AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

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 manifests with either subcutaneous nodules or lung parenchymal disease that may be asymptomatic. The significance of infection in humans is that pulmonary and some subcutaneous lesions are commonly labeled as 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 do not reach adulthood; therefore, microfilariae are almost always absent.

Pathophysiology

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

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 are all suitable intermediate hosts and vectors. Some species of fleas, lice, and ticks may also act as vectors.

In the dog, adult D immitis reside in the right ventricle and pulmonary arteries. Female worms produce and release thousands of microfilariae larvae into the circulation daily, which mosquitoes ingest in a blood meal. Larvae develop into infective larvae over the next 10-16 days, depending on the environmental conditions, before being reintroduced 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 over another 6-7 months. Adult worms are 1-3 mm in diameter; females are 15-35 cm in length and males are typically shorter.

The adults of D repens, in contrast, reside in the subcutaneous tissues of dogs and cats, although the life cycle and release of microfilariae in the peripheral circulation remain the same as in D immitis.

Humans are accidental, dead-end hosts of Dirofilaria organisms 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 are usually not microfilaremic. Only one case of circulating diromicrofilaremia in humans has been reported in the medical literature. Because human disease is a chance event, one can predict amicrofilaremia; only one degenerate immature (fourth-stage) larvae or adult worm (fifth-stage larvae) is usually isolated from an ectopic position of the body, and Dirofilaria species, 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. Human dirofilariasis in the United States, in most cases, is due to D immitis, with occasional cases of Dirofilaria tenuis.

The prevalence of canine dirofilariasis has increased during the last 3 decades. Traditionally, human pulmonary dirofilariasis (HPD) has been localized predominantly to the Gulf of Mexico and 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 of the lower 48 states, except Nevada. The geographic spread of human disease has paralleled that in the dog population.

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

International

The most commonly reported manifestation of human dirofilariasis worldwide is subcutaneous nodular disease caused by D repens, with more than 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 has 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, but they have been traced back to patient exposure during a southern European visit.

HPD has been described in many other countries (including Brazil, France, Italy, Spain, Ukraine, Japan, India,¹ Africa, and Australia) on all continents of the world, although it appears less common than D repens–induced subcutaneous disease. Exposure of humans to D immitis larvae has also been reported in isolated communities of Indians of the Colombian Amazon rain forest.

According to some suggestions, the true prevalence of human exposure to and disease with D immitis is underestimated, because canine infection is widespread throughout the world and most infected people are asymptomatic.

A seroprevalence study in Spain, where 33% of dogs are infected with D immitis,² revealed that 22% of humans were seropositive (immunoglobulin G [IgG], 5.8%; immunoglobulin M [IgM], 3.5%; immunoglobulin E [IgE], 12.6%).³ IgG seroconversion was most prevalent in people older than 60 years, whereas IgM seropositivity was most common in those younger than 19 years. The level of IgE also decreased with age. The authors concluded that repeated contact with D immitis in this endemic population was common and began at an early age.

D immitis infection is usually associated with pulmonary lesions or radiologic coin lesions of the lung. Isolated reports describe D immitis or D immitis–like worms causing cutaneous or abdominal nodular disease and conjunctival disease.

D repens infection is the most common and widespread dirofilariasis in the world. The most common localization is a subcutaneous or submucosal nodule. Ophthalmic involvement is also described and the worm can be directly visualized in the bulbar conjunctiva. Breast nodules due to D repens are also commonly misdiagnosed as potential tumorous masses and are observed in people in hyperendemic areas for the parasite, usually Italy and Sri Lanka. Imported cases of breast D repens have been reported in the United States, Canada, Japan, and Australia. Pulmonary and abdominal lesions due to D repens have also been reported in endemic areas of Italy, France, and Greece.

Other Dirofilaria infections have been reported. D tenuis has been described as a cause of subcutaneous facial nodules and ophthalmic dirofilariasis in Florida in the United States. A living adult female D striata was removed from the orbit of a 6-year-old boy living in North Carolina in the United States. Dirofilaria spectans has been extracted from a digital artery lesion of a Brazilian man.

Mortality/Morbidity

• No fatality directly due to dirofilariasis has been recorded in the medical literature. HPD infection is symptomatic in 38-45% of patients. The infection is rarely 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 radiologic 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.

Race

All American studies of HPD have reported a predominance of infection in persons of European descent (up to 95%) compared with African Americans. This figure probably indicates a selection bias, with more whites presenting for screening radiologic investigations.

Sex

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

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

Age

The incidence and prevalence of human dirofilariasis favors middle-aged adults in endemic areas for the parasite.

• D immitis: All reviews of HPD have described most cases in adults aged 50-60 years. Again, a selection bias is probably occurring in adults because of the use of screening chest radiography, a history of cigarette smoking, and a heightened concern of malignancy with chest symptoms. HPD has been described in children as young as 8 years.
• D repens: D repens is likewise more common in adults, peaking in those 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 child reported with D repens infection was aged 4 months. This pediatric predominance is attributed to the custom of allowing toddler males to wear no clothing or to be bare below the waist. 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.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

History

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

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

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 radiography.

• D immitis infection
• • Most cases (approximately 56-62%) of pulmonary D immitis infection (HPD) are asymptomatic. Symptoms of HPD, when present, include localized retrosternal chest pain, cough, hemoptysis, wheezing, low-grade fever, chills, and malaise. One patient reported loss of consciousness following chest pain. Another patient experienced acute bilateral knee pain and swelling with fever.
  • One reference describes an 8-year-old American girl with HPD who presented with chest pains and wheezing.
  • Aberrant mucocutaneous sites may be involved (eg, conjunctiva), the most common symptom of which is eye pain.
• D repens and other dirofilarial infections: Typically, patients notice a single painful subcutaneous lump in the affected area. The most common areas include the face and eyelid, chest wall, upper arm, thigh, 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 findings of patients with HPD are usually noncontributory, regardless of whether patients are symptomatic.
  • A subcutaneous or subconjunctival lesion due to D immitis is rare but is detected more easily than HPD.
• D repens and other dirofilarial infections
• • Superficial infections (subcutaneous or subconjunctival lesions) are easily detected. A single nodule is the usual presentation. A review of all reported cases of D repens dirofilariasis emphasizes a predilection of upper body sites (76%) for infection over the lower body (24%). This is thought to reflect the biting patterns of the mosquito vector. In order of involvement, upper body sites are the head (46%), including the eyelid or conjunctiva (31%) and face (15%); chest wall or breast (15%); upper limb (12%); and neck (3%). The lower body sites affected include lower limb (11%), abdominal wall (5%), and male genitalia (6%).
  • A minority of D repens infections have been isolated from deep internal body sites, including the lung (associated with subpleural infarction), gastrosplenic ligament, omentum, peritoneal cavity, mesocolon, and pancreas. A perirectal nodule has been discovered.
  • As mentioned above, a predilection for male genitalia infection (21%) with D repens occurs in Sri Lanka, where it outnumbers other separate sites, such as conjunctiva (19%), eye adnexa (16%), upper limb (11%), face or cheek (9%), chest wall or breast (7%), neck (6%), lower limb (4%), abdominal wall (3%), and peritoneal cavity (1%).

Causes

The dog and cat parasites D immitis (heart worm) and D (Nochtiella) repens are the most commonly described etiologic agents of human infection. Human disease caused by Dirofilaria species that infect 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) are occasionally reported in the medical literature.

• Dog ownership and dirofilariasis: Infection with Dirofilaria 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 geographic region throughout the United States. All states, except Nevada, have reported D immitis infection in dogs. The prevalence varies from low levels in some states (0.3%, 0.5%, and 1.2% in Colorado, Washington, and Montana, respectively) to 40% in Florida and South Carolina. In Michigan, 3% of stray cats were found to have adult D immitis worms on autopsy following euthanasia. In general, the infection is more prevalent in dogs than in 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 in Japan, where as many as 10% of stray cats are infected.⁴ 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 is highest, at 59%, in the Canary Islands, Spain. In Australia, rates in stray dogs vary among states, from 1-15%, with approximately only 1% of cats affected.^{5, 6, 7} Rates 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.⁸ A prevalence of 55% was recorded in dogs in northern Taiwan.
  • In endemic areas of southern Europe, D repens is more prevalent than D immitis. The rates known include 7-22% in Greece, 20% in France, 29% in Sicily, and up to 37-85% in areas of Spain.
  • In Sri Lanka, another endemic area for D repens, dirofilariasis is high, with rates of 30-60%.⁹
• Immunodeficiency predisposing to dirofilariasis: The increased incidence of HPD in elderly patients with a corresponding low incidence of the condition in children was initially attributed to failing immunity. This theory is 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 that may share environments with human activity (ie, coyotes, foxes, wolves, black bears). This may become increasingly relevant in the control of dirofilariasis, because domestic canines can be administered prophylactic antifilarials to eradicate and control Dirofilaria in urban areas.
• • Dirofilariasis in wild canids: In the United States, the prevalence of D immitis in coyotes varies from 7% in Missouri¹⁰ to 75% in Georgia¹¹ to 91% in northern California.¹² D immitis was detected in 14% of red wolves released into the wild in the Alligator River National Wildlife Refuge in North Carolina 2-24 months after these wolves tested negative for microfilariae during the captive stage prior to release. In Australia, 56% of dingoes (Australian wild dog or Canis familiaris dingo) in a tropical region of the Northern Territory 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% in Missouri to 21% in South Carolina.¹³ The urban prevalence of D immitis in red foxes in Australia ranges from 6.4% in Melbourne to 8.8% in Sydney.¹⁴ In the Melbourne study, 2 known species of mosquito vector were identified as increasing the risk of human infection. In Spain, 11% of red foxes in the Pyrenean region were infected.
  • Dirofilariasis in raccoons: D tenuis was detected in 20% of wild raccoons trapped in southeast Georgia in the United States.¹⁵
  • Dirofilariasis in bears: D ursi has been detected in 0.2% of black bears in New Brunswick in Canada.¹⁶

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Other Problems to be Considered

Primary carcinoma of the lung (in adults)
Pulmonary metastasis
Benign tumors of the lung
Mycotic infections of the lung
Caseous granulomas of the lung
Eosinophilic granuloma
Conjunctivitis
Nonspecific subcutaneous nodule
Lipoma or other benign subcutaneous tumour
Mycosis fungoides
Infected subcutaneous cyst (adnexal or abscess)
Sparganosis
Breast carcinoma (in adults)

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Lab Studies

• CBC count: At best, eosinophilia may be detected in only 20% of patients with HPD.
• Sputum cytologic studies: The presence of eosinophils may support a diagnosis of HPD in patients with a coin lesion on radiography, although the test lacks specificity for accurate diagnosis.
• Dirofilarial serologic tests
• • Use of complement fixation tests, indirect hemagglutination, and enzyme-linked immunosorbent assays (ELISA) using whole body or somatic antigens has been attempted in the diagnosis of dirofilariasis. Although they are useful tools in epidemiologic surveys in known endemic areas, these tests have a low specificity in the general population and are not routinely available. As many as 30% of tests may show false-positive results because of cross-reactions with other nematode antigens (ie, Toxocara canis).
  • Improved specificity with ELISA has been shown if a 22-kD protein (Di22) from adult D immitis or recombinant antigens (a 35-kD fusion protein, P22U, and PLA2) is used for antibody capture. P22U and PLA2 are larval excretory or secretory proteins of D immitis. P22U is probably related to Di22 and is not recognized in Western blot analysis by 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.
  • Because of the low pretest probability of HPD, the positivity of ELISA using Di22 or other antigens must be added to the radiologic characteristics, the antecedents to presentation, the area where the patient lives or travels, and other data to help the clinician decide whether to use invasive techniques to reach a definitive diagnosis.

Imaging Studies

• Chest radiography and CT scan
• • The incidental finding of a pulmonary lesion on chest radiography is the usual presentation for HPD. The lesion is usually a well-circumscribed peripheral coin lesion or nodule. Transitory pulmonary nodules and calcified pulmonary granulomas (7%) are occasionally described. At least 90% of patients present with a solitary nodule. Lesions are predominantly subpleural (68%), are in the right lung (76%), and show a preference for the right lower lobe (46%). The lesions vary from 1-4 cm, with an average size of 2 cm. Multiple lesions can be present, either in the same lobe or in multiple lobes.
  • The shortest interval noted between normal findings on chest radiography and the presence of a coin lesion due to D immitis is 5 months.
  • The diagnosis may be made less often in children, because Dirofilaria lesions may be mistakenly labeled as Ghon foci secondary to pulmonary tuberculosis and, as such, are not followed or treated.
  • Chest or abdominal CT scanning may be performed to further evaluate pulmonary or abdominal lesions and may be used to assess for mediastinal lymphadenopathy. It may also be used as a guide for fine-needle aspiration and biopsy of suspicious lesions.
• MRI: MRI may be useful in differentiating subcutaneous dirofilarial lesions of the head and eyes from other etiologies (eg, histiocytosis, neuroblastoma).
• Ultrasonography: Ultrasonography of abdominal or cutaneous lesions assists in the etiologic diagnosis and may guide fine-needle aspiration biopsy.

Other Tests

• Pulsed-field gel electrophoresis: Multiloci electrophoresis analysis of DNA of worms recovered from pulmonary or subcutaneous nodules may be useful in the species identification of the zoonotic dirofilarials, especially in areas where more than one species of Dirofilaria may be present (ie, D repens, D immitis). Histologic and phenotypic features of recovered worms may degenerate or be damaged in removal, preventing accurate speciation.
• Polymerase chain reaction (PCR): 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 infections. Remember that biopsy material or worms for intended PCR should be not be stored in formalin, because formalin fragments genomic DNA and interferes with Taq polymerase.

Procedures

• Surgical biopsy of subcutaneous nodules: Patients with D repens infection usually present with a subcutaneous nodule in the body sites listed above. The nodule is almost always excised for histopathologic diagnosis and confirmation of infection. The nodules vary from 0.5-2.5 cm in diameter.
• Fine-needle aspiration of peripheral pulmonary lesions: Diagnosis of HPD using transthoracic needle aspiration with and without CT guidance has been successfully used on 2 occasions to reveal morphologic features of D immitis and prevent invasive surgery.
• Bronchoscopy with cytology and transbronchial biopsy: Bronchoscopy has been attempted in patients with HPD with little success in positively revealing the cause of the pulmonary lesion. Results of cytologic study of bronchoalveolar lavage specimens and brushings should be interpreted with caution, because bronchial mucosa in HPD may be focally metaplastic and mimic invasive squamous cell carcinoma. A predominance of eosinophils or eosinophilic pneumonia may indicate a diagnosis of HPD.
• Open lung biopsy with wedge resection of affected lung segment: On removal, most lesions are well-circumscribed, spherical, and gray-yellow in appearance. Wedge-shaped lesions may be observed in 32% of patients.
• Fine-needle aspiration of retroperitoneal dirofilarial masses: One case report has described the successful use of ultrasonographically guided fine-needle aspiration and biopsy of a pseudotumorous para-aortic mass in a 60-year-old French woman. Morphologic and epidemiologic features suggested D repens.

Histologic Findings

Human pulmonary dirofilariasis with D immitis infection

On 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, finally, a fibrous capsule rich in eosinophils (66%). The overlying pleura are usually inflamed and fibrotic (75%). Calcification and caseous necrosis (41%) may be present. Charcot-Leyden crystals may be detected in nodules (27%).

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 patients.

Anatomic features of the worm are better appreciated with Movat pentachrome, Gomori methenamine silver, or periodic acid-Schiff–stained histologic sections. Identification of internal features of the worm (ie, digestive system, genital tract) is often possible. Nonspecific fluorescent whitener stains have also been used to rapidly reveal 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 (ie, myoid fibers, lateral chords) show more degeneration than others. Other features, such as the cuticle (outer covering), walls of the digestive tract, and sexual tubules, offer a certain resistance to attack. D repens is most easily distinguished from D immitis in such lesions through the presence of external ridges of the cuticle.

A high number of eosinophils and other inflammatory cells of varying degrees surround the worm. An epithelioid granulomatous reaction with multinucleate giant cells occurs in at least 33% of patients and may resemble that observed in mycobacterial or fungal infections. Lymphocytes may form large aggregates and follicles with germinal centers that can extend out into the connective tissue, mimicking a lymphoma. A fibrotic capsule and calcification may be present in 6% of patients. 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 the diagnosis of dirofilariasis. Sparganosis, a parasitic zoonosis caused by the larval stage of Spirometra species, is another infection that may cause a similar lesion.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Medical Care

Administering antifilarial medication (eg, prior to surgical resection of dirofilarial lesions) is not generally 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 in retrospect when histopathologic sections of biopsy samples or excised material are viewed.

Surgical Care

• Surgical excision of the lesion and affected area is the treatment of choice for human dirofilariasis.
• Some authors have recommended a period of observation of chest coin lesions for several months if dirofilariasis is suspected and no other suggestive features on history or examination for 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 dirofilariasis.

Activity

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

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Drug Category: Anthelmintics

Parasite biochemical pathways are different from the human host; thus, toxicity is directed to the parasite, egg, or larvae. Mechanism of action varies within the drug class. Antiparasitic actions may include the following:

• Inhibition of microtubules, causing irreversible block of glucose uptake
• Tubulin polymerization inhibition
• Depolarizing neuromuscular blockade
• Cholinesterase inhibition
• Increased cell membrane permeability, resulting in intracellular calcium loss
• Vacuolization of the schistosome tegument
• Increased cell membrane permeability to chloride ions via chloride channels alteration

Drug Name	Diethylcarbamazine (DEC, Hetrazan)
Description	A piperazine derivative. Precise mechanism is not understood. Has been shown to induce immobilization of microfilariae by decreasing muscle activity because of hyperpolarization effects. Alteration of the surface membrane also occurs, with enhanced destruction by the host's immune system. Evidence suggests that DEC may enhance adhesion of granulocytes via antibody-dependent and antibody-independent mechanisms. Interference by microfilarial intracellular processing and transport of specific macromolecules by DEC has also been hypothesized.
Adult Dose	6 mg/kg/d PO for at least 12 d, preferably 3 wk 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
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; DEC provocation (ie, provocation of microfilariae for bancroftian filariasis is contraindicated in areas where Loa loa and Onchocerca volvulus are endemic because of the risk of a severe Mazzotti reaction)
Interactions	None reported
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Nonteratogenic and safe in pregnancy, although induced febrile reactions may induce spontaneous abortion or premature labor and delivery; microfilaricidal treatment can induce allergic reactions of fever, urticaria, and lymphangitis in lymphatic filariasis (Mazzotti reaction); nonspecific adverse effects include headache, malaise, nausea, vertigo, and vomiting

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Further Inpatient Care

• Patients with HPD who have undergone wedge resection of a lung lesion require routine postoperative care for thoracic surgery (eg, intercostal drainage, monitoring of blood loss, chest wound care).
• Patients with subcutaneous dirofilarial lesions can usually be treated as outpatients or undergo day-case surgical procedures.

Further Outpatient Care

• Patients with dirofilariasis whose lesions are removed surgically are usually seen at least once in the postoperative period for the removal of sutures and monitoring of wound healing.

In/Out Patient Meds

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

Transfer

• Transfer to an institution performing thoracic surgery may be required in patients with HPD in whom a fine-needle aspiration lung biopsy, wedge resection, or both is thought necessary for diagnosis.

Deterrence/Prevention

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

Complications

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

Prognosis

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

Patient Education

• Patient education in known endemic areas regarding the avoidance of mosquito bites may decrease exposure to infection.
• For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article Bronchoscopy.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Medical/Legal Pitfalls

• Incorrect diagnosis
• • Initially missing the diagnosis of dirofilariasis is certainly possible because of the infrequency of cases throughout the world, specifically in the Western Hemisphere.
  • Major complications in this scenario include a late diagnosis resulting in a greater degree of individual patient morbidity and failure to make a timely epidemiologic notification of a case.
• Inappropriate treatment
• • Although this scenario is much less likely than the one above, inappropriate treatment of dirofilariasis may be an issue even if the diagnosis were 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 is reported in the literature.
  • Consult an infectious diseases specialist for patients with suspected dirofilariasis outside of endemic nations to prevent inappropriate treatment.
• Reaction to treatment
• • Care must be taken to ascertain whether the patient with dirofilariasis has ever received antiparasitic drugs and if the medications caused problems.
  • Failure to obtain a relevant drug history with a resultant adverse reaction to prescribed medication is a clear-cut legal pitfall that should be eliminated in practice through following the standards of care and obtaining an appropriate patient history.

Special Concerns

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

FURTHER READING

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

See Image 8 at the McGill Faculty of Medicine Web site.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Media file 1:  Plain chest radiograph revealing pulmonary coin lesion secondary to Dirofilaria immitis in an adult man.
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Media type:  Radiograph

Media file 2:  Adult worm of Dirofilaria immitis extracted from the heart and pulmonary artery of a dog. Worms are usually 1-3 mm in diameter and females may reach 35 cm in length.
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Media type:  Photo

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

Media file 4:  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 the diagnosis in Sydney, Australia. Features characteristic of Dirofilaria include 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:  A higher-magnification image of the Dirofilaria repens from the eye of a 67-year-old man described in Media file 4. The features characteristic of D repens are the longitudinal ridges on the cuticle, 6-7 mm wide, spaced at 11- to 12-mm intervals.
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Media type:  Photo

Media file 6:  Low-power view of bulbar conjunctival biopsy sample from a 72-year-old man from Queensland, Australia, showing degenerate pieces of an immature Dirofilaria immitis worm in cross-section and longitudinal section (Masson stain). See Media files 7-8.
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Media type:  Photo

Media file 7:  Midpower view of bulbar conjunctival biopsy sample in Media files 6 and 8 showing degenerate pieces of an immature Dirofilaria immitis worm in cross-section and longitudinal section (Masson stain).
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Media type:  Photo

Media file 8:  High-power view of bulbar conjunctival biopsy sample in Media files 6-7 showing 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 are diagnostic of an immature D immitis (hematoxylin and eosin stain).
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Media type:  Photo

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

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