Dipetalonema viteae and Brugia pahangi transplant infections in gerbils for use in antifilarial screening

Abstract

Transplanted infections of Dipetalonema viteae and Brugia pahangi have been evaluated as tools for experimental chemotherapy. Attempts were made to establish these filariae in similar pharmacokinetic sites within the same host, so that direct comparisons of in vivo drug susceptibilities could be made. Unfortunately, it was not possible to establish B. pahangi in the subcutaneous tissues, the preferred site of D. viteae. Therefore, intraperitoneal B. pahangi and subcutaneously implanted D. viteae in gerbils were used for the study. D. viteae infections were significantly enhanced by concomitant infections with B. pahangi, while B. pahangi infection rates were unaffected by the presence of D. viteae. Experiments with amoscanate, CGP6140 and Mel W demonstrated the importance of employing both B. pahangi and D. viteae for antifilarial discovery work and the fundamental effect of parasite location on drug efficacy. D. viteae rapidly migrate from the peritoneal cavity of gerbils following implantation; twenty one hours after infection 73% of transplanted worms were found in the subcutaneous tissues. It was shown that the migration response could be used as a stringent parameter for demonstrating antifilarial activity. D. viteae were exposed to antifilarial drugs for 24 hours in vitro, washed and implanted into the peritoneal cavity of gerbils. At autopsy, 5 days later, 10−8M ivermectin and milbemycin D had prevented migration; CGP6140, amoscanate, suramin, flubendazole and furapyrimidone were also detected at <10−6M using this parameter. In all cases the migration response was more sensitive to drugs than parasite kill. Ivermectin's ability to inhibit worm migration through the tissues is discussed, with respect to the role of itinerant males in the reproductive cycle of Onchocerca volvulus.

Chemotherapy of Onchocerca lienalis microfilariae in mice: a model for the evaluation of novel compounds for the treatment of onchocerciasis

“…The most widely used models for chemotherapy studies at present are Brugia pahangi, transplanted into the peritoneal cavity of the jird (Meriones unguiculatus), and Acanthocheilonema viteae infections in the jird or multimammate rat {Mastomys natalensis), (reviewed by DENHAM in 1979 andby STRIEBEL in 1986). Some researchers have recently adopted the dual implant screen, which employs adults of both B. pahangi and A. viteae transplanted into the same jird (WHO, 1985a;COURT et al, 1988). With infective larvae-induced infections both species of parasite have blood-dwelling microfilariae (mf), while mf may be concentrated in the peritoneal cavity if adult worms are transplanted into this site.…”

Human filariasis—contributions of the Litomosoides sigmodontis and Acanthocheilonema viteae animal model

“…A. viteae was one of the first rodent filarial models used for preclinical drug testing, demonstrating (in parallel with Brugia pahangi ) macrofilaricidal efficacy of flubendazole in jirds in the 1970s/1980s (Denham et al 1979 ; Denham 1980 ; Court et al 1988 ) and the recrudescence of MF in amicrofilaremic golden hamsters after treatment with immunosuppressive drugs (e.g., methyl prednisolone acetate and cyclophosphamide) (Neilson 1978 ). Subsequent studies in the A. vit ea e Mastomys model showed a predominant microfilaricidal efficacy of the macrocyclic lactones ivermectin and moxidectin (Zahner et al 1987 ; Rao et al 1987 ; Schares et al 1994 ) and addressed the adverse reactions caused by diethylcarbamazine (DEC) (Singh et al 1985 ).…”