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

被引：63

作者：

Miglianico, Marie ^{[1
]}

Eldering, Maarten ^{[1
]}

Slater, Hannah ^{[2
]}

Ferguson, Neil ^{[2
]}

Ambrose, Pauline ^{[3
]}

Lees, Rosemary S. ^{[3
]}

Koolen, Karin M. J. ^{[1
]}

Pruzinova, Katerina ^{[4
]}

Jancarova, Magdalena ^{[4
]}

Volf, Petr ^{[4
]}

Koenraadt, Constantianus J. M. ^{[5
]}

Duerr, Hans-Peter ^{[6
]}

Trevitt, Graham ^{[7
]}

Yang, Baiyuan ^{[8
]}

Chatterjee, Arnab K. ^{[8
]}

Wisler, John ^{[8
]}

Sturm, Angelika ^{[1
]}

Bousema, Teun ^{[9
]}

Sauerwein, Robert W. ^{[1
,9
]}

Schultz, Peter G. ^{[8
]}

Tremblay, Matthew S. ^{[8
]}

Dechering, Koen J. ^{[1
]}

机构：

[1] TropIQ Hlth Sci, NL-6534 Nijmegen, Netherlands

[2] Imperial Coll London, MRC Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London SW7 2AZ, England

[3] Univ Liverpool Liverpool Sch Trop Med, Liverpool Insect Testing Estab, Liverpool L3 5QA, Merseyside, England

[4] Charles Univ Prague, Fac Sci, Dept Parasitol, Prague 11636, Czech Republic

[5] Wageningen Univ & Res, Entomol Lab, NL-6700 Wageningen, Netherlands

[6] Numerus Ltd, RG40 2AY, Tubingen, Germany

[7] XenoGesis Ltd, Nottingham NG1 1GF, England

[8] Calif Inst Biomed Res, La Jolla, CA 92037 USA

[9] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 Nijmegen, Netherlands

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 29期

基金：

欧盟地平线“2020”;

关键词：

vector control; insecticide; malaria; zika fever; isoxazoline; PLASMODIUM-FALCIPARUM MALARIA; ANOPHELES-GAMBIAE; IVERMECTIN; TRANSMISSION; MOSQUITOS; DOGS; ECTOPARASITICIDE; INSECTICIDE; AFOXOLANER; RESISTANCE;

D O I：

10.1073/pnas.1801338115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 Anopheles, Aedes, and Culex mosquitoes and Phlebotomus sand flies after feeding on a drug-supplemented blood meal, with IC50 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 Phlebotomus 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.

引用

页码：E6920 / E6926

页数：7