RESUMO
BACKGROUND The massive use of insecticides in public health has exerted selective pressure resulting in the development of resistance in Aedes aegypti to different insecticides in Venezuela. Between 2010 and 2020, the only insecticides available for vector control were the organophosphates (Ops) fenitrothion and temephos which were focally applied. OBJECTIVES To determine the state of insecticide resistance and to identify the possible biochemical and molecular mechanisms involved in three populations of Ae. aegypti from Venezuela. METHODS CDC bottle bioassays were conducted on Ae. aegypti collected between October 2019 and February 2020 in two hyperendemic localities for dengue in Aragua State and in a malaria endemic area in Bolívar State. Insecticide resistance mechanisms were studied using biochemical assays and polymerase chain reaction (PCR) to detect kdr mutations. FINDINGS Bioassays showed contrasting results among populations; Las Brisas was resistant to malathion, permethrin and deltamethrin, Urbanización 19 de Abril was resistant to permethrin and Nacupay to malathion. All populations showed significantly higher activity of mixed function oxidases and glutathione-S-transferases (GSTs) in comparison with the susceptible strain. The kdr mutations V410L, F1534C, and V1016I were detected in all populations, with F1534C at higher frequencies. MAIN CONCLUSION Insecticide resistance persists in three Ae. aegypti populations from Venezuela even in the relative absence of insecticide application.
RESUMO
La warfarina es el anticoagulante oral (AO) más utilizado en la profilaxis a largo plazo de las complicaciones tromboembólicas que acompañan a diversas enfermedades. Sus indicaciones se han ampliado en los últimos años, a medida que son detectadas nuevas situaciones clínicas que predisponen a sufrir eventos trombóticos. Debido a sus características especiales, tales como: dosis muy variable en cada individuo, estrecho margen entre la dosis adecuada y la inadecuada, interacciones con múltiples fármacos, interferencia de su efecto por el alto consumo de vitamina K en la dieta y la posibilidad de que aparezcan complicaciones hemorrágicas o recurrencia de la trombosis, el empleo de este medicamento requiere un estricto control de su dosificación y una continua vigilancia, tanto desde el punto de vista clínico como de laboratorio. A pesar de sus numerosas desventajas y de tener más de cincuenta años de uso clínico, la warfarina no ha sido sustituida hasta la fecha, por los anticoagulantes orales de reciente aparición. En el año 1999, la warfarina llegó a ocupar el décimo primer lugar entre los medicamentos de mayor consumo en el mundo.
Warfarin is the most utilized oral anticoagulant for the long term prophylaxes of thrombosis. Its use has been increased as new clinical conditions, capable of leading to thrombosis, have been detected. Due to the special characteristics of warfarin, such as the variability of doses for each individual, the narrow margin between adequate and inadequate doses, interaction with multiple pharmaceutical products, interference of its action by vitamin K present in the diet and the possibility of hemorrhagic complications or thrombotic recurrence, this drug requires a very careful dosage and strict laboratory and clinical monitoring. Despite being in the market for more than de fifty years and its many disadvantages, warfarin has not been substituted for the new oral anticoagulants. In 1999, warfarin was positioned eleventh on the list of the most used medicines in the world.