BackgroundA genetically-engineered strain of the dengue mosquito vector Aedes aegypti, designated OX3604C, was evaluated in large outdoor cage trials for its potential to improve dengue prevention efforts by inducing population suppression. OX3604C is engineered with a repressible genetic construct that causes a female-specific flightless phenotype. Wild-type females that mate with homozygous OX3604C males will not produce reproductive female offspring. Weekly introductions of OX3604C males eliminated all three targeted Ae. aegypti populations after 10–20 weeks in a previous laboratory cage experiment. As part of the phased, progressive evaluation of this technology, we carried out an assessment in large outdoor field enclosures in dengue endemic southern Mexico.Methodology/Principal FindingsOX3604C males were introduced weekly into field cages containing stable target populations, initially at 10∶1 ratios. Statistically significant target population decreases were detected in 4 of 5 treatment cages after 17 weeks, but none of the treatment populations were eliminated. Mating competitiveness experiments, carried out to explore the discrepancy between lab and field cage results revealed a maximum mating disadvantage of up 59.1% for OX3604C males, which accounted for a significant part of the 97% fitness cost predicted by a mathematical model to be necessary to produce the field cage results.Conclusions/SignificanceOur results indicate that OX3604C may not be effective in large-scale releases. A strain with the same transgene that is not encumbered by a large mating disadvantage, however, could have improved prospects for dengue prevention. Insights from large outdoor cage experiments may provide an important part of the progressive, stepwise evaluation of genetically-engineered mosquitoes.

Genetic approaches for controlling disease vectors have aimed either to reduce wild-type populations or to replace wild-type populations with insects that cannot transmit pathogens. Here, we propose a Reduce and Replace (R&R) strategy in which released insects have both female-killing and anti-pathogen genes. We develop a mathematical model to numerically explore release strategies involving an R&R strain of the dengue vector Aedes aegypti. We show that repeated R&R releases may lead to a temporary decrease in mosquito population density and, in the absence of fitness costs associated with the anti-pathogen gene, a long-term decrease in competent vector population density. We find that R&R releases more rapidly reduce the transient and long-term competent vector densities than female-killing releases alone. We show that releases including R&R females lead to greater reduction in competent vector density than male-only releases. The magnitude of reduction in total and competent vectors depends upon the release ratio, release duration, and whether females are included in releases. Even when the anti-pathogen allele has a fitness cost, R&R releases lead to greater reduction in competent vectors than female-killing releases during the release period; however, continued releases are needed to maintain low density of competent vectors long-term. We discuss the results of the model as motivation for more detailed studies of R&R strategies.

Climate change is leading to increases in global temperatures and erratic precipitation patterns, both of which are contributing to the expansion of mosquito-borne arboviruses and the populations of the mosquitos that vector them. Herein, we review recent evidence of emergence and expansion of arboviruses transmitted by Aedes mosquitos that has been driven in part by environmental changes. We present as a case study of recent work from Có rdoba, Argentina, where dengue has been actively emerging in the past decade. We review recent empirical and modeling studies that aim to understand the impact of climate on future expansion of arboviruses, and we highlight gaps in empirical studies linking climate to arbovirus transmission at regional levels.

Expansion of mosquito-borne pathogens into more temperate regions of the world necessitates tools such as mathematical models for understanding the factors that contribute to the introduction and emergence of a disease in populations naïve to the disease. Often, these models are not developed and analyzed until after a pathogen is detected in a population. In this study, we develop a spatially explicit stochastic model parameterized with publicly available U.S. Census data for studying the potential for disease spread in Urbanized Areas of the United States. To illustrate the utility of the model, we specifically study the potential for introductions of dengue to lead to autochthonous transmission and outbreaks in a population representative of the Miami Urbanized Area, where introductions of dengue have occurred frequently in recent years. We describe seasonal fluctuations in mosquito populations by fitting a population model to trap data provided by the Miami-Dade Mosquito Control Division. We show that the timing and location of introduced cases could play an important role in determining both the probability that local transmission occurs as well as the total number of cases throughout the entire region following introduction. We show that at low rates of clinical presentation, small outbreaks of dengue could go completely undetected during a season, which may confound mitigation efforts that rely upon detection. We discuss the sensitivity of the model to several critical parameter values that are currently poorly characterized and motivate the collection of additional data to strengthen the predictive power of this and similar models. Finally, we emphasize the utility of the general structure of this model in studying mosquito-borne diseases such as chikungunya and Zika virus in other regions.

Two basic strategies have been proposed for using transgenic Aedes aegypti mosquitoes to decrease dengue virus transmission: population reduction and population replacement. Here we model releases of a strain of Ae. aegypti carrying both a gene causing conditional adult female mortality and a gene blocking virus transmission into a wild population to assess whether such releases could reduce the number of competent vectors. We find this “reduce and replace” strategy can decrease the frequency of competent vectors below 50% two years after releases end. Therefore, this combined approach appears preferable to releasing a strain carrying only a female-killing gene, which is likely to merely result in temporary population suppression. However, the fixation of anti-pathogen genes in the population is unlikely. Genetic drift at small population sizes and the spatially heterogeneous nature of the population recovery after releases end prevent complete replacement of the competent vector population. Furthermore, releasing more individuals can be counter-productive in the face of immigration by wild-type mosquitoes, as greater population reduction amplifies the impact wild-type migrants have on the long-term frequency of the anti-pathogen gene. We expect the results presented here to give pause to expectations for driving an anti-pathogen construct to fixation by relying on releasing individuals carrying this two-gene construct. Nevertheless, in some dengue-endemic environments, a spatially heterogeneous decrease in competent vectors may still facilitate decreasing disease incidence.

The distribution of arbovirus disease transmission is expanding from the tropics and subtropics into temperate regions worldwide. The temperate city of Córdoba, Argentina has been experiencing the emergence of dengue virus, transmitted by the mosquito Aedes aegypti, since 2009, when autochthonous transmission of the virus was first recorded in the city. The aim of this work is to characterize the emergence of dengue and related arboviruses (Zika and chikungunya) in Córdoba since 2009. Herein, we present a data set with all known information about transmission of dengue, Zika, and chikungunya viruses in Córdoba, Argentina from 2009–2018, including what information is known of dengue virus (DENV) serotypes in circulation and origins of imported cases. The data presented in this work will assist researchers in investigating drivers of arbovirus emergence and transmission in Córdoba, Argentina and contribute to a better understanding of the global problem of the expanding distribution of arbovirus disease transmission.

Tropical mosquito-borne viruses have been expanding into more temperate regions in recent decades. This is partly due to the coupled effects of temperature on mosquito life history traits and viral infection dynamics and warming surface temperatures, resulting in more suitable conditions for vectors and virus transmission. In this study, we use a deterministic ordinary differential equations model to investigate how seasonal and diurnal temperature fluctuations affect the potential for dengue transmission in six U.S. cities. We specifically consider temperature-dependent mosquito larval development, adult mosquito mortality, and the extrinsic incubation period of the virus. We show that the ability of introductions to lead to outbreaks depends upon the relationship between a city’s temperature profile and the time of year at which the initial case is introduced. We also in-vestigate how the potential for outbreaks changes with predicted future increases in mean temperatures due to climate change. We find that climate change will likely lead to increases in suitability for dengue transmission and will increase the periods of the year in which introductions may lead to outbreaks, particularly in cities that typically have mild winters and warm summers, such as New Orleans, Louisiana, and El Paso, Texas. We discuss our results in the context of temperature heterogeneity within and across cities and how these differences may impact the potential for dengue emergence given present day and predicted future temperatures.

With the recent global spread of a number of mosquito-borne viruses, there is an urgent need to understand the factors that contribute to the ability of viruses to expand into naïve populations. Using dengue and chikungunya viruses as case studies, we detail the necessary components of the expansion process: presence of the mosquito vector; introduction of the virus; and suitable conditions for local transmission. For each component we review the existing modelling approaches that have been used to understand recent emergence events or to assess the risk of future expansions. We identify gaps in our knowledge that are related to each of the distinct aspects of the human-mosquito transmission cycle: mosquito ecology; human-mosquito contact; mosquito-virus interactions; and human-virus interactions. Bridging these gaps poses challenges to both modellers and empiricists, but only through further integration of models and data will we improve our ability to better understand, and ultimately control, several infectious diseases that exert a significant burden on human health.