Studies on the Stage of Action of Ionophorous Antibiotics against Eimeria

Abstract

Sporozoites of Eimeria tenella were treated with different anticoccidial drugs in vitro and their subsequent viability was tested by inoculating them into chicken embryos. Monensin, salinomycin, lasalocid, and arprinocid, at concentrations between 0.01 and 1.0 micrograms/ml, greatly reduced sporozoite viability as judged by mortality, hemorrhage and specific lesions in the embryo chorioallantois. Monensin was also effective in reducing the viability of sporozoites of E. mivati and E. tenella as judged by oocyst production occurring in embryos; activity of monensin was greater against E. tenella than against E. mivati. Monensin (0.1 mg) inoculated into embryos inhibited development of E. tenella. Oocysts which were produced in the presence of the drug sporulated normally and sporozoites obtained from them were fully infective. By initiating treatment of chickens with monensin at different times in relation to infection, it was shown that the drug exerts its anticoccidial effect on the primary invasive stage and on the gametogonous stage of E. tenella and E. necatrix. The effect of gametogony was tested by initiating infections with second generation merozoites of E. tenella. Significant reduction in oocyst production occurred in three of four strains of E. tenella tested. Medication with monensin initiated before merozoite inoculation was effective in inhibiting oocyst production, but medication starting 5 hr after merozoite inoculation was not. This differed from the effects of arprinocid and sulfaquinoxaline which were expressed both before and 5 hr after merozoite inoculation. The results show that the ionophorous anticoccidial drugs exert their anticoccidial action primarily against the invasive stages of Eimeria.

The infectivity ofEimeriasporozoites recovered from Monensin medicated chickens1

“…(1981) demonstrated that the amount of the ionophorous antibiotics accumulated by cell-free E. tenella sporozoites during in vitro pretreatment is sufficient to reduce host cell penetration and virtually eliminate parasite development in a cell culture system. These results were further supported by the work of Long and Jeffers (1982) who demonstrated that sporozoites of E. tenella and if. mitis treated with monensin in vitro failed to develop when inoculated into chicken embryos.…”

“…In any case, the results of these studies confirm the importance of continuously maintaining an effective concentration of monensin in the lumen of the intestine to assure optimum anticoccidial activity. Furthermore, continuous uninterrupted monensin medication produces an additional reduction in gametogony mediated through uptake of the drug by merozoites during transition from the asexual to the sexual life-cycle stages as previously reported by Long and Jeffers (1982).…”

“…DISCUSSION When the present studies were initiated, it was known that pretreatment of Eimeria sporozoites with ionophorous anticoccidials resulted in a reduction in invasion of cells in vitro and an almost complete inhibition of asexual development for those which did invade (Smith et al, 1981). A similar observation was later made with monensin alone in a chicken embryo system (Long and Jeffers, 1982). Although certainly demonstrative, these studies suffer from two shortcomings.…”

Coccidiosis in poultry: anticoccidial products, vaccines and other prevention strategies

“…These drugs are accumulated by extracellular stages (like sporozoites and merozoites) of the parasite in the lumen of the intestine (Long and Jeffers 1982).…”

First solid state alkaline-earth complexes of monensic acid A (MonH): crystal structure of [M(Mon)2(H2O)2] (M = Mg, Ca), spectral properties and cytotoxicity against aerobic Gram-positive bacteria

“…Recently the most powerful drugs in veterinary medicine effective against coccidiosis and infections induced by Gram-positive organisms represent the group of naturally occurring polyether ionophorous antibiotics (Agtarap et al 1967;Stern 1977;Berg and Hamill 1978;Liu et al 1978;Chappe 1979;Long and Jeffers 1982;Westley et al 1983;Augustine et al 1987;Koinarski and Sherkov 1987;Folz et al 1988;Augustine et al 1992;Varga and Sreter 1996;Wang et al 2006;Kevin et al 2009). Their main representative-monensin-is well known and its ability of binding monovalent metal ions is extensively studied.…”