Lymphovenous Canada: Filariasis Poster

This image was created in 2003 by Marisa Bonofiglio (BSc, MScBMC) graduate student in medical illustration (Biomedical Communications) at the University of Toronto, with the scientific advice of Professor Jack Hay University of Toronto, Immunology Department.

This medical graphic won a "Student Award of Merit in Instructional Colour" in the July 2003 Association of Medical Illustrators Annual Conference in New Orleans, Louisiana. It is reproduced for Lymphovenous Canada with the permission of the artist.

This graphic is the artists depiction of a new theory on the cause of Lymphatic Filariasis, based on recent scientific from the following sources:

• Taylor MJ, Cross HF, Bilo K. "Inflammatory responses induced by the filarial nematode Brugia malayi are mediated by lipopolysaccharide-like activity from endosymbiotic Wolbachia bacteria." J Exp Med 2000 April 17:191(8):1429-36. Cellular Immunology Laboratory, Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom. E-mail: mark.taylor@liverpool.ac.uk
• Freedman, David O, author of "Filariasis" (Chapter 434, pp 1990-1992) in Goldman: Cecil Textbook of Medicine, 21st ed., Copyright 2000 W.B.Saunders Company.

As the research above suggests, Lymphatic Filariasis begins with the infectious bite of a mosquito. Worm larvae migrate to lymphatic capillaries and lymphatic vessels where they continue to mature into adult worms.

An initial acute inflammatory response is a natural reaction to any foreign substance which enters the body. In this case our bodies' defense cells attack the worm and begin to digest it. An intracellular endosymbiotic bacteria (Wolbachia sp.) which lives inside the worm, is released as a body's defence cells attack it. Wolbachia induces TNF-a (tumour necrosis factor alpha) which is followed by (induces) a granulomatous inflammatory response, triggering the following symptoms associated with lymphedema: vessel dilatation, intramural polyposis, hypertrophy of vessel walls, and eventually, **fibrosis** in the vessel walls. This diminishes normal lymphatic function.

Over time, fibrosis and obstruction of lymph flow within the lumen lead to irreversible elephantiasis of the affected part. The lymph node itself enlarges, and adult worms are found to reside within. The worm itself does not appear to cause blockage of the vessel, but rather the bacteria within the worm which triggers the inflammatory response.

Note to reader: Since this poster was put together a number of new developments have taken place. Dr. Mark Taylor has been part of an international team of researchers which has demonstrated the effectiveness of an inexpensive antibiotic, doxycycline, which they have found cures most cases of advanced elephantiasis. The antibiotic kills the parasite through indirect means by destroying a bacteria inside the filariasis worm, which the parasite relies on to survive. The study on doxycycline and lymphatic filariasis was published in the June 18, 2005 issue of the medical journal, The Lancet. (Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A. (2005). Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet 365 (9477), 2116-21.)

Writes Dr. Taylor, Head of the Filariasis Research Laboratory and Director of Studies for B.Sc. in Tropical Disease Biology at the Liverpool School of Tropical Medicine:

The areas of this poster, which could do with revision, relate mostly to the parasitological facts. In brief, the major ones include; 1) Mosquitoes release third-stage (L3) infective larvae onto the skin, which migrate into the wound left by the mosquito proboscis. The microfilariae are the first stage larvae, which are found in the blood and are consumed when the mosquito takes the first blood meal from an infected person. The microfilariae (L1), moult twice and develop over a couple of weeks (L1-L2-L3) before becoming L3 infective larvae able to infect another host. 2) Adult worms mostly live in the dilated afferent lymphatic vessels rather than the lymph node (although in children this can be a site of infection). Lymph node enlargement is due to the immune response to the infection rather than the growth of adult worms."

For more information view the following publications:

• Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A. (2005). Lancet 365 (9477), 2116-21.
• The role of Wolbachia in the biology and pathogenesis of filariasis. Joseph Turner, Jeremy M. Foster, Mehul Ganatra, Barton E. Slatk and Mark Taylor. Pages 187-195, In Insect Symbiosis, Volume 2 (K. Bourtzis and T.A. Miller, eds., 2006.

Marisa Bonofiglio may be approached for permission to reproduce this graphic for educational purposes. Use of the image without permission of the artist is strictly prohibited. She can be contacted at: marisa.bonofiglio@utoronto.ca or marisa.bonofiglio@gmail.com. Her web site is located at: www.marisabonofiglio.com

Click the image to see a larger, high-resolution version of the poster. This is a large file which may take a while to download.