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 doses of 25 and 100 mg/kg to Acanthocheilonema viteae, Brugia malayi, and Litomosoides sigmodontis infected Mastomys coucha on various dates during prepatency, aiming to affect third stage larvae, fourth stage larvae or preadult worms. Microfilaraemia levels were controlled in comparison to untreated controls until necropsies were performed 100 days p.i. (A. viteae, L. sigmodontis) and 150 days p.i. (B. malayi) to determine the numbers of surviving worms and the condition of intrauterine developing stages. A significant proportion (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 insignificant effects on the developing parasites, however, it strongly reduced microfilaraemia levels caused by surviving worms in the early phase of patency. Larval and preadult B. malayi and L. sigmodontis were not killed by Bay 44-4400 to a significant degree. Microfilaraemia developing by surviving parasites was generally and significantly reduced throughout the observation period when treatment was performed to affect the preadult parasites. In the other cases variable results were obtained. Intrauterine early embryonic stages were found to be pathologically altered in worms which had been treated at a preadult stage.
Zahner
H
H
Institute of Parasitology, Justus Liebig University Giessen, Rudolf-Buchheim-Strasse 2, D-35392, Giessen, Germany. horst.zahner@vetmed.uni-giessen.de
Taubert
A
A
Harder
A
A
von Samson-Himmelstjerna
G
G
D000279:Administration, Cutaneous; D000818:Animals; D017178:Brugia malayi / Q000187:drug effects*; D004153:Dipetalonema / Q000187:drug effects*; D004154:Dipetalonema Infections / Q000188:drug therapy* / Q000469:parasitology; D004195:Disease Models, Animal; D005368:Filariasis / Q000188:drug therapy* / Q000469:parasitology; D005369:Filaricides / Q000494:pharmacology / Q000627:therapeutic use*; D005370:Filarioidea / Q000187:drug effects*; D007814:Larva / Q000187:drug effects; D008842:Microfilariae / Q000187:drug effects; D009115:Muridae; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*
C439266:Bay 44-4400; D005369:Filaricides; D010456:Peptides, Cyclic