The potential of mice as animal models for antifilarial screening.
Transplanted infections of Brugia pahangi and Dipetalonema viteae in male BALB/c and CDI mice were investigated as models for evaluating potential antifilarial compounds. The physiology and genetics of the above mouse strains are better defined than any of the rodent species currently used for primary in vivo screening, facilitating a more reproducible means for predicting the filaricidal activity of compounds. The recoveries of B. pahangi macrofilariae, implanted intraperitoneally were greater than or equal to 50% up to six weeks after implant in both CDI and BALB/c mice. The recoveries of D. viteae macrofilariae, implanted subcutaneously, were greater than 50% up to four weeks post implant but had fallen to less than 30% by six weeks. The survival of B. pahangi and D. viteae macrofilariae simultaneously implanted into mice mimicked that seen with the mono-infections, but significantly better recoveries were obtained from dual implanted CDI mice compared to the BALB/c mice when the numbers of macrofilariae implanted were varied. Standard antifilarials were evaluated against D. viteae and B. pahangi dual implanted into either CDI mice or gerbils. The mouse dual implant detected significant worm reductions against D. viteae, B. pahangi or both with all antifilarials tested except CGP 6140. Similarly under the test conditions CGP 6140 was not detected in the gerbil assay, but there were marked differences in the results obtained with the mice and gerbil models. The reasons for these differences are discussed.
Stables
J N
JN
Department of Biochemical Microbiology, Wellcome Research Laboratories, Beckenham, Kent, England.
Lees
G M
GM
Rankin
R
R
D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D002009:Brugia / Q000187:drug effects / Q000254:growth & development; D004153:Dipetalonema / Q000187:drug effects / Q000254:growth & development; D004154:Dipetalonema Infections / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004605:Elephantiasis, Filarial / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005368:Filariasis / Q000188:drug therapy*; D005369:Filaricides / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000871:Anthelmintics; D005369:Filaricides