Enlarge Lymph Nodes, Lymphedema. Lymphatic Cancer?

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.)

“Your poster is a good attempt at an overview of what is a complex series of events, which result in filarial lymphoedema, only some of which we understand. Since the discovery of the role of Wolbachia in filarial disease pathogenesis, the field has grown and been supported by further experimental and clinical studies, the most exciting of which is the ability to use doxycycline antibiotics to kill the adult worms and resolve LF pathology. As a result of this success we have recently been awarded a $23m grant from the Bill and Melinda Gates Foundation to continue this work to find new anti-wolbachia treatments that can be used as tools for public health in the endemic areas afflicted by filariasis.

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.
Lymphovenous Canada: Filariasis Poster


This image was created in 2003 by Marisa Bonofiglio (BSc, MScBMC) as a graduate student in medical illustration (Biomedical Communications) at the University of Toronto, with the scientific advice of Dr. Jack Hay (University of Toronto, Immunology Department). Use of the image for purposes other than personal education without permission of the artist is strictly prohibited. Please feel free to contact her at: marisa.bonofiglio@utoronto.ca

View her on-Line portfolio: http://www.bmc.med.utoronto.ca/~marisabonofiglio/


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