Increasing importance of anthelmintic resistance in European livestock: creation and meta-analysis of an open database

Abstract

Helminth infections are ubiquitous in grazing ruminant production systems, and are responsible for significant costs and production losses. Anthelmintic Resistance (AR) in parasites is now widespread throughout Europe, although there are still gaps in our knowledge in some regions and countries. AR is a major threat to the sustainability of modern ruminant livestock production, resulting in reduced productivity, compromised animal health and welfare, and increased greenhouse gas emissions through increased parasitism and farm inputs. A better understanding of the extent of AR in Europe is needed to develop and advocate more sustainable parasite control approaches. A database of European published and unpublished AR research on gastrointestinal nematodes (GIN) and liver fluke (Fasciola hepatica) was collated by members of the European COST Action "COMBAR" (Combatting Anthelmintic Resistance in Ruminants), and combined with data from a previous systematic review of AR in GIN. A total of 197 publications on AR in GIN were available for analysis, representing 535 studies in 22 countries and spanning the period 1980-2020. Reports of AR were present throughout the European continent and some reports indicated high within-country prevalence. Heuristic sample size-weighted estimates of European AR prevalence over the whole study period, stratified by anthelmintic class, varied between 0 and 48%. Estimated regional (country) prevalence was highly heterogeneous, ranging between 0% and 100% depending on livestock sector and anthelmintic class, and generally increased with increasing research effort in a country. In the few countries with adequate longitudinal data, there was a tendency towards increasing AR over time for all anthelmintic classes in GIN: aggregated results in sheep and goats since 2010 reveal an average prevalence of resistance to benzimidazoles (BZ) of 86%, macrocyclic lactones except moxidectin (ML) 52%, levamisole (LEV) 48%, and moxidectin (MOX) 21%. All major GIN genera survived treatment in various studies. In cattle, prevalence of AR varied between anthelmintic classes from 0-100% (BZ and ML), 0-17% (LEV) and 0-73% (MOX), and both Cooperia and Ostertagia survived treatment. Suspected AR in F. hepatica was reported in 21 studies spanning 6 countries. For GIN and particularly F. hepatica, there was a bias towards preferential sampling of individual farms with suspected AR, and research effort was biased towards Western Europe and particularly the United Kingdom. Ongoing capture of future results in the live database, efforts to avoid bias in farm recruitment, more accurate tests for AR, and stronger appreciation of the importance of AR among the agricultural industry and policy makers, will support more sophisticated analyses of factors contributing to AR and effective strategies to slow its spread.

Keywords: Anthelmintic resistance; Database; Europe; Gastrointestinal nematodes; Liver fluke; Maps; Prevalence; Ruminants.

Figure 1

Number of publications investigating anthelmintic resistance in gastro-intestinal nematodes reported from each country and included in the database.

Figure 2

Number of publications investigating anthelmintic resistance in gastrointestinal nematodes for each ruminant host species. Green colours represent the number of publications. Grey indicates no data. Note the different symbology ranges for each ruminant species. Variation within countries is not shown.

Figure 3

Estimated prevalence of resistance against the benzimidazoles (BZ), levamisole (LEV), avermectins (ML; macrocyclic lactones), and moxidectin (MOX) in gastrointestinal nematodes in sheep. Points and whiskers represent the weighted prevalence estimate and standard deviation, respectively. The weighted prevalence and standard deviation across all studies are represented by the dashed black and grey vertical lines, respectively. Note that points without whiskers represent single studies, for which standard deviations could not be estimated (i.e. they do not represent points which the prevalence is known with a high level of confidence). Corresponding figures for goats and cattle, and for sheep, goats and cattle using only studies with n > 9 can be found in the Supplementary Material.

Figure 4

Level of anthelmintic resistance in each country, using a composite index across all drugs tested, in relation to research effort (= confidence) as a function of number of studies, farms and anthelmintics investigated. See methods for details of indices. Note that horizontal scales are different for each panel. For gastrointestinal nematodes in sheep in Ireland, the confidence score was modified to take account of a single large study that assessed treatment efficacy through pooled faecal sampling by farmers at and after treatment [54]. GIN = Gastrointestinal nematodes. Country abbreviations: AT = Austria, BE = Belgium, CH = Switzerland, CZ = Czechia, DE = Germany, DK = Denmark, EL = Greece, ES = Spain, FR = France, IE = Ireland, IT = Italy, LT = Lithuania, NL = Netherlands, NO = Norway, PL = Poland, RO = Romania, RS = Serbia, SE = Sweden, SK = Slovakia, UK = United Kingdom.

Figure 5

Average farm-level prevalence of anthelmintic resistance in gastrointestinal nematodes in sheep and goats, by decade. The arithmetic mean was taken of all reports including more than one farm, from countries with a minimum of three reports in different years, excluding Italy (see text). BZ = benzimidazoles, n = 64; LEV = levamisole, n = 14; ML = macrocyclic lactones excluding moxidectin, n = 23; MOX = moxidectin, n = 10. Error bars are standard deviations.

Figure 6

Change in the prevalence of anthelmintic resistance (= proportion of farms testing positive) for benzimidazoles (BZ) in Switzerland (CH; dotted black line) and the United Kingdom (UK; dashed red line), and macrocyclic lactones excluding moxidectin (MOX) in the United Kingdom (solid blue line). Only studies testing more than one farm were included. For regression equations, see https://www.parasite-journal.org/10.1051/parasite/2020062">Table S4(a–c). Data point for CH-BZ at (2016, 1) is partly concealed.