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US-20260124161-A1 - NITISINONE ADMINISTRATION TO LIVESTOCK FOR HEMATOPHAGOUS ARTHROPOD CONTROL

US20260124161A1US 20260124161 A1US20260124161 A1US 20260124161A1US-20260124161-A1

Abstract

The present application provides methods for the control of hematophagous arthropods by administration of nitisinone to animals from which the arthropods feed. Hematophagous arthropods have evolved mechanisms of detoxifying the tyrosine in blood meals. Nitisinone (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione) inhibits the detoxification of tyrosine and leads to the death of hematophagous arthropods. Blood from cattle treated with nitisinone kills blood-feeding arthropods and presents a novel means of protecting cattle from such arthropods.

Inventors

  • Georgina Bingham
  • Roberto Cortinas
  • Sean Avedissian

Assignees

  • BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA

Dates

Publication Date
20260507
Application Date
20251103

Claims (18)

  1. 1 . A method for controlling hematophagous arthropods in animals, comprising: administering nitisinone to an animal in an amount effective to cause mortality in hematophagous arthropods that feed on blood from the animal and result in control of the hematophagous arthropods.
  2. 2 . The method of claim 1 , wherein the animal is selected from the group consisting of cattle, sheep, goats, horses, swine, and zoological animals.
  3. 3 . The method of claim 1 , wherein the animal is a bird.
  4. 4 . The method of claim 3 wherein the bird is selected from the group consisting of chickens, quail, turkeys, ducks, and pigeons.
  5. 5 . The method of claim 1 , wherein the animal belongs to the family Canidae.
  6. 6 . The method of claim 5 , wherein the animal is a domesticated dog.
  7. 7 . The method of claim 1 , wherein the animal belongs to family Felidae.
  8. 8 . The method of claim 7 , wherein the animal is a domesticated cat.
  9. 9 . The method of claim 1 , wherein the animal is of the family Cervidae.
  10. 10 . The method of claim 9 , wherein the animal is a deer and moose.
  11. 11 . The method of claim 1 , wherein the hematophagous arthropods are selected from the group consisting of stable flies ( Stomoxys calcitrans ), horn flies ( Haematobia irritans ), tsetse flies ( Glossina spp.), ticks ( Rhipicephalus, Dermacentor ), mosquitoes ( Aedes, Culex , and Anopheles spp.), biting midges ( Culicidae spp.), and kissing bugs ( Triatominae spp.).
  12. 12 . The method of claim 1 , wherein the nitisinone is administered via a route selected from the group consisting of orally, via injection, or topically.
  13. 13 . The method of claim 12 , wherein the administration is via injection and the injection is intramuscular or intravenous.
  14. 14 . The method of claim 12 , wherein the administration is topical by applying a spray on, wipe on or pour on formulation.
  15. 15 . The method of claim 12 , wherein the administration is oral and through a mineral lick, a rumen delivered pellet or feed.
  16. 16 . The method of claim 1 , wherein the effective amount of nitisinone is from about 0.5 mg/kg to about 2 mg/kg body weight of the animal.
  17. 17 . The method of claim 1 , wherein the mortality of the hematophagous arthropods occurs within about 24 to 48 hours after feeding on the blood.
  18. 18 . The method of claim 1 , wherein the nitisinone does not negatively impact rumen function or feed digestibility in the animal.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This patent application claims the benefit of U.S. Provisional Application No. 63/715,261 filed on Nov. 1, 2024, the entire contents of which are incorporated herein by reference. FIELD OF INVENTION The present disclosure relates to methods for controlling hematophagous arthropods by administering nitisinone to subjects, such as livestock. BACKGROUND Blood-feeding arthropods, including flies, ticks, mosquitos and other arthropods, are key vectors in the transmission of zoonotic pathogens. Stable flies pose a large threat to cattle production with an annual estimate of over two billion dollars in economic damage associated with direct feeding on livestock. The impact of blood-feeding on agricultural animal production includes reduced weight gain, decreased milk production, impaired grazing efficiency, overall diminished animal welfare, and increased transmission of disease to domesticated animals and humans. Current approaches to address blood-feeding arthropods include backrubbers, pesticide tags, chemical sprays, pour-ons, and abamectin injectables. However, these methods are limited in controlling arthropod populations for various reasons. Accordingly, there is a need in the art for novel, targeted approaches to control blood-feeding arthropods. Blood meals require the digestion of a high flux of metabolites, some being highly toxic. Tyrosine, although a minor component of blood meals, becomes toxic at high concentrations. For this reason, blood-feeding arthropods have evolved specialized mechanisms to degrade tyrosine post-ingestion. Thus, the exploration of novel biochemical targets within the tyrosine degradation pathway presents a strategic alternative. SUMMARY A method for controlling hematophagous arthropods in animals is provided. The method comprises administering nitisinone to an animal in an amount effective to cause mortality in hematophagous arthropods that feed on blood from the animal and result in control of the hematophagous arthropods. The animal may be selected from the group consisting of cattle, sheep, goats, horses, swine, poultry, domesticated animals including dogs and cats, poultry or other birds and zoological animals. The hematophagous arthropods may be any blood feeding arthropod such as stable flies (Stomoxys calcitrans), horn flies (Haematobia irritans), tsetse flies (Glossina spp.), ticks (Rhipicephalus, Dermacentor), mosquitoes (Aedes, Culex, and Anopheles spp.), biting midges (Culicidae spp.), and kissing bugs (Triatominae spp.). The nitisinone may be administered via a route selected from orally, via injection, or topically. The effective amount of nitisinone may be from about 0.5 mg/kg to about 2 mg/kg body weight of the animal. The control of the arthropods may be direct killing of the arthropods via the toxicity of the blood meal in the presence of nitisinone. The mortality of the hematophagous arthropods may occur within about 24 to 48 hours after feeding on the blood. BRIEF DESCRIPTION OF THE DRAWINGS The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. FIG. 1 shows that topical and oral exposure of NTBC is lethal to stable flies. (A) In oral treatments associated with a citrated (3.7 g sodium citrate/L) blood meal (USDA, Lincoln, NE), a Hemotek feeder (Hemotek, United Kingdom) was utilized to feed the flies for the designated treatment (0.0, 0.0005, 0.00075, 0.001, 0.0015, 0.002, 0.005 mg/mL NTBC) for approximately ten minutes. If any of the flies failed to consume any of the blood, they were removed from the experiment. (B) Topical exposure of NTBC to stable flies was tested by using a Hamilton syringe to apply concentrations of 0 (control), 0.0005, 0.005, 0.01, 0.025, 0.05, and 0.1 mg/mL NTBC (Ambeed, Inc.—Batch No. A384235-011) onto the flies prior to placement in jars). All treatments were fed at 24 hours with 10% sucrose solution using cotton balls in addition to data recording. Data was then repeated at 48 hours (and 72 hours for oral treatment). FIG. 2 shows the direct effects of NTCB-mediated inhibition of tyrosine degradation on stable flies. Stable flies fed a control (PBS) were compared visually with stable flies fed with NTBC and bovine blood. An Olympus SZX16 microscope (Olympus, Tokyo) was utilized for magnification while the OLYMPUS cellSems Dimension application was used to digitally capture images of the flies. Three images were captured of each fly with a focus on the eyes, abdomen, and body side-profile. FIG. 3 shows that stable flies fed on blood from intravenous or intramuscular NTBC cattle result in mortality. (A) Intramuscular exposure of nitisinone (NTBC) is lethal to Stable flies. Calf blood was collected from animals treated intramuscularly with NTBC and presented to stable flies using a Hemotek membrane feeder for approxi