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Pediatrics: General Medicine > Parasitology
Bancroftian Filariasis
Article Last Updated: Feb 7, 2008
AUTHOR AND EDITOR INFORMATION
Section 1 of 12  
Author: Robert W Tolan Jr, MD, Chief 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, 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
Coauthor(s):
Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA, Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital;
John Charles Walker, MSc, PhD, Head, Department of Parasitology, Center for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, Australia; Senior Lecturer, Department of Medicine, University of Sydney, Australia
Editors: 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; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Martin Weisse, MD, Program Director, Associate Professor, Department of Pediatrics, West Virginia University; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; Russell W Steele, MD, Professor and Vice Chairman, Department of Pediatrics, Head, Division of Infectious Diseases, Louisiana State University Health Sciences Center
Author and Editor Disclosure
Synonyms and related keywords:
adenolymphangitis, ADL, Aedes, Anopheles, bancroftian filariasis, Culex, elephantiasis, filarial arthritis, filarial-associated immune complex glomerulonephritis, filarial breast abscess, filarial disease, filarial infection, filariasis, human filariasis, lymphatic filariasis, Mansonia, microfilaremia, occult bancroftian filariasis, tropical pulmonary eosinophilia, TPE, Wuchereria bancrofti, W bancrofti, chyluria, elephantiasis, hepatomegaly, hydrocele
Background
Bancroftian filariasis specifically refers to filarial infection with the nematode parasite Wuchereria bancrofti. Adult worms usually reside in the large lymphatics of the human host. For a description of other helminths that cause lymphatic filariasis (ie, Brugia malayi, Brugia timori), see Filariasis.
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 a feeding insect vector ingests. 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 observed when the local vector is feeding most actively. Microfilariae then undergo 2 developmental changes within the insect. Third-stage larvae are inoculated back into the vertebral host when the insect feeds, beginning the final 2 stages of development.
Frequency
United States
No form of bancroftian filariasis is currently endemic. W bancrofti was once prevalent in Charleston, SC because of the presence of suitable mosquito vectors.1 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 because of the long prepatent period between exposure to infective insect bites and the development of sexually mature adult worms and the relatively high intensity of exposure required.
International
Lymphatic filariasis is found throughout the tropics and subtropics. Worldwide prevalence is more than 90 million. The World Health Organization (WHO) initiated a program in 1997 to eliminate lymphatic filariasis globally as a public health priority.
Mortality/Morbidity
Filarial diseases are rarely fatal, but the consequences of infection can cause significant personal and socioeconomic hardship for those who are infected. The WHO has identified lymphatic filariasis as the second leading cause (after leprosy) of permanent and long-term disability in the world. Morbidity of human filariasis is due mainly to the host reaction to microfilariae or to developing adult worms in different areas of the body.
Race
No racial predilection for bancroftian filariasis 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
People of all ages are susceptible and potentially microfilaremic. Microfilaremia rates increase with age through childhood and early adulthood, although clinical infection may be inapparent. Typically, acute and chronic filariasis manifests only after years of repeated and intense exposure to infected vectors in endemic areas.
History
Symptoms of bancroftian filariasis may be acute or chronic in nature.
- Lymphatic filariasis: Lymphatic filariasis symptoms predominantly result from the presence of adult worms residing in the lymphatics. Symptoms include fever; inguinal or axillary lymphadenopathy; testicular pain, inguinal pain, or both; skin exfoliation; and limb or genital swelling. People with microfilaremia are generally considered to be asymptomatic, although those 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.
Physical
Signs of filariasis present on examination may be acute or chronic.
- Lymphatic filariasis
- Acute manifestations of lymphatic filariasis are usually referred to as adenolymphangitis (ADL). Episodic attacks of fever associated with inflammation of the inguinal lymph nodes, testis, spermatic cord, lymphedema, or a combination of these symptoms characterize ADL. 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.
- Lymphadenopathy and hepatomegaly may be present.
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, and males measure 40 mm.
- Nodes in the femoral and epitrochlear regions are the most commonly affected. Abscesses may form at the nodes or anywhere along the distal vessel. Cellular invasion with plasma cells, eosinophils, and macrophages, together with hyperplasia of the lymphatic endothelium, occurs with repeated inflammatory episodes. 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 result; all of these contribute to the appearance of elephantiasis.
- Occult bancroftian filariasis
- Occult bancroftian filariasis denotes infection in which microfilariae are not observed in the blood, although they may be found in other body fluids, tissues, or both.
- The occult syndromes include TPE, filarial arthritis, filarial breast abscess, and filarial-associated immune complex glomerulonephritis. TPE symptoms result from allergic and inflammatory reactions elicited by the microfilariae and parasite antigens that the lungs clear from the bloodstream.
Acute Poststreptococcal Glomerulonephritis
Asthma
Dirofilariasis
Filariasis
Sporotrichosis
Other Problems to be Considered
Lymphatic filariasis
Recurrent streptococcal lymphadenitis (relapsing erysipelas)
Congenital or hereditary lymphedema (Milroy syndrome)
Nonfilarial elephantiasis (highlands of East Africa)
Congenital hydrocele
Epididymal cysts
Carcinoma of testis, scrotum, or both
Lymphosarcoma
Occult filariasis
Bacterial monoarthritis
Bacterial breast abscess
Idiopathic glomerulonephritis
Allergic bronchopulmonary aspergillosis
Systemic vasculitides
Chronic eosinophilic pneumonia
Idiopathic hypereosinophilic syndrome
Lab Studies
- Detection of microfilariae: The traditional diagnostic method is to demonstrate microfilariae in the peripheral 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 being examined microscopically.
- Microfilariae may periodically appear in the peripheral circulation (timing of sample collection is critical; follow the periodicity of the microfilariae in the endemic region); thus, blood should be examined at different intervals during a 24-hour period to maximize chances of detection.
- Nocturnally periodic W bancrofti microfilariae may be provoked with a daytime dose of diethylcarbamazine (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 in late chronic lymphatic disease.
- 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.
- Urine examination and microscopy: If lymphatic filariasis is suspected, urine should be examined macroscopically for chyluria and then concentrated for microfilariae.
- CBC count: Eosinophilia is marked in all forms of patent filarial infection.
- Serum immunoglobulin concentrations: Elevated serum immunoglobulin E and immunoglobulin G4 may be observed with active filarial disease.
Imaging Studies
- Chest radiography: Patients with TPE show diffuse pulmonary infiltrates.
- Ultrasonography: Lymphatic obstruction of the inguinal and scrotal lymphatics can be demonstrated and monitored ultrasonographically.
Procedures
- Lymph node or skin nodule biopsy is recommended only in those with cutaneous filariasis because excision of nodes may further impede lymphatic drainage in patients with lymphatic filariasis.
Histologic Findings
In those with lymphatic filariasis, affected lymph nodes fibrose. Lymphatics stenose and obstruct, with the creation of collateral channels. The skin of patients with elephantiasis reveals hyperkeratosis, acanthosis, lymph and fatty tissue, loss of elastin fibers, and fibrosis.
Medical Care
The medical treatment for bancroftian filarial infection should be specific and based on whether microfilariae are isolated or antigenemia is detected.
- Lymphatic bancroftian filariasis
- Asymptomatic microfilaremia can be treated on an outpatient basis. Supervision of oral diethylcarbamazine (DEC) therapy and provocation with postadministration observation is recommended to ensure compliance and to manage febrile reactions in heavily infected patients.
- Inpatient care may be required initially for those with ADL and chronic filariasis. These patients may need 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.
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.
Consultations
- Infectious diseases specialist
- Urologist
- Ophthalmologist
- General surgeon
- Plastic surgeon
Diet
Fatty foods are restricted in those with proven chyluria associated with lymphatic filariasis.
Activity
In patients with chronic lymphatic filariasis, mobilization of the affected limb is encouraged with compression bandage support.
Ivermectin is now considered the drug of choice for the treatment of bancroftian filariasis, except in Mansonella infections, in which its effects are unproved. 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.2, 3, 4 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).5 Doxycycline therapy may be more readily available and may be better tolerated by some patients. Findings 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.6, 7
Drug Category: Anthelminthics
Anthelminthic agents include macrocyclic lactone derivatives of avermectin, piperazine derivatives, and benzimidazole derivatives.
| Drug Name | Ivermectin (Mectizan, Stromectol) |
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| Description | Exerts its antiparasitic action by acting as a potent agonist at gamma-butyric acid (GABA) receptors and potentiating the inhibitory signals sent to motor neurons that paralyze 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. Mechanism of action is thought to involve GABA pathways and chloride ion channel permeability. Potent microfilaricide and macrofilaricidal for W bancrofti in multiple doses. Used alone or in combination with DEC. |
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| Adult Dose | 150-200 mcg/kg of body weight PO as a single dose, repeat at 2-3 monthly intervals |
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| Pediatric Dose | <5 years or <15 kg (33 lb): Do not administer
>5 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; concurrent illness |
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| Interactions | May interact with other ligand-gated chloride channels, such as those gated by GABA |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | Although inadvertent use in pregnancy has not been associated with an increased number of birth defects, avoid while pregnant, if possible; treat mothers who intend to breastfeed only if risk of delayed treatment outweighs possible risks to the newborn caused by ivermectin excretion in milk; may cause nausea, vomiting, and mild CNS depression; may cause drowsiness |
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| Drug Name | Diethylcarbamazine (Hetrazan) |
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| Description | Has been shown to induce immobilization of microfilariae by decreasing muscle activity due to hyperpolarization effects, but the precise mechanism of DEC is not understood. Alteration of the surface membrane also occurs, with enhanced destruction by the host's immune system. Evidence also 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. |
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| Adult Dose | 6 mg/kg PO qd for at least 12 d, preferably 3 wk; low doses (approximately 2-3 mg/kg/d) usually recommended for first 3 d of treatment to decrease risk of adverse effects |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity; DEC provocation (provocation of microfilariae for bancroftian filariasis is contraindicated in areas where Loa loa and Onchocerca volvulus are endemic because of risk of severe Mazzotti reaction) |
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| Interactions | None reported |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
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| Precautions | Nonteratogenic and safe in pregnancy but spontaneous abortion or premature labor and delivery are possible with induced febrile reactions; DEC provocation; caution in individuals with potentially heavy infections of lymphatic filariids because a DEC dose of 2 mg/kg of body weight may provoke febrile and inflammatory reaction secondary to worm death; antipyretics and steroids may decrease risk of these symptoms; possible allergic reactions of fever, urticaria, and lymphangitis in lymphatic filariasis; nonspecific adverse effects include headache, malaise, nausea, vertigo, and vomiting |
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| Drug Name | Albendazole (Albenza, Eskazole, Zentel) |
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| Description | Methyl [5-(propylthio)-1H-benzimidazol-2yl] carbamate. A broad-spectrum anthelminthic. Action is thought to be mainly intraintestinal, although, at higher doses, a sufficient amount is absorbed and metabolized to an active sulfoxide metabolite to have a therapeutic effect against tissue parasites. |
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| Adult Dose | 400 mg PO as a single dose |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity; pregnancy or possibility of pregnancy |
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| Interactions | Coadministration with carbamazepine may decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase toxicity |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Mild-to-moderate elevations of liver enzyme levels reported, especially with high-dose regimens; liver enzymes usually normalize upon discontinuation of treatment; rare reports of severe hepatic abnormalities associated with jaundice and histological hepatocellular damage, possibly irreversible; has been shown to be teratogenic and embryotoxic in rats and rabbits; advise women of childbearing age to take effective precautions against conception during and within 1 mo of completion of treatment |
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Drug Category: Antibiotics
These agents may provide an alternative to anthelminthics.
| Drug Name | Doxycycline (Bio-Tab, Doxy, Vibramycin) |
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| Description | Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. |
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| Adult Dose | 100 mg PO bid for 6-8 weeks |
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| Pediatric Dose | <8 years: Not recommended
>8 years: 2-5 mg/kg/d PO in 2 divided doses; not to exceed 200 mg/d |
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| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
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| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one-half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines |
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Further Inpatient Care
- Observe the patient for complications of therapy, especially if DEC is used.
Further Outpatient Care
- Schedule a posttreatment follow-up visit for 12 months after treatment, with examination of peripheral blood 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
- Avoid insect vector bites. This is usually not feasible for residents of endemic areas but visitors should use insect repellent and mosquito nets.
Complications
- Secondary bacterial infection of elephantiasis may occur.
Prognosis
- Prognosis is good if bancroftian filariasis is recognized and treated early.
Patient Education
- Educate patients regarding protection against insect vectors; patients should refrain from using self-treatment regimens, especially with DEC.
Medical/Legal Pitfalls
- Incorrect diagnosis: Initially missing the diagnosis of bancroftian filariasis is certainly possible because of the infrequency of cases in the developed world and Western Hemisphere. Major consequences in this scenario include a late diagnosis that results in a greater degree of individual patient morbidity and failure to issue a timely epidemiologic notification of a case. Obtain a travel history from patients with suspicious lesions.
- Inappropriate treatment: Although this scenario is much less likely, inappropriate treatment of bancroftian filariasis is a potential issue, even if the diagnosis is correctly made. Consult an infectious diseases specialist in cases of suspected bancroftian filariasis outside of endemic nations.
- Reaction to treatment: Ascertain whether the patient with bancroftian filariasis has ever taken any antiparasitic drugs and whether an 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 bancroftian filariasis are at risk of other parasitic infections, because areas endemic for bancroftian filariasis are also endemic for other parasites. After treatment, monitor patients for other symptomatology characteristic of parasitic infections.
See Image 28 and Image 56 at the McGill Faculty of Medicine Web site.
| Media file 1:
Life cycle of Wuchereria bancrofti in humans and the mosquito vectors (Aedes, Anopheles, Culex, and Mansonia species). |
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| Media file 2:
Filarial abscess scar of left upper thigh in a teenaged adolescent male positive for Wucheria bancrofti microfilariae. |
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| Media file 3:
Lymphatic filariasis due to Wuchereria bancrofti causing limb lymphoedema, inguinal lymphadenopathy, and hydrocele. Photograph taken by Professor Bruce McMillan and donated by Dr. John Walker. |
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| Media file 4:
Unilateral left lower leg elephantiasis secondary to Wuchereria bancrofti infection in a male. |
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| Media file 5:
This is a close-up view of the unilateral lower leg elephantiasis shown in Media file 4. Note lymphedema and typical skin appearance of depigmentation and verrucosities (warty changes). |
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| Media file 6:
Lateral view of right outer aspect of leg of young man affected by gross elephantiasis secondary to Wuchereria bancrofti is shown. He was amicrofilaremic. |
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| Media file 7:
Inner aspect of lower leg of young man in Media file 6 with gross elephantiasis secondary to Wuchereria bancrofti infection. |
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| Media file 8:
Unilateral left hydrocele and testicular enlargement secondary to Wuchereria bancrofti in a man who was also positive for microfilariae. |
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| Media file 9:
Bilateral hydrocele, testicular enlargement, and inguinal lymphadenopathy secondary to Wuchereria bancrofti is shown. This man was microfilaremic. |
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| Media file 10:
Adult worms of Wuchereria bancrofti in cross section isolated from a testicular lump. |
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| Media file 11:
Microfilaria of Wuchereria bancrofti in a peripheral blood smear. |
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| Media file 12:
Appearance of microfilariae of Wuchereria bancrofti after concentration of venous blood with a Nuclepore filter. |
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Bancroftian Filariasis excerpt Article Last Updated: Feb 7, 2008
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