Abstract
Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populations of insect pollinator species. Here we present a promising, environment-friendly alternative to current insecticides that targets the insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded and eliminated. RNA interference (RNAi) of either the first two enzymes in the tyrosine degradation pathway (tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, oral administration of NTBC to bumblebees did not affect their survival. Using a novel mathematical model, we show that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current disease elimination programmes.
Highlights
Human African trypanosomiasis (HAT), known as sleeping sickness, is a parasitic disease caused predominantly by the parasite Trypanosoma brucei gambiense
The genes encoding tyrosine aminotransferase (TAT) and hydroxyphenylpyruvate dioxygenase (HPPD) proteins were identified in five Glossina species [16], as well as in all hematophagous arthropod species with sequenced genomes (S1 Fig)
This lethality was further validated by feeding flies with blood supplemented with mesotrione, an HPPD inhibitor widely used as a selective herbicide on corn crops under the brand name Callistro, Syngenta (S3A Fig)
Summary
Human African trypanosomiasis (HAT), known as sleeping sickness, is a parasitic disease caused predominantly by the parasite Trypanosoma brucei gambiense These parasites are transmitted to a vertebrate host when infected tsetse flies (Glossina spp.) blood feed. Tsetse control tools such as aerial spraying of insecticides (pyrethroids), visual- and odour-baited tsetse traps, insecticidetreated livestock, live traps, insecticide-impregnated traps and targets, and sterile male releases have been employed [3,4,5,6,7] Despite such efforts, because AAT and HAT persist in these endemic areas, both economic development and public health continue to be jeopardised [8]. A novel complementary strategy to control these parasitic diseases is highly desired
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