# Evaluating the impact of nitisinone at mosquito-lethal doses on Lutzomyia longipalpis

## TL;DR

Nitisinone, a drug that kills mosquitoes and tsetse flies, does not work against sand flies that spread leishmaniasis, likely due to differences in their metabolism.

## Contribution

The study reveals that Lutzomyia longipalpis is tolerant to nitisinone at mosquito-lethal doses, highlighting the need for species-specific evaluations.

## Key findings

- Nitisinone at 250 ng/mL did not significantly affect the survival of Lutzomyia longipalpis over 14 days.
- Sand flies may be more tolerant to nitisinone due to species-specific metabolic differences.
- Higher doses or alternative compounds may be needed for nitisinone to be effective against sand flies.

## Abstract

Nitisinone, a systemic inhibitor of tyrosine catabolism, has recently emerged as a promising endectocide with demonstrated lethality against mosquitoes and tsetse flies. To assess its efficacy against Lutzomyia longipalpis, an important vector of Leishmania infantum —the causative agent of zoonotic visceral leishmaniasis prevalent in the Mediterranean basin, Latin America, and parts of the Middle East—, we exposed sand flies to a concentration previously shown to be lethal to Anopheles mosquitoes (250 ng/mL). Survival was monitored over 14 days and showed no significant difference between treated and control groups, indicating a lack of insecticidal effect at this dose. These findings suggest that Lu. longipalpis exhibits tolerance to nitisinone, likely due to species-specific metabolic differences. Although nitisinone remains a promising tool for systemic vector control, its effectiveness against sand flies may require higher doses or alternative compounds.

We investigated whether nitisinone could help control sand flies, which are insects responsible for transmitting Leishmania infantum, the parasite that causes visceral leishmaniasis. Previous studies showed that nitisinone can kill mosquitoes and tsetse flies when present in treated animal blood. To test if the same approach could work for sand flies, we exposed them to a dose of nitisinone lethal for mosquitoes. Unlike mosquitoes, sand flies, after two weeks survival monitoring, were not affected by this treatment and survived as well as untreated flies. This result indicates that sand flies may be more tolerant to nitisinone, probably because of differences in their metabolism compared to other insect species. While nitisinone remains an interesting option for controlling some disease vectors, it may not be effective against sand flies at the tested dose. This highlights the need to evaluate each vector species individually and to explore other drugs or higher doses when developing systemic tools to reduce the spread of vector-borne diseases.