A ticket to ride: genetic structure andkdrmutations inAedes aegyptipopulations along a road crossing the Amazon Rainforest in Amapá State, Brazil

Abstract Insecticide resistance in Aedes aegypti is a major threat to the control of this mosquito species that transmits viruses that cause diseases like dengue, Zika, and chikungunya. One type of resistance is caused by alterations in the Na v gene, known as kdr mutations. In Brazil, different kdr haplotypes are present in Ae. aegypti and they may impede vector control operations based on pyrethroids. Although natural populations tend to accumulate genetic differences among isolated localities, this mosquito can actively and passively disperse, hitchhiked with human transportation. In this study, we investigated the genetic structure and kdr dispersion in Ae. aegypti populations in six localities of the Amapá State, Brazil located along a north-south transect of the Amazonian Forest. Genetic structure was assessed using 12 microsatellite loci in a fragment analysis sequencing procedure, and qPCR methods were used to detect the presence and frequency of three well known kdr mutations (V410L, V1016I and F1534C). We found a high prevalence of kdr alleles in all localities, indicating that kdr is spreading in the Amapá State. The microsatellite analyses suggested a certain level of differentiation among the mosquito populations, dividing them into two well-defined clusters, as evidenced by Bayesian and DAPC analyses. The population from Oiapoque (located in the north along the border with French Guiana) had the highest kdr frequencies and the highest genetic differentiation compared to the other localities. Our findings suggest that there is genetic structure among Ae. aegypti from the Amapá State, but with some level of passive gene flow between population clusters. The study highlights the importance of continued surveillance of Ae. aegypti populations to monitor the spread of insecticide resistance and inform on vector control strategies. Author summary Amapá, a State in northern Brazil, is crucial as a gateway for diseases due to its border with French Guiana. One notable example was chikungunya, transmitted by the Aedes aegypti mosquito, also responsible for dengue, Zika, and yellow fever viruses. Chemical insecticides have been the primary means of control, however, resistance to these compounds is spreading among Ae. aegypti populations, compromising their effectiveness. Mutations known as “ kdr ” contribute to resistance to pyrethroid insecticides. Our study focused on these mutations and genetic differentiation in Ae. aegypti populations from six cities along the road nestled amidst the Amazonian Forest, linking the capital, Macapá, to Oiapoque on the Brazil-French Guiana border. The results revealed high frequencies of kdr mutations in all populations, indicating probable resistance to pyrethroids. Genetic analysis showed two distinct groups among the mosquitoes, with evidence of mosquito flow, particularly between Macapá and Oiapoque, facilitated by human transportation. Monitoring insecticide resistance and mosquito migration is essential for effective vector control strategies. Understanding these factors enables us to combat mosquito-borne diseases and safeguard public health.