The lymphatic pathology of chronic Brugia pahangi infection in the dog

Abstract

The dog infected with Brugia pahangi is an excellent model for studying the clinical and immunological pathogenesis of lymphatic filarial infection and disease. Dogs demonstrated a range of clinical changes including varying levels of microfilaraemia, episodic lymphadenopathy, lymphangitis, and limb oedema similar to the clinical spectrum reported in man. Histologically, tissues from parasite-infected dogs were characterized by fibrosis of the lymph nodes and their afferent and efferent lymphatic ducts in the infected limbs. Some nodes were atrophied while others were characterized by reactive hyperplasia. Duct walls of some afferent lymphatics were thickened with a mononuclear inflammatory infiltrate. Parasite antigen deposition was detected in the subcapsular sinuses and middle of germinal centres of infected popliteal lymph nodes, using an immunohistochemical technique.

Association of elevated lymph node cell release of histamine and tumor necrosis factor with genetic predisposition to limb edema formation in dogs infected with Brugia pahangi.

“…Whereas loss of function indicated by dye leakage correlated well with edema formation, the structural changes, no matter how dramatic, did not correlate with coincident or subsequent edema manifestation. 1 This is similar to observations made in human lymphatic filariasis cases. [2][3][4][5] These observations support the hypothesis that edema formation in lymphatic filariasis involves complex host-parasite interactions in addition to or exclusive of dilation and deformation of lymphatic ducts, which have been proposed to be associated with the mechanical presence and physical activity of adult worms in ducts.…”

“…The host-parasite interactions most often cited and studied in lymphatic filariasis are those dependent upon an active immune response involving antigen-specific [6][7][8][9] and antigen-nonspecific components. [10][11][12][13] In our description of the interaction of the lymphatic filarial parasite, B. pahangi, with its natural host, the dog, we have reported acute and chronic pathologic lesions, 1 pathogenesis, 1,10 and immunologic responses 6 that are nearly identical with those reported in human lymphatic filariasis. [2][3][4][5] In addition, we have reported on a strong familial association between amicrofilaremia and edema formation in its acute and chronic manifestation.…”

“…Phenotypic status (E or NE) was determined by the risk for development of acute limb edema formation at the onset of patency after infection, as judged by previous breeding and infection experiments. 1,10,14,17 At the time puppies were born all mothers had patent Brugia infections. Brugia pahangi infective larvae (L3) were obtained as previously described from infected jirds.…”

Canine Filarial Infections in a HumanBrugia malayiEndemic Area of India

“…So, the possibility for dogs acting as reservoirs of B. malayi in these areas is very remote. In addition, the clinical symptoms reported in dogs of Thrissur, Kerala [20], were similar to that of dogs infected with B. pahangi [37] which include varying levels of microfilaraemia, episodic lymphadenopathy, lymphangitis, and limb oedema. For these reasons, the detection of B. malayi in dogs of Thrissur might be a false detection.…”

Challenges in drug discovery for novel antifilarials

“…Among the early reports is a description of the biological features of infection in domestic cats using B. malayi , a human pathogen [87] . While other Brugia spp., such as B. pahangi , in the cat or dog are available [89,91] , the B. malayi animal model in the multimammate mouse, Mastomys coucha and the Mongolian jird, Meriones unguiculatus [92][93][94][95] , are by far the most suitable as a source of viable mf and adult worms for in vitro compound screening. In addition, the rodent model of B. malayi also allows for further in vivo testing (secondary screen) of in vitro active compounds.…”