United States, the prevalence of D immitis in foxes varies from 6% (Missouri) to 21% (South Carolina).
    • The urban prevalence of D immitis in red foxes in Australia ranges from 6.4% (Melbourne) to 8.8% (Sydney). In the Melbourne study, 2 known species of mosquito vector were identified, increasing the risk of human infection.
    • In Spain, 11% of red foxes in the Pyrenees region were infected.
  • Dirofilariasis in raccoons: D tenuis was detected in 20% of wild raccoons trapped in southeast Georgia, United States.
  • Dirofilariasis in bears: D ursi has been detected in 0.2% of black bears in New Brunswick, Canada.



Ascariasis
Benign Lung Tumors
Echinococcosis
Eosinophilic Granuloma (Histiocytosis X)
Filariasis
Histoplasmosis
Hodgkin Disease
Hookworms
Lymphoma, Non-Hodgkin
Mycosis Fungoides
Sarcoidosis
Strongyloidiasis
Tuberculosis
Wegener Granulomatosis

Other Problems to be Considered

Atypical mycobacterial infection
Chronic granulomatous disease
Cutaneous larva migrans
Cystic adenomatoid malformation
Histiocytoses
Lymphoproliferative disorders
Paragonimiasis
Pulmonary infarction
Thromboembolism
Pulmonary metastasis
Mycotic infections of the lung
Caseous granulomas of the lung
Eosinophilic granuloma
Conjunctivitis
Nonspecific subcutaneous nodule
Lipoma or other benign subcutaneous tumour
Infected subcutaneous cyst/adnexal or abscess
Sparganosis
Breast carcinoma (in adults)



Lab Studies

  • CBC count: At best, eosinophilia may be detected in only 20% of cases of HPD.
  • Sputum cytology: The presence of eosinophils may support a diagnosis of HPD in patients with a coin lesion observed on radiograph, although the test lacks the specificity for an accurate diagnosis.
  • Dirofilariae serology
    • Complement fixation tests, indirect hemagglutination, and enzyme-linked immunosorbent assays (ELISAs) using whole body or somatic antigens (SA) all have been attempted for the diagnosis of dirofilariasis. While these are useful tools in epidemiological surveys in known endemic areas, they have low specificity in the general population and also are not routinely available. Findings in as many as 30% of cases may be false-positive because of cross-reactions with other nematode antigens (eg, Toxocara canis).
    • An improved specificity with ELISA has been shown if a 22-kD protein (Di22) from adult D immitis or recombinant antigens (ie, a 35-kD fusion protein, P22U, phospholipase A2 [PLA2]) are used for antibody capture. P22U and PLA2 are larval excretory/secretory proteins of D immitis. P22U probably is related to Di22 and is not recognized in Western blot tests of sera of patients with other parasitic and nonparasitic pulmonary diseases. PLA2 is not related to Di22 but reacts specifically with sera from patients with subcutaneous dirofilariasis.
    • Nevertheless, because of the low pretest probability of detecting HPD, the positivity of ELISA using Di22 or other antigens must be supported by radiological characteristics, the antecedents to presentation, the area where the patient lives, and other data so that the clinician can decide whether to use invasive techniques to reach a definitive diagnosis.
  • Polymerase chain reaction
    • Polymerase chain reaction (PCR) amplification of genomic DNA extracted from single worms isolated in patients with clinical dirofilariasis has been successful for the diagnosis of D immitis and D repens infection.
    • Remembering that biopsy material or worms intended for PCR should be not be stored in formalin is important because formalin fragments genomic DNA and interferes with Taq polymerase.

Imaging Studies

  • Chest radiograph and tomograms
    • The incidental finding of a pulmonary lesion on chest radiograph is the usual presentation for HPD. The lesion usually is a well-circumscribed peripheral coin lesion or nodule. Transitory pulmonary nodules and calcified pulmonary granulomas (7%) sometimes are described. In as many as 90% of cases, the presentation is a solitary nodule. Lesions predominantly are subpleural (68%), in the right lung (76%), and show a preference for the right lower lobe (46% of all cases). The size of lesions varies from 1-4 cm, with an average size of 2 cm. Multiple lesions can be observed in either the same lobe or multiple lobes.
    • The shortest interval noted between a normal finding on chest radiograph and the presence of a coin lesion resulting from D immitis infection is 5 months.
    • The diagnosis in children may be less recognized because dirofilarial lesions may be labeled as Ghon foci secondary to pulmonary tuberculosis and not be followed up or treated.
  • Chest or abdominal CT scan
    • A CT scan may be performed for further evaluation of pulmonary or abdominal lesions and to assess for mediastinal lymphadenopathy.
    • It also may be used to guide fine-needle aspiration and biopsy of suspicious lesions.
  • MRI may be useful in differentiating subcutaneous dirofilarial lesions of the head and eyes from lesions of other etiologies (eg, histiocytosis, neuroblastoma).
  • Ultrasonography of abdominal or cutaneous lesions assists in the etiologic diagnosis and/or in guiding fine-needle aspiration biopsy of the lesions.

Other Tests

  • Pulsed-field gel electrophoresis
    • Multilocus electrophoresis analysis of DNA of worms recovered from pulmonary or subcutaneous nodules may be useful in the identification of species of the zoonotic dirofilariae, especially in areas where more than one species of Dirofilaria may be present (ie, D repens, D immitis).
    • Histological and phenotypic features of recovered worms may be damaged during removal or they may degenerate, preventing accurate identification.

Procedures

  • Surgical biopsy of subcutaneous nodules
    • D repens usually presents as a subcutaneous nodule in the body sites discussed in Physical.
    • The nodule almost always is excised for histopathological diagnosis and confirmation of infection.
    • The size of the nodules can vary from 0.5-2.5 cm in diameter.
  • Fine-needle aspiration of peripheral pulmonary lesions: Diagnosis of HPD using transthoracic needle aspiration with or without CT guidance has been used successfully on 2 occasions to identify morphological features of D immitis and prevent invasive surgery.
  • Bronchoscopy with cytology and transbronchial biopsy
    • Bronchoscopy has been attempted in cases of HPD, with little success in positively identifying the cause of the pulmonary lesion.
    • Results of cytology of bronchoalveolar lavage specimens and brushings should be interpreted with caution because bronchial mucosa in patients with HPD may be focally metaplastic and mimic invasive squamous cell carcinoma.
    • A predominance of eosinophils or the presence of eosinophilic pneumonia may be a clue to the correct diagnosis of HPD.
  • Open lung biopsy with wedge resection of affected lung segment
    • Upon removal, most lesions are well-circumscribed, spherical, and gray-yellow in appearance.
    • Wedge-shaped lesions may be observed in 32% of cases.
  • Fine-needle aspiration of retroperitoneal dirofilarial masses: One case report exists of the successful use of ultrasonographic-guided fine-needle aspiration to obtain a biopsy of a pseudotumorous para-aortic mass in a 60-year-old French woman (Roussel, 1990). Morphological and epidemiological features suggested D repens infection.

Histologic Findings

HPD with D immitis infection

Upon microscopy, lesions reveal a necrotic center of lung tissue around a centrally thrombosed artery, with fragments of a nonviable immature worm. This core is surrounded by a granulomatous zone of epithelial cells, plasma cells, lymphocytes, and a fibrous capsule rich in eosinophils (66% of cases). The overlying pleura usually is inflamed and fibrotic (75%). Calcification and caseous necrosis may be present (41%). Charcot-Leyden crystals may be detected in nodules (27%).

The adjacent lung may show a desquamative interstitial pneumonia–like reaction (66%), follicular bronchiolitis (46%), and patchy organizing pneumonia (34%). A focal vasculitis involving the muscular arteries and capillaries is recognized in 51% of cases.

Anatomical features of the worm are better appreciated when histological sections are stained with Movat pentachrome, Gomori methenamine-silver (GMS), or periodic acid-Schiff (PAS) stains. The ability to identify internal features of the worm (ie, digestive system, genital tract) is common. Nonspecific fluorescent whitener stains also have been used to rapidly identify worms in pulmonary specimens. Worms have been identified on frozen section biopsy specimens in 2 cases.

Infection with D repens

In most cases, the worm contained in the lesion shows varying grades of degradation. Some areas of the worm show more degeneration than others (ie, myoid fibers, lateral chords). Other features, such as the cuticle (outer covering), walls of the digestive tract, and sexual tubules, offer a certain resistance to attack. The external ridges of the cuticle are the feature that most easily distinguishes D repens from D immitis in such lesions.

The worm is surrounded by a large number of eosinophils and other inflammatory cells of varying degrees. An epithelioid granulomatous reaction with multinucleate giant cells is observed in as many as 33% of cases and may resemble that observed in mycobacterial or fungal infections. Lymphocytes may form large aggregates and follicles with germinal centers that can extend into the connective tissue, mimicking a lymphoma. A fibrotic capsule and calcification may be observed in 6% of cases. The subcutaneous fat shows a septal and lobular inflammation mediated by eosinophils and lymphocytes. The absence of fat necrosis in the presence of inflammation with such cells indicates a diagnosis of dirofilariasis. Sparganosis, a parasitic zoonosis caused by the larval stage of Spirometra species, is an infection that may cause a similar lesion.



Medical Care

Administering antifilarial medication (eg, prior to surgical resection of dirofilarial lesions) generally is not supported in the medical literature. One group of authors has recommended a single dose of ivermectin followed by 3 doses of diethylcarbamazine (DEC) if the syndrome is recognized prior to surgery. However, most cases are diagnosed retrospectively, when histopathological sections of biopsy or excision material are viewed.

Surgical Care

Surgical excision of lesions and affected areas is the treatment of choice for patients with human dirofilariasis. Some authors have recommended a period of observing chest coin lesions for several months if dirofilariasis is suspected and no other features in the history or examination suggesting malignancy or other infection are present.

Consultations

  • Infectious diseases specialist
  • General surgeon
  • Cardiothoracic surgeon
  • Ophthalmologist
  • Otorhinolaryngologist
  • Plastic surgeon

Diet

No specific diet is recommended for patients with dirofilariasis.

Activity

No limits on activity usually are imposed unless a high risk of embolic thromboembolism is present.



The goals of pharmacotherapy are to reduce morbidity, prevent complications, and eradicate the infection.

Drug Category: Anthelmintics

Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Drug NameIvermectin (Mectizan)
DescriptionMacrocyclic lactone derivative of avermectin. Binds selectively with glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, causing cell death. Does not cross the blood-brain barrier and has no paralytic action in humans.
Adult Dose150-200 mcg/kg/d PO as single dose
Pediatric Dose<5 years: Not established
>5 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsMay interact with other ligand-gated chloride channels (eg, those gated by GABA)
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsTreat women who are breastfeeding only when risk of delayed treatment outweighs possible risks to the newborn caused by ivermectin excretion in milk; repeat courses of therapy may be required in patients who are immunocompromised; may cause nausea, vomiting, fever, headache, myalgia, sore throat, cough, and drowsiness

Drug NameDiethylcarbamazine (Hetrazan)
DescriptionPrecise mechanism is not understood. Has been shown to induce immobilization of microfilariae by decreasing muscle activity resulting from hyperpolarization effects. Alteration of surface membrane also occurs, with enhanced destruction by the host's immune system. May enhance adhesion of granulocytes via antibody-dependent and independent mechanisms. Interference by microfilarial intracellular processing and transport of specific macromolecules also has been hypothesized.
Low doses (approximately 2-3 mg/kg/d) are usually recommended for the first 3 d of treatment to decrease the risk of adverse effects.
Adult Dose6 mg/kg/d PO for at least 12 d, preferably 3 wk
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; provocation of microfilariae for bancroftian filariasis is contraindicated in areas where Loa loa and Onchocerca volvulus are endemic because of risk of severe Mazzotti reaction
InteractionsNone reported
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsCaution with potential heavy infections of lymphatic filarioids because dose of 2 mg/kg may provoke febrile and inflammatory reaction secondary to worm death, antipyretics and steroids may decrease risk of these symptoms; adverse effects include headache, malaise, nausea, vertigo, and vomiting; nonteratogenic, although induced febrile reactions may cause spontaneous abortion or premature labor and delivery



Further Inpatient Care

  • Patients with HPD who have had a wedge resection of a lung lesion require routine postoperative care for thoracic surgery, ie, intercostal drainage, monitoring of blood loss, and chest wound care.

Further Outpatient Care

  • Patients with subcutaneous dirofilarial lesions usually can be treated as outpatients.
  • Patients with dirofilariasis who have surgical removal of lesions usually receive follow-up care at least once in the postoperative period for the removal of sutures and to monitor wound healing.

In/Out Patient Meds

  • The use of anthelminthic chemotherapy is not routinely recommended after the removal of nodules. If secondary lesions are suspected or confirmed in deep body sites (ie, chest, abdomen), a course of ivermectin and DEC may be advisable to prevent further invasive surgery. A course of chemotherapy also may be warranted after heavy exposure to mosquitoes in an area known to be endemic for dirofilariasis.

Transfer

  • Transfer to an institution where thoracic surgery can be performed may be required in cases of HPD where a fine-needle aspiration lung biopsy and/or wedge resection is considered necessary to make the diagnosis.

Deterrence/Prevention

  • Avoidance of mosquito bites during peak biting times of the day in areas known to be endemic for D immitis and D repens is the best method of preventing dirofilariasis.

Complications

  • Complications with dirofilariasis are rare. The most common complication is respiratory symptoms and a small pulmonary infarct that brings the infection to medical attention.
  • Patients with HPD or other deep-seated infections may have complications following surgical resection of lesions; complications may also occur if the lesion is mistaken for a malignancy and treated too aggressively.

Prognosis

  • In general, following diagnosis and resection of the affected tissue, prognosis is excellent.

Patient Education

  • Educating patients to avoid mosquito bites in areas known to be endemic may decrease exposure to infection.
  • For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article Bronchoscopy.



Medical/Legal Pitfalls

  • Incorrect diagnosis
    • Initially missing the diagnosis of dirofilariasis certainly is possible because of the infrequency of cases throughout the world and, specifically, in the Western Hemisphere.
    • Major complications in this scenario may include a late diagnosis that results in a greater degree of individual patient morbidity and a failure in the timely epidemiologic notification of a case.
  • Inappropriate treatment
    • Although this scenario is much less likely than incorrect diagnosis, inappropriate treatment of dirofilariasis is a potential issue, even if the diagnosis is made correctly.
    • One case of breast dirofilariasis in which a mastectomy was mistakenly performed because of a presumptive diagnosis of carcinoma in the affected breast exists in the literature.
    • To prevent inappropriate treatment from occurring, consult an infectious disease specialist in all cases of suspected dirofilariasis outside of endemic nations.
  • Reaction to treatment
    • Care must be taken to ascertain whether a patient with dirofilariasis has ever had any antiparasitic drugs and if the drugs were ever noted to cause problems.
    • A failure to do this and a resultant adverse reaction to a prescribed medication is a clear-cut legal pitfall that should be eliminated in practice by following the standards of care and obtaining an appropriate patient history.

Special Concerns

  • Patients with dirofilariasis may be at risk for other parasites. After treatment, patients should be monitored for other symptomology characteristic of parasitic infections.



Media file 1:  Dirofilariasis. Plain chest radiograph appearance of pulmonary coin lesion secondary to Dirofilaria immitis infection in a man.
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Media type:  X-RAY

Media file 2:  Dirofilariasis. This is an adult Dirofilaria immitis worm extracted from the heart and pulmonary artery of a dog. Worms usually are 8 mm in diameter, and females may grow to as long as 30 cm.
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Media type:  Photo

Media file 3:  Dirofilariasis. This is a transverse section through an immature adult Dirofilaria immitis removed from the right chest wall of an 18-month-old child in Sydney, Australia. The large lateral chords and multilayered cuticle are typical of Dirofilaria. The smooth cuticle is a feature of D immitis.
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Media type:  Photo

Media file 4:  Dirofilariasis. This is a transverse section through a mature female Dirofilaria repens removed from the superomedial orbital rim of a 67-year-old man. He was infected in Corfu, Greece, 6 months prior to diagnosis in Sydney, Australia. Features characteristic of Dirofilaria are the arrangement of the longitudinal muscles and the multilayered cuticle, which is expanded in the region of the large lateral chords.
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Media type:  Photo

Media file 5:  Dirofilariasis. This is a higher-magnification image of the Dirofilaria repens displayed in Image 4, which was removed from the eye of a 67-year-old man. The features characteristic of D repens are the longitudinal ridges on the cuticle that are 6-7 micrometers wide, spaced at 11- to 12-micrometer intervals.
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Media type:  Photo

Media file 6:  Dirofilariasis. Low-power view of a bulbar conjunctival biopsy specimen obtained from a 72-year-old man from Queensland, Australia, showing degenerate pieces of an immature Dirofilaria immitis worm in cross-sections and longitudinal sections with Masson stain.
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Media type:  Photo

Media file 7:  Dirofilariasis. Mid-power view of bulbar conjunctival biopsy specimen in Image 6 showing degenerate pieces of an immature Dirofilaria immitis worm in cross-section and longitudinal section view with Masson stain.
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Media type:  Photo

Media file 8:  Dirofilariasis. This is a high-power view of the bulbar conjunctival biopsy specimen shown in Images 6-7 showing a cross-section of immature Dirofilaria immitis. The thin, smooth cuticle with internal lateral longitudinal ridges, thin hypodermis, large lateral cords, well-developed coelomyarial muscles, and ill-defined reproductive organs is diagnostic of an immature D immitis (hematoxylin and eosin stain).
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Media type:  Photo



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Dirofilariasis excerpt

Article Last Updated: Jun 9, 2006