Screening Large Numbers of New Chemical Compounds for Anthelmintic Activity Using Infections with Nippostrongylus muris in Mice

Abstract

Factors of importance in selecting a parasite-host combination for use in large-scale screening of new compounds for leads to anthelmintic activity are: (1) ease of producing standardized exptl. infections in large numbers of test animals, (2) smallness of host in order to conserve drug, (3) availability of uniform strain of host in large numbers at low cost, (4) ease of caring for and dosing host, (5) an easily read endpoint, and (6) reproducibility of results. Experimentally induced infections with N. muris in young mice (10-14 g.) using worm counts at autopsy as the endpoint, have been found to meet to a satisfactory extent all of the above requirements and permits the screening of large numbers of new compounds using as little as 0.3 g. of each compound. Greatest emphasis has been on drug-diet method of drug admn. Standard anthelminthics such as hexylresorcinal, pheno-thiazine, beta-naphthol, santonin, gentian violet and arecoline, which are not too volatile to be tested in this way, are ineffective. Of over 1500 compounds tested thus far, the only ones found to have unquestionable activity, namely trichloroacetamide and related compounds, only affect the larval stages migrating in the tissues. Trichloroacetamide is not active against Strongyloides ratti or Trichinella spiralis in rats; Litomosoides carinii in cotton rats; Hvmenolepis nana or oxyurids in mice; nor Schistosoma mansoni in mice.