Effects of Bay 44-4400, a new cyclodepsipeptide, on developing stages of filariae (Acanthocheilonema viteae, Brugia malayi, Litomosoides sigmodontis)in the rodent Mastomys coucha

Bay 44-4400 was used as a spot on formulation and administered in single do ses of 25 and 100 mg/kg to Acanthocheilonema viteae, Brugia malayi, and Lit omosoides sigmodontis infected Mastomys coucha on various dates during prep atency, aiming to affect third stage larvae, fourth stage larvae or preadul t worms. Microfilaraemia levels were controlled in comparison to untreated controls until necropsies were performed 100 days p.i. (A. viteae, L. sigmo dontis) and 150 days p.i. (B. malayi) to determine the numbers of surviving worms and the condition of intrauterine developing stages. A significant p roportion (86-100%) of larval and preadult stages of A. viteae were killed by Bay 44-4400 at a dose of 100 mg/kg. A dose of 25 mg/kg had only insignif icant effects on the developing parasites, however, it strongly reduced mic rofilaraemia levels caused by surviving worms in the early phase of patency . Larval and preadult B. malayi and L. sigmodontis were not killed by Bay 4 4-4400 to a significant degree. Microfilaraemia developing by surviving par asites was generally and significantly reduced throughout the observation p eriod when treatment was performed to affect the preadult parasites. In the other cases variable results were obtained. Intrauterine early embryonic s tages were found to be pathologically altered in worms which had been treat ed at a preadult stage. (C) 2001 Elsevier Science B.V. All rights reserved.