Model Number 368

Lymphatic Filariasis

Human Disease: Lymphatic Filariasis

putorius furo)

Reprinted from:

AMERICAN JOURNAL OF PATHOLOGY

1 34(6):1 373.1376, 1989

Stephen A. Hines, Richard B. Crandall,

Catherine A. Crandall, and James P. Thompson

From the Colleges of Medicine and Veterinary Medicine,

University of Florida, Gainesville, Florida

Biologic Features

Ferrets inoculated subcutaneously with infective larvae of Brugia malayi develop pathologic conditions that resemble several of the clinical syndromes recognized in human infection with lymphatic dwelling filaria, Wuchereria bancrofti, B. ma!ayi, and B. timori. Injection of larvae into the hind paw allows adult filariae to become established in regional lymphatic vessels and circulating microfilariae to appear during the 3rd month after inoculation. A persistent eosinophilia develops (1000 to 10,000/ul), concurrent with microfilaremia. Most ferrets subsequently clear circulating microfilariae before month 8 but in 10 to 15% of the ferrets there is a prolonged microfilaremia.1’2 With multiple infections, a majority of the amicrofilaremic ferrets develop conspicuous edema that has been observed to persist for more than 1 year (Figure 1).3

Characteristic pathologic changes are associated with both adult and microfilarial stages of the parasite. The establishment of adult parasites results in progressive changes in regional lymphatics demonstrated by lymphangiography. These changes include lymphangiectasia, lymphadenopathy, occlusion of major lymph collecting ducts, and development of small collateral vessels. With lymphedema, no afferent lymphatic trunks are visualized and dermal backflow is evident. This disruption of lymphatic drainage of the limb is present well before obvious lymphedema.4

Histopathologic examination of the infected limbs demonstrates marked focal granulomatous perilymphan

gitis and endolymphangitis. Affected lympnatics often have thickened fibrotic walls and valves and are occluded by inflammatory exudate (Figure 2). Draining lymph nodes (popliteal and inguinal) are initially hyperplastic and frequently have lymphatic sinusoidal dilation and histiocytosis.2 In swollen limbs skin thickening is due to edema, an inflammatory infiltrate, and variable fibrosis. Skin lymphatics are dilated, fibrotic, and associated with chronic inflammation. These vessels are obliterated focally by inflammatory infiltrates that occasionally form lymph thrombi.

Necropsy of ferrets during microfilarial clearance from the circulation or at periods up to several months after clearance reveals random, discrete, 0.5 to 2 mm white foci throughout the hepatic parenchyma. These lesions are not seen in ferrets with high sustained microfilaremia. Microscopically, the lesions are eosinophilic abscesses surrounding the remnants of degenerating microfilariae. Many of the microfllariae are encased in an eosinophilic, refractile substance characteristic of Splendore-Hoeppli (SH) deposits and morphologically identical to the Meyers-Kouwenaar (MK) body described in the tropical eosinophilia (TE) syndrome of occult human filariasis (Figure 3)5 Some ferrets also have lesions in the spleen and other organs. Pulmonary lesions often are evident only microscopically and are characterized by scattered interstitial microgranulomas that sometimes surround microfilariae encased in SH deposits. The few ferrets necropsied during or immediately after clearance of microfilariae have

For reference citation—Hines, S. A., Crandall R. B., Crandall C. A. and Thompson J. P.: Lymphatic

Filariasis, Model No. 368. In Handbook: Animal Models of Human Disease. Fasc. 18. Edited by C. C.

Capen, T. C. Jones and G. Migaki. Registry of Comparative Pathology, Armed Forces Institute of Pathology,

Washington, DC (1991).