Fenbendazole resistance in Heterakis gallinarum, the vector of Histomonas meleagridis, the causative agent of Blackhead Disease in poultry

Abstract

Due to their ubiquity, management of parasites is a common and important factor for profitable production of poultry. Heterakis gallinarum, the cecal nematode, is the most common nematode parasite of poultry. While typically causing no pathology on its own, H. gallinarum is the vector of Histomonas meleagridis, a protozoan parasite that causes blackhead disease. Histomonas meleagridis is highly pathogenic in turkeys, potentially causing high mortality. In contrast, disease caused by H. meleagridis is much less severe in chickens, where it primarily reduces productivity without manifestations of clinical disease. There are no approved treatments for H. meleagridis, making control reliant on control of the helminth vector through the use of fenbendazole (FBZ) the only drug labeled for treatment of H. gallinarum in the United States We were contacted by an industry veterinarian regarding health-related concerns in a breeder-broiler house due to histomoniasis, despite frequent anthelmintic treatments. Since we had recently diagnosed resistance to FBZ in Ascaridia dissimilis, a closely related nematode of turkeys, we were interested to determine if H. gallinarum had also evolved resistance to FBZ. Heterakis gallinarum eggs were isolated from litter collected from the house and used to infect 108 chickens. Treatment groups included a non-treated control, a label-dose and a 2X-label dose of FBZ, with 36 birds per group divided into two replicate pens of 18 birds each. Birds were placed at 1-day post hatch, and at 3 weeks of age were infected with 150 embryonated eggs via oral gavage. Two weeks post infection, treated birds were administered a minimum of either a label- or 2X label-dose of FBZ in water for 5 days (SafeGuard® Aquasol, 1mg/kg BW). To ensure that all birds consumed the full intended dose at a minimum, the dosage was calculated using 1.25 times the average body weight. One-week post treatment, birds were euthanized, ceca removed, and parasites enumerated. Efficacy was calculated by comparing the total numbers of worms recovered from each treatment group to the numbers recovered in the non-treated control group. There were no significant differences in worm numbers recovered from any of the three groups (p-value=0.81). There also was no efficacy benefit to treatment with a 2X dose; H. gallinarum worm counts were reduced by 42.7% and 41.4%, for the label and 2X dosages, respectively. These data provide strong evidence that H. gallinarum has developed resistance to FBZ. Consequently, in houses infected with FBZ-resistant H. gallinarum, H. meleagridis will be able to cycle through the birds in an unrestricted manner. Further investigation is needed to determine the prevalence of resistance in H. gallinarum on chicken farms, but it is clear this has the potential to have a large-scale economic impact on the poultry industry. These data when viewed together with our recent findings of FBZ resistance in A. dissimilis, suggest that drug resistance in ascarid nematodes may be an important emerging problem on poultry operations.

Implementation of a targeted treatment strategy for the sustainable control of Ascaridia galli infections in laying hens

“…Evidence of AR in the closely related nematodes A. dissimilis and H. gallinarum has been described in turkeys and chickens (broilers) in the USA. 10,11 A reasonable approach to tackle this issue could be to monitor resistance development in A. galli. Evaluation of the efficacy of anthelmintics on each farm is essential to any ongoing control programme.…”

“…7,8 While the evidence presented thus far suggests a lack of anthelmintic resistance (AR) in A. galli, it has been reported in Ascaridia dissimilis and H. gallinarum, two closely related parasites to A. galli. [9][10][11] Many years ago, two concepts were launched to promote the long-term sustainable use of deworming agents: (i) targeted treatment (TT), where the whole group is treated based on knowledge of the extent of the infection, and (ii) targeted selective treatment, where individual animals within the grazing group are treated, which of course requires the correct identification of the animals that need treatment. 12,13 These approaches are used to prevent worm-related adverse production effects while preserving the long-term efficacy of deworming agents by maintaining a pool of parasites in refugia (i.e., parasites that are not exposed to the drug).…”

“…In ruminants and horses, this has already become a major problem requiring ongoing investigations into the underlying molecular mechanisms of resistance 7,8 . While the evidence presented thus far suggests a lack of anthelmintic resistance (AR) in A. galli , it has been reported in Ascaridia dissimilis and H. gallinarum , two closely related parasites to A. galli 9–11 …”

Evaluation of in vitro methods of anthelmintic efficacy testing against Ascaridia galli

“…Heavy reliance on a limited number of drugs combined with application of sub-therapeutic doses during mass application are likely to increase selection pressure for anthelmintic resistance (AR) in poultry nematodes (Knapp-Lawitzke et al , 2015; Tarbiat et al , 2016). At present, evidence of AR in chicken nematodes is scarce although the expansion of the free-range production system usually involving regular application of anthelmintics may further increase the risk of resistance (Tarbiat et al , 2016; Collins et al , 2021; Soudkolaei et al , 2021; Feyera et al , 2021a) et al . In order to delay the onset and spread of AR and ensure optimal use of the available anthelmintics, regular monitoring of the efficacy of anthelmintics is essential (Coles et al , 2006; Demeler et al , 2010).…”