Pfizer Animal Health, 23/25 avenue du Docteur Lannelongue, 75668 Paris Cedex 14, France.
Vet Parasitol. 2012 May 25;186(3-4):151-8. doi: 10.1016/j.vetpar.2011.11.030. Epub 2011 Nov 12.
Combinations of anthelmintics with a similar spectrum of activity and different mechanisms of action and resistance are widely available in several regions of the world for the control of sheep nematodes. There are two main justifications for the use of such combinations: (1) to enable the effective control of nematodes in the presence of single or multiple drug resistance, and (2) to slow the development of resistance to the component anthelmintic classes. Computer model simulations of sheep nematode populations indicate that the ability of combinations to slow the development of resistance is maximised if certain prerequisite criteria are met, the most important of which appear to concern the opportunity for survival of susceptible nematodes in refugia and the pre-existing levels of resistance to each of the anthelmintics in the combination. Combinations slow the development of a resistant parasite population by reducing the number of resistant genotypes which survive treatment, because multiple alleles conferring resistance to all the component anthelmintic classes must be present in the same parasite for survival. Individuals carrying multiple resistance alleles are rarer than those carrying single resistance alleles. This enhanced efficacy leads to greater dilution of resistant genotypes by the unselected parasites in refugia, thus reducing the proportion of resistant parasites available to reproduce with other resistant adults that have survived treatment. Concerns over the use of anthelmintic combinations include the potential to select for resistance to multiple anthelmintic classes concurrently if there are insufficient parasites in refugia; the potential for shared mechanisms of resistance between chemical classes; and the pre-existing frequency of resistance alleles may be too high on some farms to warrant the introduction of certain combinations. In conclusion, anthelmintic combinations can play an important role in resistance management. However, they are not a panacea and should always be used in accordance with contemporary principles for sustainable anthelmintic use.
在世界上的几个地区，有许多具有相似作用谱和不同作用机制的驱虫药组合可用于控制绵羊线虫。使用这些组合有两个主要的理由：(1) 在存在单一或多种耐药性的情况下，能够有效地控制线虫；(2) 减缓对驱虫药成分类别的耐药性的发展。绵羊线虫种群的计算机模型模拟表明，如果满足某些前提条件，组合减缓耐药性发展的能力可以最大化，其中最重要的似乎是考虑到易感线虫在避难所中生存的机会和组合中每种驱虫药的预先存在的耐药水平。组合通过减少存活治疗的耐药基因型数量来减缓耐药寄生虫种群的发展，因为生存需要在同一寄生虫中存在赋予对所有成分驱虫药类别的耐药性的多个等位基因。携带多个耐药等位基因的个体比携带单个耐药等位基因的个体更为罕见。这种增强的功效导致未被选择的避难所中的寄生虫更大程度地稀释耐药基因型，从而减少可用的具有耐药性的寄生虫与其他幸存的耐药成虫繁殖的比例。对抗虫药组合的使用的担忧包括如果避难所中的寄生虫不足，可能会同时选择对多种驱虫药类别的耐药性；化学类别的耐药性可能存在共同机制；并且在某些农场，耐药等位基因的预先存在频率可能过高，以至于不需要引入某些组合。总之，驱虫药组合可以在耐药性管理中发挥重要作用。然而，它们不是万灵药，应始终根据可持续驱虫药使用的当代原则来使用。
