Vector competence of lambda-cyhalothrin resistant Aedes aegypti strains for dengue-2, Zika and chikungunya viruses in Colombia.

Aedes aegypti is the primary vector of dengue, Zika, and chikungunya viruses. Studies have shown that insecticide resistance affects vector competence (VC) of some mosquito species. This study evaluates the effect of resistance to lambda-cyhalothrin and kdr V1016I mutation genotypes on the VC of Ae. aegypti strains for DENV-2, ZIKV, and CHIKV. Three Ae. aegypti strains with gradual lambda-cyhalothrin resistance (susceptible, resistant, and highly resistant) were infected with DENV-2, ZIKV, and CHIKV. Individual mosquitoes were tested to detect virus infection in the abdomen and head-salivary glands, using RT-PCR, and genotypes for V1016I mutations using allele-specific PCR. Recorded VC variables were midgut infection rate (MIR), dissemination rate (DIR), and dissemination efficiency (DIE). Lambda-cyhalothrin resistance affects differentially VC variables for ZIKV, DENV-2, and CHIKV. For ZIKV, an apparent gradual increase in DIR and DIE with the increase in insecticide resistance was observed. For DENV-2 the MIR and DIE were higher in insecticide resistant strains. For CHIKV, only MIR could be evaluated, this variable was higher in insecticide resistance strains. The presence of kdr V1016I mutation on mosquito resistant strains did not affect VC variables for three study viruses.

Integration of phlebotomine ecological niche modelling, and mapping of cutaneous leishmaniasis surveillance data, to identify areas at risk of under-estimation.

INTRODUCTION: Passive surveillance systems are thought to under-estimate the true incidence of American cutaneous leishmaniasis (ACL) by two- to five-fold. Ecological niche models based on remotely sensed data can identify environmental factors which favor phlebotomine vectors. Here we report an integrated approach to identifying areas at risk of cutaneous leishmaniasis by applying spatial analysis methods to niche model results, and local surveillance data, in two locations in Colombia with differing vector ecology. The objective was to identify townships in which later phases of the project could implement community-based surveillance to obtain direct estimates of under-reporting. MATERIALS AND METHODS: The study was carried out in one municipality in each of two departments of the Andean region of Colombia: Pueblo Rico in Risaralda, and Rovira in Tolima. Niche mapping by maximum entropy, based on published and unpublished existing locations of Pintomyia (Pifanomyia) longiflocosa and Psychodopygus panamensis, and using variables on land cover, climate and elevation. Field catches were done in each municipality to test predictions of high relative probability of presence. The niche model results were included as a predictor in a conditional autoregressive spatial model, in which the outcome variable was the number of cases by township, as detected by passive surveillance. RESULTS: Having rarefied 173 geolocated records, 46 of Pi. longiflocosa and 57 of Ps. panamensis were used for the niche modelling. At the national level, both species had high relative probability of presence on parts of the slopes of the three Andean cordilleras. Pi. longiflocosa also has a high relative probability of presence in the higher parts of the Magdalena valley, as does Ps. panamensis in some areas close to the Caribbean coast. At the local level, field catches confirmed that Pi. longiflocosa was the most abundant species in Rovira, and likewise Ps. panamensis in Pueblo Rico. The spatial regression showed that the incidence of ACL, according to surveillance, was positively, but not statistically significantly, associated with the relative probability of presence from the risk model. CONCLUSIONS: These niche maps bring together published and unpublished results on phlebotomine species which are important vectors in Colombia. Maps of the fitted values of incidence were used to guide the selection of townships in which further phases of the study will attempt to quantify the extent of under-estimation of ACL incidence.

Transcriptome comparison of dengue-susceptible and -resistant field derived strains of Colombian Aedes aegypti using RNA-sequencing.

BACKGROUND: Forty percent of the world's population live in areas where they are at risk from dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Dengue viruses are transmitted primarily by the mosquito Aedes aegypti. In Cali, Colombia, approximately 30% of field collected Ae. aegypti are naturally refractory to all four dengue serotypes. OBJECTIVES: Use RNA-sequencing to identify those genes that determine refractoriness in feral mosquitoes to dengue. This information can be used in gene editing strategies to reduce dengue transmission. METHODS: We employed a full factorial design, analyzing differential gene expression across time (24, 36 and 48 h post bloodmeal), feeding treatment (blood or blood + dengue-2) and strain (susceptible or refractory). Sequences were aligned to the reference Ae. aegypti genome for identification, assembled to visualize transcript structure, and analyzed for dynamic gene expression changes. A variety of clustering techniques was used to identify the differentially expressed genes. FINDINGS: We identified a subset of genes that likely assist dengue entry and replication in susceptible mosquitoes and contribute to vector competence. MAIN CONCLUSIONS: The differential expression of specific genes by refractory and susceptible mosquitoes could determine the phenotype, and may be used to in gene editing strategies to reduce dengue transmission.

Transcriptome comparison of dengue-susceptible and -resistant field derived strains of Colombian Aedes aegypti using RNA-sequencing

BACKGROUND Forty percent of the world's population live in areas where they are at risk from dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Dengue viruses are transmitted primarily by the mosquito Aedes aegypti. In Cali, Colombia, approximately 30% of field collected Ae. aegypti are naturally refractory to all four dengue serotypes. OBJECTIVES Use RNA-sequencing to identify those genes that determine refractoriness in feral mosquitoes to dengue. This information can be used in gene editing strategies to reduce dengue transmission. METHODS We employed a full factorial design, analyzing differential gene expression across time (24, 36 and 48 h post bloodmeal), feeding treatment (blood or blood + dengue-2) and strain (susceptible or refractory). Sequences were aligned to the reference Ae. aegypti genome for identification, assembled to visualize transcript structure, and analyzed for dynamic gene expression changes. A variety of clustering techniques was used to identify the differentially expressed genes. FINDINGS We identified a subset of genes that likely assist dengue entry and replication in susceptible mosquitoes and contribute to vector competence. MAIN CONCLUSIONS The differential expression of specific genes by refractory and susceptible mosquitoes could determine the phenotype, and may be used to in gene editing strategies to reduce dengue transmission.

Land use in relation to composition and abundance of phlebotomines (Diptera: Psychodidae) in five foci of domiciliary transmission of cutaneous leishmaniasis in the Andean region of Colombia.

American cutaneous leishmaniasis is a public health concern in Colombia, its incidence being sustained or focally increased principally by the emergence of domestic transmission concomitantly with the adaptation of the phlebotomine vectors to habitat transformation around households. The objective of the study is to scale up a rapid characterization methodology for evaluating the relationship of land use around the house to the composition and abundance of phlebotomines. Five sites with a history of domestic leishmaniasis transmission in the Andean area of Colombia were selected. The peri-domestic habitat was evaluated at 10 m intervals along eight radial transects, centered on each house, at 45° intervals using a web pattern. Phlebotomines were captured by placing three CDC light traps over two nights both indoors and outdoors (10 m from the house). Blood source and infection were determined by PCR. Spearman rank correlation coefficients and negative binomial regression were used to quantify associations between the phlebotomine abundance and habitat categories. The study demonstrated that the vectors were largely anthropophagic (62% of 79 were human blood) and that a single species in each site was favored by the pertaining agriculture monoculture. Specifically, Pintomyia (Pifanomyia) quasitownsendi was associated with sugar cane in Novillero and La Esmeralda; while Pi. (Pif.) longiflocosa was associated with coffee plantations in Agua Bonita and El Cucal. Honda Alta had a more diverse array of land use and forest coverage with a lower number of specimens but higher species diversity. In terms of distance from the house to an area of a given land use, the abundance of Pi. (Pif.) quasitownsendi was inversely related to the distance to sugar cane plantation (Spearman correlation coefficient, ρ = -0.56, p < 0.001 for outdoor catches, and ρ = -0.50, p < 0.001 indoors). A similar inverse relationship was observed for Pi. (Pif.) longiflocosa with regard to technified coffee (ρ = -0.51, p < 0.001 outdoors, and ρ = -0.48, p < 0.001 indoors). This rapid characterization methodology could guide public heath decision makers in identifying those houses at higher risk of domestic transmission, and also educate farmers to increase the distance between their crops and any neighboring houses.

VECTOS: An Integrated System for Monitoring Risk Factors Associated With Urban Arbovirus Transmission.

In Colombia, as in many Latin American countries, decision making and development of effective strategies for vector control of urban diseases such as dengue, Zika, and chikungunya is challenging for local health authorities. The heterogeneity of transmission in urban areas requires an efficient risk-based allocation of resources to control measures. With the objective of strengthening the capacity of local surveillance systems to identify variables that favor urban arboviral transmission, a multidisciplinary research team collaborated with the local Secretary of Health officials of 3 municipalities in Colombia (Giron, Yopal, and Buga), in the design of an integrated information system called VECTOS from 2015 to 2018. Information and communication technologies were used to develop 2 mobile applications to capture entomological and social information, as well as a web-based system for the collection, geo-referencing, and integrated information analysis using free geospatial software. This system facilitates the capture and analysis of epidemiological information from the Colombian national surveillance system (SIVIGILA), periodic entomological surveys-mosquito larvae and pupae in premises and peridomestic breeding sites-and surveys of knowledge, attitudes, and practices (KAP) in a spatial and temporal context at the neighborhood level. The data collected in VECTOS are mapped and visualized in graphical reports. The system enables real-time monitoring of weekly epidemiological indicators, entomological indices, and social surveys. Additionally, the system enables risk stratification of neighborhoods, using selected epidemiological, entomological, demographic, and environmental variables. This article describes the VECTOS system and the lessons learned during its development and use. The joint analysis of epidemiological and entomological data within a geographic information system in VECTOS gives better insight to the routinely collected data and identifies the heterogeneity of risk factors between neighborhoods. We expect the system to continue to strengthen vector control programs in evidence-based decision making and in the design and enhanced follow-up of vector control strategies.

Mechanisms of pyrethroid resistance in Aedes (Stegomyia) aegypti from Colombia.

In Colombia Aedes (Stegomyia) aegypti is the main vector of urban arboviruses such as dengue, chikungunya and Zika. This urban mosquito has a well-established capacity to develop insecticide resistance to different types of insecticides (pyrethroids, organochlorides, organophosphates), using multiple resistance mechanisms. An understanding of ongoing resistance mechanisms is critical to determining the activities of vector control programs. In order to identify the biochemical and molecular mechanisms associated with pyrethroid resistance in Colombia, three laboratory-selected strains resistant to DDT, Propoxur and lambdacyhalothrin, and 7 field-collected strains were evaluated. CDC bioassays were performed to measure the susceptibility status to pyrethroid type I (permethrin) and II (deltamethrin and lambdacyhalothrin), and potential cross-resistance to different types of insecticides; organochlorine (DDT), carbamates (propoxur) and organophosphates (malathion). The enzymatic activity of esterases, glutathione S-transferases (GST) and P450 monooxygenases were biochemically determined. Frequencies of kdr mutations Val1016Ile and Phe1534cys were determined through real-time PCR. The Rockefeller strain of Aedes (Stegomyia) aegypti was used as the susceptible control. The laboratory-selected strains "propoxur" and "lambdacyhalothrin" and one field population (Medellín (BF) F2 were resistant to all evaluated pyrethroids. Six of the seven field populations as well as the laboratory- selected "DDT" strain were resistant to permethrin. All the evaluated strains were resistant to DDT. Cross-resistance between lambdacyhalothrin and propoxur was observed in the laboratory-selected strains; however, all field-collected strains were susceptible to propoxur and no evidence of malathion resistance was found. The main biochemical mechanism for resistance observed in the field-collected strains was related to the enzyme GST. Further, the frequencies of kdr mutations alleles associated with insecticide resistance were high and ranged from 0.02 to 0.72 for Ile1016 and from 0.44 to 0.99 for Cys1534. Strains with high frequencies of both kdr mutations were resistant to both type I and II pyrethroids. These results suggest that Ae. aegypti from Colombia have developed multiple resistance mechanisms associated with pyrethroid resistance; therefore a resistance management strategy against these field populations of Ae. Aegypti, incorporating these findings is strongly recommended.

Immune response-related genes associated to blocking midgut dengue virus infection in Aedes aegypti strains that differ in susceptibility.

Aedes (Stegomyia) aegypti, the principal global vector of dengue viruses, has differences in its susceptibility to dengue virus infection. We compared the global expression of genes in the midguts of Colombian Ae. aegypti dengue-susceptible (Cali-S) and dengue-refractory (Cali-MIB) field derived strains after ingesting either a sugarmeal, a bloodmeal, or a bloodmeal containing dengue virus serotype 2 (DENV-2). Microarray-based transcriptome analysis among treatments indicated a total of 4725 transcripts with differential expression between the two strains. Eleven genes were selected from different functional groups based on their significant up or down expression levels as well as reports in the literature suggesting they are associated with dengue virus elimination. We measured mRNA abundance of these 11 genes at 0, 8, 24, and 36 h postinfection using quantitative real time PCR (qPCR) to confirm the microarray results and assess any temporal patterns. Four genes were selected (Gram-negative binding protein-GNBP [AAEL009176], Niemann Pick Type-C2-NPC2 [AAEL015136], Keratinocyte lectin [AAEL009842], and Cathepsin-b [AAEL007585]) for knockdown experiments using RNA interference (RNAi) methodology to determine the phenotype (DENV-2 susceptible or refractory). Silencing GNBP, Cathepsin-b and Keratinocyte lectin reduced the percentage of mosquitoes with disseminated virus in the Cali-S strain to 8%, 20%, and 12% respectively compared with 96% in the controls. Silencing of NPC2 increased the percentage of mosquitos with disseminated virus infections in Cali-MIB to 66% compared with 35% in the controls. This study provides insight into genes that may contribute to the Cali-S susceptible and Cali-MIB refractory phenotypes in Ae. aegypti.

The Composition of Midgut Bacteria in Aedes aegypti (Diptera: Culicidae) That Are Naturally Susceptible or Refractory to Dengue Viruses.

The composition, abundance, and diversity of midgut bacteria in mosquitoes can influence pathogen transmission. We used 16S rRNA microbiome profiling to survey midgut microbial diversity in pooled samples of laboratory colonized dengue-refractory, Cali-MIB, and dengue-susceptible, Cali-S Aedes aegypti (Linnaeus). The 16S rRNA sequences from the sugar-fed midguts of adult females clustered to 63 amplicon sequence variants (ASVs), primarily from Proteobacteria, Firmicutes, Flavobacteria, and Actinobacteria. An average of five ASVs dominated the midguts, and most ASVs were present in both Cali-MIB and Cali-S midguts. No differences in abundance were noted at any phylogenetic level (Phylum, Class, Order, Family, Genus) by analysis of composition of microbiome (w = 0). No community diversity metrics were significantly different between refractory and susceptible mosquitoes. These data suggest that phenotypic differences in the susceptibility to dengue virus between Cali-MIB and Cali-S are not likely due to major differences in midgut bacterial communities.

[Costs of an Aedes aegypti vector control program in municipalities in Colombia: a case study in Girón and Guadalajara de Buga, 2016]. / Costos de un programa de control del vector Aedes aegypti en municipios de Colombia: el caso de Girón y Guadalajara de Buga, 2016.

The aim of this study was to measure the costs of vector-borne disease control programs at the local level in Colombia (2016). A cost analysis was performed for this purpose from the policymaker's perspective in the municipalities (counties) of Girón and Guadalajara de Buga, specifically for the Aedes aegypti control program, the principal mosquito vector of dengue, Zika, and chikungunya. The analysis involved the quantification of all the costs required for each of the prevention and control strategies in vector-borne diseases. The costs were classified as operating and capital costs, and for purposes of comparison the costs were also calculated per case and per capita. The programs' total estimated costs were USD 146,651 in Girón and USD 97,936 in Guadalajara de Buga. Per capita cost was USD 0.88 in Girón and USD 0.99 in Guadalajara de Buga. In general, the predominant cost strategies were chemical spraying of adult mosquitos, accounting for 26% of the total costs in Girón and 47% in Guadalajara de Buga, with personnel representing 40% of the total costs for this strategy in Girón and 66% of the operating costs in Guadalajara de Buga.

El objetivo de este estudio fue cuantificar los costos de los programas de control de enfermedades transmitidas por vectores a nivel local en Colombia (2016). Para ello, fue realizado un análisis de costos desde la perspectiva del hacedor de política en los municipios de Girón y Guadalajara de Buga, específicamente para el programa de control del Aedes aegypti, principal vector trasmisor del dengue, Zika y chikungunya. Este análisis implicó la cuantificación de todos los costos requeridos para cada una de las estrategias de prevención y control de enfermedades transmitidas por vectores. Los costos fueron clasificados en recurrentes y de capital, además, con fines comparativos se obtuvo el costo por caso y a nivel per cápita. El costo total estimado de los programas fue de USD 146.651 en el municipio de Girón y USD 97.936 en el municipio de Guadalajara de Buga; a nivel per cápita el costo fue de USD 0,88 en Girón y en Guadalajara de Buga fue de USD 0,99. En general, las estrategias predominantes en costos fueron el control químico de vectores adultos, con un 26% del total de los costos en Girón y un 47% en Guadalajara de Buga, esta fue intensiva en costos recurrentes, con un costo de personal 40% del total de costos para esta estrategia en Girón y un 66% de costos operacionales en Guadalajara de Buga.

O objetivo deste estudo foi quantificar os custos dos programas de controle de doenças transmitidas por vetores ao nível local na Colômbia em (2016). Para isso, foi realizada uma análise de custos desde a perspectiva do criador de políticas nos municípios de Girón e Guadalajara de Buga, especificamente para o programa de controle do Aedes aegypti, principal vector transmissor da dengue, Zika e chikungunya. Esta análise implicou a quantificação de todos os custos requeridos para cada uma das estratégias de prevenção e controle de doenças transmitidas por vetores. Os custos foram classificados em recorrentes e do capital, ademais, para fins comparativos foi obtido o custo por caso e nível per capita. O custo total estimado dos programas foi de USD 146.651 no Município de Girón e USD 97.936 no Município de Guadalajara de Buga; ao nível per capita o custo foi de USD 0,88 em Girón e em Guadalajara de Buga foi de USD 0,99. Em geral, as estratégias predominantes em custos foram o controle químico de vetores adultos, com um 26% do total dos custos em Girón e um 47% em Guadalajara de Buga, essa foi intensiva em custos recorrentes, com um custo de pessoal de um 40% do total de custos para esta estratégia em Girón e um 66% de custos operacionais em Guadalajara de Buga.

Costos de un programa de control del vector Aedes aegypti en municipios de Colombia: el caso de Girón y Guadalajara de Buga, 2016 / Costs of an Aedes aegypti vector control program in municipalities in Colombia: a case study in Girón and Guadalajara de Buga, 2016 / Custos de um programa de controle ao vetor Aedes aegypti em municípios da Colômbia: o caso de Girón e Guadalajara de Buga, 2016

Resumen: El objetivo de este estudio fue cuantificar los costos de los programas de control de enfermedades transmitidas por vectores a nivel local en Colombia (2016). Para ello, fue realizado un análisis de costos desde la perspectiva del hacedor de política en los municipios de Girón y Guadalajara de Buga, específicamente para el programa de control del Aedes aegypti, principal vector trasmisor del dengue, Zika y chikungunya. Este análisis implicó la cuantificación de todos los costos requeridos para cada una de las estrategias de prevención y control de enfermedades transmitidas por vectores. Los costos fueron clasificados en recurrentes y de capital, además, con fines comparativos se obtuvo el costo por caso y a nivel per cápita. El costo total estimado de los programas fue de USD 146.651 en el municipio de Girón y USD 97.936 en el municipio de Guadalajara de Buga; a nivel per cápita el costo fue de USD 0,88 en Girón y en Guadalajara de Buga fue de USD 0,99. En general, las estrategias predominantes en costos fueron el control químico de vectores adultos, con un 26% del total de los costos en Girón y un 47% en Guadalajara de Buga, esta fue intensiva en costos recurrentes, con un costo de personal 40% del total de costos para esta estrategia en Girón y un 66% de costos operacionales en Guadalajara de Buga.

Abstract: The aim of this study was to measure the costs of vector-borne disease control programs at the local level in Colombia (2016). A cost analysis was performed for this purpose from the policymaker's perspective in the municipalities (counties) of Girón and Guadalajara de Buga, specifically for the Aedes aegypti control program, the principal mosquito vector of dengue, Zika, and chikungunya. The analysis involved the quantification of all the costs required for each of the prevention and control strategies in vector-borne diseases. The costs were classified as operating and capital costs, and for purposes of comparison the costs were also calculated per case and per capita. The programs' total estimated costs were USD 146,651 in Girón and USD 97,936 in Guadalajara de Buga. Per capita cost was USD 0.88 in Girón and USD 0.99 in Guadalajara de Buga. In general, the predominant cost strategies were chemical spraying of adult mosquitos, accounting for 26% of the total costs in Girón and 47% in Guadalajara de Buga, with personnel representing 40% of the total costs for this strategy in Girón and 66% of the operating costs in Guadalajara de Buga.

Resumo: O objetivo deste estudo foi quantificar os custos dos programas de controle de doenças transmitidas por vetores ao nível local na Colômbia em (2016). Para isso, foi realizada uma análise de custos desde a perspectiva do criador de políticas nos municípios de Girón e Guadalajara de Buga, especificamente para o programa de controle do Aedes aegypti, principal vector transmissor da dengue, Zika e chikungunya. Esta análise implicou a quantificação de todos os custos requeridos para cada uma das estratégias de prevenção e controle de doenças transmitidas por vetores. Os custos foram classificados em recorrentes e do capital, ademais, para fins comparativos foi obtido o custo por caso e nível per capita. O custo total estimado dos programas foi de USD 146.651 no Município de Girón e USD 97.936 no Município de Guadalajara de Buga; ao nível per capita o custo foi de USD 0,88 em Girón e em Guadalajara de Buga foi de USD 0,99. Em geral, as estratégias predominantes em custos foram o controle químico de vetores adultos, com um 26% do total dos custos em Girón e um 47% em Guadalajara de Buga, essa foi intensiva em custos recorrentes, com um custo de pessoal de um 40% do total de custos para esta estratégia em Girón e um 66% de custos operacionais em Guadalajara de Buga.

Changing paradigms in Aedes control: considering the spatial heterogeneity of dengue transmission / Cambio de paradigma en el control de Aedes: consideración de la heterogeneidad espacial de la transmisión del dengue

Current dengue vector control strategies, focusing on reactive implementation of insecticide- based interventions in response to clinically apparent disease manifestations, tend to be inefficient, short-lived, and unsustainable within the worldwide epidemiological scenario of virus epidemic recrudescence. As a result of a series of expert meetings and deliberations, a paradigm shift is occurring and a new strategy, using risk stratification at the city level in order to concentrate proactive, sustained efforts in areas at high risk for transmission, has emerged. In this article, the authors 1) outline this targeted, proactive intervention strategy, within the context of dengue epidemiology, the dynamics of its transmission, and current Aedes control strategies, and 2) provide support from published literature for the need to empirically test its impact on dengue transmission as well as on the size of disease outbreaks. As chikungunya and Zika viruses continue to expand their range, the need for a science-based, proactive approach for control of urban Aedes spp. mosquitoes will become a central focus of integrated disease management planning.

Las estrategias actuales de control de vectores del dengue, centradas en la ejecución reactiva de intervenciones con insecticidas en respuesta a la aparición de cuadros clínicos evidentes de la enfermedad, suelen ser ineficientes, de duración limitada e insostenibles en el contexto epidemiológico mundial, caracterizado por la recrudescencia de las epidemias virales. Como resultado de una serie de reuniones y deliberaciones entre expertos, está en proceso un cambio de paradigma y ha surgido una nueva estrategia, que consiste en estratificar el riesgo de cada ciudad para concentrar y mantener los esfuerzos proactivos donde hay un alto riesgo de transmisión. En este artículo, los autores 1) describen esta estrategia de intervención específica y proactiva dentro del contexto de las características epidemiológicas del dengue, la dinámica de su transmisión y las estrategias actuales de control de Aedes y 2) fundamentan con fuentes bibliográficas la necesidad de demostrar empíricamente las repercusiones de esta estrategia sobre la transmisión del dengue y el tamaño de los brotes. Dado que los virus del chikunguña y el Zika siguen ampliando su alcance, uno de los objetivos primordiales de la planificación de la atención integrada de estas enfermedades estará determinado por la necesidad de adoptar un enfoque científico y proactivo del control urbano de los mosquitos del género Aedes.

Changing paradigms in Aedes control: considering the spatial heterogeneity of dengue transmission.

Current dengue vector control strategies, focusing on reactive implementation of insecticide-based interventions in response to clinically apparent disease manifestations, tend to be inefficient, short-lived, and unsustainable within the worldwide epidemiological scenario of virus epidemic recrudescence. As a result of a series of expert meetings and deliberations, a paradigm shift is occurring and a new strategy, using risk stratification at the city level in order to concentrate proactive, sustained efforts in areas at high risk for transmission, has emerged. In this article, the authors 1) outline this targeted, proactive intervention strategy, within the context of dengue epidemiology, the dynamics of its transmission, and current Aedes control strategies, and 2) provide support from published literature for the need to empirically test its impact on dengue transmission as well as on the size of disease outbreaks. As chikungunya and Zika viruses continue to expand their range, the need for a science-based, proactive approach for control of urban Aedes spp. mosquitoes will become a central focus of integrated disease management planning.

Las estrategias actuales de control de vectores del dengue, centradas en la ejecución reactiva de intervenciones con insecticidas en respuesta a la aparición de cuadros clínicos evidentes de la enfermedad, suelen ser ineficientes, de duración limitada e insostenibles en el contexto epidemiológico mundial, caracterizado por la recrudescencia de las epidemias virales. Como resultado de una serie de reuniones y deliberaciones entre expertos, está en proceso un cambio de paradigma y ha surgido una nueva estrategia, que consiste en estratificar el riesgo de cada ciudad para concentrar y mantener los esfuerzos proactivos donde hay un alto riesgo de transmisión. En este artículo, los autores 1) describen esta estrategia de intervención específica y proactiva dentro del contexto de las características epidemiológicas del dengue, la dinámica de su transmisión y las estrategias actuales de control de Aedes y 2) fundamentan con fuentes bibliográficas la necesidad de demostrar empíricamente las repercusiones de esta estrategia sobre la transmisión del dengue y el tamaño de los brotes. Dado que los virus del chikunguña y el Zika siguen ampliando su alcance, uno de los objetivos primordiales de la planificación de la atención integrada de estas enfermedades estará determinado por la necesidad de adoptar un enfoque científico y proactivo del control urbano de los mosquitos del género Aedes.

Changing paradigms in Aedes control: considering the spatial heterogeneity of dengue transmission / Cambio de paradigma en el control de Aedes: consideración de la heterogeneidad espacial de la transmisión del dengue

ABSTRACT Current dengue vector control strategies, focusing on reactive implementation of insecticide-based interventions in response to clinically apparent disease manifestations, tend to be inefficient, short-lived, and unsustainable within the worldwide epidemiological scenario of virus epidemic recrudescence. As a result of a series of expert meetings and deliberations, a paradigm shift is occurring and a new strategy, using risk stratification at the city level in order to concentrate proactive, sustained efforts in areas at high risk for transmission, has emerged. In this article, the authors 1) outline this targeted, proactive intervention strategy, within the context of dengue epidemiology, the dynamics of its transmission, and current Aedes control strategies, and 2) provide support from published literature for the need to empirically test its impact on dengue transmission as well as on the size of disease outbreaks. As chikungunya and Zika viruses continue to expand their range, the need for a science-based, proactive approach for control of urban Aedes spp. mosquitoes will become a central focus of integrated disease management planning.

RESUMEN Las estrategias actuales de control de vectores del dengue, centradas en la ejecución reactiva de intervenciones con insecticidas en respuesta a la aparición de cuadros clínicos evidentes de la enfermedad, suelen ser ineficientes, de duración limitada e insostenibles en el contexto epidemiológico mundial, caracterizado por la recrudescencia de las epidemias virales. Como resultado de una serie de reuniones y deliberaciones entre expertos, está en proceso un cambio de paradigma y ha surgido una nueva estrategia, que consiste en estratificar el riesgo de cada ciudad para concentrar y mantener los esfuerzos proactivos donde hay un alto riesgo de transmisión. En este artículo, los autores 1) describen esta estrategia de intervención específica y proactiva dentro del contexto de las características epidemiológicas del dengue, la dinámica de su transmisión y las estrategias actuales de control de Aedes y 2) fundamentan con fuentes bibliográficas la necesidad de demostrar empíricamente las repercusiones de esta estrategia sobre la transmisión del dengue y el tamaño de los brotes. Dado que los virus del chikunguña y el Zika siguen ampliando su alcance, uno de los objetivos primordiales de la planificación de la atención integrada de estas enfermedades estará determinado por la necesidad de adoptar un enfoque científico y proactivo del control urbano de los mosquitos del género Aedes.

Spatial modeling of cutaneous leishmaniasis in the Andean region of Colombia

The objective of this research was to identify environmental risk factors for cutaneous leishmaniasis (CL) in Colombia and map high-risk municipalities. The study area was the Colombian Andean region, comprising 715 rural and urban municipalities. We used 10 years of CL surveillance: 2000-2009. We used spatial-temporal analysis - conditional autoregressive Poisson random effects modelling - in a Bayesian framework to model the dependence of municipality-level incidence on land use, climate, elevation and population density. Bivariable spatial analysis identified rainforests, forests and secondary vegetation, temperature, and annual precipitation as positively associated with CL incidence. By contrast, livestock agroecosystems and temperature seasonality were negatively associated. Multivariable analysis identified land use - rainforests and agro-livestock - and climate - temperature, rainfall and temperature seasonality - as best predictors of CL. We conclude that climate and land use can be used to identify areas at high risk of CL and that this approach is potentially applicable elsewhere in Latin America.

Spatial modeling of cutaneous leishmaniasis in the Andean region of Colombia.

The objective of this research was to identify environmental risk factors for cutaneous leishmaniasis (CL) in Colombia and map high-risk municipalities. The study area was the Colombian Andean region, comprising 715 rural and urban municipalities. We used 10 years of CL surveillance: 2000-2009. We used spatial-temporal analysis - conditional autoregressive Poisson random effects modelling - in a Bayesian framework to model the dependence of municipality-level incidence on land use, climate, elevation and population density. Bivariable spatial analysis identified rainforests, forests and secondary vegetation, temperature, and annual precipitation as positively associated with CL incidence. By contrast, livestock agroecosystems and temperature seasonality were negatively associated. Multivariable analysis identified land use - rainforests and agro-livestock - and climate - temperature, rainfall and temperature seasonality - as best predictors of CL. We conclude that climate and land use can be used to identify areas at high risk of CL and that this approach is potentially applicable elsewhere in Latin America.

First report of Warileya rotundipennis (Psychodidae: Phlebotominae) naturally infected with Leishmania (Viannia) in a focus of cutaneous leishmaniasis in Colombia.

The expansion of transmission of cutaneous leishmaniasis from sylvatic ecosystems into peri-urban and domestic settings has occurred as sand flies have adapted to anthropogenic environmental modifications. Assessment of the intradomiciliary presence of sand flies in households of the settlement "La Cabaña", in the Department of Risaralda, Colombia, revealed an abundance of Warileya rotundipennis. This unexpected observation motivated further analyses to evaluate the participation of this species in the transmission of cutaneous leishmaniasis. Collections using CDC light traps were conducted during two consecutive nights in May and August 2011.The total of 667 sand flies collected were classified into five species: W. rotundipennis (n=654; 98.05%), Nyssomyia trapidoi (n=7; 1.04%); Lutzomyia (Helcocyrtomyia) hartmanni (n=3; 0.44%); Lutzomyia lichyi (n=2; 0.29%) and Psychodopygus panamensis (n=1; 0.14%). The striking predominance of W. rotundipennis within households during both wet (May) and dry (August) seasons, anthropophilic behavior demonstrated by human blood in 95.23% (60/63) evaluable blood-engorged specimens, and natural infection (5/168-3%) with genetically similar parasites of the Leishmania (Viannia) subgenus observed in a patient in this community, support the involvement of W. rotundipennis in the domestic transmission of cutaneous leishmaniasis in "La Cabaña".

Reduction in dengue cases observed during mass control of Aedes (Stegomyia) in street catch basins in an endemic urban area in Colombia.

Dengue incidence continues to increase globally and, in the absence of an efficacious vaccine, prevention strategies are limited to vector control. It has been suggested that targeting the most productive breeding sites instead of all water-holding containers could be a cost-effective vector control strategy. We sought to identify and continuously control the most productive Aedes (Stegomyia) breeding site in an endemic urban area in Colombia and followed the subsequent incidence of dengue. In the urban area of Guadalajara de Buga, southwestern Colombia, potential breeding sites inside and outside houses were first characterized, and local personnel trained to assess their productivity based on the pupae/person index. Simultaneously, training and monitoring were implemented to improve the dengue case surveillance system. Entomological data and insecticide resistance studies were used to define the targeted intervention. Then, a quasi-experimental design was used to assess the efficacy of the intervention in terms of the positivity index of the targeted and non- targeted breeding sites, and the impact on dengue cases. Street catch basins (storm drains) were the potential breeding site most frequently found containing Aedes immature stages in the baseline (58.3% of 108). Due to the high resistance to temephos (0% mortality after 24h), the intervention consisted of monthly application of pyriproxyfen in all the street catch basins (n=4800). A significant decrease in catch basins positivity for Aedes larvae was observed after each monthly treatment (p<0.001). Over the intervention period, a reduction in the dengue incidence in Buga was observed (rate ratio 0.19, 95% CI 0.12-0.30, p<0.0001) after adjusting for autocorrelation and controlling with a neighboring town, Palmira, This study highlights the importance of street catch basins as Aedes breeding sites and suggests that their targeted control could help to decrease dengue transmission in such areas.