The fight against diseases spread by mosquitoes and other insects has enormous environmental, economic and social consequences. Chemical insecticides remain the first line of defence but the control of diseases, especially malaria and dengue fever, is being increasingly undermined by insecticide resistance. Mosquitoes have a large repertoire of P450s (over 100 genes). By pinpointing the key enzymes associated with insecticide resistance we can begin to develop new tools to aid the implementation of control interventions and reduce their environmental impact on Earth. Recent technological advances are helping us to build a functional profile of the P450 determinants of insecticide metabolic resistance in mosquitoes. Alongside, the cross-responses of mosquito P450s to insecticides and pollutants are also being investigated. Such research will provide the means to produce diagnostic tools for early detection of P450s linked to resistance. It will also enable the design of new insecticides with optimized efficacy in different environments.

https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2012.0429

Role of cytochrome P450s in insecticide resistance: impact on the control of mosquito-borne diseases and use of insecticides on Earth

Key aspects of 36 mosquito-borne arboviruses indigenous to Africa are summarized, including lesser or poorly-known viruses which, like Zika, may have the potential to escape current sylvatic cycling to achieve greater geographical distribution and medical importance. Major vectors are indicated as well as reservoir hosts, where known. A series of current and future risk factors is addressed. It is apparent that Africa has been the source of most of the major mosquito-borne viruses of medical importance that currently constitute serious global public health threats, but that there are several other viruses with potential for international challenge. The conclusion reached is that increased human population growth in decades ahead coupled with increased international travel and trade is likely to sustain and increase the threat of further geographical spread of current and new arboviral disease.

/pdf/mosquito-borne-arboviruses-of-african-origin-review-of-key-26t54x8k9a.pdf

Mosquito-borne arboviruses of African origin: review of key viruses and vectors

Zika virus outbreak in the Americas: the need for novel mosquito control methods

Pyrethroids in human breast milk: occurrence and nursing daily intake estimation.

Background: Control and prevention of dengue relies heavily on the application of insecticides to control dengue vector mosquitoes. In Colombia, application of the larvicide temephos to the aquatic breeding sites of Aedes aegypti is a key part of the dengue control strategy. Resistance to temephos was recently detected in the dengue-endemic city of Cucuta, leading to questions about its efficacy as a control tool. Here, we characterize the underlying mechanisms and estimate the operational impact of this resistance. Methodology/Principal Findings: Larval bioassays of Ae. aegypti larvae from Cucuta determined the temephos LC50 to be 0.066 ppm (95% CI 0.06‐0.074), approximately 156higher than the value obtained from a susceptible laboratory colony. The efficacy of the field dose of temephos at killing this resistant Cucuta population was greatly reduced, with mortality rates ,80% two weeks after application and ,50% after 4 weeks. Neither biochemical assays nor partial sequencing of the ace-1 gene implicated target site resistance as the primary resistance mechanism. Synergism assays and microarray analysis suggested that metabolic mechanisms were most likely responsible for the temephos resistance. Interestingly, although the greatest synergism was observed with the carboxylesterase inhibitor, DEF, the primary candidate genes from the microarray analysis, and confirmed by quantitative PCR, were cytochrome P450 oxidases, notably CYP6N12, CYP6F3 and CYP6M11. Conclusions/Significance: In Colombia, resistance to temephos in Ae. aegypti compromises the duration of its effect as a vector control tool. Several candidate genes potentially responsible for metabolic resistance to temephos were identified. Given the limited number of insecticides that are approved for vector control, future chemical-based control strategies should take into account the mechanisms underlying the resistance to discern which insecticides would likely lead to the greatest control efficacy while minimizing further selection of resistant phenotypes.

/pdf/temephos-resistance-in-aedes-aegypti-in-colombia-compromises-4lenwl9h82.pdf

Temephos Resistance in Aedes aegypti in Colombia Compromises Dengue Vector Control

Organophosphates and pyrethroids are used widely in Brazil to control Aedes aegypti, the main vector of dengue viruses, under the auspices of the National Programme for Dengue Control. Resistance to these insecticides is widespread throughout Brazil. In Ceara the vector is present in 98% of districts and resistance to temephos has been reported previously. Here we measure resistance to temephos and the pyrethroid cypermethrin in three populations from Ceara and use biochemical and molecular assays to characterise resistance mechanisms. Resistance to temephos varied widely across the three studied populations, with resistance ratios (RR95) of 7.2, 30 and 192.7 in Juazeiro do Norte, Barbalha and Crato respectively. The high levels of resistance detected in Barbalha and Crato (RR95 ≥ 30) imply a reduction of temephos efficacy, and indeed in simulated field tests reduced effectiveness was observed for the Barbalha population. Two populations (Crato and Barbalha) were also resistant to cypermethrin, whilst Juazeiro do Norte showed only an altered susceptibility. The Ile1011Met kdr mutation was detected in all three populations and Val1016Ile in Crato and Juazeiro do Norte. 1011Met was significantly associated with resistance to cypermethrin in the Crato population. Biochemical tests showed that only the activity of esterases and GSTs, among the tested detoxification enzymes, was altered in these populations when compared with the Rockefeller strain. Our results demonstrate that two A. aegypti populations from Ceara are under strong selection pressure by temephos, compromising the field effectiveness of this organophosphate. Our results also provide evidence that the process of reducing resistance to this larvicide in the field is difficult and slow and may require more than seven years for reversal. In addition, we show resistance to cypermethrin in two of the three populations studied, and for the first time the presence of the allele 1016Ile in mosquito populations from northeastern Brazil. A significant association between 1011M et and resistance was observed in one of the populations. Target-site mechanisms seem not to be implicated in temephos resistance, reinforcing the idea that for the studied populations, detoxification enzymes most likely play a major role in the resistance to this insecticide.

/pdf/insecticide-resistance-in-aedes-aegypti-populations-from-3h3lde499k.pdf

Lúcia Nogueira de Oliveira

Papers

Insecticide resistance in Aedes aegypti populations from Ceará, Brazil