Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries. Disturbingly, the geographic range of dengue is currently expanding and the severity of outbreaks is increasing. Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti. These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control. For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines. This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression.
"Resistance to pyrethroid insecticides, the primary insecticide family used against adult mosquitoes, is particularly worrying in the context of the re-emergence of dengue and other arboviruses worldwide (Bhatt et al. 2013). Although attempts are made to develop new insecticides or alternative mosquito control strategies (Scholte et al. 2004; Lacey 2007; Hoffmann et al. 2011; Walker et al. 2011; Harris et al. 2012), their large-scale implementation in tropical regions will require at least a decade. Until this, characterizing molecular mechanisms underlying resistance is crucial for tracking down resistance alleles and improving resistance management strategies (Corbel et al. 2013). "
[Show abstract][Hide abstract] ABSTRACT: The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.
Genome Research 07/2015; 25(9). DOI:10.1101/gr.189225.115 · 14.63 Impact Factor
"In the absence of a vaccine and suitable drugs, new paradigms for vector control approaches are needed to replace archaic ones. One of the novel methods proposed is bio control approach where Wolbachia from naturally infected arthropods are introduced into Aedes aegypti to reduce the transmission of dengue (Moreira et al., 2009; Bian et al., 2010; Walker et al., 2011). Wolbachia are a group of intracellular bacteria which are maternally transmitted and found in most arthropods and nematodes (Werren, 1997; Stouthamer et al., 1999). "
"This is partly because of the danger that females could be released accidentally as a part of a CI strategy that could permit the Wolbachia infection type to become established in the host field population. Another strategy shifts from population suppression to replacement by use of CI mechanisms and matrilineal inheritance, which can lead to populations of uninfected mosquitoes being replaced by infected ones, despite releases of only small numbers of the latter    . At present, two kinds of mathematical models, involving both discrete-time and continuous-time models, have been investigated for the spread of Wolbachia infection       . "
[Show abstract][Hide abstract] ABSTRACT: Dengue fever, which affects more than 50 million people a year, is the most important arboviral disease in tropical countries. Mosquitoes are the principal vectors of the dengue virus but some endosymbiotic Wolbachia bacteria can stop the mosquitoes from reproducing and so interrupt virus transmission. A birth-pulse model of the spread of Wolbachia through a population of mosquitoes, incorporating the effects of cytoplasmic incompatibility (CI) and different density dependent death rate functions, is proposed. Strategies for either eradicating mosquitoes or using population replacement by substituting uninfected mosquitoes with infected ones for dengue virus prevention were modeled. A model with a strong density dependent death function shows that population replacement can be realized if the initial ratio of number of infected to the total number of mosquitoes exceeds a critical value, especially when transmission from mother to offspring is perfect. However, with a weak density dependent death function, population eradication becomes difficult as the system’s solutions are sensitive to initial values. Using numerical methods, it was shown that population eradication may be achieved regardless of the infection ratio only when parameters lie in particular regions and the initial density of uninfected is low enough.
Nonlinear Analysis Real World Applications 04/2015; 22:236–258. DOI:10.1016/j.nonrwa.2014.09.004 · 2.52 Impact Factor
E O Juárez-Hernández, L E Casados-Vázquez, M.C. del Rincón-Castro, R Salcedo-Hernández, D K Bideshi, J E Barboza-Corona
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