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Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases.

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Miglianico, Marie, Eldering, Maarten, Slater, Hannah, Ferguson, Neil, Ambrose, Pauline, Lees, Rosemary ORCID: https://orcid.org/0000-0002-4232-9125, Koolen, Karin M J, Pruzinova, Katerina, Jancarova, Magdalena, Volf, Petr, Koenraadt, Constantianus J M, Duerr, Hans-Peter, Trevitt, Graham, Yang, Baiyuan, Chatterjee, Arnab K, Wisler, John, Sturm, Angelika, Bousema, Teun, Sauerwein, Robert W, Schultz, Peter G, Tremblay, Matthew S and Dechering, Koen J (2018) 'Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases.'. Proceedings of the National Academy of Sciences of the United States of America, Vol 115, Issue 29, e6920-e6926.

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Abstract

Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite control in companion animals. Here we propose their use in humans for the reduction of vector-borne disease incidence. Fluralaner and afoxolaner rapidly killed , , and mosquitoes and sand flies after feeding on a drug-supplemented blood meal, with IC values ranging from 33 to 575 nM, and were fully active against strains with preexisting resistance to common insecticides. Based on allometric scaling of preclinical pharmacokinetics data, we predict that a single human median dose of 260 mg (IQR, 177-407 mg) for afoxolaner, or 410 mg (IQR, 278-648 mg) for fluralaner, could provide an insecticidal effect lasting 50-90 days against mosquitoes and sand flies. Computational modeling showed that seasonal mass drug administration of such a single dose to a fraction of a regional population would dramatically reduce clinical cases of Zika and malaria in endemic settings. Isoxazolines therefore represent a promising new component of drug-based vector control.

Item Type: Article
Uncontrolled Keywords: insecticide, isoxazoline, malaria, vector control, zika fever
Subjects: QW Microbiology and Immunology > Environmental Microbiology > QW 70 Veterinary microbiology
QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by)
WC Communicable Diseases > Virus Diseases > Infectious Mononucleosis. Arbovirus Infections > WC 524 Arbovirus infections
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1073/pnas.1801338115
SWORD Depositor: JISC Pubrouter
Depositing User: Stacy Murtagh
Date Deposited: 19 Jul 2018 08:49
Last Modified: 02 Jan 2019 02:02
URI: http://archive.lstmed.ac.uk/id/eprint/8924

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