Fipronil resistence

Hello, Summarians!

Our lead article discusses a clinical impression that has been out there for a bit. Kinda scary to see how fast this resistance occurred though…

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Fipronil Effectivness

In recent years, fleas have become a significant problem for domestic animals, causing discomfort for both pets and their owners due to their bites, which can induce itching and allergic reactions. Fleas are also known for transmitting various disease-causing pathogens, both to animals and humans. Ectoparasiticide products are commonly used to prevent insect bites and the transmission of disease agents in companion animals. Fipronil, a phenylpyrazole insecticide, has been widely utilized since the late 1980s as a prominent solution for flea control on pets worldwide. However, over the past decade, some veterinarians have observed a decrease in the effectiveness of fipronil in controlling flea infestations. Previous research conducted by the same group of authors suggested that an increase in the activity of detoxifying enzymes from the esterase family might be responsible for the faster elimination of fipronil from fleas in a laboratory strain that had developed resistance to the insecticide. Building on this insight, the present study aimed to confirm the existence of metabolic resistance by comparing the amount of fipronil present in susceptible and resistant laboratory flea strains after 24 hours of exposure to blood containing a controlled concentration of fipronil. The study involved three replicates, each consisting of 250 fleas from two different strains: a susceptible laboratory strain known as the "Felis strain," and a fipronil-resistant strain referred to as the "Phoenix strain." These fleas were exposed to blood mixed with a fipronil solution (500 ng/mL) using an artificial feeding system for 24 hours. The researchers then collected and counted the fleas, noting whether they were alive or dead, to determine the mortality percentage for each strain and replicate. Control replicates were subjected to blood mixed with ethanol to establish a baseline. The results indicated that the mean mortality percentage after 24 hours of exposure to fipronil was 63% for the Felis strain, demonstrating susceptibility, while it was only 9% for the Phoenix strain, confirming its phenotypic resistance to fipronil. In contrast, the control replicates from both strains exhibited a mortality percentage of less than 10%. The researchers also analyzed the concentration of fipronil and its main metabolite, fipronil-sulfone, within the fleas and their feces using a technique called UPLC–MS/MS (Ultra Performance Liquid Chromatography-Mass Spectrometry). These preliminary findings suggest that resistant fleas exhibit an enhanced detoxification mechanism for fipronil, resulting in lower levels of fipronil-sulfone accumulation compared to susceptible fleas. This aligns with the concept of metabolic resistance. The research team is currently conducting similar experiments with fleas exposed to fipronil-sulfone. To the best of the authors' knowledge, this study represents the first instance of quantifying fipronil and its metabolite within fleas using UPLC–MS/MS technology. 

Flea resistance to fipronil: Confirmation of metabolic detoxification through innovative HPLC dosage within fleas. J Vet Pharmacol Therap, 46: 41-41.https://doi.org/10.1111/jvp.13193 

Bottom line — 9% mortality in resistant strain—Yikes …

Rebound Hyperacidity After Omeprazole Use in Horses

The provided text is an excerpt from a research article discussing the effects of omeprazole treatment on horses' gastric health. The study focuses on the impact of omeprazole administration and subsequent discontinuation on serum gastrin and chromogranin A (CgA) concentrations in horses. The researchers are interested in understanding whether omeprazole treatment leads to elevated gastrin levels and increased ECL cell density, potentially contributing to rebound gastric hyperacidity (RGH) and the recurrence of gastric issues after treatment ends. The text highlights concerns about overusing proton pump inhibitors (PPIs) in humans and horses, particularly the reoccurrence of diseases due to rebound gastric hyperacidity. It explains the role of gastrin in regulating gastric acid secretion and how PPI administration can lead to hypergastrinemia by disrupting the negative feedback loop on gastrin production. This can affect ECL cell density and increase the stomach's acid secretory capacity. The study's design involved administering omeprazole to horses and observing its effects on serum gastrin and CgA concentrations. The results showed that serum gastrin concentrations increased shortly after starting omeprazole and returned to baseline within a few days after discontinuation. The study suggests that this hypergastrinemia might contribute to the swift recurrence of equine squamous gastric disease after omeprazole withdrawal. Interestingly, while serum gastrin levels responded to omeprazole treatment, serum CgA concentrations did not show a clear change in response. The study proposes that these findings do not support the need for tapering periods after medium-term omeprazole treatment in horses, suggesting that other management practices might be more effective in reducing the risk of gastric issues post-treatment. The study acknowledges limitations such as the lack of CgA testing validation in horses, variations in omeprazole administration, and the absence of control horses. The authors call for further research to validate CgA testing, investigate uninterrupted omeprazole administration, and study other populations where continuous treatment is common. In summary, the article delves into the effects of omeprazole on horses' gastric health, particularly focusing on serum gastrin and CgA concentrations, with implications for the recurrence of gastric issues following omeprazole treatment discontinuation. 

Clark, B, Steel, C, Vokes, J, et al. Evaluation of the effects of medium-term (57-day) omeprazole administration and of omeprazole discontinuation on serum gastrin and serum chromogranin A concentrations in the horse. J Vet Intern Med. 2023; 37(4): 1537-1543. doi:10.1111/jvim.16795 

Bottom line — extensive tapering may not be needed but withdrawal may lead to swift reoccurrence.

Possible Prognostic Tool for Metastasis in Bone Cancer

The study focuses on the survival and metastasis patterns of dogs with appendicular osteosarcoma (OSA) after amputation or limb sparing surgery and chemotherapy. The median survival time for these dogs varies widely, and the study aims to understand the factors influencing this heterogeneity. The research involves the detection of circulating tumor cells (CTCs) in the blood of these dogs, which are released from tumors and have the potential to form distant metastases. The detection of CTCs is challenging due to limitations in sensitivity and specificity of imaging techniques. The study discusses the development and validation of a flow cytometric assay to detect CTCs in dogs with OSA. Results from the pilot study indicate that CTCs are more common in dogs with OSA than in humans with other types of cancer, and an increase in CTCs is predictive of disease progression. The study hypothesizes that a rising frequency of CTCs in dogs with OSA could predict the development of overt metastasis. However, due to the limited sample size and variability in disease progression, the establishment of clear cut-off values for imminent metastasis was not possible. The study also explores the persistence of CTCs even after amputation and chemotherapy, suggesting that these cells may represent undetectable micrometastases present at the time of primary tumor removal. The authors propose that surgical removal of the primary tumor might trigger the release of dormant tumor cells into circulation, leading to a pre-metastatic CTC spike. The study acknowledges various limitations, such as the small sample size, variability in disease stages, and the lack of standardized assays for veterinary use. Despite these limitations, the study concludes that detecting a CTC spike is associated with shorter survival in dogs with OSA. However, the inability to define a specific cut-off value for impending metastasis means that the technique is not practically applicable for clinical use at the moment. Overall, the study contributes to the understanding of osteosarcoma in dogs, highlighting the potential of CTC enumeration as a prognostic tool, while also recognizing the need for further research and refinement of the technique. 

Wright, TF, Brisson, BA, Belanger, CR, et al. Quantification of circulating tumor cells over time in dogs with appendicular osteosarcoma. Vet Comp Oncol. 2023; 21(3): 541-550. doi:10.1111/vco.12918 

Bottom line — A potentially useful tool for these challenging cases.

Just putting things in perspective …