In putatively chronic cases, nodules were found additionally

on the tunica adventitia (up to 2.5 cm diameter). Some of these nodules resembled lymph nodes (Fig. 3C). Older, larger nodules were capsular and contained calcified material and/or a creamy yellow, caseous exudate. On a few occasions, marked atrophy was apparent where a large, well-defined nodule spanned the majority of the aorta wall originating from the tunica media. No parasites were found free, or partially free, in the lumen of the vessel. Microscopically lesions due to worm presence were principally found in the tunica media, but Trametinib some encroached the intima and, in chronic infections, the adventitia. Cell responses ranged from no or few inflammatory cells in the early stage (Fig. 4), to high numbers of granulocytes, macrophages, fibroblasts and multinucleate giant cells in older lesions. A degenerating worm with a surrounding inflammatory infiltrate could be found in the same histological section as a viable worm with no inflammatory response or an empty tunnel. This suggests that individual hosts are repeatedly re-infected. Worms appeared to reside within a cavity, with a space between the worm section

and the host-derived lining. Factor VIII-related antigen staining (data not shown) showed this lining not to be composed of endothelia, but rather to be continuous with the tunica media. Degenerate, dead and calcified worms caused a more marked inflammatory response learn more consisting predominantly of macrophages (Fig. 5A). Typically, macrophages of one or several layers occupied the region closest to the worm cuticle, with small numbers of eosinophils

(Fig. 5B) and neutrophils (Fig. 5A) more peripherally. Chronic inflammation (composed of lymphocytes, plasma cells and multinucleate giant cells) characterised the most peripheral aspect of the local immune response (Fig. 5C). Fibroblasts and collagen were interspersed amongst the inflammatory cells. A thin capsule of circularly arranged fibrous tissue circumscribing the cavity was apparent in older lesions (granuloma formation). Microvasculature was apparent in some capsules, but not all, and evidence of vascular injury was present in several specimens (Fig. 5B). Large multinucleate giant cells were often found in regions of the media not occupied by a parasite (Fig. 5D) and perivascularly. Inflammatory cells were never found Cysteine desulfurase adherent to the worm cuticle, and no degranulation onto the cuticle was observed. Prussian blue staining did not reveal the presence of haemosiderin within the gut of worm sections; and von Kossa staining did not detect tissue mineralization in the samples examined (data not shown). The majority of filarial nematodes have been found to contain the endosymbiont Wolbachia. It has been suggested that Wolbachia may be important in evading the host immune response in those species of Onchocerca associated with the bacteria ( Brattig et al., 2001 and Nfon et al., 2006). In the present study, O.