BLOCKAGE OF SKIN INVASION BY SCHISTOSOME CERCARIAE BY SERINE PROTEASE INHIBITORS

Abstract. Invasion of skin by schistosome cercariae is facilitated by a serine protease secreted from the acetabular cells of cercariae in response to skin lipid. Specific inhibitors of the protease, when applied to human skin in for-mulations designed to retain the inhibitor on and in the upper stratum corneum layers, block cercarial invasion of human skin. Both peptide-based, irreversible inhibitors and non-peptide, reversible inhibitors block cercarial invasion when applied in a propylene glycol: isopropyl alcohol (3:1) formulation in vitro. Arrest of cercarial invasion could be achieved even after immersion of treated skin in water for 2 hr. Peptide-based irreversible inhibitors in the presence of three different Topicare Delivery Compoundst optimized arrest of cercarial invasion. The three Topicare Delivery Compoundst applied alone prevented 80–100 % of cercarial invasion. With inclusion of the inhibitor, there was 97– 100 % inhibition in vitro. The optimal formulation with inhibitor was then applied to the tails of BALB/c mice, and the mice were exposed to 120 cercariae by tail immersion. With the carrier lotion alone, there was a 50 % reduction in worm burden and a 70 % reduction in egg burden. When inhibitor was included, an 80 % reduction in worm burden and a 92 % reduction in egg burden was observed. The initial step in infection of the human host by schis-tosome cercariae is penetration of intact skin by aquatic cer-cariae.1,2 Attempts to develop a topical formulation to pre