Guest guest Posted September 4, 2006 Report Share Posted September 4, 2006 http://www.emedicine.com/ped/topic782.htm Filariasis Last Updated: June 23, 2006 Rate this Article Email to a Colleague Get CME/CE for article Synonyms and related keywords: bancroftian filariasis, elephantiasis, hanging groins, leopard skin, river blindness, sowda, loaiasis, loiasis, Calabar swelling, fugitive swelling, Loa loa, Onchocerca volvulus, Mansonella streptocerca, Wuchereria bancrofti, Brugia malayi, Brugia timori, Mansonella perstans, Mansonella ozzardi AUTHOR INFORMATION Section 1 of 11 Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Author: Robert W Tolan, Jr, MD, Chief of Allergy, Immunology and Infectious Diseases, The Children's Hospital at St Peter's University Hospital, Clinical Associate Professor of Pediatrics, Drexel University College of Medicine Coauthor(s): Michael D Nissen, BMedSc, MBBS, FRACP, FRCPA, Director of Infectious Diseases, Royal Children's Hospital at Brisbane, Australia; Senior Lecturer, Department of Pediatrics and Child Health, University of Queensland, Australia; 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 Robert W Tolan, Jr, MD, is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Disease Society, Phi Beta Kappa, and Physicians for Social Responsibility Editor(s): 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, 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; and Russell W Steele, MD, Professor and Vice Chairman, Department of Pediatrics, Head, Division of Infectious Diseases, Louisiana State University Health Sciences Center Disclosure INTRODUCTION Section 2 of 11 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Background: Filariasis is a disease group that affects humans and animals and is caused by nematode parasites of the order Filariidae, commonly called filariae. Of the hundreds of described filarial parasites, only 8 species 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 o Loa loa o Onchocerca volvulus o Mansonella streptocerca * Lymphatic group o Wuchereria bancrofti o Brugia malayi o Brugia timori * Body cavity group o Mansonella perstans o 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. 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 feeding most actively. 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: * In the US: No form of human filariasis is currently endemic in the United States. 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. * Internationally: 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, and social 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. Manifestation of acute and chronic filariasis usually occurs only after years of repeated and intense exposure to infected vectors in endemic areas. CLINICAL Section 3 of 11 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography 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, though 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 are usually 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 o Symptoms of L loa infection are usually confined to subcutaneous swellings on the extremities, together with localized pain, pruritus, and urticaria. o Microfilaremia tends to be asymptomatic. * M ozzardi, M perstans, and M streptocerca o Infections due to Mansonella species are usually asymptomatic. o If present, symptoms may include fever, pruritus, skin lumps, lymphadenitis, and abdominal pain. Physical: Signs of filariasis present on examination are species dependent and may be acute or chronic. * Lymphatic filariasis o Acute manifestations of lymphatic filariasis usually are 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. o Repeated episodes of inflammation and lymphedema lead to lymphatic damage, chronic swelling, and elephantiasis of the legs, arms, scrotum, vulva, and breasts. o 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 are usually a painless lump in the subcutaneous tissue, submucosa, or eyelid. * Onchocerciasis o The clinical triad of infection is dermatitis, skin nodules (onchocercomas), and ocular lesions. o Skin lesions include edema, pruritus, erythema, papules, scablike eruptions, altered pigmentation, and lichenification. o Skin nodules tend to be common over bony prominences. o 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 are punctate keratitis, pannus formation, corneal fibrosis, iridocyclitis, glaucoma, choroiditis, and optic atrophy. * Loaiasis o A Calabar swelling is the diagnostic feature of disease. Most common around the joints, a Calabar swelling is a transient large area of localized nonerythematous subcutaneous edema. o 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 o Mosquitoes of the genera Aedes, Anopheles, Culex, and Mansonia are the intermediate hosts and vectors of all lymphatic filariasis species. o 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. o 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 o Occult bancroftian filariasis denotes infection in which microfilariae are not seen in the blood, though they may be found in other body fluids and/or tissues. o 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. o 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 Microfilariae from the skin are ingested by Simulium species of blackflies. o 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 o Mango flies or deerflies of the Chrysops species transmit loaiasis. o 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 o Meningoencephalopathy is a severe and often fatal complication of infection. This syndrome usually is related to DEC administration in individuals with high-density microfilaremia, but it may occur without drug therapy. o 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 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Acute Poststreptococcal Glomerulonephritis Asthma Bancroftian Filariasis Dirofilariasis 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 Quick Find Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Click for related images. Related Articles Acute Poststreptococcal Glomerulonephritis Asthma Bancroftian Filariasis Dirofilariasis Continuing Education CME available for this topic. Click here to take this CME. Patient Education Click here for patient education. WORKUP Section 5 of 11 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Lab Studies: * Detection of microfilariae: The traditional diagnostic method is to demonstrate microfilariae in the peripheral blood or skin. o 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 diethylcarbamazine (DEC) at 1-2 mg/kg 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. o 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. o Detection of microfilariae in the eye: Microfilariae of O volvulus also may be detected in the cornea or anterior chamber of the eye on slitlamp 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: 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 o Lymphatic obstruction of the inguinal and scrotal lymphatics can be demonstrated and monitored by means of ultrasonography. o Deep onchocercomas and vitreous changes in the eye can sometimes be detected by means of ultrasonography. Other Tests: * Mazzotti test o 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. o 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 causing a localized skin reaction may be used in such patients. Procedures: * Lymph node or skin nodule biopsy o Biopsy is only recommended in cutaneous filariasis because excision of nodes may further impede lymphatic drainage in lymphatic filariasis. o 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 subcutaneous tissues. 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 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Medical Care: The medical treatment for filarial infection should be specific and based on the microfilariae isolated or antigenemia detected. * Lymphatic filariasis o 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. o Patients with ADL or chronic filariasis may initially require inpatient care for administration of antihistamines, steroids, pain relief, and intravenous antibiotics for secondary infections. o Bed rest, limb elevation, and compression bandages have traditionally been used to treat chronic lymphedema. Steroids 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 disease 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 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Ivermectin is now considered the drug of choice for the treatment of all forms of filariasis, except in Mansonella infections, 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: 1. Inhibition of microtubules causing irreversible block of glucose uptake 2. Tubulin polymerization inhibition 3. Depolarizing neuromuscular blockade 4. Cholinesterase inhibition 5. Increased cell membrane permeability, resulting in intracellular calcium loss 6. Vacuolization of the schistosome tegument 7. Increased cell membrane permeability to chloride ions via alteration of chloride channels Drug Name Ivermectin (Mectizan, 22,23-dihydroavermectin) -- Macrocyclic lactone derivative of Avermectin. Exerts its antiparasitic action by acting as a potent agonist at GABA receptors and potentiating the inhibitory signals sent to motor neurons that paralyze the parasite. Has no paralytic action in humans because GABA is confined to CNS in humans, and ivermectin does not cross the blood brain barrier. Mechanism of action 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. Adult Dose 150-200 mcg/kg PO as single dose; may repeat q2-3mo Pediatric Dose <5 years or <15 kg: Not established >5 years or >15 kg: Administer as in adults Contraindications Documented hypersensitivity; concurrent illness Interactions May interact with other ligand-gated chloride channels, such as those gated by GABA Pregnancy C - Safety for use during pregnancy has not been established. Precautions Avoid in pregnancy, though inadvertent use in pregnancy not associated with increased birth defects; treat mothers who intend to breastfeed only when risk of delayed treatment outweighs possible risks to newborn caused by ivermectin excretion in milk; repeat courses of therapy may be required in immunocompromised patients; may cause nausea, vomiting, mild CNS depression, fever, headache, myalgia, sore throat, or cough Drug Name Diethylcarbamazine (DEC, Hetrazan) -- Piperazine derivative. Immobilizes microfilariae by decreasing muscle activity due to hyperpolarization effects, but precise mechanism not understood. Alteration of surface membrane and enhanced destruction by host's immune system also occur. May enhance adhesion of granulocytes via antibody-dependent and antibody-independent mechanisms. Interference by microfilarial intracellular processing and transport of specific macromolecules by DEC is also hypothesized. Adult Dose 6 mg/kg/d PO divided tid for >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 Pediatric Dose <2 years: Not established >2 years: Administer as in adults Contraindications Documented hypersensitivity; DEC provocation; provocation of microfilariae for bancroftian filariasis contraindicated in areas where Loa loa and Onchocerca volvulus are endemic because of risk of severe Mazzotti reaction Interactions None reported Pregnancy C - Safety for use during pregnancy has not been established. Precautions Possible spontaneous abortion or premature labor and delivery with induced febrile reactions; DEC provocation; caution in individuals with potential heavy infections of lymphatic filariids because a dose of 2 mg/kg may provoke febrile and inflammatory reaction secondary to worm death; antipyretics and corticosteroids 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 Drug Name Suramin (Germanin, Antrypol, Naganol) -- Antitrypanosome and antihelminthic. Only drug currently in clinical use for onchocerciasis that is effective against adult worms. Use is restricted because of frequency of associated complications and its intrinsic toxicity. WHO advises to consider only for curative treatment of individuals in areas without transmission of onchocerciasis, for treatment of individuals leaving an endemic area, and for severe hyperreactive onchodermatitis in which symptoms are not adequately controlled with ivermectin. Adult Dose 66.7 mg/kg body weight total dose, in 6 incremental weekly doses Pediatric Dose <10 years: Contraindicated >10 years: Administer as in adults Contraindications Documented hypersensitivity; severe liver or renal disease; old age or infirmity; delay treatment in pregnancy until after delivery; nephrotoxic combination therapy with DEC well tolerated; immediate and potentially fatal reaction with nausea, vomiting, shock, and loss of consciousness may follow the injection, thus give small test dose before initiating treatment; hypersensitivity reactions thought to be common with onchocerciasis; children <10 y; blindness (unless require relief from intensely itchy lesions), mild-to-moderate infections with no symptoms, and in patients whose eyes are not at risk Interactions None reported Pregnancy C - Safety for use during pregnancy has not been established. Precautions Delay treatment in pregnancy until after delivery; administer under close medical supervision and with general condition of patients improved as much as possible before treatment begins; not to be given to patients who experience a severe reaction after first dose; caution in liver and renal failure; measure protein in urine before treatment starts and at weekly intervals during treatment; reduce dosage if moderate proteinuria develops; discontinue with severe proteinuria or if casts appear in urine; adverse reactions include abdominal pain, mouth ulceration, and skin reactions such as urticaria and pruritus; later reactions include paraesthesia, polyneuropathy, hyperesthesia of the palms and soles, skin eruptions, fever, polyuria, increased thirst, raised liver enzymes, photophobia, and lacrimation; proteinuria common, with hematuria and casts in the urine also occurring; occasional reports of adrenal insufficiency have been made Drug Name Mebendazole (Banworm, SQ Worm, Vermox) -- Benzimidazole derivative. Causes worm death by selectively and irreversibly blocking uptake of glucose and other nutrients in susceptible adult intestine where helminths dwell. Adult Dose 100 mg bid for 3 d; repeat in 2-3 wk if severe case Pediatric Dose <2 years: Not established >2 years: Administer as in adults Contraindications Documented hypersensitivity Interactions Carbamazepine and phenytoin may decrease effects; cimetidine may increase levels Pregnancy C - Safety for use during pregnancy has not been established. Precautions Teratogenic and embryotoxic in animals; dosage adjustments required in liver disease; adverse effects include abdominal pain, diarrhea, and rash Drug Name Flubendazole (Flicum, Fluvermal) -- Not available in United States. Benzimidazole carbamate antihelminthic that is an analogue of mebendazole. Adult Dose 100 mg PO bid for 3 d; may repeat treatment in 2-3 wk if severe case Pediatric Dose Administer as in adults Contraindications Documented hypersensitivity Interactions Carbamazepine and phenytoin may decrease effects; cimetidine may increase levels Pregnancy C - Safety for use during pregnancy has not been established. Precautions Dosage adjustments required in liver disease; adverse effects include abdominal pain, diarrhea, and rash Drug Name Albendazole (Albenza) -- Methyl [5-(propylthio)-1H-benzimidazol-2yl] carbamate. Broad-spectrum antihelminthic. Action is thought to mainly be intraintestinal; although, at higher doses, sufficient amount is absorbed and metabolized to an active sulfoxide metabolite to have therapeutic effect against tissue parasites. Adult Dose 400 mg PO as a single dose Pediatric Dose >2 years: Administer as in adults Contraindications Documented hypersensitivity or hypersensitivity to other benzimidazole derivatives Interactions Coadministration with carbamazepine may decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase toxicity Pregnancy C - Safety for use during pregnancy has not been established. Precautions Caution in pregnancy or in women who may be pregnant; 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 therapy completion; mild-to-moderate elevations of liver enzymes reported, especially with high-dose regimens; usually normalize on discontinuation of treatment; rare reports of severe hepatic abnormalities associated with jaundice and histologic hepatocellular damage, possibly irreversible; discontinue use if LFTs increase significantly (resume when levels decrease to pretest values); abdominal pain, nausea, vomiting, diarrhea, dizziness, vertigo, fever, increased intracranial pressure, and alopecia may occur Drug Category: Antibiotics -- These agents may provide an alternative to anthelminthics. Drug Name Doxycycline (Bio-Tab, Vibramycin) -- 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. Adult Dose 100 mg PO bid for 6-8 wk Pediatric Dose <8 years: Not recommended >8 years: 2-5 mg/kg/d PO in 2 divided doses; not to exceed 200 mg/d Contraindications Documented hypersensitivity; severe hepatic dysfunction 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 oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy Pregnancy D - Unsafe in pregnancy 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 FOLLOW-UP Section 8 of 11 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography 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 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography 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 and remember to avoid this pitfall. * Inappropriate treatment: Although this scenario is much less likely, inappropriate treatment of filariasis is a potential issue, even if the diagnosis is made correctly. Consult an infectious disease specialist in any and all cases of suspected filariasis outside of endemic nations to prevent inappropriate treatment from occurring. * 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. PICTURES Section 10 of 11 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Caption: Picture 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. Click to see larger picture Click to see detailView Full Size Image Click to ZoomeMedicine Zoom View (Interactive!) Picture Type: Photo Caption: Picture 2. 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. Click to see larger picture Click to see detailView Full Size Image Click to ZoomeMedicine Zoom View (Interactive!) Picture Type: Photo Caption: Picture 3. Adult worms of Wuchereria bancrofti in a cross section isolated from a testicular lump. Click to see larger picture Click to see detailView Full Size Image Click to ZoomeMedicine Zoom View (Interactive!) Picture Type: Photo Caption: Picture 4. Microfilaria of Wuchereria bancrofti in a peripheral blood smear. Click to see larger picture Click to see detailView Full Size Image Click to ZoomeMedicine Zoom View (Interactive!) Picture Type: Photo Caption: Picture 5. Shown here are onchocercomas of the forearm skin, also called sowda, in a Sudanese man. Click to see larger picture Click to see detailView Full Size Image Click to ZoomeMedicine Zoom View (Interactive!) Picture Type: Photo Caption: Picture 6. Adult Onchocerca volvulus contained within onchocercomas of the skin. Click to see larger picture Click to see detailView Full Size Image Click to ZoomeMedicine Zoom View (Interactive!) Picture Type: Photo Caption: Picture 7. Microfilariae of Loa loa detected in skin snips. Click to see larger picture Click to see detailView Full Size Image Click to ZoomeMedicine Zoom View (Interactive!) Picture Type: Photo Caption: Picture 8. Microfilariae of Mansonella perstans in peripheral blood. Click to see larger picture Click to see detailView Full Size Image Click to ZoomeMedicine Zoom View (Interactive!) Picture Type: Photo BIBLIOGRAPHY Section 11 of 11 Click here to go to the previous section in this topic Click here to go to the top of this page Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography * Baird JK, Neafie RC, Lanoie L, Connor DH: Adult Mansonella perstans in the abdominal cavity in nine Africans. Am J Trop Med Hyg 1987 Nov; 37(3): 578-84[Medline]. * Carme B, Boulesteix J, Boutes H, Puruehnce MF: Five cases of encephalitis during treatment of loiasis with diethylcarbamazine. Am J Trop Med Hyg 1991 Jun; 44(6): 684-90[Medline]. * Connor DH, Gibson DW, Neafie RC, et al: Sowda--onchocerciasis in north Yemen: a clinicopathologic study of 18 patients. Am J Trop Med Hyg 1983 Jan; 32(1): 123-37[Medline]. * Connor DH, George GH, Gibson DW: Pathologic changes of human onchocerciasis: implications for future research. 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NOTE: Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. 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