Aug 2026· Molecular and biochemical parasitology (Print)· Vol 268, pp.
111779
· 0 citations· 185 references
Medicine
TL;DR
A multidisciplinary and sustainable approach is essential to mitigate the impact of AR and ensure long-term effectiveness of parasite control strategies in small ruminant production systems.
Abstract
Gastrointestinal nematode (GIN) infections represent one of the most significant constraints to the health and productivity of small ruminants worldwide, leading to substantial economic losses and animal welfare concerns. Control of these parasites has historically relied on the extensive use of anthelmintic drugs; however, the rapid emergence and global spread of anthelmintic resistance (AR) have compromised their effectiveness. Resistance is now reported across all major classes of anthelmintics and is particularly prevalent in key species such as Haemonchus contortus. The development of AR is driven by complex mechanisms, including genetic mutations in drug target genes, enhanced drug efflux mediated by transport proteins, alterations in receptor function, and polygenic adaptations. Accurate detection of resistance remains challenging, with conventional methods such as fecal egg count reduction tests and in vitro assays offering limited sensitivity, while molecular diagnostics provide improved specificity but remain constrained by technical and economic factors. Sustainable control of GIN infections requires a shift toward integrated parasite management strategies. Approaches such as targeted selective treatment, maintenance of refugia, improved nutrition, genetic selection for host resistance, and alternative control methods including phytotherapy and biological control have shown promise in reducing reliance on anthelmintics. In conclusion, a multidisciplinary and sustainable approach is essential to mitigate the impact of AR and ensure long-term effectiveness of parasite control strategies in small ruminant production systems.
Gastrointestinal nematode infections cause severe production losses in sheep, but intensive anthelmintic use has led to widespread resistance. Therefore, alternative control strategies are needed. This dissertation implements a multi-pronged approach combining broad in vitro screening, phytochemical profiling, and host transcriptomics to identify sustainable parasite-control solutions. The first experiment focused on evaluating aqueous extracts of 24 plant species (forages, common weeds and herbs) in larval mortality assays against infective H. contortus and S. papillosus. Several extracts caused >70 percent mortality by 48 h. The most effective extracts were from species such as Ageratum conyzoides and Chenopodium album. To investigate the cause of antiparasitic effect of those plant extracts, the second experiment further investigated untargeted LC-MS/MS metabolomics of the active extracts and in silico docking to three H. contortus target proteins. From 1,370 detected metabolites, 72 compounds enriched in the most effective extracts were prioritized. Key candidates included flavonoids, terpenoids, alkaloids, phenolic compounds and other bioactive compounds. Although botanical interventions may offer an alternative to chemical dewormers, sustainable parasite control also depends on improving the host's innate ability to resist infection. Therefore, the last chapter examined phenotypic and transcriptomic signatures of GIN resistance in Katahdin sheep. Ten ewes were selected based on fecal egg count (FEC) at three times. RNA from both whole blood and fecal samples was sequenced and analyzed. Blood RNA-seq identified 19 differentially expressed genes at the first time point and 13 DEGs at the second time point, including candidate immune genes (e.g., C3AR1, ADGRE3, ATP5IF1, ALAS2) and three consistently upregulated long non-coding RNAs (lcRNA) in resistant ewes. In contrast, fecal-derived host RNA showed low mapping rates to the ovine genome and yielded no significant differential expression. Though no DEGs were displayed in fecal samples between the two groups, approximately 8,600 ovine genes were annotated, therefore, further study in a larger sample size may validate the feasibility of this non-invasive approach in sheep. Collectively, these studies identified potential and critical roles of the plant extracts and gene candidates, respectively, that may be useful for implementing organic gastrointestinal nematode control in small ruminants.
This review systematically synthesizes key advances over the past decade concerning host-Eimeria interactions, molecular regulatory mechanisms, and novel control strategies, while contextualizing these findings with earlier seminal discoveries.
Anthelmintic resistance constitutes a global threat to the control of parasitic nematodes. Current research has primarily focused on parasite-intrinsic genetic mechanisms, while the contribution of the symbiotic microbial community remains a key knowledge gap. Here, we report that ivermectin (IVM) resistance in the gastrointestinal nematode Haemonchus contortus is associated with the abundance of the bacterium Stenotrophomonas maltophilia. A representative strain, designated SM1, was isolated from resistant populations, and its abundance was associated with the resistant phenotype. Depletion of SM1 increased larval susceptibility to IVM, whereas reintroduction of the bacterium partially enhanced IVM tolerance. Metabolic analysis indicated that SM1 converts IVM into demethylated and oxo-derivatives (M1, M4, and M7). Using in silico analysis, the putative cytochrome P450 monooxygenase (Cmp08160) with a possible participation in IVM biotransformation was identified. Collectively, these findings suggest that symbiotic bacteria can influence IVM susceptibility in H. contortus and highlight the relevance of considering host–microbiota interactions in studies of anthelmintic resistance.
Si-Min Wu, Chun-Qun Wang, Jun-Cheng Li et al.· International Journal for Pa...· 0 citations
ABSTRACT Background Gastrointestinal nematode (GIN) infections are widely distributed across the country and are responsible for considerable losses in small ruminant production and the emergence of anthelmintic resistance has intensified the challenge. This study evaluated the efficacy of widely used commercial anthelmintics and examined whether combining different drug classes enhances their effectiveness in naturally infected sheep in Kaffa Zone. Materials and Methods An experimental trial was conducted using 275 sheep that shed at least 150 eggs per gram count, randomly divided into six groups. Faecal samples were collected from each animal before and after treatment using selected anthelmintics, and the faecal egg count reduction test was employed to identify resistance towards each drug. Results Faecal egg count reduction test values and corresponding lower 95% confidence limit were 90.31% and 88.51% for albendazole, 91.39% and 89.53% for tetramisole, and 95.84% and 95.05% for ivermectin, respectively. The findings indicated reduced effectiveness of albendazole and tetramisole, while ivermectin maintained acceptable efficacy. Combination treatments showed markedly higher reductions—99.11% for albendazole with ivermectin and 99.27% for tetramisole with ivermectin. The range of faecal egg counts of infected sheep was from 350 to 6750 EPG before treatment and from 0 to 1550 EPG after treatment. The overall mean of faecal egg counts of infected sheep was 1881.5 ± 69.7 (95% CI: 1744.2–2018.9) and 229.9 ± 28.4 (95% CI: 174.1–285.8) pre‐treatment and post‐treatment, respectively. Conclusion The findings suggest the presence of emerging anthelmintic resistance to albendazole and tetramisole in the study area and highlight the potential usefulness of combination anthelmintic strategies. Continued monitoring and integrated parasite management practices are recommended.
Nahom Belay, A. Arke, L. Tesfaye· Veterinary Medicine and Scie...· 0 citations
Anthelmintics are central to parasite control in companion animals, but drug targets in helminths remain limited. Anthelmintic resistance is a clinically significant threat, with emerging multiple anthelmintic drug-resistant Ancylostoma caninum, macrocyclic lactone-resistant Dirofilaria immitis and praziquantel-resistant Dipylidium caninum. Each treatment is a selection event which eliminates susceptible parasites and enriches resistant survivors. Drug-resistant helminths often go undetected due to limited diagnostics and sole reliance on treatment. While some molecular tools can detect gene polymorphisms associated with resistance, their use is somewhat limited. Sustainable control will require strategic evidence-based use, targeted surveillance, and continued research into resistance mechanisms and detection tools.
J. J. Jesudoss Chelladurai, M. Brewer· The Veterinary clinics of No...· 0 citations
Background: Gastrointestinal nematode infections remain a major constraint on productivity and welfare in sheep, goats, and cattle. Routine anthelmintic administration is central to parasite control; however, reports of intoxication associated with overdose and misuse have raised safety concerns.
Aims: This study aimed to synthesize published evidence on documented anthelmintic intoxication in domestic ruminants.
Methods: A systematic literature search was conducted in Scopus, PubMed/MEDLINE, and Web of Science following PRISMA guidelines. Studies reporting confirmed or strongly suspected intoxication in sheep, goats, or cattle were included. Fifteen studies met the eligibility criteria and were analyzed qualitatively. The search strategy used combinations of keywords related to anthelmintics, toxicity or intoxication, and domestic ruminant species. Titles and abstracts were screened for relevance, followed by full-text evaluation of potentially eligible articles. Data extracted from the included studies covered animal species, type of anthelmintic involved, exposure circumstances, clinical manifestations, and reported pathological findings to enable a descriptive synthesis of intoxication patterns.
Results: Most intoxication events involved overdose or inaccurate weight-based dosing. Macrocyclic lactones and levamisole were primarily linked to neurological dysfunction, including ataxia and tremors. Closantel was consistently associated with optic nerve degeneration and blindness, whereas nitroxinil exposure resulted in acute hepatic and renal injury with high mortality in outbreak settings. High extra-label benzimidazole dosing was reported to cause intestinal crypt necrosis and bone marrow suppression.
Conclusion: The findings indicate that clinically significant toxicity arises mainly under misuse conditions rather than routine labeled administration, emphasizing accurate dosing and veterinary oversight to improve drug safety in ruminant production systems.
A. Haryo, J. Joesoef· Acta Veterinaria Indonesiana· 0 citations
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