Bryan Steven Valencia-Marín                                                
 
                                                Laboratório de Morfologia e Fisiologia de Culicidae e Chironomidae, Departamento de Zoologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Avenida Coronel Francisco H. dos Santos, 100, Centro Politécnico Jardim das Américas, C.P. 19031, 81531-980, Curitiba, Paraná, Brazil
                                                 Escuela de Investigación en Biomatemática, Facultad de Ciencias Básicas y Tecnologías, Universidad del Quindío. Carrera 15 Calle 12 Norte, Armenia, Colombia
                                                                        
                                                                        
                     
                                        
                        Oscar Alexander Aguirre-Obando                                                
 
                                                Escuela de Investigación en Biomatemática, Facultad de Ciencias Básicas y Tecnologías, Universidad del Quindío. Carrera 15 Calle 12 Norte, Armenia, Colombia
                                                 Programa de Biología, Universidad del Quindío. Carrera 15 Calle 12 Norte, Armenia, Colombia
                                                                        
                                                                        
                     
                                        
                        Angela María Palacio-Cortés                                                
 
                                                Laboratório de Morfologia e Fisiologia de Culicidae e Chironomidae, Departamento de Zoologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Avenida Coronel Francisco H. dos Santos, 100, Centro Politécnico Jardim das Américas, C.P. 19031, 81531-980, Curitiba, Paraná, Brazil
                                                                        
                                                                        
                     
                                        
                        Patrícia Lawane de Freitas                                                
 
                                                Laboratório de Morfologia e Fisiologia de Culicidae e Chironomidae, Departamento de Zoologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Avenida Coronel Francisco H. dos Santos, 100, Centro Politécnico Jardim das Américas, C.P. 19031, 81531-980, Curitiba, Paraná, Brazil
                                                                        
                                                                        
                     
                                        
                        Juliane Maria Vink                                                
 
                                                Laboratório de Morfologia e Fisiologia de Culicidae e Chironomidae, Departamento de Zoologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Avenida Coronel Francisco H. dos Santos, 100, Centro Politécnico Jardim das Américas, C.P. 19031, 81531-980, Curitiba, Paraná, Brazil
                                                                        
                                                                        
                     
                                        
                        Mário Antônio Navarro-Silva                                                
 
                                                Laboratório de Morfologia e Fisiologia de Culicidae e Chironomidae, Departamento de Zoologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Avenida Coronel Francisco H. dos Santos, 100, Centro Politécnico Jardim das Américas, C.P. 19031, 81531-980, Curitiba, Paraná, Brazil
                                                                        
                                                                        
                     
                    
                                        
                                                            Communicated by John Wang
                                     
                
                    Among the mechanisms of insecticide resistance, knockdown resistance (kdr), causes alterations in the functioning of the voltage-gated sodium channel (Nav), which is the target site for pyrethroids (PYs) and dichloro diphenyl chloroethane (DDT). In Aedes aegypti, 13 kdr mutations associated with PYs resistance have been identified, with V410L, V1016I, V1016G, and F1534C being the most reported mutations in the literature. To assess global and temporal trends in the allelic frequencies of these V410L, V1016I/G and F1534C mutations, a PRISMA-guided systematic review was conducted to analyzed their distribution and frequency, incorporating new genotyping data from five southeastern Brazilian populations. Genotyping in these populations was performed using allele-specific PCR (AS-PCR), thereby complementing the findings of the review. The results revealed that, out of a total of 187 studies, the F1534C mutation is the most studied (144 studies) and has the widest geographical distribution (47 countries, 4 continents), followed by the V410L, V1016I, and V1016G mutations. In southeast Brazil, resistant alleles were detected both individually and in co-occurrence (e.g., V410L + V1016I + F1534C), and were associated with PY resistance. These mutations alter Nav, reducing insecticide binding affinity and leading to high-level resistance—particularly when specific genotypic combinations are present. Their global spread poses a significant threat to A. aegypti control efforts, as PYs remain a cornerstone of public health interventions. Urgent, systematic monitoring of kdr allele frequencies and their synergistic effects is essential to optimize insecticide rotation strategies and prevent operational failures. This calls for coordinated international efforts to develop adaptive control strategies.