title: Evaluation of impact of long-lasting insecticidal house screening (LLIS) on pyrethroid resistant population of the dengue vector Aedes aegypti in Mexico
Creators: name: Che Mendoza, A
Publisher: name: University of Liverpool Repository
Year: 2016

description: The public health importance of the endophilic mosquito Aedes aegypti has increased dramatically in the recent decade, because it is the vector of current outbreaks of dengue, chikungunya, Zika and Yellow fever viruses. The use of long-lasting insecticide nets fixed on doors and windows (LLIS) is one innovative approach recently proposed for Aedes control and under initial evaluation in different settings. Nevertheless, there is an urgent need to evaluate the efficacy of this intervention in endemic areas of dengue, where insecticide resistance in the mosquito populations has already developed after many years of selection pressure by the local vector control programmes. The aim of this PhD was to evaluate the efficacy of LLIS and assess the impact of insecticide resistance on this intervention. In 2012, cluster randomised controlled trials were conducted in two Mexican cities -Acapulco (Guerrero state) and Merida (Yucatan state). The study compared ten control and ten intervention areas of 100 households each across both cities. Intervention clusters included LLIS (Acapulco and Merida during the first year), followed by targeted treatment (TT) in the productive water container types (in Acapulco during the second year). Cross-sectional entomologic surveys quantified mosquito infestations at baseline (pre-intervention) and in four post-intervention samples surveys approximately at 6-monthly intervals corresponding to dry/rainy seasons. Sequentially over two years from 2012-2014, WHO cone bioassays were performed in order to determine the insecticidal activity of LLIS under operational conditions, susceptibility tests using CDC bottles, biochemical assays and genotyping for kdr were performed on F1 adult mosquitoes emerged from eggs collected using ovitraps. Overall, results showed significant reductions on adult vector densities in houses in the treated clusters with LLIS after two years at Merida and Acapulco: ca. 50% on the presence (OR≤0.62, P&lt;0.05) and abundance (IRR≤0.58, P&lt;0.05) of indoor-resting adults. In Acapulco, the combination of house screening with LLIS and TT of the most productive Ae. aegypti breeding sites had a significant impact on dengue vector populations and sustained that impact for up to 24 months. Based on the WHO efficacy criteria, the LLIS were efficient in killing susceptible Ae. aegypti (most of them achieving 80% of mortality) when first installed, but their activity rapidly declined. Much lower levels of mortality were achieved against the local and resistant Aedes population (less than 40%). The Ae. aegypti local populations demonstrated high levels of resistance to pyrethroids, mainly permethrin, some signs of decreased susceptibility for organophosphates but susceptibility to carbamates. Biochemical analysis showed a significant elevation of oxidases and GST enzyme activity and kdr-1016I and -1534C mutations were found at high frequencies in the two study sites. There was no clear effect attributable to the instalment of LLIS on the mechanism of insecticide resistance (kdr frequencies and levels of enzyme activity), but in terms of intensity of resistance, resistance seemed to be higher within the study arms with LLIS after the intervention. Although the efficacy of LLIS can be compromised by the degradation of the insecticide and/or the resistance of Aedes populations to pyrethroid-based insecticides, the physical barrier would still work as a preventive measure, as demonstrated in this study. The positive entomological impact observed in this study provides evidence of a sustained effect of LLIS on Ae. aegypti, and encourages the development of cluster randomised trials evaluating the epidemiological impact of this intervention.