- Author: Siddharth Wayangankar, MD, MPH; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD more...
The traditional diagnostic method for filariasis is to demonstrate microfilariae in the peripheral blood or skin. For example, the microfilariae of all species that cause lymphatic filariasis and the microfilariae of L loa, M ozzardi, and M perstans are detected in blood.
O volvulus and M streptocerca infections are diagnosed when microfilariae are detected in multiple skin snip specimens from different sites located on both sides of the body. In addition, microfilariae of O volvulus may be detected in the cornea or anterior chamber of the eye, using slit-lamp examination.
Urine examination and microscopy
Microfilariae may also be observed in chylous urine and hydrocele fluid. If lymphatic filariasis is suspected, urine should be examined macroscopically for chyluria and then concentrated to examine for microfilariae.
Detection of Microfilariae in the Skin and Eye
O volvulus and M streptocerca infections are diagnosed when microfilariae are detected in multiple skin-snip specimens from different sites located on both sides of the body.
In suspected cases of African onchocerciasis, the recommended sites for skin snips are the gluteus and calf. For American onchocerciasis, the scapula and deltoid skin are preferred.
The Mazzotti test allows a presumptive diagnosis of cutaneous filariasis to be made when skin snips are negative for microfilariae. An intense pruritus is elicited within hours after a single small dose of DEC (50-100 mg). Steroids may be necessary to control this inflammatory reaction. The test must be used with caution in individuals who may be heavily infected, because a severe systemic reaction can be provoked. A DEC patch test that causes a localized skin reaction may be used in such patients.
Microfilariae of O volvulus may be detected in the cornea or anterior chamber of the eye using slit-lamp examination.
Detection of Microfilariae in Blood
As mentioned, the microfilariae of all species that cause lymphatic filariasis and the microfilariae of L loa, M ozzardi, and M perstans are detected in blood. (See the image below.)
Capillary finger-prick or venous blood is used for thick blood films. Venous blood also can be concentrated or passed through a Nuclepore filter before being examined microscopically. The species of infection then can be determined by the microscopic appearance. W bancrofti and Brugia species have an acellular sheath. W bancrofti has no nuclei in its tail, whereas B malayi has terminal and subterminal nuclei. (See the image below.)
Microfilariae may periodically appear in the peripheral circulation. For the best chance of detection, the blood should be examined at different intervals over a 24-hour period. (See the image below.)
Bancroftian and brugian filariasis tend to show nocturnal periodicity, so it is recommended that samples be collected between 10:00 pm and 2:00 am. Provocation of nocturnally periodic microfilariae may be achieved with a daytime dose of DEC at 1-2 mg/kg.
Microfilariae may be absent in the following cases:
Patients with ADL or late chronic lymphatic disease
Typically, patients with loiasis, unless the infection has been present for many years
Complete blood count
Eosinophilia is marked in all forms of patent filarial infection.
Serum immunoglobulin concentrations
Elevated serum IgE and IgG4 may be observed with active filarial disease. Testing based on polymerase chain reaction assay has been described.
A multiplex bead assay to monitor serial levels of serum antibody during treatment has been proposed.
Detection of filarial antigen
The presence of circulating filarial antigen in the peripheral blood, with or without microfilariae, is considered diagnostic of patent filarial infection and is also used to monitor the effectiveness of therapy. Commercial kits are available to test venous blood and can be quantitative (enzyme-linked immunoassay [ELISA]) Og4C3 monoclonal antibody–based assay) or qualitative (immunochromatographic).
The ELISA is one of the best predictors of worm burden ; the other, although not as sensitive, was once considered the test of choice in field surveys. However, results from this test remain positive for 3 years posttreatment; hence, immunochromatographic testing has been shown to be ineffective.
Detection of filarial antibodies
The use of recombinant antigens for the diagnosis of onchocerciasis IgG4 antibodies (which are a marker of active infection) has improved the sensitivity and specificity of serologic assays. The usual IgG and IgE lack specificity (species differentiation) and usually crossreact with antigens of Strongyloides. In addition, they do not differentiate between past and recent infections. Thus, diagnosis based on recombinant antigens is useful in expatriates but not in persons living in endemic regions.
The following imaging studies can be used in the evaluation of filariasis:
Chest radiography - Diffuse pulmonary infiltrates are visible in patients with tropical pulmonary eosinophilia (TPE)
Ultrasonography - Can be used to demonstrate and monitor lymphatic obstruction of the inguinal and scrotal lymphatics
Ultrasonography has also been used to demonstrate the presence of viable worms, which are seen to be in continuous motion (ie, "filarial dance" sign). This imaging characteristic has been used to monitor the effectiveness of treatment. In addition, deep onchocercomas and vitreous changes in the eye can sometimes be detected with ultrasonography.
It is recommended that biopsy specimens be obtained only in patients with cutaneous filariasis, as excising nodes may further impede lymphatic drainage in patients with lymphatic filariasis. Adult worms of O volvulus and L loa are found in the nodules and fibrotic tissue of the skin. L loa worms occasionally can be dissected from the conjunctiva of the eye or bridge of the nose as they migrate through subcutaneous tissue.
Affected lymph nodes demonstrate fibrosis and lymphatic obstruction with the creation of collateral channels. The skin of individuals with elephantiasis is characterized by hyperkeratosis, acanthosis, lymph and fatty tissue, loss of elastin fibers, and fibrosis. (See the image below.)
Two areas are evident in onchocercomas: (1) a central stromal and granulomatous, inflammatory region where the adult worms are found and (2) a peripheral, fibrous section. Microfilariae in the skin incite a low-grade inflammatory reaction with loss of elasticity and fibrotic scarring. (See the image below.)
Knopp S, Steinmann P, Hatz C, Keiser J, Utzinger J. Nematode infections: filariases. Infect Dis Clin North Am. 2012 Jun. 26(2):359-81. [Medline].
Okon OE, Iboh CI, Opara KN. Bancroftian filariasis among the Mbembe people of Cross River state, Nigeria. J Vector Borne Dis. 2010 Jun. 47(2):91-6. [Medline].
Addiss DG, Louis-Charles J, Roberts J, Leconte F, Wendt JM, Milord MD, et al. Feasibility and effectiveness of basic lymphedema management in Leogane, Haiti, an area endemic for bancroftian filariasis. PLoS Negl Trop Dis. 2010 Apr 20. 4(4):e668. [Medline]. [Full Text].
Mathieu E, Dorkenoo A, Otogbe FK, Budge PJ, Sodahlon YK. A laboratory-based surveillance system for Wuchereria bancrofti in Togo: a practical model for resource-poor settings. Am J Trop Med Hyg. 2011 Jun. 84(6):988-93. [Medline]. [Full Text].
Uttah EC. Prevalence of endemic Bancroftian filariasis in the high altitude region of south-eastern Nigeria. J Vector Borne Dis. 2011 Jun. 48(2):78-84. [Medline].
Molyneux DH. Tropical lymphedemas--control and prevention. N Engl J Med. 2012 Mar 29. 366(13):1169-71. [Medline].
Meyrowitsch DW, Simonsen PE, Garred P, Dalgaard M, Magesa SM, Alifrangis M. Association between mannose-binding lectin polymorphisms and Wuchereria bancrofti infection in two communities in North-Eastern Tanzania. Am J Trop Med Hyg. 2010 Jan. 82(1):115-20. [Medline]. [Full Text].
Rosenblatt JE. Laboratory diagnosis of infections due to blood and tissue parasites. Clin Infect Dis. 2009 Oct 1. 49(7):1103-8. [Medline].
Marcos LA, Arrospide N, Recuenco S, Cabezas C, Weil GJ, Fischer PU. Genetic characterization of atypical Mansonella (Mansonella) ozzardi microfilariae in human blood samples from northeastern Peru. Am J Trop Med Hyg. 2012 Sep. 87(3):491-4. [Medline]. [Full Text].
[Guideline] World Health Organization. Lymphatic filariasis: the disease and its control. Fifth report of the WHO Expert Committee on Filariasis. World Health Organ Tech Rep Ser. 1992. 821:1-71. [Medline].
Babu BV, Swain BK, Rath K. Impact of chronic lymphatic filariasis on quantity and quality of productive work among weavers in an endemic village from India. Trop Med Int Health. 2006 May. 11(5):712-7. [Medline].
Ramaiah KD, Das PK, Michael E, Guyatt H. The economic burden of lymphatic filariasis in India. Parasitol Today. 2000 Jun. 16(6):251-3. [Medline].
Witt C, Ottesen EA. Lymphatic filariasis: an infection of childhood. Trop Med Int Health. 2001 Aug. 6(8):582-606. [Medline].
Wammes LJ, Hamid F, Wiria AE, Wibowo H, Sartono E, Maizels RM, et al. Regulatory T cells in human lymphatic filariasis: stronger functional activity in microfilaremics. PLoS Negl Trop Dis. 2012. 6(5):e1655. [Medline]. [Full Text].
Baird JB, Charles JL, Streit TG, Roberts JM, Addiss DG, Lammie PJ. Reactivity to bacterial, fungal, and parasite antigens in patients with lymphedema and elephantiasis. Am J Trop Med Hyg. 2002 Feb. 66(2):163-9. [Medline].
Tripathi PK, Mahajan RC, Malla N, Mewara A, Bhattacharya SM, Shenoy RK, et al. Circulating filarial antigen detection in brugian filariasis. Parasitology. 2015 Dec 9. 1-8. [Medline].
King CL. Transmission intensity and human immune responses to lymphatic filariasis. Parasite Immunol. 2001 Jul. 23(7):363-71. [Medline].
Lamb TJ, Le Goff L, Kurniawan A, Guiliano DB, Fenn K, Blaxter ML, et al. Most of the response elicited against Wolbachia surface protein in filarial nematode infection is due to the infective larval stage. J Infect Dis. 2004 Jan 1. 189(1):120-7. [Medline].
Li J, Wei QK, Hu SL, Xiao T, Xu C, Liu X, et al. Establishment of lymphatic filarial specific IgG4 indirect ELISA detection method. Int J Clin Exp Med. 2015. 8 (9):16496-16503. [Medline].
Lammie PJ, Cuenco KT, Punkosdy GA. The pathogenesis of filarial lymphedema: is it the worm or is it the host?. Ann N Y Acad Sci. 2002 Dec. 979:131-42; discussion 188-96. [Medline].
Panda AK, Sahoo PK, Kerketta AS, Kar SK, Ravindran B, Satapathy AK. Human lymphatic filariasis: genetic polymorphism of endothelin-1 and tumor necrosis factor receptor II correlates with development of chronic disease. J Infect Dis. 2011 Jul 15. 204(2):315-22. [Medline].
Ottesen EA. The Wellcome Trust Lecture. Infection and disease in lymphatic filariasis: an immunological perspective. Parasitology. 1992. 104 Suppl:S71-9. [Medline].
Taylor MJ, Hoerauf A. Wolbachia bacteria of filarial nematodes. Parasitol Today. 1999 Nov. 15(11):437-42. [Medline].
Murugan K, Nataraj D, Madhiyazhagan P, et al. Carbon and silver nanoparticles in the fight against the filariasis vector Culex quinquefasciatus: genotoxicity and impact on behavioral traits of non-target aquatic organisms. Parasitol Res. 2015 Nov 28. [Medline].
Tamarozzi F, Halliday A, Gentil K, Hoerauf A, Pearlman E, Taylor MJ. Onchocerciasis: the role of Wolbachia bacterial endosymbionts in parasite biology, disease pathogenesis, and treatment. Clin Microbiol Rev. 2011 Jul. 24(3):459-68. [Medline]. [Full Text].
Zouré HG, Wanji S, Noma M, Amazigo UV, Diggle PJ, Tekle AH, et al. The geographic distribution of Loa loa in Africa: results of large-scale implementation of the Rapid Assessment Procedure for Loiasis (RAPLOA). PLoS Negl Trop Dis. 2011 Jun. 5(6):e1210. [Medline]. [Full Text].
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].
Eberhard ML, Ostovar GA, Chundu K, Hobohm D, Feiz-Erfan I, Mathison BA, et al. Zoonotic Onchocerca lupi infection in a 22-month-old child in Arizona: first report in the United States and a review of the literature. Am J Trop Med Hyg. 2013 Mar. 88(3):601-5. [Medline]. [Full Text].
Centers for Disease Control and Prevention. Progress toward elimination of lymphatic filariasis--Togo, 2000--2009. MMWR Morb Mortal Wkly Rep. 2011 Jul 29. 60(29):989-91. [Medline].
Kazura J. Guerrant R, Walker DH, Weller PF, eds. Tropical Infectious Diseases: Principles, Pathogens and Practice. Philadelphia, PA: Churchill Livingstone; 1999. Vol 2: 852.
Pani SP, Yuvaraj J, Vanamail P, Dhanda V, Michael E, Grenfell BT. Episodic adenolymphangitis and lymphoedema in patients with bancroftian filariasis. Trans R Soc Trop Med Hyg. 1995 Jan-Feb. 89(1):72-4. [Medline].
Kaiser C, Rubaale T, Tukesiga E, Kipp W, Kabagambe G, Ojony JO, et al. Association between onchocerciasis and epilepsy in the Itwara hyperendemic focus, West Uganda: controlling for time and intensity of exposure. Am J Trop Med Hyg. 2011 Aug. 85(2):225-8. [Medline]. [Full Text].
Gobbi F, Boussinesq M, Mascarello M, Angheben A, Gobbo M, Rossanese A, et al. Case report: Loiasis with peripheral nerve involvement and spleen lesions. Am J Trop Med Hyg. 2011 May. 84(5):733-7. [Medline]. [Full Text].
Garg PK, Bhatt S, Kashyap B, George A, Jain BK. Genital filariasis masquerading as testicular torsio. J Vector Borne Dis. 2011 Jun. 48(2):119-21. [Medline].
Mehlotra RK, Gray LR, Blood-Zikursh MJ, Kloos Z, Henry-Halldin CN, Tisch DJ, et al. Molecular-based assay for simultaneous detection of four Plasmodium spp. and Wuchereria bancrofti infections. Am J Trop Med Hyg. 2010 Jun. 82(6):1030-3. [Medline]. [Full Text].
Moss DM, Priest JW, Boyd A, Weinkopff T, Kucerova Z, Beach MJ, et al. Multiplex bead assay for serum samples from children in Haiti enrolled in a drug study for the treatment of lymphatic filariasis. Am J Trop Med Hyg. 2011 Aug. 85(2):229-37. [Medline]. [Full Text].
Chanteau S, Moulia-Pelat JP, Glaziou P, Nguyen NL, Luquiaud P, Plichart C, et al. Og4C3 circulating antigen: a marker of infection and adult worm burden in Wuchereria bancrofti filariasis. J Infect Dis. 1994 Jul. 170(1):247-50. [Medline].
Nguyen NL, Plichart C, Esterre P. Assessment of immunochromatographic test for rapid lymphatic filariasis diagnosis. Parasite. 1999 Dec. 6(4):355-8. [Medline].
Schuetz A, Addiss DG, Eberhard ML, Lammie PJ. Evaluation of the whole blood filariasis ICT test for short-term monitoring after antifilarial treatment. Am J Trop Med Hyg. 2000 Apr. 62(4):502-3. [Medline].
Lal RB, Ottesen EA. Enhanced diagnostic specificity in human filariasis by IgG4 antibody assessment. J Infect Dis. 1988 Nov. 158(5):1034-7. [Medline].
Dreyer G, Noroes J, Amaral F, Nen A, Medeiros Z, Coutinho A, et al. Direct assessment of the adulticidal efficacy of a single dose of ivermectin in bancroftian filariasis. Trans R Soc Trop Med Hyg. 1995 Jul-Aug. 89(4):441-3. [Medline].
Ottesen EA. Major progress toward eliminating lymphatic filariasis. N Engl J Med. 2002 Dec 5. 347(23):1885-6. [Medline].
Ashton RA, Kyabayinze DJ, Opio T, Auma A, Edwards T, Matwale G, et al. The impact of mass drug administration and long-lasting insecticidal net distribution on Wuchereria bancrofti infection in humans and mosquitoes: an observational study in northern Uganda. Parasit Vectors. 2011 Jul 15. 4:134. [Medline]. [Full Text].
Drexler N, Washington CH, Lovegrove M, Grady C, Milord MD, Streit T, et al. Secondary mapping of lymphatic filariasis in Haiti-definition of transmission foci in low-prevalence settings. PLoS Negl Trop Dis. 2012. 6(10):e1807. [Medline]. [Full Text].
van den Berg H, Kelly-Hope LA, Lindsay SW. Malaria and lymphatic filariasis: the case for integrated vector management. Lancet Infect Dis. 2013 Jan. 13(1):89-94. [Medline].
Arndts K, Deininger S, Specht S, Klarmann U, Mand S, Adjobimey T, et al. Elevated adaptive immune responses are associated with latent infections of Wuchereria bancrofti. PLoS Negl Trop Dis. 2012. 6(4):e1611. [Medline]. [Full Text].
Gass K, Beau de Rochars MV, Boakye D, Bradley M, Fischer PU, Gyapong J, et al. A multicenter evaluation of diagnostic tools to define endpoints for programs to eliminate bancroftian filariasis. PLoS Negl Trop Dis. 2012 Jan. 6(1):e1479. [Medline]. [Full Text].
Dembele B, Coulibaly YI, Dolo H, Konate S, Coulibaly SY, Sanogo D, et al. Use of high-dose, twice-yearly albendazole and ivermectin to suppress Wuchereria bancrofti microfilarial levels. Clin Infect Dis. 2010 Dec 1. 51(11):1229-35. [Medline].
WHO. Global programme to eliminate lymphatic filariasis. Wkly Epidemiol Rec. 2008 Sep 12. 83(37):333-41. [Medline].
Linehan M, Hanson C, Weaver A, Baker M, Kabore A, Zoerhoff KL, et al. Integrated implementation of programs targeting neglected tropical diseases through preventive chemotherapy: proving the feasibility at national scale. Am J Trop Med Hyg. 2011 Jan. 84(1):5-14. [Medline]. [Full Text].
Tisch DJ, Alexander ND, Kiniboro B, Dagoro H, Siba PM, Bockarie MJ, et al. Reduction in acute filariasis morbidity during a mass drug administration trial to eliminate lymphatic filariasis in Papua New Guinea. PLoS Negl Trop Dis. 2011 Jul. 5(7):e1241. [Medline]. [Full Text].
Karmakar PR, Mitra K, Chatterjee A, Jana PK, Bhattacharya S, Lahiri SK. A study on coverage, compliance and awareness about mass drug administration for elimination of lymphatic filariasis in a district of West Bengal, India. J Vector Borne Dis. 2011 Jun. 48(2):101-4. [Medline].
Grieve RB, Wisnewski N, Frank GR, Tripp CA. Vaccine research and development for the prevention of filarial nematode infections. Pharm Biotechnol. 1995. 6:737-68. [Medline].
Mand S, Debrah AY, Klarmann U, Batsa L, Marfo-Debrekyei Y, Kwarteng A, et al. Doxycycline improves filarial lymphedema independent of active filarial infection: a randomized controlled trial. Clin Infect Dis. 2012 Sep. 55(5):621-30. [Medline]. [Full Text].
Ottesen EA. Filarial infections. Infect Dis Clin North Am. 1993 Sep. 7(3):619-33. [Medline].
Critchley J, Addiss D, Ejere H, Gamble C, Garner P, Gelband H. Albendazole for the control and elimination of lymphatic filariasis: systematic review. Trop Med Int Health. 2005 Sep. 10(9):818-25. [Medline].
Critchley J, Addiss D, Gamble C, Garner P, Gelband H, Ejere H. Albendazole for lymphatic filariasis. Cochrane Database Syst Rev. 2005 Oct 19. CD003753. [Medline].
Ottesen EA, Ismail MM, Horton J. The role of albendazole in programmes to eliminate lymphatic filariasis. Parasitol Today. 1999 Sep. 15(9):382-6. [Medline].
Murdoch ME. Onchodermatitis. Curr Opin Infect Dis. 2010 Apr. 23(2):124-31. [Medline].
Debrah AY, Mand S, Specht S, Marfo-Debrekyei Y, Batsa L, Pfarr K, et al. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis. PLoS Pathog. 2006 Sep. 2(9):e92. [Medline]. [Full Text].
Mand S, Pfarr K, Sahoo PK, Satapathy AK, Specht S, Klarmann U, et al. Macrofilaricidal activity and amelioration of lymphatic pathology in bancroftian filariasis after 3 weeks of doxycycline followed by single-dose diethylcarbamazine. Am J Trop Med Hyg. 2009 Oct. 81(4):702-11. [Medline].
Sanprasert V, Sujariyakul A, Nuchprayoon S. A single dose of doxycycline in combination with diethylcarbamazine for treatment of bancroftian filariasis. Southeast Asian J Trop Med Public Health. 2010 Jul. 41(4):800-12. [Medline].
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. Trans R Soc Trop Med Hyg. 2000 Jul-Aug. 94(4):437-43. [Medline].
Ottesen EA, Vijayasekaran V, Kumaraswami V, Perumal Pillai SV, Sadanandam A, Frederick S, et al. A controlled trial of ivermectin and diethylcarbamazine in lymphatic filariasis. N Engl J Med. 1990 Apr 19. 322(16):1113-7. [Medline].
Kazura JW. Higher-dose, more frequent treatment of Wuchereria bancrofti. Clin Infect Dis. 2010 Dec 1. 51(11):1236-7. [Medline].
Schiefer A, Schmitz A, Schäberle TF, Specht S, Lämmer C, Johnston KL, et al. Corallopyronin A specifically targets and depletes essential obligate Wolbachia endobacteria from filarial nematodes in vivo. J Infect Dis. 2012 Jul 15. 206(2):249-57. [Medline]. [Full Text].
Coulibaly YI, Dembele B, Diallo AA, Lipner EM, Doumbia SS, Coulibaly SY, et al. A randomized trial of doxycycline for Mansonella perstans infection. N Engl J Med. 2009 Oct 8. 361(15):1448-58. [Medline].