Animal model of human disease. Lymphatic filariasis.

A Ewert, D Folse - The American journal of pathology, 1984 - ncbi.nlm.nih.gov
A Ewert, D Folse
The American journal of pathology, 1984ncbi.nlm.nih.gov
Biologic Features Lymphadenitis and lymphangitis progressing to lymphatic dysfunction can
be produced in the hind legs of domestic cats by inoculation of Brugia malayi. Infections are
established in such a way that the filariae develop in the regional lymphatics. Within 24
hours after infection on the foot, the larvae, from appropriate laboratory-reared mosquito
vectors, enter the afferent lymphatics and migrate to the periphery of the first intervening
lymph node, the popliteal. The lymphatic vessels harboring growing larvaedilate and …
Biologic Features Lymphadenitis and lymphangitis progressing to lymphatic dysfunction can be produced in the hind legs of domestic cats by inoculation of Brugia malayi. Infections are established in such a way that the filariae develop in the regional lymphatics. Within 24 hours after infection on the foot, the larvae, from appropriate laboratory-reared mosquito vectors, enter the afferent lymphatics and migrate to the periphery of the first intervening lymph node, the popliteal. The lymphatic vessels harboring growing larvaedilate and become tortuous, and the valves become incompe-tent. By 4-6 months after infection many of the worms are redistributed within the lymphatic vessels between the popliteal node and the foot.'Pathologic changes occur as the worms moult, change location, and/or die in the afferent vessels. Endothelial cells hypertrophy (Figure 1), valves thicken and become distorted, and lymph thrombi sometimes form, partially occluding the lumen (Fig-ure 2). Within the vessel walls elastic fibers and smooth muscle cells are disrupted and displaced by extensive collagen deposition. 2 Inflammatory cells accumulate along the inner lining of the lymphatic vessel, within the wall itself, and in aggregates in the surrounding connective tissue. Affected lymph nodes and vessels may increase up to 10-fold in size. Lymphedema is seenat varying times after infection and may involve the entire lower leg and foot. If a Brugia-infected leg is concomitantly infected with a microorganismsuch as Group G Streptococcus or a lymphocutaneous fungus like Sporothrix schenckii, these organisms proliferate in the static lymphand cause an increase in inflamma-tion, edema, and necrosis. 34 Chronicand repeated infections result in blockage, fibrotic lymph vessel walls, and the proliferation of fine collateral vessels that by-pass the malfunctioning node and vessels5 (Figure 3).
Comparison With Human Disease Early signs and symptoms of human lymphatic filariasis often include lymphadenitis and lymphan-gitis. However, many individuals have circulating microfilariae in the bloodstream without showing lymph node and vessel enlargement or inflammation. 6 A similar patternis seen in experimental infection in cats. The popliteal lymph node usually enlarges soon after infection but eventually returns to normal size in most cases. In some animals progressive changes occur in the lymphatics. Worm movement or death causes irritation, tissue reaction, and lymph blockage. A spectrum of tissue response to lymphatic filariasis has been reported from human autopsy cases in which the parasites were positively identified.'Many of these changes, including lymphangiectasia, lymph-angiohemorrhage, parietal lymphangitis, organizing lymphangitis, and granulomatous thrombolymph-angitis, are also seen in the catmodel. In man, transient edema and acute inflammation of lymph vessels and nodes with febrile episodes are called" filarial fevers." Experimental infection with
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