Strategies to Optimize the Efficacy of Anthelmintic Drugs in Ruminants

Abstract

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity. Multidrug resistance is a widespread problem in livestock animals. The use of available pharmacology-based information is critical to the design of successful future approaches for parasite control. Relevant scientific work supporting the main strategies to optimize anthelmintic therapy in ruminants under the current drug-resistance scenario is described here. We emphasize the need for further integrated pharmaco-parasitological knowledge to extend the lifespan of both traditional and novel anthelmintic compounds, and to progress in the identification of complementary/alternative measures of parasite control in livestock animals.

Sub-lethal doses of albendazole induce drug metabolizing enzymes and increase albendazole deactivation in Haemonchus contortus adults

“…Although induced expression of certain DMEs in resistant isolates in comparison to sensitive ones has been reported repeatedly [5,6,12,14], the mechanisms and circumstances of this induction have not been elucidated. As the contact of nematodes with sub-lethal doses of anthelmintics may play an important role, we incubated ex vivo H. contortus adults from ISE strain (sensitive to all anthelmintics) with the anthelmintic drug albendazole (ABZ) and its active metabolite ABZ-sulfoxide (ABZSO) at three sub-lethal doses for 4 and 12 h. Two different incubation duration were used because it is known that the time required to induce different DMEs differs significantly [29].…”

“…The efficacy of anthelmintic therapy, however, decreases due to drug-resistance development in helminths, with the helminths' high fertility and short generational interval providing an enviable developmental plasticity in terms of adaptation and the fast development of drug resistance in H. contortus [1]. Among the many mechanisms of drug resistance, some are based on the increased expression and activity of drug-metabolizing enzymes (DME) [5,6]. These proteins protect all organisms against the potential negative action of drugs and other xenobiotics, which can be metabolized (in series or independently) by three processes, termed Phase I to Phase III.…”

Effects of Plant Extracts as Pre-Milking Dairy Cow Teat Sanitizer

“…Due to lack of awareness and increased ratio of quackery lead to inappropriate use of drugs which in turn resulted in development of resistance along with residual effects in milk, meat and other by-products (Tsiboukis et al, 2013). Among various alternative strategies, use of various pharmacokinetic-based approaches with an objective of increasing the parasitic exposure (Lanusse et al, 2018), various combinations of drugs, using alternative approaches (bioactive compounds) like tannins , ethnobotanicals (Hussain et al, 2008;, phytotherapeutic approaches (Razzaq et al, 2019), and mineral supplementation strategies (Qudoos et al, 2017;Ahmad et al, 2020) have been adapted as useful tools to attain sustainability in parasitic control.…”

Perspectives on the utility of moxidectin for the control of parasitic nematodes in the face of developing anthelmintic resistance

“…It is also clearly evident in the macrofilaricidal action of flubendazole, for which prolonged exposure to low concentrations in vivo is much more effective than shorter exposures to high concentrations (Mackenzie and Geary, 2011; Geary et al, 2019). These findings form the basis of a more rational choice of dosing regimens to enhance efficacy of MLs, including MOX, and other anthelmintics (Lanusse and Prichard, 1993; Lloberas et al, 2012b; Lanusse et al, 2014, 2018, 2016; Leathwick and Luo, 2017; Lifschitz et al, 2017; Fazzio et al, 2019) based on increasing either the intensity of exposure to the anthelmintic at the site of infection, or the duration of exposure, although neither manipulation is uniformly able to fully overcome AR and may vary with different MLs.…”