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Digital, objectiveTo investigate the link between fluctuations in the prevalence of dengue virus (DENV)serotypes and the number of dengue cases in the metropolitan area of Bucaramanga, Santander State,Colombia, in the 2007–2010 and 2014–2017 periods.methodViruses were isolated from febrile patient samples by direct application to C6/36-HT cellsand typed using monoclonal antibodies. We performed autocorrelation and cross-correlation analysesto determine whether fluctuations in the prevalence of DENV serotypes and dengue cases werecorrelated. Full envelope (E) gene sequences were employed to examine the genetic diversity ofserotypes circulating by using a phylogenetic approach.resultsAll four dengue virus serotypes were detected. DENV-1 was the dominant serotype in bothperiods followed by DENV-3 or DENV-2 depending on the period; DENV-4 was the least prevalentvirus in both periods. Cross-correlation analyses suggest a temporal relation between the fluctuationsin the prevalence of DENV serotypes, which were almost simultaneous (lag=0) or related to recentpast fluctuations (lag>1.0) in the number of dengue cases. Data suggest that a sustainedpredominance of DENV-1, an increase of the DENV-4 prevalence, and a switch from DENV-3 toDENV-2 could be linked to an outbreak. Circulating viruses were grouped into Genotype V, Asia/American III and II for DENV-1, -2, -3 and -4, respectively; intragenotypic diversity was detected.conclusionsThe present work highlights the need of comprehensive studies on dynamics of DENV inColombia to understand transmission of dengue and evaluate the effectiveness of a vaccination programme., Ciencias Médicas y de la Salud

Background: The cardiopulmonary dirofilariasis caused by Dirofilaria immitis, is a vector-born infection, which can be transmitted to humans. The main host are both domestic and wild canids. It mainly occurs in tropical and subtropical climates, temperature and humidity are the main factors that favor the presence and proliferation of Culicidae mosquitoes. There are few reports of this disease in dogs and humans in Colombia, a region with favorable climatic conditions for the development of this disease. Therefore, this research aimed to study its current prevalence in dogs and the risk of human exposure to the disease in Bucaramanga, one of the most populated areas in Colombia located at the center of the country. Furthermore, its demographic and environmental characteristics could be useful as a study model for other similar locations and neighboring countries.Method: Serum samples from 351 dogs and 506 humans from the Bucaramanga metropolitan area were analyzed. All dog samples were tested with a commercial immunochromatographic test kit to detect the presence of circulating antigens of D. immitis. Human samples were analyzed using a non-commercial ELISA test kit to detect IgG against the somatic antigens of adult D. immitis and Wolbachia. Positive results were further confirmed using a Western blot analysis.Results: Dirofilaria immitis prevalence was 10.82% (95% CI) in dogs and 5.12% (95% CI) in microfilaremic dogs. Seroprevalence in humans was 6.71% (95% CI) and was significantly higher in individuals aged 16–34 years and in women than in men.Conclusions:This study describes seropositivity to D. immitis for the first time in a Colombian human population located in the same area as that of dogs infected with D. immitis, which represents a potential threat to public health. In humans, age and sex can be considered risk factors for exposure to D. immitis.

Background: Cardiopulmonary dirofilariosis caused by Dirofilaria immitis is a zoonotic, vector-borne infection, whose main hosts are both domestic and wild canids and which can be transmitted to humans. It mainly occurs in tropical and subtropical climates, and temperature and humidity are the main factors that favor the presence and proliferation of Culicidae mosquitoes. There have been few reports of this disease in dogs and humans in Colombia, a region with favorable climatic conditions for the development of this disease. Therefore, this research aimed to study its current prevalence in dogs and the risk of human exposure to the disease in Bucaramanga, one of the most populated areas in Colombia located at the center of the country. Furthermore, its demographic and environmental characteristics could be useful as a study model for other similar locations and neighboring countries. Method: Serum samples from 351 dogs and 506 humans from the Bucaramanga metropolitan area were analyzed. All dog samples were tested with a commercial immunochromatographic test kit to detect the presence of circulating antigens of D. immitis. Human samples were analyzed using a non-commercial ELISA test kit to detect IgG against the somatic antigens of adult D. immitis and Wolbachia. Positive results were further confirmed using a Western blot analysis. Results: Dirofilaria immitis prevalence was 10.82% (95% CI) in dogs and 5.12% (95% CI) in microfilaremic dogs. Seroprevalence in humans was 6.71% (95% CI) and was significantly higher in individuals aged 16–34 years and in women than in men. Conclusions: This study describes seropositivity to D. immitis for the first time in a Colombian human population located in the same area as that of dogs infected with D. immitis, which represents a potential threat to public health. In humans, age and sex can be considered risk factors for exposure to D. immitis.

Background Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS2B/NS3 protease complex is a target for designing specific antivirals due to its importance in viral replication and its high degree of conservation. Methods NS2B/NS3 protease complex structural information was employed to find small molecules that are capable of inhibiting the activity of the enzyme complex. This inhibitory activity was probed with in vitro assays using a fluorescent substrate and the complex NS2B/NS3 obtained by recombinant DNA techniques. HepG2 cells infected with dengue virus serotype 2 were used to test the activity against dengue virus replication. Results A total of 210,903 small molecules from PubChem were docked in silico to the NS2B/NS3 structure (PDB: 2FOM) to find molecules that were capable of inhibiting this protein complex. Five of the best 500 leading compounds, according to their affinity values (−11.6 and −13.5 kcal/mol), were purchased. The inhibitory protease activity on the recombinant protein and antiviral assays was tested. Conclusions Chemicals CID 54681617, CID 54692801 and CID 54715399 were strong inhibitors of NS2B/NS3, with IC 50 values (μM) and percentages of viral titer reductions of 19.9, 79.9%; 17.5, 69.8%; and 9.1, 73.9%, respectively. Multivariate methods applied to the molecular descriptors showed two compounds that were structurally different from other DENV inhibitors. General significance: This discovery opens new possibilities for obtaining drug candidates against Dengue virus.