Differences in efficacy of monepantel, derquantel and abamectin against multi-resistant nematodes of sheep

Abstract

Drug resistance has become a global phenomenon in gastrointestinal nematodes of sheep, particularly resistance to macrocyclic lactones. New anthelmintics are urgently needed for both the control of infections with multi-resistant nematodes in areas where classical anthelmintics are no longer effective, and the prevention of the spread of resistance in areas where the problem is not as severe. Recently, two new active ingredients became commercially available for the treatment of nematode infections in sheep, monepantel (Zolvix®) and derquantel, the latter used only in a formulated combination with the macrocyclic lactone, abamectin (Startect®). In order to assess the potential of the new actives for the control and prevention of spread of anthelmintic resistance, two characterized multi-resistant field isolates from Australia were used in a GLP (good laboratory practice) conducted efficacy study in sheep. Eight infected sheep in each group were treated orally according to the product labels with 2.5 mg/kg body weight monepantel, 0.2 mg/kg abamectin, or with the combination of 2.0 mg/kg derquantel and 0.2 mg/kg abamectin. The results demonstrate that monepantel was fully effective against multi-resistant species, Trichostrongylus colubriformis and Haemonchus contortus (99.9%). In contrast, the combination of derquantel and abamectin was effective against T. colubriformis (99.9%), but was not effective against larval stages of the barber's pole worm H. contortus (18.3%).

Overview of anthelmintic resistance of gastrointestinal nematodes of small ruminants in Brazil

“…Bustamante et al (2009) found that monepantel was 100% effective in sheep in Brazil, Argentina and Uruguay. However, resistance to monepantel (SCOTT et al, 2013;MEDEROS et al, 2014a; VAN DEN BROM et al, 2015) and to derquantel (KAMINSKY et al, 2011) has been reported around the world, demonstrating the high vulnerability of these drugs. It is likely that reports of resistance to these anthelmintics will soon be published in Brazil.…”

“…Recently, two new classes of anthelmintics were launched, an amino-acetonitrile derivative, monepantel (KAMINSKY et al, 2008), and derquantel, which was marketed in association with abamectin (LITTLE et al, 2010). However, there have been reports of resistance to monepantel (SCOTT et al, 2013;MEDEROS et al, 2014a; VAN DEN BROM et al, 2015) and to derquantel (KAMINSKY et al, 2011), indicating the high vulnerability of these drugs. Additional to the loss of effectiveness there are the effects of toxic residues on nontarget organisms in the environment (LUMARET et al, 2012) and of residues in meat (COOPER et al, 2011), milk and other animal products associated to anthelmintics (IMPERIALE et al, 2004;ANASTASIO et al, 2005;WHELAN et al, 2010).…”

Multiple anthelmintic resistance in Southern Brazil sheep flocks

“…Monepantel, a derivative of aminoacetonitrile, is the most recent alternative in the chemical control of gastrointestinal parasites in sheep (HOSKING et al, 2010;KAMINSKY et al, 2011;SAGER et al, 2012). However, after three years of commercialization, it has already demonstrated resistant cases in New Zealand (SCOTT et al, 2013), Uruguay (MEDEROS et al, 2014) and the Netherlands ( VAN DEN BROM et al, 2015).…”

EVOLUTION IN CHEMOTHERAPY OF HUMAN AND ANIMAL HELMINTHIASES (review)

“…Derquantel is semisynthetic derivative of paraherquamide A isolated from natural spiroindoles -products of Penicillium paraherquei (86,87). Derquantel inhibits nAChR (88), it has a broad spectrum of anthelmintic actions; the mixture derquantel-abamectin is often used in treatment and control of various nematodes in the gastrointestinal tract (even ones resistant to other drugs), which allows to expect finding anthelmintic properties in similar compounds. Tribendimidin is an aminophenyldimidin derivative of amidantel; it was first synthesized in China in 1980 (89) and introduced in local medical practice in 2004 (90-92).…”