Abstract
Aedes aegypti is the primary vector of dengue, chikungunya, Zika, and urban yellow fever. Insecticides are often the most effective tools to rapidly decrease the density of vector populations, especially during arbovirus disease outbreaks. However, the intense use of insecticides, particularly pyrethroids, has selected for resistant mosquito populations worldwide. Mutations in the voltage gated sodium channel (NaV) are among the principal mechanisms of resistance to pyrethroids and DDT, also known as "knockdown resistance," kdr. Here we report studies on the origin and dispersion of kdr haplotypes in samples of Ae. aegypti from its worldwide distribution. We amplified the IIS6 and IIIS6 NaV segments from pools of Ae. aegypti populations from 15 countries, in South and North America, Africa, Asia, Pacific, and Australia. The amplicons were barcoded and sequenced using NGS Ion Torrent. Output data were filtered and analyzed using the bioinformatic pipeline Seekdeep to determine frequencies of the IIS6 and IIIS6 haplotypes per population. Phylogenetic relationships among the haplotypes were used to infer whether the kdr mutations have a single or multiple origin. We found 26 and 18 haplotypes, respectively for the IIS6 and IIIS6 segments, among which were the known kdr mutations 989P, 1011M, 1016I and 1016G (IIS6), 1520I, and 1534C (IIIS6). The highest diversity of haplotypes was found in African samples. Kdr mutations 1011M and 1016I were found only in American and African populations, 989P + 1016G and 1520I + 1534C in Asia, while 1534C was present in samples from all continents, except Australia. Based primarily on the intron sequence, IIS6 haplotypes were subdivided into two well-defined clades (A and B). Subsequent phasing of the IIS6 + IIIS6 haplotypes indicates two distinct origins for the 1534C kdr mutation. These results provide evidence of kdr mutations arising de novo at specific locations within the Ae. aegypti geographic distribution. In addition, our results suggest that the 1534C kdr mutation had at least two independent origins. We can thus conclude that insecticide selection pressure with DDT and more recently with pyrethroids is selecting for independent convergent mutations in NaV.
Highlights
Aedes aegypti is considered one of the most successful invasive species worldwide
We investigate whether the same kdr mutations found in Ae. aegypti populations from distinct regions of the world have a common origin and subsequently dispersed or if they emerged in unrelated populations at distinct moments
From Africa and found throughout the tropics and subtropics, i t has been divided into two subspecies Aedes aegypti aegypti (Aaa) and Aedes aegypti formosus (Aaf)
Summary
Aedes aegypti is considered one of the most successful invasive species worldwide. Originally from Africa and found throughout the tropics and subtropics, i t has been divided into two subspecies Aedes aegypti aegypti (Aaa) and Aedes aegypti formosus (Aaf). Ae. aegypti is generally referred to as the yellow fever mosquito, as it was the vector of yellow fever virus in the urban cycle of the disease in the Americas until the first half of the last century and more recently in West Africa [2]. Vaccination against yellow fever and intense vector control eliminated the urban cycle of the disease in most countries by mid-20th Century [3]. Decreasing entomological surveillance along with rapid increases in urbanization and demographic changes has led to the re-establishment of this species. Ae. aegypti occurs on six continents [4], reaching high densities in urban centers of tropical and subtropical cities and acts as the primary vector of viruses causing dengue, chikungunya and, Zika, as well as re-emerging yellow fever [5]. The risk of epidemic arboviral diseases is the highest in history [6] and it is predicted that in response to increased urbanization and climate change, 2.25 billion more people (or 60% of global population) will be at risk of dengue in 2080 compared to 2015 [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
