Model Number 368

.

Lymphatic Filariasis

Human Disease: Lymphatic Filariasis

Animal Model:

Brugia maiayi infection in the Ferret (Mustela

putoriusfuro)

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 resem-

ble several of the clinical syndromes recognized in human

infection with lymphatic dwelling filaria, Wuchereria ban-

crofti, 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 persis-

tent eosinophilia develops (1000 to 10,000/ul), concur-

rent 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 es-

tablishment of adult parasites results in progressive

changes in regional lymphatics demonstrated by lymph-

angiography. 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 lym-

phatic 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 lympnaiius 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 fre-

quently have lymphatic sinusoidal dilation and histio-

cytosis.2 In swollen limbs skin thickening is due to edema,

an inflammatory infiltrate, and variable fibrosis. Skin lym-

phatics are dilated, fibrotic, and associated with chronic

inflammation. These vessels are obliterated focally by in-

flammatory 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 Mey-

ers-Kouwenaar (MK) body described in the tropical eosin-

ophilia (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 micro-

scopically and are characterized by scattered interstitial

microgranulomas that sometimes surround microfilariae

encased in SH deposits. The few ferrets necropsied dur-

ing 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).