Detection of pyrethroid resistance mutations in the major leishmaniasis vector Phlebotomus papatasi

Authors: FOTAKIS, M - Agricultural University Of Athens; GIANTSIS, I - American Farm School; DEMIR, S - Ege University; VONTAS, J - Agricultural University Of Athens; CHASKOPOULOU, ALEXANDRA - European Biological Control Laboratory (EBCL)

Submitted to: Journal of Medical Entomology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/18/2018
Publication Date: 8/29/2018
Citation: Fotakis, M., Giantsis, I., Demir, S., Vontas, J., Chaskopoulou, A. 2018. Detection of pyrethroid resistance mutations in the major leishmaniasis vector Phlebotomus papatasi. Journal of Medical Entomology. 55(5):1225-1230. doi.org/10.1093/jme/tjy066.
DOI: https://doi.org/10.1093/jme/tjy066

Interpretive Summary: Phlebotomine sand flies are primary vectors of leishmaniasis, one of the world’s most neglected diseases. Human visceral (VL) and human cutaneous leishmaniasis (CL) are endemic in over 75 and 90 countries, respectively, resulting in 2 million new cases and approximately 25,000 deaths every year. Insecticide based treatments are still considered one of the main prevention and response strategies against vector borne diseases within the framework of an Integrated Vector Management (IVM) approach. An IVM program relies on the appropriate use of all available sources and targets all stages of a vector's life cycle in an attempt to increase precision and effectiveness of treatments while minimizing the chemical discharge in the environment. Sand flies present a big challenge to vector control because of the limited knowledge on their larval habitats, which inevitably limits control efforts to mostly adulticiding interventions. With adulticiding being the primary means of controlling sand flies, the development of resistance to adulticides poses a serious threat to the efficacy of insecticide interventions worldwide. Very scarce information however is available regarding the resistance status and the underlying mechanisms of resistance in sand fly populations. To the best of our knowledge this study represents the first investigation of resistance mutations in wild sand fly populations in Europe and Turkey (both Asian & European regions) and the first global detection of resistance mutations in the major leishmaniasis vector P. papatasi. The current study provides important information on the pyrethroid resistance status of sand fly populations and emphasizes the need for pyrethroid resistance monitoring and investigation of the underlying molecular resistance mechanisms in sand fly leishmania vectors.

Technical Abstract: Phlebotomine sand flies are primary vectors of leishmaniasis, one of the world’s most neglected diseases. Visceral and cutaneous leishmaniasis are endemic in Greece and Turkey, where people and domestic animals are widely affected by the disease. Measures commonly applied for controlling sand flies rely on the use of insecticides, predominantly pyrethroids. A worldwide problem associated with the intensive use of insecticides is the development of insecticide resistance. Little information is available regarding the resistance status and the underlying mechanisms of resistance in sand fly populations. This study represents the first investigation of pyrethroid resistance mutations in wild sand fly populations in Europe and Turkey. Sand flies were collected from the wild in Greece (Thessaloniki, Peloponnesus, Chios) and Turkey (Sanliurfa) and were analyzed for the presence and frequency of target-site knockdown resistance (KDR) mutations on the voltage-gated sodium channel (Vgsc) gene. Sand fly species analysis revealed the presence of 5 species (Phlebotomus perifiewi, P. neglectus, P. simici, P. tobbi, and P. papatasi). The mutation 1014F (Phe), which is associated with pyrethroid resistant phenotypes, was detected in P. papatasi sand flies from Sanliurfa at an allele frequency of 48%. Homozygotes for the wild type allele 1014L, (Leu/Leu) represented 36% of the population while homozygotes for the resistant allele 1014F, (Phe/Phe) and heterozygotes encompassing both alleles (Leu/Phe) each had a frequency of 32%. In the sand fly populations from Greece only the wild type allele 1014L was detected. To our knowledge this is the first detection of resistance mutations in the major leishmaniasis vector P. papatasi ever reported. Taking into account the association of the kdr mutation 1014F with DDT and pyrethroid resistance, this finding is of major concern regarding leishmaniasis control.