Pathology of lymphatic filariasis

Developing and adult worms of the humanlymphatic filarial parasites (Wuchereria bancrofti,Brugia malayi, and Brugia timori) are located mainly inthe lymphatic system and occasionally in aberrant siteslike subcutaneous and conjunctival cysts. Lymphaticpathology ranging from dilatation of lymphatic channelsand lymphangiectasia are detected on ultrasonography inapparently healthy, amicrofilaraemic, but filarial antigenpositive individuals in endemic areas. Microfilariae aredistributed in various organs and may be associatedwith immune mediated pathology at these sites; tropicalpulmonary eosinophilia is characterized by intenseimmune mediated destruction of microfilariae in thelung parenchyma. In the spleen and other sites, nodulargranulomatous lesions can occur where microfilariaeare trapped and destroyed. The finding of Wolbachiaendosymbionts in all stages of lymphatic filarial parasiteshas provided new insight on the adverse reactionsassociated with anti-filarial chemotherapy. Inflammatorymolecules mainly lipopolysaccharide (LPS)-likemolecules released from endosymbionts on death of theparasites are largely responsible for the adverse reactionsencountered during anti-filarial chemotherapy. Prenataltolerance or sensitization to parasite derived moleculescan immune-modulate and contribute to both pathologyand susceptibility/resistance to infection. Pathologicalresponses thus depend not only on exposure tofilarial antigens/infection, but also on host-parasiteendosymbiontfactors and to intervention with antifilarialtreatment. Treatment induced or host mediateddeath of parasites are associated with various grades ofinflammatory response, in which eosinophils and LPSfrom endosymbionts play prominent roles, leadingto death of the parasite, granulomatous formation,organization and fibrosis.The non-human primate (Presbytis spp.) model ofBrugia malayi developed for the tertiary screeningof anti-filarial compounds has provided uniqueopportunities for the longitudinal study of the pathologyassociated with lymphatic filariasis. The pathology in thisnon-human primate model closely follows that seen in human lymphatic filarial infections and correlates withclinical evidence of lymphatic pathology as detectedwith ultrasonography. These studies also show thatsuccessful treatment as detected by loss of motility andcalcification of worms on ultrasonography is associatedwith reversal of early dilatations of lymphatic channels.