Filariasis

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Practice Essentials

Filariasis is a disease group affecting humans and animals, caused by filariae; ie, nematode parasites of the order Filariidae.[1] Of the hundreds of described filarial parasites, only 8 species cause natural infections in humans. The World Health Organization (WHO) has identified lymphatic filariasis as the second leading cause of permanent and long-term disability in the world, after leprosy.

Signs and symptoms

Lymphatic filariasis

The following acute syndromes have been described in filariasis:

Onchocerciasis

The clinical triad of infection in onchocerciasis is as follows:

Loiasis

The diagnostic feature of loiasis is a Calabar swelling, ie, a large, transient area of localized, nonerythematous subcutaneous edema. This is most common around the joints.

Mansonella infections

These are usually asympt omatic. If symptoms are present, they may include fever, pruritus, skin lumps, lymphadenitis, and abdominal pain.

See Clinical Presentation for more detail.

Diagnosis

Microfilariae can be detected through examination of the following:

The following imaging studies can be used in the evaluation of filariasis:

Histologic findings include the following:

See Workup for more detail.

Management

Anthelmintics used in the treatment of filariasis include the following:

Surgery

In lymphatic filariasis, large hydroceles and scrotal elephantiasis can be managed with surgical excision. Correcting gross limb elephantiasis with surgery is less successful and may necessitate multiple procedures and skin grafting.

In onchocerciasis, nodulectomy with local anesthetic is a common treatment to reduce skin and eye complications.

See Treatment and Medication for more detail.

Image library


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Filariasis. This figure displays the life cycle of Wuchereria bancrofti in humans and mosquito vectors (ie, Aedes, Anopheles, Culex, Mansonia species)....

Background

Filariasis is a disease group affecting humans and animals, caused by filariae; ie, nematode parasites of the order Filariidae.[1] Filarial parasites can be classified according to the habitat of the adult worms in the vertebral host, as follows (see Pathophysiology, Etiology, and Workup):

Of the hundreds of described filarial parasites, only 8 species cause natural infections in humans. The parasites of the cutaneous and lymphatic groups are the most clinically significant. Other species of filariae may cause incomplete infections, because they are unable to reach adult maturity in human hosts and therefore cannot produce first-stage larvae, known as microfilariae (eg, Dirofilaria immitis [dog heartworm], D [Nochtiella] repens, and D tenuis [raccoon heartworm]). (See the image below.)


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Filariasis. This figure displays the life cycle of Wuchereria bancrofti in humans and mosquito vectors (ie, Aedes, Anopheles, Culex, Mansonia species)....

Filariasis has a significant economic and psychosocial impact in endemic areas, disfiguring and/or incapacitating more than 40 million individuals.[5] Studies from the Indian subcontinent have shown that infected patients lose significant time from work because of the disease,[6] costing the national treasury a minimum of $842 million per year. (See Epidemiology, Prognosis, Clinical Presentation, and Treatment.)[7]

Filariae have a specific geographic distribution. For example, W bancrofti is found in sub-Saharan Africa, Southeast Asia, India, and the Pacific Islands. B malayi is found in similar locations but not in sub-Saharan Africa. B timori occurs on Timor island, in Indonesia. (See Epidemiology.)

It has been observed (especially in endemic areas), that the prevalence of microfilaremia increases with age, as adult worms are gradually acquired over years. Lymphatic filariasis is first contracted in childhood, and most individuals in endemic areas have been exposed by the third or fourth decade of life. The proportion of infected individuals remains constant. (See Pathophysiology and Etiology.)[8]

As with most helminths, adult filarial parasites replicate in a secondary host. The adult worm burden in an individual cannot increase unless the host is exposed to additional microfilaria. Infected individuals cannot sustain higher levels of parasitemia once they leave the endemic area.

Because the mosquito vector is inefficient, a relatively prolonged stay in an endemic area is usually required to acquire the infection. Disorganized urbanization is adding to the vector population and hence to the increased incidence and prevalence of such diseases in developing countries.

Patient education

Patients should learn to protect against insect vectors and to refrain from self-treatment regimens, especially with diethylcarbamazine (DEC), since this drug can lead to meningoencephalopathy. (See Treatment and Medication.)

Pathophysiology

The filarial life cycle, like that of all nematodes, consists of 5 developmental (larval) stages in a vertebral host and an arthropod intermediate host and vector. Adult female worms produce thousands of first-stage larvae, or microfilariae, which are ingested by a feeding insect vector. Some microfilariae have a unique daily circadian periodicity in the peripheral circulation. 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 feeding most actively.[9]

Microfilariae undergo 2 developmental changes in the insect. Third-stage larvae then are inoculated back into the vertebral host during the act of feeding for the final 2 stages of development. These larvae travel through the dermis and enter regional lymphatic vessels. During the next 9 months, the larvae develop into mature worms (20-100 mm in length). An average parasite can survive for about 5 years.

The prepatent period is defined as the interval between a vector bite and the appearance of microfilariae in blood, with an estimated duration of about 12 months.

The following factors affect the pathogenesis of filariasis:

Filarial infection generates significant inflammatory immune responses that participate in the development of symptomatic lymphatic obstruction. Increased levels of immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) secondary to antigenic (from dead worms) stimulation of Th2-type immune response have been demonstrated.

Studies have shown that there is a familial tendency to lymphatic obstruction, providing support for the hypothesis that host genes influence lymphedema susceptibility.[13] Studies also suggest that microfilaremia may be increased in individuals with low levels of mannose-binding lectin, suggesting a genetic predisposition.[14] Further, a propensity to develop chronic disease has been demonstrated in patients with polymorphisms of endothelin-1 and tumor necrosis factor receptor II.[15]

Prenatal exposure seems to be an important determinant in conferring greater immune tolerance to parasite antigen.[16] Thus, individuals from endemic areas are often asymptomatic until late in the disease when they have high worm burden, whereas nonimmune expatriates tend to have brisk immune responses and more severe early clinical symptoms, even in light infections.

Studies have shown that lymphatic filarial parasites contain rickettsialike Wolbachia endosymbiotic bacteria. This association has been recognized as contributing to the inflammatory reaction seen in filariasis.[17]

Etiology

Lymphatic filariasis

Mosquitoes of the genera Aedes, Anopheles, Culex, or Mansonia are the intermediate hosts and vectors of all species that cause lymphatic filariasis.

Acute lymphatic filariasis is related to larval molting and adult maturation to fifth-stage larvae. Adult worms are found in lymph nodes and lymphatic vessels distal to the nodes. Females measure 80-100 mm in length and males are 40 mm.

The most commonly affected nodes are in the femoral and epitrochlear regions. Abscess formation may occur at the nodes or anywhere along the distal vessel. Infection with B timori appears to result in more abscesses than infection with B malayi or W bancrofti. (See the image below.)


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Filarial abscess scar on the left upper thigh in a young male who is positive for Wuchereria bancrofti microfilariae

Cellular invasion with plasma cells, eosinophils, and macrophages, together with hyperplasia of the lymphatic endothelium, occurs with repeated inflammatory episodes. The consequence is lymphatic damage and chronic leakage of protein-rich lymph in the tissues, thickening and verrucous changes of the skin, and chronic streptococcal and fungal infections, which all contribute to the appearance of elephantiasis. (The skin of individuals with elephantiasis is characterized by hyperkeratosis, acanthosis, lymph and fatty tissue, loss of elastin fibers, and fibrosis.)

B malayi elephantiasis is more likely to affect the upper and lower limbs, with genital pathology and chyluria being rare. Secondary bacterial infection in elephantiasis can result in blindness.

Occult filariasis

Occult filariasis denotes filarial infection in which microfilariae are not observed in the blood but may be found in other body fluids and/or tissues.

The occult syndromes are as follows:

Tropical pulmonary eosinophilia (TPE) - Most likely results from a hyperresponsiveness to W bancrofti or B malayi antigen; symptoms result from allergic and inflammatory reactions elicited by the microfilariae and parasite antigens that the lungs clear from the bloodstream

D immitis or D repens infection - Human infection with D immitis may result in pulmonary lesions of immature Dirofilaria worms in the lung periphery; if D immitis larvae lodge in branches of the pulmonary arteries, they can cause pulmonary infarcts.

Onchocerciasis

O volvulus microfilariae from the skin are ingested by the Simulium species of blackflies. Chronic onchocerciasis cases are hyperresponsive to parasite antigen, have increased eosinophilia, and result in the presence of high levels of serum IgE. Patterns of onchocercal eye disease also are associated with parasite strain differences at the DNA level.[18]

Loiasis

Mango flies or deerflies of Chrysops transmit loiasis. Response to L loa infection appears to differ between residents and nonresidents in endemic areas. Nonresidents with infection appear to be more prone to symptoms than residents, despite lower levels of microfilaremia. Eosinophil, serum IgE, and antibody levels are also higher in nonresidents with infection. (See the image below.)[19]


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Filariasis. Microfilariae of Loa loa detected in skin snips.

L loa meningoencephalopathy

Meningoencephalopathy is a severe and often fatal complication of infection. This syndrome is usually related to diethylcarbamazine (DEC) administration in individuals with high-density microfilaremia but it may occur without drug therapy.[20]

DEC causes a large influx of microfilariae into the cerebrospinal fluid, leading to capillary obstruction, cerebral edema, hypoxia, and coma. Localized necrotizing granulomas are also present, in response to microfilariae. Endomyocardial fibrosis, nephritic syndrome, and venous thrombosis may also be observed.

Epidemiology

Occurrence in the United States

No form of human filariasis is currently endemic to the United States. W bancrofti was once prevalent in Charleston, South Carolina, because of the presence of suitable mosquito vectors. Immigrant populations and persons who have traveled long-term to the tropics are potential reservoirs of infection.

Returning missionaries and Peace Corps volunteers are at particular risk for lymphatic filariasis and onchocerciasis, because of the long prepatent period and relatively high intensity of exposure required between exposure to infective insect bites and the development of sexually mature adult worms.

Two cases of ocular onchocerciasis have been reported in the United States,[21] as has a single case of spinal mass in a toddler due to Onchocerca lupi infection.[22]

International occurrence

Lymphatic filariasis affects more than 90 million people worldwide and is found throughout the tropics and subtropics. At least 21 million people are infected with O volvulus in equatorial Africa and foci in Central and South America. Approximately 3 million people in Central Africa are infected with L loa. In 1997, the World Health Organization (WHO) initiated a program to globally eliminate lymphatic filariasis as a public health problem.[23, 19]

Sex- and age-related demographics

Both sexes are equally susceptible to filariasis. Because of different local and cultural practices, however, as well as differences in exposure to insect vectors, one sex or the other may be exposed to infection more often.

Individuals of all ages are susceptible to infection and are potentially microfilaremic. Microfilaremia rates increase with age through childhood and early adulthood, although clinical infection may not be apparent. The manifestation of acute and chronic filariasis usually occurs only after years of repeated and intense exposure to infected vectors in endemic areas.

Prognosis

The prognosis in filariasis is good if infection is recognized and treated early. Filarial diseases are rarely fatal, but the consequences of infection can cause significant personal and socioeconomic hardship for those who are affected.

The morbidity of human filariasis results mainly from the host reaction to microfilariae or developing adult worms in different areas of the body. The WHO has identified lymphatic filariasis as the second leading cause of permanent and long-term disability in the world, after leprosy.

History

Symptoms of filariasis are dependent on species and body type and can be acute or chronic in nature. Up to 70% of infected individuals remain asymptomatic. Symptoms usually do not manifest until adolescence or adulthood, when worm burden is usually the highest. Several variations have been observed.[24]

Because cases of filariasis in the industrialized world and the Western Hemisphere are uncommon, the diagnosis may initially be missed. To avoid this pitfall, obtain and document a travel history from patients with suspicious lesions.

Lymphatic filariasis

The clinical course of lymphatic filariasis is broadly divided into the following:

Lymphatic filariasis symptoms predominantly result from the presence of adult worms residing in the lymphatics. They include the following:

The following acute syndromes have been described in filariasis:

Acute ADL

This refers to the sudden onset of febrile, painful lymphadenopathy. Pathologically, the lymph node is characterized by a retrograde lymphangitis, distinguishing it from bacterial lymphadenitis. Symptoms usually abate within 1 week, but recurrences are possible.[25]

Signs and symptoms of ADL include episodic attacks of fever associated with inflammation of the inguinal lymph nodes, testis, and spermatic cord, as well as with lymphedema. Skin exfoliation of the affected body part usually occurs with resolution of an episode.

Tropical pulmonary eosinophilia

TPE is a form of occult filariasis. Presenting symptoms include a dry, paroxysmal cough; wheezing; dyspnea; anorexia; malaise; and weight loss.

Symptoms of TPE are usually due to the inflammatory response to the infection. Characteristically, peripheral blood eosinophilia and abnormal findings on chest radiography are observed. TPE is usually related to W bancrofti or B malayi infection.

Onchocerciasis

This also is known as hanging groins, leopard skin, river blindness, or sowda. Symptoms result from the presence of microfilariae in the skin and include pruritus, subcutaneous lumps, lymphadenitis, and blindness.

Patients with onchocerciasis may report impaired visual acuity due to corneal fibrosis. Epilepsy has been associated with onchocerciasis in some studies.[26]

Loiasis

The symptoms of L loa infection are usually confined to subcutaneous swellings on the extremities, localized pain, pruritus, and urticaria.

Rare manifestations of infection include the following:

M ozzardi, M perstans, and M streptocerca infection

Mansonella infections are usually asymptomatic. If symptoms are present, they may include fever, pruritus, skin lumps, lymphadenitis, and abdominal pain.

Dirofilaria infection

Symptoms of D immitis infection involve the respiratory system and include chest discomfort, cough, fever, and hemoptysis.

Symptoms of D repens infection usually include a lump in the subcutaneous tissue, submucosa, or eyelid.

Physical Examination

Signs of filariasis present on examination are species-dependent and may be acute or chronic in nature.

Lymphatic filariasis

In lymphatic filariasis, repeated episodes of inflammation and lymphedema lead to lymphatic damage, chronic swelling, and elephantiasis of the legs, arms, scrotum, vulva, and breasts. (See the images below.)[27, 28, 29, 30, 31, 14]


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Lymphatic filariasis resulting from Wuchereria bancrofti infection, which is causing limb lymphoedema, inguinal lymphadenopathy, and hydrocele. Photog....


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Filariasis. Unilateral left lower leg elephantiasis secondary to Wuchereria bancrofti infection in a boy.


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Filariasis. This is a close-up view of the unilateral lower leg elephantiasis shown in Image 4. Note the lymphedema and typical skin appearance of dep....


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Filariasis. Lateral view of the right outer aspect of a leg affected by gross elephantiasis secondary to Wuchereria bancrofti infection.


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Filariasis. Inner aspect of the lower leg of the male patient in Image 6, showing gross elephantiasis secondary to Wuchereria bancrofti infection.


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Filariasis. Unilateral left hydrocele and testicular enlargement secondary to Wuchereria bancrofti infection in a man who also was positive for microf....


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Filariasis. Bilateral hydrocele, testicular enlargement, and inguinal lymphadenopathy secondary to Wuchereria bancrofti infection in a man who also wa....

The WHO has developed a system to grade the severity of edema, as follows[5] :

Grade 1 - Pitting edema reversible with limb elevation

Grade 2 - Nonpitting edema irreversible with limb elevation

Grade 3 - Severe swelling with sclerosis and skin changes

Hydrocele is the most common manifestation of chronic W bancrofti infection in males in endemic areas but is rare with B malayi and B timori infection.

Chyluria also may be present in chronically infected persons. Since large amounts of fat and protein are lost in the urine, these conditions can lead to nutritional deficiencies.

Tropical pulmonary eosinophilia

Scattered wheezes and crackles are heard in both lung fields. Lymphadenopathy and hepatomegaly may be present.

Onchocerciasis

The clinical triad of infection is as follows:

Common eye findings in onchocerciasis include the following:

Loiasis

The diagnostic feature of loiasis is a Calabar swelling, ie, a large, transient area of localized, nonerythematous subcutaneous edema. This is most common around the joints.

Peripheral nerve involvement in loiasis has been described.[32] Microfilaremia tends to be asymptomatic. Occasionally, the worm is observed migrating through subconjunctival or other tissues.

M ozzardi, M perstans, and M streptocerca infection

Subcutaneous or conjunctival nodules and lymphadenopathy may be detected in symptomatic persons.

Dirofilaria infection

These infections are characterized as follows:

Approach Considerations

The traditional diagnostic method for filariasis is to demonstrate microfilariae in the peripheral blood or skin. For example, the microfilariae of all species that cause lymphatic filariasis and the microfilariae of L loa, M ozzardi, and M perstans are detected in blood.[2]

O volvulus and M streptocerca infections are diagnosed when microfilariae are detected in multiple skin snip specimens from different sites located on both sides of the body. In addition, microfilariae of O volvulus may be detected in the cornea or anterior chamber of the eye, using slit-lamp examination.

Urine examination and microscopy

Microfilariae may also be observed in chylous urine and hydrocele fluid. If lymphatic filariasis is suspected, urine should be examined macroscopically for chyluria and then concentrated to examine for microfilariae.

Detection of Microfilariae in the Skin and Eye

Skin

O volvulus and M streptocerca infections are diagnosed when microfilariae are detected in multiple skin-snip specimens from different sites located on both sides of the body.

In suspected cases of African onchocerciasis, the recommended sites for skin snips are the gluteus and calf. For American onchocerciasis, the scapula and deltoid skin are preferred.

Mazzotti test

The Mazzotti test allows a presumptive diagnosis of cutaneous filariasis to be made when skin snips are negative for microfilariae. An intense pruritus is elicited within hours after a single small dose of DEC (50-100 mg). Steroids may be necessary to control this inflammatory reaction. The test must be used with caution in individuals who may be heavily infected, because a severe systemic reaction can be provoked. A DEC patch test that causes a localized skin reaction may be used in such patients.

Eye

Microfilariae of O volvulus may be detected in the cornea or anterior chamber of the eye using slit-lamp examination.

Detection of Microfilariae in Blood

As mentioned, the microfilariae of all species that cause lymphatic filariasis and the microfilariae of L loa, M ozzardi, and M perstans are detected in blood. (See the image below.)


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Filariasis. Microfilariae of Mansonella perstans in peripheral blood.

Capillary finger-prick or venous blood is used for thick blood films. Venous blood also can be concentrated or passed through a Nuclepore filter before being examined microscopically. The species of infection then can be determined by the microscopic appearance. W bancrofti and Brugia species have an acellular sheath. W bancrofti has no nuclei in its tail, whereas B malayi has terminal and subterminal nuclei. (See the image below.)


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Filariasis. Appearance of microfilariae after concentration of venous blood with a Nuclepore filter.

Microfilariae may periodically appear in the peripheral circulation. For the best chance of detection, the blood should be examined at different intervals over a 24-hour period. (See the image below.)


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Filariasis. Microfilaria of Wuchereria bancrofti in a peripheral blood smear.

Bancroftian and brugian filariasis tend to show nocturnal periodicity, so it is recommended that samples be collected between 10:00 pm and 2:00 am. Provocation of nocturnally periodic microfilariae may be achieved with a daytime dose of DEC at 1-2 mg/kg.

Microfilariae may be absent in the following cases:

Complete blood count

Eosinophilia is marked in all forms of patent filarial infection.

Serum immunoglobulin concentrations

Elevated serum IgE and IgG4 may be observed with active filarial disease. Testing based on polymerase chain reaction assay has been described.[34]

A multiplex bead assay to monitor serial levels of serum antibody during treatment has been proposed.[35]

Detection of filarial antigen

The presence of circulating filarial antigen in the peripheral blood, with or without microfilariae, is considered diagnostic of patent filarial infection and is also used to monitor the effectiveness of therapy. Commercial kits are available to test venous blood and can be quantitative (enzyme-linked immunoassay [ELISA]) Og4C3 monoclonal antibody–based assay) or qualitative (immunochromatographic).

The ELISA is one of the best predictors of worm burden[36] ; the other, although not as sensitive,[37] was once considered the test of choice in field surveys. However, results from this test remain positive for 3 years posttreatment; hence, immunochromatographic testing has been shown to be ineffective.[38]

Detection of filarial antibodies

The use of recombinant antigens for the diagnosis of onchocerciasis IgG4 antibodies (which are a marker of active infection) has improved the sensitivity and specificity of serologic assays.[39] The usual IgG and IgE lack specificity (species differentiation) and usually crossreact with antigens of Strongyloides. In addition, they do not differentiate between past and recent infections. Thus, diagnosis based on recombinant antigens is useful in expatriates but not in persons living in endemic regions.

Imaging Studies

The following imaging studies can be used in the evaluation of filariasis:

Ultrasonography has also been used to demonstrate the presence of viable worms, which are seen to be in continuous motion (ie, "filarial dance" sign). This imaging characteristic has been used to monitor the effectiveness of treatment.[40] In addition, deep onchocercomas and vitreous changes in the eye can sometimes be detected with ultrasonography.

Biopsy

It is recommended that biopsy specimens be obtained only in patients with cutaneous filariasis, as excising nodes may further impede lymphatic drainage in patients with lymphatic filariasis. Adult worms of O volvulus and L loa are found in the nodules and fibrotic tissue of the skin. L loa worms occasionally can be dissected from the conjunctiva of the eye or bridge of the nose as they migrate through subcutaneous tissue.

Histologic Findings

Lymphatic filariasis

Affected lymph nodes demonstrate fibrosis and lymphatic obstruction with the creation of collateral channels. The skin of individuals with elephantiasis is characterized by hyperkeratosis, acanthosis, lymph and fatty tissue, loss of elastin fibers, and fibrosis. (See the image below.)


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Filariasis. Adult worms of Wuchereria bancrofti in cross section isolated from a testicular lump.

Onchocerciasis

Two areas are evident in onchocercomas: (1) a central stromal and granulomatous, inflammatory region where the adult worms are found and (2) a peripheral, fibrous section. Microfilariae in the skin incite a low-grade inflammatory reaction with loss of elasticity and fibrotic scarring. (See the image below.)


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Filariasis. Adult Onchocerca volvulus contained within onchocercomas of the skin.

Approach Considerations

The medical management of a filarial infection should be specific and based on the microfilariae isolated or antigenemia detected.

Mass drug administration reduces the transmission of filarial infection and disease morbidity by decreasing the burden of microfilaremia, resulting in suboptimal levels for transmission by disease vectors.[41, 42, 43, 44, 45, 46]

For example, annual mass treatment with albendazole and ivermectin is employed to interrupt the transmission of W bancrofti. Since this species has no alternative hosts, this approach could theoretically result in eventual eradication of bancroftian filariasis.

One study evaluated the effect of higher dose and increased frequency (twice yearly) of albendazole-ivermectin therapy for W bancrofti and found that it resulted in complete microfilarial clearance, as well as a more sustained clearance than that resulting from standard-dose albendazole-ivermectin treatment.[47]

The effects of mass treatment on filariasis have reportedly been sustained for up to 6 years.[48, 49, 50, 51] No filariasis vaccine is currently available, but efforts to develop an effective one are under way.[52]

Surgery

Lymphatic filariasis

Large hydroceles and scrotal elephantiasis can be managed with surgical excision. Correcting gross limb elephantiasis with surgery is less successful and may necessitate multiple procedures and skin grafting.

Onchocerciasis

Nodulectomy with local anesthetic is a common treatment to reduce skin and eye complications.

Diet and activity

Fatty foods are restricted in individuals with proven chyluria that is associated with lymphatic filariasis.

Individuals with chronic lymphatic filariasis are encouraged to mobilize (with compression bandage support) the affected limb.

Prevention

Avoidance of bites from insect vectors is usually not feasible for residents of endemic areas, but visitors to these regions should use insect repellent and mosquito nets.

Consultations

To prevent inappropriate treatment, consult an infectious disease specialist in all cases of suspected filariasis outside of endemic nations. Other possible consultations include:

Pharmacologic Therapy

Lymphatic filariasis

Patients with asymptomatic microfilaremia can be treated on an outpatient basis. Supervision of oral DEC therapy and provocation with postadministration observation is recommended for patient compliance with therapy and for the management of febrile reactions in heavily infected patients.[23]

Inpatient care may initially be required for adenolymphangitis (ADL) and chronic filariasis. Such care includes the use of antihistamines, steroids, pain relief, and intravenous antibiotics for secondary infections.

Lymphedema

Steroids can be used to soften and reduce the swelling of lymphedematous tissues. Mild to moderate filarial lymphedema has been shown to improve with a 6-week course of doxycycline, independent of ongoing infection.[53]

Bed rest, limb elevation, and compression bandages traditionally have been used for the management of chronic lymphedema.

Chronic filariasis

Treatment of chronic filariasis does not change the prognosis, as irreversible fibrosis usually destroys lymphatic tissue. However, asymptomatic patients, hoping to diminish progression of the disease, still typically undergo treatment, although the benefit of this is unclear.[54]

Chyluria

In the treatment of chyluria, a special low-fat, high-protein diet supplemented with medium-chain triglycerides may prove beneficial. In addition, the sclerosing action conferred by diagnostic lymphangiography may plug the leak.

Secondary infection

Supportive care should include the prevention of secondary infection, especially in patients with advanced disease. Individuals with chronic infections should wash the affected area frequently, apply antiseptic creams to abrasions, keep their nails clean, wear comfortable footwear, and exercise the affected limb to aid lymphatic flow.

Onchocerciasis

If DEC and suramin (currently the only drug in clinical use for onchocerciasis that is effective against adult worms) are used, inpatient care is recommended to monitor for reactions and complications of therapy.[20]

Moxidectin is being investigated as an alternative to ivermectin for the treatment of river blindness. This agent may shorten the number of annual treatments to 6.

Bancroftian filariasis

Ivermectin is now considered the drug of choice for the treatment of bancroftian filariasis. In the United States, it can be obtained from the Centers for Disease Control and Prevention (CDC); in endemic areas of the world, it is provided free by the Mectizan Donation Program. The addition of albendazole seems to improve response.[55, 56, 57, 58]

Six-week and 8-week courses of doxycycline have compared favorably with ivermectin plus albendazole.[59] Doxycycline therapy may be more readily available and may be better tolerated by some patients. It may also be capable of preventing or reversing lymphatic pathology.[60]

In one study, a 3-week course of doxycycline followed by a single dose of DEC was shown to be microfilaricidal.[60]

Findings have validated the use of single-dose regimens of ivermectin and DEC or albendazole for large-scale control and eradication programs aimed at reducing Wuchereria bancrofti microfilaremia, antigenemia, and clinical manifestations.[47, 61, 62, 63, 64]

M perstans infection

Because M perstans is resistant to standard antiparasitic treatment, doxycycline is sometimes used to eradicate Wolbachia, an endosymbiont found in most filarial species.[18, 65]

Doxycycline treatment typically kills or sterilizes the filarial nematode. In an open-label, randomized trial, Coulibaly et al recruited patients with M perstans infection from 4 African villages in Mali. Patients were randomly assigned to receive 200 mg of doxycycline orally every day for 6 weeks or no treatment.[66]

At 12 months, 97% of patients who received doxycycline had no detectable blood levels of M perstans, compared with 16% of patients in the group that did not receive treatment. At 36 months, M perstans remained suppressed in 75% of patients who had received doxycycline.[66]

Long-Term Monitoring

Patient monitoring includes posttreatment follow-up for 12 months, with examination of peripheral blood and skin snips for microfilariae.

Observe and monitor oral therapeutic plans with DEC because compliance with therapy is poor and usually incomplete.

Patients with filariasis are, by default, at risk for other parasitic infections because areas endemic for bancroftian filariasis are also endemic for other parasites. After treatment, patients should be monitored for symptoms that are characteristic of parasitic infections.

Medication Summary

Patients with asymptomatic microfilaremia in lymphatic filariasis can be treated on an outpatient basis. Supervision of oral DEC therapy and provocation with postadministration observation is recommended for patient compliance with therapy and for the management of febrile reactions in heavily infected patients. Inpatient care may initially be required for adenolymphangitis (ADL) and chronic filariasis.

Mass drug administration in filariasis reduces the transmission of filarial infection and disease morbidity by decreasing the burden of microfilaremia, resulting in suboptimal levels for transmission by disease vectors.[41]

Ivermectin (Mectizan)

Clinical Context:  Ivermectin is a potent microfilaricide and macrofilaricide for W bancrofti in multiple doses. It is used alone or in combination with DEC. It is the drug of choice for the treatment of bancroftian filariasis.

Ivermectin exerts its antiparasitic action by acting as a potent agonist at gamma-aminobutyric acid (GABA) receptors and potentiating the inhibitory signals sent to motor neurons, thus paralyzing the parasite. Because GABA is confined to the CNS in humans and ivermectin does not cross the blood-brain barrier, the drug has no paralytic action in humans.

Diethylcarbamazine (Hetrazan)

Clinical Context:  Diethylcarbamazine (DEC) is a microfilaricide. Its precise mechanism of action is not understood, but it has been shown to induce immobilization of microfilariae by using hyperpolarization effects to decrease muscle activity. Alteration of the surface membrane also occurs, with enhanced destruction by the host's immune system. Evidence exists that DEC may enhance adhesion of granulocytes via antibody-dependent and -independent mechanisms. Hypotheses also include interference by microfilarial intracellular processing and transport of specific macromolecules by DEC.

Concurrent administration of corticosteroids should be considered with DEC treatment to minimize the allergic manifestations secondary to the disintegration of microfilariae, particularly in O volvulus and L loa infections.

Suramin

Clinical Context:  Suramin is an antitrypanosome and an anthelminthic. It is currently the only drug in clinical use for onchocerciasis that is effective against adult worms, but its use is restricted because of its intrinsic toxicity and the frequency with which associated complications occur. The WHO has advised that it only be considered for the curative treatment of individuals in areas without transmission of onchocerciasis, in individuals leaving an endemic area, and in individuals with severe hyperreactive onchodermatitis if their symptoms are not adequately controlled with ivermectin.

The WHO has also recommended that suramin not be used to treat onchocerciasis in individuals who are elderly or infirm, in patients with severe liver or renal disease, in children younger than 10 years, in totally blind persons (unless they require relief from intensely itchy lesions), in lightly to moderately infected people with no symptoms and whose eyes are not at risk, or in pregnant women (who should be treated after delivery).

Mebendazole

Clinical Context:  Mebendazole causes worm death by selectively and irreversibly blocking uptake of glucose and other nutrients in a susceptible adult intestine where helminths dwell.

Albendazole

Clinical Context:  Albendazole is a broad-spectrum anthelmintic. It decreases adenosine triphosphate (ATP) production in worms, causing energy depletion, immobilization, and, finally, death.

Class Summary

Anthelminthic agents include macrocyclic lactone derivatives of avermectin, piperazine derivatives, and benzimidazole derivatives.

The biochemical pathways of parasites differ from those of their human host. Thus, the toxicity of anthelminthic agents can be directed at the parasite or its egg or larvae. The antiparasitic actions of these drugs vary; they include the following:

Doxycycline (Doxy 100, Vibramycin, Doryx, Monodox, Alodox)

Clinical Context:  Doxycycline is a broad-spectrum, synthetically derived, bacteriostatic antibiotic in the tetracycline class. This agent is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.

Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl transfer RNA (t-RNA) from ribosomes, causing RNA-dependent protein synthesis to arrest.

Class Summary

These agents may provide an alternative to anthelminthics.

Author

Siddharth Wayangankar, MD, MPH, Resident Physician, Department of Internal Medicine, Oklahoma University Health Sciences Center

Disclosure: Nothing to disclose.

Coauthor(s)

Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Disclosure: Nothing to disclose.

Rhett L Jackson, MD, Associate Professor and Vice Chair for Education, Department of Medicine, Director, Internal Medicine Residency Program, University of Oklahoma College of Medicine; Assistant Chief, Medicine Service, Oklahoma City Veterans Affairs Hospital

Disclosure: Nothing to disclose.

Chief Editor

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

Disclosure: Nothing to disclose.

Additional Contributors

Rosemary Johann-Liang, MD Medical Officer, Infectious Diseases and Pediatrics, Division of Special Pathogens and Immunological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration

Rosemary Johann-Liang, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Thomas M Kerkering, MD Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Charles S Levy, MD Associate Professor, Department of Medicine, Section of Infectious Disease, George Washington University School of Medicine

Charles S Levy, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, and Medical Society of the District of Columbia

Disclosure: Nothing to disclose.

Michael D Nissen, MBBS, 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

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Robert W Tolan Jr, MD Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility

Disclosure: Novartis Honoraria Speaking and teaching

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

Disclosure: Nothing to disclose.

Martin Weisse, MD Program Director, Associate Professor, Department of Pediatrics, West Virginia University

Martin Weisse, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Filariasis. This figure displays the life cycle of Wuchereria bancrofti in humans and mosquito vectors (ie, Aedes, Anopheles, Culex, Mansonia species). Life cycles of other lymphatic nematodes (ie, Brugia malayi, Brugia timori) are identical, while the life cycles for other filariae differ in the body location of adult worms, the microfilariae present, and the arthropod intermediate hosts and vectors.

Filariasis. This figure displays the life cycle of Wuchereria bancrofti in humans and mosquito vectors (ie, Aedes, Anopheles, Culex, Mansonia species). Life cycles of other lymphatic nematodes (ie, Brugia malayi, Brugia timori) are identical, while the life cycles for other filariae differ in the body location of adult worms, the microfilariae present, and the arthropod intermediate hosts and vectors.

Filarial abscess scar on the left upper thigh in a young male who is positive for Wuchereria bancrofti microfilariae

Filariasis. Microfilariae of Loa loa detected in skin snips.

Lymphatic filariasis resulting from Wuchereria bancrofti infection, which is causing limb lymphoedema, inguinal lymphadenopathy, and hydrocele. Photograph taken by Professor Bruce McMillan and donated by John Walker, MD.

Filariasis. Unilateral left lower leg elephantiasis secondary to Wuchereria bancrofti infection in a boy.

Filariasis. This is a close-up view of the unilateral lower leg elephantiasis shown in Image 4. Note the lymphedema and typical skin appearance of depigmentation and verrucosities (warty changes).

Filariasis. Lateral view of the right outer aspect of a leg affected by gross elephantiasis secondary to Wuchereria bancrofti infection.

Filariasis. Inner aspect of the lower leg of the male patient in Image 6, showing gross elephantiasis secondary to Wuchereria bancrofti infection.

Filariasis. Unilateral left hydrocele and testicular enlargement secondary to Wuchereria bancrofti infection in a man who also was positive for microfilariae.

Filariasis. Bilateral hydrocele, testicular enlargement, and inguinal lymphadenopathy secondary to Wuchereria bancrofti infection in a man who also was microfilaremic.

Filariasis. Onchocercomas of the forearm skin (sowda) in a Sudanese man.

Filariasis. Microfilariae of Mansonella perstans in peripheral blood.

Filariasis. Appearance of microfilariae after concentration of venous blood with a Nuclepore filter.

Filariasis. Microfilaria of Wuchereria bancrofti in a peripheral blood smear.

Filariasis. Adult worms of Wuchereria bancrofti in cross section isolated from a testicular lump.

Filariasis. Adult Onchocerca volvulus contained within onchocercomas of the skin.

Filariasis. This figure displays the life cycle of Wuchereria bancrofti in humans and mosquito vectors (ie, Aedes, Anopheles, Culex, Mansonia species). Life cycles of other lymphatic nematodes (ie, Brugia malayi, Brugia timori) are identical, while the life cycles for other filariae differ in the body location of adult worms, the microfilariae present, and the arthropod intermediate hosts and vectors.

Filarial abscess scar on the left upper thigh in a young male who is positive for Wuchereria bancrofti microfilariae

Lymphatic filariasis resulting from Wuchereria bancrofti infection, which is causing limb lymphoedema, inguinal lymphadenopathy, and hydrocele. Photograph taken by Professor Bruce McMillan and donated by John Walker, MD.

Filariasis. Unilateral left lower leg elephantiasis secondary to Wuchereria bancrofti infection in a boy.

Filariasis. This is a close-up view of the unilateral lower leg elephantiasis shown in Image 4. Note the lymphedema and typical skin appearance of depigmentation and verrucosities (warty changes).

Filariasis. Lateral view of the right outer aspect of a leg affected by gross elephantiasis secondary to Wuchereria bancrofti infection.

Filariasis. Inner aspect of the lower leg of the male patient in Image 6, showing gross elephantiasis secondary to Wuchereria bancrofti infection.

Filariasis. Unilateral left hydrocele and testicular enlargement secondary to Wuchereria bancrofti infection in a man who also was positive for microfilariae.

Filariasis. Bilateral hydrocele, testicular enlargement, and inguinal lymphadenopathy secondary to Wuchereria bancrofti infection in a man who also was microfilaremic.

Filariasis. Adult worms of Wuchereria bancrofti in cross section isolated from a testicular lump.

Filariasis. Microfilaria of Wuchereria bancrofti in a peripheral blood smear.

Filariasis. Appearance of microfilariae after concentration of venous blood with a Nuclepore filter.

Filariasis. Onchocercomas of the forearm skin (sowda) in a Sudanese man.

Filariasis. Adult Onchocerca volvulus contained within onchocercomas of the skin.

Filariasis. Microfilariae of Loa loa detected in skin snips.

Filariasis. Microfilariae of Mansonella perstans in peripheral blood.