Distribution of Voltage-Gated Sodium Channel (Nav) Alleles among the Aedes aegypti Populations In Central Java Province and Its Association with Resistance to Pyrethroid Insecticides

Abstract

The emergence of insecticide resistant Aedes aegypti mosquitoes has hampered dengue control efforts. WHO susceptibility tests, using several pyrethroid compounds, were conducted on Ae. aegypti larvae that were collected and raised to adulthood from Semarang, Surakarta, Kudus and Jepara in Java. The AaNaV gene fragment encompassing kdr polymorphic sites from both susceptible and resistant mosquitoes was amplified, and polymorphisms were associated with the resistant phenotype. The insecticide susceptibility tests demonstrated Ae, aegypti resistance to the pyrethroids, with mortality rates ranging from 1.6%–15.2%. Three non-synonymous polymorphisms (S989P, V1016G and F1534C) and one synonymous polymorphism (codon 982) were detected in the AaNaV gene. Eight AaNaV alleles were observed in specimens from Central Java. Allele 3 (SGF) and allele 7 (PGF) represent the most common alleles found and demonstrated strong associations with resistance to pyrethroids (OR = 2.75, CI: 0.97–7.8 and OR = 7.37, CI: 2.4–22.5, respectively). This is the first report of 8 Ae. aegypti AaNaV alleles, and it indicates the development of resistance in Ae. aegypti in response to pyrethroid insecticide-based selective pressure. These findings strongly suggest the need for an appropriate integrated use of insecticides in the region. The 989P, 1016G and 1534C polymorphisms in the AaNaV gene are potentially valuable molecular markers for pyrethroid insecticide resistance monitoring.

Characterization of metabolic detoxifying enzymes in an insecticide resistant strain of <i>Aedes aegypti</i> harboring homozygous S989P and V1016G <i>kdr</i> mutations

“…aegypti. Since the frequencies of P989 and G1016 alleles are very high in Myanmar (Kawada et al, 2014) and there is an increasing trend for these alleles in Thailand (Plernsub et al, 2016a) and Indonesia (Sayono et al, 2016), we emphasize the importance of monitoring the occurrence of kdr mutations in field populations of Ae. aegypti.…”

“…This strain harbors P989+G1016 homozygous mutations, and is resistant to DDT, permethrin and deltamethrin. This kdr genotypic form is also common in Myanmar, Singapore and Indonesia (Kawada et al, 2014;Sayono et al, 2016). Although kdr mutations are generally considered to be important in conferring pyrethroid resistance, the role of metabolic enzymes in the UPK-R strain is not known.…”

Combined target site (kdr) mutations play a primary role in highly pyrethroid resistant phenotypes of Aedes aegypti from Saudi Arabia

“…Each of these has been linked to pyrethroid resistance [42–44], but none have previously been identified in the Middle Eastern region. The 1011 M/V mutation described in Latin America, Mexico and French Guiana [21, 45, 46] was absent.…”

“…aegypti from Thailand, the triple heterozygous genotype S/P989 + V/G1016 + F/C1534 significantly improved deltamethrin survival and was relatively common, suggesting an important intermediate step for otherwise recessive mutations [50]. Triple mutant haplotypes have now been detected at low frequency in in Myanmar [47], Java [44], and now in Saudi Arabia, and the potential for combined impact of the three Vgsc mutations must remain a cause for concern. TaqMan qPCR assays provide useful tools for high throughput screening for the presence of F1534C in addition to the other mutations.…”

Knockdown resistance (kdr) of the voltage-gated sodium channel gene of Aedes aegypti population in Denpasar, Bali, Indonesia

“…This haplotype is commonly found in Ae. aegypti [6, 13, 16, 17, 33] but not in South America where the haplotype V1016I is mainly dominating [34]. Conversely, the haplotype F1534C is much less frequently found in Aedes populations when compared to V1016G and S989P genes.…”