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

Published online by Cambridge University Press:  05 June 2009

J. P. Court ,
J. N. Stables ,
G. M. Lees ,
M. R. Martin-Short  and
R. Rankin
J. P. Court
Affiliation:
Department of Biochemical Microbiology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent, BR3 3BS, England
J. N. Stables
Affiliation:
Department of Biochemical Microbiology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent, BR3 3BS, England
G. M. Lees
Affiliation:
Department of Biochemical Microbiology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent, BR3 3BS, England
M. R. Martin-Short
Affiliation:
Department of Biochemical Microbiology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent, BR3 3BS, England
R. Rankin
Affiliation:
Department of Biochemical Microbiology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent, BR3 3BS, England
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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.

Keywords

Dipetalonema viteaeBrugia pahangifilaricidestransplanted infectionsgerbil
Type
Research Papers
Information
Journal of Helminthology , Volume 62 , Issue 1 , March 1988 , pp. 1 - 9
Copyright
Copyright © Cambridge University Press 1988

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References

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