Sections

Filariasis

Medication

Medication Summary

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

Mass drug administration in filariasis reduces the transmission of filarial infection and disease morbidity by decreasing the burden of microfilaremia, resulting in suboptimal levels for transmission by disease vectors.^{[49, 50, 51, 52, 53, 54]}

Class Summary

Anthelminthic agents include the macrocyclic lactone derivatives ivermectin and moxidectin, piperazine derivatives, and benzimidazole derivatives.

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

- Inhibition of microtubules, causing irreversible block of glucose uptake

- Tubulin polymerization inhibition

- Depolarization of 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

Ivermectin (Mectizan)

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Ivermectin is a potent microfilaricide against W bancrofti and O volvulus; however, it has limited macrofilaricidal activity.^[74]

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

Moxidectin

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Moxidectin, a macrocyclic lactone, is an anthelmintic indicated for the treatment of onchocerciasis due to Onchocerca volvulus in patients aged 12 years and older. Plasma half-life is 20-43 days and thereby reduces and maintains low skin microfilarial density effectively. Moxidectin does not kill adult O volvulus. Follow-up evaluation is advised. Safety and efficacy of repeat administration has not been studied.

Diethylcarbamazine (Hetrazan)

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Diethylcarbamazine (DEC) is commonly used in lymphatic filariasis and acts as both a microfilaricidal and macrofilaricidal agent. Its precise mechanism of action is not understood, but it has been shown to induce immobilization of microfilariae by using hyperpolarization effects to decrease muscle activity. Alteration of the surface membrane also occurs, with enhanced destruction by the host's immune system. Evidence exists that DEC may enhance adhesion of granulocytes via antibody-dependent and -independent mechanisms. Hypotheses also include interference by microfilarial intracellular processing and transport of specific macromolecules by DEC.^[75]

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

Suramin

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

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

Mebendazole

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Mebendazole causes worm death by selective and irreversible blockade of uptake of glucose and other nutrients in a susceptible adult intestine where helminths dwell.

Albendazole

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

Class Summary

These agents may provide an alternative to traditional antihelminthics.

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

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Doxycycline is a broad-spectrum, synthetically derived, bacteriostatic antibiotic in the tetracycline class. In filariasis, it is primarily used to target Wolbachia, an endosymbiotic bacterium in onchocerciasis and lymphatic filariasis. Doxycycline is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.

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

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Media Gallery

Filariasis. This figure displays the life cycle of Wuchereria bancrofti in humans and mosquito vectors (ie, Aedes, Anopheles, Culex, Mansonia species). Life cycles of other lymphatic nematodes (ie, Brugia malayi, Brugia timori) are identical, while the life cycles for other filariae differ in the body location of adult worms, the microfilariae present, and the arthropod intermediate hosts and vectors.
Filarial abscess scar on the left upper thigh in a young male who is positive for Wuchereria bancrofti microfilariae
Lymphatic filariasis resulting from Wuchereria bancrofti infection may result in limb lymphedema, inguinal lymphadenopathy, and hydrocele. Photograph taken by Professor Bruce McMillan and donated by John Walker, MD.
Filariasis. Unilateral left lower leg elephantiasis secondary to Wuchereria bancrofti infection in a boy.
Filariasis. This is a close-up view of the unilateral lower leg elephantiasis shown in the previous image. Note the lymphedema and typical skin appearance of depigmentation and verrucous “warts.”
Filariasis. Lateral view of the right outer aspect of a leg affected by elephantiasis secondary to Wuchereria bancrofti infection.
Filariasis. Inner aspect of the lower leg of the male patient in the previous image, showing gross elephantiasis secondary to Wuchereria bancrofti infection.
Filariasis. Unilateral left hydrocele and testicular enlargement secondary to Wuchereria bancrofti infection in a man who also was positive for microfilariae.
Filariasis. Bilateral hydrocele, testicular enlargement, and inguinal lymphadenopathy secondary to Wuchereria bancrofti infection.
Filariasis. Adult worms of Wuchereria bancrofti in cross section isolated from a testicular lump.
Filariasis. Microfilaria of Wuchereria bancrofti in a peripheral blood smear.
Filariasis. Appearance of microfilariae after concentration of venous blood with a Nuclepore filter.
Filariasis. Onchocercomas of the forearm skin (sowda) in a Sudanese man.
Filariasis. Adult Onchocerca volvulus contained within onchocercomas of the skin.
Filariasis. Microfilariae of Loa loa detected in skin snips.
Filariasis. Microfilariae of Mansonella perstans in peripheral blood.

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Author

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

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

Siddharth Wayangankar, MD, MPH is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Rhett L Jackson, MD, MACP David Ross Boyd Professor and Chief, Section of General Internal Medicine, Department of Medicine, University of Oklahoma College of Medicine; Assistant Chief, Medicine Service, Oklahoma City Veterans Affairs Hospital

Rhett L Jackson, MD, MACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association

Disclosure: Nothing to disclose.

Brian F Lich, MD, DTM&H, FACP Director of Global Health and Social Justice, Assistant Professor of Medicine, Associate Program Director, Internal Medicine Training Program, Department of Medicine, University of Oklahoma College of Medicine

Brian F Lich, MD, DTM&H, FACP is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Acknowledgements

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

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

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

Michael D Nissen, MBBS, FRACP, FRCPA Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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

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

Disclosure: Novartis Honoraria Speaking and teaching

John Charles Walker, MSc, PhD Head, Department of Parasitology, Center for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, Australia; Senior Lecturer, Department of Medicine, University of Sydney, Australia

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

Filariasis Medication

Medication Summary

Anthelminthics