AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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

INTRODUCTION

Section 2 of 11  

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

Background

Filariasis is a disease that affects humans and animals and is caused by nematode parasites of the order Filariidae, commonly called filariae. Only 8 species of the hundreds of described filarial parasites cause natural infections in humans. These 8 filarial parasites may be classified according to the habitat of the adult worms in the vertebral host, as follows:

• Cutaneous group
• • Loa loa
  • Onchocerca volvulus
  • Mansonella streptocerca
• Lymphatic group
• • Wuchereria bancrofti
  • Brugia malayi
  • Brugia timori
• Body cavity group
• • Mansonella perstans
  • Mansonella ozzardi

Parasites of the cutaneous and lymphatic groups are of the most significant clinical interest. Other species of filariae, such as Dirofilaria immitis (dog heartworm), Dirofilaria (Nochtiella) repens, and Dirofilaria tenuis (raccoon heartworm), may cause incomplete infections because they are unable to reach adult maturity in human hosts and, therefore, do not produce microfilaria (see Bancroftian Filariasis and Dirofilariasis).

Pathophysiology

As with all nematodes, the filarial life cycle consists of 5 developmental or larval stages in a vertebral host and an arthropod 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 in which they obtain blood meals. The highest concentration of microfilariae is usually seen when the local vector is most actively feeding. Microfilariae then undergo 2 developmental changes within the insect. While in the act of feeding, third-stage larvae are then inoculated back into the vertebral host for the final 2 stages of development.

Frequency

United States

No form of human filariasis is currently endemic. W bancrofti was once prevalent in Charleston, SC because of the presence of suitable mosquito vectors. Immigrant populations and long-term travelers to the tropics are more likely to be affected and are potential reservoirs of infection. Returning missionaries and Peace Corps volunteers are particularly at risk for lymphatic filariasis and onchocerciasis because of the relatively high intensity of exposure required and the long prepatent period between exposure to infective insect bites and the development of sexually mature adult worms.

International

Worldwide, prevalence of lymphatic filariasis is more than 90 million; throughout the tropics and subtropics, prevalence is even higher. In 1997, the World Health Organization (WHO) initiated a program to globally eliminate lymphatic filariasis as a public health problem. At least 21 million people are infected with O volvulus in equatorial Africa and in foci in Central and South America. Approximately 3 million people are infected with L loa in Central Africa.

Mortality/Morbidity

Filarial diseases are rarely fatal, but the consequences of infection can cause significant personal and socioeconomic hardship for those who are infected. WHO has identified lymphatic filariasis as the second leading cause of permanent and long-term disability in the world, after leprosy. Morbidity of human filariasis is mainly due to the host reaction to microfilariae or to developing adult worms in different areas of the body.

Race

No racial predilection is known.

Sex

Both sexes are equally susceptible to infection. Because of different local, cultural, social, and work practices, as well as exposure to insect vectors, either sex may be more exposed to infection.

Age

All ages are susceptible and potentially microfilaremic. Rates of microfilaremia increase with age through childhood and early adulthood, though clinical infection may be inapparent. Manifestations of acute and chronic filariasis usually occur only after years of repeated and intense exposure to infected vectors in endemic areas.

CLINICAL

Section 3 of 11  

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

History

Symptoms of filariasis are dependent on species and body site and can be acute or chronic in nature.

• Lymphatic filariasis: Lymphatic filariasis symptoms predominantly result from the presence of adult worms residing in the lymphatics and include (1) fever, (2) inguinal or axillary lymphadenopathy, (3) testicular and/or inguinal pain, (4) skin exfoliation, and (5) limb or genital swelling. Microfilaremia is generally considered to be asymptomatic, although subjects with heavy microfilarial loads may develop acute and chronic inflammatory granulomas secondary to splenic destruction. Passage of cloudy milklike urine may denote chyluria.
• Tropical pulmonary eosinophilia (TPE): TPE is a form of occult bancroftian filariasis. Presenting symptoms include a paroxysmal dry cough, wheezing, dyspnea, anorexia, malaise, and weight loss.
• D immitis infection: Symptoms involve the respiratory system and include chest discomfort, cough, fever, and hemoptysis.
• D repens infection: Symptoms usually include a lump in the subcutaneous tissue, submucosa, or eyelid
• Onchocerciasis (ie, hanging groins, leopard skin, river blindness, sowda): The symptoms of onchocerciasis are due to the presence of microfilariae in the skin and include pruritus, subcutaneous lumps, lymphadenitis, and blindness.
• Loaiasis
• • Symptoms of L loa infection are usually confined to subcutaneous swellings on the extremities, together with localized pain, pruritus, and urticaria.
  • Microfilaremia tends to be asymptomatic.
• M ozzardi, M perstans, and M streptocerca
• • Infections due to Mansonella species are usually asymptomatic.
  • If present, symptoms may include fever, pruritus, skin lumps, lymphadenitis, and abdominal pain.

Physical

Signs of filariasis present upon examination are species dependent and may be acute or chronic.

• Lymphatic filariasis
• • Acute manifestations of lymphatic filariasis are usually referred to as adenolymphangitis (ADL). ADL is characterized by episodic attacks of fever associated with inflammation of the inguinal lymph nodes, testis, spermatic cord, and/or lymphedema. Skin exfoliation of the affected body part usually occurs with resolution of an episode.
  • Repeated episodes of inflammation and lymphedema lead to lymphatic damage, chronic swelling, and elephantiasis of the legs, arms, scrotum, vulva, and breasts.
  • Hydrocele is the most common manifestation of chronic W bancrofti infection in males in endemic areas. Chyluria may also be present in individuals who are chronically infected.
• TPE: Scattered wheezes and crackles are heard in both lung fields. Lymphadenopathy and hepatomegaly may be present.
• D immitis infection: Reduced localized air entry on chest auscultation may be detected.
• D repens infection: Signs usually include a painless lump in the subcutaneous tissue, submucosa, or eyelid.
• Onchocerciasis
• • The clinical triad of infection is dermatitis, skin nodules (onchocercomas), and ocular lesions.
  • Skin lesions include edema, pruritus, erythema, papules, scablike eruptions, altered pigmentation, and lichenification.
  • Skin nodules tend to be common over bony prominences.
  • Eye lesions are usually related to the duration and severity of infection and are due to an abnormal host immune response to microfilariae. Common eye findings include punctate keratitis, pannus formation, corneal fibrosis, iridocyclitis, glaucoma, choroiditis, and optic atrophy.
• Loaiasis
• • A Calabar swelling is the diagnostic feature of disease. A Calabar swelling is a transient large area of localized nonerythematous subcutaneous edema that is most common around the joints. 
  • Other rare manifestations of infection include arthritis, breast calcification, meningoencephalopathy, endomyocardial fibrosis, peripheral neuropathy, pleural effusions, and retinopathy.
• M ozzardi, M perstans, and M streptocerca: Subcutaneous and/or conjunctival nodules and lymphadenopathy may be detected in symptomatic patients.

Causes

• Lymphatic filariasis
• • Mosquitoes of the genera Aedes, Anopheles, Culex, and Mansonia are the intermediate hosts and vectors of all lymphatic filariasis species.
• • 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; males measure 40 mm.
  • Nodes in the femoral and epitrochlear regions are the most commonly affected. Abscess formation may occur at the nodes or anywhere along the distal vessel. B timori appear to form more abscesses than B malayi or W bancrofti. Cellular invasion with plasma cells, eosinophils, and macrophages, together with hyperplasia of the lymphatic endothelium, occurs with repeated inflammatory episodes. What results 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. B malayi elephantiasis is more likely to affect the upper and lower limbs; genital pathology and chyluria are rare.
• Occult filariasis
• • Occult bancroftian filariasis denotes infection in which microfilariae are not seen in the blood, although they may be found in other body fluids and/or tissues.
  • The occult syndromes include TPE, D immitis or D repens infection, filarial arthritis, filarial breast abscess, and filarial-associated immune complex glomerulonephritis. TPE is most likely due to a hyperresponsiveness to W bancrofti or B malayi antigen.
  • 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
• • Microfilariae from the skin are ingested by Simulium species of blackflies.
  • Patients with chronic onchocerciasis are hyporesponsive to parasite antigen. They have increased eosinophilia and high levels of serum immunoglobulin E (IgE). Patterns of onchocercal eye disease are also associated with parasite strain differences at the DNA level.
• Loaiasis
• • Mango flies or deerflies of the Chrysops species transmit loaiasis.
  • Response to L loa infection appears to differ between residents and nonresidents in endemic areas. Nonresidents with infection seem 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.
  • 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.¹
    • 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.

DIFFERENTIALS

Section 4 of 11  

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

Other Problems to be Considered

Lymphatic filariasis

Bacterial or fungal lymphadenitis (eg, sporotrichosis due to Sporothrix schenckii)
Recurrent streptococcal lymphadenitis (relapsing erysipelas)
Congenital or hereditary lymphedema (Milroy syndrome)
Nonfilarial elephantiasis (Highlands of East Africa)
Congenital hydrocele
Epididymal cyst
Carcinoma of testis and/or scrotum
Lymphosarcoma

Occult filariasis

Bacterial monoarthritis
Bacterial breast abscess
Idiopathic glomerulonephritis

Onchocerciasis

Vitiligo
Trachoma
Lepromatous leprosy

Loaiasis

Hereditary and/or localized idiopathic angioedema

WORKUP

Section 5 of 11  

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

Lab Studies

• Detection of microfilariae: The traditional diagnostic method is to demonstrate microfilariae in the peripheral blood or skin.
• • Detection of microfilariae in blood
  • • The microfilariae of all species of lymphatic filariasis, L loa, M ozzardi, and M perstans, are detected in blood. Capillary finger-prick or venous blood is used for thick blood films. Venous blood can also be concentrated or passed through a Nuclepore filter before undergoing microscopic examination. The species of infection can then be determined by the microscopic appearance.
    • Microfilaria may be periodic in appearance in the peripheral circulation; thus, blood should be examined at different intervals of a 24-hour period to maximize the chance of detection.
    • Provocation of nocturnally periodic W bancrofti microfilariae may be achieved using a daytime dose of DEC at 1-2 mg/kg of body weight. Microfilariae may also be observed in chylous urine and hydrocele fluid.
    • Microfilariae may be absent in ADL or late chronic lymphatic disease and are typically absent in loaiasis unless the infection has been present for many years.
  • Detection of microfilariae in skin
  • • O volvulus and M streptocerca infections are diagnosed when microfilariae are detected in multiple skin snip specimens from different body sites of both sides of the body.
    • In cases of suspected onchocerciasis in Africa, the recommended sites are the gluteal and calf skin. For onchocerciasis in America, the scapula and deltoid skin are preferred.
  • Detection of microfilariae in the eye: Microfilariae of O volvulus may also be detected in the cornea or anterior chamber of the eye upon slit-lamp examination.
• Detection of filarial antigen: The presence of circulating filarial antigen in the peripheral blood, with or without microfilariae, is also considered diagnostic of patent filarial infection and is used to monitor the effectiveness of therapy. Commercial kits are available to test venous blood.
• Detection of filarial antibodies: The use of recombinant antigens for detecting onchocerciasis immunoglobulin G4 (IgG4) antibodies has improved the sensitivity and specificity of serologic assays.
• Urine examination and microscopy: If lymphatic filariasis is suspected, examine the urine macroscopically for chyluria and then concentrated for microfilariae.
• CBC count: Eosinophilia is marked in all forms of patent filarial infection.
• Serum immunoglobulin assessment: Elevated serum IgE and IgG4 may be seen in active filarial disease.

Imaging Studies

• Chest radiography: The chest radiograph in patients with TPE depicts diffuse pulmonary infiltrates.
• Ultrasonography
• • Lymphatic obstruction of the inguinal and scrotal lymphatics can be demonstrated and monitored using ultrasonography.
  • Deep onchocercomas and vitreous changes in the eye can sometimes be detected using ultrasonography.

Other Tests

• Mazzotti test: The test establishes a presumptive diagnosis of cutaneous filariasis when skin snips are negative for microfilariae. An intense pruritus is elicited by a single small dose of DEC (50-100 mg) within hours. 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.

Procedures

• Lymph node or skin nodule biopsy: Biopsy is only recommended in cutaneous filariasis because excision of nodes may further impede lymphatic drainage in lymphatic filariasis. Adult worms of O volvulus and L loa are found in the nodules and fibrotic tissue of the skin. L loa worms can occasionally be dissected from the conjunctiva of the eye or bridge of the nose as they migrate through the

Histologic Findings

• Lymphatic filariasis: Affected lymph nodes fibrose. With the creation of collateral channels, lymphatics stenose and obstruct. The skin of patients with elephantiasis reveals hyperkeratosis, acanthosis, lymph and fatty tissue, loss of elastin fibers, and fibrosis.
• Onchocerciasis: Two areas are evident in onchocercomas: a peripheral fibrous section and a central stromal and granulomatous inflammatory region where the adult worms are found. Microfilariae in the skin incite a low-grade inflammatory reaction with loss of elasticity and fibrotic scarring.

TREATMENT

Section 6 of 11  

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

Medical Care

The medical treatment for filarial infection should be specific and based on the microfilariae isolated or antigenemia detected.

• Lymphatic filariasis
• • Asymptomatic microfilaremia can be treated on an outpatient basis. Supervision of oral DEC therapy and provocation with postadministration observation is recommended to ensure compliance and to manage febrile reactions in patients with heavy infection.
  • Patients with ADL or chronic filariasis may initially require inpatient care for administration of antihistamines, corticosteroids, pain relief, and intravenous antibiotics for secondary infections.
  • Bed rest, limb elevation, and compression bandages have traditionally been used to treat chronic lymphedema. Corticosteroids can be used to soften and reduce the swelling of lymphedematous tissues.
• Onchocerciasis: If DEC and suramin are used, inpatient care is recommended to monitor for reactions and complications of therapy.

Surgical Care

• Lymphatic filariasis: Large hydroceles and scrotal elephantiasis can be managed with surgical excision. Correction of gross limb elephantiasis with surgery is less successful and may require multiple procedures and skin grafting.
• Onchocerciasis: Nodulectomy with a local anesthetic is a common treatment to reduce skin and eye complications.

Consultations

• Infectious diseases specialist
• Urologist
• Ophthalmologist
• General surgeon
• Plastic surgeon

Diet

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

Activity

Mobilization of the affected limb in chronic lymphatic filariasis is encouraged with compression bandage support.

MEDICATION

Section 7 of 11  

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

Ivermectin is now considered the drug of choice for the treatment of all forms of filariasis, except Mansonella, in which its effects are unproven. In the United States, ivermectin 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. More recently, 6- and 8-week courses of doxycycline have compared favorably to ivermectin plus albendazole (a 3-week course induced amicrofilaremia but was not curative). Doxycycline therapy may be more readily available and better tolerated for some patients.

Recent studies have validated the use of single-dose regimens of ivermectin and DEC or albendazole to reduce W bancrofti microfilaremia, antigenemia, and clinical manifestations for large-scale control and eradication programs.

Drug Category: Antihelmintic agents

Parasite biochemical pathways are different from the human host, thus toxicity is directed to the parasite, egg, or larvae. The 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 alteration of chloride channels

Drug Category: Antibiotics

These agents may provide an alternative to anthelminthics.

FOLLOW-UP

Section 8 of 11  

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

Further Inpatient Care

• Observe for complications of therapy, especially if DEC is used.

Further Outpatient Care

• Schedule a follow-up visit for 12 months after treatment; during this appointment, peripheral blood is examined for microfilariae.

In/Out Patient Meds

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

Deterrence/Prevention

• Advise patients to avoid insect vector bites.

Complications

• Secondary bacterial infection of elephantiasis may occur.

Prognosis

• Prognosis is good if filariasis is recognized and treated early.

Patient Education

• Educate patients about protection against insect vectors and how to refrain from using self-treatment regimens, especially with DEC.

MISCELLANEOUS

Section 9 of 11  

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

Medical/Legal Pitfalls

• Incorrect diagnosis: Initially missing the diagnosis of filariasis is certainly possible because of the infrequency of cases in the developed world and Western Hemisphere. Major consequences in this scenario may be a late diagnosis, resulting in a greater degree of patient morbidity and failure to issue timely epidemiologic notification of a case. In suspicious lesions, obtain a travel history.
• Inappropriate treatment: Although this scenario is much less likely, inappropriate treatment of filariasis is a potential issue, even if the diagnosis is correctly made. Consult an infectious diseases specialist in cases of suspected filariasis outside of endemic nations.
• Reaction to treatment: Take care to ascertain whether the patient with filariasis has ever taken any antiparasitic drugs and whether any adverse reaction was observed. Failure to do so, with a resultant adverse reaction to 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 filariasis are at risk for other parasitic infections because areas endemic for filariasis are also endemic for other parasites. After treatment, monitor patients for other symptomatology characteristic of parasitic infections.

MULTIMEDIA

Section 10 of 11  

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

Media file 1:  The life cycle of lymphatic filarioids in humans (Wuchereria bancrofti, Brugia malayi, Brugia timori) and the mosquito vectors (Aedes, Anopheles, Culex, and Mansonia genera) is shown. Life cycles for other filarioid nematodes (Onchocerca volvulus, Loa loa, Mansonella perstans) are identical. The body location of adult worms and the microfilariae differ, as do the arthropod intermediate hosts and vectors.
	View Full Size Image
Media type:  Image

Media file 2:  Lymphatic filariasis due to Wuchereria bancrofti causing limb lymphedema, inguinal lymphadenopathy, and hydrocele. Photograph taken by Professor Bruce McMillan and donated by Dr John Walker.
	View Full Size Image
Media type:  Photo

Media file 3:  Adult worms of Wuchereria bancrofti in a cross section isolated from a testicular lump.
	View Full Size Image
Media type:  Photo

Media file 4:  Microfilaria of Wuchereria bancrofti in a peripheral blood smear.
	View Full Size Image
Media type:  Photo

Media file 5:  Shown here are onchocercomas of the forearm skin, also called sowda, in a Sudanese man.
	View Full Size Image
Media type:  Photo

Media file 6:  Adult Onchocerca volvulus contained within onchocercomas of the skin.
	View Full Size Image
Media type:  Photo

Media file 7:  Microfilariae of Loa loa detected in skin snips.
	View Full Size Image
Media type:  Photo

Media file 8:  Microfilariae of Mansonella perstans in peripheral blood.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

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

1. Carme B, Boulesteix J, Boutes H, Puruehnce MF. Five cases of encephalitis during treatment of loiasis with diethylcarbamazine. Am J Trop Med Hyg. Jun 1991;44(6):684-90. [Medline].
2. Baird JK, Neafie RC, Lanoie L, Connor DH. Adult Mansonella perstans in the abdominal cavity in nine Africans. Am J Trop Med Hyg. Nov 1987;37(3):578-84. [Medline].
3. Beyrer C, Villar JC, Suwanvanichkij V, Singh S, Baral SD, Mills EJ. Neglected diseases, civil conflicts, and the right to health. Lancet. Aug 18 2007;370(9587):619-27. [Medline].
4. Connor DH, George GH, Gibson DW. Pathologic changes of human onchocerciasis: implications for future research. Rev Infect Dis. Nov-Dec 1985;7(6):809-19. [Medline].
5. Connor DH, Gibson DW, Neafie RC, et al. Sowda--onchocerciasis in north Yemen: a clinicopathologic study of 18 patients. Am J Trop Med Hyg. Jan 1983;32(1):123-37. [Medline].
6. Davidson RN, Godfrey-Faussett P, Bryceson AD. Adverse reactions in expatriates treated with ivermectin [letter]. Lancet. Oct 20 1990;336(8721):1005. [Medline].
7. De Sole G, Remme J, Awadzi K, et al. Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials. Bull World Health Organ. 1989;67(6):707-19. [Medline].
8. Dondero TJ Jr, Ramachandran CP, Bin Yusoff O. Filariasis due to Brugia malayi in west Malayasia. I. Clinical, laboratory, and parasitological aspects. Southeast Asian J Trop Med Public Health. Dec 1971;2(4):503-15. [Medline].
9. Dreyer G, Figueredo-Silva J, Neafie RC, Addiss DG. Lymphatic filariasis. In: Nelson AM, Horsburgh CR eds. Pathology of Emerging Infections. Vol 2. Washington, DC: American Society for Microbiology; 1998:317-42.
10. Dreyer G, Noroes J, Figueredo-Silva J, Piessens WF. Pathogenesis of lymphatic disease in bancroftian filariasis: A clinical perspective [In Process Citation]. Parasitol Today. Dec 2000;16(12):544-8. [Medline].
11. Duke BO, Zea-Flores G, Castro J, et al. Effects of three-month doses of ivermectin on adult Onchocerca volvulus. Am J Trop Med Hyg. Feb 1992;46(2):189-94. [Medline].
12. Dunyo SK, Appawu M, Nkrumah FK, et al. Lymphatic filariasis on the coast of Ghana. Trans R Soc Trop Med Hyg. Nov-Dec 1996;90(6):634-8. [Medline].
13. Dunyo SK, Nkrumah FK, Simonsen PE. Single-dose treatment of Wuchereria bancrofti infections with ivermectin and albendazole alone or in combination: evaluation of the potential for control at 12 months after treatment.[In Process Citation]. Trans R Soc Trop Med Hyg. Jul-Aug 2000;94(4):437-43. [Medline].
14. Eberhard ML, Lammie PJ. Laboratory diagnosis of filariasis. Clin Lab Med. Dec 1991;11(4):977-1010. [Medline].
15. Farid HA, Morsy ZS, Helmy H, Ramzy RM, El Setouhy M, Weil GJ. A critical appraisal of molecular xenomonitoring as a tool for assessing progress toward elimination of Lymphatic Filariasis. Am J Trop Med Hyg. Oct 2007;77(4):593-600. [Medline].
16. Garcia LS, Bruckner DA. Filarial nematodes. In: Diagnostic Medical Parasitology. 3^rd ed. Washington, DC: American Society for Microbiology; 1997:275-307.
17. Ghedin E, Wang S, Spiro D, et al. Draft genome of the filarial nematode parasite Brugia malayi. Science. Sep 21 2007;317(5845):1756-60. [Medline].
18. Global programme to eliminate lymphatic filariasis. Wkly Epidemiol Rec. Oct 19 2007;82(42):361-80. [Medline].
19. Grady CA, de Rochars MB, Direny AN, et al. Endpoints for lymphatic filariasis programs. Emerg Infect Dis. Apr 2007;13(4):608-10. [Medline].
20. Grove DI. Tissue nematodes including trichinosis, dracunculiasis, and the filariases. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6^th ed. New York, NY: Churchill Livingston; 2004:3267-76.
21. Hoerauf A. New strategies to combat filariasis. Expert Rev Anti Infect Ther. Apr 2006;4(2):211-22. [Medline].
22. Klion AD, Massougbodji A, Sadeler BC, et al. Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. J Infect Dis. Jun 1991;163(6):1318-25. [Medline].
23. Lammie P, Milner T, Houston R. Unfulfilled potential: using diethylcarbamazine-fortified salt to eliminate lymphatic filariasis. Bull World Health Organ. Jul 2007;85(7):545-9. [Medline].
24. Lammie PJ. The promise of wolbachia-targeted chemotherapy as a public health intervention for lymphatic filariasis and onchocerciasis. Clin Infect Dis. Apr 15 2006;42(8):1090-2. [Medline].
25. Limaye AP, Abrams JS, Silver JE, et al. Interleukin-5 and the posttreatment eosinophilia in patients with onchocerciasis. J Clin Invest. Oct 1991;88(4):1418-21. [Medline].
26. Mand S, Supali T, Djuardi J. Detection of adult Brugia malayi filariae by ultrasonography in humans in India and Indonesia. Trop Med Int Health. Sep 2006;11(9):1375-81. [Medline].
27. McMahon JE, Simonsen PE. Filariases. In: Cook GC, ed. Manson's Tropical Diseases. 20^th ed. London: WB Saunders; 1996:1321-1368.
28. Molyneux DH. Elimination of transmission of lymphatic filariasis in Egypt. Lancet. Mar 25 2006;367(9515):966-8. [Medline].
29. Nanduri J, Kazura JW. Clinical and laboratory aspects of filariasis. Clin Microbiol Rev. Jan 1989;2(1):39-50. [Medline].
30. Newland HS, White AT, Greene BM, et al. Ocular manifestations of onchocerciasis in a rain forest area of west Africa. Br J Ophthalmol. Mar 1991;75(3):163-9. [Medline].
31. Noireau F, Apembet JD, Nzoulani A, Carme B. Clinical manifestations of loiasis in an endemic area in the Congo. Trop Med Parasitol. Mar 1990;41(1):37-9. [Medline].
32. Noireau F, Pichon G. Population dynamics of Loa loa and Mansonella perstans infections in individuals living in an endemic area of the Congo. Am J Trop Med Hyg. Jun 1992;46(6):672-6. [Medline].
33. Nuchprayoon S, Junpee A, Poovorawan Y, Scott AL. Detection and differentiation of filarial parasites by universal primers and polymerase chain reaction-restriction fragment length polymorphism analysis. Am J Trop Med Hyg. Nov 2005;73(5):895-900. [Medline].
34. Nutman TB, Nash TE, Ottesen EA. Ivermectin in the successful treatment of a patient with Mansonella ozzardi infection. J Infect Dis. Oct 1987;156(4):662-5. [Medline].
35. Ottesen EA. Lymphatic filariasis: treatment, control and elimination. Adv Parasitol. 2006;61:395-441. [Medline].
36. Ottesen EA, Duke BO, Karam M, Behbehani K. Strategies and tools for the control/elimination of lymphatic filariasis. Bull World Health Organ. 1997;75(6):491-503. [Medline].
37. Ottesen EA, Ismail MM, Horton J. The role of albendazole in programmes to eliminate lymphatic filariasis. Parasitol Today. Sep 1999;15(9):382-6. [Medline].
38. Pani SP, Das LK, Vanamail P. Tolerability and efficacy of a three-age class dosage schedule of Diethylcarbamazine citrate (DEC) in the treatment of microfilaria carriers of Wuchereria bancrofti and its implications in mass drug administration (MDA) strategy for elimination of lympha. J Commun Dis. Mar 2005;37(1):12-7. [Medline].
39. Partono F, Cross JH, Borahina, et al. Observations on the diurnal diagnosis of filariasis after a single dose of hetrazan. Southeast Asian J Trop Med Public Health. Sep 1972;3(3):366-70. [Medline].
40. Partono F, Pribadi PW, Soewarta A. Epidemiological and clinical features of Brugia timori in a newly established village. Karakuak, West Flores, Indonesia. Am J Trop Med Hyg. Sep 1978;27(5):910-5. [Medline].
41. Poltera AA, Reyna O, Zea-Flores G, et al. Use of an ophthalmologic ultrasoundscanner in human onchocercal skin nodules for non-invasive sequential assessment during a macrofilaricidal trial with amocarzine in Guatemala. The first experiences. Trop Med Parasitol. Sep 1991;42(3):303-7. [Medline].
42. Ramaiah KD, Das PK, Vanamail P, Pani SP. Impact of 10 years of diethylcarbamazine and ivermectin mass administration on infection and transmission of lymphatic filariasis. Trans R Soc Trop Med Hyg. Jun 2007;101(6):555-63. [Medline].
43. Ramzy RM, El Setouhy M, Helmy H, et al. Effect of yearly mass drug administration with diethylcarbamazine and albendazole on bancroftian filariasis in Egypt: a comprehensive assessment. Lancet. Mar 25 2006;367(9515):992-9. [Medline].
44. Reddy M, Gill SS, Kalkar SR, Wu W, Anderson PJ, Rochon PA. Oral drug therapy for multiple neglected tropical diseases: a systematic review. JAMA. Oct 24 2007;298(16):1911-24. [Medline].
45. Regu K, Showkath Ali MK, Rajendran R, Koya SM, Ganesh B, Dhariwal AC. Mass drug administration against lymphatic filariasis: experiences from Kozhikode district of Kerala State. J Commun Dis. Dec 2006;38(4):333-8. [Medline].
46. Rizzo JA, Belo C, Lins R, Dreyer G. Children and adolescents infected with Wuchereria bancrofti in Greater Recife, Brazil: a randomized, year-long clinical trial of single treatments with diethylcarbamazine or diethylcarbamazine-albendazole. Ann Trop Med Parasitol. Jul 2007;101(5):423-33. [Medline].
47. Scheiber P, Braun-Munzinger RA, Southgate BA. A new technique for the determination of microfilarial densities in onchocerciasis. Bull World Health Organ. 1976;53(1):130-3. [Medline].
48. Seybolt LM, Christiansen D, Barnett ED. Diagnostic evaluation of newly arrived asymptomatic refugees with eosinophilia. Clin Infect Dis. Feb 1 2006;42(3):363-7. [Medline].
49. Stingl P, Ross M, Gibson DW, et al. A diagnostic "patch test" for onchocerciasis using topical diethylcarbamazine. Trans R Soc Trop Med Hyg. 1984;78(2):254-8. [Medline].
50. Sunish IP, Rajendran R, Mani TR, et al. Evidence for the use of albendazole for the elimination of lymphatic filariasis. Lancet Infect Dis. Mar 2006;6(3):125-6. [Medline].
51. Turner JD, Mand S, Debrah AY, Muehlfeld J, Pfarr K, McGarry HF. A randomized, double-blind clinical trial of a 3-week course of doxycycline plus albendazole and ivermectin for the treatment of Wuchereria bancrofti infection. Clin Infect Dis. Apr 15 2006;42(8):1081-9. [Medline].
52. Vieira JC, Cooper PJ, Lovato R, et al. Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection. BMC Med. 2007;5:9. [Medline].
53. Weil GJ, Lammie PJ, Weiss N. The ICT Filariasis Test: A rapid-format antigen test for diagnosis of bancroftian filariasis. Parasitol Today. Oct 1997;13(10):401-4. [Medline].
54. Weil GJ, Steel C, Liftis F, et al. A rapid-format antibody card test for diagnosis of onchocerciasis [In Process Citation]. J Infect Dis. Dec 2000;182(6):1796-9. [Medline].
55. Weitzel T, Jelinek T. Images in clinical medicine. Loiasis. N Engl J Med. Aug 17 2006;355(7):e6. [Medline].
56. WHO-based tropical disease research programme to focus on emerging diseases. Wkly Epidemiol Rec. Jun 29 2007;82(26-27):243-4. [Medline].
57. World Health Organization. The World Health Report 1995: Bridging the gaps. World Health Organization, Geneva. 1995.
58. Wynd S, Melrose WD, Durrheim DN, Carron J, Gyapong M. Understanding the community impact of lymphatic filariasis: a review of the sociocultural literature. Bull World Health Organ. Jun 2007;85(6):493-8. [Medline].

Article Last Updated: Feb 6, 2008