Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study.

Nicolas, Patricia; Kiuru, Caroline; Wagah, Martin G; Muturi, Martha; Duthaler, Urs; Hammann, Felix; Maia, Marta; Chaccour, Carlos (2021). Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study. Parasites & Vectors, 14(1), p. 172. BioMed Central 10.1186/s13071-021-04675-9

[img]
Preview
Text
Nicolas__Parasites_Vectors_2021.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

BACKGROUND

Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals for malaria control set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively.

METHODS

We determined the lethal concentration 50 for ivermectin in colonized Anopheles gambiae; then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification.

RESULTS

Dual inhibition of xenobiotic pumps and cytochromes was found to have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin.

CONCLUSION

There is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine

UniBE Contributor:

Hammann, Felix

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1756-3305

Publisher:

BioMed Central

Language:

English

Submitter:

Tobias Tritschler

Date Deposited:

08 Jun 2021 15:33

Last Modified:

07 Sep 2021 17:17

Publisher DOI:

10.1186/s13071-021-04675-9

PubMed ID:

33743783

Uncontrolled Keywords:

ABC transporter Bioassay CYP Endectocide Insecticide resistance Ivermectin P-gp Resistance Synergists

BORIS DOI:

10.48350/155862

URI:

https://boris.unibe.ch/id/eprint/155862

Actions (login required)

Edit item Edit item
Provide Feedback