J Parasitol. 2013 Feb;99(1):168-9.

Efficacy of ivermectin versus dual infections of Haemonchus contortus and Heligmosomoides polygyrus in the mouse.

Ostlind DA, Mickle WG, Smith S, Ewanciw DV, Cifelli S.

Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.

 

ABSTRACT 

This report describes a novel assay for the detection of gastrointestinal anthelmintics using mice infected with Haemonchus contortus and adapted to the 1 animal per group protocol.   Mice infected with both H. contortus and Heligmosomoides polygyrus were fed ivermectin-medicated diets for 6 days.  A dietary level of 0.09375 ppm was 98.1% effective against the 0 to 6-day-old abomasal stomach worm of sheep, whereas a level of  0.75 ppm reduced the 3 to 9-day-old Hpolygyrus worm burden by 94.0%.  H. contortus was approximately 8-fold more sensitive to ivermectin than H. polygyrus in this model.  The sensitivity of this assay rivals that of the gerbil-Trichostrongylus colubriformis model.

PMID: 23145469

 

SUPPLEMENT

The first operational in vivo assay to use the 1-animal/ group screening concept was introduced at the Merck Institute for Therapeutic Research in 1968.  The concept was used for more than 25 yrs at the Merck Research Laboratories.    The 1-animal/group screening protocol was used to discover the fasciolicide, clorsulon in 1969 (Ostlind et al., 1977), the avermectins in 1975 (Stapley and Woodruff, 1982), paraherquamide (Ostlind et al., 1990), the systemic ectoparasiticide nodulisporic acid in 1992 (Ostlind et al., 2001) as well as the development of the anthelmintic eprinomectin (Shoop et al., 1996), thus validating the concept.  All of the major anthelmintics commercially available up to 1996 (DA Ostlind retired) that were tested demonstrated their expected activity against  Haemonchus contortus, thus validating the concept.    It also fascilitated the in vivo testing of natural products (Campbell, 1992).

The results described herein led to the development of an assay (unpublished data) whereby the  anthelmintic and systemic ectoparasiticide activity could be simultaneously ascertained in a single rodent and was in operation for more than 10 yrs.

 

References

1.      Ostlind DA, Campbell WC, Riek RF, Baylis P, Cifelli S, Hartman RK, Lang RK, Butler RW, Mrozik H, Bochis RJ, Eskola P, Linn BO, Lusi A, Wu MT, Shunk CH, Peterson LH, Milkowski JD, Hoff DR, Kulsa P and Harman RE  1977 The efficacy of 4-amino-6-trichloroethenyl-1,2-benzene disulphonamide against liver fluke in sheep and cattle.  British Veterinary Journal 133:  211-214.

2.      Stapley EO and Woodruff HB 1982  Avermectins, antiparasitic lactones produced by Streptomyces avermitilis isolated from a soil in Japan.  In “Trends in Antibiotic Research” (H. Umezawa, AL Demain, T Hata and CR Hutchinson, eds.), pp. 154-170.  Jpn. Antibiot. Res. Assoc., Tokyo.

3.      Ostlind DA, Mickle WG, Ewanciw DV, Andriuli FJ, Campbell WC, Hernandez S, Mochales S and Munquira E  1990  Efficacy of paraherquamide against immature Trichostrongylus colubriformis in the gerbil (Meriones unguiculatis).  Research in Veterinary Science 48:  260-261.

4.      Campbell WC  1992  The genesis of the antiparasitic drug Ivermectin. In:  Inventive Minds (RJ Weber and DN Perkins, eds.), pp. 194-214.  Oxford University Press, New York.

5.      Shoop WL, Demontigny P, Fink DW, Williams JB, Egerton JR, Mrozik H, Fisher MH, Skelly BJ and Turner MJ  1996  Efficacy in sheep and pharmacokinetics in cattle that led to the selection of eprinomectin as a topical endectocide for cattle.  International Journal for Parasitology, 26:  1227-1235.

6.      Ostlind DA, Cifelli S, Conroy JA, Mickle WG, Ewanciw DV, Andriuli FJ and Ho P  2001 A novel Cimex lectularius-rodent assay for the detection of systemic ectoparasiticide activity.  Southwestern Entomologist 26:  181-186.

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